Very Low-Density Lipoprotein Cholesterol May Mediate a Substantial Component of the Effect of Obesity on Myocardial Infarction Risk: The Copenhagen General Population Study

Abstract

Background

Individuals with obesity have higher concentrations of very low-density lipoprotein (VLDL) cholesterol and increased risk of myocardial infarction. We hypothesized that VLDL cholesterol explains a fraction of the excess myocardial infarction risk in individuals with obesity.

Methods

We included 29 010 individuals free of myocardial infarction at baseline, nested within 109 751 individuals from the Copenhagen General Population Study. During 10 years of follow-up, 2306 individuals developed myocardial infarction. Cholesterol content in large and small VLDLs, in intermediate-density lipoprotein (IDL), and in LDL was measured directly with nuclear magnetic resonance spectroscopy.

Results

Median concentrations of cholesterol in large and small VLDLs were 0.12 mmol/L (interquartile range [IQR], 0.07–0.20 mmol/L; 4.5 mg/dL [IQR, 2.6–6.9 mg/dL]) and 0.6 mmol/L (IQR, 0.5–0.8 mmol/L; 25 mg/dL [IQR, 20–30 mg/dL]) in individuals with obesity vs 0.06 mmol/L (IQR, 0.03–0.1 mmol/L; 2.2 mg/dL [IQR, 1.1–3.8 mg/dL]), and 0.5 mmol/L (IQR, 0.4–0.6 mmol/L; 20 mg/dL (IQR, 16–25 mg/dL]) in individuals with normal weight; in contrast, concentrations of IDL and LDL cholesterol were similar across body mass index (BMI) categories. Cholesterol in large and small VLDLs combined explained 40% (95% CI, 27%–53%) of the excess risk of myocardial infarction associated with higher BMI. In contrast, IDL and LDL cholesterol did not explain excess risk of myocardial infarction, whereas systolic blood pressure explained 17% (11%–23%) and diabetes mellitus explained 8.6% (3.2%–14%).

Conclusions

VLDL cholesterol explains a large fraction of excess myocardial infarction risk in individuals with obesity. These novel findings support a focus on cholesterol in VLDL for prevention of myocardial infarction and atherosclerotic cardiovascular disease in individuals with obesity.