Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis

Alterations in the renin angiotensin aldosterone system (RAAS) contribute to the underlying pathophysiology of insulin resistance in humans; however, individual differences in the treatment response of insulin resistance to RAAS blockade persist. Thus, understanding inter-individual differences in the relationship between the RAAS and insulin resistance may provide insights into improved personalized treatments and improved outcomes. The effects of the systemic RAAS on blood pressure regulation and glucose metabolism have been studied extensively; however, recent discoveries on the influence of local tissue RAAS in the skeletal muscle, heart, vasculature, adipocytes, and pancreas have led to an improved understanding of how activated tissue RAAS influences the development of insulin resistance and diabetes in humans. Angiotensin II (ANGII) is the predominant RAAS component contributing to insulin resistance; however, other players such as aldosterone, renin, and ACE2 are also involved. This review examines the role of local ANGII activity on insulin resistance development in skeletal muscle, adipocytes, and pancreas, followed by a discussion of the other RAAS components implicated in insulin resistance, including ACE2, Ang1-7, renin, and aldosterone.

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The renin angiotensin aldosterone system and insulin resistance in humans.

Primary aldosteronism (PA), the most common form of secondary hypertension, can be either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone-specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. Confirmatory testing is indicated in most patients with positive case detection testing results. The next step is to determine whether patients with confirmed PA have a disease that can be cured with surgery or whether it should be treated medically; this step is guided by computed tomography scan of the adrenal glands and adrenal venous sampling. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low-sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to maintain a high-normal serum potassium concentration without the aid of oral potassium supplements.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/joim.12831

Diagnosis and treatment of primary aldosteronism: practical clinical perspectives.

Systematic review and meta-analysis of the prevalence of resistant hypertension in treated hypertensive populations.

DESIGN Abnormalities in glucose homeostasis have been described in patients with primary aldosteronism (PA) but most studies show inconsistent results. Therefore, we aimed to compare the prevalence of type 2 diabetes mellitus and metabolic syndrome (MetS) in newly diagnosed PA patients to a matched control cohort of the background population. METHODS In total, 305 PA patients of the prospective German Conn's Registry were compared to the population-based Study of Health In Pomerania (SHIP1; n=2454). A 1:1 match regarding sex, age, and BMI resulted in 269 matched pairs regarding type 2 diabetes and 183 matched pairs regarding MetS. Of the total, 153 PA patients underwent oral glucose tolerance testing (OGTT) at diagnosis and 38 PA patients were reevaluated at follow-up. RESULTS Type 2 diabetes and MetS were significantly more frequent in PA patients than in the control population (17.2% vs 10.4%, P=0.03; 56.8% vs 44.8%, P=0.02 respectively). Also, HbA1c levels were higher in PA patients than in controls (P<0.01). Of the total, 35.3% of non-diabetic PA patients showed an abnormal OGTT (¼ newly diagnosed type 2 diabetes and ¾ impaired glucose tolerance). PA patients with an abnormal OGTT at baseline presented with significantly improved 2 h OGTT glucose (P=0.01) at follow-up. We detected a negative correlation between 2 h OGTT glucose levels and serum potassium (P<0.01). CONCLUSIONS Type 2 diabetes and MetS are more prevalent in patients with PA than in controls matched for sex, age, BMI, and blood pressure. This may explain in part the increased cardiovascular disease morbidity and mortality in PA patients.

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Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn's Registry.

Metabolic syndrome (MS) is frequent clinical condition in patients with hypertension. Primary aldosteronism (PA) is a common form of secondary hypertension. This study was aimed at investigating the prevalence of the MS and its components in the two major forms of PA, in unilateral aldosterone-producing adenoma (APA) and bilateral aldosterone overproduction because of idiopathic hyperaldosteronism (IHA). The diagnosis of the particular form of PA was based on adrenal venous sampling and/or successful surgery confirmed by histopathological examination. We analyzed clinical and laboratory data from 100 patients with PA (50 patients with IHA and 50 patients with APA) and from 90 patients with essential hypertension (EH). Metabolic profiles of patients with bilateral form of PA (because of IHA) were similar to EH, but differed from those in patients with unilateral form of PA (APA). The prevalence of the MS (62% in IHA, 34% in APA and 56% in EH), the body mass index value (30±4 kg m(-2) in IHA, 27±5 kg m(-2) in APA and 29±5 kg m(-2) in EH) and triglycerides levels (1.9±0.9 mmol l(-1) in IHA,1.4±0.8 mmol l(-1) in APA and 2.01±1.39 mmol l(-1) in EH) were all significantly (P<0.05) higher in IHA compared with APA patients. Metabolic profile of patients with bilateral form of PA (because of IHA) is similar to EH in contrast to unilateral form of PA (APA).

The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism.

Central blood pressure (BP) has been shown to be a better predictor of target organ damage and cardiovascular events than brachial BP. Whether central BP is a better predictor of left ventricular hypertrophy (LVH) determined by electrocardiography (ECG) is not known. Radial applanation tonometry and ECG were performed in 728 subjects from the Czech Post-MONICA Study (a randomly selected 1% population sample). LVH was determined using the Sokolow–Lyon index and Cornell product; central pressure was derived from radial pulse. Of 657 subjects included in the analysis, 17 (9.4%) below 45 years and 43 (9%) over 45 years had LVH. In multiple linear regression analysis, the Sokolow–Lyon index in younger individuals was only associated with male sex and low BMI, with no association with BP found. In older individuals, LVH was associated with higher central and brachial BP. In separate binary logistic regression analyses adjusted for covariates, the odds ratio for central systolic pressure was higher than those for brachial systolic and pulse pressure in LVH prediction. Noninvasively determined central pressure in subjects over 45 years is more strongly related to ECG LVH than brachial pressure. This further supports a closer association of central pressure with target organ damage. Voltage criteria of LVH are not independently associated with central or brachial BP in younger individuals.

D. Wichterle

Papers

The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism.

Relation of central and brachial blood pressure to left ventricular hypertrophy. The Czech Post-MONICA Study.

Relation of Central and Brachial Blood Pressure to Left Ventricular Hypertrophy.

Relation of central and brachial blood pressure to ECG left ventricular hypertrophy. The Czech post-MONICA study