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
(p
interaction = 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; p
interaction = 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.
Keywords
coronary disease - epidemiology - factor VIII - protein C - stroke
