Does Lowering Low‐Density Lipoprotein Cholesterol With Statin Restore Low Risk in Middle‐Aged Adults? Analysis of the Observational MESA Study

BACKGROUND: It is unclear if statin therapy in midlife can restore low cardiovascular risk in hypercholesterolemic individuals. METHODS AND RESULTS: At baseline, we grouped 5687 MESA (Multi‐Ethnic Study of Atherosclerosis) participants aged ≥50 years without clinical cardiovascular disease (CVD) by Adult Treatment Panel III statin treatment recommendation and statin treatment status. We used Cox regression to compare the risks for coronary heart disease and CVD between the untreated group with low‐density lipoprotein cholesterol (LDL‐C) <100 mg/dL (reference) and other groups, adjusting for CVD risk factors. We also grouped participants by LDL‐C level (< or ≥100 mg/dL), coronary artery calcium score (0 or >0 Agatston units), and statin status (untreated or treated) with the untreated LDL‐C <100 mg/dL and coronary artery calcium=0 Agatston units as the reference. There were 567 coronary heart disease and 848 CVD events over 15 years of follow‐up. The hazard ratios (HRs) for coronary heart disease and CVD in the group with statin‐treated LDL‐C <100 mg/dL were 1.16 (95% CI, 0.85–1.58) and 1.02 (95% CI, 0.78–1.32), respectively. However, participants with coronary artery calcium >0 Agatston units, treated to LDL‐C <100 mg/dL had HRs of 2.6 (95% CI, 1.7–4.2) for coronary heart disease and 1.8 (95% CI, 1.2–2.6) for CVD. CONCLUSIONS: Individuals treated with statins to LDL‐C <100 mg/dL had similar levels of risk for atherosclerotic CVD as individuals with untreated LDL‐C <100 mg/dL. However, individuals with coronary artery calcium >0 Agatston units have substantially higher risks despite lipid‐lowering therapy, suggesting that statin treatment in midlife may not restore a low‐risk state in primary prevention patients with established coronary atherosclerosis.