Vascular function and cardiovascular risk factors in women with severe flushing

Background Seventy per cent of postmenopausal women suffer from hot flushes causing significant morbidity in 25%. Oestrogen replacement provides symptom relief, but its use has declined following safety issues and there is, as yet, no good alternative. Pathophysiology is poorly understood, but one proposed mechanism is altered peripheral vascular reactivity. It has recently been suggested that the presence of flushing may be a marker of underlying cardiovascular risk. Aim To measure (i) peripheral vascular reactivity in subcutaneous vessels (ii) routine and novel cardiovascular risk factors in postmenopausal women who flush, and compare results to a matched group of women who do not flush. Methods Thirty-two postmenopausal women with at least 20 flushes/week and 14 nonflushing postmenopausal women were recruited. Cutaneous microvascular perfusion was measured using laser Doppler imaging, and endothelial function was assessed by iontophoresis (administration of vasoactive agents through the skin by an electric current) of acetylcholine [Ach] (endothelial-dependent) and sodium nitroprusside [SNP] (endothelial independent). Blood samples for risk factors were taken following vascular assessment. Results Both study groups were well matched demographically. The response of the subcutaneous vessels was greater in women who flushed than those who did not, following administration of both the endothelium-dependent and independent vasodilators, (ACh, P <= 0.001, SNP, P = 0.001, 2-way ANOVA). By contrast, levels of High Density Lipoprotein (HDL)-cholesterol and ApoA1 were significantly lower in the flushing women compared with the control women (P = 0.02 and 0.002, respectively), and levels of inter-cellular adhesion molecule-1 (ICAM-1) were higher (P = 0.03), findings robust to adjustment for confounders, suggesting an adverse cardiovascular risk profile. Conclusion These results confirm a better vascular response in women but paradoxically, such women appear to have worse (not better) cardiovascular disease risk factors in particular lower HDL-cholesterol but also higher non-HDL-c to HDL-c ratio and increased ICAM-1. Further studies are needed to assess vascular risk factors in women who flush.