Long-Term Cardiac Effects of Adrenalectomy or Mineralocorticoid Antagonists in Patients With Primary Aldosteronism

Abstract

Abstract-Exposure to excess aldosterone results in cardiac damage in hypertensive states. We evaluated the long-term cardiac structural and functional evolution in patients with primary aldosteronism after surgical or medical treatment. Fifty-four patients with primary aldosteronism were enrolled in a prospective study and were followed for a mean of 6.4 years after treatment with adrenalectomy (nϭ24) or spironolactone (nϭ30). At baseline, echocardiographic measurements of patients with primary aldosteronism were compared with those of 274 patients with essential hypertension. Patients with primary aldosteronism had greater left ventricular mass, more prevalent left ventricular hypertrophy, lower early:late-wave diastolic filling velocities ratio, and longer deceleration time than patients with essential hypertension but no differences in relative wall thickness and systolic function. During follow-up, average blood pressure was 135/82 and 137/82 mm Hg in patients treated with adrenalectomy and spironolactone, respectively. In the initial 1-year period, left ventricular mass decreased significantly only in adrenalectomized patients. Subsequent changes in left ventricular mass were greater in patients treated with spironolactone, with an overall change from baseline to the end of follow-up that was comparable in the 2 groups. Prevalence of hypertrophy decreased in both treatment groups, whereas diastolic parameters had only mild and nonsignificant improvement. Changes in blood pressure and pretreatment plasma aldosterone were independent predictors of left ventricular mass decrease in both treatment groups. Thus, in the long-term, both adrenalectomy and spironolactone are effective in reducing left ventricular mass in patients with primary aldosteronism, with effects that are partially independent of blood pressure changes. Key Words: adrenalectomy Ⅲ echocardiography Ⅲ left ventricular hypertrophy Ⅲ spironolactone Ⅲ diastolic filling F or many decades, aldosterone has been seen as a hormone almost exclusively involved in the regulation of body fluids, maintenance of electrolyte balance, and blood pressure homeostasis. 1 More recent views, however, indicate that aldosterone can contribute to cardiac damage independent of blood pressure. 2 In animal studies, exposure to excess aldosterone levels has been associated with collagen deposition, myocardial fibrosis, and ventricular remodeling, 3 and 2 large clinical trials have reported a significant decrease in the mortality rate of patients with heart failure who were treated with aldosterone antagonists. 4,5 Primary aldosteronism is a disease associated with hypertension that offers an important clinical opportunity for assessing the effects of excess aldosterone on the cardiovascular system because, in this condition, its effects are isolated from those of the renin-angiotensin axis. The widespread use of the aldosterone:renin ratio as a screening test has led to more efficient identification of this endocrine disorder. 6,7 Cardiac structural and functional changes ...

Hyperaldosteronism and Left Ventricular Hypertrophy

“…In fact, LV mass decreased in both patients with higher and lower plasma aldosterone, but the degree of LV mass regression tended to be greater in the former group (21 versus 12%), suggesting, in this case, a direct involvement of aldosterone in the development of LV hypertrophy. These findings are in partial agreement with those of a long-term prospective study, 3 in which we reported significant reduction of LV mass to occur in 30 patients with primary hyperaldosteronism who were treated with spironolactone and in whom a multivariate analysis demonstrated that pretreatment aldosterone levels predict treatment-induced LV mass decrease independent of blood pressure change. In our study, however, decrease in LV mass was much slower that in Gaddam's study, reaching statistical significance only after a few years, and occurred in the absence of significant changes in cardiac and systemic markers of the volume status.…”

The effect of treatment on monocyte and lymphocyte cytokine release in patients with aldosteronoma

“…Although mineralocorticoid receptor antagonists produced multi-directional anti-inflammatory effects, their monocyte-and lymphocyte-suppressive effects did not increase with time, and cytokine release was higher than in control subjects during the entire observation period. These findings are in disagreement with those of other authors [8][9][10] who observed similar cardiovascular and nephroprotective benefits after adrenalectomy and spironolactone treatment. However, their study populations included both patients with aldosteronoma (most of whom underwent adrenalectomy) and patients with bilateral adrenal hyperplasia (treated with spironolactone), and this fact may explain the differences between our results and their results.…”

Outcomes of Drug-Based and Surgical Treatments for Primary Aldosteronism

“…84 Spironolactone may appear to be less potent than adrenalectomy for improving left ventricular hypertrophy, but studies with long-term follow-up have shown that the same improvement is ultimately achieved, even though the regression of left ventricular mass is slower with spironolactone than with adrenalectomy. 29,34,85 The benefits of PA treatment were similar for specific drugs and surgery in both studies comparing the incidence of cardiovascular events in treated PA patients and matched controls with essential hypertension. 36,37 The relative glomerular hyperfiltration and microalbuminuria of PA patients are corrected on specific drugs (Figure 1).…”

“…28 Many studies have shown that left ventricular mass decreases and that aortic pulse wave velocity and carotid intima-media thickness improve after adrenalectomy. [29][30][31][32][33][34][35] A prospective study compared cardiovascular events in 54 PA patients treated by adrenalectomy (unilateral disease) or with spironolactone (unilateral or bilateral disease) with 323 patients with essential hypertension. 36 The composite endpoint was myocardial infarction, stroke, any type of revascularization procedure, and sustained arrhythmia.…”