Abstract 21316: Mitochondrial DNA Copy Number and Ventricular Remodeling

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Abstract

Introduction: The effect of mitochondrial DNA copy number (mtDNA-CN), which reflects energy reserves and oxidative stress, on left ventricular (LV) remodeling in the general population may provide insights into heart failure development.

Hypothesis: Lower mtDNA-CN values from blood samples will be associated with concentric remodeling.

Methods: Longitudinal analyses of MESA participants with mtDNA-CN and MRI-measured LV mass to volume ratio (MVR) at baseline and the 10-year follow-up (n=2735) were performed. mtDNA-CN was estimated using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Analyses were adjusted for age, sex, and field center, and standardized. LV mass and volumes were measured from cine images. Concentric remodeling was assessed by higher MVR. The association of mtDNA-CN with MVR, adjusted for the ASCVD/AHA risk score as a time-varying covariate, was assessed with mixed-effects models. Longitudinal change in MVR and LV ejection fraction (LVEF) was assessed with an interaction term of mtDNA-CN and time.

Results: Population average age (SD) was 60 (9) years, with 48% males, 42% Caucasians, 12% Chinese, 22% African-American and 21% Hispanics. Mean MVR was 0.95 (0.18) g/ml at baseline and 1.05 (0.23) g/ml at follow-up. Lower mtDNA-CN was associated with higher MVR values (coef=-0.006, p=0.01, Fig 1), as well as greater longitudinal change in slope of this association (interaction term coef =-0.008, p=0.03) with small effect sizes (Cohens f2= -0.018 and -0.019 respectively). The longitudinal change reflected greater increase in concentric remodeling in those with low mtDNA-CN at baseline. mtDNA-CN values were not associated with LVEF.

Conclusions: Lower mtDNA-CN was associated with both high levels at baseline and longitudinally increasing levels of concentric remodeling in a multiethnic population free of CVD at baseline. Altered myocardial energy reserves may contribute to concentric remodeling

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