Medical research continues to fascinate. We do know more each year, and each year we understand better how much we do not know. I love studies that turn conventional wisdom 90-180 degrees. Important studies make us re-evaluate our assumptions, testing new hypotheses.

Yes, medicine is a developing science. We know much, but we have much to learn. Clearly the renin-angiotensin-aldosterone system has great importance. Each year we learn more about how its regulation, or maladaption, can impact health.

Today’s NEJM has another clue. Medscape reviews the article here – Aldosterone Levels Linked to Hypertension

In the Framingham Offspring Study, the investigators studied the relationship of baseline serum aldosterone levels to increases in blood pressure and to the incidence of hypertension after four years. Of 1,688 nonhypertensive participants, 58% were women, and mean age was 55 years. Increase in blood pressure was defined as an increment of at least one blood-pressure category as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension was defined as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications.

At follow-up, 33.6% of the participants had an increase in blood-pressure category, and hypertension had developed in 14.8%. Multivariable models revealed a 16% increase in the risk of an elevation in blood pressure (P = .002) and a 17% increase in the risk of hypertension (P = .03) per quartile increment in serum aldosterone level.

Compared with the lowest serum aldosterone quartile, the highest was associated with a 1.60-fold risk of an elevation in blood pressure (95% confidence interval [CI], 1.19 – 2.14) and a 1.61-fold risk of hypertension (95% CI, 1.05 – 2.46). Adjustment for urinary sodium excretion or left ventricular thickness or internal dimensions did not significantly affect the associations between the serum aldosterone level and blood-pressure outcomes.

So how should we use these data. First, I believe that these data provide a rationale for including ACE inhibitors or ARBs in most 2 drug regimens. Second, they suggest further investigation. This comment summarizes:

“…[I]f we assume that all the participants had an ample sodium intake, the association between the highest aldosterone levels and the increase in blood pressure in this study suggests that the aldosterone levels were inappropriate for the salt intake,” Drs. Dluhy and Williams write. “If so, one potentially important interpretation of these data is that the risk of the development of hypertension in some persons is related to the presence of underlying mild primary hyperaldosteronism. Thus, in these persons, aldosterone may indeed be a villain rather than a bystander in a society in which dietary sodium intake is high.”

We will undoubtedly read more about aldosterone and hypertension. And this epidemiological study supports focusing there.