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Factor VIII, Protein C and Cardiovascular Disease Risk: The REasons for Geographic and Racial Differences in Stroke Study (REGARDS).

TitleFactor VIII, Protein C and Cardiovascular Disease Risk: The REasons for Geographic and Racial Differences in Stroke Study (REGARDS).
Publication TypeJournal Article
Year of Publication2018
AuthorsZakai, NA, Judd, SE, Kissela, B, Howard, G, Safford, MM, Cushman, M
JournalThromb Haemost
Volume118
Issue7
Pagination1305-1315
Date Published2018 Jul
ISSN2567-689X
Abstract

BACKGROUND:  Haemostatic balance represented by low protein C (PC) and elevated factor VIII (FVIII) has been inconsistently associated with stroke and coronary heart disease (CHD) risk.OBJECTIVE:  This article assesses whether an elevated FVIII and a low PC would increase cardiovascular risk more than either individually.PATIENTS AND METHODS:  REGARDS recruited 30,239 black and white U.S. participants aged ≥ 45 years between 2003 and 2007. FVIII and PC were measured in a case-cohort sample of 646 stroke, 654 CHD, and a 1,104-person random sample with follow-up for approximately 4.5 years. Hazard ratios (HRs) were estimated using Cox models adjusted for demographic and cardiovascular risk factors.RESULTS:  Elevated FVIII (per standard deviation [SD] increase) was associated with increased risk of both stroke (HR, 1.26; 95% confidence interval [CI], 1.08, 1.46) and CHD (HR, 1.52; 95% CI, 1.29, 1.79), while there was no association of PC per SD decrease. For PC, there was a trend towards increased cardiovascular disease risk in the lowest values (bottom 5%). For stroke, there was no interaction between FVIII and low PC ( = 0.55). For CHD, the adjusted HR of FVIII per SD increase was significantly greater with PC in the bottom 5% (HR, 3.59; 95% CI, 1.39, 8.29) than PC in the upper 95% (HR, 1.45; 95% CI, 1.23, 1.71;  = 0.07).CONCLUSION:  Higher FVIII was associated with both CHD and stroke risk and the risk potentiated by low PC for CHD. Findings demonstrate that risks for cardiovascular diseases conferred by adverse levels of haemostasis biomarkers may be augmented by levels of other biomarkers.

DOI10.1055/s-0038-1655766
Alternate JournalThromb. Haemost.
PubMed ID29890521
PubMed Central IDPMC6028294
Grant ListK08 HL096841 / HL / NHLBI NIH HHS / United States
R01 HL080477 / HL / NHLBI NIH HHS / United States
U01 NS041588 / NS / NINDS NIH HHS / United States