Sex differences in individuals with high normal blood pressure who developed hypertension in three-year follow-up
Authors: Kalos T , Dimitriadis K , Manta E , Kakouri N , Siafi E , Konstantinidis D , Fragoulis C , Tsioufis P A , Karioiri M , Iliakis P , Drogaris S , Leontsinis I , Tatakis F , Thomopoulos C , Tsioufis C 
Published: November 2023

Abstract

Background
Recent data demonstrated that females are at risk for cardiovascular disease at a lower blood pressure (BP) level than males.

Purpose
Identify normotensive individuals with high normal BP who are going to develop hypertension in three-year follow-up and demonstrate differences according to their gender.

Methods
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 assessed by muscle sympathetic nerve activity (MSNA), 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 ABPM. All participants offered lifestyle advise to lower their BP. Endpoint was development of hypertension (HTN).

Results
19 males and 21 females developed HTN. Office and ABPM measurements did not differ significantly but women who developed HTN demonstrate higher pulse pressure 50vs45 mmHg (p=0.03). In ABPM systolic blood pressure (SBP) differ (123 vs 119 mmHg, p=0.01) in future hypertensive females. Additionally night-time SBP differ in both genders who were going to develop HTN (women: 116vs111 mmHg, p=0.007 and men: 116vs111 mmHg, p=0.043). Both genders demonstrate significantly different PWV values among future hypertensives and those who remained normotensives (women: 8.2vs7.2 m/s, p&lt;0.001, men: 8.3vs7.2 m/s, p&lt;0.001). Males and females who developed hypertension had higher sympathetic activity as reflected from MSNA levels (men: 33vs27 bursts/minute, p&lt;0.001, women: 36vs28 bursts/minute, p&lt;0.001). Both genders who developed HTN had higher SBP at peak exercise (men: 208vs184 mmHg, p&lt;0.0001, women: 197vs173 mmHg, p&lt;0.0001) as also steeper SBP/MET slope (men: 6.7vs5.0, p=0.038, women: 7.1vs3.8, p&lt;0.0001), while their maximal heart rate achieved differ (men: 158bpm vs 167bpm, p=0.014, women: 153bpm vs 162bpm, p&lt;0.0001). Only in women's baseline ECG who developed HTN had wider p-wave duration (103vs94ms, p=0.032) and QRS length (88vs80ms, p=0.018). While echocardiographicly they displayed increased left ventricular mass index (LVMI) (81vs72 g/m²,p=0.006), atrial diameter (37vs34 mm,p&lt;0.0001) and decrease E/A ratio of transmitral flow velocity (0.8vs1.0, p=0.005). Kidney function assessed by 2021 CKD-EPI eGFR reveals a deterioration in those women who are going to develop HTN (87 vs 97 mL/min/1.73 m², p=0.009).

Conclusions
Both men and women benefit from treadmill exercise stress test as a prognostic tool that can reveal the likelihood of development of hypertension in both sexes and arouse the need to research for target organ damage in women who are in prehypertensive state and may benefit from an early intervention until clarify sex-specific thresholds for diagnosis of hypertension.