Abstract
BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is a well-established cardiovascular risk predictor. However, it remains unclear whether the changes in LDL-C over time characterized by time in target range (TTR) are associated with adverse clinical outcomes. OBJECTIVES: This study aimed to investigate the association between LDL-C TTR and adverse outcomes in the general population. METHODS: In 8,813 ARIC (Atherosclerosis Risk In Communities) study participants with ≥2 LDL-C measures between the first (1987-1989) and fifth (2011-2013) visits, LDL-C TTR was defined as <70 mg/dL or <130 mg/dL for participants with or without prevalent atherosclerotic cardiovascular disease (CVD). Multivariable Cox models, competitive risk analysis, and a 10-year landmark analysis were used to estimate the association of LDL-C TTR with myocardial infarction (MI), CVDs, heart failure (HF), and stroke. RESULTS: Over 6.2 years (median), 1,010 participants experienced MI, 1,308 participants experienced CVD, 1,863 participants experienced HF, and 753 participants experienced stroke. In multivariable-adjusted analyses, compared with participants with LDL-C TTR of 0% to 25%, those with LDL-C TTR of 75% to 100% had 33.2% lower risk of MI (HR: 0.668; 95% CI: 0.539-0.829), 33.8% for CVD (HR: 0.662; 95% CI: 0.548-0.799), 15.3% for HF (HR: 0.847; 95% CI: 0.729-0.984), and 23.7% for stroke (HR: 0.763; 95% CI: 0.603-0.964). Adding LDL-C TTR to a conventional risk model significantly improved risk prediction (P < 0.001) assessed by C statistics, net reclassification improvement, and integrated discrimination improvement for MI (0.70, 33.95%, and 1.01%) and for CVD (0.71, 35.42%, and 1.30%). CONCLUSIONS: In the general population, higher LDL-C TTR was significantly associated with lower risks of adverse clinical outcomes.