The Endothelium, Arterial Stiffness, and von Willebrand Factor Levels in Hypertensive Women: Effects of Ethnicity

Hypertension is an ever-expanding worldwide epidemic. Unfortunately—yet not surprisingly—hypertension remains an obscure entity in many underdeveloped parts of the world, such as Africa and south Asia. The available data, largely from predominantly white Caucasian hypertensive populations, have implicated endothelial damage/dysfunction as a fundamental pathophysiological mechanism in the pathogenesis of hypertension and its many complications.1 However, there is still debate whether the measures of endothelial damage/dysfunction in these white Caucasian hypertensive populations equally apply and have the same pathogenic implications in other nonwhite ethnic groups. The first issue is how best to assess endothelial damage/dysfunction. Functional methods such as flow-mediated dilatation at the brachial artery, arterial stiffness measurements, and laser Doppler flowmetry all allow “real-time” functional assessment of the endothelium in the macro- and microvasculature, albeit in relatively small populations that need access to specialized equipment and researchers. In contrast, plasma indices of endothelial damage/dysfunction such as von Willebrand factor (vWF) has allows measurement by a simple blood sample, in large epidemiological studies, and have important diagnostic and prognostic significance in many cardiovascular disorders.1,2 In the current issue of the American Journal of Hypertension, Schutte et al.3 study a cohort of apparently healthy African (n = 99) and Caucasian (n = 114) women, and measured blood pressure and arterial compliance noninvasively, and serum vWf levels. No ethnic difference were apparent for mean vWf levels, but Caucasian and African women showed opposite associations of blood pressure and arterial compliance with vWf. In Caucasian women, blood pressure correlated positively and arterial compliance negatively with vWf levels; in contrast, systolic blood pressure correlated weakly—but negatively—with vWf levels, in African women. Thus, Schutte et al.3 conclude that the associations of vWf with blood pressure and arterial compliance were not comparable between Caucasian and African women, suggesting that the vWf may not be a useful marker of vascular alterations in African women. Of note, this opposite tendency amongst blacks was found to be partly due to the confounding influence of the depot medroxyprogesterone acetate contraceptive injection. Although these differences may reflect fundamental pathophysiological mechanisms among dissimilar ethnic groups, this may also suggest that currently well-established (at least in white Caucasian populations) markers of endothelial damage/dysfunction may not be universal for all ethnic groups, nor all geographical populations. In the black ethnic group, hypertension has diverse factors regulating blood pressure control and its treatment—ranging from salt sensitivity to a low-renin state. A genetic predisposition due to various gene polymorphisms, for example, in renin and angiotensin genes, as well as abnormal sodium gating and higher peripheral resistance are other possible specific attributes involved in the development of hypertension amongst the black African population.4,5 As with most populations, socioeconomic and environmental considerations also feature, as hypertension is even more pronounced in urbanized and westernized black populations.6 In their relatively small cross-sectional study, Schutte et al.3 would not be able to address all these major issues, and statistical methods cannot account for all biological processes. Furthermore, the weak, negative correlation between systolic blood pressure and vWf in blacks (which were numerically fewer than whites) was not statistically significant (P = 0.059), and once the use of depot medroxyprogesterone acetate contraceptive injection was taken into account, the relationship was nonsignificant. Weak correlations do not translate into causation, and biological plausibility is not fully explained. In addition, the study recruited African women employed at a government institution, which may not be generalizable to the rest of rural black populations in South Africa. While recruitment of Caucasian women was stated as being “from an urban area,” few details are provided, and the possibility of a “volunteer/responder effect” has to be considered. In addition, classification as “apparently healthy” really depends on how hard one looks, and even asymptomatic left ventricular dysfunction or mild renal impairment can influence vWf and arterial stiffness. Although this study provides some novel insight into our understanding of the different pathogenesis of hypertension among whites and blacks, further large and well-powered studies would need to explore the effect of confounders (e.g., renin–angiotensin system) as well as future prognostic and therapeutic scope of such observations. The authors declared no conflict of interest.