Sex Differences in Hypertension and Its Management Throughout Life

Abstract

Background: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex.

Methods: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models.

Results: The prevalence of hypertension increased with age from 40% (ages, 43-46 years) to 93% (ages, 91-94 years). Within hypertensive individuals, the prevalence of uncontrolled hypertension was higher in men (33%) than women (23%) at ages 43 to 46 years but became higher in women than men starting at ages 61 to 64, with 56% of women and 40% men having uncontrolled hypertension at ages 91 to 94. This sex difference was not explained by differences in coronary heart disease, diabetes, body mass index, estimated glomerular filtration rate, number of antihypertension medications, classes of medications, or adherence to medications. In both sexes, uncontrolled hypertension was associated with a higher risk for chronic kidney disease progression (hazard ratio, 1.5 [1.2-1.9]; P=4.5×10^-4), heart failure (hazard ratio, 1.6 [1.4-2.0]; P=8.1×10^-7), stroke (hazard ratio, 2.1 [1.6-2.8]; P=1.8×10^-8), and mortality (hazard ratio, 1.5 [1.3-1.6]; P=6.2×10^-19).

Conclusions: Sex differences in the prevalence of hypertension and uncontrolled hypertension vary by age, with the latter having implications for health throughout the life course.

Keywords: health; hypertension; medication adherence; sex characteristics.

Figure 1.

(a) Plot of mean systolic blood pressure (SBP) by sex and 3-year age categories. (b) Plot of mean diastolic blood pressure (DBP) by sex and 3-year age categories. Mean SBP increased with age, whereas mean DBP decreased with age. Both SBP and DBP were higher in middle-aged men relative to the opposite sex, and SBP was higher in older women relative to older men. The shaded bars in Figure 1(a) depict the age distribution within each visit, with darker shades of gray representing higher counts. (c) Prevalence of hypertension (HTN) by sex and 3-year age categories. (d) Prevalence of uncontrolled HTN within hypertensive individuals by sex and 3-year age categories. The prevalence of HTN increased with age. Middle-aged hypertensive men had a higher prevalence of uncontrolled HTN relative to women; beyond the ages of 61–64, women had a higher prevalence on uncontrolled HTN than men.

Figure 2.

(a) Mean number of anti-hypertensive medications by sex and 3-year age categories. Middle-aged women were on more anti-hypertensive medications than men up to ages 67–70, after which there was no significant sex difference. Asterisks denote a statistically significant sex difference in number of anti-hypertensive mediation use within each age category (Wilcoxon test). (b) Proportion of reported anti-hypertensive medication class use by sex and 3-year age category. Men were more likely to be on beta blockers (BBs) and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEIs/ARBs) relative to women, whereas women were more likely to report use of thiazides relative to men. Between the ages of 46–67 years, men were more likely to report using CCBs relative to women, but starting at 79 years of age, women became more likely to report using CCBs than men. Asterisks denote a statistically significant sex difference in the proportion of individuals on each drug class within each age category (Chi-squared test). (c) List of all 18 quantifiable anti-hypertensive drugs in serum or urine metabolomic data, with prescription counts and adherences. Bold entries with an asterisk denote a statistically significant sex difference in the proportion of individuals adherent to each anti-hypertensive medication class or medication (Chi-squared test). (d) Mean anti-hypertensive medication adherence by sex and 3-year age categories at visit 5. Anti-hypertensive medication adherence generally did not vary by sex or age, and consistently remained high at above 75%. Asterisks denote a statistically significant sex difference in adherence within each age category (Wilcoxon test). (e) Proportion of anti-hypertensive medication class adherences by sex at visit 5. There were no sex differences in adherence for each medication class apart from thiazides (hydrochlorothiazides), where women were more adherent. Asterisks denote a statistically significant sex difference in the proportion of individuals adherent to each medication class (Chi-squared test).