Cholesterol levels and cardiovascular outcomes following statin initiation for primary prevention: a cohort study

Background — Non-high-density lipoprotein cholesterol (HDL-C) is increasingly incorporated into guidelines along with low-density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions.

Objectives — The purpose of this study was to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention and their association with incident cardiovascular events.

Methods — This was a population-based cohort study in Ontario, Canada, among persons aged ≥66 years starting a statin for primary prevention between January 1, 2012, and December 31, 2019. We identified those with a lipid panel in the 1-year after starting a statin and categorized individuals based on LDL-C and non-HDL-C thresholds for intensification in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines. We stratified by diabetes/chronic kidney disease (CKD) status. The primary outcome was the composite of all-cause mortality or cardiovascular events, with follow-up to December 31, 2020. We used a Cox proportional hazards model for analysis.

Results — Our cohort comprised 125,013 people. The median follow-up was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C thresholds, being above both thresholds was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR: 1.10; 95% CI: 1.05-1.15) and for those with diabetes/CKD (HR: 1.16; 95% CI: 1.09-1.23). Being below the LDL-C threshold but above non-HDL-C threshold was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR: 1.16; 95% CI: 1.03-1.30).

Conclusions — These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after statin initiation for primary prevention.