Plasma proprotein convertase subtilisin/kexin type 9 levels and the risk of first cardiovascular events.
OBJECTIVE
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that enhances degradation of the LDL receptor. While agents that inhibit PCSK9 markedly reduce atherogenic lipoproteins and show great promise for event reduction, it is unknown whether plasma PCSK9 levels predict incident cardiovascular events.


RESULTS
In a nested case-control evaluation conducted in a prospective cohort of >28 000 initially healthy American women, we measured plasma concentrations of PCSK9 at baseline among 358 participants who subsequently developed major cardiovascular events (cases) and among 358 age, smoking, and hormone replacement therapy matched participants who remained free of disease during 17 years of follow-up (controls). Proprotein convertase subtilisin/kexin type 9 level was not significantly related to smoking status, hypertension, obesity, or a family history of premature cardiovascular disease but was positively associated with apolipoprotein B-100 (r = 0.20, P< 0.001), and triglycerides (r = 0.13, P = 0.004). No associations were observed between PCSK9 and apo A1, HDLC, lipoprotein(a), or high-sensitivity C-reactive protein. Despite modest positive association with atherogenic lipids, baseline levels of PCSK9 did not predict the first cardiovascular events; the odds ratios (ORs) for future vascular events for the lowest (referent) to highest baseline quartiles of PCSK9 were 1.0, 0.94, 0.98, and 1.15 (P-trend = 0.53). In contrast, the corresponding ORs for baseline apo B levels were 1.0, 1.14, 1.34, and 1.94 (P-trend = 0.002).


CONCLUSIONS
In a large-scale primary prevention cohort, plasma levels of PCSK9 measured at baseline did not predict future cardiovascular events.
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, 900 Commonwealth Avenue, Boston, MA 02215, USA Divisions of Preventive Medicine and Cardiovascular Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA pridker@partners.org.
Paul M
PM
Ridker
Department of Laboratory Medicine, Children's Hospital Medical Center, Boston, MA, USA.
Nader
N
Rifai
Department of Laboratory Medicine, Children's Hospital Medical Center, Boston, MA, USA.
Gary
G
Bradwin
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, 900 Commonwealth Avenue, Boston, MA 02215, USA.
Lynda
L
Rose
D000368:Aged; D001055:Apolipoproteins B / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000209:etiology*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000378:metabolism; D005260:Female; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D000071449:Proprotein Convertase 9 / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors
D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D002097:C-Reactive Protein; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
Apolipoprotein B; Epidemiology; Myocardial infarction; PCSK9; Prevention