Objectives: To assess the prevalence of primary aldosteronism and its association with cardiometabolic complications in patients with resistant and refractory hypertension. Methods: One hundred and ten consecutive patients with true resistant hypertension [insufficient blood pressure control despite appropriate lifestyle measures and treatment with at least three classes of antihypertensive medication, including a diuretic] and without previous cardiovascular events were screened for secondary hypertension. Refractory hypertension was diagnosed in case of uncontrolled blood pressure despite the use of at least five antihypertensive drugs. Results: Primary aldosteronism was diagnosed in 32 cases (29.1%). The multivariate analysis showed that primary aldosteronism is a strong factor positively associated with left ventricular hypertrophy [odds ratio (OR) = 12.98, 95% confidence interval (CI) 3.82–60.88; P < 0.001], microalbuminuria (OR = 3.67, 95% CI 1.44–9.78; P = 0.007), carotid intima–media thickness at least 0.9 mm (OR = 2.69, 95% CI 1.02–7.82; P = 0.037), aortic ectasia (OR = 4.08, 95% CI 1,18–15.04; P = 0.027) and atrial fibrillation (OR 8.80, 95% CI 1.53–73.98; P = 0.022). Moreover, primary aldosteronism was independently associated with the presence of at least one (OR = 8.60, 95% CI 1.73–69.88; P = 0.018) and at least two types of organ damage (OR = 3.08, 95% CI 1.19–8.24; P = 0.022). Thirteen patients (11.8%) were affected by refractory hypertension. This group was characterized by significantly higher values of carotid intima–media thickness, higher rate of aldosterone-producing adenoma and atrial fibrillation, compared with the other individuals with resistant hypertension. Conclusion: The current study indicates that primary aldosteronism is a frequent cause of secondary hypertension and cardiovascular complications among patients with resistant and refractory hypertension, suggesting a crucial role of aldosterone in the pathogenesis of severe hypertensive phenotypes and cardiovascular disease.

Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of “non-classical” effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.

Objective: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. Design: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. Results: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. Conclusions: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.