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

Abstract

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.

Keywords: LDL; cardiovascular disease; lipids; residual risk; subclinical disease.

Figure 1

OR for the binary trait ‘carotid ultrasound abnormality’ in an age- and sex-adjusted model (A), as well as in a multivariable-adjusted model (B), including age, sex, systolic blood pressure, antihypertensive medication, smoking and diabetes mellitus. ‘Carotid ultrasound abnormality’ was defined as (1) increased (≥80^th sex-specific percentile) carotid IMT, a combined standardised measure including information from the internal and common carotid arteries, (2) an extreme increase of the common carotid IMT ≥1 mm, or (3) significant stenosis (≥25% narrowing) of the common or internal carotid arteries, consistent with prior publications. IMT, intima media thickness; LDL, low-density lipoprotein; LLT, lipid-lowering treatment; w/out, without.

Figure 2

Survival free of CVD, stratified by LDL group. CVD, cardiovascular disease; LDL, low-density lipoprotein; LLT, lipid-lowering treatment.

Figure 3

HRs for incident CVD by LDL group, adjusted for age, sex, systolic blood pressure, antihypertensive medication, smoking and diabetes mellitus. CVD, cardiovascular disease; LDL, low-density lipoprotein; LLT, lipid-lowering treatment; w/out, without.