Abstract
BACKGROUND: Currently total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are used in clinical practice to estimate future cardiovascular risk. We assessed whether other lipoprotein subclasses also contribute to cause-specific and all-cause mortality in the general population. METHODS: Two independent cohorts of the Study of Health in Pomerania (SHIP-START and SHIP-TREND) were used. Participants were selected from population registration offices. The primary outcomes were all-cause, cardiovascular and cancer mortality. TC, total triglycerides (TG), phospholipids as well as the fractional concentrations of cholesterol, TG, phospholipids, and apolipoproteins of all lipoprotein subclasses were measured using nuclear magnetic resonance spectroscopy. Cox proportional hazard regression models were applied to assess the association between lipoprotein subclasses and mortality. Additionally, cause-specific hazards for cardiovascular disease (CVD) and cancer mortality were modelled considering competing events. RESULTS: Data from 3,579 SHIP-START and 4,267 SHIP-TREND individuals were included. During follow-up, 946 (26.4%) SHIP-START and 387 (9.1%) SHIP-TREND participants died. In both cohorts, total LDL-TG and LDL1-TG to LDL6-TG but not total TG were positively or U-shaped related with all-cause mortality. In SHIP-START, total TG, VLDL-TG, IDL-TG and LDL-TG (including subclasses) were associated with CVD mortality. HDL4-C as well as small and dense LDL-C (e.g. LDL6-C) represented risk factors for mortality with mutually enhancing effects. CONCLUSIONS: The findings suggest that lipoprotein subclasses, especially LDL-TGs or HDL4-C/LDL6-C, provide information beyond the established TC and LDL-C levels and therefore might be of use for an early identification of subjects at risk.