Abstract
Background: Dyslipidemia is a major risk factor for CVD. Left ventricular mass (LVM) is an independent predictor of heart failure and other cardiovascular events. It is unclear whether and how altered plasma lipidome (all lipids in a plasma sample) affects LVM. The relationship between longitudinal change in plasma lipidome and change in LVM is also unstudied in any racial/ethnic group. Objective: To identify molecular lipid species associated with LVM, independent of traditional risk factors. Methods: Using an untargeted LC-MS, we repeatedly measured 1,542 lipids in 3,162 fasting plasma samples collected at two time points (2001-2003, 2006-2009, mean 5.5 years apart) from 1,581 American Indians in the Strong Heart Family Study. All participants were free of overt CVD at both time points. LVM was measured by M-mode echocardiography and LVM index (LVMI) was calculated as LVM/height 2.7 . Lipids associated with LVMI were identified by generalized estimating equation (GEE) models, adjusting for age, sex, center, BMI, smoking, blood pressure, renal function, LDL-c, and diabetes. We first conducted the analysis at each time point, separately, and then combined the results by meta-analysis. The longitudinal association between change in lipids and change in LVMI was examined by GEE, adjusting for the same covariates plus baseline lipids and LVMI. Multiple testing was controlled by false discovery rate at 0.05. Results: The mean age of participants was 39.8 years (62.5% women) at baseline and 45.1 years at follow-up. We identified 325 lipids (125 known), largely fatty acyls, sterol lipids, sphingolipids, glycerolipids, and glycerophospholipids, significantly associated with LVMI at both time points. Longitudinal changes in 17 lipids, including glycerolipids, glycerophospholipids, and sphingolipids, were either positively (ORs: 1.09 -1.95) or negatively (ORs: 0.50 - 0.69) associated with change in LVMI over 5 years of follow-up. Changes in lipids explain up to 1.58% of the variability in the change of LVMI during follow-up. Additional adjustments for use of anti-hypertensive and lipid-lowering drugs did not change the results. Conclusion: Altered fasting plasma lipidome and its longitudinal change over time were significantly associated with LVMI beyond clinical factors and baseline lipids. Our results shed light on the mechanisms through which dyslipidemia may affect LV remodeling, thereby contributing to heart failure or other cardiovascular events.
Published Version
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