Www.research.manchester.ac.uk
Cardiovascular Risk and its Modification in Patients with Connective Tissue DiseasesMiriam O’Sullivan PhD MRCPVisiting clinical research fellow*Ian N Bruce MD FRCPProfessor of RheumatologyDeborah PM Symmons MD FRCPProfessor of Rheumatology and Musculoskeletal EpidemiologyArthritis Research UK Centre for EpidemiologyCentre for Musculoskeletal ResearchUniversity of ManchesterStopford Building, Oxford RoadManchester M13 9PTNIHR Manchester Musculoskeletal Biomedical Research UnitCentral Manchester NHS Foundation TrustManchester Academic Health Science CentreManchesterDeborah.symmons@manchester.ac.ukTelephone: +44 161 275 5044 / FAX: +44 161 275 5043*Future address:Sligo University HospitalSligo, IrelandCorresponding author: Deborah Symmons Abstract It is well documented that patients with SLE are at an increased risk of atherosclerotic cardiovascular disease. There is evidence that traditional risk factors and disease-related factors are involved in this increased risk. Less is known about cardiovascular (CV) risk and outcomes in other connective tissue diseases (CTDs). Future longitudinal observational studies may help to answer these important questions, however, because CTDs are rare, collaboration between clinicians with similar research interests is needed to ensure large enough cohorts are available to address these issues.Here we review the evidence available for CV risk in CTDs and discuss the benefits of longitudinal observational studies in identifying CV outcomes. Structured care protocols for management of cardiovascular risk in CTDs are lacking. We propose a target-based approach to assessing and managing CV risk in CTDs. Key wordsConnective tissue diseasesSLESystemic sclerosisPrimary Sjogren’s syndromeIdiopathic Inflammatory MyopathiesCardiovascular diseaseCardiovascular risk managementIntroduction (Level A)Patients with inflammatory musculoskeletal diseases have an excess risk of atherosclerotic cardiovascular disease (ACVD) compared to the general population. A meta-analysis of 24 mortality studies in patients with rheumatoid arthritis (RA) reported a weighted combined all-cause standardized mortality ratio (meta-SMR) of 1.50 (95% 1.39-1.61) with similar increases for ischaemic heart disease (meta-SMR 1.59; 95%CI 1.46-1.73) and stroke (meta-SMR 1.52; 95% CI 1.40-1.67) ADDIN EN.CITE <EndNote><Cite><Author>Avina-Zubieta</Author><Year>2008</Year><RecNum>70</RecNum><DisplayText>(1)</DisplayText><record><rec-number>70</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">70</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Avina-Zubieta, J. A.</author><author>Choi, H. K.</author><author>Sadatsafavi, M.</author><author>Etminan, M.</author><author>Esdaile, J. M.</author><author>Lacaille, D.</author></authors></contributors><auth-address>University of British Columbia and Arthritis Research Centre of Canada, British Columbia, Canada. azubieta@arthritisresearch.ca</auth-address><titles><title>Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies</title><secondary-title>Arthritis Rheum</secondary-title><alt-title>Arthritis and rheumatism</alt-title></titles><periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></alt-periodical><pages>1690-7</pages><volume>59</volume><number>12</number><edition>2008/11/28</edition><keywords><keyword>Arthritis, Rheumatoid/*complications</keyword><keyword>Cardiovascular Diseases/*mortality</keyword><keyword>Confidence Intervals</keyword><keyword>Humans</keyword><keyword>Myocardial Ischemia/mortality</keyword><keyword>Stroke/mortality</keyword></keywords><dates><year>2008</year><pub-dates><date>Dec 15</date></pub-dates></dates><isbn>0004-3591 (Print)
0004-3591 (Linking)</isbn><accession-num>19035419</accession-num><work-type>Comparative Study
Meta-Analysis
Research Support, Non-U.S. Gov't</work-type><urls><related-urls><url>;(1). The bimodal pattern of death associated with systemic lupus erythematosus (SLE) was first described in 1976 ADDIN EN.CITE <EndNote><Cite><Author>Urowitz</Author><Year>1976</Year><RecNum>329</RecNum><DisplayText>(2)</DisplayText><record><rec-number>329</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">329</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Urowitz, M. B.</author><author>Bookman, A. A.</author><author>Koehler, B. E.</author><author>Gordon, D. A.</author><author>Smythe, H. A.</author><author>Ogryzlo, M. A.</author></authors></contributors><titles><title>The bimodal mortality pattern of systemic lupus erythematosus</title><secondary-title>The American journal of medicine</secondary-title><alt-title>Am J Med</alt-title></titles><periodical><full-title>The American journal of medicine</full-title><abbr-1>Am J Med</abbr-1></periodical><alt-periodical><full-title>The American journal of medicine</full-title><abbr-1>Am J Med</abbr-1></alt-periodical><pages>221-5</pages><volume>60</volume><number>2</number><dates><year>1976</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0002-9343 (Print)
0002-9343 (Linking)</isbn><accession-num>1251849</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(2), with the first mortality peak (within 1 year of diagnosis) being due mainly to active lupus and infection and the second peak (>5 years from diagnosis) being due mainly to cardiovascular events (CVEs). In 1997 Manzi et al reported that the risk of myocardial infarction (MI) was over 50 times higher in women aged 35-44 in the University of Pittsburgh lupus cohort than in age-matched women from the Framingham offspring cohort ADDIN EN.CITE <EndNote><Cite><Author>Manzi</Author><Year>1997</Year><RecNum>384</RecNum><DisplayText>(3)</DisplayText><record><rec-number>384</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">384</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Manzi, S.</author><author>Meilahn, E. N.</author><author>Rairie, J. E.</author><author>Conte, C. G.</author><author>Medsger, T. A., Jr.</author><author>Jansen-McWilliams, L.</author><author>D'Agostino, R. B.</author><author>Kuller, L. H.</author></authors></contributors><auth-address>Department of Medicine, University of Pittsburgh, PA 15213, USA.</auth-address><titles><title>Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study</title><secondary-title>Am J Epidemiol</secondary-title><alt-title>Am J Epidemiol</alt-title></titles><periodical><full-title>Am J Epidemiol</full-title><abbr-1>American journal of epidemiology</abbr-1></periodical><alt-periodical><full-title>Am J Epidemiol</full-title><abbr-1>American journal of epidemiology</abbr-1></alt-periodical><pages>408-15</pages><volume>145</volume><number>5</number><dates><year>1997</year><pub-dates><date>Mar 1</date></pub-dates></dates><isbn>0002-9262 (Print)
0002-9262 (Linking)</isbn><accession-num>9048514</accession-num><work-type>Comparative Study
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(3). In this chapter we summarise the most recent literature on the risk of ACVD and the risk factors for ACVD in patients with SLE, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease and primary Sjogren’s syndrome. We performed a Medline search up until 30th November 2015 searching for “ cardiovascular risk” and “cardiovascular mortality” and combined each with “ systemic lupus erythematosus”, “ systemic sclerosis”, “Sjogren’s syndrome”, “idiopathic inflammatory myopathy” and “mixed connective tissue disease”. We have focussed on reporting relevant systematic reviews and papers published in the last 5 years. We highlight the importance of longitudinal observational studies (LOS) in contributing to this knowledge and on the value of embedding research into routine clinical practice. Finally we review strategies for cardiovascular (CV) risk management in patients with connective tissue diseases (CTD). Cardiovascular disease in patients with SLE (Level A)SLE is a chronic inflammatory autoimmune condition with significant morbidity and mortality. Survival rates for SLE have improved dramatically in recent years ADDIN EN.CITE <EndNote><Cite><Author>Mak</Author><Year>2012</Year><RecNum>386</RecNum><DisplayText>(4)</DisplayText><record><rec-number>386</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">386</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mak, A.</author><author>Cheung, M. W.</author><author>Chiew, H. J.</author><author>Liu, Y.</author><author>Ho, R. C.</author></authors></contributors><auth-address>Division of Rheumatology, Department of Medicine, University Medicine Cluster, National University of Singapore, Singapore. mdcam@nus.edu.sg</auth-address><titles><title>Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s</title><secondary-title>Semin Arthritis Rheum</secondary-title><alt-title>Semin Arthritis Rheum</alt-title></titles><periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></alt-periodical><pages>830-9</pages><volume>41</volume><number>6</number><dates><year>2012</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1532-866X (Electronic)
0049-0172 (Linking)</isbn><accession-num>22257558</accession-num><work-type>Meta-Analysis</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(4). In an international study of 9547 patients from 23 centres the all-cause SMR estimates decreased significantly between the 1970s and 2001. However, the CV SMR increased slightly PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXJuYXRza3k8L0F1dGhvcj48WWVhcj4yMDA2PC9ZZWFy
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ADDIN EN.CITE.DATA (5). CVEs remain one of the main causes of death in SLE. Cardiovascular mortality in patients with SLE (Level B)CV mortality is increased in SLE patients compared to the general population. In a meta-analysis of 27,123 SLE patients from 12 studies published prior to 2011, there was a 3-fold increased risk of all-cause mortality (meta-SMR 2.98, 95% CI 2.32–3.83) and an increased risk of death from cardiovascular disease (CVD) (meta-SMR 2.72, 95% CI 2.32- 3.83) ADDIN EN.CITE <EndNote><Cite><Author>Yurkovich</Author><Year>2014</Year><RecNum>325</RecNum><DisplayText>(6)</DisplayText><record><rec-number>325</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">325</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yurkovich, M.</author><author>Vostretsova, K.</author><author>Chen, W.</author><author>Avina-Zubieta, J. A.</author></authors></contributors><auth-address>University of British Columbia, Vancouver, British Columbia, Canada.</auth-address><titles><title>Overall and cause-specific mortality in patients with systemic lupus erythematosus: a meta-analysis of observational studies</title><secondary-title>Arthritis Care Res (Hoboken)</secondary-title><alt-title>Arthritis Care Res (Hoboken)</alt-title></titles><periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></periodical><alt-periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></alt-periodical><pages>608-16</pages><volume>66</volume><number>4</number><dates><year>2014</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>2151-4658 (Electronic)
2151-464X (Linking)</isbn><accession-num>24106157</accession-num><work-type>Meta-Analysis
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(6). None of the studies of mortality published since 2011 has had sufficient numbers of deaths to be able to report a CV specific SMR PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FbGZ2aW5nPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA (7, 8). The most recent study followed 2740 incident cases of SLE identified using the UK primary-care based Clinical Practice Research Datalink and then linked to the national death register ADDIN EN.CITE <EndNote><Cite><Author>Rees</Author><Year>2016</Year><RecNum>338</RecNum><DisplayText>(9)</DisplayText><record><rec-number>338</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">338</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rees, F.</author><author>Doherty, M.</author><author>Grainge, M. J.</author><author>Lanyon, P.</author><author>Davenport, G.</author><author>Zhang, W.</author></authors></contributors><auth-address>Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Rheumatology Department, Nottingham University Hospitals NHS Trust, frees@.uk.
Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham.
Division of Epidemiology and Public Health, University of Nottingham, Nottingham and.
Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Rheumatology Department, Nottingham University Hospitals NHS Trust.
Arthritis Research UK Primary Care Centre, Keele University, Keele, UK.</auth-address><titles><title>Mortality in systemic lupus erythematosus in the United Kingdom 1999-2012</title><secondary-title>Rheumatology (Oxford, England)</secondary-title><alt-title>Rheumatology (Oxford)</alt-title></titles><alt-periodical><full-title>Rheumatology (Oxford)</full-title><abbr-1>Rheumatology</abbr-1></alt-periodical><dates><year>2016</year><pub-dates><date>Jan 8</date></pub-dates></dates><isbn>1462-0332 (Electronic)
1462-0324 (Linking)</isbn><accession-num>26748350</accession-num><work-type>Journal article</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>Eng</language></record></Cite></EndNote>(9). The mortality rate ratio compared to age, sex and practice matched controls was 1.67 (95%CI 1.43, 1.94). Another UK-based study followed an inception cohort of 382 SLE patients recruited from 1989-2010. The all-cause SMR was 2.0 (95% CI 1.5, 2.8), with CVEs being one of the most common causes of death ( 27%) ADDIN EN.CITE <EndNote><Cite><Author>Yee</Author><Year>2015</Year><RecNum>335</RecNum><DisplayText>(10)</DisplayText><record><rec-number>335</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">335</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yee, C. S.</author><author>Su, L.</author><author>Toescu, V.</author><author>Hickman, R.</author><author>Situnayake, D.</author><author>Bowman, S.</author><author>Farewell, V.</author><author>Gordon, C.</author></authors></contributors><titles><title>Birmingham SLE cohort: outcomes of a large inception cohort followed for up to 21 years</title><secondary-title>Rheumatology (Oxford)</secondary-title></titles><periodical><full-title>Rheumatology (Oxford)</full-title><abbr-1>Rheumatology</abbr-1></periodical><pages>836-43</pages><volume>54</volume><number>5</number><dates><year>2015</year></dates><isbn>1462-0332 (Electronic)
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ADDIN EN.CITE.DATA (11). CVEs accounted for 11.5% of all deaths whereas death from infection accounted for 33% of all deaths.Traditionally mortality studies have focussed on the underlying cause of death as recorded on the death certificate. A new methodology called multiple-cause-of-death analysis enables all the diagnoses recorded on the death certificate to be analysed. Two recently published studies have used this methodology in SLE. One study included 4815 death certificates from Sao Paulo, Brazil on which SLE was listed as a cause of death between 1985-2005 ADDIN EN.CITE <EndNote><Cite><Author>Souza</Author><Year>2012</Year><RecNum>387</RecNum><DisplayText>(12)</DisplayText><record><rec-number>387</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">387</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Souza, D. C.</author><author>Santo, A. H.</author><author>Sato, E. I.</author></authors></contributors><auth-address>Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.</auth-address><titles><title>Mortality profile related to systemic lupus erythematosus: a multiple cause-of-death analysis</title><secondary-title>J Rheumatol</secondary-title><alt-title>J Rheumatol</alt-title></titles><periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></periodical><alt-periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></alt-periodical><pages>496-503</pages><volume>39</volume><number>3</number><dates><year>2012</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0315-162X (Print)
0315-162X (Linking)</isbn><accession-num>22247362</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(12). The most common contributory causes of death were renal failure and sepsis. Only in 2003-7, and in individuals aged less than 50 years when they died, was CVD a more common cause of death than in the general population. The second study utilised the death certificates from all 1593 adults who died in France between 2000 and 2009 and in whom SLE was mentioned on the death certificate ADDIN EN.CITE <EndNote><Cite><Author>Thomas</Author><Year>2014</Year><RecNum>341</RecNum><DisplayText>(13)</DisplayText><record><rec-number>341</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">341</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thomas, G.</author><author>Mancini, J.</author><author>Jourde-Chiche, N.</author><author>Sarlon, G.</author><author>Amoura, Z.</author><author>Harle, J. R.</author><author>Jougla, E.</author><author>Chiche, L.</author></authors></contributors><auth-address>Hopital de la Conception, AP-HM, and Universite Aix-Marseille, Marseille, France.</auth-address><titles><title>Mortality associated with systemic lupus erythematosus in France assessed by multiple-cause-of-death analysis</title><secondary-title>Arthritis & rheumatology (Hoboken, N.J.)</secondary-title><alt-title>Arthritis Rheumatol</alt-title></titles><periodical><full-title>Arthritis & rheumatology (Hoboken, N.J.)</full-title><abbr-1>Arthritis Rheumatol</abbr-1></periodical><alt-periodical><full-title>Arthritis & rheumatology (Hoboken, N.J.)</full-title><abbr-1>Arthritis Rheumatol</abbr-1></alt-periodical><pages>2503-11</pages><volume>66</volume><number>9</number><dates><year>2014</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>2326-5205 (Electronic)</isbn><accession-num>24910304</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(13). The mean (SD) age at death of the SLE patients was 63.5 (18.4) years. The age-standardised mortality rate fell from 4.1 per million in 2000 to 3.0 per million in 2009. Amongst patients in whom SLE was listed as the underlying cause of death, 49.5% had CVD listed as another main cause. In patients in whom SLE was listed as a non-underlying cause of death, CVD was listed as the underlying cause of death more frequently than in the general population (relative risk (RR) 1.58; 95%CI 1.42-1.76). Myocardial infarction in patients with SLE (Level B)Patients with SLE have an increased risk of MI compared to the general population PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW56aTwvQXV0aG9yPjxZZWFyPjE5OTc8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (3, 14). Using health administrative databases from Canada between 1990-2007, Avina-Zubieta et al found that the overall multivariable RR for MI in patients with physician-diagnosed SLE, compared with age and sex matched controls, was 2.5 (95%CI 2.1, 3.1) ADDIN EN.CITE <EndNote><Cite><Year>2013</Year><RecNum>392</RecNum><DisplayText>(15)</DisplayText><record><rec-number>392</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">392</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors></contributors><titles><title>Abstracts of the10th International Congress on SLE. April 18-21, 2013. Buenos Aires, Argentina</title><secondary-title>Lupus</secondary-title><alt-title>Lupus</alt-title></titles><periodical><full-title>Lupus</full-title></periodical><alt-periodical><full-title>Lupus</full-title></alt-periodical><pages>1-196</pages><volume>22 Suppl 1</volume><dates><year>2013</year></dates><isbn>1477-0962 (Electronic)
0961-2033 (Linking)</isbn><accession-num>23462274</accession-num><work-type>Congresses
Overall</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(15). The subsequent incidence of MI in 1207 patients with SLE from Taiwan, was 2.10 per 1000 person-years (pyrs) compared with 0.49 in age-and sex- matched controls, adjusted hazard ratio (HR) 5.11 (95% CI 2.63, 9.92) ADDIN EN.CITE <EndNote><Cite><Author>Lin</Author><Year>2014</Year><RecNum>336</RecNum><DisplayText>(16)</DisplayText><record><rec-number>336</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">336</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lin, C. Y.</author><author>Shih, C. C.</author><author>Yeh, C. C.</author><author>Chou, W. H.</author><author>Chen, T. L.</author><author>Liao, C. C.</author></authors></contributors><titles><title>Increased risk of acute myocardial infarction and mortality in patients with systemic lupus erythematosus: two nationwide retrospective cohort studies</title><secondary-title>Int J Cardiol</secondary-title></titles><periodical><full-title>Int J Cardiol</full-title><abbr-1>International journal of cardiology</abbr-1></periodical><pages>847-51</pages><volume>176</volume><number>3</number><dates><year>2014</year></dates><isbn>1874-1754 (Electronic)
0167-5273 (Linking)</isbn><work-type>Research Support, Non-U S Gov't</work-type><urls></urls></record></Cite></EndNote>(16). Patients with SLE have a higher prevalence of CVD even before diagnosis. The prior incidence of CVD was higher in 70 incident cases of SLE identified from The Marshfield Epidemiologic Study Area in Wisconsin, USA than in matched controls (23% vs 10%); OR 3.7 (1.8, 7.9) ADDIN EN.CITE <EndNote><Cite><Author>Bartels</Author><Year>2014</Year><RecNum>330</RecNum><DisplayText>(17)</DisplayText><record><rec-number>330</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">330</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bartels, C. M.</author><author>Buhr, K. A.</author><author>Goldberg, J. W.</author><author>Bell, C. L.</author><author>Visekruna, M.</author><author>Nekkanti, S.</author><author>Greenlee, R. T.</author></authors></contributors><titles><title>Mortality and cardiovascular burden of systemic lupus erythematosus in a US population-based cohort</title><secondary-title>J Rheumatol</secondary-title></titles><periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></periodical><pages>680-7</pages><volume>41</volume><number>4</number><dates><year>2014</year></dates><isbn>0315-162X (Print)
0315-162X (Linking)</isbn><work-type>Comparative Study
Research Support, N I H , Extramural
Research Support, Non-U S Gov't</work-type><urls></urls></record></Cite></EndNote>(17). A study from the US National Heart, Lung and Blood Institute Dynamic Registry of patients undergoing percutaneous coronary interventions (PCI) found no significant differences in the mean percent of coronary artery stenosis and total occlusion in SLE vs non-SLE subjects ADDIN EN.CITE <EndNote><Cite><Author>Maksimowicz-McKinnon</Author><Year>2008</Year><RecNum>395</RecNum><DisplayText>(18)</DisplayText><record><rec-number>395</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">395</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Maksimowicz-McKinnon, K.</author><author>Selzer, F.</author><author>Manzi, S.</author><author>Kip, K. E.</author><author>Mulukutla, S. R.</author><author>Marroquin, O. C.</author><author>Smitherman, T. C.</author><author>Kuller, L. H.</author><author>Williams, D. O.</author><author>Wasko, M. C.</author></authors></contributors><titles><title>Poor 1-year outcomes after percutaneous coronary interventions in systemic lupus erythematosus: report from the National Heart, Lung, and Blood Institute Dynamic Registry</title><secondary-title>Circ Cardiovasc Interv</secondary-title></titles><periodical><full-title>Circ Cardiovasc Interv</full-title></periodical><pages>201-8</pages><volume>1</volume><number>3</number><dates><year>2008</year></dates><isbn>1941-7632 (Electronic)
1941-7640 (Linking)</isbn><work-type>Multicenter Study
Research Support, N I H , Extramural</work-type><urls></urls></record></Cite></EndNote>(18). However, SLE patients had significantly worse CV outcomes at one year following PCI including a higher risk of MI (15.6% vs. 4.8%, p=0.01), and repeat PCI (31.3% vs. 11.8%, p=0.009). A retrospective cohort study from Taiwan found that SLE was an independent predictor of inpatient mortality after PCI, OR 3.81 (95% CI 2.02, 7.16) ADDIN EN.CITE <EndNote><Cite><Author>Lai</Author><Year>2015</Year><RecNum>340</RecNum><DisplayText>(19)</DisplayText><record><rec-number>340</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">340</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lai, C. H.</author><author>Lai, W. W.</author><author>Chiou, M. J.</author><author>Lin, W. C.</author><author>Yang, Y. J.</author><author>Li, C. Y.</author><author>Tsai, L. M.</author></authors></contributors><auth-address>Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.</auth-address><titles><title>Outcomes of percutaneous coronary intervention in patients with rheumatoid arthritis and systemic lupus erythematosus: an 11-year nationwide cohort study</title><secondary-title>Ann Rheum Dis</secondary-title><alt-title>Ann Rheum Dis</alt-title></titles><periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></periodical><alt-periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></alt-periodical><dates><year>2015</year><pub-dates><date>Aug 18</date></pub-dates></dates><isbn>1468-2060 (Electronic)
0003-4967 (Linking)</isbn><accession-num>26286017</accession-num><work-type>Journal article</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>Eng</language></record></Cite></EndNote>(19).Congestive Heart Failure in patients with SLE (Level B)The risk of hospitalization for congestive heart failure (CHF) in SLE appears to be substantially increased ADDIN REFMGR.CITE <Refman><Cite><Author>Ward</Author><Year>1999</Year><RecNum>63</RecNum><IDText>Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>63</Ref_ID><Title_Primary>Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus</Title_Primary><Authors_Primary>Ward,M.M.</Authors_Primary><Date_Primary>1999</Date_Primary><Keywords>Adolescent Adult Aged California</Keywords><Keywords>epidemiology Cerebrovascular Disorders</Keywords><Keywords>complications</Keywords><Keywords>*epidemiology Female Heart Failure</Keywords><Keywords>complications</Keywords><Keywords>*epidemiology Hospitalization</Keywords><Keywords>statistics & numerical data Humans Lupus Erythematosus,Systemic</Keywords><Keywords>complications</Keywords><Keywords>*epidemiolo</Keywords><Reprint>Not in File</Reprint><Start_Page>338</Start_Page><End_Page>346</End_Page><Periodical>Arthritis and Rheumatism</Periodical><Volume>42</Volume><Issue>2</Issue><ISSN_ISBN>0004-3591 (Print) 0004-3591 (Linking)</ISSN_ISBN><Address>Veterans Affairs Palo Alto Health Care System, California 94305, USA</Address><Web_URL> name="System">Arthritis Rheum</f></ZZ_JournalFull><ZZ_JournalStdAbbrev><f name="System">Arthritis and Rheumatism</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Ward</Author><Year>2004</Year><RecNum>75</RecNum><IDText>Outcomes of hospitalizations for myocardial infarctions and cerebrovascular accidents in patients with systemic lupus erythematosus</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>75</Ref_ID><Title_Primary>Outcomes of hospitalizations for myocardial infarctions and cerebrovascular accidents in patients with systemic lupus erythematosus</Title_Primary><Authors_Primary>Ward,M.M.</Authors_Primary><Date_Primary>2004</Date_Primary><Keywords>Aged Coronary Artery Bypass Female Heart Failure</Keywords><Keywords>etiology *Hospitalization Humans Length of Stay Lupus Erythematosus,Systemic</Keywords><Keywords>*complications Male Middle Aged Myocardial Infarction</Keywords><Keywords>complications</Keywords><Keywords>mortality</Keywords><Keywords>surgery</Keywords><Keywords>*therapy Outcome Assessment (Health Care)</Keywords><Reprint>Not in File</Reprint><Start_Page>3170</Start_Page><End_Page>3176</End_Page><Periodical>Arthritis and Rheumatism</Periodical><Volume>50</Volume><Issue>10</Issue><ISSN_ISBN>0004-3591 (Print) 0004-3591 (Linking)</ISSN_ISBN><Address>National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA20892-1828. wardm1@mail.</Address><Web_URL> name="System">Arthritis Rheum</f></ZZ_JournalFull><ZZ_JournalStdAbbrev><f name="System">Arthritis and Rheumatism</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite><Cite><Author>Shah</Author><Year>2009</Year><RecNum>73</RecNum><IDText>Poor outcomes after acute myocardial infarction in systemic lupus erythematosus</IDText><MDL Ref_Type="Journal"><Ref_Type>Journal</Ref_Type><Ref_ID>73</Ref_ID><Title_Primary>Poor outcomes after acute myocardial infarction in systemic lupus erythematosus</Title_Primary><Authors_Primary>Shah,M.A.</Authors_Primary><Authors_Primary>Shah,A.M.</Authors_Primary><Authors_Primary>Krishnan,E.</Authors_Primary><Date_Primary>2009</Date_Primary><Keywords>Adult African Americans Aged Case-Control Studies Diabetes Mellitus</Keywords><Keywords>mortality European Continental Ancestry Group Female Hispanic Americans Hospital Mortality Humans Length of Stay Lupus Erythematosus,Systemic</Keywords><Keywords>*complications</Keywords><Keywords>ethnology</Keywords><Keywords>mortality Male Midd</Keywords><Reprint>Not in File</Reprint><Start_Page>570</Start_Page><End_Page>575</End_Page><Periodical>The Journal of rheumatology</Periodical><Volume>36</Volume><Issue>3</Issue><ISSN_ISBN>0315-162X (Print) 0315-162X (Linking)</ISSN_ISBN><Address>Department of Internal Medicine, University of Kentucky, Lexington, Kentucky, USA</Address><Web_URL> name="System">J Rheumatol</f></ZZ_JournalFull><ZZ_JournalStdAbbrev><f name="System">The Journal of rheumatology</f></ZZ_JournalStdAbbrev><ZZ_WorkformID>1</ZZ_WorkformID></MDL></Cite></Refman>. Using the California Hospital Discharge Database, Ward found that the proportionate morbidity ratio for CHF in women with SLE compared to women without SLE was 3.22 (95%CI 2.55, 4.05) in those aged 18-44 years; 1.34 (95%CI 1.14, 1.56) in those aged 45-64 years; and 1.30 (95% 1.16, 1.45) in those aged 65 years and over ADDIN EN.CITE <EndNote><Cite><Author>Ward</Author><Year>1999</Year><RecNum>322</RecNum><DisplayText>(20)</DisplayText><record><rec-number>322</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">322</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ward, M. M.</author></authors></contributors><titles><title>Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus</title><secondary-title>Arthritis Rheum</secondary-title></titles><periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></periodical><pages>338-46</pages><volume>42</volume><number>2</number><dates><year>1999</year></dates><isbn>0004-3591 (Print)
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ADDIN EN.CITE.DATA (22).Stroke in patients with SLE (Level B) In a recent meta-analysis of 10 population-based cohort studies the pooled RR in patients with SLE for all types of stroke combined was 2.53 (95%CI 1.96, 3.26) ADDIN EN.CITE <EndNote><Cite><Author>Holmqvist</Author><Year>2015</Year><RecNum>400</RecNum><DisplayText>(23)</DisplayText><record><rec-number>400</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">400</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Holmqvist, M.</author><author>Simard, J. F.</author><author>Asplund, K.</author><author>Arkema, E. V.</author></authors></contributors><auth-address>Clinical Epidemiology Unit, Department of Medicine Solna , Karolinska Institute , Stockholm , Sweden.
Clinical Epidemiology Unit, Department of Medicine Solna , Karolinska Institute , Stockholm , Sweden ; Division of Epidemiology, Department of Health Research & Policy , Stanford School of Medicine , Stanford, California , USA.
Department of Public Health and Clinical Medicine , Umea University , Umea , Sweden.</auth-address><titles><title>Stroke in systemic lupus erythematosus: a meta-analysis of population-based cohort studies</title><secondary-title>RMD open</secondary-title><alt-title>RMD Open</alt-title></titles><periodical><full-title>RMD open</full-title><abbr-1>RMD Open</abbr-1></periodical><alt-periodical><full-title>RMD open</full-title><abbr-1>RMD Open</abbr-1></alt-periodical><pages>e000168</pages><volume>1</volume><number>1</number><dates><year>2015</year></dates><isbn>2056-5933 (Electronic)
2056-5933 (Linking)</isbn><accession-num>26719816</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(23). The risks of ischaemic stroke (RR 2.10; 95%CI 1.68, 2.62), intracerebral haemorrhage (RR 2.72; 95%CI 2.15, 3.44) and subarachnoid haemorrhage (RR 3.85; 95%CI 3.20, 4.64) were all increased. The RR for stroke was highest in adults aged less than 50 years.Peripheral arterial disease in patients with SLE (Level B)Peripheral arterial disease (PAD) is more common in SLE than the general population PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CdXJnb3M8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (24, 25). A study from the National Health Insurance Research Database of Taiwan of over 10,000 SLE patients reported a 9-fold higher incidence of PAD compared with non-SLE patients ADDIN EN.CITE <EndNote><Cite><Author>Chuang</Author><Year>2015</Year><RecNum>405</RecNum><DisplayText>(26)</DisplayText><record><rec-number>405</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">405</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chuang, Y. W.</author><author>Yu, M. C.</author><author>Lin, C. L.</author><author>Yu, T. M.</author><author>Shu, K. H.</author><author>Kao, C. H.</author></authors></contributors><auth-address>From the Division of Nephrology, Taichung Veterans General Hospital, Taichung (Y-WC, T-MY, K-HS); Department of Pediatric Nephrology, Chang Gung Children's Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan (M-CY); Management Office for Health Data, China Medical University Hospital (C-LL); College of Medicine, China Medical University, Taichung (C-LL); Graduate Institute of Clinical Medicine Science, School of Medicine (T-MY); Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University (C-HK); and Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan (C-HK).</auth-address><titles><title>Risk of Peripheral Arterial Occlusive Disease in Patients With Systemic Lupus Erythematosus: A Nationwide Population-Based Cohort Study</title><secondary-title>Medicine (Baltimore)</secondary-title><alt-title>Medicine (Baltimore)</alt-title></titles><periodical><full-title>Medicine (Baltimore)</full-title><abbr-1>Medicine</abbr-1></periodical><alt-periodical><full-title>Medicine (Baltimore)</full-title><abbr-1>Medicine</abbr-1></alt-periodical><pages>e2121</pages><volume>94</volume><number>46</number><dates><year>2015</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1536-5964 (Electronic)
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ADDIN EN.CITE.DATA (27). Plaque and IMT measurement on carotid ultrasound in SLE can independently predict CVEs ADDIN EN.CITE <EndNote><Cite><Author>Kao</Author><Year>2013</Year><RecNum>423</RecNum><DisplayText>(28)</DisplayText><record><rec-number>423</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">423</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kao, A. H.</author><author>Lertratanakul, A.</author><author>Elliott, J. R.</author><author>Sattar, A.</author><author>Santelices, L.</author><author>Shaw, P.</author><author>Birru, M.</author><author>Avram, Z.</author><author>Thompson, T.</author><author>Sutton-Tyrrell, K.</author><author>Ramsey-Goldman, R.</author><author>Manzi, S.</author></authors></contributors><auth-address>Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania. Electronic address: akao@.</auth-address><titles><title>Relation of carotid intima-media thickness and plaque with incident cardiovascular events in women with systemic lupus erythematosus</title><secondary-title>Am J Cardiol</secondary-title><alt-title>Am J Cardiol</alt-title></titles><periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></periodical><alt-periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></alt-periodical><pages>1025-32</pages><volume>112</volume><number>7</number><dates><year>2013</year><pub-dates><date>Oct 1</date></pub-dates></dates><isbn>1879-1913 (Electronic)
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ADDIN EN.CITE.DATA (29). The following section summarises the results of this systematic review.Traditional risk factors for CVD in patients with SLE (Level C)Classic TRFs include increasing age, male gender, smoking status, diabetes, hypertension and dyslipidaemia. A number of these factors are more common in patients with SLE including hypertension and diabetes, but not smoking or hypercholesterolaemia ADDIN EN.CITE <EndNote><Cite><Author>Bruce</Author><Year>2003</Year><RecNum>448</RecNum><DisplayText>(30)</DisplayText><record><rec-number>448</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">448</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bruce, I. N.</author><author>Urowitz, M. B.</author><author>Gladman, D. D.</author><author>Ibanez, D.</author><author>Steiner, G.</author></authors></contributors><auth-address>University of Toronto Lupus Clinic, and Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada.</auth-address><titles><title>Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study</title><secondary-title>Arthritis Rheum</secondary-title><alt-title>Arthritis Rheum</alt-title></titles><periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></alt-periodical><pages>3159-67</pages><volume>48</volume><number>11</number><dates><year>2003</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0004-3591 (Print)
0004-3591 (Linking)</isbn><accession-num>14613278</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(30). More recently described TRFs in the general population include a positive family history of CVD, high levels of high sensitivity C-reactive protein (hs-CRP), ethnicity, low levels of physical activity, obesity and the metabolic syndrome (MetS). MetS is a clustering of CV risk factors including abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein (HDL) levels. There is a higher prevalence of MetS in patients with SLE compared with matched controls ADDIN EN.CITE <EndNote><Cite><Author>Parker</Author><Year>2010</Year><RecNum>346</RecNum><DisplayText>(31)</DisplayText><record><rec-number>346</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">346</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Parker, B.</author><author>Bruce, I. N.</author></authors></contributors><auth-address>ARC Epidemiology Unit, Manchester Academic Health Sciences Centre, The University of Manchester Stopford Building, Oxford Road, Manchester M13 9PT, UK.</auth-address><titles><title>The metabolic syndrome in systemic lupus erythematosus</title><secondary-title>Rheum Dis Clin North Am</secondary-title><alt-title>Rheum Dis Clin North Am</alt-title></titles><periodical><full-title>Rheum Dis Clin North Am</full-title><abbr-1>Rheumatic diseases clinics of North America</abbr-1></periodical><alt-periodical><full-title>Rheum Dis Clin North Am</full-title><abbr-1>Rheumatic diseases clinics of North America</abbr-1></alt-periodical><pages>81-97, viii</pages><volume>36</volume><number>1</number><dates><year>2010</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1558-3163 (Electronic)
0889-857X (Linking)</isbn><accession-num>20202592</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(31). There is evidence that SLE-related factors including active disease, damage and renal involvement are independently associated with MetS and that MetS is prevalent early in the course of the disease PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYXJrZXI8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (29). Smoking has been shown to be associated with CVEs, carotid plaque and CAC in SLE. Total cholesterol has been shown to be an independent risk factor for CVEs and subclinical atherosclerosis. Although not an independent risk factor for CVE or CAC, high LDL levels were an independent predictor of increased cIMT and plaque formation ADDIN EN.CITE <EndNote><Cite><Author>Tselios</Author><Year>2014</Year><RecNum>442</RecNum><DisplayText>(33)</DisplayText><record><rec-number>442</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">442</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tselios, K.</author><author>Koumaras, C.</author><author>Urowitz, M. B.</author><author>Gladman, D. D.</author></authors></contributors><auth-address>Second Department of Internal Medicine, 424 General Military Hospital of Thessaloniki, Thessaloniki, Greece.
Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8. Electronic address: m.urowitz@utoronto.ca.
Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8.</auth-address><titles><title>Do current arterial hypertension treatment guidelines apply to systemic lupus erythematosus patients? a critical appraisal</title><secondary-title>Semin Arthritis Rheum</secondary-title><alt-title>Semin Arthritis Rheum</alt-title></titles><periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></alt-periodical><pages>521-5</pages><volume>43</volume><number>4</number><dates><year>2014</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1532-866X (Electronic)
0049-0172 (Linking)</isbn><accession-num>23953498</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(33). MetS is associated with increased cIMT, CAC and arterial stiffness.Disease specific risk factors for CVD in patients with SLE (level C)TRFs alone do not fully explain the increased risk of CVD seen in patients with SLE ADDIN EN.CITE <EndNote><Cite><Author>Esdaile</Author><Year>2001</Year><RecNum>345</RecNum><DisplayText>(34)</DisplayText><record><rec-number>345</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">345</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Esdaile, J. M.</author><author>Abrahamowicz, M.</author><author>Grodzicky, T.</author><author>Li, Y.</author><author>Panaritis, C.</author><author>du Berger, R.</author><author>Cote, R.</author><author>Grover, S. A.</author><author>Fortin, P. R.</author><author>Clarke, A. E.</author><author>Senecal, J. L.</author></authors></contributors><auth-address>University of British Columbia, Vancouver, Canada. jesdaile@bc.arthritis.ca</auth-address><titles><title>Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus</title><secondary-title>Arthritis Rheum</secondary-title><alt-title>Arthritis Rheum</alt-title></titles><periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></alt-periodical><pages>2331-7</pages><volume>44</volume><number>10</number><dates><year>2001</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0004-3591 (Print)
0004-3591 (Linking)</isbn><accession-num>11665973</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(34) either as a group or individually. What is more, in a study from the Toronto clinic, lupus patients with CVEs had more TRFs than those without events but they did not have a higher Framingham risk score ADDIN EN.CITE <EndNote><Cite><Author>Urowitz</Author><Year>2007</Year><RecNum>492</RecNum><DisplayText>(35)</DisplayText><record><rec-number>492</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">492</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Urowitz, M. B.</author><author>Ibanez, D.</author><author>Gladman, D. D.</author></authors></contributors><titles><title>Atherosclerotic vascular events in a single large lupus cohort: prevalence and risk factors</title><secondary-title>J Rheumatol</secondary-title></titles><periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></periodical><pages>70-5</pages><volume>34</volume><number>1</number><dates><year>2007</year></dates><isbn>0315-162X (Print)
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ADDIN EN.CITE.DATA (29, 36-38). Antiphospholipid syndrome (APS) frequently co-exists with SLE ADDIN EN.CITE <EndNote><Cite><Author>Rojas-Villarraga</Author><Year>2010</Year><RecNum>504</RecNum><DisplayText>(39)</DisplayText><record><rec-number>504</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">504</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rojas-Villarraga, A.</author><author>Toro, C. E.</author><author>Espinosa, G.</author><author>Rodriguez-Velosa, Y.</author><author>Duarte-Rey, C.</author><author>Mantilla, R. D.</author><author>Iglesias-Gamarra, A.</author><author>Cervera, R.</author><author>Anaya, J. M.</author></authors></contributors><auth-address>Center for Autoimmune Diseases Research (CREA), School of Medicine, Rosario University, Bogota, Colombia.</auth-address><titles><title>Factors influencing polyautoimmunity in systemic lupus erythematosus</title><secondary-title>Autoimmunity reviews</secondary-title><alt-title>Autoimmun Rev</alt-title></titles><periodical><full-title>Autoimmunity reviews</full-title><abbr-1>Autoimmun Rev</abbr-1></periodical><alt-periodical><full-title>Autoimmunity reviews</full-title><abbr-1>Autoimmun Rev</abbr-1></alt-periodical><pages>229-32</pages><volume>9</volume><number>4</number><dates><year>2010</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1873-0183 (Electronic)
1568-9972 (Linking)</isbn><accession-num>19819350</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(39). Patients who have a diagnosis of both SLE and APS represent a more severe disease phenotype with higher risk of CVD ADDIN EN.CITE <EndNote><Cite><Author>Franco</Author><Year>2014</Year><RecNum>506</RecNum><DisplayText>(40)</DisplayText><record><rec-number>506</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">506</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Franco, J. S.</author><author>Molano-Gonzalez, N.</author><author>Rodriguez-Jimenez, M.</author><author>Acosta-Ampudia, Y.</author><author>Mantilla, R. D.</author><author>Amaya-Amaya, J.</author><author>Rojas-Villarraga, A.</author><author>Anaya, J. M.</author></authors></contributors><auth-address>Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia; Mederi, Hospital Universitario Mayor, Bogota, Colombia.
Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia.</auth-address><titles><title>The coexistence of antiphospholipid syndrome and systemic lupus erythematosus in Colombians</title><secondary-title>PLoS One</secondary-title><alt-title>PLoS One</alt-title></titles><periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></periodical><alt-periodical><full-title>PLoS One</full-title><abbr-1>PloS one</abbr-1></alt-periodical><pages>e110242</pages><volume>9</volume><number>10</number><dates><year>2014</year></dates><isbn>1932-6203 (Electronic)
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ADDIN EN.CITE.DATA (41). Current steroid use, independent of disease activity, also predicts CVE ADDIN EN.CITE <EndNote><Cite><Author>Magder</Author><Year>2012</Year><RecNum>413</RecNum><DisplayText>(38)</DisplayText><record><rec-number>413</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">413</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Magder, L. S.</author><author>Petri, M.</author></authors></contributors><auth-address>Department of Epidemiology and Public Health, University of Maryland, Baltimore, MD 21201-1596, USA. lmagder@epi.umaryland.edu</auth-address><titles><title>Incidence of and risk factors for adverse cardiovascular events among patients with systemic lupus erythematosus</title><secondary-title>Am J Epidemiol</secondary-title><alt-title>Am J Epidemiol</alt-title></titles><periodical><full-title>Am J Epidemiol</full-title><abbr-1>American journal of epidemiology</abbr-1></periodical><alt-periodical><full-title>Am J Epidemiol</full-title><abbr-1>American journal of epidemiology</abbr-1></alt-periodical><pages>708-19</pages><volume>176</volume><number>8</number><dates><year>2012</year><pub-dates><date>Oct 15</date></pub-dates></dates><isbn>1476-6256 (Electronic)
0002-9262 (Linking)</isbn><accession-num>23024137</accession-num><work-type>Research Support, N.I.H., Extramural</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(38).The protective role of hydroxychloroquine has been demonstrated in a number of studies. In a Chinese SLE cohort, lack of use of hydroxychloroquine was an independent risk factor for CVD ADDIN EN.CITE <EndNote><Cite><Author>Yang</Author><Year>2012</Year><RecNum>509</RecNum><DisplayText>(42)</DisplayText><record><rec-number>509</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">509</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Yang, L.</author><author>Tao, J.</author><author>Tang, X.</author><author>Wang, Y.</author><author>He, X.</author><author>Xu, G.</author><author>Ren, Y.</author><author>Tu, Y.</author></authors></contributors><auth-address>Department of Dermatology, Tongji Medical College, Affiliated Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.</auth-address><titles><title>Prevalence and correlation of conventional and lupus-specific risk factors for cardiovascular disease in Chinese systemic lupus erythematosus patients</title><secondary-title>Journal of the European Academy of Dermatology and Venereology : JEADV</secondary-title><alt-title>J Eur Acad Dermatol Venereol</alt-title></titles><periodical><full-title>Journal of the European Academy of Dermatology and Venereology : JEADV</full-title><abbr-1>J Eur Acad Dermatol Venereol</abbr-1></periodical><alt-periodical><full-title>Journal of the European Academy of Dermatology and Venereology : JEADV</full-title><abbr-1>J Eur Acad Dermatol Venereol</abbr-1></alt-periodical><pages>95-101</pages><volume>26</volume><number>1</number><dates><year>2012</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1468-3083 (Electronic)
0926-9959 (Linking)</isbn><accession-num>21851424</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(42). In a prospective study in the Toronto lupus cohort, patients who developed coronary artery disease (CAD) were significantly less likely to have been treated with hydroxychloroquine than those who did not develop CAD ADDIN EN.CITE <EndNote><Cite><Author>Nikpour</Author><Year>2011</Year><RecNum>428</RecNum><DisplayText>(43)</DisplayText><record><rec-number>428</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">428</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Nikpour, M.</author><author>Urowitz, M. B.</author><author>Ibanez, D.</author><author>Harvey, P. J.</author><author>Gladman, D. D.</author></authors></contributors><auth-address>University of Toronto Lupus Clinic and the Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.</auth-address><titles><title>Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a prospective proof-of-concept cohort study</title><secondary-title>Arthritis Res Ther</secondary-title><alt-title>Arthritis Res Ther</alt-title></titles><periodical><full-title>Arthritis Res Ther</full-title><abbr-1>Arthritis research & therapy</abbr-1></periodical><alt-periodical><full-title>Arthritis Res Ther</full-title><abbr-1>Arthritis research & therapy</abbr-1></alt-periodical><pages>R156</pages><volume>13</volume><number>5</number><dates><year>2011</year></dates><isbn>1478-6362 (Electronic)
1478-6354 (Linking)</isbn><accession-num>21955652</accession-num><work-type>Comparative Study
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(43).Cardiovascular disease in patients with systemic sclerosis (Level A)Systemic sclerosis (SSc) is an autoimmune CTD characterised by multiorgan fibrosis, vasculopathy triggered by endothelial injury, and autoantibody production. Inflammation plays a less prominent role in SSc than in SLE. SSc may directly affect the heart leading to myocardial fibrosis, conduction defects, left ventricular systolic and diastolic dysfunction and pericardial disease ADDIN EN.CITE <EndNote><Cite><Author>Meune</Author><Year>2010</Year><RecNum>366</RecNum><DisplayText>(44)</DisplayText><record><rec-number>366</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">366</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Meune, C.</author><author>Vignaux, O.</author><author>Kahan, A.</author><author>Allanore, Y.</author></authors></contributors><auth-address>Service de cardiologie, hopital Cochin, AP-HP, universite Paris Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France. christophe.meune@cch.aphp.fr</auth-address><titles><title>Heart involvement in systemic sclerosis: evolving concept and diagnostic methodologies</title><secondary-title>Archives of cardiovascular diseases</secondary-title><alt-title>Arch Cardiovasc Dis</alt-title></titles><periodical><full-title>Archives of cardiovascular diseases</full-title><abbr-1>Arch Cardiovasc Dis</abbr-1></periodical><alt-periodical><full-title>Archives of cardiovascular diseases</full-title><abbr-1>Arch Cardiovasc Dis</abbr-1></alt-periodical><pages>46-52</pages><volume>103</volume><number>1</number><dates><year>2010</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1875-2128 (Electronic)
1875-2128 (Linking)</isbn><accession-num>20142120</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(44). Heart disease may also occur secondary to pulmonary hypertension in SSc. Although microvascular disease is the hallmark of SSc, there is growing evidence that macrovascular damage, resulting in ACVD is contributing to excess morbidity and mortality ADDIN EN.CITE <EndNote><Cite><Author>Cannarile</Author><Year>2015</Year><RecNum>368</RecNum><DisplayText>(45)</DisplayText><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cannarile, F.</author><author>Valentini, V.</author><author>Mirabelli, G.</author><author>Alunno, A.</author><author>Terenzi, R.</author><author>Luccioli, F.</author><author>Gerli, R.</author><author>Bartoloni, E.</author></authors></contributors><auth-address>Department of Medicine, Rheumatology Unit, University of Perugia, Via dal Pozzo 06132, Perugia, Italy.</auth-address><titles><title>Cardiovascular disease in systemic sclerosis</title><secondary-title>Annals of translational medicine</secondary-title><alt-title>Ann Transl Med</alt-title></titles><periodical><full-title>Annals of translational medicine</full-title><abbr-1>Ann Transl Med</abbr-1></periodical><alt-periodical><full-title>Annals of translational medicine</full-title><abbr-1>Ann Transl Med</abbr-1></alt-periodical><pages>8</pages><volume>3</volume><number>1</number><dates><year>2015</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>2305-5839 (Print)
2305-5839 (Linking)</isbn><accession-num>25705640</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(45).Cardiovascular mortality in patients with SSc (Level B)A meta-analysis including 9239 SSc patients from 17 studies published prior to 2005 reported an all-cause meta-SMR of 2.72 (95%CI 1.93, 3.83) ADDIN EN.CITE <EndNote><Cite><Author>Rubio-Rivas</Author><Year>2014</Year><RecNum>407</RecNum><DisplayText>(46)</DisplayText><record><rec-number>407</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">407</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rubio-Rivas, M.</author><author>Royo, C.</author><author>Simeon, C. P.</author><author>Corbella, X.</author><author>Fonollosa, V.</author></authors></contributors><auth-address>Autoimmune Diseases Unit, Bellvitge University Hospital, Barcelona, Spain. Electronic address: mrubio@bellvitgehospital.cat.
Autoimmune Diseases Unit, Bellvitge University Hospital, Barcelona, Spain.
Vall d'Hebron University Hospital, Barcelona, Spain.</auth-address><titles><title>Mortality and survival in systemic sclerosis: systematic review and meta-analysis</title><secondary-title>Semin Arthritis Rheum</secondary-title><alt-title>Semin Arthritis Rheum</alt-title></titles><periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></alt-periodical><pages>208-19</pages><volume>44</volume><number>2</number><dates><year>2014</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1532-866X (Electronic)
0049-0172 (Linking)</isbn><accession-num>24931517</accession-num><work-type>Meta-Analysis
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ADDIN EN.CITE.DATA (47).There is evidence of a higher case fatality for MI but not for stroke in patients with SSc compared with patients without CTD. Using the US Nationwide Inpatient Survey, Dave et al found that 5.5% of 61,734 admissions in patients with SSc were for a CVD diagnosis or procedure compared with 4.9% of SLE admissions, 7.1% of RA admissions and 6.7% of control admissions. Patients with SSc and MI were more likely to die during that admission than patients with SLE and MI, patients with RA and MI, or controls with MI ADDIN EN.CITE <EndNote><Cite><Author>Dave</Author><Year>2014</Year><RecNum>412</RecNum><DisplayText>(48)</DisplayText><record><rec-number>412</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">412</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Dave, A. J.</author><author>Fiorentino, D.</author><author>Lingala, B.</author><author>Krishnan, E.</author><author>Chung, L.</author></authors></contributors><auth-address>Stanford University School of Medicine, Palo Alto, California.</auth-address><titles><title>Atherosclerotic cardiovascular disease in hospitalized patients with systemic sclerosis: higher mortality than patients with lupus and rheumatoid arthritis</title><secondary-title>Arthritis Care Res (Hoboken)</secondary-title><alt-title>Arthritis Care Res (Hoboken)</alt-title></titles><periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></periodical><alt-periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></alt-periodical><pages>323-7</pages><volume>66</volume><number>2</number><dates><year>2014</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>2151-4658 (Electronic)
2151-464X (Linking)</isbn><accession-num>24022876</accession-num><work-type>Comparative Study
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(48).Atherosclerotic CVD in patients with SSc (Level B)A number of large studies have reported an increased risk of ACVD in patients with SSc compared to the general population. A study of 850 patients with SSc from the Australian Scleroderma Cohort Study reported an odds ratio (OR) for self-reported coronary heart disease, after adjusting for TRFs, of 3.2 (95% CI: 2.3-4.5) compared with a control group from the Australian Diabetes, Obesity and Lifestyle Study and of 2.0 (95% CI: 2.3- 4.5) when compared with a cohort from the National Health Survey ADDIN EN.CITE <EndNote><Cite><Author>Ngian</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText>(49)</DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">376</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ngian, G. S.</author><author>Sahhar, J.</author><author>Proudman, S. M.</author><author>Stevens, W.</author><author>Wicks, I. P.</author><author>Van Doornum, S.</author></authors></contributors><auth-address>Department of Medicine (RMH/WH)The University of Melbourne, Grattan StParkville 3050, Victoria, Australia. gngian@student.unimelb.edu.au</auth-address><titles><title>Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis</title><secondary-title>Ann Rheum Dis</secondary-title><alt-title>Ann Rheum Dis</alt-title></titles><periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></periodical><alt-periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></alt-periodical><pages>1980-3</pages><volume>71</volume><number>12</number><dates><year>2012</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1468-2060 (Electronic)
0003-4967 (Linking)</isbn><accession-num>22532628</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(49). In a study of 865 patients with SSc identified from a UK primary care database, the HR for MI, after adjusting for TRFs and steroid use, was 1.8 (95% CI: 1.07- 3.05), for stroke was 2.61 (95%CI: 1.54-4.44) and for PAD was 4.35 (95%CI: 2.74- 6.93) compared to age and sex matched controls ADDIN EN.CITE <EndNote><Cite><Author>Man</Author><Year>2013</Year><RecNum>377</RecNum><DisplayText>(50)</DisplayText><record><rec-number>377</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">377</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Man, A.</author><author>Zhu, Y.</author><author>Zhang, Y.</author><author>Dubreuil, M.</author><author>Rho, Y. H.</author><author>Peloquin, C.</author><author>Simms, R. W.</author><author>Choi, H. K.</author></authors></contributors><auth-address>Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118, USA. adaman@bu.edu</auth-address><titles><title>The risk of cardiovascular disease in systemic sclerosis: a population-based cohort study</title><secondary-title>Ann Rheum Dis</secondary-title><alt-title>Ann Rheum Dis</alt-title></titles><periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></periodical><alt-periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></alt-periodical><pages>1188-93</pages><volume>72</volume><number>7</number><dates><year>2013</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1468-2060 (Electronic)
0003-4967 (Linking)</isbn><accession-num>22904260</accession-num><work-type>Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(50). The adjusted HR for MI between 1344 incident cases of SSc and 13440 controls from Taiwan was 2.45 (95%CI 1.60, 3.75) ADDIN EN.CITE <EndNote><Cite><Author>Chu</Author><Year>2013</Year><RecNum>494</RecNum><DisplayText>(51)</DisplayText><record><rec-number>494</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">494</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chu, S. Y.</author><author>Chen, Y. J.</author><author>Liu, C. J.</author><author>Tseng, W. C.</author><author>Lin, M. W.</author><author>Hwang, C. Y.</author><author>Chen, C. C.</author><author>Lee, D. D.</author><author>Chen, T. J.</author><author>Chang, Y. T.</author><author>Wang, W. J.</author><author>Liu, H. N.</author></authors></contributors><auth-address>Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Dermatology, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.</auth-address><titles><title>Increased risk of acute myocardial infarction in systemic sclerosis: a nationwide population-based study</title><secondary-title>The American journal of medicine</secondary-title><alt-title>Am J Med</alt-title></titles><periodical><full-title>The American journal of medicine</full-title><abbr-1>Am J Med</abbr-1></periodical><alt-periodical><full-title>The American journal of medicine</full-title><abbr-1>Am J Med</abbr-1></alt-periodical><pages>982-8</pages><volume>126</volume><number>11</number><dates><year>2013</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1555-7162 (Electronic)
0002-9343 (Linking)</isbn><accession-num>24157289</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(51). Subclinical atherosclerosis in patients with SSc (Level B)A recent systematic review and meta-analysis reported on 31 studies which had examined angiography, cIMT, carotid plaque, computed tomography or magnetic resonance imaging, flow mediated dilatation, ankle-brachial index or autopsy in patients with SSc and controls ADDIN EN.CITE <EndNote><Cite><Author>Au</Author><Year>2011</Year><RecNum>498</RecNum><DisplayText>(52)</DisplayText><record><rec-number>498</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">498</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Au, K.</author><author>Singh, M. K.</author><author>Bodukam, V.</author><author>Bae, S.</author><author>Maranian, P.</author><author>Ogawa, R.</author><author>Spiegel, B.</author><author>McMahon, M.</author><author>Hahn, B.</author><author>Khanna, D.</author></authors></contributors><auth-address>University of California, Los Angeles, CA, USA.</auth-address><titles><title>Atherosclerosis in systemic sclerosis: a systematic review and meta-analysis</title><secondary-title>Arthritis Rheum</secondary-title><alt-title>Arthritis Rheum</alt-title></titles><periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></alt-periodical><pages>2078-90</pages><volume>63</volume><number>7</number><dates><year>2011</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1529-0131 (Electronic)
0004-3591 (Linking)</isbn><accession-num>21480189</accession-num><work-type>Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(52). Compared to controls, patients with SSc had a higher prevalence of coronary atherosclerosis, peripheral vascular disease and cerebrovascular calcification. Risk factors for CVD in patients with SSc (Level B)TRFs have been less studied in SSc than in SLE. Overall there appear to be fewer differences between SSc patients and general population controls than is the case for SLE. In the study from the UK database ADDIN EN.CITE <EndNote><Cite><Author>Man</Author><Year>2013</Year><RecNum>377</RecNum><DisplayText>(50)</DisplayText><record><rec-number>377</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">377</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Man, A.</author><author>Zhu, Y.</author><author>Zhang, Y.</author><author>Dubreuil, M.</author><author>Rho, Y. H.</author><author>Peloquin, C.</author><author>Simms, R. W.</author><author>Choi, H. K.</author></authors></contributors><auth-address>Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118, USA. adaman@bu.edu</auth-address><titles><title>The risk of cardiovascular disease in systemic sclerosis: a population-based cohort study</title><secondary-title>Ann Rheum Dis</secondary-title><alt-title>Ann Rheum Dis</alt-title></titles><periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></periodical><alt-periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></alt-periodical><pages>1188-93</pages><volume>72</volume><number>7</number><dates><year>2013</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1468-2060 (Electronic)
0003-4967 (Linking)</isbn><accession-num>22904260</accession-num><work-type>Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(50), the SSc cohort had a lower frequency of overweight and obesity than matched controls, but a higher frequency of past smoking and oral corticosteroid use. The frequency of hypertension, dyslipidaemia and diabetes were similar in the SSc group and matched controls. Hypercholesterolaemia, diabetes and obesity were less prevalent in the Australian Scleroderma Cohort than in community-based controls, while past smoking was more prevalent. The prevalence of hypertension was similar ADDIN EN.CITE <EndNote><Cite><Author>Ngian</Author><Year>2012</Year><RecNum>376</RecNum><DisplayText>(49)</DisplayText><record><rec-number>376</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">376</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ngian, G. S.</author><author>Sahhar, J.</author><author>Proudman, S. M.</author><author>Stevens, W.</author><author>Wicks, I. P.</author><author>Van Doornum, S.</author></authors></contributors><auth-address>Department of Medicine (RMH/WH)The University of Melbourne, Grattan StParkville 3050, Victoria, Australia. gngian@student.unimelb.edu.au</auth-address><titles><title>Prevalence of coronary heart disease and cardiovascular risk factors in a national cross-sectional cohort study of systemic sclerosis</title><secondary-title>Ann Rheum Dis</secondary-title><alt-title>Ann Rheum Dis</alt-title></titles><periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></periodical><alt-periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></alt-periodical><pages>1980-3</pages><volume>71</volume><number>12</number><dates><year>2012</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>1468-2060 (Electronic)
0003-4967 (Linking)</isbn><accession-num>22532628</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(49). Cardiovascular disease in patients with Idiopathic Inflammatory Myopathies (Level A)Idiopathic inflammatory myopathies (IIM) such as dermatomyositis and polymyositis are rare autoimmune diseases characterized by inflammation of skeletal muscle, proximal muscle weakness and elevated muscle enzymes. IIM can directly affect the heart causing myocarditis, myocardial fibrosis and arrhythmias ADDIN EN.CITE <EndNote><Cite><Author>Gupta</Author><Year>2011</Year><RecNum>350</RecNum><DisplayText>(53)</DisplayText><record><rec-number>350</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">350</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gupta, R.</author><author>Wayangankar, S. A.</author><author>Targoff, I. N.</author><author>Hennebry, T. A.</author></authors></contributors><titles><title>Clinical cardiac involvement in idiopathic inflammatory myopathies: a systematic review</title><secondary-title>Int J Cardiol</secondary-title></titles><periodical><full-title>Int J Cardiol</full-title><abbr-1>International journal of cardiology</abbr-1></periodical><pages>261-70</pages><volume>148</volume><number>3</number><dates><year>2011</year></dates><isbn>1874-1754 (Electronic)
0167-5273 (Linking)</isbn><work-type>Review</work-type><urls></urls></record></Cite></EndNote>(53). Until recently evidence on the risk of ACVD in IIM has been scarce.The all-cause SMR was 1.75 (95%CI 1.41, 2.15) in 370 patients diagnosed with IIM since 1980 from the South Australian Myositis Database ADDIN EN.CITE <EndNote><Cite><Author>Limaye</Author><Year>2012</Year><RecNum>358</RecNum><DisplayText>(54)</DisplayText><record><rec-number>358</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">358</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Limaye, V.</author><author>Hakendorf, P.</author><author>Woodman, R. J.</author><author>Blumbergs, P.</author><author>Roberts-Thomson, P.</author></authors></contributors><titles><title>Mortality and its predominant causes in a large cohort of patients with biopsy-determined inflammatory myositis</title><secondary-title>Intern Med J</secondary-title></titles><periodical><full-title>Intern Med J</full-title></periodical><pages>191-8</pages><volume>42</volume><number>2</number><dates><year>2012</year></dates><isbn>1445-5994 (Electronic)
1444-0903 (Linking)</isbn><work-type>Comparative Study
Research Support, Non-U S Gov't</work-type><urls></urls></record></Cite></EndNote>(54). CVD accounted for 30.5% of deaths. A meta-analysis, published in 2014, identified 4 LOS that had examined CAD as an outcome in 13,201 IIM patients ADDIN EN.CITE <EndNote><Cite><Author>Ungprasert</Author><Year>2014</Year><RecNum>351</RecNum><DisplayText>(55)</DisplayText><record><rec-number>351</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">351</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ungprasert, P.</author><author>Suksaranjit, P.</author><author>Spanuchart, I.</author><author>Leeaphorn, N.</author><author>Permpalung, N.</author></authors></contributors><auth-address>Department of Medicine, Faculty of medicine Siriraj hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: P.ungprasert@.
Department of Cardiology, University of Utah School of Medicine, Salt Lake City, UT.
Department of Internal Medicine, John A. Burns School of medicine, University of Hawaii, Honolulu, HI.
Department of Internal Medicine, Bassett Medical Center, Columbia University College of Physicians and Surgeons, Cooperstown, NY.</auth-address><titles><title>Risk of coronary artery disease in patients with idiopathic inflammatory myopathies: a systematic review and meta-analysis of observational studies</title><secondary-title>Semin Arthritis Rheum</secondary-title><alt-title>Semin Arthritis Rheum</alt-title></titles><periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></alt-periodical><pages>63-7</pages><volume>44</volume><number>1</number><dates><year>2014</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1532-866X (Electronic)
0049-0172 (Linking)</isbn><accession-num>24684974</accession-num><work-type>Meta-Analysis
Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(55). There was a significantly increased risk of CAD in patients with IIM compared with controls (pooled risk ratio 2.24 (95% CI: 1.02, 4.92)). In a more recent study from Taiwan the risk of acute coronary syndrome was significantly higher in patients with IIM than in controls, adjusted hazard ratio 1.98 (95% CI: 1.17 -3.35) ADDIN EN.CITE <EndNote><Cite><Author>Lin</Author><Year>2015</Year><RecNum>363</RecNum><DisplayText>(56)</DisplayText><record><rec-number>363</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">363</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lin, Y. N.</author><author>Lin, C. L.</author><author>Chang, K. C.</author><author>Kao, C. H.</author></authors></contributors><auth-address>Division of Cardiology, Department of Internal Medicine, China Medical University Hospital , Taichung , Taiwan.</auth-address><titles><title>Increased subsequent risk of acute coronary syndrome for patients with dermatomyositis/polymyositis: a nationwide population-based retrospective cohort study</title><secondary-title>Scandinavian journal of rheumatology</secondary-title><alt-title>Scand J Rheumatol</alt-title></titles><periodical><full-title>Scandinavian journal of rheumatology</full-title><abbr-1>Scand J Rheumatol</abbr-1></periodical><alt-periodical><full-title>Scandinavian journal of rheumatology</full-title><abbr-1>Scand J Rheumatol</abbr-1></alt-periodical><pages>42-7</pages><volume>44</volume><number>1</number><dates><year>2015</year></dates><isbn>1502-7732 (Electronic)
0300-9742 (Linking)</isbn><accession-num>25205256</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(56). There is evidence of an increased risk of ischaemic stroke in patients with dermatomyositis. In a study of 907 patients with dermatomyositis from Taiwan, the adjusted HR for ischaemic stroke over the first 2 years of disease was 1.67 (95% CI: 1.19, 2.34) compared to controls ADDIN EN.CITE <EndNote><Cite><Author>Lai</Author><Year>2013</Year><RecNum>361</RecNum><DisplayText>(57)</DisplayText><record><rec-number>361</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">361</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lai, Y. T.</author><author>Dai, Y. S.</author><author>Yen, M. F.</author><author>Chen, L. S.</author><author>Chen, H. H.</author><author>Cooper, R. G.</author><author>Pan, S. L.</author></authors></contributors><auth-address>Department of Physical Medicine and Rehabilitation, Sijhih Cathay General Hospital, New Taipei, Taiwan.</auth-address><titles><title>Dermatomyositis is associated with an increased risk of cardiovascular and cerebrovascular events: a Taiwanese population-based longitudinal follow-up study</title><secondary-title>The British journal of dermatology</secondary-title><alt-title>Br J Dermatol</alt-title></titles><periodical><full-title>The British journal of dermatology</full-title><abbr-1>Br J Dermatol</abbr-1></periodical><alt-periodical><full-title>The British journal of dermatology</full-title><abbr-1>Br J Dermatol</abbr-1></alt-periodical><pages>1054-9</pages><volume>168</volume><number>5</number><dates><year>2013</year><pub-dates><date>May</date></pub-dates></dates><isbn>1365-2133 (Electronic)
0007-0963 (Linking)</isbn><accession-num>23330740</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(57). A study using a health administrative database from Quebec followed 607 patients with IIM for a mean of 4 years. The stroke rate (5.2/1000 pyrs) was similar to that reported in patients with RA ADDIN EN.CITE <EndNote><Cite><Author>Tisseverasinghe</Author><Year>2009</Year><RecNum>362</RecNum><DisplayText>(58)</DisplayText><record><rec-number>362</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">362</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tisseverasinghe, A.</author><author>Bernatsky, S.</author><author>Pineau, C. A.</author></authors></contributors><auth-address>Department of Medicine, Internal Medicine, McGill University Health Centre, Montreal, QC, Canada.</auth-address><titles><title>Arterial events in persons with dermatomyositis and polymyositis</title><secondary-title>J Rheumatol</secondary-title><alt-title>J Rheumatol</alt-title></titles><periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></periodical><alt-periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></alt-periodical><pages>1943-6</pages><volume>36</volume><number>9</number><dates><year>2009</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0315-162X (Print)
0315-162X (Linking)</isbn><accession-num>19648306</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(58). In this study, dyslipidaemia and hypertension were associated with arterial events, while immunosuppressive therapy was inversely associated. There is some evidence that TRFs are more prevalent in patients with IIM than in the general population. A cross-sectional study of 84 dermatomyositis patients identified 47% with MetS compared with 7% of healthy controls ADDIN EN.CITE <EndNote><Cite><Author>de Moraes</Author><Year>2013</Year><RecNum>354</RecNum><DisplayText>(59)</DisplayText><record><rec-number>354</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">354</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>de Moraes, M. T.</author><author>de Souza, F. H.</author><author>de Barros, T. B.</author><author>Shinjo, S. K.</author></authors></contributors><auth-address>Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.</auth-address><titles><title>Analysis of metabolic syndrome in adult dermatomyositis with a focus on cardiovascular disease</title><secondary-title>Arthritis Care Res (Hoboken)</secondary-title><alt-title>Arthritis Care Res (Hoboken)</alt-title></titles><periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></periodical><alt-periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></alt-periodical><pages>793-9</pages><volume>65</volume><number>5</number><dates><year>2013</year><pub-dates><date>May</date></pub-dates></dates><isbn>2151-4658 (Electronic)
2151-464X (Linking)</isbn><accession-num>23139205</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(59). Diabetes was also more prevalent in the dermatomyositis group. Other cross-sectional studies have found higher rates of obesity, hypertension, diabetes and dyslipidaemia in patients with IIM compared with controls PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW1heWU8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (62).Cardiovascular disease in patients with mixed connective tissue disease (Level A)Mixed connective tissue disease (MCTD) has features of several CTDs including SLE, SSc, PM and RA in association with high titre antibody to U1 ribonucleoprotein (anti-RNP). A recent systematic review of 11 studies, including 616 patients with MCTD, found that the prevalence of cardiac involvement varied from 13% to 65% depending on the methodology used. Pericarditis was the most common cardiac manifestation ADDIN EN.CITE <EndNote><Cite><Author>Ungprasert</Author><Year>2014</Year><RecNum>373</RecNum><DisplayText>(63)</DisplayText><record><rec-number>373</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">373</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ungprasert, P.</author><author>Wannarong, T.</author><author>Panichsillapakit, T.</author><author>Cheungpasitporn, W.</author><author>Thongprayoon, C.</author><author>Ahmed, S.</author><author>Raddatz, D. A.</author></authors></contributors><auth-address>Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, USA. Electronic address: Patompong.Ungprasert@.
Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY, USA.</auth-address><titles><title>Cardiac involvement in mixed connective tissue disease: a systematic review</title><secondary-title>Int J Cardiol</secondary-title><alt-title>Int J Cardiol</alt-title></titles><periodical><full-title>Int J Cardiol</full-title><abbr-1>International journal of cardiology</abbr-1></periodical><alt-periodical><full-title>Int J Cardiol</full-title><abbr-1>International journal of cardiology</abbr-1></alt-periodical><pages>326-30</pages><volume>171</volume><number>3</number><dates><year>2014</year><pub-dates><date>Feb 15</date></pub-dates></dates><isbn>1874-1754 (Electronic)
0167-5273 (Linking)</isbn><accession-num>24433611</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(63). By far the largest included study followed 280 patients for a mean of 13 years; 7.8% of the cohort died with one third of deaths attributed to CVEs ADDIN EN.CITE <EndNote><Cite><Author>Hajas</Author><Year>2013</Year><RecNum>372</RecNum><DisplayText>(64)</DisplayText><record><rec-number>372</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">372</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hajas, A.</author><author>Szodoray, P.</author><author>Nakken, B.</author><author>Gaal, J.</author><author>Zold, E.</author><author>Laczik, R.</author><author>Demeter, N.</author><author>Nagy, G.</author><author>Szekanecz, Z.</author><author>Zeher, M.</author><author>Szegedi, G.</author><author>Bodolay, E.</author></authors></contributors><auth-address>Division of Clinical Immunology, Department of Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary.</auth-address><titles><title>Clinical course, prognosis, and causes of death in mixed connective tissue disease</title><secondary-title>J Rheumatol</secondary-title><alt-title>J Rheumatol</alt-title></titles><periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></periodical><alt-periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></alt-periodical><pages>1134-42</pages><volume>40</volume><number>7</number><dates><year>2013</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0315-162X (Print)
0315-162X (Linking)</isbn><accession-num>23637328</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(64). Bodolay et al reported more endothelial dysfunction and increased cIMT in patients with MCTD compared with healthy controls ADDIN EN.CITE <EndNote><Cite><Author>Soltesz</Author><Year>2010</Year><RecNum>516</RecNum><DisplayText>(65)</DisplayText><record><rec-number>516</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">516</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Soltesz, P.</author><author>Bereczki, D.</author><author>Szodoray, P.</author><author>Magyar, M. T.</author><author>Der, H.</author><author>Csipo, I.</author><author>Hajas, A.</author><author>Paragh, G.</author><author>Szegedi, G.</author><author>Bodolay, E.</author></authors></contributors><auth-address>3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Moricz Zs, Str, 22, Debrecen 4032, Hungary. soltesz@</auth-address><titles><title>Endothelial cell markers reflecting endothelial cell dysfunction in patients with mixed connective tissue disease</title><secondary-title>Arthritis Res Ther</secondary-title><alt-title>Arthritis Res Ther</alt-title></titles><periodical><full-title>Arthritis Res Ther</full-title><abbr-1>Arthritis research & therapy</abbr-1></periodical><alt-periodical><full-title>Arthritis Res Ther</full-title><abbr-1>Arthritis research & therapy</abbr-1></alt-periodical><pages>R78</pages><volume>12</volume><number>3</number><dates><year>2010</year></dates><isbn>1478-6362 (Electronic)
1478-6354 (Linking)</isbn><accession-num>20459625</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(65).Evidence on the prevalence of TRFs in MCTD is limited. One study reported significantly higher levels of total cholesterol and triglycerides in 37 patients with MCTD compared to 30 controls ADDIN EN.CITE <EndNote><Cite><Author>Bodolay</Author><Year>2008</Year><RecNum>515</RecNum><DisplayText>(66)</DisplayText><record><rec-number>515</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">515</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bodolay, E.</author><author>Seres, I.</author><author>Szodoray, P.</author><author>Csipo, I.</author><author>Jakab, Z.</author><author>Vegh, J.</author><author>Szilagyi, A.</author><author>Szegedi, G.</author><author>Paragh, G.</author></authors></contributors><auth-address>Division of Clinical Immunology, 3rd Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. bodolai@iiibel.dote.hu</auth-address><titles><title>Evaluation of paraoxonase activity in patients with mixed connective tissue disease</title><secondary-title>J Rheumatol</secondary-title><alt-title>J Rheumatol</alt-title></titles><periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></periodical><alt-periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></alt-periodical><pages>237-43</pages><volume>35</volume><number>2</number><dates><year>2008</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>0315-162X (Print)
0315-162X (Linking)</isbn><accession-num>18085736</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(66). A large proportion of the MCTD group were taking corticosteroids. Cardiovascular disease in patients with primary Sjogren’s syndrome (Level A)Primary Sjogren’s syndrome (pSS) is an auto-immune disease characterised by lymphocytic infiltration of exocrine glands and associated with a wide range of auto-antibodies, in particular anti-SS-A/Ro and anti-SS-B/La antibodies. Mortality in pSS is increased compared to the general population. In 1045 Spanish patients with pSS followed for a mean of almost 10 years the SMR was 4.66 (95%CI 3.85, 5.60) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Ccml0by1aZXJvbjwvQXV0aG9yPjxZZWFyPjIwMTQ8L1ll
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ADDIN EN.CITE.DATA (67). CVD was the main cause of death. Reports on the occurrence of ACVD in patients with pSS have been inconsistent. A study of 5205 patients with a new diagnosis of pSS and no prior history of MI from Taiwan found similar numbers of acute MIs in the patients with pSS compared with age, gender and comorbidity matched controls: HR 0.86 (95%CI 0.55, 1.35) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGlhbmc8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (68). These researchers also found a similar incidence of ischaemic stroke in both groups: HR 0.84 (95% CI 0.63-1.12) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGlhbmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGlhbmc8L0F1dGhvcj48WWVhcj4yMDE0PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (69). Contrary to these findings, Bartoloni et al reported a higher prevalence of self-reported cerebrovascular events (2.5% vs 1.4%) and MI (1.0% vs 0.4%) in 788 Italian women with pSS compared to 4774 age-matched female controls PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJ0b2xvbmk8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy
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ADDIN EN.CITE.DATA (70). There is some evidence of an increased prevalence of subclinical atherosclerosis in pSS. In a study of 200 women with pSS and 200 age matched female controls from the UK, hypertension (adjusted RR 2.02; 95%CI 1.19, 3.44) and hypertriglyceridaemia (adjusted RR 2.26; 1.26, 4.08) were more common in pSS ADDIN EN.CITE <EndNote><Cite><Author>Juarez</Author><Year>2014</Year><RecNum>462</RecNum><DisplayText>(71)</DisplayText><record><rec-number>462</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">462</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Juarez, M.</author><author>Toms, T. E.</author><author>de Pablo, P.</author><author>Mitchell, S.</author><author>Bowman, S.</author><author>Nightingale, P.</author><author>Price, E. J.</author><author>Griffiths, B.</author><author>Hunter, J.</author><author>Gupta, M.</author><author>Bombardieri, M.</author><author>Sutdliffe, N.</author><author>Pitzalis, C.</author><author>Pease, C.</author><author>Andrews, J.</author><author>Emery, P.</author><author>Regan, M.</author><author>Giles, I.</author><author>Isenberg, D.</author><author>Moots, R.</author><author>Collins, K. S.</author><author>Ng, W. F.</author><author>Kitas, G. D.</author></authors></contributors><titles><title>Cardiovascular risk factors in women with primary Sjogren's syndrome: United Kingdom primary Sjogren's syndrome registry results</title><secondary-title>Arthritis Care Res (Hoboken)</secondary-title><alt-title>Arthritis Care Res (Hoboken)</alt-title></titles><periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></periodical><alt-periodical><full-title>Arthritis Care Res (Hoboken)</full-title><abbr-1>Arthritis care & research</abbr-1></alt-periodical><pages>757-64</pages><volume>66</volume><number>5</number><dates><year>2014</year><pub-dates><date>May</date></pub-dates></dates><isbn>2151-4658 (Electronic)
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ADDIN EN.CITE.DATA (70). This may be because smoking exacerbates the symptoms of xerostomia. Much of the excess hypertension found in the UK study was previously undiagnosed, suggesting that patients with pSS should have their blood pressure monitored regularly. Mechanisms for the accelerated development of atherosclerosis in patients with CTDIn addition to TRFs, there are other important mechanisms related to CTDs that contribute to the increased CV risk. Chronic inflammation is a cornerstone of the pathogenesis of many CTDs and is also central to the development of atherosclerosis ADDIN EN.CITE <EndNote><Cite><Author>Mankad</Author><Year>2015</Year><RecNum>518</RecNum><DisplayText>(72)</DisplayText><record><rec-number>518</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">518</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mankad, R.</author></authors></contributors><auth-address>Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA, mankad.rekha@mayo.edu.</auth-address><titles><title>Atherosclerotic vascular disease in the autoimmune rheumatologic patient</title><secondary-title>Current atherosclerosis reports</secondary-title><alt-title>Curr Atheroscler Rep</alt-title></titles><periodical><full-title>Current atherosclerosis reports</full-title><abbr-1>Curr Atheroscler Rep</abbr-1></periodical><alt-periodical><full-title>Current atherosclerosis reports</full-title><abbr-1>Curr Atheroscler Rep</abbr-1></alt-periodical><pages>497</pages><volume>17</volume><number>4</number><dates><year>2015</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1534-6242 (Electronic)
1523-3804 (Linking)</isbn><accession-num>25721102</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(72). Immune-mediated changes play a role in the pathogenesis of both CTD and atherosclerosis. Autoantibody formation, which is a hallmark of CTD, contributes to vascular damage and risk of thrombosis ADDIN EN.CITE <EndNote><Cite><Author>Mankad</Author><Year>2015</Year><RecNum>518</RecNum><DisplayText>(72)</DisplayText><record><rec-number>518</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">518</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mankad, R.</author></authors></contributors><auth-address>Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA, mankad.rekha@mayo.edu.</auth-address><titles><title>Atherosclerotic vascular disease in the autoimmune rheumatologic patient</title><secondary-title>Current atherosclerosis reports</secondary-title><alt-title>Curr Atheroscler Rep</alt-title></titles><periodical><full-title>Current atherosclerosis reports</full-title><abbr-1>Curr Atheroscler Rep</abbr-1></periodical><alt-periodical><full-title>Current atherosclerosis reports</full-title><abbr-1>Curr Atheroscler Rep</abbr-1></alt-periodical><pages>497</pages><volume>17</volume><number>4</number><dates><year>2015</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1534-6242 (Electronic)
1523-3804 (Linking)</isbn><accession-num>25721102</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(72).The mechanisms at play in the development of ACVD in SSc have not being fully elucidated and microvascular disease may also contribute. Endothelial cell injury induced by anti-endothelial antibodies, ischaemia/reperfusion damage, and immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism ADDIN EN.CITE <EndNote><Cite><Author>Cannarile</Author><Year>2015</Year><RecNum>368</RecNum><DisplayText>(45)</DisplayText><record><rec-number>368</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">368</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cannarile, F.</author><author>Valentini, V.</author><author>Mirabelli, G.</author><author>Alunno, A.</author><author>Terenzi, R.</author><author>Luccioli, F.</author><author>Gerli, R.</author><author>Bartoloni, E.</author></authors></contributors><auth-address>Department of Medicine, Rheumatology Unit, University of Perugia, Via dal Pozzo 06132, Perugia, Italy.</auth-address><titles><title>Cardiovascular disease in systemic sclerosis</title><secondary-title>Annals of translational medicine</secondary-title><alt-title>Ann Transl Med</alt-title></titles><periodical><full-title>Annals of translational medicine</full-title><abbr-1>Ann Transl Med</abbr-1></periodical><alt-periodical><full-title>Annals of translational medicine</full-title><abbr-1>Ann Transl Med</abbr-1></alt-periodical><pages>8</pages><volume>3</volume><number>1</number><dates><year>2015</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>2305-5839 (Print)
2305-5839 (Linking)</isbn><accession-num>25705640</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(45).Contribution of LOS to understanding the development of CVD in the clinical course of CTD (level A)The clinical course of treated CTD can be studied in a number of contexts including randomised controlled trials (RCTs) and longitudinal observational studies (LOS). LOS comprise cohorts of patients with the CTD of interest, with few exclusion criteria, followed prospectively. Investigation and treatment will be according to local practice and may or may not be protocol driven. The cohort may either be assembled as close as possible to disease onset (inception cohorts) or assembled from prevalent cases, or both. The quality of a LOS is determined by (i) the representativeness of the cohort (and thus the generalisability of the results); (ii) the breadth, quality and completeness of the data; and (iii) the comprehensiveness of the capture and validation of outcome data. LOS may recruit specifically for research purposes or may be derived from disease registers compiled within clinical practice. Some studies are a hybrid. Alternatively CTD cohorts may be assembled from within large administrative health databases or from national disease registers. Each of these sources has its own strengths and weaknesses. As illustrated earlier in this Chapter, most of the information on the incidence and prevalence of fatal and non-fatal CVEs in CTD is derived from LOS and administrative datasets. Modifying cardiovascular risk in clinical practice (Level A)Evidence-based protocols for the screening and management of CV risk factors in CTD do not currently exist. However, the elevated risk of CVD in SLE and the need to address this risk has been acknowledged by experts in two consensus documents PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3NjYTwvQXV0aG9yPjxZZWFyPjIwMTA8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (73). The American Heart Association Guidelines for the prevention of CVD in women have included SLE as a group at increased CVD risk PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Nb3NjYTwvQXV0aG9yPjxZZWFyPjIwMTE8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (74). There is evidence that composite risk scores such as the Framingham risk score underestimate risk in SLE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CcnVjZTwvQXV0aG9yPjxZZWFyPjIwMDM8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (30, 34, 75). In one study, a multiplication of the Framingham risk score components by 2 was shown to improve accuracy ADDIN EN.CITE <EndNote><Cite><Author>Urowitz</Author><Year>2011</Year><RecNum>465</RecNum><DisplayText>(76)</DisplayText><record><rec-number>465</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">465</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Urowitz, M. B.</author><author>Ibanez, D.</author><author>Gladman, D. D.</author></authors></contributors><auth-address>Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada</auth-address><titles><title>Adjusted Framingham Risk Factor Scoring for Systemic Lupus Erythematosus</title><secondary-title>Arthritis Rheum</secondary-title><alt-title>Arthritis Rheum-Us</alt-title></titles><periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></periodical><pages>S884-S885</pages><volume>63</volume><number>10</number><dates><year>2011</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0004-3591</isbn><accession-num>ISI:000297621502648</accession-num><urls><related-urls><url><Go to ISI>://000297621502648</url></related-urls></urls><language>English</language></record></Cite></EndNote>(76). In the absence of evidence-based guidelines for CV risk assessment in CTDs in general, we propose using previously published recommendations for CV risk management in SLE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XYWplZDwvQXV0aG9yPjxZZWFyPjIwMDQ8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (71, 79). Hypertension is defined as values >140mmHg systolic and/or >90mmHg diastolic blood pressure. Tselios et al point out that current hypertension guidelines may not apply to patients with SLE ADDIN EN.CITE <EndNote><Cite><Author>Tselios</Author><Year>2014</Year><RecNum>442</RecNum><DisplayText>(33)</DisplayText><record><rec-number>442</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">442</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tselios, K.</author><author>Koumaras, C.</author><author>Urowitz, M. B.</author><author>Gladman, D. D.</author></authors></contributors><auth-address>Second Department of Internal Medicine, 424 General Military Hospital of Thessaloniki, Thessaloniki, Greece.
Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8. Electronic address: m.urowitz@utoronto.ca.
Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, Ontario, Canada M5T 2S8.</auth-address><titles><title>Do current arterial hypertension treatment guidelines apply to systemic lupus erythematosus patients? a critical appraisal</title><secondary-title>Semin Arthritis Rheum</secondary-title><alt-title>Semin Arthritis Rheum</alt-title></titles><periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Semin Arthritis Rheum</full-title><abbr-1>Seminars in arthritis and rheumatism</abbr-1></alt-periodical><pages>521-5</pages><volume>43</volume><number>4</number><dates><year>2014</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1532-866X (Electronic)
0049-0172 (Linking)</isbn><accession-num>23953498</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(33). Patients with CTDs have not, however, been previously included in treatment recommendations. We recommend that blood pressure should be measured at each clinic visit. When elevated, it should be monitored closely and an assessment of steroid use and renal function should be made ADDIN EN.CITE <EndNote><Cite><Author>Wajed</Author><Year>2004</Year><RecNum>415</RecNum><DisplayText>(77)</DisplayText><record><rec-number>415</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">415</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wajed, J.</author><author>Ahmad, Y.</author><author>Durrington, P. N.</author><author>Bruce, I. N.</author></authors></contributors><auth-address>The University of Manchester, Rheumatism Research Centre, Central Manchester and Manchester Children's University Hospitals NHS Trust, Oxford Road, Manchester M13 9WL, UK.</auth-address><titles><title>Prevention of cardiovascular disease in systemic lupus erythematosus--proposed guidelines for risk factor management</title><secondary-title>Rheumatology (Oxford, England)</secondary-title><alt-title>Rheumatology (Oxford)</alt-title></titles><alt-periodical><full-title>Rheumatology (Oxford)</full-title><abbr-1>Rheumatology</abbr-1></alt-periodical><pages>7-12</pages><volume>43</volume><number>1</number><dates><year>2004</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1462-0324 (Print)
1462-0324 (Linking)</isbn><accession-num>12867578</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(77). Advice should be given on non-pharmacological interventions such as exercise, weight loss and dietary salt restriction. Pharmacological treatment should be initiated if blood pressure remains consistently elevated above 140/90mmHg PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5jaWE8L0F1dGhvcj48WWVhcj4yMDEzPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (80).Smoking (Level C)We believe that smoking status should be ascertained in all CTD patients. In SLE, smoking may increase disease activity ADDIN EN.CITE <EndNote><Cite><Author>Ghaussy</Author><Year>2003</Year><RecNum>416</RecNum><DisplayText>(81)</DisplayText><record><rec-number>416</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">416</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ghaussy, N. O.</author><author>Sibbitt, W., Jr.</author><author>Bankhurst, A. D.</author><author>Qualls, C. R.</author></authors></contributors><auth-address>Department of Internal Medicine, The University of New Mexico Health Sciences Center, Albuquerque 87131, USA.</auth-address><titles><title>Cigarette smoking and disease activity in systemic lupus erythematosus</title><secondary-title>J Rheumatol</secondary-title><alt-title>J Rheumatol</alt-title></titles><periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></periodical><alt-periodical><full-title>J Rheumatol</full-title><abbr-1>The Journal of rheumatology</abbr-1></alt-periodical><pages>1215-21</pages><volume>30</volume><number>6</number><dates><year>2003</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0315-162X (Print)
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ADDIN EN.CITE.DATA (84, 85).In general, it is important to establish patients’ willingness to stop smoking and methods available to assist them. We hope that reminding patients repeatedly of the risks associated with smoking will improve cessation rates. Pharmacological treatments and nicotine replacement therapy may be offered PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZXJrPC9BdXRob3I+PFllYXI+MjAxMjwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (86). In addition to drugs, referral to smoking cessation clinics to provide and support behavioural interventions improves the likelihood of success. Dyslipidaemia (Level C)An abnormal lipid profile is prevalent in SLE and has also been reported in some studies in pSS PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb2RkZTwvQXV0aG9yPjxZZWFyPjIwMDY8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (87, 88). A meta-analysis of 3 trials in SLE found that despite significant reductions in cholesterol with statin therapy, measures of subclinical atherosclerosis did not improve ADDIN EN.CITE <EndNote><Cite><Author>Ye</Author><Year>2013</Year><RecNum>526</RecNum><DisplayText>(89)</DisplayText><record><rec-number>526</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">526</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ye, Y.</author><author>Zhao, X.</author><author>Xie, H.</author><author>Tian, Z.</author><author>Zhang, S.</author></authors></contributors><titles><title>Efficacy and safety of statins in the prevention of atherosclerosis in patients with systemic lupus erythematosus--a meta-analysis of randomized controlled trials</title><secondary-title>Int J Cardiol</secondary-title><alt-title>Int J Cardiol</alt-title></titles><periodical><full-title>Int J Cardiol</full-title><abbr-1>International journal of cardiology</abbr-1></periodical><alt-periodical><full-title>Int J Cardiol</full-title><abbr-1>International journal of cardiology</abbr-1></alt-periodical><pages>301-3</pages><volume>167</volume><number>1</number><dates><year>2013</year><pub-dates><date>Jul 15</date></pub-dates></dates><isbn>1874-1754 (Electronic)
0167-5273 (Linking)</isbn><accession-num>23084817</accession-num><work-type>Letter
Meta-Analysis
Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(89). Therefore, whilst ‘all’ patients with SLE should not automatically be prescribed a statin, we believe that statins still have a key role in CTD patients to enable patients to achieve their ideal target LDL. We recommend that CTD patients have a baseline and annual lipid profile measured. If dyslipidaemia is discovered, treatment should be initiated and the lipid profile repeated to ensure normalisation. Therapeutic lifestyle changes, including reduction in dietary saturated fat content, weight loss and moderate physical activity should be employed and may be sufficient to enable the patient to achieve an ideal LDL in those with moderate LDL elevations, i.e. LDL of 2.6 to 3.4mmol/L. This step is particularly relevant in SLE as steroid dose modification and the introduction of an antimalarial (where appropriate) may both add to lipid lowering in such patients. When the LDL cholesterol is > 3.4 mmol/L, unless the patient is on high dose glucocorticoids, it is unlikely that lifestyle modification alone will be sufficient to achieve an ideal LDL; such patients most likely will require statin therapy. The Adult Treatment Panel III guidelines recommend an LDL target of 2.6mmol/L for diabetic patients ADDIN EN.CITE <EndNote><Cite><Author>Stone</Author><Year>2005</Year><RecNum>435</RecNum><DisplayText>(90)</DisplayText><record><rec-number>435</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">435</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Stone, N. J.</author><author>Bilek, S.</author><author>Rosenbaum, S.</author></authors></contributors><auth-address>Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. n-stone@northwestern.edu</auth-address><titles><title>Recent National Cholesterol Education Program Adult Treatment Panel III update: adjustments and options</title><secondary-title>Am J Cardiol</secondary-title><alt-title>Am J Cardiol</alt-title></titles><periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></periodical><alt-periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></alt-periodical><pages>53E-59E</pages><volume>96</volume><number>4A</number><dates><year>2005</year><pub-dates><date>Aug 22</date></pub-dates></dates><isbn>0002-9149 (Print)
0002-9149 (Linking)</isbn><accession-num>16098845</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(90). Given the high CV risk nature of SLE, we recommend using these diabetic treatment targets. If LDL is >2.6mmol/L despite lifestyle changes, lipid lowering therapy should be commenced and titrated according to response ADDIN EN.CITE <EndNote><Cite><Author>Wajed</Author><Year>2004</Year><RecNum>415</RecNum><DisplayText>(77)</DisplayText><record><rec-number>415</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">415</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wajed, J.</author><author>Ahmad, Y.</author><author>Durrington, P. N.</author><author>Bruce, I. N.</author></authors></contributors><auth-address>The University of Manchester, Rheumatism Research Centre, Central Manchester and Manchester Children's University Hospitals NHS Trust, Oxford Road, Manchester M13 9WL, UK.</auth-address><titles><title>Prevention of cardiovascular disease in systemic lupus erythematosus--proposed guidelines for risk factor management</title><secondary-title>Rheumatology (Oxford, England)</secondary-title><alt-title>Rheumatology (Oxford)</alt-title></titles><alt-periodical><full-title>Rheumatology (Oxford)</full-title><abbr-1>Rheumatology</abbr-1></alt-periodical><pages>7-12</pages><volume>43</volume><number>1</number><dates><year>2004</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1462-0324 (Print)
1462-0324 (Linking)</isbn><accession-num>12867578</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(77). Currently, we recommend following lipid target guidelines as for the general population in patients with other CTDs. Obesity and the metabolic syndrome (MetS) (Level C)We recommend that weight, height and calculation of body mass index (BMI) should be measured at baseline. Measurement of waist circumference gives additional information about CV risk. A BMI of <25Kg/m2 and a waist circumference of < 40 inches for males and <35 inches for females are ideal targets in Caucasian patients. If patients are overweight or have a high waist circumference, advice regarding a healthy diet low in saturated fat and the importance of regular exercise should be given. MetS in SLE can be present without central obesity. Therefore it is important to consider this diagnosis in patients whose waist circumference is normal but have clustering of other factors PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYXJrZXI8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (32).Diabetes Mellitus (DM) (Level C)DM is more prevalent in CTD than the general population ADDIN EN.CITE <EndNote><Cite><Author>Bruce</Author><Year>2003</Year><RecNum>448</RecNum><DisplayText>(30)</DisplayText><record><rec-number>448</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">448</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bruce, I. N.</author><author>Urowitz, M. B.</author><author>Gladman, D. D.</author><author>Ibanez, D.</author><author>Steiner, G.</author></authors></contributors><auth-address>University of Toronto Lupus Clinic, and Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada.</auth-address><titles><title>Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study</title><secondary-title>Arthritis Rheum</secondary-title><alt-title>Arthritis Rheum</alt-title></titles><periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></periodical><alt-periodical><full-title>Arthritis Rheum</full-title><abbr-1>Arthritis and rheumatism</abbr-1></alt-periodical><pages>3159-67</pages><volume>48</volume><number>11</number><dates><year>2003</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0004-3591 (Print)
0004-3591 (Linking)</isbn><accession-num>14613278</accession-num><work-type>Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(30). Patients should therefore have a baseline and annual fasting glucose (and/or HbA1C) measured. A fasting glucose >7.0mmol/L and/or a random glucose > 11.1mmol/L confirms a diagnosis of DM. Such patients should be managed in conjunction with their primary care physician and /or a diabetologist. A glucose tolerance test should be considered in patients with a fasting glucose of >6.1mmol/L. Hydroxychloroquine can help to improve glycaemic control ADDIN EN.CITE <EndNote><Cite><Author>Gerstein</Author><Year>2002</Year><RecNum>433</RecNum><DisplayText>(91)</DisplayText><record><rec-number>433</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">433</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gerstein, H. C.</author><author>Thorpe, K. E.</author><author>Taylor, D. W.</author><author>Haynes, R. B.</author></authors></contributors><auth-address>Department of Medicine, McMaster University, Room 3V38, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. gerstein@mcmaster.ca</auth-address><titles><title>The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a randomized trial</title><secondary-title>Diabetes research and clinical practice</secondary-title><alt-title>Diabetes Res Clin Pract</alt-title></titles><periodical><full-title>Diabetes research and clinical practice</full-title><abbr-1>Diabetes Res Clin Pract</abbr-1></periodical><alt-periodical><full-title>Diabetes research and clinical practice</full-title><abbr-1>Diabetes Res Clin Pract</abbr-1></alt-periodical><pages>209-19</pages><volume>55</volume><number>3</number><dates><year>2002</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0168-8227 (Print)
0168-8227 (Linking)</isbn><accession-num>11850097</accession-num><work-type>Clinical Trial
Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(91). In established DM, the addition of an anti-malarial can potentially induce hypoglycaemia and the patient should be informed that their insulin or oral hypoglycaemic agent dosing may need some adjustment. Exercise prescription (Level C)Physicians should discuss the benefits of exercise with their CTD patients. Three to 5 hours of moderate intensity aerobic activity per week is recommended in healthy individuals. There is evidence of improvements in disease activity and vascular function with regular exercise in patients with CTD ADDIN EN.CITE <EndNote><Cite><Author>Barnes</Author><Year>2012</Year><RecNum>432</RecNum><DisplayText>(92)</DisplayText><record><rec-number>432</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">432</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Barnes, J. N.</author><author>Tanaka, H.</author></authors></contributors><auth-address>Department of Anesthesiology, Mayo Clinic, Rochester, MN. barnes.jill@mayo.edu.</auth-address><titles><title>Cardiovascular benefits of habitual exercise in systemic lupus erythematosus: a review</title><secondary-title>The Physician and sportsmedicine</secondary-title><alt-title>Phys Sportsmed</alt-title></titles><periodical><full-title>The Physician and sportsmedicine</full-title><abbr-1>Phys Sportsmed</abbr-1></periodical><alt-periodical><full-title>The Physician and sportsmedicine</full-title><abbr-1>Phys Sportsmed</abbr-1></alt-periodical><pages>43-8</pages><volume>40</volume><number>3</number><dates><year>2012</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0091-3847 (Print)
0091-3847 (Linking)</isbn><accession-num>23528620</accession-num><work-type>Review</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(92). However, exercise recommendations should be individualized, as factors such as fatigue, CVD and musculoskeletal manifestations of the disease will alter patient’s ability to participate in regular physical activity.Disease-related risk factor modification (Level C)Early control of disease activity is very important. At each clinic visit, patients should have a renal function assessment and urine quantified for proteinuria. Chronic kidney disease is a CVD-risk equivalent so early diagnosis and management is imperative. All patients with a CTD should also be screened for the presence of co-existing antiphospholipid antibodies, i.e. antibodies to lupus anticoagulant, anti-cardiolipin antibodies and where available, β2-microglobulin, at time of diagnosis. The opportunity to rationalize corticosteroid dose and use should be taken at every clinical assessment to minimise negative CV effects. Use of hydroxychloroquine is recommended in all SLE patients unless there is a contraindication, as it is proposed to have cardio protective properties PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYWdkZXI8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (93). Future considerations (Level C)Dedicated CV screening clinics for CTD may be the way forward, with evidence of their benefit in other inflammatory rheumatic conditions already available ADDIN EN.CITE <EndNote><Cite><Author>Rollefstad</Author><Year>2013</Year><RecNum>425</RecNum><DisplayText>(94)</DisplayText><record><rec-number>425</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">425</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rollefstad, S.</author><author>Kvien, T. K.</author><author>Holme, I.</author><author>Eirheim, A. S.</author><author>Pedersen, T. R.</author><author>Semb, A. G.</author></authors></contributors><titles><title>Treatment to lipid targets in patients with inflammatory joint diseases in a preventive cardio-rheuma clinic</title><secondary-title>Ann Rheum Dis</secondary-title></titles><periodical><full-title>Ann Rheum Dis</full-title><abbr-1>Annals of the rheumatic diseases</abbr-1></periodical><pages>1968-74</pages><volume>72</volume><number>12</number><dates><year>2013</year></dates><isbn>1468-2060 (Electronic)
0003-4967 (Linking)</isbn><work-type>Research Support, Non-U S Gov't</work-type><urls></urls></record></Cite></EndNote>(94). Another consideration for the future is the use of screening tools such as carotid ultrasound to assess cIMT and presence of plaque as these markers have been shown to be independent predictors of CVEs ADDIN EN.CITE <EndNote><Cite><Author>Kao</Author><Year>2013</Year><RecNum>423</RecNum><DisplayText>(28)</DisplayText><record><rec-number>423</rec-number><foreign-keys><key app="EN" db-id="0ez5se9eb9t2apert94v55defpfe9dd0rz5d">423</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kao, A. H.</author><author>Lertratanakul, A.</author><author>Elliott, J. R.</author><author>Sattar, A.</author><author>Santelices, L.</author><author>Shaw, P.</author><author>Birru, M.</author><author>Avram, Z.</author><author>Thompson, T.</author><author>Sutton-Tyrrell, K.</author><author>Ramsey-Goldman, R.</author><author>Manzi, S.</author></authors></contributors><auth-address>Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania. Electronic address: akao@.</auth-address><titles><title>Relation of carotid intima-media thickness and plaque with incident cardiovascular events in women with systemic lupus erythematosus</title><secondary-title>Am J Cardiol</secondary-title><alt-title>Am J Cardiol</alt-title></titles><periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></periodical><alt-periodical><full-title>Am J Cardiol</full-title><abbr-1>The American journal of cardiology</abbr-1></alt-periodical><pages>1025-32</pages><volume>112</volume><number>7</number><dates><year>2013</year><pub-dates><date>Oct 1</date></pub-dates></dates><isbn>1879-1913 (Electronic)
0002-9149 (Linking)</isbn><accession-num>23827400</accession-num><work-type>Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't</work-type><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(28). Summary (Level A)Information on the risk of ACVD and risk factors for the development of CVD in patients with CTDs other than SLE is sparse. This is, in part, because the study of cause-specific mortality and morbidity requires large cohorts of patients followed over long periods of time with robust identification of the outcomes of interest. Assembling such cohorts is a challenge in rare CTDs and often requires multi-centre collaboration. There is an increasing body of evidence that TRFs, disease specific factors and treatment all contribute to the excess risk of CVD in patients with SLE. It is probable that a similar pattern will emerge in non-SLE CTDs although the relative contribution of these factors is likely to differ. The minimisation of CV risk in the individual patient with CTD will require attention to optimise TRFs and control of disease activity whilst minimising exposure to steroids.Practice points (Level C)CTD patients should have a CV risk assessment, ideally at baseline and annually thereafterTRFs and disease related factors, including medications, must be considered when assessing CV risk If TRFs are identified they should be managed at least as stringently as recommended in guidelines for the general population As a validated composite CV risk assessment model for CTD is not currently available, we recommend a target-based approach to the assessment and management of CV risk for these patientsResearch agenda (Level C)Further research is necessary to expand on what is known with respect to CV risk in CTDs other than SLE.Whether CV outcomes in SLE and other CTDs improve with the use of more stringent targets than is recommended in the general population needs to be determined.When disease activity is controlled and TRF have been addressed, research will be important to investigate whether CV risk in CTD is then level with that in the general population or whether other non-modifiable risk factors are involved.Conflict of interest statement (Level C)Miriam O’Sullivan, Ian Bruce and Deborah Symmons have no conflicts of interestReferences: * most important ADDIN EN.REFLIST 1.Avina-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. 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Arthritis Rheum 2006;54(8):2550-7.*6.Yurkovich M, Vostretsova K, Chen W, Avina-Zubieta JA. Overall and cause-specific mortality in patients with systemic lupus erythematosus: a meta-analysis of observational studies. Arthritis Care Res (Hoboken) 2014;66(4):608-16.7.Elfving P, Puolakka K, Kautiainen H, Virta LJ, Pohjolainen T, Kaipiainen-Seppanen O. Mortality and causes of death among incident cases of systemic lupus erythematosus in Finland 2000-2008. Lupus 2014;23(13):1430-4.8.Lerang K, Gilboe IM, Steinar Thelle D, Gran JT. Mortality and years of potential life loss in systemic lupus erythematosus: a population-based cohort study. Lupus 2014;23(14):1546-52.9.Rees F, Doherty M, Grainge MJ, Lanyon P, Davenport G, Zhang W. Mortality in systemic lupus erythematosus in the United Kingdom 1999-2012. Rheumatology (Oxford, England) 2016.10.Yee CS, Su L, Toescu V, Hickman R, Situnayake D, Bowman S, et al. Birmingham SLE cohort: outcomes of a large inception cohort followed for up to 21 years. 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