Hypertension in women: no “silent” lady-killer

Introduction

Hypertension is acknowledged as the number one risk factor for cardiovascular disease (CVD) worldwide [1]. At a younger age, high blood pressure (BP) is more often present in men than in women, but this reverses gradually after the age of 50 [2].  Elevated sympathetic nerve activity in older women may be an important contributor to the increased prevalence of hypertension after the menopause [3]. Hypertensive women develop more arterial stiffness, heart failure with preserved ejection fraction (HFpEF), atrial fibrillation and dementia at an older age compared to hypertensive men [4,5]. As they also have a smaller diameter of their arterial system and aortic aneurysms tend to rupture at a smaller size, it remains to be elucidated whether the threshold for normal BP should be lower in women than in men [6,7].  Only half of all patients with hypertension are currently treated appropriately and this accounts even more for women than for men [8,9].

Female-specific risk factors and premature hypertension

Parental high BP gives a 3x higher risk of hypertension in all adolescents [10]. In women, sex-specific risk factors may be an important indication for the development of premature hypertension. Premenstrual migraine is present in 15% of teens/adolescents and migraine headaches occur 3-4 times more often in women than in men. It is related to a higher family risk for CVD, a higher susceptibility for inflammation and the development of premature hypertension [11]. Migraine attacks are often seen in the second half of the menstrual cycle. At an older age, recurrent and persistent headaches may also be related to hypertension [12].

Although ovarian stimulation in infertile women activates the renin-angiotensin-aldosterone system (RAAS), there are no indications thus far that women who undergo infertility treatment are at higher risk for hypertension [13]. In the Women’s Health Initiative (WHI), it was found that recurrent miscarriage was associated with a higher risk for hypertension [14]. Hypertensive pregnancy disorders, pre-eclampsia in particular, have been acknowledged as important risk factors in women, leading to a twofold increased risk for ischaemic heart disease (IHD) and a fourfold elevated risk for hypertension [15,16]. We previously showed that almost 40% of women after severe early pre-eclampsia already have hypertension just before the age of forty [17]. Many of these women remained hypertensive after their high-risk pregnancy. Despite the mention of this specific risk factor in several guidelines over the  years, it is still underused as a risk indicator in clinical practice and therefore an important missed opportunity for timely recognition and treatment of high BP.

Hypertension in young and middle-aged women is often symptomatic

Whereas hypertension may be asymptomatic in elderly patients with stiffened and atherosclerotic arteries, it can induce many symptoms in younger patients [18]. Elevated BP causes shear stress on the arterial wall, promoting endothelial dysfunction that may translate into angina-like symptoms of chest pain. This can be present for minutes to hours and often radiates to the jaws and shoulder blades. Chest pain can be felt as a continuously tight rope over the chest, worsening with (slight) exercise and/or stress. Women often report taking off their bra at home in the evenings. Symptoms may respond well to short-acting nitrates causing vasodilatation and a lowering of BP. In the Women’s Ischemia Syndrome Evaluation Study (WISE), hypertension was prevalent in 55% of women, mean age 58 years, who were referred for coronary angiography because of chest pain [19]. Other symptoms such as sleep disturbances, palpitations, paroxysmal tachycardias or atrial fibrillation, dizziness, fluid retention, extreme tiredness and loss of energy are also frequently mentioned. Frequently reported symptoms associated with hypertension in women are described in Table 1.

Table 1. 

Many of these disabling symptoms overlap with vasomotor symptoms (VMS) during menopause transition and disappear once BP is adequately controlled [20,21]. Women on hypertensive medication also report that they sleep better and have more energy to undertake activities. VMS and other menopausal symptoms are associated with increased risk of CVD, mainly mediated by the traditional risk factors such as hypertension [22]. In addition, women who have had a hypertensive pregnancy more often report VMS during menopause transition [23]. We therefore recommend that women seeking advice for VMS should be evaluated in the first place for their family risk, sex-specific risk factors and traditional CVD risk factors such as hypertension.

No uniform treatment advice

The choice of treatment for symptomatic hypertension should be tailored to the individual patient. A combination of two to three medications in moderate dosage is often more effective in women, with fewer side effects than high-dose monotherapy. When fluid retention and chest pain dominate, a combination of ACE/ARB with diltiazem (90 to 200 mg) is often very effective. In perimenopausal women with hypertension and a fast rise in heart rate on exercise, a combination of ACE/ARB with a (selective) beta-blocker may be more appropriate. In women having severe VSM and a modestly elevated BP, the combined use of drospirenone, a synthetic progestogen with mineralocorticoid properties, with 17-β-estradiol can be very effective in alleviating climacteric symptoms and lowering of both systolic and diastolic BP [24].

Conclusion

Hypertension may cause a variety of vague symptoms in younger and middle-aged women that are often taken for “stress” or “menopause-related”.  If there is a positive family risk and previous medical history indicates a higher susceptibility for hypertension, a more intensive blood pressure control and timely treatment are advised.