Non-ST Segment Elevation Myocardial Infarction



Non-ST Segment Elevation Myocardial InfarctionRachel KrogstieMethodist University4/17/2016AbstractAccording to the American Heart Association (2016), cardiovascular disease is the leading cause of death in the United States and around the globe. It strikes every race, gender, and age, and has an estimated global cost of $863 billion and rising CITATION Moz16 \l 1033 (Mozaffarian, et al., 2016). Despite these overwhelming numbers, incidence of mortality from myocardial infarctions has decreased dramatically in the last five years CITATION Foc \l 1033 \m Moz16(Pellico, 2013; Mozaffarian, et al., 2016). This decrease can be attributed to education on the modifiable risk factors, pathophysiology, and clinical manifestations. In order to provide to best care to the population, healthcare professions at all levels must keep current on the latest research on myocardial infarction and pass this information on to their patients.Keywords: pathophysiology, STEMI, Non-STEMI, gender, risk factors, manifestationsNon-ST Segment Elevation Myocardial InfarctionIn 2000, the joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction issued an internationally accepted definition of myocardial infarction CITATION Mar11 \l 1033 (Marshall, 2011) that defined myocardial infarction by infarct size, circumstances leading to the infarct, and timing of heart muscle death to the time of observation CITATION Thy12 \l 1033 (Thygesen, et al., 2012). The definition was updated by Thygesen, et al. on behalf of the Joint Task Force for the Redefinition of Myocardial Infarction in 2007, and again in 2012 CITATION Whi14 \l 1033 (White, Thygesen, Alpert, & Jaffe, 2014). The new definition states, “[t]he term acute myocardial infarction should be use when there is evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia” CITATION Whi14 \l 1033 (White, Thygesen, Alpert, & Jaffe, 2014). The definition continues with criteria that meet this diagnosis, including cardiac biomarkers, electrocardiogram changes, and medical imaging findings (see Figure 1) CITATION Whi14 \l 1033 (White, Thygesen, Alpert, & Jaffe, 2014). Myocardial infarction (MI) can be further broken down into two diagnostic categories: ST segment elevation or non-ST segment elevation CITATION Foc \l 1033 (Pellico, 2013). In Non-ST segment elevation myocardial infarction (Non-STEMI), there are no definite ECG changes, so diagnosis must rely on cardiac biomarkers and imaging, particularly echocardiogram CITATION Foc \l 1033 (Pellico, 2013). In addition, Non-STEMI patients are more likely to present with atypical symptoms and delay seeking medical treatmentCITATION Canto \l 1033 (Canto, et al., 2012). These atypical symptoms may be vague complains such as fatigue, shoulder blade pain, and nausea but no chest pain CITATION Foc \l 1033 (Pellico, 2013). All of these factors lead to a drastic delay in crucial medical interventions. Acute MI (MI) is a major public health concern here in the United States, and worldwideCITATION Lav15 \l 1033 (Lavall, et al., 2015). In 2008, it was estimated 900,000 people each year experience an acute myocardial infarction and 25 percent of these were fatal; of the fatal incidents, half of the patients never made it to the hospital CITATION Foc \l 1033 (Pellico, 2013). The most recent statistics according to the American Heart AssociationCITATION Moz16 \n \t \l 1033 (2016), state that those number have decreased to 750,000 MIs a year, 15 percent being fatal. This significant decrease in mortality can be directly attributed to two factors: medical intervention (47 percent) and risk factor reduction (44 percent) CITATION Moz16 \l 1033 (Mozaffarian, et al., 2016). Both of these factors can be directly linked to an increase of education of patients, lay peoples, and medical professions. Although there have been significant decreases in the incidence of MIs, heart disease still remains the number one cause of death in the United States and around the worldCITATION Lav15 \m Moz16 \m NZRC \l 1033 (Lavall, et al., 2015; Mozaffarian, et al., 2016; Australian Resuscitation Council (ARC) & New Zealand Resuscitation Council (NZRC), 2016). At the onset of symptoms, timely recognition and medical care will reduce the incidence of cardiac arrest and sudden deathCITATION Moz16 \m NZRC \n \l 1033 (Mozaffarian, et al., 2016; ARC & NZRC, 2016). Thus, a current and through understanding of the pathophysiology and clinical manifestations of acute MI, particularly the less recognizable non-ST segment elevation myocardial infarction, has the potential to decrease the incidence these events further, and mortality associated with them.This paper will first conceptualize the pathophysiology of non-ST segment elevation myocardial Infarctions, including any risk factors, mediators, and epidemiology. This will include any likenesses and differences to the more well-known ST-segment elevation myocardial infarction. Second, this paper will compare and contrast the clinical manifestations of myocardial infarction in men and women. The paper will conclude in a summary of the current understanding of non-ST segment elevation myocardial infarctions, including any gaps in knowledge and areas future research to close those gaps.MethodologyData collection for this paper included a search of OneSearch, a collection of all of Davis Memorial Library’s digital subscriptions. The initial search terms were “non-STEMI.” Results were limited to full text, peer-reviewed journal articles dating January 2011 to February 2016. The search was further limited to the key subjects to myocardial infarction, acute coronary syndrome, heart attack, pathophysiology, and risk factors. Exclusion factors were disciplines outside of the medicine or nursing and publications in non-English languages. Another search with the same inclusion and exclusion criteria was done with the search terms “non-STEMI in women” to include the significant difference of clinical presentation between men and women. The writer also consulted with a research librarian to conduct a more through and targeted search of publications. This search was conducted in the PubMed databases using the search terms “non-ST elevation myocardial infarction” and limited to full text, human subjects, women, pathophysiology, and last 5 years. Literature ReviewPathophysiologyThe most common etiology of Acute Coronary Syndrome (ACS) is a sudden imbalance between myocardial oxygen consumption and demand CITATION ACCAHA \l 1033 (Amsterdam, et al., 2014). This is usually caused by an obstruction of a coronary arteryCITATION ACCAHA \l 1033 (Amsterdam, et al., 2014) from the disruption of atherosclerotic plaque CITATION Mar11 \l 1033 (Marshall, 2011). The disruption of the plaque can be caused by activity or emotional stress CITATION Mar11 \l 1033 (Marshall, 2011). ACS can also be caused by coronary insufficiency from other underlying causes (such as coronary embolism) and non-coronary causes of mismatch (such as hypotension or hypertension)CITATION ACCAHA \l 1033 (Amsterdam, et al., 2014). Risk FactorsAssessing to what degree of risk a patient is of experiencing an adverse event is a key early intervention for patients with ACS. CITATION Mar11 \l 1033 (Marshall, 2011). Using only one variable, such as troponin or ECG, is not as reliable as a multi-variable, multi-component risk assessment system CITATION Mar11 \l 1033 (Marshall, 2011). Two of the most commonly used tools are the Thrombolysis In Myocardial Infarction (TIMI) risk score and the GRACE (Global Registry of Acute Coronary Events) risk score CITATION Mar11 \l 1033 (Marshall, 2011). TIMI was developed to predict the need for further complications, such as death or subsequent MI, at 14 days post event; the GRACE risk assessment was developed using the whole spectrum of ACS, however it is most widely used to estimate the probability of MI or death in the hospital and at 6 months CITATION Mar11 \l 1033 (Marshall, 2011). There is no substantial research showing better performance from either one of these assessments, however they both are very helpful predicting further complications. One of the leading risk factors for Non- STEMI is prior MI and these patients tend to have worse long-term outcomes compared with patients without prior MI CITATION Shen \l 1033 (Shen, et al., 2014). As a result, prior MI is listed as a known risk factor for subsequent adverse events on both TIMI and GRACE risk assessments CITATION Shen \l 1033 (Shen, et al., 2014). In a study done 2007 to 2012, the incidence of prior MI was greater in Non-STEMI (29%) than in STEMI (19%)CITATION Shen \l 1033 (Shen, et al., 2014). According to one study from 2014, for both STEMI and NON-STEMI patients, patients were more likely to be older, be male, and have comorbidities such as hypertension, hyperlipidemia, and diabetes, which all lead to atherosclerosis, which is independently a risk factor for ACS CITATION Shen \l 1033 (Shen, et al., 2014). These patients are also more likely to have a prior history of chronic renal failure CITATION Mar11 \l 1033 (Marshall, 2011), congestive heart failure and are more likely to be treated with secondary prevention medications at home compared with those without prior MICITATION Shen \l 1033 (Shen, et al., 2014). STEMI versus Non-STEMI The GRACE investigators and the Myocardial Infarction National Audit Project (MINAP) have shown that Non-STEMI is more prevalent than STEMI CITATION Mar11 \l 1033 (Marshall, 2011). Initial mortality rates for STEMI are 50 % higher than Non-STEMI CITATION Fitchett \l 1033 (Fitchett, et al., 2011), but death rates at 6 to 12 months were higher among patients with Non-STEMI than STEMI CITATION BrenerPROSPECT \l 1033 (Brener, et al., 2012), with a twofold difference at four years CITATION Mar11 \l 1033 (Marshall, 2011). In general, patients with STEMI tend to be younger and have fewer risk factors for adverse outcomes than the Non-STEMI patients CITATION BrenerPROSPECT \l 1033 (Brener, et al., 2012). While the type of MI is a strong predictor of in-hospital mortality, the presence or absence of chest pain also is a significant predictor. Patients who presented without chest pain or discomfort have a higher in-hospital mortality rate, and they are also less likely to receive aggressive treatment for MI CITATION Canto \l 1033 (Canto, et al., 2012). The initial difference in pathophysiology and early outcomes between STEMI and Non-STEMI lead to contrasting early treatment strategies: In STEMI, prompt reopening of the occluded artery is the therapeutic priority and Non-STEMI management are to prevent progression of the thrombus to total occlusion, plaque thrombo-embolization, and recurrent infarctionCITATION Fitchett \l 1033 (Fitchett, et al., 2011). A survey done on 1939 patients diagnosed with ACS in Sweden assessed the characteristics and severity of symptoms via questionnaire and found that patients with STEMI were more likely to experience vertigo, syncope, nausea, cold sweat, and vomiting than those with Non-STEMICITATION Kirchberger \l 1033 (Kirchberger, et al., 2011). They also experienced higher pain or discomfort levels, and more frequently, that pain had a more abrupt onset and reached its highest intensity within minutesCITATION Kirchberger \l 1033 (Kirchberger, et al., 2011). Alternatively, dyspnea and pain in the throat or jaw were less common in patients with STEMI than in those with Non-STEMICITATION Kirchberger \l 1033 (Kirchberger, et al., 2011). Patients with Non-STEMI are about twice as likely to present with atypical symptoms, such as an absence of chest pain, compared to those with STEMICITATION Canto \l 1033 (Canto, et al., 2012). It has also been found that patients with atypical presentations were more likely to delay seeking medical attention, delaying an average of two hoursCITATION Canto \l 1033 (Canto, et al., 2012). These patients are also less likely to receive aggressive treatment with reperfusion therapies, medications, and invasive cardiac proceduresCITATION Canto \l 1033 (Canto, et al., 2012). Clinical Manifestations Based on SexWomen are more likely to present with atypical histories and symptoms than men are. A study on gender differences in acute coronary syndrome states that women are more likely to present with dyspnea, indigestion, nausea, vomiting, palpitations, and general weakness CITATION Kostapanos \l 1033 (Kostapanos, Florentin, & Elisaf, 2013). Another study on gender differences in coronary artery disease shows that women had a significantly more rapid heart rate and higher blood pressure at presentation CITATION LeeGenderDiff \l 1033 (Lee, et al., 2013). If a woman does present with chest pain, it is of a lower intensity, and longer period (1-12 hours) than compared to men (30-60 minutes) CITATION Kostapanos \l 1033 (Kostapanos, Florentin, & Elisaf, 2013). This leads to the conclusion that women would experience Non-STEMI more often than men would. In fact, one study shows men had more frequent ST elevation on the first ECG recorded as compared with women CITATION Rav12 \l 1033 (Ravn-Fischer, et al., 2012).Studies like the Framingham study, a longitudinal study of the risk of heart disease, have showed that heart disease presents at an earlier age in men than in women CITATION Kostapanos \l 1033 (Kostapanos, Florentin, & Elisaf, 2013). These studies show significant evidence that women experience their first MI at a later age than men, a median of 65 years vs median of 56 years in men CITATION Kostapanos \l 1033 (Kostapanos, Florentin, & Elisaf, 2013). It theorized that endogenous estrogens protect women from cardiovascular disease until they reach a post-menopause status, at which the risk and rate of development of heart disease matches that of men CITATION Kostapanos \l 1033 \m LeeGenderDiff (Kostapanos, Florentin, & Elisaf, 2013; Lee, et al., 2013). One study from Sweden states that men were found to have a higher prevalence of heart failure CITATION Rav12 \l 1033 (Ravn-Fischer, et al., 2012). However, another study from Malaysia states that women had higher rates of prior heart failure CITATION LeeGenderDiff \l 1033 (Lee, et al., 2013). The differences in locale and inclusion criteria may be to blame for the difference in the statistics for these two studies. While the study done in Sweden was more inclusive (all patients presenting with chest pain versus patients who underwent percutaneous coronary intervention), the population was significantly less (2588 patients versus 10554 patients) CITATION LeeGenderDiff \l 1033 \m Rav12 (Lee, et al., 2013; Ravn-Fischer, et al., 2012).In a study done in 2008 on patients admitted to an emergency room with chest pain, women were found to have a significantly higher prevalence of previous hypertension and depression or psychiatric disease than did men CITATION Rav12 \l 1033 (Ravn-Fischer, et al., 2012). Multiple studies agree that men were more likely to present with a history of angina pectoris, MI, and previous invasive procedures CITATION Rav12 \l 1033 \m LeeGenderDiff (Ravn-Fischer, et al., 2012; Lee, et al., 2013). As mentioned above, patients being diagnosed with STEMI and Non-STEMI were more likely to have comorbidities when presenting for treatment. Studies were done to see if these comorbidities were gender specific. Studies show women had significantly higher rates of certain disease processes, such as diabetes mellitus, hypertension, chronic renal failure, obesity, and dyslipidemia CITATION Kyto \m Kostapanos \l 1033 (Kyt?, Sipil?, & Rautava, 2015; Kostapanos, Florentin, & Elisaf, 2013). However, the study done by Lee, et al., states that there is no significant difference between the genders in terms of incidence of obesity and dyslipidemia CITATION LeeGenderDiff \l 1033 (Lee, et al., 2013). This may be a cultural or dietary anomaly based on the population studied. The study goes on to state that there is also no significant difference in the incidence of coronary artery disease between the sexes CITATION LeeGenderDiff \l 1033 (Lee, et al., 2013). This study, as stated above, only includes patients undergoing PCI, therefore the population is of the older, postmenopausal women that are experiencing MIs. Overall, men are more likely to have a history of coronary artery disease, accounting for all ages of patients CITATION Kyto \l 1033 (Kyt?, Sipil?, & Rautava, 2015). Differences in Outcome Based on SexBecause women are more likely to have an atypical presentation, they are also at risk of delaying recognition and treatment of the coronary event. This also affects the type and timeliness of appropriately aggressive treatments and mortality rates CITATION Kostapanos \l 1033 (Kostapanos, Florentin, & Elisaf, 2013). According to a study done in Sweden by Ravn-Fischer, et al., women had a significantly longer delay time (~236 minutes) from arrival to admission to a hospital floor as compared with men (~200 minutes) CITATION Rav12 \l 1033 (Ravn-Fischer, et al., 2012). Women also had longer delay times from the first physical contact until the first dose of aspirin and delay from admission until undergoing coronary angiography CITATION Rav12 \l 1033 (Ravn-Fischer, et al., 2012). However, delay from the first physical contact until the first ECG did not differ significantly between sexes CITATION Rav12 \l 1033 (Ravn-Fischer, et al., 2012). This can be attributed to standard procedures of initial assessment of acute chest pain in emergency rooms. While men and women had similar rates of PCI overall, women are less likely to receive emergent rescue PCI CITATION LeeGenderDiff \l 1033 (Lee, et al., 2013). Women are more likely than men to have left main stem disease and smaller diameter vessels, however, the rate of vessel disease and lesions are similar between the sexes CITATION LeeGenderDiff \l 1033 (Lee, et al., 2013). Among all hospitalized patients with chest pain, men were more likely to be diagnosed with an acute MI, and coronary angiography and echocardiogram are more often performed on menCITATION OttenDifferinOutcome \l 1033 (Otten, et al., 2013). However, the results of the angiogram and echocardiogram are more often normal in womenCITATION OttenDifferinOutcome \l 1033 (Otten, et al., 2013). There is conflicting evidence as to whether or not women have higher mortality rates post-MI than men. Several studies have shown that while women have higher mortality rates, but that this could be explained by differences in age and comorbidities CITATION Kyto \l 1033 (Kyt?, Sipil?, & Rautava, 2015). Other studies have shown that regardless of comorbidities, the mortality rates are higher in women CITATION OttenDifferinOutcome \l 1033 (Otten, et al., 2013). The stronger evidence of multihospital data and higher patient population is present with Kyt?, Sipil?, & Rautava, however, Otten, et al. did determine that higher mortality rates may be caused by age, longer delay before treatment, and less use of invasive medical procedures CITATION OttenDifferinOutcome \l 1033 (Otten, et al., 2013). However, the study also determined that younger women still had higher mortality rates, regardless of any other factors CITATION OttenDifferinOutcome \l 1033 (Otten, et al., 2013). Zhang, et al., also agree with the higher mortality rates in younger women, but this study differentiates STEMI being the cause of higher mortality rates, and that Non-STEMI the genders have similar outcomes CITATION Zhang \l 1033 (Zhang, et al., 2012).ConclusionIt is clear from the extensive body of knowledge covered here in this paper, that there is much that is known about the pathophysiology, risk factors, and clinical manifestations on myocardial infarctions. Overall, the studies discussed in this paper agree on most topics. However, there are several areas that are not consistent across multiple studies, or have only been studied in one or two smaller studies. All current research for this paper agrees on the pathophysiology of acute coronary syndrome, which includes STEMI and Non-STEMI. The etiology is a sudden imbalance between myocardial oxygen consumption and demand, and is normally caused by an obstruction or narrowing of a vessel CITATION ACCAHA \l 1033 \m Mar11 \m Foc (Amsterdam, et al., 2014; Marshall, 2011; Pellico, 2013). STEMI are caused by a complete blockage with a plaque and/or blood clot and Non-STEMI is a partial occlusion caused by a plaque CITATION Fitchett \l 1033 (Fitchett, et al., 2011). The consensus of recent studies state the risk factors for coronary artery disease, which leads to myocardial infarction, are history of smoking, diabetes, hypertension, hyperlipidemia, chronic kidney disease, and heart failureCITATION LeeGenderDiff \m Kyto \m Kostapanos \l 1033 (Lee, et al., 2013; Kyt?, Sipil?, & Rautava, 2015; Kostapanos, Florentin, & Elisaf, 2013). However, it is unclear if these risk factors are more predominant in men or women because the studies presented in this paper have conflicting views. This could be due to the scope of the studies done. More research needs to be done to answer the questions of whether or not risk factors differ based on gender, and how to better predict risk for myocardial infarctions and heart disease in general. Clinical presentation for myocardial infarction is pretty consistent across all studies presented. These manifestations include dyspnea, indigestion, nausea, vomiting, palpitations, general weakness, fatigue, shoulder blade pain, vertigo, syncope. All of these symptoms can appear with or with chest pain CITATION Canto \l 1033 \m Kostapanos \m Kirchberger \m Foc (Canto, et al., 2012; Kostapanos, Florentin, & Elisaf, 2013; Kirchberger, et al., 2011; Pellico, 2013). Areas for further research include the differences in gender presentation. One study states that there is no difference in presentation between the genders, while other studies state that there are differences, while attributing conflicting symptoms to each gender. More research needs to be done on if there is a difference in clinical presentation between men and women, and if there is, what they are. The two articles included in this paper were studies done on small populations in very specific locales. A multi-national study would give results that are more conclusive. Another area that requires further research is the mortality rates of women post-MI. The studies indicated in this paper explain the higher mortality rates by age and comorbidities CITATION Kyto \l 1033 (Kyt?, Sipil?, & Rautava, 2015). However, other studies indicate the higher rates are caused by the difference in the pathophysiology of STEMI and Non-STEMI CITATION OttenDifferinOutcome \l 1033 \m Zhang (Otten, et al., 2013; Zhang, et al., 2012). Further research need to be done at a multinational level to examine morality rates of myocardial infarction overall, and then to distinguish morbidity and mortality rates between the different types of myocardial infarction and gender. All of the research proposed in this paper would have the benefits of increasing knowledge of the underlying conditions and risk factors that could potentially lead to acute coronary syndrome and coronary artery disease. After getting a better understanding of these factors, this knowledge could be used to lower the modifiable risk factors and curb the incidence of ACS and MIs worldwide. As it stands now, there are several countries doing research on hospitals in their own region. However, studies done on a multi-national level would benefit countries that do not have the resources to do their own research. The incidence of myocardial infarction is a worldwide issue, so there needs to be a worldwide initiative to further the research and knowledge base in order to continue to decrease the mortality from myocardial infarction. References BIBLIOGRAPHY Amsterdam, E. A., Wenger, N. K., Brindis, R. G., Casey Jr., D. E., Ganiats, T. G., Holmes Jr., D. R., . . . Zieman, S. J. (2014, December 23). 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes : A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 64(24), e139-e228. doi:doi:10.1016/j.jacc.2014.09.017Australian Resuscitation Council (ARC), New Zealand Resuscitation Council (NZRC). (2016, January). Acute coronary syndromes: Presentation with ACS. ARC and NZRC guideline 2011. Emergency Medicine Australasia, 23, 302-307. doi:10.1111/j.1742-6723.2011.01422_18.xBrener, S. J., Weisz, G., Maehara, A., Mehran, R., McPherson, J., Farhat, N., . . . Stone, G. W. (2012, October). Does clinical presentation affect outcome among patients with acute coronary syndromes undergoing percutaneous coronary intervention? Insights from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study. American Heart Journal, 164(4), 561-567.Canto, A. J., Kiefe, C. I., Goldberg, R. J., Rogers, W. J., Peterson, E. D., Wenger, N. K., . . . Canto, J. G. (2012, April). Differences in symptom presentation and hospital mortality according to type of acute myocardial infarction. American Heart Journal, 163(4), 572-579. doi:10.1016/j.ahj.2012.01.020Fitchett, D. H., Theroux, P., Brophy, J. M., Cantor, W. J., Cox, J. L., Gupta, M., . . . Goodman, S. G. (2011). Assessment and Management of Acute Coronary Syndromes (ACS): A Canadian Perspective on Current Guideline-Recommended Treatment – Part 1: Non-ST–Segment Elevation ACS. Canadian Journal of Cardiology, 27, S387-S401. doi:10.1016/j.cjca.2011.08.110Kirchberger, I., Meisiner, C., Heier, M., Kling, B., Wende, R., Greschik, C., . . . Kuch, B. (n.d.). Patient-reported symptoms in acute myocardial infarction: differences related to ST-segment elevation. Journal of Internal Medicine, 270, 58-64. doi:10.1111/j.1365-2796.2011.02365.xKostapanos, M. S., Florentin, M., & Elisaf, M. S. (2013). Gender differences in the epidemiology, clinical presentation, prevention, and prognosis of acute coronary syndromes. Angiology, 64(1), 5-8. doi:10.1177/0003319712446188Kyt?, V., Sipil?, J., & Rautava, P. (2015). Gender and in-hospital mortality of ST-segment elevation myocardial infarction (from a multihospital nationwide registry study of 31,689 patients). The American Journal of Cardiology, 115, 303-306. doi:10.1016/j.amjcard.2014.11.001Lavall, M. C., Bagatini, M. D., Thome, G. R., Bonfanti, G., Moretto, M. B., Zimmermann de Oliveira, L., . . . Schetinger, M. C. (2015, July). Extracellular hydrolysis of adenine nucleotides and nucleoside adenosine is higher in patients with ST elevation than non-ST elevation in acute myocardial infarction. Clinical Laboratory, 61, 761-767.Lee, C. Y., Hairi, N. N., Wan Ahmanad, W., Ismail, O., Liew, H. B., Zambahari, R., . . . Sim, K. H. (2013, August). Are there gender differences in coronary artery disease? The Malaysian national cardiovascular disease database - percutaneous coronary intervention (NCVD-PCI) registry. PLoS ONE, 8(8), e72382. doi:10.1371/journal.pone.0072382Marshall, K. (2011, April). Acute coronary syndrome: diagnosis, risk assessment and management. Nursing Standard, 25(23), 47-57.Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., . . . Jiménez, M. C. (2016). Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation, 133, 000-000.Otten, A. M., Maas, A. H., Ottervanger, J., Kloosterman, A., van 't Hof, A. W., Dambrink, J. E., . . . de Boer, M. J. (2013). Is the difference in outcome between men and women treated by primary percutaneous coronary intervention age dependent? Gender difference in STEMI stratified on age. European Heart Journal: Acute Cardiovascular Care, 2(4), 334-341. doi:10.1177/2048872612475270Pellico, L. H. (2013). Focus on Adult Health: Medical-Surgical Nursing. Philadelphia: Lippincott Williams & Wilkins.Ravn-Fischer, A., Karlsson, T., Santos, M., Bergman, B., Herlitz, J., & Johanson, P. (2012). Inequalities in the early treatment of women and men with acute chest pain? The American Journal of Emergency Medicine, 30, 1515-1521. doi:10.1016/j.ajem.2011.12.020Shen, L., Shah, B. R., Nam, A., Holmes, D., Alexander, K. P., Bhatt, D. I., . . . Roe, M. T. (2014, June). Implications of prior myocardial infarction for patients presenting with an acute myocardial infarction. American Heart Journal, 167(6), 840-845. doi:10.1016/j.ahj.2014.03.009Thygesen, K., Alpert, J. S., Jaffe, A. S., Simoons, M. L., Chaitman, B. R., & White, H. D. (2012). Third Universal Definition of Myocardial Infarction. Circulation, 126, 2020-2035.White, H., Thygesen, K., Alpert, J. S., & Jaffe, A. (2014). Universal MI definition update for cardiovascular disease. Current Cardiology Report, 16(492), 1-10.Wilkinson, J. M., & Treas, L. S. (2011). Fundamentals of Nursing (2nd ed., Vol. 1). Philadelphia: F.A. Davis.Zhang, Z., Fang, J., Gillespie, C., Wang, G., Hong, Y., & Yoon, P. W. (2012). Age-Specific gender differences in in-hospital mortality by type of acute myocardial infarction. The American Journal of Cardiology, 109, 1097-1103. doi:10.1016/j.amjcard.2011.12.001 AppendixFigure SEQ Figure \* ARABIC 1: Definition of myocardial infarctionCITATION Thy12 \p 2020 \l 1033 (Thygesen, et al., 2012, p. 2020)Table SEQ Table \* ARABIC 1: MI characteristics according to gender and ageWomen < 65 years (n=708)Men < 65 years (n=3006)Women ≥ 65 years(n=1047)Men ≥ 65 years (n=1985)History of:MI385%2248%777%30115%CABG112%562%353%1156%PCI193%1625%576%19510%Stroke172%502%333%1106%Risk Factors:HTN24535%79927%49548%69035%DM7010%2358%21421%25113%Hyperlipidemia13720%70125%20421%37220%Family History37555%140048%31432%55429%Current Smoking46867%176660%23623%56530%Adapted from CITATION OttenDifferinOutcome \l 1033 (Otten, et al., 2013). Is the difference in outcome between men and women treated by primary percutaneous coronary intervention age dependent? Gender difference in STEMI stratified on age. European Heart Journal: Acute Cardiovascular Care, 2(4), 334-341. ................
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