Romil R Parikh1, Aaron R Folsom2, Jeffrey R Misialek3, Wayne D Rosamond4, Patricia P Chang5, Weihong Tang6, Mary Cushman7. 1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 3nd Street, Suite 300, Minneapolis, MN 55454, United States. Electronic address: parik075@umn.edu. 2. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 3nd Street, Suite 300, Minneapolis, MN 55454, United States. Electronic address: folso001@umn.edu. 3. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 3nd Street, Suite 300, Minneapolis, MN 55454, United States. Electronic address: misi0020@umn.edu. 4. Department of Epidemiology, University of North Carolina, 137 East Franklin Street, Suite 306, CB# 7435, Chapel Hill, NC 27514, United States. Electronic address: wayne_rosamond@unc.edu. 5. Division of Cardiology, Department of Medicine, University of North Carolina, 300 Meadowmont Village Cir #104, Chapel Hill, NC 27517, United States. Electronic address: patricia_chang@med.unc.edu. 6. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 3nd Street, Suite 300, Minneapolis, MN 55454, United States. Electronic address: tang0097@umn.edu. 7. Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Main Pavilion, 111 Colchester Ave, Burlington, VT 05401, United States; Department of Medicine, University of Vermont College of Medicine, Main Pavilion, 111 Colchester Ave, Burlington, VT 05401, United States. Electronic address: Mary.Cushman@uvm.edu.
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.
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.
Authors: W D Rosamond; A R Folsom; L E Chambless; C H Wang; P G McGovern; G Howard; L S Copper; E Shahar Journal: Stroke Date: 1999-04 Impact factor: 7.914
Authors: Aaron R Folsom; Weihong Tang; Saonli Basu; Jeffrey R Misialek; David Couper; Susan R Heckbert; Mary Cushman Journal: Thromb Haemost Date: 2019-02-19 Impact factor: 5.249
Authors: Dasha Cherepanov; Tanya G K Bentley; Wendy Hsiao; Pin Xiang; Frank O'Neill; Yi Qian; Nicole Yurgin; David Beenhouwer Journal: Curr Med Res Opin Date: 2018-01-04 Impact factor: 2.580