Left ventricular changes in primary aldosteronism

In their report Goldkorn et al1 compared patients with primary aldosteronism (PA) and patients with essential hypertension (EH) and concluded that left ventricular (LV) mass index was not increased in the latter compared to the former patients. On the basis of this finding and on the lack of an association of LV mass with plasma or urine aldosterone, they concluded that there is no evidence for an association of aldosterone with LV structure or geometry. This conclusion is at variance with previous studies from our2 and other groups,3 which they did not mention. Several considerations concur, in our view, to suggest caution in drawing such conclusion. First, experience during the past decades has shown that although the diagnosis of Conn's adenoma can be conclusively made, that of idiopathic hyperaldosteronism cannot.4 It has been established three decades ago that this latter condition is almost indistinguishable from low renin EH,5,6 unless a combination of dynamic tests, imaging studies, and adrenal vein sampling,7 which apparently were not performed in the series studied by Goldkorn et al, is carefully used to diagnose this condition. Only 7 of 19 patients in the New York cohort and 12 of 16 in the Moscow cohort had Conn's adenoma, but, unfortunately, they did not provide any information on how this diagnosis was made. They also did not furnish any data on blood pressure (BP), serum potassium, plasma renin activity, aldosterone and, more important, LV mass after adrenalectomy. Thus, one wonders how the diagnosis of idiopathic hyperaldosteronism was made and uncertainties remain on the diagnosis in the Conn's adenoma group. Second, this was a two-center study and, therefore, it is likely that differences in diagnostic criteria for PA, as well as in the assessment of echocardiographic parameters did occur. For example, the plasma aldosterone levels were unavailable in the New York cohort, and the urine aldosterone values were not reported in the Moscow cohort. Third, a prerequisite for the validity of this type of comparative cross-sectional studies is the lack of biases in the selection of the patients for the two groups. Goldkorn et al claim that their PA and EH groups were well matched for gender, age, and BP. However, the patients were not matched for the known duration of hypertension, a variable that notoriously affects LV geometry and structure. Furthermore, the groups differed remarkably in terms of ongoing antihypertensive treatment. As they stated, 14 PA and 2 EH in the New York cohort and 12 PA v 9 EH patients in the Moscow cohort were on treatment; collectively 74% PA patients were treated versus 31% EH patients (χ2 = 4.49, P < .05). Needless to say that this difference might have also precluded detection of any differences in LV structure or geometry. Fourth, as already mentioned, the plasma and urine aldosterone levels were unavailable in the New York and Moscow cohort, respectively. Thus, the regression analysis could not be performed in the entire group. Consequently, it appears evident that the failure to detect an association between the hormone and LV mass can simply be due to the lack of statistical power. In the only study of ours that Goldkorn et al quoted,2 we carefully matched PA patients and EH patients for demography and BP values and, most important, our two groups did not differ significantly for duration of hypertension. Although all of our PA patients had previously been on regular antihypertensive treatment, whereas only 2 of the 34 EH had been treated, we found a higher LV mass index in PA than EH patients. In another study, which Goldkorn et al ignored, on a large series of patients (n = 26) with proven Conn's adenoma, not only did we confirm this finding, but also found a significant relationship of plasma aldosterone with both interventricular septum and LV posterior wall thickness.8 The occurrence of excess LV hypertrophy in PA patients was also confirmed in a Japanese study by Shigematsu et al,3 another article that Goldkorn et al evidently ignored, which documented that LV hypertrophy, mostly of the eccentric type, preceded the other signs of target organ damage in PA patients. With regard to the hypothesis that aldosterone might be associated with changes of LV diastolic function, which Goldkorn et al put forward in their discussion, in both our studies, as well as in another study,9 we documented clear-cut changes in LV diastolic filling that indicated the greater dependency of the LV on the atrial contraction for its filling in PA compared to EH patients. Thus, this hypothesis has already been tested, albeit Goldkorn et al were evidently unaware of it. Incidentally, we would like to recall that in an additional report, which Goldkorn et al failed to mention, extensive cardiovascular fibrosis was reported at necropsy in a patient with aldosterone-producing adenoma.10 In addition, we would like to point out that the LV midwall shortening that Goldkorn et al claimed they measured for the first time in PA patients, was already reported in another study from our group in 1998, again not quoted. We are pleased to see that Goldkorn et al's finding of similar values in PA and EH patients, confirms our earlier report.9 Finally, the hypothesis that aldosterone exerts a pivotal role in causing cardiac fibrosis stands not only on a wealth of experimental studies, but also on a more recent study from our group. Using video-densitometry to assess LV texture, we found a significant decrease in cyclic variation index in the interventricular septum of PA patients, as compared to EH.11 This index was found to correlate with cardiac fibrosis in a few studies. Thus, in our view, because of a number of methodologic flaws as well as failure to adequately mention and discuss previous published findings, the conclusions of Goldkorn et al are unwarranted.