Sex differences in individuals with office high normal blood pressure who developed hypertension in 3-year follow-up

Objective: Recent data demonstrated that females develop target organ damage earlier than men. Normotensive individuals with office high normal blood pressure (BP) who remain at normotensive range for at least 3 years demonstrate hemodynamic differences according to their gender. Design and method: 100 individuals with high normal BP were followed-up for 3 consecutive years. During enrolment they underwent ambulatory BP monitor (ABPM), electrocardiogram (ECG), echocardiogram, carotid-femoral pulse wave velocity (PWV), sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) to assess sympathetic drive, a negative for ischemia treadmill exercise stress test (TST) (Bruce protocol) and blood sampling. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advise to lower their BP. Endpoint was development of hypertension (HTN). Then they divided into males and females (postmenopausal). Results: 19 males and 21 females developed HTN. Men were younger than women (51vs58y, p = 0.03). Office and ABPM measurements did not differ significantly. Men exhibit higher waist to hip ratio (0.92vs0.86, p = 0.012), higher uric acid levels (5.6vs4.7mg/dL) and better kidney function according 2021 CKD-EPI GFR (97vs87,p = 0.03). Contrary HDL levels were lower (54vs66mg/dL, p = 0.048). From those who remained normotensive (24 males and 36 females), men exhibit increased left ventricular mass index (90vs82, p = 0.045) compared to women. Interestingly to those who became hypertensive left ventricular mass index was similar (79vs81gr/m 2 , p = 0.53). Women had greater sympathetic drive as recorded from MSNA levels (33vs36bursts/min,p = 0.012) and MSNA per 100bpm (47vs54burst,p = 0.041). Arterial stiffness as recorded from c-fPWV (8.3vs8.2m/s) did not differ significantly among genders. In TST (Bruce protocol) men exercised two extra minutes on average (9vs7min, p < 0.0001), achieving greater exercise duration and METs (11.2vs8.8, p = < 0.0001) accordingly. SBP at peak exercise was higher in men (208vs197mmHg, p = 0.03). Conclusions: Women who became hypertensive equalized their heart volume with men, demonstrate greater sympathetic activity and worsening of their kidney function. Additionally, their exercise capacity was significantly reduced in comparison with men. Overall, it seems there are structural alterations in heart and kidneys that demonstrates the need to prevent earlier the organ damage during high blood pressure stage in women.