Association between remnant cholesterol at the age of 30 and all-cause mortality during long-term follow-up: a cohort study

Background Remnant cholesterol refers to cholesterol carried in triglyceride-rich lipoproteins. Elevated remnant cholesterol in middle-aged and older adults is associated with cardiovascular (CV) mortality. However, whether remnant cholesterol measured at the age of 30 is associated with the risk of long-term mortality remains unresolved. Purpose We aimed to test the hypothesis that elevated remnant cholesterol measured at the age of 30 is associated with long-term mortality. In exploratory analyses we also tested if elevated remnant cholesterol is associated with cause-specific mortality. Methods Individuals were recruited from the “Oslo Health Study” (HUBRO) in the year 2000. Briefly, all 30-year-old inhabitants of Oslo, Norway, were invited to a health survey including assessment of health status and non-fasting blood samples. Remnant cholesterol was calculated as total cholesterol minus (LDL cholesterol + HDL cholesterol). Long-term clinical follow-up was obtained through linkage with the mandatory Norwegian Cause of Death Registry, up to 24 years after inclusion. Multivariate Cox analyses were adjusted for sex and ancestry in “model 1” and additionally for smoking status, cumulative smoking (pack years), systolic blood pressure, body mass index, diabetes mellitus, LDL cholesterol, alcohol consumption and education ≤ 12 years in “model 2”. Results A total of 5966 individuals were included (56% women). Mean age was 30.6 ± 0.8 years and <1% had self-reported previous CV disease at baseline. After 24 years of follow-up 108 individuals (1.8%) died. The causes of death were cancer in 55 individuals, CV disease in 12 individuals and 41 had other causes of death. When remnant cholesterol was divided into clinically relevant groups (< 0.5 mmol/L, 0.5-1.0 mmol/L and ≥ 1.0 mmol/L), the cumulative incidence of total mortality was 78, 62 and 112 per 100.000 person-years, respectively. The adjusted hazard ratio (HR) for total mortality per 1 mmol/L increase in remnant cholesterol was 1.8 (95% confidence interval [CI] 1.2-2.6, P-value: 0.0020) in model 1 and 1.6 (95% CI 1.1-2.5, P-value: 0.021) in model 2 (Figure). In exploratory analyses the HR for cancer related mortality was 1.8 (95% CI 1.0-3.1, P-value: 0.044) in model 1 and 2.0 (95% CI 1.1-3.5, P-value: 0.022) in model 2 per 1 mmol/L increase in remnant cholesterol. For CV mortality, although rare, the HR was 2.4 (95% CI 1.1-5.0, P-value 0.020) in model 1 and non-significant in model 2. Mortality from other causes was not associated with elevated remnant cholesterol. Conclusion In young adults from the general population, elevated remnant cholesterol at the age of 30 years was associated with increased risk of all-cause mortality during long-term follow-up. In exploratory analyses, an increased risk of cancer-related and cardiovascular mortality with elevated remnant cholesterol was observed.