Aldosterone: Yet Another Path to Blood Pressure Variability and Target Organ Damage

In this issue of The Journal of Clinical Hypertension, Grillo and colleagues1 demonstrated that blood pressure (BP) variability (BPV) as determined by ambulatory BP monitoring (ABPM) was greater for patients with primary aldosteronism and those with essential hypertension in comparison to patients with no hypertension. The clinical implications of their findings are significant as they demonstrate another important subgroup of patients who are at increased risk for target organ damage from BPV. In addition, these investigators provide more evidence of the clinical utility of ABPM in diagnosing BPV in at‐risk patient populations.

There is growing evidence from both short‐term (24‐hour) and long‐term assessments that BPV is associated with a higher risk for stroke, myocardial infarction, and kidney disease in patients with essential hypertension.2, 3 A study of 169 hypertensive patients showed that short‐term BPV was associated with increased risk for left ventricular hypertrophy, increased carotid artery intimal‐media thickness, and albuminuria, and prognosis was related to the number of sites of target organ damage.4 Similarly, Tatasciore and colleagues5 demonstrated increased carotid intima‐media thickness and left ventricular mass in patients with greater BPV. These findings were specific for systolic BPV while awake and were independent of mean awake BP levels.5 Long‐term BPV with measurements spanning weeks, months, or years is typically assessed by patient home BP monitoring or clinic BP measurements.2 As with short‐term BPV, long‐term BPV has also been associated with an increased risk of target organ damage in patients with essential hypertension.2 In multiple studies, patients with greater long‐term variability in their home BP measurements had a higher prevalence of cardiovascular and kidney damage2, 6 and a higher risk of cardiovascular events and mortality.2, 7, 8, 9, 10

Significantly compounding the cardiovascular risk of BPV, hypertensive patients with primary aldosteronism appear to be even more vulnerable to target organ damage compared with patients with only essential hypertension. A study of cardiovascular outcomes compared patients with primary aldosteronism from solitary adenomas or bilateral adrenal hyperplasia with patients who had essential hypertension.11 These cardiovascular events included stroke, myocardial infarction, atrial fibrillation, and echocardiographic and electrocardiographic evidence of left ventricular hypertrophy.11 The investigators found that patients with primary aldosteronism experienced more cardiovascular events than patients with essential hypertension.11 Importantly, the excess cardiovascular event burden in the primary aldosteronism patient group was independent of BP control.11 In a subsequent study, Catena and colleagues12 showed that the prevalence of cardiovascular events was significantly greater in a group of patients with primary aldosteronism (35%) than in patients with essential hypertension (11%). This excess cardiovascular complication burden was also independent and out of proportion to the patient's BP.12 Although both of these studies did not specifically evaluate BPV, it is certainly possible that the findings of Grillo and colleagues, which implicated BPV and target organ damage, is a causative factor for the increased cardiovascular events found in patients with primary aldosteronism.

Given the increased risk of target organ damage associated with BPV, it may become critical that clinicians now consider another metric to assess whether their hypertensive patients are receiving optimal antihypertensive treatment; it is now not enough to just achieve a BP below a recommended threshold. A substantial body of clinical research has demonstrated that BPV is a significant causative factor in target organ damage even when BP is adequately controlled with medical therapies. For patients with primary aldosteronism who are already more vulnerable to target organ damage than patients with essential hypertension, BPV may be an even more important factor to measure. As Grillo and colleagues demonstrated in this study, ABPM is a well‐suited and useful tool to assess BPV in patients with primary aldosteronism. Currently, the use of ABPM is limited and typically confined to the diagnosis of white‐coat hypertension, episodic hypertension, resistant hypertension, and hypotensive symptoms while taking antihypertensive medications and autonomic dysfunction.13, 14, 15 However, we suggest that ABPM also be considered as a tool to evaluate the extent of BPV in patients with primary aldosteronism and to determine the effectiveness of an antihypertensive regimen.

Finally, the authors discuss potential mechanisms for BPV. We are left concluding that there is much more to learn, including whether the fluctuations in BP are incurring injury or simply reflecting an aspect of target organ changes. Does the fact that one finds BPV in patients with primary aldosteronism offer any clues? Certainly volume expansion is a mediator of the increase in BP in primary aldosteronism and it would seem unlikely that volume per se would vary enough to account for the BPV. A volume‐expanded state, however, could sensitize BP to changes in, for example, sympathetic tone. It would be interesting to know how much BPV might decrease following removal of an adrenal tumor that produced aldosterone. An underlying role for aldosterone in the development of hypertensive states as well as hypertensive complications seem to continually widen.