Renin-angiotensin status, sympathetic nervous activity and associated factors among hypertensive patients not on medications at Mulago hypertension clinic

Abstract

Background The sympathetic nervous activity (SNS) and renin-angiotensin - aldosterone system (RAAS) are essential for the development and sustenance of hypertension. Accordingly, antihypertensive agents targeting these two systems are considerably used in Mulago Hospital medical out patient’s hypertension clinic. However, the status of these systems and factors associated with them in patients attending the Mulago Hospital medical out patient’s hypertension clinic has not been evaluated. Objective To determine the renin-angiotensin status and sympathetic nervous activity, and their associated factors in hypertensive patients not on antihypertensive medications attending the Mulago medical out patient’s Hospital hypertension clinic. Methods This was a cross sectional study where 162 newly diagnosed or previously treated and defaulting hypertensive patients, attending the Mulago Hospital medical out patient’s hypertension clinic, were enrolled consecutively. After consenting to participate in the study, data on; socio-demographics, physical parameters of blood pressure and body mass index, and social characteristics including alcohol use, raw salt addition and smoking status was collected in a questionnaire. Blood and urine samples were taken to measure; renal function, angiotensin II, metanephrine, normetanephrine levels, and calculation of urine fraction excretion of sodium was done. A p-value of ≤ 0.05 was taken as statistically significant. Data were analysed using StataIC version 12.0. Results A total of 136 (84%) participants had low angiotensin II levels, 15 (9%) had normal levels, while, 11 (7%) had high levels of angiotensin II. For metanephrine, 85/88 (97%) participants had normal levels, while, 3 (3%) had raised levels. While for normetanephrine 142 (88%) participants had normal levels and 20 (12%) participants had above normal levels. Normal urine sodium was associated with low angiotensin II levels and normal angiotensin II levels (P-value 0.007). Female gender as well as low and high diastolic blood pressure were associated with a protective effect from high normetanephrine (OR- 0.29, P value 0.015, 80-89 mmHg (OR - 0.19, p value 0.053), above 100 mmHg (OR - 0.27, p value 0.022). Current smoking status was associated with an increased risk of abnormal normetanephrine levels (OR-17.6, P-value -0.022). All other factors assessed like; alcohol intake, raw salt intake, pulse rate, body mass index, serum sodium and fractional excretion of sodium were not significantly associated with either renin-angiotensin status or sympathetic nervous activity. Conclusions 1. Hypertensive patients in our setting have predominantly low angiotensin II, salt sensitive or volume dependent hypertension, and hence could have apparent mineralo-corticoid excess. 2. Sympathetic nervous activation is not a significant mechanism of hypertension in patients in out setting, more so in the females, and with the exception of smokers. 3. Female gender, smoking and raw salt intake are the main factors associated with the renin-angiotensin and sympathetic nervous activity in hypertensive participants in our population. Recommendations 1. Clinicians should be cautious about the use of ACEI/ARBs or beta blockers as single antihypertensive therapy except in compelling situations. 2. Health messages to hypertensive patients in Uganda should target reduction of salt intake and smoking. 3. A full evaluation of renin-angiotensin - aldosterone axis & II hydroxysteroid dehydrogenase mutation status is required.