Mutations in Multinodular Adrenals With Aldosterone-Producing Adenoma (p 1014)
Primary aldosteronism is the most common curable form of secondary hypertension. The early detection of primary aldosteronism is a key to targeted management and clinical outcome, given the major cardiovascular adverse effects of aldosterone excess. Primary aldosteronism is considered in the majority of cases to be caused by either unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. However, APA may not be solitary, or of homogeneous histology, and the same adrenal often shows zona glomerulosa hyperplasia and multiple secondary aldosterone-producing nodules. In the past few years, impressive progress has been made in our understanding of the genetic causes of APA and familial forms of bilateral adrenal hyperplasia, with the identification of somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 in >50% of APA. In this issue of Hypertension, Fernandes-Rosa et al report the occurrence of different somatic mutations in APA and secondary aldosterone-producing nodules from the same adrenal. In 1 case, a genetic defect was identified in the secondary nodule but not in the APA. These findings enhance recognition of different genotypes among nodules in the same adrenal, and are consistent with a polyclonal origin for multinodular adrenals with APA. The identification of independent molecular events causing multiple nodules further blurs the clinical distinction between patients with bilateral adrenal hyperplasia and APA, both of which may result from shared genetic susceptibility to develop primary aldosteronism.
Blood Pressure and Cerebral Blood Flow in Old Age (p 954)
Studies showing a relation between low blood pressure and adverse health outcomes in older persons proposed the resulting reduction in cerebral blood flow and hypoxia as possible underlying mechanism. However, in an older population using antihypertensive medication, we could neither confirm the hypothesis that low blood pressure is associated with low cerebral blood flow, nor that an increase in blood pressure leads to increased cerebral blood flow. The absence of associations could imply that the blood pressure range needed to keep cerebral blood flow at a constant level is relatively wide. Therefore, the suggestion that lowering blood pressure in older persons using antihypertensive agents gives rise to reduced cerebral blood flow may be questionable. However, for safety reasons, in our study we did not include persons with severe cardiovascular disease, whereas it is expected that cerebral autoregulation is more likely to be impaired in these persons.
To date, firm evidence relating blood pressure to cerebral blood flow is lacking. On the basis of the limited evidence to date, we cannot give clear recommendations for clinical practice. Because observational studies have shown that the optimum blood pressure may differ for different patient groups such as for frail older patients (with more severe vascular disease), we advise a tailored and possibly less stringent approach for (initiating) antihypertensive treatment in frail older persons.
B Cells, IgG, and Hypertension (p 1023)
Essential hypertension in humans has been known since the 1970s to be associated with elevated serum antibody levels, but no previous studies have tested whether hypertension-associated antibodies are innocent bystanders or causative agents in the disease process. In this issue, we provide direct evidence that B-cell activation and IgG production are essential for the development of angiotensin II–dependent hypertension in mice. Specifically, we demonstrate that hypertension in mice, like in humans, is associated with elevated serum concentrations of IgG antibodies, which accumulate in the aortic adventitia. Importantly, B-cell deficiency resulting from either knockout of the B cell–activating factor receptor, or treatment with a B cell–depleting anti-CD20 antibody, reduced IgG levels and afforded protection against hypertension, vascular fibrosis, and stiffening. The observation that anti-CD20 treatment prevented hypertension is important because similar therapies (eg, rituximab) are used clinically to treat autoimmune diseases and could conceivably be rebadged as novel antihypertensive agents. Should such a therapy prove effective at reversing hypertension in humans, it could have major clinical implications, especially for patients with severe refractory hypertension for whom current antihypertensive therapies are ineffective, and in whom the benefits of blood pressure lowering may outweigh risks associated with potential suppression of immune function. We suggest that a logical next step toward clinical translation may be to analyze blood pressure profiles of hypertensive patients receiving B-cell therapy for conditions such as rheumatoid arthritis or lymphoma so as to identify if there is any existing evidence to support an antihypertensive effect.
- © 2015 American Heart Association, Inc.