Elevated triglycerides are related to higher residual cardiovascular disease and mortality risk independent of lipid targets and lipid-lowering therapy intensity in cardiovascular disease patients

Abstract Background and aims Despite optimal management of low-density lipoprotein cholesterol (LDL-C), substantial residual cardiovascular risk persists in patients with cardiovascular disease (CVD). This persistent residual risk may be attributed, at least in part, to other atherogenic lipoproteins, including triglyceride-rich lipoproteins. We tested the hypotheses that elevated triglycerides (TGs) are related to higher residual CVD and mortality risk in patients with established CVD, and that such relationships depend on guideline-recommended lipid target achievement, high-density lipoprotein cholesterol (HDL-C) levels, and intensity of lipid-lowering therapy. Methods In a prospective cohort study of 9,436 patients with manifest CVD, the relationships between log-transformed TG levels and recurrent cardiovascular events and all-cause mortality were analyzed overall using Cox regression models. Subsequently, analyses were stratified by achievement of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) treatment goals, HDL-C levels, and intensity of lipid-lowering therapy. Effect modification across all strata was assessed by including interaction terms in the main model for all outcomes. Results During a median follow-up of 9.0 years (interquartile range IQR: 4.5–14.1 years), 2,075 recurrent cardiovascular events, 736 myocardial infarctions, 586 strokes, 1,231 cardiovascular deaths, and 2,729 all-cause deaths occurred. Per 1-unit higher log-TG levels, the hazard ratio was 1.17 (95% confidence interval CI: 1.07–1.28) for recurrent cardiovascular events, 1.34 (95% CI: 1.16–1.56) for myocardial infarction, 1.10 (95% CI: 0.92–1.30) for stroke, 1.23 (95% CI: 1.09–1.38) for cardiovascular mortality, and 1.12 (95% CI: 1.03–1.21) for all-cause mortality (Figure 1). These hazard ratios did not depend on achievement of LDL-C and non-HDL-C treatment goals, HDL-C levels, or lipid-lowering therapy intensity (all p for interaction ≥0.05; Figure 2). Conclusions Elevated TGs are related to higher residual CVD and mortality risk in patients with established CVD. These relationships were unrelated to guideline-recommended lipid target achievement, HDL-C levels, and lipid-lowering therapy intensity. These findings highlight the importance of addressing TG-related residual risk in secondary prevention settings.