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Elevated Aldosterone: A New Player in the Cardiovascular Disease Epidemic?

Elevated Aldosterone: A New Player in the Cardiovascular Disease Epidemic?

Under what circumstances is it worthwhile to measure aldosterone levels in hypertensive patients? An increasing number of cardiovascular risk factors are being packaged into individual "epidemics." The well-publicized obesity epidemic has contingently led to a type 2 diabetes mellitus epidemic. The "cholesterol" epidemic has resulted in an increased incidence of ischemic cardiovascular disease and has prompted the introduction of a variety of statins and interventional responses. Is elevated aldosterone the next epidemic? Recent evidence suggests that high aldosterone levels can increase cardiovascular risk.

PREVALENCE OF PRIMARY ALDOSTERONE EXCESS
A generation ago, it was taught that primary aldosterone excess was responsible for hypertension in fewer than 1% of all persons with the disorder.1,2 Screening for hyperaldosteronism was limited to hypertensive patients who had an unexplained low serum potassium level. Since this was "standard of care," aldosterone-secreting adrenal adenomas were detected, but adrenal hyperplasia—a condition that does not consistently lower serum potassium levels—often went undiagnosed.

Use of the aldosterone-renin ratio as a screening test in hypertensive patients who do not have hypokalemia reveals that up to 12% of persons with high blood pressure may have excessive aldosterone levels.1 The aldosterone level rises autonomously from the hypersecretion of either a benign adenoma or adrenal hyperplasia, and the resultant volume expansion lowers the renin level; thus, the ratio rises, and an increased value (greater than 20 to 1) suggests primary aldosteronism.

ALDOSTERONE AND CARDIOVASCULAR RISK: WHAT THE EVIDENCE SHOWS
Animal studies have demonstrated that excess aldosterone can cause myocardial fibrosis.3 In humans, when aldosterone antagonists are administered to patients with chronic heart failure, mortality decreases.3 Catena and associates3 sought to determine whether excess aldosterone in hypertensive patients may have similar untoward effects on cardiovascular risk.

Primary excess of aldosterone was diagnosed in 54 patients (the cause was adenoma in 54% and hyperplasia in 46%). The diagnosis was based on screening results (aldosterone-renin ratio greater than 20), a lack of suppression of the elevated aldosterone with saline, and CT scanning with venous localization for adenomas. The patients with aldosterone excess at baseline had more cardiovascular events (35%) than those who did not have excess aldosterone (11%). After treatment (surgery for adenomas, spironolactone for hyperplasia), blood pressure decreased and the number of cardiovascular events fell to levels observed in the group without an excess of aldosterone.

IMPLICATIONS FOR YOUR PRACTICE
Although I do not believe every patient with hypertension needs to have an aldosterone-renin ratio measured, too few are probably performed overall. Unexplained hypokalemia definitely warrants measurement of the ratio, and patients with a normal serum potassium level whose blood pressure is difficult to control on 2-drug antihypertensive regimens may benefit from screening. Another possibility might be a trial of spironolactone in patients with resistant hypertension, to combat the putative effects of excess aldosterone levels with an antagonist.

 

References

REFERENCES:
1. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004;89:1045-1050.
2. Stowasser M, Gordon RD, Gunasekera TG, et al. High rate of detection of primary aldosteronism, including surgically treatable forms, after "non-selective" screening of hypertensive patients. J Hypertens. 2003;21:2149-2157.
3. Catena C, Colussi GL, Nadalini E, et al. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med. 2008;168:80-85.
 
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