Determining propensity for sub-optimal low-density lipoprotein cholesterol response to statins and future risk of cardiovascular disease

Weng, Stephen Franklin; Akyea, Ralph Kwame; Man, Kenneth KC; Lau, Wallis C. Y.; Iyen, Barbara; Blais, Joseph Edgar; Chan, Esther W; Siu, Chung Wah; Qureshi, Nadeem; Wong, Ian C. K.; Kai, Joe

Abstract

Background: Variability in low-density lipoprotein cholesterol (LDL-C) response to statins is underappreciated. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease (CVD) and 10-year CVD outcomes.

Methods and Results: A multivariable model was developed using 183,213 United Kingdom (UK) patients without CVD to predict probability of sub-optimal SR, defined by guidelines as <40% reduction in LDL-C. We externally validated the model in a Hong Kong (HK) cohort (n=170,904). Patients were stratified into four groups by predicted SR and 10-year CVD risk score: [SR1] optimal SR & low risk; [SR2] sub-optimal SR & low risk; [SR3] optimal SR & high risk; [SR4] sub-optimal SR & high risk; and 10-year hazard ratios (HR) determined for first major adverse cardiovascular event (MACE).

Our SR model included 12 characteristics, with an area under the curve of 0.70 (95% confidence interval [CI] 0.70–0.71; UK) and 0.68 (95% CI 0.67–0.68; HK). HRs for MACE in predicted sub-optimal SR with low CVD risk groups (SR2 to SR1) were 1.39 (95% CI 1.35–1.43, p<0.001; UK) and 1.14 (95% CI 1.11–1.17, p<0.001; HK). In both cohorts, patients with predicted sub-optimal SR with high CVD risk (SR4 to SR3) had elevated risk of MACE (UK HR 1.36, 95% CI 1.32–1.40, p<0.001: HK HR 1.25, 95% CI 1.21–1.28, p<0.001).

Conclusions: Patients with sub-optimal response to statins experienced significantly more MACE, regardless of baseline CVD risk. To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment.

• Journal Article Type: Article
• Acceptance Date: Nov 17, 2021
• Online Publication Date: Dec 2, 2021
• Publication Date: Dec 2, 2021
• Deposit Date: Nov 29, 2021
• Publicly Available Date: Dec 7, 2021
• Journal: PLoS ONE
• Electronic ISSN: 1932-6203
• Publisher: Public Library of Science (PLoS)
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 12
• Article Number: e0260839
• DOI: https://doi.org/10.1371/journal.pone.0260839
• Keywords: propensity, sub-optimal low-density lipoprotein cholesterol response, statins, cardiovascular disease
• Public URL: https://nottingham-repository.worktribe.com/output/6841316
• Publisher URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260839