Sympathetic overdive is related to hypertension development in 3-year follow-up study of individuals with high normal blood pressure

Objective: Assess the relation of blood pressure response to treadmill exercise test in subjects with high normal blood pressure (BP) while sympathetic overactivity assessed by muscle sympathetic nerve activity (MSNA) are linked with development of hypertension (HTN) in both genders. 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, sympathetic drive was assessed by MSNA, a negative for ischemia treadmill exercise stress test (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 HTN. Then they divided into males(M) and females(F) who remained normotensive or developed HTN. Results: 19 males(officeBP:134/85mmHg) and 21 females(officeBP:134/83mmHg) developed HTN. Both genders who developed HTN had higher night systolic BP (M:116vs111mmHg,p = 0.043, F:p = 0.007). Additionally, hypertensive women had higher office pulse pressure (50vs45mmHg,p = 0.03) and 24hour SBP(123vs119mmHg,p = 0.01). MSNA was higher for both hypertensive genders (M:33vs27burst/min,p < 0.0001 & F:36vs28burst/min,p < 0.0001). In both genders hypertensives developed hypertensive response to exercise (M:0.78vs0.04,p < 0.0001 and F:0.85vs0.27,p < 0.0001), exhibit greater increases of SBP at all stages of Bruce protocol (3min M:156vs148mmHg,p = 0.04, F:162vs145mmHg,p < 0.0001, 6min M:181vs165,p = 0.017, F:185vs158,p < 0.0001, peak M:208vs184,p < 0.0001, F:197vs173,p < 0.0001, peak SBP/MET-slope M:6.7vs5.0,p = 0.038, F:7.1vs3.8,p < 0.0001). Their maximum exercise heart rate was lower (M:158vs167bpm,p = <0.014 and F:153vs162bpm,p < 0.0001). Only hypertensive women exhibit echocardiographicly increased left ventricular mass index (81vs72 gr/m 2 ,p = 0.006), left atrium diameter (3.7vs3.4mm p < 0.0001), intraventricular septum (0.94vs0.89cm,p = 0.007), isovolumic relaxation time (106vs80ms,p = 0.042) and decreased transmitral flow E/A (0.8vs1.0,p = 0.005). At their baseline ECG had longer P-wave duration (103vs94ms,p = 0.032) and QRS (88vs80ms,p = 0.018). Finally, the 2021 CKD-EPI GFR demonstrated a deterioration in women's renal function (87vs97, p = 0.009). Conclusions: In both men and women with high normal BP, MSNA identifies a state of increased sympathetic activation and exercise testing provides a prognostic value as a hypertension screening tool identifying a state of increased sympathetic drive which leads to development of hypertension. Moreover, women suffer a deterioration of kidney function as also an increase of heart's volume indicating an earlier target organ damage than men.