SY 11-3 HYPERTENSION IN WOMEN: MORE DANGEROUS THAN IN MEN?

Heart disease, stroke, and kidney failure are leading causes of death worldwide, and hypertension is a significant risk factor for each. Hypertension is less common in women, compared to men, in those younger than 45 years of age. This trend is reversed in those 65 years and older. In the US between 2011-2014, the prevalence of hypertension in women and men by age group was 6% vs 8% (18-39 years), 30% vs 35% (40-59 years), and 67% vs 63% (60 years and over). Awareness, treatment, and control rates differ between genders with women being more aware of their diagnosis (85% vs 80%), more likely to take their medications (81% vs 71%) and more frequently having controlled hypertension (55% vs 49%). Analysis of >12,000 patient visits with primary care physicians in the US showed no gender difference in the number of anti-hypertensive medications, but did reveal women were more commonly prescribed diuretics and less frequently prescribed ACE-inhibitors.Data on blood pressure (BP) and hypertension prevalence have traditionally been based on manual/automated sphygmomanometer measurements in office. However, extensive epidemiologic data indicate that up to 30% of persons diagnosed with hypertension in office are normotensive outside of clinic. Multiple large population based meta-analyses have shown the superiority of ambulatory blood pressure monitoring (ABPM) and home BP monitoring (or self-monitoring) to in-clinic BP measurements in predicting cardiovascular outcomes (cardiovascular death, stroke, and cardiac/coronary events). Further, night-time BP recorded by ABPM has emerged as a better predictor of total mortality, stroke, and cardiovascular death in patients with hypertension and a history cardiovascular disease (CVD) than either day-time ABPM or in-clinic BP measurements. Importantly, the United States Preventive Services Task Force is now recommending ABPM in all patients prior to initiation of anti-hypertensive treatment as a Grade-A recommendation. ABPM data show a higher percentage of women (43%) than men (34%) have white coat hypertension (elevated in clinic BP, normal out of clinic BP). White coat hypertension has been associated with development of sustained hypertension and increased stroke risk on long term follow-up. In contrast, masked hypertension (elevated out of clinic BP, normal in clinic BP), which has been associated with increased cardiovascular risk, is less common in women compared to men. The prevalence of masked hypertension in women increases with body mass index (adjusted OR = 1.65 for BMI≥27, 95% CI = 1.14-2.39) and alcohol intake (adjusted OR = 2.12 for at least six drinks per week, 95% CI = 1.34-3.35), perhaps accounting for the increased rate of cardiovascular outcomes in this patient group.Randomized controlled trials (RCTs) with CVD outcomes have provided definitive evidence that BP lowering medications benefit hypertensive women. While these trials have largely shown similar CVD outcome benefits in both genders, some differences in response to therapy have been reported. In the ALLHAT study, amlodipine, compared to lisinopril, was associated with a greater reduction in BP, as well as a decreased stroke rate in women. In the VALUE study, cardiovascular morbidity/mortality was higher with valsartan than with amlodipine in women. In the LIFE study, a lower primary composite endpoint (CVD death, stroke, and myocardial infarction) was seen in women treated with losartan. The BP Lowering Treatment Trialists' Collaboration overview of 31 RCTs included comparisons of active agents with placebos, intensive vs less intensive anti-hypertensive medications, and one active agent versus another. In all cases, average baseline BP was higher for women than men, but BP reduction was comparable between genders. No differences in the effects of various anti-hypertensive regimens on CVD outcomes by gender were identified. However, clinically significant gender specific adverse effects of various anti-hypertensive drug classes have been identified. Women more commonly develop hyponatremia/hypokalemia from diuretic therapy; men more frequently develop gout. Women are 3 times more likely to develop an ACE-inhibitor related cough, and more commonly experience CCB-related peripheral edema and minoxidil-induced hirsutism. Importantly, ACEIs/ARBs, direct renin inhibitors, and mineralocorticoid antagonists are contraindicated in women of reproductive age due to the potential of developing fetal abnormalities. Thiazide type diuretics are preferred for the use in elderly women because of decreased risk of hip fractures.Several forms of hypertension, including post-menopausal, oral contraceptive (OCP) induced, and pregnancy related hypertension occur only in women. Following menopause, there is an age independent increase in systolic BP thought to be secondary to the withdrawal of endogenous estrogen, increased salt sensitivity, diminished endothelial nitric oxide production, and increased angiotensin II receptor expression. OCP use is associated with increases in both BP and risk of cardiovascular events, which are reversible with cessation of OCP use. Hypertension in pregnancy (including chronic hypertension, gestational hypertension, preeclampsia, and eclampsia) is associated with increased maternal and fetal cardiovascular and non-cardiovascular risk during pregnancy and long-term mortality risk, particularly for Alzheimer disease, stroke, diabetes, and ischemic heart disease.