Circulating PCSK9 Predicts Future Cardiovascular Risk

Study Questions:

The relationship between secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) and incident cardiovascular disease (CVD) in the general population is unknown. Is the serum PCSK9 concentration associated with incident CVD?


Incident CVD was recorded by matching to national registries. In a prospective cohort study of 4,232 men and women 60 years of age at the time of recruitment, after 15 years of follow-up, a total number of 491 incident events (fatal and nonfatal myocardial infarctions, unstable angina, deaths from coronary heart disease, fatal and nonfatal ischemic strokes) were recorded. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).


During >490,000 person-years at risk, baseline serum PCSK9 concentration predicted incident CVD. Concentration in quartile 4, as compared to quartile 1, was associated with an HR of 1.69 (95% CI, 1.30-2.19) after adjustment for sex. Further adjustment for low-density lipoprotein 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 to 1.48.


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.


The association of future risk of CVD and PCSK9 levels when comparing the 4th and 1st quartile in a healthy cohort has little meaning. The utility of the PCSK9 inhibitors (monoclonal antibody agents) does not appear to be related to the serum concentration. And PCSK9 levels do not correlate with vascular function or structure. However, there is some evidence that PCSK9 may have a prothrombotic role.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Novel Agents

Keywords: Angina, Unstable, Biological Markers, Cardiovascular Diseases, Coronary Artery Disease, Myocardial Infarction, Primary Prevention, Proprotein Convertases, Risk Factors, Stroke

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