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On-line SupplementInsulin Resistance-Associated Decreases in Left Ventricular Diastolic Function Are Strongly Modified by the Extent of Concentric Remodelling in a Community Sample.Vernice Peterson1, Gavin R Norton1, Andrew Raymond2, Carlos D Libhaber2, Aletta ME Millen2, Olebogeng HI Majane2, Muzi J Maseko2, Angela J Woodiwiss1.Cardiovascular Pathophysiology and Genomics Research Unit, Schools of Physiology (VP, GRN, AR, AMEM, OHIM, MJM, AJW) and Clinical Medicine (CDL), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Running title: Obesity and LV diastolic function.Conflict of interest: None VP, GRN and AJW contributed equally to this work.This study was supported by the Medical Research Council of South Africa, the University Research Council of the University of the Witwatersrand, the South African National Research Foundation, the Circulatory Disorders Research Trust, and the Carnegie Corporation.Correspondence and reprint requests: Angela J Woodiwiss: Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa. Tel: +27 11 717 2363, e-mail: angela.woodiwiss@wits.ac.zaFig. S1. Relations (partial r) between blood pressure (BP) and left ventricular (LV) diastolic function in participants with a LV relative wall thickness (RWT) above and below the median for the sample. See table 1 for abbreviations. Adjustments are for age, sex, pulse rate (E/A), regular smoking, regular alcohol consumption, diabetes mellitus or an HbA1c>6.1%, treatment for hypertension, and left ventricular mass index.Table S1. Multivariate adjusted relationships between indexes of adiposity or the homeostasis model of insulin resistance (HOMA-IR) and left ventricular diastolic function in a community sample.Adjustments Partial r p value (95% CI)___________________________________________________________Waist circumference versus Log septal e’ (n=430)* -0.18 (-0.27 to -0.08)<0.0005* + LVMI -0.16 (-0.26 to -0.06)=0.001* + RWT -0.17 (-0.26 to -0.07)<0.001Log LA vol (n=430) * 0.05 (-0.05 to 0.15)=0.28* + LVMI 0.01 (-0.09 to 0.11)=0.81* + RWT 0.05 (-0.05 to 0.15)=0.33Body mass index versusLog septal e’ (n=430)* -0.17 (-0.26 to -0.07)=0.0005* + LVMI -0.14 (-0.23 to -0.05)<0.005* + RWT -0.15 (-0.25 to -0.06)<0.005Log LA vol (n=430)* 0.07 (-0.03 to 0.16)=0.15* + LVMI 0.02 (-0.08 to 0.11)=0.73* + RWT 0.06 (-0.03 to 0.16)=0.19Log HOMA-IR versusLog septal e’ (n=430)* -0.11 (-0.20 to -0.02)<0.05* + LVMI -0.10 (-0.20 to -0.01)<0.05* + RWT -0.10 (-0.19 to -0.01)<0.05Log LA vol (n=430)* 0.05 (-0.05 to 0.15)=0.30* + LVMI 0.03 (-0.06 to 0.13)=0.49* + RWT 0.05 (-0.05 to 0.14)=0.36__________________________________________________________LVMI, left ventricular mass index; RWT, relative wall thickness; e’, velocity of the septal wall myocardial tissue lengthening in early diastole at the mitral annulus; LA vol, left atrial volume. *Adjustments are for age, sex, systolic blood pressure, regular tobacco use, regular alcohol consumption, treatment for hypertension, diabetes mellitus or an abnormal blood glucose control (HbA1c>6.1%), and L VMI or RWT as indicated.Table S2. Independent associations between adiposity index (or the homeostasis model of insulin resistance [HOMA-IR])-left ventricular (LV) relative wall thickness (RWT) interactions and LV diastolic function in a community sample.Adjustments ____________________________________________________________________________ Partial r (95% CI) p valueLog E/A vs Waist circumference*RWT interaction *0.07 (-0.01 to 0.14) =0.09 Body mass index*RWT interaction *0.07 (0.00 to 0.14) =0.05 Log HOMA-IR*RWT interaction * -0.09 (-0.17 to -0.02) <0.02Log E/e’ vs Waist circumference*RWT interaction *0.04 (-0.06 to 0.14) =0.39 Body mass index*RWT interaction * -0.01 (-0.10 to 0.09) =0.89 Log HOMA-IR*RWT interaction *0.11 (0.02 to 0.21) <0.02Log lateral e’ vs Waist circumference*RWT interaction *0.03 (-0.07 to 0.13) =0.56 Body mass index*RWT interaction * 0.08 (-0.02 to 0.17) =0.12 Log HOMA-IR*RWT interaction * -0.11 (-0.24 to -0.05) <0.005 Odds ratio* (95% CI) Wald Х2 p value E/A<0.80 vs Waist circumference*RWT interaction *1.045 (0.844 to 1.293) 0.16=0.69 Body mass index*RWT interaction *1.052 (0.706 to 1.567) 0.06=0.80 Log HOMA-IR*RWT interaction *7.305 (1.821 to 29.305) 7.87<0.005Moderate-to-severe DD (Lateral e’<10, Septal e’<8, LA volume≥34, E/e’≥13, E/A≥0.80) vs Waist circumference*RWT interaction *0.879 (0.696 to 1.110) 1.17=0.28 Body mass index*RWT interaction *0.668 (0.412 to 1.084) 2.66=0.10 Log HOMA-IR*RWT interaction *5.829 (1.296 to 26.223) 6.09=0.014 ___________________________________________________________________________E/A, ratio of transmitral early-to-atrial (late) blood flow velocity; E/e’, E/velocity of the mean value of lateral and septal wall myocardial tissue lengthening in early diastole at the mitral annulus. *Adjustments are for age, sex, diastolic blood pressure (E/A) or systolic blood pressure (E/e’ and lateral e’), regular tobacco use, regular alcohol consumption, treatment for hypertension, diabetes mellitus or an abnormal blood glucose control (HbA1c>6.1%), and pulse rate (E/A).Table S3. Independent associations between adiposity index (or the homeostasis model of insulin resistance [HOMA-IR])-left ventricular (LV) relative wall thickness (RWT) interactions and LV diastolic function in a community sample.AdjustmentsPartial r (95% CI) p value____________________________________________________________________________Log septal e’ vs Waist circumference*RWT interaction *0.02 (-0.07 to 0.12) =0.63 Body mass index*RWT interaction * 0.05 (-0.05 to 0.14) =0.32 Log HOMA-IR*RWT interaction * -0.10 (-0.20 to -0.01) <0.05Log LA volume vs Waist circumference*RWT interaction * -0.03 (-0.13 to 0.07) =0.57 Body mass index*RWT interaction * -0.04 (-0.10 to 0.06) =0.43 Log HOMA-IR*RWT interaction * -0.06 (-0.15 to 0.04) =0.24___________________________________________________________________________e’, velocity of the septal wall myocardial tissue lengthening in early diastole at the mitral annulus; LA, left atrial. *Adjustments are for age, sex, systolic blood pressure, regular tobacco use, regular alcohol consumption, treatment for hypertension, diabetes mellitus or an abnormal blood glucose control (HbA1c>6.1%).Table S4. Lack of independent associations between age or blood pressure-left ventricular (LV) relative wall thickness (RWT) interactions and LV diastolic function in a community sample.AdjustmentsPartial r (95% CI) p value____________________________________________________________________________Log E/A vs Age*RWT interaction *0.04 (-0.04 to 0.11) =0.31 DBP*RWT interaction * 0.05 (-0.02 to 0.12) =0.18Log E/e’ vs Age*RWT interaction *0.07 (-0.02 to 0.16) =0.15 SBP*RWT interaction * 0.03 (-0.06 to 0.13) =0.49Log lateral e’ vs Age*RWT interaction *-0.03 (-0.13 to 0.06) =0.51 SBP*RWT interaction * -0.04 (-0.13 to 0.06) =0.44Log septal e’ vs Age*RWT interaction *-0.07 (-0.17 to 0.02) =0.13 SBP*RWT interaction * -0.06 (-0.16 to 0.03) =0.19___________________________________________________________________________e’, velocity of the septal wall myocardial tissue lengthening in early diastole at the mitral annulus; LA, left atrial. *Adjustments are for age, sex, diastolic blood pressure (E/A), systolic blood pressure (E/e’, lateral e’ and septal e’), regular tobacco use, regular alcohol consumption, treatment for hypertension, diabetes mellitus or an abnormal blood glucose control (HbA1c>6.1%) and pulse rate (E/A).Table S5. Strength (partial r) of relations between the homeostasis model of insulin resistance (HOMA-IR) and septal e’ in participants with a LV relative wall thickness (RWT) above or below the median for the sample.Adjustments Partial r p value (95% CI)____________________________________________________________RWT<0.361Log HOMA-IR versus Log septal e’ (n=215)* -0.03 (-0.17 to 0.11)=0.66RWT≥0.361Log HOMA-IR versusLog septal e’ (n=215)* -0.14 (-0.27 to -0.01)=0.05____________________________________________________________e’, velocity of the septal wall myocardial tissue lengthening in early diastole at the mitral annulus; LA vol, left atrial volume. *Adjustments are for age, sex, systolic blood pressure, regular tobacco use, regular alcohol consumption, treatment for hypertension, diabetes mellitus or an abnormal blood glucose control (HbA1c>6.1%) and left ventricular mass index.Table S6. Adjusted septal e’ across tertiles of the homeostasis model of insulin resistance (HOMA-IR) in participants with a LV relative wall thickness (RWT) above or below the median for the sample. Tertiles of HOMA-IR 123RWT<0.361HOMA-IR<1.091.09 – 2.37≥2.37n= 717470Adjusted septal e’ 10.27±0.3210.71±0.3110.18±0.32RWT≥0.361HOMA-IR<1.111.11 – 2.76≥2.76n= 707471Adjusted septal e’ 9.54±0.32 9.19±0.308.58±0.31*e’, velocity of the septal wall myocardial tissue lengthening in early diastole at the mitral annulus. Adjustments are for age, sex, systolic blood pressure, regular tobacco use, regular alcohol consumption, treatment for hypertension, diabetes mellitus or an abnormal blood glucose control (HbA1c>6.1%) and left ventricular mass index. *p<0.05 versus tertile 1. ................
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