Cardiometabolic Risk and Cardiovascular Disease in Young Women With Uterine Fibroids

Abstract

Uterine fibroids are associated with hypertension and cardiometabolic risk factors, yet the onset and severity of cardiovascular disease (CVD) in women with fibroids remain understudied. We used data from the National Health and Nutrition Examination Survey to assess the association between uterine fibroids, cardiometabolic risk, and CVD (ischemic heart disease, heart failure, and stroke). Among 5,552 women aged 20-54 years in our sample. Hypertension was more common in those diagnosed with fibroids (n=700; 33.4% vs. 15.3% in controls, p<0.001), but these women were also older (44 (SD=7) years vs. 35 (SD=10) years). When stratified by median age, women aged 35 or younger with fibroids (n=97) were more likely than controls (n=2771) to have hypertension (14.1% vs. 2.4%), obesity (51.5% vs. 32.5%), and diabetes mellitus (4.8% vs. 1.9%). Women older than 35 with fibroids also had higher cardiometabolic risk and rates of CVD than controls (8.5% vs. 4.5%). The odds ratio of CVD in women with fibroids, compared to the controls, was 3.10 with 95% confidence interval (CI) of 2.21 to 4.34. The odds ratio decreased to 1.63 (95%CI: 1.11 to 2.38) after adjusting for age, BMI, African ancestry, fasting plasma glucose, cholesterol, education, smoking history, and postmenopausal status and to 1.60 (95%CI: 1.08 to 2.37) after further adjusting for systolic blood pressure. These data indicate that uterine fibroids are associated with a worse cardiovascular risk profile, including hypertension, in relatively young women, leading to early CVD. A women-specific research agenda is urgently needed to study the nature of these associations and design preventive strategies to prevent cardiovascular events in young women with fibroids.

Arterial Hypertension in Women: State of the Art and Knowledge Gaps

“…Indeed, this difference is further evident by the strong association of hypertension and CVD with disorders of female reproductive organs (see Box 2). 6,[12][13][14][15][16]28 However, these differences are understudied, incompletely understood, and insufficiently translated into clinical guidelines.…”

“…35 Hypertension, gynecological disorders, (central) obesity, and a wide range of other risk factors for CVD tend to cluster in women, including perturbations in the regulation of sex hormones, leptin and insulin resistance, sodium sensitivity, chronic inflammation, metabolic-associated fatty liver disease, sympathetic nervous system activation, and endothelial and neuroendocrine dysfunction. 12,14,15,20,36,37 The neuroendocrine hormone leptin is thought to have a key role in obesity, regulating food intake, metabolism, and fat distribution. 38 It may in some instances be the link between female sex and increased cardiovascular risk.…”

“…6 However, there are almost no specific treatment recommendations in clinical practice guidelines to manage hypertension in women, [1][2][3] including the greater hypertension and cardiovascular risk with uterine fibroids, PCOS, premenstrual syndrome, or adverse pregnancy outcomes. 12,[14][15][16]40,45,50,51 Earlier pharmacological therapy for women with stage 1 hypertension and a history of pregnancy-induced hypertension has been recently suggested. 76 Sparse data suggest that blood pressure lowering in women is greater with beta-adrenergic or calcium channel blockers, 77 but no consistent sex or gender differences in cardiovascular outcomes were observed.…”

“…12,39 Uterine fibroids are generally unrecognized in woman-specific overviews or clinical cardiovascular guidelines, 1–4,6–9 despite an independent association with (gestational) hypertension, cardiometabolic risk factors including obesity, hypertension-mediated organ damage (HMOD), and CVD. 12,13,39,45 A higher risk of CVD is observed with uterine fibroids even in the absence of clinical hypertension. 12 In line with this, extensive ultrastructural endothelial and myocyte abnormalities were reported in resistance arterioles of both normotensive and hypertensive young, premenopausal women with fibroids.…”

“…These risk factors are related not only to menarche, reproduction, menopause, and (the pharmacological use of) sex hormones but also to variation in access to and intensity of health care. [4][5][6][7][8][9][12][13][14][15][16][17][18][19][20][21][22][23][24] Women are assumed to be protected from hypertension and associated increased cardiovascular risk until menopause. However, recent sex-specific analyses suggest that blood pressure increases more rapidly among premenopausal women compared with aged-matched men, whereas control declines with aging.…”