Low-Density Lipoprotein Cholesterol Time in Target Range and Clinical Outcomes in the General Population

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.

This study aimed to investigate the association between LDL-C TTR and adverse outcomes in the general population.

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.

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%).

In the general population, higher LDL-C TTR was significantly associated with lower risks of adverse clinical outcomes.