Roberto Fiszman

Efficacy of Spironolactone Therapy in Patients With True Resistant Hypertension

The role of spironolactone in resistant hypertension management is unclear. The aim of this prospective trial was to evaluate the antihypertensive effect of spironolactone in patients with true resistant hypertension diagnosed by ambulatory blood pressure monitoring. A total of 175 patients had clinical and complementary exams obtained at baseline and received spironolactone in doses of 25 to 100 mg/d. A second ambulatory blood pressure monitoring was performed after a median interval of 7 months. Paired Student t test was used to assess differences in blood pressure before and during spironolactone administration, and multivariate analysis adjusted for age, sex, and number of antihypertensive drugs to assess the predictors of blood pressure fall. There were mean reductions of 16 and 9 mm Hg, respectively, in 24-hour systolic and diastolic blood pressures (95% CIs: 13 to 18 and 7 to 10 mm Hg; P<0.001). Office systolic blood pressure and diastolic blood pressure also decreased (14 and 7 mm Hg). Controlled ambulatory blood pressure was reached in 48% of patients. Factors associated with better response were higher waist circumference, lower aortic pulse wave velocity, and lower serum potassium. No association with plasma aldosterone or aldosterone:renin ratio was found. Adverse effects were observed in 13 patients (7.4%). A third ambulatory blood pressure monitoring performed in 78 patients after a median of 15 months confirmed the persistence of the spironolactone effect. In conclusion, spironolactone administration to true resistant hypertensive patients is safe and effective in decreasing blood pressure, especially in those with abdominal obesity and lower arterial stiffness. Its addition to an antihypertensive regimen as the fourth or fifth drug is recommended.

Relation of Left Ventricular Hypertrophy With Systemic Inflammation and Endothelial Damage in Resistant Hypertension

The relation between left ventricular hypertrophy (LVH) and unfavorable cardiovascular prognosis may involve systemic inflammation and endothelial dysfunction/damage. The aim of this study was to investigate in a cross-sectional design the relationships of LVH with C-reactive protein (CRP) levels (a marker of systemic low-grade inflammation) and with microalbuminuria (a marker of glomerular endothelial damage) in 705 patients with resistant hypertension. At baseline, all were submitted to a laboratory evaluation including 24-hour urinary albumin excretion, 2D echocardiogram, and 24-hour ambulatory blood pressure monitoring. A total of 463 patients also had high-sensitivity CRP levels determined. LVH was defined as an indexed left ventricular mass >110 g/m2 in women and >125 g/m2 in men. Microalbuminuria was evaluated in 3 categories: low normal (<15 mg/24 hours), high normal (between 15 and 29 mg/24 hours), and abnormal (between 30 and 299 mg/24 hours). CRP was dichotomized at the median value (3.7 mg/L). Associations with LVH were examined after adjustment for all of the potential confounders by multivariate logistic regression. A total of 534 patients (75.7%) had LVH. After full adjustment, both abnormal microalbuminuria (odds ratio: 1.97; 95% CI: 1.04 to 3.73) and high CRP (OR: 1.76; 95% CI: 1.06 to 2.93) were independently associated with LVH occurrence. The high-normal albuminuria was associated with a borderline significant 46% increased chance of having LVH. Furthermore, the association between high CRP and LVH was observed exclusively in the subgroup with normal albuminuria. In conclusion, both systemic inflammation and endothelial damage were associated with LVH occurrence. These relationships offer insight into the pathophysiological mechanisms linking LVH to atherosclerosis and to increased cardiovascular morbidity and mortality.

A blunted decrease in nocturnal blood pressure is independently associated with increased aortic stiffness in patients with resistant hypertension

Increased arterial stiffness may be causally related to resistant hypertension. Our objective was to investigate the variables, particularly those derived from ambulatory blood pressure (BP) monitoring (ABPM), associated with increased aortic stiffness in resistant hypertensives. In a cross-sectional study, 600 resistant hypertensive patients without peripheral arterial disease were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (PWV), and was considered increased if >12 m s−1. Statistical analyses included multiple linear and logistic regressions to assess the independent correlates of increased aortic stiffness. One hundred and sixty-eight patients (28%) had aortic PWV >12 m s−1. Patients with increased PWV were older and had a higher prevalence of cardiovascular risk factors than did those patients with low PWV. On ABPM, patients with elevated PWV had higher daytime and night time systolic BP (SBP) and pulse pressures (PP), less nocturnal decrease in SBP and a higher prevalence of non-dipping pattern. On multiple linear regression, the independently associated variables with aortic PWV were age (P<0.001), 24-h PP (P<0.001), high-density lipoprotein (HDL)-cholesterol (P<0.001), microalbuminuria (P<0.001), fasting glycemia (P=0.001) and a decrease in nocturnal SBP (P=0.002). Multivariate logistic regression confirmed these results, with the non-dipping patients having a 72% higher likelihood of presenting with increased aortic stiffness (95% confidence interval: 1.12–2.65, P=0.013). This association was observed in both the reduced and reverted dipping patterns, but not in the extreme dipping pattern. In conclusion, a blunted nocturnal decrease in BP is independently associated with increased aortic stiffness in resistant hypertensive patients. Other independent correlates are older age, diabetes, microalbuminuria, low HDL-cholesterol and a widened 24-h PP.

Financing reform and productivity change in Brazilian teaching hospitals: Malmquist approach

This study evaluates the performance and productivity changes for the Brazilian Federal University Hospitals, considering the years of 2003 and 2006, that is, before and after a 2004 financing reform. The analysis is based on the Malmquist index approach. Results indicate that the financing reform provided improvement in the technical efficiency, although the technological frontier has not presented a positive shift. This suggests that increased budgets were a good stimulus for efficiency but the intended enhancement of the technology through the financing reform has not yet taken place.

Appropriate Time Interval to Repeat Ambulatory Blood Pressure Monitoring in Patients With White-Coat Resistant Hypertension

Resistant hypertension is defined as uncontrolled office blood pressure, despite the use of ≥3 antihypertensive drugs. Ambulatory blood pressure monitoring (ABPM) is mandatory to diagnose 2 different groups, those with true and white-coat resistant hypertension. Patients are found to change categories between controlled/uncontrolled ambulatory pressures without changing their office blood pressures. In this way, ABPM should be periodically repeated. The aim of this study was to evaluate the most appropriate time interval to repeat ABPM to assure sustained blood pressure control in patients with white-coat resistant hypertension. This prospective study enrolled 198 patients (69% women; mean age: 68.9±9.9 years) diagnosed as white-coat resistant hypertension on ABPM. Patients were submitted to a second confirmatory examination 3 months later and repeated twice at 6-month intervals. Statistical analyses included Bland-Altman repeatability coefficients and multivariate logistic regression. Mean office blood pressure was 163±20/84±17 mm Hg, and mean 24-hour blood pressure was 118±8/66±7 mm Hg. White-coat resistant hypertension diagnosis presented a moderate reproducibility and was confirmed in 144 patients after 3 months. In the third and fourth ABPMs, 74% and 79% of patients sustained the diagnosis. In multivariate regression, a daytime systolic blood pressure ⩽115 mm Hg in the confirmatory ABPM triplicated the chance of white-coat resistant hypertension status persistence after 1 year. In conclusion, a confirmatory ABPM is necessary after 3 months of the first white-coat–resistant hypertension diagnosis, and the procedure should be repeated at 6-month intervals, except in patients with daytime systolic blood pressure ⩽115 mm Hg, in whom it may be repeated annually.

Ambulatory Arterial Stiffness Index or Pulse Pressure: Which Correlates Better with Arterial Stiffness in Resistant Hypertension?

The ambulatory arterial stiffness index (AASI) is a recently proposed index derived from 24-h ambulatory blood pressure monitoring (ABPM) for the evaluation of arterial stiffness. In this cross-sectional study we investigated whether AASI reflects arterial stiffness in patients with resistant hypertension by comparing AASI and ambulatory pulse pressure (PP) with aortic pulse wave velocity (PWV), a measure of arterial stiffness, in 391 resistant hypertensives. Clinical, laboratory and echocardiographic variables, 24-h ABPM and aortic PWV (measured using the Complior device) were obtained. AASI was calculated as 1 − the regression slope of 24-h diastolic on systolic blood pressure (BP). Statistical analysis involved single and multiple linear regressions to assess the correlations between the two ABPM variables and PWV, both unadjusted and adjusted for potential confounders (age, gender, body height, presence of diabetes, 24-h mean arterial pressure [MAP], heart rate, and nocturnal BP reduction). Ambulatory PP and aortic PWV were independently associated with age, gender, presence of diabetes, and 24-h MAP, whereas AASI was associated with age, diabetes, and nocturnal diastolic BP reduction. PP showed stronger unadjusted (r=0.39, p<0.001) and adjusted (r=0.22, p<0.001) correlations with aortic PWV than AASI (r=0.12, p=0.032 and r=−0.04, p=0.47, respectively). In the analysis of subgroups stratified by gender, age, presence of atherosclerotic diseases and diabetes, dipping pattern, and ambulatory BP control, the superiority of PP over AASI was apparent in all subgroups. In conclusion, 24-h ambulatory PP was better correlated to arterial stiffness, as evaluated by aortic PWV, than the novel AASI, in patients with resistant hypertension.

O uso da Análise Envoltória de Dados (DEA) para avaliação de hospitais universitários brasileiros

In order to demonstrate how DEA modeling can be helpful for hospital performance assessments conducted in compliance with Brazils Teaching Hospital Policy, a case study is presented of 31 general hospitals linked to Federal Universities. It considers data on assistance, teaching and research and the use of the IDEAL (Interactive Data Envelopment Analysis Laboratory) software as a tool for assessing their efficiency. Developed in Brazil, this unique software provides a three-dimensional view of the productivity frontier, for easier exploratory analyses and selection of pertinent variables, with a better understanding of the outputs of the model (multiplier and envelope) for specialists and decision-makers. As an example, a University Hospital benchmark is presented through outputs that take structural and regional input differences into consideration. This modeling also indicates the changes required in the inefficient units (alterations to input and/or /output vectors), setting forth recommendations on public financing based on quality/efficiency.

Prognostic significance of a reduced glomerular filtration rate and interaction with microalbuminuria in resistant hypertension: a cohort study.

Objective The prognostic importance of a reduced glomerular filtration rate (GFR) is unsettled in resistant hypertension. The aim was to evaluate GFR and its interaction with microalbuminuria as prognostic predictors in resistant hypertensive patients. Methods In a prospective study, 531 resistant hypertensive patients had albuminuria measured and GFR estimated by Cockroft–Gault (eGFRCG) and Modification of Diet in Renal Disease (MDRD; eGFRMDRD) equations. Primary endpoints were a composite of fatal and nonfatal cardiovascular events, all-cause and cardiovascular mortality. Multiple Cox regression assessed the associations between reduced GFR and endpoints, and interaction with microalbuminuria. Results After a median follow-up of 4.9 years, 72 patients died, 42 from cardiovascular causes; and 96 cardiovascular events occurred. Decreasing grades of eGFRMDRD were predictors of the composite endpoint with hazard ratios of 2.1 [95% confidence interval (CI) 1.1–3.8], 2.2 (1.2–3.9) and 3.5 (1.4–8.7) for the subgroups with eGFR between 60–89, 30–59 and less than 30 mg/min per 1.73 m2, respectively. A decreased eGFRCG was predictive of the composite endpoint only in the lowest GFR subgroup (hazard ratio 2.7, 95% CI 1.0–7.1). The lowest eGFR subgroups were also associated with all-cause mortality, regardless of the estimated equation used. The presence of both reduced eGFR and microalbuminuria significantly increased cardiovascular risk in relation to one or another isolated, with hazard ratios of 3.0 (1.7–5.3), 2.9 (1.5–5.5) and 4.6 (2.2–10.0), respectively for the composite endpoint, all-cause and cardiovascular mortality. Conclusion A reduced GFR, mainly estimated by the MDRD equation, is an independent predictor of increased cardiovascular morbidity and mortality in resistant hypertension. The combination of a reduced GFR and increased albuminuria identifies patients with a very high cardiovascular risk.

Evaluating the performance of Brazilian university hospitals

In order to demonstrate how DEA modeling can be helpful to aid decision making relative to the Brazilian Teaching Hospital Policy by means of hospital performance assessment, we develop a case study with 30 general hospitals linked to Brazilian Federal Universities. We consider data on medical care (Medical Model—MM), teaching and research (Teaching-Research Model—TRM) and use the software IDEAL (Interactive Data Envelopment Analysis Laboratory) as a tool for the units’ efficiency evaluation. IDEAL, developed in Brazil, is unique in providing a 3-D frontiers visualization, assisting in exploratory analysis and allowing a better understanding of the DEA modeling (envelopment and multiplier). Both models are input-oriented and each hospital is categorized according to its relative efficiency in the MM and TRM. In this phase, it is very important to discuss with the decision-makers the results and patterns of the DEA models. Finally, the modelling indicates the necessary changes for the inefficient units and generates recommendations for teaching ratios and public financing.

Prognostic importance of baseline and serial changes in microalbuminuria in patients with resistant hypertension

OBJECTIVE The prognostic value of microalbuminuria is unsettled in resistant hypertension. The objective was to evaluate the importance of baseline and serial changes in albuminuria as predictors of cardiovascular morbidity and mortality in patients with resistant hypertension. METHODS 531 resistant hypertensives had urinary albumin excretion rate (UAER) measured prospectively at baseline and at the 2nd year of follow-up. Primary endpoints were a composite of fatal and non-fatal cardiovascular events, all-cause and cardiovascular mortalities. Total strokes and coronary heart disease (CHD) events were secondary endpoints. Multiple Cox regression assessed the associations between UAER and endpoints. RESULTS After a median follow-up of 4.9 years, 72 patients died, 42 from cardiovascular causes; 96 cardiovascular events occurred, 42 strokes and 47 CHD events. After adjustment for several cardiovascular risk factors, baseline UAER, either analyzed as a continuous variable or dichotomized at different cut-off values, was an independent predictor of the composite endpoint, all-cause and cardiovascular mortality, strokes and CHD events. Each 10-fold increase in UAER implied a significant 1.6, 1.5, 2.0, 1.5 and 1.6-fold higher risk, respectively, for each of the above endpoints. Serial changes in microalbuminuria status during follow-up tended to parallel changes in cardiovascular risk, regression of microalbuminuria was associated with a 27% lower risk and development with a 65% higher risk of having a cardiovascular event. CONCLUSIONS Baseline albuminuria strongly predicts cardiovascular morbidity and mortality in resistant hypertensive patients and serial changes in microalbuminuria may translate into changes in risk. Microalbuminuria reduction may be a goal of anti-hypertensive treatment.