Abstract

Primary aldosteronism (PA) is now recognized as the most common cause of secondary hypertension. Although the aldosterone-to-renin ratio is recommended for case detection, screening rates for PA remain low. Based on our prior study in low-renin hypertension, we hypothesized that a statistical adjustment for age, sex, and sodium status would improve the diagnostic accuracy of aldosterone measurements. Data from the cohort of 3,345 individuals in the sixth examination cycle of the Framingham Offspring Study was analyzed. In addition to the standard study protocol, blood was drawn for later measurement of aldosterone. After exclusions, the final analysis consisted of 1,468 normotensives (652 men and 834 women), aged 29 to 85. To compare levels of continuous variables in two groups, we used independent samples t tests. We regressed natural-log-transformed values of aldosterone on age, sex, and the urine sodium/creatinine ratio. Unimodality of aldosterone (adjusted and unadjusted) was tested utilizing dotplots and the dip test. The mean aldosterone levels were 10.4 ± 5.89 ng/dL in women and 11.3 ± 6.14 ng/dL in men (p < 0.005). Age, sex, and urine sodium/creatinine ratio were each significantly associated with aldosterone (p < 0.005). The proportion of variability explained by age, sex, and urine sodium/creatinine was 0.91%,1.3%, and 8%, respectively. The fully adjusted model r 2 = 0.0948. When adjusted for age, sex, and urine sodium/creatinine ratio, the distribution of aldosterone was unimodal (dip test: 2.26 ± 0.17 ng/dL, p = 0.9973); when unadjusted, the distribution of aldosterone was not unimodal (dip test, p ≤ 0.005). The dotplot and Q-Q plot showed a normal distribution of aldosterone after adjustment. In this large, community-based population, adjustment for age, sex, and sodium status resulted in a more normal distribution of aldosterone. PA has been described as a condition “in which aldosterone production is inappropriately high for sodium status.” Our study suggests that appropriate adjustment of the measured serum aldosterone concentration may provide a more accurate approximation of the renin-angiotensin aldosterone system. Studies in populations of PA are needed to test for improved diagnostic accuracy that may result from this adjustment.

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