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Life sciences · Journal article
American Journal of Preventive Cardiology · August 6, 2026
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While proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an effective therapeutic target in secondary prevention of cardiovascular disease (CVD), its role in primary prevention remains unclear. Therefore, we examined the prospective association between PCSK9 and CVD risks in the general population. In the Gusu cohort, 1876 community members (mean age 57 years, 38% males) who were free of CVD in 2014 were included. Serum PCSK9 was measured by enzyme-linked immunosorbent assay kits at baseline and CVD events were followed every 2 years through 2020. Associations between PCSK9 and CVD were examined using a Cox regression model in males and females, respectively. During a median follow-up of 6.7 years, 93 participants developed incident CVD. A higher level of serum PCSK9 at baseline was associated with a lower risk of CVD in males (HR=0.71, 95%CI: 0.52-0.96, P = 0.027 for log-PCSK9), but with a higher risk of CVD in females (HR=1.38, 95%CI: 1.03-1.84, P = 0.032 for log-PCSK9), independently of conventional risk factors. There was a significant heterogeneity between these two sex-specific associations (P = 0.002). Compared with participants with the lowest level of serum PCSK9, those with the highest level had a similar risk of CVD in males (HR=0.57, 95% CI: 0.27-1.20, P = 0.138), but a significantly increased risk in females (HR=2.78, 95%CI: 1.33-5.82, P = 0.006). Hypertension, dyslipidemia, and diabetes did not deliver a significant mediation effect on the association between serum PCSK9 and CVD (all P > 0.05). A higher serum PCSK9 at baseline predicted a higher future risk of CVD in the general female population. PCSK9 may be a candidate circulating biomarker for the risk of CVD in females. Leveraging a prospective cohort study including 1876 community members, this article examined for the first time the association between serum PCSK9 at baseline and the incidence of CVD during a median 6-year follow-up. A higher serum PCSK9 at baseline predicted a higher future risk of CVD in the general female population. Our findings suggest that PCSK9 may be a candidate circulating biomarker for the risk of CVD in females.