A New Enemy in the Hypertension Wars: Aldosterone

September 18, 2013

Aldosterone has significant effects on vascular function and can decrease flow-mediated vasodilation.

For many years, renin was the target in the battle against hypertension. Now aldosterone has achieved prominence, and its pathological characteristics warrant clinical concern and further study. Aldosterone’s increased activity in hypertensive persons is being appreciated more frequently-and that activity may lead to serious vascular consequences if unchecked.

As many as 5% to 13% of hypertensive patients have primary aldosteronism.1 As the severity of hypertension increases, so does the likelihood of aldosterone excess.1 Most recently, resistant hypertension has received increased attention. It is defined as failure to control blood pressure on a good 3-drug regimen that includes an appropriate diuretic. As many as 14% to 23% of persons with resistant hypertension have primary aldosteronism.1 Thus, it is not surprising that spironolactone, a mineralocorticoid receptor antagonist, has become agent number 1 in the treatment of resistant hypertension.

Aldosterone is not just a Na+-K+ hormone: it has significant effects on vascular function. Aldosterone increases vascular tone and reactivity to circulating vasoconstrictors such as angiotensin II and epinephrine, and it can decrease flow-mediated vasodilatation, possibly as a result of a nitric oxide–lowering mechanism.1 Furthermore, aldosterone can foster perivascular fibrosis (it is not surprising that spironolactone is being used for systolic heart failure).1 Putting aldosterone into the central nervous system through intracerebroventricular catheters-in minute doses-can raise blood pressure.1

Because excess aldosterone has many potential downsides, it is important to suspect its presence. Patients who have hypertension and elevated aldosterone are prone to serious consequences. Compared with persons who do not have these disorders, their risk of myocardial infarction is increased approximately 2.5 times; stroke, 3 to 4 times; cardiac arrhythmia, 5 times; and peripheral vascular disease, 3 times.1 But if the aldosterone excess is treated, the risk of these complications returns to the same level as that of any other patient with essential hypertension.1

What are some “dos and don’ts” for primary care practice regarding elevated aldosterone in a hypertensive population?

• Be suspicious of an excess aldosterone syndrome in your hypertensive patients. Do not keep adding antihypertensives to the regimen when patients do not reach target blood pressure. After 3 medications fail, you can measure aldosterone levels (often indexed in a ratio with renin). If the aldosterone/renin ratio exceeds 25 and the aldosterone value is at least 15 ng/dL, you are dealing with excess aldosterone. This is the time for consultation or at least a trial of spironolactone for blood pressure control.
• The response to spironolactone may take as long as 1 month.1 Do not give up too early! Seventy-five percent of patients with resistant hypertension who are treated with spironolactone respond.
• Use spironolactone in those with resistant hypertension who do not have elevated aldosterone. It still works in these patients as well.

More data about aldosterone in vascular disease and hypertension will be forthcoming.

This hormone is contemporary target number 1 in hypertensive persons, and we have the medication to combat it as long as we suspect its presence.

1. Weiner ID. Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism. Semin Nephrol. 2013;33:265-276. (Abstract)