Residual cardiovascular risk in individuals on lipid-lowering treatment: Quantifying absolute and relative risk in the community

Objective The residual cardiovascular disease (CVD) risk in individuals on long-term lipid-lowering treatment (LLT) in the general population is not well described. Methods We estimated absolute CVD risks by age and sex for different categories of low-density lipoprotein cholesterol (LDL-C) levels, stratified by LLT status, and assessed subclinical carotid atherosclerosis in 3012 Framingham Study participants (mean age, 58.4 years; 55% women) free of CVD. Individuals were categorised into five groups: (1) LDL-C <100 mg/dL without LLT; (2) LDL-C ≥100 mg/dL to <130 mg/dL without LLT; (3) LDL-C <130 mg/dL on LLT; (4) LDL-C ≥130 mg/dL without LLT; and (5) LDL-C ≥130 mg/dL on LLT. Results Individuals in groups 3-5 had significantly more carotid atherosclerosis compared with group 1. During follow-up (median, 13.7 years), 548 CVD events occurred. Individuals on LLT (groups 3 and 5) had substantial residual CVD risk (26.7 (95% CI 19.5 to 34.0) and 24.1 (95% CI 16.2 to 31.9) per 1000 person-years, respectively), representing approximately three times the risk for untreated individuals with LDL <100 mg/dL (group 1: 9.0 (95% CI 6.8 to 11.3) per 1000 person-years). Absolute CVD risks rose with age and were slightly greater in men than in women. After adjustment for traditional risk factors, groups 3-5 displayed increased hazards for CVD (HR=1.47, 1.42 and 1.54, respectively) compared with group 1. Further adjustment for carotid atherosclerosis modestly attenuated these results. Conclusions There is substantial residual CVD risk in individuals on LLT, compared with participants with optimal LDL-C (<100 mg/dL), even when LDL-C levels <130 mg/ dL are reached.