Primary Aldosteronism in Hypertensive Patients
By Michael H. Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: Primary aldosteronism was discovered in 6% of hypertensive patients in a group of primary care practices in Italy, and these patients exhibited more target organ damage. Thus, the authors recommended screening all hypertensive patients for primary aldosteronism.
SOURCES: Monticone S, Burrello J, Tizzani D, et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017;69:1811-1820.
Maiolino G, Calo LA, Rossi GP. The time has come for systematic screening for primary aldosteronism in all hypertensives. J Am Coll Cardiol 2017;69:1821-1823.
Controversy over the true prevalence of primary aldosteronism (PA) in a primary care population of hypertensive patients led to the PA in Torino (PATO) study. To avoid selection bias, 3,272 consecutive patients 18-60 years of age with new or previously diagnosed hypertension who presented to 19 general practitioners in Torino, Italy, between 2009-2014 were recruited. About half (1,672) agreed to participate. Their initial visit required prior cessation of all drugs that could affect the renin-angiotensin-aldosterone system so that blood for plasma renin activity (PRA) and aldosterone concentration (AC) could be determined. The diagnosis of PA was made if the AC/PRA ratio was > 30 and the AC was > 10 mg/dL. PA was found in 232 (14%) patients. These patients underwent an intravenous saline loading test, or a captopril challenge test in those with a contraindication to saline loading, to confirm the diagnosis of PA. The 99 patients (6% overall) with PA confirmed underwent a CT scan of the adrenal glands, and 91 patients underwent adrenal vein aldosterone sampling, to subtype the PA patients into those with bilateral adrenal hyperplasia (BAH in 64) and an aldosterone-producing adenoma (APA in 27). In eight patients, the subtype could not be determined. Clinical events such as coronary or cerebral vascular events, arrhythmias, and heart failure were noted. The prevalence of PA was 4% in stage one hypertension, 10% in stage two, and 12% in stage three. Hypokalemia off diuretics and other drugs was present in 29% of the PA patients and was more common in APA patients compared to BAH patients (52% vs. 22%; P = 0.013). PA patients demonstrated a higher incidence of metabolic syndrome compared to non-PA patients (45% vs. 30%; P < 0.001), echo left ventricular hypertrophy (54% vs. 32%; P < 0.001), microalbuminuria (22% vs. 13%; P < 0.001), and cardiovascular events (15% vs. 6%; P < 0.001). The authors concluded that PA is frequent in a primary care population of hypertensive patients and that all hypertensive patients should be screened for it.
Studies have shown that PA is the most common cause of secondary hypertension. Traditional wisdom has supported investigating hypertensive patients for possible PA if they have hypokalemia, more severe hypertension, or refractory hypertension. This study shows clearly that normokalemia is the most frequent presentation (71%) and most have stage one hypertension (45%). Even in those with adrenal adenomas, 33% are stage one. Also, PA is not rare, occurring in 4% of those with mild hypertension, 10-12% of those with more severe hypertension, and 6% overall. In addition, those with PA had a more severe clinical phenotype with higher rates of coronary and cerebrovascular disease, metabolic syndrome, and albuminuria. Finally, the discovery of PA can result in a cure (adrenal tumor resection) or a more targeted pharmacologic therapy of hypertension. Thus, the authors’ recommendation that all hypertensives should be screened is compelling.
The strengths of this study include the large population of unselected patients, the rigorous diagnosis of PA, and the identification of comorbidities. Limitations include the lack of home or ambulatory blood pressure monitoring to exclude the white-coat effect, the low recruitment rate, and the lack of screening for other secondary causes of hypertension. Also, although the Endocrine Society Guidelines for diagnosing PA were followed, there is no agreed-upon cutpoint for the AC/PRA ratio. Many clinics use a ratio > 40 and an AC > 15. These investigators used > 30 and > 10 to maximize sensitivity. This resulted in the necessity for further confirmatory testing, which resulted in a 57% false-positive rate. Consequently, the authors recommended that each clinic set their own diagnostic standards. Additionally, there are no data on the cost-effectiveness of screening. The other problem with screening is that the patients must be off all drugs that could affect the PRA and AC for four to six weeks, which may not be feasible for all patients. These investigators used calcium channel blockers and doxazosin to control blood pressure prior to the lab work. Some have suggested that a more therapeutically targeted approach is to not screen those with mild hypertension, no hypokalemia, and the absence of a renal mass on imaging. Given the observation that PA patients exhibit more target organ damage than non-PA hypertensives, we should be paying more attention to this secondary cause of hypertension.
Primary aldosteronism was discovered in 6% of hypertensive patients in a group of primary care practices in Italy, and these patients exhibited more target organ damage.
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