Prognostic role of remnant cholesterol and traditional cardiovascular risk factors in young adults: results of long-term follow-up of a cohort of 30-year-old norwegians

Abstract Background There are limited data on the prevalence and impact of traditional cardiovascular (CV) risk factors among young adults. In addition, more knowledge on novel CV risk factors is needed to explain the residual risk beyond that of the traditional risk factors. Increasing evidence suggest a causal role of remnant cholesterol (RC) in the development of atherosclerotic cardiovascular disease (CVD) and subsequent clinical events. However, the role of RC in young adults is unresolved. Purpose We aimed to evaluate the prevalence of traditional risk factors and the respective sex-differences in young adults, as well as their association with long-term CV events. Further, we hypothesized that higher RC concentrations are associated with impaired CV prognosis. Methods In year 2000, all 30-year-old inhabitants of our city were invited to a cross-sectional study including assessment of health status, anthropometric measurements, and non-fasting blood samples. RC was calculated as total cholesterol minus (LDL-C + HDL-C). Long-term clinical follow-up was performed through linkage with mandatory national registries, 22 years after inclusion. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for unstable angina and coronary revascularization. Results A total of 5950 individuals were included (56% women). At baseline, men displayed significantly higher systolic and diastolic blood pressure, total cholesterol, LDL-C and triglycerides, as compared with women (Table 1). Also, men had higher levels of RC (Table 1). During a mean follow-up time of 22 years, 108 events (1.8%) occurred. In multivariable Cox regression analysis, non-West-European ancestry (adjusted [a] HR 1.76, 95% confidence interval [CI] 1.03-2.99), diabetes mellitus (aHR 6.39, 95% CI 2.52-16.2), systolic blood pressure (aHR 1.03, 95% CI 1.01-1.04), and LDL-cholesterol (aHR 1.37, 95% CI 1.11-1.68) were associated with an increased risk of CV events during long-term follow-up. Female gender was associated with a reduced risk of CV events (aHR 0.38, 95% CI 0.23-0.64), whereas smoking status did not show any significant association. RC was identified as a significant predictor of CV events (aHR 1.55, 95% CI 1.11-2.18, per 1.0 mmol/L increase). The highest RC quartile (mean RC: 1.1 mmol/L), had the highest event rate (Figure 1, p<0.001 with log-rank test). Conclusion This study uncovers significant sex-differences in modifiable CV risk factors among young adults at the age of 30, which are associated with increased risk for long-term CV events. Interestingly, increasing concentrations of RC at the age of 30 were strongly associated with impaired long-term CV outcome and should be accounted for in early risk prediction.Baseline characteristics.Remnant cholesterol and CVD events.