Circulating PCSK9 Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors
Background—The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering of plasma low-density lipoprotein (LDL) cholesterol and prevention of cardiovascular disease (CVD). The relationship between circulating PCSK9 and incident CVD in the general population is unknown. We investigated whether serum PCSK9 concentration is associated with incident CVD in a prospective cohort study of 4,232 men and women aged 60 at the time of recruitment.
Methods and Results—Incident CVD was recorded by matching to national registries. After 15 years of follow-up, a total number of 491 incident events (fatal and non-fatal myocardial infarctions, unstable angina, deaths from coronary heart disease, fatal and non-fatal ischemic strokes) were recorded. Cox Proportional Hazards model was used to calculate Hazard ratios (HR) with 95% confidence intervals (CI). Baseline serum PCSK9 concentration predicted incident CVD; concentration in quartile 4, as compared to quartile 1, was associated with a HR of 1.69 (95% CI 1.30-2.19) after adjustment for sex. Further adjustment for LDL cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), triglycerides, hypertension, diabetes, smoking, overweight, obesity, physical inactivity and statin use resulted in a decrease of the HR: 1.48 (95% CI 1.12-1.95).
Conclusions—Serum PCSK9 concentration is associated with future risk of CVD even after adjustments for established CVD risk factors. Further studies are needed to confirm this observation.
- Received July 15, 2015.
- Revision received February 8, 2016.
- Accepted February 12, 2016.