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

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

doi:10.1371/journal.pone.0260839

Ian C. K. Wong, Joseph Edgar Blais + Show 9 more

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https://doi.org/10.1371/journal.pone.0260839

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Abstract

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. 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). 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.

Highlights

Cardiovascular disease (CVD) is a significant cause of mortality and morbidity, accounting for almost a third of all deaths globally [1]
Patients were stratified into four groups by predicted statin response (SR) and 10-year cardiovascular disease (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)
To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment

Summary

Introduction

Cardiovascular disease (CVD) is a significant cause of mortality and morbidity, accounting for almost a third of all deaths globally [1]. Statin use is set to rise further in many countries as guidelines recommend their use in greater proportions of the population [3, 4]. In the United States alone, the proportion of adults whom statins are indicated has increased from 17.9% (21.8 million) to 27.8% (39.2 million) from 2002 to 2013 [5], with similar magnitude increases in most European [6] and Asian countries [7]. Guidelines in the United States (US), United Kingdom (UK), Europe (EU) and Hong Kong (HK) recommend intended LDL-C reduction targets for statin therapy to reduce CVD. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline suggests a fixed dose (or intensity) of statin depending on absolute CVD risk, with intended LDL-C reduction of 30–50% [4]. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease (CVD) and 10-year CVD outcomes

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