The effect of common beta2-receptor haplotypes on catecholamine levels and hemostasis after standing up

Introduction: Standing up increases the levels of several coagulation factors, partially due to a decrease in plasma volume. Whether this hemostatic response is additionally mediated by catecholamine release, is unknown. Furthermore, common haplotypes of the beta2- adrenergic receptor, which are associated with increased cardiovascular risk at older ages, may also affect catecholamine release and the hemostatic response. Methods: Catecholamine levels and hemostatic parameters were measured at rest and 10 min after standing up in healthy individuals, homozygous for the Arg16/Gln27 (n = 13) or Gly16/Glu27 (n = 24) haplotype. Mean age was 63 ± 1 years. Hemostatic parameters included coagulation factors, platelet activation by flow cytometric analysis of P-selectin and PAC-1 surface presentation, and endogenous thrombin potential (ETP). Results: Standing up resulted in an increase in the levels of catecholamine and clotting factors, notably factor VIII (116 ± 5% to 137 ± 5%, P <0.001). ETP remained constant. Platelet activation as measured by PAC-1 increased from 1.6 ± 0.2% to 2.2 ± 0.2% (P = 0.01). Norepinephrine concentrations showed positive correlations with nearly all hemostatic parameters, but only significantly with factor VIII (r = 0.20, P <0.05). Furthermore, subjects with Arg16/Gln27 haplotype had higher norepinephrine levels compared to Gly16/Glu27 individuals (4.1 ± 0.5 vs. 2.9 ± 0.2 nM, respectively, P <0.05). Platelet activation tended to be higher in Arg16/Gln27 individuals, while clotting factors were not different. Conclusion: In healthy elderly, 10 min of standing leads to an increase in procoagulant proteins, partially mediated by norepinephrine release. The latter effect may be mediated by the Arg16/Gln27 beta2-receptor haplotype, a known risk factor for cardiovascular risk.