Risk factors for arterial disease and cardiovascular mortality include male sex, ageing and smoking (Bolego et al. 2002; Hayward et al. 2000). In this study, I have performed some preliminary studies to test the hypothesis that menopause and smoking have synergistically disruptive effects on endothelial function.

The study involved young menstruating women and postmenopausal hormone replacement therapy (HRT) users or non-users. Subjects were either long-term smokers (at least 10/day for 1 year) or non-smoking controls. With institutional ethical approval, young (23 ± 2 years, mean ± S.E.M.) ovulating women in the menstrual phase of their cycle, postmenopausal (56 ± 3 years) women and postmenopausal HRT users (58 ± 2 years) attended the laboratory. Smokers were asked to abstain for at least 1 h prior to testing. A blood sample was taken for plasma analysis of circulating endothelial cells (CECs), von Willebrand factor (vWF) and thrombomodulin (TM) levels. Resting mean arterial pressure (MAP) was measured using applanation tonometry. Forearm reactive hyperaemia following 3 min arterial occlusion was measured by venous occlusion plethysmography as an index of endothelium-dependent vasodilator capacity. Two-tailed paired (longitudinal comparisons) or unpaired (cross-sectional comparisons) t-tests were used in analysis. P < 0.05 was deemed significant.

The postmenopausal controls (n = 10) had elevated MAP when compared with the young group (n = 10) and there was no difference in MAP between older controls using (88±2.5 mmHg) or not using (91 ± 4.0 cf 76 ± 1.6 mmHg, P < 0.05) HRT. Ageing was not associated with diminution of reactive hyperaemia (area under the curve: HRT 119 ± 26.7, non-HRT 116±25.3, young 185±54 ((ml min^-1) 100 ml^-1) s) and no age-related changes in plasma levels of CECs, vWF or TM were seen. Among the young women, smokers (n = 7) had elevated CECs (117 ± 22.1 cf 59 ± 10.6 cells ml^-1 blood) but similar levels of vWF (72 ± 34.9 cf 70 ± 25 Units) and TM (8.9 ± 0.74 cf 7.3 ± 0.76 ng ml^-1) and similar reactive hyperaemic responses (205 ± 58.6 ((ml min^-1) 100ml^-1) s) as controls. These characteristics did not alter further with age but postmenopausal smokers (n = 7) exhibited marked attenuation of reactive hyperaemia (36 ± 7.0 ((ml min^-1) 100 ml^-1) s).

In conclusion, moderate ageing is accompanied by an elevation in resting MAP that is not reversed with HRT. This age-dependent rise in MAP is not related to impaired reactive hyperaemia or to altered levels of plasma markers thought to reflect endothelial damage. Long-term smoking is however linked to a functional loss of vasodilator activity that is independent of plasma changes in endothelial markers.

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