Contralateral suppression in adrenal venous sampling predicts clinical and biochemical outcome in primary aldosteronism.

CONTEXT: The role for hormone parameters at adrenal venous sampling (AVS) in predicting clinical and biochemical outcome remains controversial. OBJECTIVE: To investigate the impact of hormone parameters at AVS under cosyntropin stimulation on lateralization and on complete biochemical and clinical outcome. METHODS: We retrospectively evaluated 150 sequential AVS under cosyntropin infusion. Bilateral successful cannulation rate was 83.3% (n = 140), 47.9% bilateral and 52.1% unilateral. The lateralization index (LI), aldosterone/cortisol ratio (A/C) in the dominant adrenal vein (AV), relative aldosterone secretion index (RASI = A/C in AV divided by A/C in inferior vena cava) were assessed. The contralateral suppression (CS) percentage was defined by (1 - nondominant RASI) *100. RESULTS: A nondominant RASI <0.5 (CS >50%) had 86.84% sensitivity and 92.96% specificity to predict contralateral lateralization. An A/C ratio in dominant AV >5.9 (74.67% sensitivity and 80% specificity) and dominant RASI >4.7 (35.21% sensitivity and 88.06% specificity) had a worst performance to predict ipsilateral lateralization. Complete biochemical and clinical cure were significantly more frequent in the patients with CS >50% [98.41% vs. 42.86% (p < 0.001) and 41.94% vs. 0% (p < 0.001)]. CS correlated with high aldosterone at diagnosis (p < 0.001) and low postoperative aldosterone levels at 1 month (p = 0.019). Postoperative biochemical hypoaldosteronism was more frequent in patients with CS >50% (70% vs. 16.67%, p = 0.014). In multivariable analysis, a CS >50% was associated with complete biochemical cure (OR 125, 95%CI 11.904-5,000; p = 0.001) and hypertension remission (OR 12.19, 95%CI 2.074-250; p = 0.023). CONCLUSION: A CS >50% was an independent predictor of complete clinical and biochemical cure. Moreover, it can predict unilateral PA and postoperative biochemical hypoaldosteronism. Our findings underscore the usefulness of CS for clinical decision-making.

Randomized Trial of Effect of Bariatric Surgery on Blood Pressure After 5 Years.

BACKGROUND: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. OBJECTIVES: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. METHODS: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. RESULTS: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m2). At 5 years, body mass index was 36.40 kg/m2 (95% CI: 35.28-37.52 kg/m2) for MT and 28.01 kg/m2 (95% CI: 26.95-29.08 kg/m2) for RYGB (P < 0.001). Compared with MT, RYGB promoted a significantly higher rate of number of medications reduction (80.7% vs 13.7%; relative risk: 5.91; 95% CI: 2.58-13.52; P < 0.001) and the mean number of antihypertensive medications was 2.97 (95% CI: 2.33-3.60) for MT and 0.80 (95% CI: 0.51-1.09) for RYGB (P < 0.001). The rates of hypertension remission were 2.4% vs 46.9% (relative risk: 19.66; 95% CI: 2.74-141.09; P < 0.001). Sensitivity analysis considering only completed cases revealed consistent results. Interestingly, the rate of apparent resistant hypertension was lower after RYGB (0% vs 15.2%). CONCLUSIONS: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).

Randomized trial of effect of bariatric surgery on blood pressure after 5 years

BACKGROUND: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. OBJECTIVES: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. METHODS: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. RESULTS: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m2). At 5 years, body mass index was 36.40 kg/m2 (95% CI: 35.28-37.52 kg/m2) for MT and 28.01 kg/m2 (95% CI: 26.95-29.08 kg/m2) for RYGB (P < 0.001). Compared with MT, RYGB promoted a significantly higher rate of number of medications reduction (80.7% vs 13.7%; relative risk: 5.91; 95% CI: 2.58-13.52; P < 0.001) and the mean number of antihypertensive medications was 2.97 (95% CI: 2.33-3.60) for MT and 0.80 (95% CI: 0.51-1.09) for RYGB (P < 0.001). The rates of hypertension remission were 2.4% vs 46.9% (relative risk: 19.66; 95% CI: 2.74-141.09; P < 0.001). Sensitivity analysis considering only completed cases revealed consistent results. Interestingly, the rate of apparent resistant hypertension was lower after RYGB (0% vs 15.2%). CONCLUSIONS: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).

Renal Function Evolution and Hypoaldosteronism Risk After Unilateral Adrenalectomy for Primary Aldosteronism.

Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism (PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.

Incident Coronary Calcium Score in Patients With OSA With and Without Excessive Sleepiness: Brazilian Longitudinal Study of Adult Health.

BACKGROUND: Uncertainty exists about the impact of OSA and its phenotypes on cardiovascular disease. RESEARCH QUESTION: Are OSA and clinical features such as daytime sleepiness associated with incident subclinical coronary atherosclerosis? STUDY DESIGN AND METHODS: In this prospective community-based cohort study, we administered a sleepiness questionnaire, actigraphy, and home sleep studies at baseline. Coronary artery calcium (CAC; 64-slice multidetector CT scan imaging) was measured at two different time points throughout the study (baseline, between 2010 and 2014, and follow-up, between 2016 and 2018). Incidence of subclinical atherosclerosis was defined as baseline CAC of 0 followed by CAC of > 0 at a 5-year follow-up visit. The association of incident CAC outcome was assessed using logistic regression. Stratified analyses based on excessive daytime sleepiness (EDS) were performed. RESULTS: We analyzed 1,956 participants with available CAC scores at baseline (mean age, 49 ± 8 years; 57.9% female; 32.4% with OSA). In covariate-adjusted analyses (n = 1,247; mean follow-up, 5.1 ± 0.9 years), we found a significant association between OSA and incidence of subclinical atherosclerosis (OR, 1.26; 95% CI, 1.06-1.48), with stronger effects among those reporting EDS (OR, 1.66; 95% CI, 1.30-2.12; P = .028 for interaction). Interestingly, EDS per se was not associated with any CAC outcome. An exploratory analysis of the square root of CAC progression (baseline CAC > 0 followed by a numerical increase in scores at follow-up; n = 319) showed a positive association for both OSA (ß = 1.084; 95% CI, 0.032-2.136; P = .043) and OSA with EDS (ß = 1.651; 95% CI, 0.208-3.094; P = .025). INTERPRETATION: OSA, particularly with EDS, predicts the incidence and progression of CAC. These results support biological plausibility for the increased cardiovascular risk observed among patients with OSA with excessive sleepiness.

Efficacy of Oral Furosemide Test for Primary Aldosteronism Diagnosis.

Context: Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved. Objective: To evaluate the efficacy of oral furosemide as a new confirmatory test for PA diagnosis. Methods: We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA. Results: The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test. Conclusion: The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation.

Gender Modulated the Association of Sleep Apnea and Sleep Duration with Arterial Stiffness: The ELSA-Brasil Study.

Increased arterial stiffness is independently associated with cardiovascular risk. Obstructive sleep apnea (OSA) and sleep duration (SDUR) may contribute to increased arterial stiffness, but it is unclear whether this association is modulated by gender. We aimed to evaluate the potential impact of gender in modulating the association of OSA and SDUR with arterial stiffness. Participants from the ELSA-Brasil study performed sleep assessments with portable polygraph to define OSA severity and SDUR by 1-week wrist actigraphy. Pulse wave velocity (PWV) was measured using a standard technique without access to the sleep data. We studied 1863 participants (42.2% male, age: 49±8 years, respiratory disturbance index (RDI): 9.9 (4.5-19.4) events/h, SDUR: 6.5 (5.9-7.1) hours, mean PWV: 7.3 ± 1.2 m/s). We found that men had higher PWV, higher frequency of diabetes, and higher blood pressure when compared to women. The regression analysis showed an independent association between increased RDI and PWV in men (ß: 0.007; 95% CI: 0.001-0.012), but not in women. In contrast, an independent association between SDUR and increased arterial stiffness was observed only in women (ß: 0.068; 95% CI: 0.002-0.134). In conclusion, the association of sleep disorders with arterial stiffness showed a distinct gender pattern depending on the sleep variable studied.

Peripheral Artery Disease Diagnosed by Pulse Palpation as a Predictor of Coronary Artery Disease in Patients with Chronic Kidney Disease.

There is a need of simple, inexpensive, and reliable noninvasive testing to predict coronary artery disease (CAD) in patients with chronic kidney disease (CKD), where the prevalence of cardiovascular (CV) events and death is elevated. We analyzed the association between peripheral artery disease (PAD) and CAD in 201 patients with stage 5 CKD on dialysis using a prospective observational cohort. Diagnosis of PAD by both palpation and USD were significantly correlated. In patients with PAD diagnosed by palpation, CAD was observed in 80%, while in those diagnosed by USD, CAD was present in 79.1%. The absence of a pulse by palpation predicted CAD with a sensitivity of 55% and a specificity of 76%; USD showed a sensitivity of 62% and specificity of 60% to predict CAD. The risk of combined serious CV events and death was significantly higher in subjects with PAD diagnosed by palpation, but not by USD. PAD assessed by palpation also correlated with the occurrence of multivessel CAD and with the probability of coronary intervention. Both methods are moderately useful for predicting CAD, but PAD diagnosis by palpation was a better predictor of combined CV events and death and was also associated with CAD severity and likelihood of intervention.

Shorter History of Hypertension as a Predictor of Hypertension Remission after 3-years of Bariatric Surgery: Data from the GATEWAY Trial.

BACKGROUND: Previous evidence explored predictors of hypertension (HTN) remission after bariatric but data are limited to observational studies and lack of ambulatory blood pressure monitoring (ABPM). This study was aimed to evaluate the rate of HTN remission after bariatric surgery using ABPM and to define predictors of mid-term HTN remission. METHODS: We included patients enrolled in the surgical arm of the GATEWAY randomized trial. HTN remission was defined as controlled blood pressure (< 130 × 80 mmHg) evaluated by 24-h ABPM while no need of anti-hypertensive medications after 36 months. A multivariable logistic regression model was used to assess the predictors of HTN remission after 36 months. RESULTS: 46 patients submitted Roux-en-Y gastric bypass (RYGB). HTN remission occurred in 39% (n = 14 out of 36 patients with complete data at 36 months). Patients with HTN remission had shorter HTN history than no remission group (5.9 ± 5.5 vs. 12.5 ± 8.1 years; p = 0.01). The baseline insulin levels were lower in patients who presented HTN remission, although not statistically significant (OR: 0.90; CI 95%: 0.80-0.99; p = 0.07). In the multivariate analysis, the HTN history (years) was the only independent predictor of HTN remission (OR: 0.85; 95% CI: 0.70-0.97; p = 0.04). Therefore, for each additional year of HTN history, the chance of HTN remission decreases by approximately 15% after RYGB. CONCLUSION: After 3 years of RYGB, HTN remission defined by ABPM was common and independently associated with a shorter HTN history. These data underscore the need of early effective approach of obesity aiming greater impact in its comorbidities.

Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors.

Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age- and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 ± 2 yr, BMI: 30 ± 1 kg/m2) and 15 well-matched control subjects (aged: 46 ± 3 yr, BMI: 29 ± 1 kg/m2) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.

Obstructive sleep apnea and hypertension-mediated organ damage in nonresistant and resistant hypertension.

The potential role of obstructive sleep apnea (OSA) in hypertension-mediated organ damage (HMOD) may be influenced by the presence of resistant hypertension (RH). Herein, we enrolled patients with hypertension from a tertiary center for clinical evaluation and performed a sleep study to identify OSA (apnea-hypopnea index ≥15 events/h) and a blinded analysis of four standard HMOD parameters (left ventricular hypertrophy [LVH], increased arterial stiffness [≥10 m/s], presence of retinopathy, and nephropathy). RH was diagnosed based on uncontrolled blood pressure (BP) (≥140/90 mmHg) despite concurrent use of at least three antihypertensive drug classes or controlled BP with concurrent use of ≥4 antihypertensive drug classes at optimal doses. To avoid the white-coat effect, ambulatory BP monitoring was performed to confirm RH diagnosis. One-hundred patients were included in the analysis (mean age: 54 ± 8 years, 65% females, body mass index: 30.4 ± 4.5 kg/m²). OSA was detected in 52% of patients. Among patients with non-RH (n = 53), the presence of OSA (52.8%) was not associated with an increased frequency of HMOD. Conversely, among patients with RH, OSA (51.1%) was associated with a higher incidence of LVH (RH-OSA,61%; RH + OSA,87%; p = 0.049). Logistic regression analysis using the total sample revealed that RH (OR:7.89; 95% CI:2.18-28.52; p = 0.002), systolic BP (OR:1.04; 95% CI:1.00-1.07; p = 0.042) and OSA (OR:4.31; 95% CI:1.14-16.34; p = 0.032) were independently associated with LVH. No significant association was observed between OSA and arterial stiffness, retinopathy, or nephropathy. In conclusion, OSA is independently associated with LVH in RH, suggesting a potential role of OSA in RH prognosis.

Interdialytic Blood Pressure and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

INTRODUCTION: Normal (120-140 mm Hg) systolic peridialysis blood pressure (BP) is associated with higher mortality in hemodialysis (HD) patients. AIM: We explored the relationship between hypertension and BP on outcomes using data collected at the interdialytic period. METHODS: This was a single-center observational cohort study with 2672 HD patients. BP was determined at inception, in mid-week, between 2 consecutive dialysis sessions. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Endpoints were major CV events and all-cause mortality. RESULTS: During a median follow-up of 31 months, 761 patients (28%) experienced CV events and 1181 (44%) died. Hypertensive patients had lower survival free of CV than normotensive patients (P = 0.031). No difference occurred in the incidence of death between groups. Compared with the reference category of SBP ≥ 171 mmHg, the incidence of cardiovascular events was reduced in patients with SBP 101-110 (HR 0.647, 95% CI 0.455 to 0.920), 111-120 (HR 0.663, 95%CI 0.492 to 0.894), 121-130 (HR 0.747, 95%CI 0.569 to 0.981), and 131-140 (HR 0.757, 95%CI 0.596 to 0.962). On multivariate analysis, systolic and diastolic BP were not independent predictors of CV events or death. Normal interdialytic BP was not associated with mortality or CV events, and hypertension predicted an increased probability of CV complications. CONCLUSIONS: Interdialytic BP may be preferred to guide treatment decisions, and HD patients should be treated according to guidelines for the general population until specific BP targets for this population are identified.

Effect of continuous positive airway pressure on atrial remodeling and diastolic dysfunction of patients with obstructive sleep apnea and metabolic syndrome: a randomized study.

OBJECTIVE: The aim of this study was to evaluate the role of obstructive sleep apnea (OSA) treatment on heart remodeling and diastolic dysfunction in patients with metabolic syndrome (MS). METHODS: This study is a prespecified analysis of a randomized placebo-controlled trial that enrolled patients with a recent diagnosis of MS and moderate-to-severe OSA to undergo continuous positive airway pressure (CPAP) or nasal dilators (placebo) for 6 months. Patients were invited to perform a transthoracic echocardiogram by a single investigator blinded to treatment assignment. RESULTS: A total of 99 (79% men; mean [SD], age: 48 [9] years; BMI: 33 [4] kg/m2 ) completed the study. At follow-up, in the placebo group, patients had a significant increase in atrial diameter: from 39.5 (37.0-43.0) mm to 40.5 (39.0-44.8) mm (p = 0.003). CPAP prevented atrial enlargement: from 40.0 (38.0-44.0) to 40.0 (39.0-45.0) mm (p = 0.194). In patients with diastolic dysfunction at baseline, almost half had diastolic dysfunction reversibility with CPAP (in comparison with only two patients in the placebo group, p = 0.039). In the regression analysis, the chance of diastolic dysfunction reversibility by CPAP was 6.8-fold (95% CI: 1.48-50.26, p = 0.025) compared with placebo. CONCLUSIONS: In patients with MS and OSA, 6 months of CPAP therapy prevented atrial remodeling and increased the chance of diastolic dysfunction reversibility.

Sleep irregularity and the association with hypertension and blood pressure levels: the ELSA-Brasil study.

OBJECTIVE: To evaluate the associations of sleep irregularity with hypertension (HTN) and blood pressure (BP) levels. METHODS: Adult participants from the ELSA-Brasil performed a clinical evaluation including objective sleep duration (actigraphy), insomnia, and a sleep study for defining obstructive sleep apnoea (OSA). To quantify sleep irregularity, we used two parameters obtained through actigraphy: 7-day standard deviation (SD) of sleep duration and 7-day SD of sleep-onset timing. A multivariate analysis was used to determine the independent associations of sleep irregularity with HTN and SBP/DBP values. RESULTS: We studied 1720 participants (age 49 ±â€Š8 years; 43.4% men) and 27% fulfilled the HTN diagnosis. After adjustments for age, gender, race, BMI, excessive alcohol consumption, physical activity intensity, urinary sodium excretion, insomnia, objective sleep duration and OSA (apnoea-hypopnoea index ≥15 events/h), we found that the continuous analysis of 7-day SD of sleep duration was modestly associated with prevalent HTN. However, 7-day SD of sleep duration more than 90 min was independently associated with SBP [ ß : 1.55; 95% confidence interval (CI) 0.23-2.88] and DBP ( ß : 1.07; 95% CI 0.12-2.01). Stratification analysis excluding participants with OSA revealed that a 7-day SD of sleep duration greater than 90 min was associated with a 48% higher chance of having HTN (OR: 1.48; 95% CI: 1.05-2.07). No significant associations were observed for the SD of sleep-onset timing. CONCLUSION: Objective measurement of sleep irregularity, evaluated by SD of sleep duration for 1 week, was associated with HTN and higher BP levels, especially in participants without OSA.

Intra-individual Variability of Serum Aldosterone and Implications for Primary Aldosteronism Screening.

CONTEXT: Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using immunoassay. OBJECTIVE: To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening. METHODS: A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings. RESULTS: The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements. CONCLUSION: Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.

Directly observed therapy for resistant/refractory hypertension diagnosis and blood pressure control.

OBJECTIVE: To test the impact of directly observed therapy (DOT) at hospital for checking not only adherence/diagnosis in patients with resistant (RHTN) and refractory (RefHTN) hypertension but also blood pressure (BP) control after hospital discharge. METHODS: During 2 years, Brazilian patients with clinical suspicion of RHTN/RefHTN after several attempts (≥3) to control BP in the outpatient setting were invited to perform DOT (including low-sodium diet and supervised medications intake) at the hospital. RHTN and RefHTN were categorised using standard definitions. After hospital discharge, we evaluated the BP values and the number of antihypertensive drugs prescribed by physicians who were not involved with the investigation. RESULTS: We studied 83 patients clinically suspected for RHTN (31%) and RefHTN (69%) (mean age: 53 years; 76% female; systolic BP 177±28 mm Hg and diastolic BP 106±21 mm Hg; number of antihypertensive drugs: 5.3±1.3). DOT confirmed RHTN in 77%, whereas RefHTN was confirmed in only 32.5%. The number of antihypertensive drugs reduced to 4.5±1.3 and systolic/diastolic BP at hospital discharge reduced to 131±17 mm Hg/80±12 mm Hg. After hospital discharge, systolic BP remained significantly lower than the last outpatient visit prehospital admission (delta changes (95% CI): 1 month: -25.7 (-33.8 to -17.6) mm Hg; 7 months: -27.3 (-35.5 to -19.1) mm Hg) despite fewer number of antihypertensive classes (1 month: -1.01 (-1.36 to -0.67); 7 months: -0.77 (-1.11 to -0.42)). Similar reductions were observed for diastolic BP. CONCLUSIONS: DOT at hospital is helpful not only in confirming/excluding RHTN/RefHTN phenotypes, but also in improving BP values and BP control and in reducing the need for antihypertensive drugs after hospital discharge.

Effects of CPAP on Metabolic Syndrome in Patients With OSA: A Randomized Trial.

BACKGROUND: OSA is associated with metabolic syndrome (MS), but it is unclear whether OSA treatment with CPAP can revert MS. RESEARCH QUESTION: Does OSA treatment with CPAP per se have effects on the MS reversibility and the associated metabolic, adiposity and vascular parameters? STUDY DESIGN AND METHODS: The TREATOSA-MS trial is a randomized placebo-controlled trial that enrolled adult patients with a recent diagnosis of MS and moderate or severe OSA (apnea-hypopnea index [AHI], ≥ 15 events/h) to undergo therapeutic CPAP or nasal dilator strips (placebo group) for 6 months. Before and after each intervention, we measured anthropometric variables, BP, glucose, and lipid profile. To control potential-related mechanisms and consequences, we also measured adiposity biomarkers (leptin and adiponectin), body composition, food intake, physical activity, subcutaneous and abdominal fat (visceral and hepatic fat), and endothelial function. RESULTS: One hundred patients (79% men; mean age, 48 ± 9 years; BMI, 33 ± 4 kg/m2; AHI, 58 ± 29 events/h) completed the study (n = 50 per group). The mean CPAP adherence was 5.5 ± 1.5 h/night. After 6 months, most patients with OSA randomized to CPAP retained the MS diagnosis, but the rate of MS reversibility was higher than observed in the placebo group (18% vs 4%; OR, 5.27; 95% CI, 1.27-35.86; P = .04). In the secondary analysis, CPAP did not promote significant reductions in the individual components of MS, weight, hepatic steatosis, lipid profile, adiponectin, and leptin, but did promote a very modest reduction in visceral fat and improved endothelial function (all analyses were adjusted for baseline values). INTERPRETATION: Despite the higher rate of MS reversibility after CPAP therapy as compared with placebo, most patients retained this diagnosis. The lack of significant or relevant effects on adiposity biomarkers and depots supports the modest role of OSA in modulating MS. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02295202; URL: www. CLINICALTRIALS: gov.

Invasive coronary artery disease assessment and myocardial infarction in patients on renal replacement therapy.

BACKGROUND: The incidence of myocardial infarction (MI) is elevated in patients receiving renal replacement therapy (RRT). We hypothesized that an invasive strategy of assessment of coronary artery disease (CAD) will identify patients more prone to developing MI. METHODS: This was a single-center observational cohort study that included 1678 patients receiving RRT (hemodialysis and renal transplantation) assessed for CAD prospectively and analyzed retrospectively. Endpoints were the incidence of MI and death. RESULTS: The median follow-up was 43 months, and 180 patients experienced an MI with a mortality rate of 74%. Multivariate analysis showed that diabetes (HR 1.633; 95% CI 1.165-2.289), prior MI (HR 1.724; 95% CI 1.153-2.579), and CAD (HR 2.073; 95% CI 1.400-3.071) were predictors of MI. Altered myocardial scan did not correlate with MI. At the discretion of the attending physicians, 20/180 patients (11%) underwent coronary intervention that was associated with a higher cumulative survival (Log-rank 0.007). CONCLUSION: Patients with CAD suffered an MI more frequently, independently of symptoms and risk factors for MI, including noninvasive testing. Because of the elevated rate of the lethality of MI, invasive coronary studies may be indicated in select patients on RRT. Once an MI occurs, our data suggest that an invasive therapeutic approach is warranted.

Diastolic and systolic left ventricular dysfunction and mortality in chronic kidney disease patients on haemodialysis.

AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.