On the Role of Hemostasis Variables in Cardiometabolic Outcomes

Background: Hemostasis variables represent well-known pathogenic determinants of venous-thromboembolism and are hypothesized to influence risk for cardiometabolic outcomes (CMOs) by effecting susceptibility to vascular inflammation and/or endothelial dysfunction.

Methods: We investigated in Mexican American (MA)-participants of the San Antonio Family Study the effects of 20 measured hemostasis variables on CMOs including type-2 diabetes (T2D), impaired-fasting glucose (IFG), insulin resistance (IR), hypertension, obesity based on sex-specific waist circumference (OBWC), low high-density lipoprotein (Low-HDL)-cholesterol, hypertriglyceridemia, and a heart distress (HD) variable comprised of history of heart attack and/or heart surgery. The hemostasis variables included PT, aPTT, TFPI, aPC-ratio, fibrinogen, von Willebrand Factor (VWF), ADAMST-13, D-dimer, fPS, tPS, plasminogen, and factor (F)II, FV, FVII, FVIII, FX, FXI, and FXII of the coagulation system. We used a backward stepwise-regression selection approach to identify the preliminary sets of hemostasis predictors.

Results: Our final regression models consisted of the final set of hemostasis variables while accounting for age and sex as covariates. For the T2D, IFG, and HD outcomes, VWF was the only significant hemostasis predictor (p<0.05). In each case, VWF was positively associated with the outcome. The hemostasis variable fibrinogen was a significant positive predictor for the IR, OBWC, and Low-HDL-cholesterol outcomes (p<0.05). For OBWC, FV was an additional significant positive predictor (p<0.05). Finally, no hemostasis variables significantly predicted hypertension or hypertriglyceridemia.

Conclusions: Our results demonstrate that, among the MA-population, all measured CMOs-except hypertension and hypertriglyceridemia-are significantly influenced by individual-variability in several hemostasis parameters with most important predictors being VWF and fibrinogen.

Keywords: Hemostasis; Venous-thromboembolism; Cardiovascular diseases/disorders; Metabolic syndrome; Inflammation; Endothelial dysfunction; Mexican American; Coagulation factors; von Willebrand Factor; and Fibrinogen