The Effect of Blood Lipids on the Left Ventricle: A Mendelian Randomization Study

BACKGROUND: Cholesterol and triglycerides are among the most well-known risk factors for cardiovascular disease. OBJECTIVES: This study investigated whether higher low-density lipoprotein (LDL) cholesterol and triglyceride levels and lower high-density lipoprotein cholesterol level are causal risk factors for changes in prognostically important left ventricular (LV) parameters. METHODS: One-sample Mendelian randomization (MR) of 17,311 European individuals from the UK Biobank with paired lipid and cardiovascular magnetic resonance data was performed. Two-sample MR was performed by using summary-level data from the Global Lipid Genetics Consortium (n = 188,577) and UK Biobank Cardiovascular Magnetic Resonance substudy (n = 16,923) for sensitivity analyses. RESULTS: In 1-sample MR analysis, higher LDL cholesterol was causally associated with higher LV end-diastolic volume (β = 1.85 ml; 95% confidence interval [CI]: 0.59 to 3.14 ml; p = 0.004) and higher LV mass (β = 0.81 g; 95% CI: 0.11 to 1.51 g; p = 0.023) and triglycerides with higher LV mass (β = 1.37 g; 95% CI: 0.45 to 2.3 g; p = 0.004). High-density lipoprotein cholesterol had no significant association with any LV parameter. Similar results were obtained by using 2-sample MR. Observational analyses were frequently discordant with those derived from MR. CONCLUSIONS: MR analysis demonstrates that LDL cholesterol and triglycerides are associated with adverse changes in cardiac structure and function, in particular in relation to LV mass. These findings suggest that LDL cholesterol and triglycerides may have a causal effect in influencing cardiac morphology in addition to their established role in atherosclerosis. (J Am Coll Cardiol 2020;76:2477-88).