Dual elevated remnant cholesterol and C-reactive protein in myocardial infarction, atherosclerotic cardiovascular disease, and mortality

Background and aims

Elevated remnant cholesterol and low-grade inflammation each cause atherosclerotic cardiovascular disease (ASCVD); however, it is unknown whether joint elevation of both factors confers the highest risk. We tested the hypothesis that dual elevated remnant cholesterol and low-grade inflammation marked by elevated C-reactive protein is associated with the highest risk of myocardial infarction, ASCVD, and all-cause mortality.

Methods

The Copenhagen General Population Study randomly recruited white Danish individuals aged 20–100 years in 2003–2015 and followed them for a median 9.5 years. ASCVD was cardiovascular mortality, myocardial infarction, stroke, and coronary revascularization.

Results

In 103,221 individuals, we observed 2,454(2.4%) myocardial infarctions, 5,437(5.3%) ASCVD events, and 10,521(10.2%) deaths. The hazard ratios increased with each of stepwise higher remnant cholesterol and stepwise higher C-reactive protein. In individuals with the highest tertile of both remnant cholesterol and C-reactive protein compared to individuals with the lowest tertile of both, the multivariable adjusted hazard ratios were 2.2(95%CI:1.9–2.7) for myocardial infarction, 1.9(1.7–2.2) for ASCVD, and 1.4(1.3–1.5) for all-cause mortality. Corresponding values for only the highest tertile of remnant cholesterol were 1.6(1.5–1.8), 1.4(1.3–1.5), and 1.1(1.0–1.1), and those for only the highest tertile of C-reactive protein were 1.7(1.5–1.8), 1.6(1.5–1.7), and 1.3(1.3–1.4), respectively. There was no statistical evidence for interaction between elevated remnant cholesterol and elevated C-reactive protein on risk of myocardial infarction (p = 0.10), ASCVD (p = 0.40), or all-cause mortality (p = 0.74).

Conclusions

Dual elevated remnant cholesterol and C-reactive protein confers the highest risk of myocardial infarction, ASCVD, and all-cause mortality, that is, compared to either of these two factors individually.

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