Should women have lower thresholds for hypertension? Severe ultrastructural abnormalities in systemic arterioles of normotensive and hypertensive women

Abstract

Abstract Background Hypertension in women is increasingly recognized to originate in the pre-menopause, but the factors that may affect the greater blood pressure increments observed in premenopausal women compared to age-matched men are understudied. Uterine fibroids, occurring in 30-50% of all women, are a strong sex-specific factor associated with hypertension and early cardiovascular events, but the nature of this association is not known. To assess a possible shared pathology of smooth muscle, we studied the ultrastructure of systemic resistance arteries of women with fibroids. Methods Resistance-sized arteries (200 to 400 μm) were harvested from omental samples obtained during fibroid surgery. Transmission electron microscopic images were taken at different magnifications and locations of the vessel wall to assess qualitative and morphological characteristics. Mean blood pressure was calculated as DBP+1/3(SBP-DBP). Results Resistance arteries of 17 women (8 hypertensive, 4 treated), mean age 42 (SE 1) y, were available for analysis. None had a history of cardiovascular disease. Mean blood pressure was 91.4 mm Hg in normotensives and 119.4 in hypertensives. The endothelium showed mitochondrial and endoplasmic reticulum stress in normotensives (Figure, Panel A), to necrosis and sloughing in hypertensives (B). Myocyte-like cells were observed to migrate across the internal elastic lamina, forming small aggregates of subendothelial myocytes in normotensives (C), and larger subendothelial myo-intimal "cushions" in hypertensives (D). Medial myocytes of all patients showed abnormalities similar to fibroids, with dilated sarco-endoplasmic reticulum, elongated mitochondria and myofilament loss involving focal areas or entire cells (E, clinically considered normotensive). Untreated hypertensives had a significantly higher intima-media thickness-to-lumen ratio (%) than normotensives and treated hypertensives as expected, respectively 15.9 (1.8), 12.5 (1.6) and 13.4 (2.1). Conclusion To our knowledge the first ultrastructure data of systemic resistance-sized arteries in women with fibroids, show that young premenopausal women considered clinically normotensive already have severe microvascular abnormalities that may cause or reflect perturbations in microvascular function and predispose to early end organ damage. While there is abundant clinical evidence that the association between blood pressure and cardiovascular events is stronger in women, hypertension in women is understudied. In particular women-specific risk factors are ill-understood. Our observations are relevant to the current discussion regarding whether the clinical threshold for hypertension treatment is too high for women and whether earlier management of cardiovascular risk is needed. Further studies are warranted in a woman-specific research agenda on cardiovascular risk factors in younger premenopausal women.Figure