Cardiovascular Outcomes in Adults with Low-Density Lipoprotein Cholesterol Levels of ≥4.9 mmol/L: 15-Year Follow-up of the CoLaus|PsyCoLaus Study.

Aims Guidelines recommend lipid-lowering treatment (LLT) in all adults with low-density lipoprotein cholesterol (LDL-C) ≥4.9 mmol/L independently of a genetic diagnosis or other cardiovascular risk factors, despite this population being very heterogeneous and limited data available on cardiovascular risk. To assess cardiovascular risk in the overall population with LDL-C ≥4.9 mmol/L vs. <4.9 mmol/L and different subgroups. Methods We analysed 5249 adults without atherosclerotic cardiovascular disease (ASCVD) and without LLT at baseline from CoLaus|PsyCoLaus, a prospective population-based cohort. ASCVD was our outcome. Results Among 5249 participants (mean [SD] age 51.7 [10.5] years, 55% female, median follow-up 14.3 years), 291 (5.5%) had LDL-C ≥4.9 mmol/L. Overall, 300 (3.7%) participants experienced a first-time ASCVD, among which 27 (9%) had LDL-C ≥4.9 mmol/L. The adjusted hazard ratio (CI) for first-time ASCVD was 1.64 (1.10-2.44) for LDL-C ≥4.9 mmol/L vs. <4.9 mmol/L, 1.43 (0.57-3.58) in participants without hypertension, diabetes, or smoking (N=2497), 1.43 (0.80-2.55) in participants without suspicion of familial hypercholesterolemia (N=5101), and 1.46 (0.93-2.27) following adjustment for a polygenic risk score (data available for N=3728). Conclusions The study reports an association between LDL-C ≥4.9 mmol/L and ASCVD in a large cohort from Switzerland. However, we found heterogeneity in risk across different subgroups. Furthermore, polygenic risk for coronary artery disease seems to partly account for this association. While further studies are needed to assess the cardiovascular risk specifically in healthier subgroups, our results suggest, that a more precise risk assessment is needed for individuals with LDL-C ≥4.9 mmol/L.This population-based cohort study assessed the cardiovascular risk in adults with very high low-density lipoprotein cholesterol (LDL-C) of ≥4.9 mmol/L who have never experienced a cardiovascular event and who do not receive lipid-lowering therapy. –LDL-C ≥4.9 mmol/L is associated with an increased risk for cardiovascular disease.–More data is needed to assess this risk in adults who do not have additional cardiovascular risk factors (hypertension, diabetes, smoking) or who do not have a suspicion of a genetic disease.