ABC | Volume 114, Nº3, March 2020

Statement Brazilian Position Statement on Resistant Hypertension – 2020 Arq Bras Cardiol. 2020; 114(3):576-596 arterial disease, congestive heart failure (CHF), kidney disease, and all-cause death compared with patients with C-RHTN. 6.4. Phenotype of the Patient with Refractory Hypertension Refractory hypertension appears to be an extreme phenotype of patients with RHTN. Recently, phenotypic characterization has shown that these patients are younger than those with RHTN in general, are more commonly women, have a higher frequency of heart failure, and have particularly higher sympathetic activity than patients with RHTN. 5 These findings are important pillars for the pathophysiology of refractoriness, potentially constituting a therapeutic target for procedures such as renal denervation. Studies in this area are currently under development. 7. Secondary Causes of Resistant Hypertension Coordinator: Fernanda Marciano Consolim-Colombo Authors: Márcio Gonçalves de Sousa, Flávio Antonio de Oliveira Borelli, Cibele Isaac Saad Rodrigues, and Fernanda Marciano Consolim-Colombo. 7.1. Introduction Secondary hypertension (SecHTN) is defined as increased BP due to an identifiable cause. 33,105 Patients with RHTN should be investigated for the most prevalent causes of “non-endocrine” and “endocrine” SecHTN after exclusion of use of medications that may interfere with BP values: antiinflammatory drugs, glucocorticoids, nasal decongestants, appetite suppressants, antidepressants, immunosuppressants, erythropoietin, contraceptives, and illicit drugs. 33,105 7.2. Secondary Hypertension due to Non-Endocrine Causes 7.2.1. Obstructive Sleep Apnea Defined as a total or partial cessation of respiratory flow during sleep, this syndrome promotes oxyhemoglobin desaturation and microarousals during sleep. OSA is estimated to have a prevalence of 17% 106 among American adults and 30% among hypertensive individuals andmay affect 60 to 80% of the patients with RHTN. 94 A recent meta-analysis 107 has concluded that the presence of OSA is related to a higher risk of RHTN. 107 Activation of the sympathetic nervous system and humoral abnormalities are responsible for changes in vascular endothelial integrity, and their consequences in patients with OSA include increased BP, development of atherosclerotic disease, and cardiac arrhythmias, among others. 108 Clinical suspicion can be verified with the Berlin questionnaire. 109 The diagnosis is established with polysomnography, which records apnea/hypopnea indices greater than five events/hour. Treatment should include recommendations on sleep hygiene and weight loss, among others. For airway clearance, the use of equipment producing continuous positive airway pressure (CPAP) is the most recommended. However, the impact of this treatment on reducing BP values is still debatable. 110,111 7.2.2. Renal Parenchymal Disease Renal parenchymal disease (RPD) is one of the most prevalent causes of SecHTN. The diagnosis of this condition is relatively simple since the assessment of renal function is part of the routine approach in patients with hypertension. Patients on dialysis and renal transplant recipients have a high prevalence of hypertension, and CV events are responsible for high morbidity and mortality in this population. 112 The progression of renal dysfunction in patients with RPD is directly related to BP values, and target BP levels should be achieved to reduce CV morbidity and mortality. In patients with RPD and renal transplant recipients, ACEIs and angiotensin-II receptor blockers have been shown to offer renal protection additional to that obtained by BP reduction, and are, therefore, the preferred medications. 33,105,113 7.2.3. Renal Artery Stenosis Renovascular disease is a term used to define renal artery involvement by different pathologies, including atherosclerotic disease, fibromuscular dysplasia, and vasculitis, which can lead to arterial obstruction. Usually, no symptoms are associated with mild arterial obstruction. However, with obstructions affecting more than 70% of the artery, severe hypertension and even ischemic nephropathy may occur. Renal artery stenosis (RAS) of atherosclerotic origin is present in 12.5% of the patients with RHTN older than 50 years of age. 114 The diagnosis should always be determined, but the treatment of this condition is still much discussed in the literature. 115,116 Adequate BP control and interruption of progressive renal function deterioration are the primary treatment goals in these patients. To achieve that, two therapeutic possibilities are available for this population: clinical and interventional (surgical or percutaneous, with or without stent implantation). Interventions are recommended for patients with RHTN or accelerated hypertension with progressive loss of renal function, bilateral RAS or stenosis in a “single” kidney, or with severe complications (CHF and recurrent acute pulmonary edema). 33,115,116 Other potential surgical indications include total renal artery obstruction, large arteriovenous fistulas, aortic lesion encompassing the renal arteries, and failure in clinical or endovascular treatment. 117 7.3. Secondary Hypertension due to Endocrine Causes 7.3.1. Primary Hyperaldosteronism Considered in the past to be a rare type of SecHTN (with a prevalence of about 1%), hyperaldosteronism is currently believed to occur in up to 22% of the cases in populations with RHTN. 118,119 The most frequent cause of hyperaldosteronism is adrenal adenoma, while unilateral or bilateral hyperplasia is less frequently detected. Carcinomas (albeit infrequent) and genetic forms of the disease may also be responsible for the occurrence of hyperaldosteronism. Aldosterone, through activation of mineralocorticoid receptors, is related to insulin resistance and endothelial 586