Abstract

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular events in high-risk patients. However, the influence of circulating PCSK9 concentration on atherosclerotic plaque formation in the younger, healthy population is not fully elucidated. We assessed the relationship between serum PCSK9 concentration and coronary artery calcium (CAC) prevalence in the general population with no history of cardiovascular disease in different age group. Methods: Community-dwelling Japanese men (n = 622) aged 46–82 years, without a history of cardiovascular disease or lipid-lowering medications, were included. Serum PCSK9 concentration and CAC score were measured using the Agatston method, and CAC was defined as an Agatston score of > 10. Multivariable Poisson regression with robust error variance were used to estimate the relative risk (RR) and 95% confidence interval (CI) per 1 SD of the serum PCSK9 concentration for the presence of CAC. We conducted further analysis stratified by age (< 60, 60–69, and 70 ≦ years). Results: The average age, LDL-C, and median serum PCSK9 concentration were 68 years, 122 mg/dL, and 240 ng/mL, respectively. After multivariable adjustment for traditional cardiovascular risk factors, no significant association was observed between serum PCSK9 concentration and CAC prevalence (adjusted relative risk [aRR] 1.05, 95% CI 0.97–1.13). With age stratification, serum PCSK9 concentration was significantly associated with CAC prevalence in men aged < 60 years (aRR 1.38, 95% CI 1.01–1.88), but not in men aged 60–69 years (aRR 0.96, 95% CI 0.85–1.10) or ≧ 70 years (aRR 1.08, 95% CI 0.99–1.19). Conclusions: A higher serum PCSK9 concentration was associated with a higher CAC prevalence in men aged < 60 years, which was independent of traditional cardiovascular risk factors. The results of our study suggest that serum PCSK9 concentration might be associated with earlier-stage atherosclerosis.

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