Effect of losartan and spironolactone on left ventricular mass and heart sympathetic activity in prehypertensive obese subjects: a 16-week randomized trial

Abstract

Obesity has been shown to be associated with increased left ventricular mass (LVM) and heart sympathetic activity even in nonhypertensive subjects. These factors are predictors of cardiovascular morbidity and mortality independent of other traditional risk factors. We evaluated the effect of losartan and spironolactone on LVM and heart sympathetic activity in prehypertensive obese subjects. A 16-week blinded randomized trial was performed in middle-aged men selected from a Health Public program. Anthropometric and clinical variables were measured at baseline and after losartan (50 mg/day; n ¼ 25) or spironolactone (25 mg/day; n ¼ 25) treatment. Heart sympathetic activity was evaluated with 60-min electrocardiograph monitoring, and spectral analysis was carried out. LVM was measured by echocardiography according to Devereux and Reicheck's formula indexed for body height (m 2.7 ) to account for obesity. Anthropometric variables, systolic, and diastolic blood pressure levels decreased in both groups of treatment without statisticall difference between them. Losartan increased heart rate variability (from 70.0 to 82.3 ms; P ¼ 0.01), and decreased low frequency-high frequency index (from 6.6 to 4.9; P ¼ 0.001), and LVM (from 49.2 to 45.2 g; P ¼ 0.004). In the multiple regression analysis for factors associated with reduction in LVM; treatment with losartan, and decrease in SBP were the only factors included in the model (R 2 ¼ 0.60; P ¼ 0.003). To conclude losartan, but not spironolactone, decreased LVM and heart sympathetic overactivity in prehypertensive obese subjects after 16 weeks of treatment. Regression on LVM was associated with reduction on SBP levels.

Prehypertension: Underlying pathology and therapeutic options

“…While others reported that permanent treatment of SHRs from conception onwards with ACEIs completely prevented hypertension [94,95] . The ARBs losartan was reported to have beneficial effect in humans [96] and rats [97,98] similar to that of captopril in SHRs, specifically, as shown by another study that transient use of losartan resulted in a long-lasting improvement of arterial contractility, an effect that was linked to endothelium-dependent vasodilatation [92,98] . Paradoxically, other authors showed that decreased BP is accompanied by severe disruption of the normal vascular architecture of intrarenal arteries [99] .…”

Hypertension and Cardiac Arrhythmias

“…Spironolactone is known to decrease collagen synthesis and therefore its use decreases myocardial fibrosis that is one of factors of arrhythmogenesis. Blockade of aldosterone receptors by spironolactone has not demonstrated decrease of LV mass in one short-term study [90], but more recent clinical studies have demonstrated improvement of myocardial function and decrease of left ventricular wall thickness [91]. Studies in spontaneous hypertensive rats have shown that combination treatment (spironolactone has been compared to spironolactone with enalapril or with verapamil) is superior in terms of reducing morphological changes like hypertrophy, fibrosis and inflammatory infiltrates [92].…”

Effect of weight loss on blood pressure changes in overweight patients: A systematic review and meta‐analysis

“…included studies, six studies contained both clinic and ambulatory BP values, [12][13][14][15][16][17] whereas 13 studies contained only clinic BP values, [18][19][20][21][22][23][24][25][26][27][28][29][30] 16 studies contained only ambulatory BP values. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] A total of 3219 patients were examined, and study populations varied from general group to populations with hypertension and the average weight-loss time was 7.7 months.…”