Autoantibodies in Primary Aldosteronism (page 526)
Primary aldosteronism (PA) is the most frequent endocrine cause of hypertension. The differential diagnosis between its 2 main subtypes, for example—aldosterone-producing adenoma and idiopathic hyperaldosteronism, is the key for selecting surgical or medical treatment, but challenging.
In this study, we detected autoantibodies against the AT1 receptor (AT1AA) at a raised titer in serum of PA patients, and particularly in those with an aldosterone-producing adenoma as compared with those with idiopathic hyperaldosteronism or essential hypertension with similar blood pressure (BP) elevation. Of clinical relevance, the AT1AA titer provided a discrimination of aldosterone-producing adenoma from idiopathic hyperaldosteronism, thus suggesting that the AT1AA titer can help in selecting the PA patients to be submitted to adrenal vein sampling. The latter test, which is expensive, invasive, and not widely available, is recommended by the Endocrine Society Guidelines in all patients who are candidates for adrenalectomy.
Finally, the mechanisms underlying PA have eluded identification thus far notwithstanding a long quest. As these AT1AA are suggested to play an agonistic effect, including stimulation of aldosterone secretion, their presence in aldosterone-producing adenoma patients could explain the persistent over-secretion of aldosterone in spite of the high BP, the suppression of the renin-angiotensin system and the hypokalemia, all factors that would be expected to blunt aldosterone secretion. Hence our data might shed a new light on the pathophysiology of PA.
Renal Denervation and Sympathetic Activity (page title>Autoantibodies in Primary Aldosteronism (page 457)
Catheter-based renal denervation has emerged as a novel treatment option for patients with resistant hypertension. The limited number of studies available thus far suggest that the procedure is safe and results in a significant and sustained BP reduction in the majority of treated patients with resistant hypertension. Although ablation of efferent renal nerves, as evident form a mean reduction in renal noradrenaline spillover of 47%, is likely to contribute to the BP lowering effects via alteration of renin release, renal blood flow, and tubular sodium retention, inhibition of central sympathetic outflow has also been documented by applying multiunit muscle sympathetic nerve activity recordings.
Here, we examined whether renal denervation may differentially influence the sympathetic discharge pattern of single vasoconstrictor neurons in patients with resistant hypertension and found that all properties of single-unit muscle sympathetic nerve activity, including firing rates of individual vasoconstrictor fibers, firing probability, and multiple firing incidence of single units within a cardiac cycle, were substantially reduced. These findings indicate that renal denervation may restrain abnormal patterns of sympathetic nerve firing commonly evident in patients with resistant hypertension and exhibit renal signaling via afferent nerves projecting to certain brain stem nuclei as a likely contributor to the BP rise in resistant hypertension.
Combination Therapy, CV Events, and BP Control (page Sympathetic Activity (page title>Autoantibodies in Primary Aldosteronism (page 309)
Combination therapy is required to achieve current BP targets in ≈75% of hypertensive patients. Previous studies indicate that initial use of a combination accelerates the time course over which BP control is attained. However, the optimal time frame for achieving BP control in clinical practice has never been defined, and criteria for using initial combination therapy remain uncertain. In a retrospective, matched cohort study, the impact of initial versus delayed combination therapy on the risk of developing a cardiovascular (CV) event was assessed in a community practice setting. The mean baseline BP was ≈150/85 mm Hg, and two thirds had stage I hypertension. Initial combination treatment led to more rapid and more effective BP control and was associated with a 34% risk reduction for CV events or death relative to patients initiated on monotherapy and subsequently uptitrated to combination treatment by their practicing physicians. Fewer patients who experienced a CV event achieved target BP, and on-treatment BP parameters accounted for most of the difference in CV event rates.
Initial combination therapy was also associated with a significant reduction in healthcare resource utilization. These results suggest that combination therapy should be initiated routinely in most patients likely to require multiple agents to reach goal BP, and that initial combination therapy is a superior treatment strategy for a large segment of the hypertensive population including many patients with mild hypertension.
- © 2013 American Heart Association, Inc.