Circulating proprotein convertase subtilisin-kexin type 9,all-cause mortality,and cardiovascular mortality: The Ludwigshafen Risk and Cardiovascular Health study

Abstract

Background

It is unclear whether proprotein convertase subtilisin-kexin type 9 (PCSK9) concentrations may be useful for cardiovascular risk stratification.

Design

The LUdwigshafen RIsk and Cardiovascular health (LURIC) study is a prospective observational registry of patients who were referred for coronary angiography.

Methods

Circulating PCSK9 was measured in 2139 participants of the LURIC study. There was a follow-up for all-cause and cardiovascular mortality with a median (interquartile range) duration of 10.1 (8.1–10.8) years.

Results

The mean (standard deviation) age of the participants (1470 males and 669 females) was 62.6 (10.8) years, body mass index 27.3 (4.0) kg/m², and low density lipoprotein cholesterol 114 (33) mg/dl. The mean (standard deviation) PCSK9 concentration was 220 (82) ng/ml. Of the participants, 1035 (48.4%) were on statins. Use of statins was associated with significantly lower low density lipoprotein cholesterol (106 vs 121 mg/dl, p < 0.001) but significantly higher circulating PCSK9 (244 vs 197 ng/ml, p < 0.001). A total of 674 (31.5%) study participants died from any cause and 431 (20.1%) from cardiovascular diseases. In the entire cohort, the third vs first tertile of PCSK9 was not associated with the risk of death from any cause (hazard ratio = 1.09, p = 0.367) and from cardiovascular diseases (hazard ratio = 1.09, p = 0.476). In participants without statins, the third vs first PCSK9 tertile was modestly associated with increased all cause mortality (hazard ratio = 1.34, p = 0.029) but not with cardiovascular mortality (hazard ratio = 1.25, p = 0.194).

Conclusions

Circulating PCSK9 may be upregulated by statin use and does not appear to be useful for cardiovascular risk stratification.