Adverse changes to cardiac structure and function were found to be associated with low-density lipoprotein cholesterol (LDL-C) and triglycerides plasma concentrations, according to results of a Mendelian randomization study published in the Journal of the American College of Cardiology.

In this study, 2006 to 2010 data from United Kingdom (UK) Biobank for 500,000 people aged 40 to 69 years were examined. In these individuals, serum concentrations of high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride were enzymatically measured.

Genetic risk scores (GRSs) were calculated using risk loci from the Global Lipids Genetic Consortium and linkage disequilibrium clumping. A 2-stage least squares Mendelian randomization analysis was performed. A total of 436,064 individuals had available cholesterol data, and 17,311 had cardiovascular magnetic resonance data.

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Individuals were stratified according to LDL-C concentrations. All demographic parameters differed significantly across LDL-C percentile groups: individuals in the highest percentile were older, more likely to be women, and had higher body mass indexes, blood pressures, and glycemic measurements.

The variances in lipid concentrations accounted for by the GRSs were: 10.8% for LDL-C (F-statistic, 2492), 7.3% for HDL-C (F-statistic, 1811), and 5.0% for triglycerides (F-statistic, 925).

A 1 mmol/L increase in lifetime LDL-C exposure was associated with higher left ventricular (LV) end-diastolic volume (LVEDV; b, 1.85; 95% CI, 0.59-3.14 ml; P =.004) and LV mass (b, 0.81; 95% CI, 0.1-1.51 g; P =.023). Similar associations between LDL-C and LVEDV (inverse-variance-weighted [IVW] b, 1.62; 95% CI, 0.32-2.91 ml; P =.014) and LDL-C and LV mass (IVW b, 0.66; 95% CI, 0.10-1.22 g; P =.021) were detected in a sensitivity analysis.

A 1 mmol/L increase in lifetime triglyceride exposure was associated with reduced LV ejection fraction (b, -0.52%; 95% CI, -0.92% to -0.13%; P =.011) and increased LV mass (b, 1.37; 95% CI, 0.45-2.3 g; P =.004). Similar associations between triglyceride concentration and LV mass (IVW b, 0.61; 95% CI, 0.04-1.18 g; P =.036) were obtained with a sensitivity analysis.

The investigators did not observe a significant association between HDL-C and cardiac structure and function variables.

Statin use was found to modify the association between phenotypic LDL-C and standardized GRS for LDL-C (Pinteraction <.0001), with lower LDL-C levels in patients treated with statins than predicted by their GRS.

Study limitations include a lack of pharmacotherapy data, and the inability to determine the mechanisms underlying the observed causal relationship between LV parameters and LDL-C/triglycerides.

These data indicate that increased exposure to LDL-C and triglycerides over a lifetime may be associated with adverse alterations to the LV.


Aung N, Sanghvi M M, Piechnick S K, et al. The Effect of Blood Lipids on the Left Ventricle: A Mendelian Randomization Study. J Am Coll Cardiol. 2020;76(21):2477–2488.