Introduction: High molecular weight kininogen (HK) and prekallikrein (PK) are proteins in the kallikrein/kinin system of the coagulation cascade. They play an important role in the contact activation system of the intrinsic coagulation pathway, renin-angiotensin activation, and inflammation. Hence these proteins have been posited to affect the occurrence of cardiovascular events and thus to be potential therapeutic targets. Previous case-control studies have provided inconsistent evidence for an association of HK and PK with cardiovascular disease. Methods: In the prospective population-based Atherosclerosis Risk in Communities(ARIC) Study, we used Cox proportional hazards regression models to investigate the association in 4195 middle-aged adults of plasma HK and PK concentrations in 1993–95 (linearly and in quartiles) with incident coronary heart disease, ischemic stroke, and heart failure through 2016. Results: Over a mean of 18 years follow-up, we identified incident cardiovascular events (coronary heart disease and ischemic stroke) in 618 participants and heart failure in 667. We observed no significant relation between HK or PK and cardiovascular disease or heart failure, before and after adjusting for several potential confounding variables. Conclusions: We found no compelling evidence to support an association of plasma HK or PK concentrations with incident CHD, ischemic stroke, or heart failure.
Bibliographical noteFunding Information:
The National Heart, Lung, and Blood Institute (NHLBI) provided support for laboratory assays via R01 HL059367 and for the Atherosclerosis Risk in Communities Study via contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I. The authors thank the participants and staff of the ARIC study for their important contributions and Elaine Cornell for assistance with laboratory measurements.
- Cardiovascular disease
- Heart failure
- High molecular weight kininogen
- Ischemic stroke
- Prospective study