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Prospective study of plasma high molecular weight kininogen and prekallikrein and incidence of coronary heart disease, ischemic stroke and heart failure.

TitleProspective study of plasma high molecular weight kininogen and prekallikrein and incidence of coronary heart disease, ischemic stroke and heart failure.
Publication TypeJournal Article
Year of Publication2019
AuthorsParikh RR, Folsom AR, Misialek JR, Rosamond WD, Chang PP, Tang W
Secondary AuthorsCushman M
JournalThromb Res
Volume182
Pagination89-94
Date Published2019 Oct
ISSN1879-2472
KeywordsBrain Ischemia, Coronary Disease, Female, Heart Failure, Humans, Incidence, Kininogen, High-Molecular-Weight, Male, Middle Aged, Prekallikrein, Prospective Studies, Stroke
Abstract

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.

DOI10.1016/j.thromres.2019.08.009
Alternate JournalThromb Res
PubMed ID31473403
PubMed Central IDPMC6825898
Grant ListR01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States