Armando da Rocha Nogueira

Combined QT Interval and Voltage Criteria Improve Left Ventricular Hypertrophy Detection in Resistant Hypertension

QT interval parameters have been associated with left ventricular hypertrophy (LVH) in hypertensive patients. The aim of this study is to assess this relationship in resistant hypertension and, in particular, to evaluate whether any QT interval parameter could provide additive information for LVH beyond that obtained from the best electrocardiographic voltage criterion. In a cross-sectional study, 471 resistant hypertensives were submitted to standard 12-lead ECGs, 24-hour ambulatory blood pressure monitoring, and 2D echocardiographic examinations. QT interval durations and QRS voltages were measured, and maximum rate–corrected QT interval duration (QTcmax) and dispersion (QTd), and Sokolow’s and Cornell’s voltage product were calculated. Statistical analyses involved bivariate tests and multivariate logistic regression, with LVH as the dependent variable. A total of 383 patients (81%) had echocardiographic LVH. In bivariate comparisons, both QT interval parameters showed a predictive performance for LVH similar to Cornell’s product, the best ECG voltage criterion. In multivariate analysis, QT parameters and Cornell’s product were independently associated with LVH, after adjustment for other LVH determinants. QTc interval >440 ms1/2 and dispersion >60 ms were associated with a 2-fold (95% confidence interval [CI], 1.1 to 3.8) greater chance of having LVH, whereas Cornell’s product >240 mV·ms implied a 2.6-fold (95% CI, 1.2 to 6.1) increased chance of LVH. The combination of prolonged QT interval and increased Cornell’s product was associated with a 5.3- to 9.3-fold higher chance of having LVH. Hence, although in isolation, no QT interval parameter performs better for LVH detection than simpler Cornell’s product, it provides additive information and can be used in combination with voltage criteria to refine LVH risk stratification in resistant hypertension.

Importance of the Electrocardiographic Strain Pattern in Patients With Resistant Hypertension

The electrocardiographic strain pattern is a marker of left ventricular hypertrophy and adverse cardiovascular prognosis. The objective of this study was to assess the factors associated with the presence of ECG strain in patients with resistant hypertension and, specifically, to evaluate the relationships between strain and left ventricular mass (LVM) and structure. In a cross-sectional design, 440 resistant hypertensive subjects were evaluated. Clinical, laboratory, electrocardiographic, 24-hour ambulatory blood pressures, and echocardiographic variables were obtained. Statistical analysis involved bivariate tests, analysis of covariance, and multivariate logistic regression. An ECG strain pattern was present in 101 patients (23%). Patients with strain were more frequently men with lower body mass index, had more target-organ damage, higher 24-hour blood pressure, higher serum creatinine and 24-hour microalbuminuria, and more prolonged QT interval duration than those without strain. After controlling for all covariates, the presence of strain remained associated with increased LVM and wall thicknesses, both in all patients and also in those with echocardiographic left ventricular hypertrophy. Furthermore, the presence of ECG strain was associated with increased LVM (P<0.001), higher 24-hour systolic blood pressure (P<0.001), prolonged maximum QTc-interval duration (P<0.001), lower waist circumference (P=0.009), male gender (P=0.011), physical inactivity (P=0.020), higher serum creatinine (P=0.031) and fasting glycemia (P=0.027), and the presence of coronary heart disease (P=0.001) and peripheral arterial disease (P=0.045). Thus, in resistant hypertension patients, the presence of ECG strain is independently associated with increased left ventricular wall thicknesses and mass and also with other potentially adverse factors. These relationships offer insight into the known association between strain and unfavorable cardiovascular prognosis.

Demographic and clinical characteristics of hypertensive patients in the internal medicine outpatient clinic of a university hospital in Rio de Janeiro

CONTEXT Hypertension is one of the most important cardiovascular risk factors but its control is still a challenge for physicians all around the world. For blood pressure control to be improved, it is important to guarantee the quality of attendance provided for hypertensive patients, especially in teaching hospitals, where future physicians are being trained. OBJECTIVE To characterize the profile of hypertensive patients attending the internal medicine outpatient clinic of a university hospital in Rio de Janeiro,describing their cardiovascular risk and identifying flaws in the treatment provided for severely hypertensive patients, in order to implement an arterial hypertension management program. TYPE OF STUDY A descriptive cross-sectional population-based study. SETTING Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro. METHODS The study was carried out over a period of four months, involving all the hypertensive patients under treatment in the outpatient unit. The attending physician obtained information relating to demographic features, cardiovascular risk factors, target organ damage, blood pressure levels, therapeutic regimens and compliance with treatment. Means and the respective standard deviations and proportions were used to describe the distribution of patient data. RESULTS Of the total number of patients seen, 24.2% (1,699 patients) were hypertensive. Women accounted for 65.0% of the patients. The mean age was 63.9 years. Dyslipidemia (49.2%) and diabetes (29.8%) were the most frequently reported risk factors and heart disease was the most prevalent end-organ damage. Seventy percent of the patients were classified as high cardiovascular risk. In spite of the high intensity treatment provided for the most severe patients (19.4% on a regimen of 3 or more antihypertensive drugs), the rate of blood pressure control was low (27%). CONCLUSIONS The patients with arterial hypertension under treatment at the university hospital had a profile of high cardiovascular risk and poor blood pressure control. Greater effort for improving hypertension control is needed, since this is the only way to reduce the morbidity and mortality rates of cardiovascular diseases.

Socioeconomic aspects of spousal concordance for hypertension, obesity, and smoking in a community of Rio de Janeiro, Brazil

OBJECTIVE The present study aims to evaluate the environmental role in the distribution of hypertension, obesity, and smoking and spousal concordance for the presence/absence of these 3 cardiovascular risk factors. METHODS A cross-sectional study was conducted in a community in Rio de Janeiro, Brazil. The households were randomly selected. Odds ratios were estimated to measure spousal concordance, across socioeconomic levels. RESULTS Overall a significant aggregation of all 3 risk factors was present. The crude odds ratio for hypertension was 1.78 (95%CI=1.02-3.08); for obesity, it was 1.80 (95%CI=1.09-2.96); and for smoking, it was 3.40 (95% CI=2.07-5.61). The spousal concordance for hypertension decreased significantly (p<0.001) from the lower to the higher educational level. In the case of obesity and smoking, the opposite was observed, although p-values for the linear trend were 0.10 and 0.08, respectively. CONCLUSION In lower socioeconomic levels, couples are more concordant for hypertension and discordant for smoking. For hypertension and smoking, education seems to be a discriminant stronger than income, but for obesity the 2 socioeconomic indicators seem to represent different aspects of the environmental determinants of risk factor distribution.

Resistant Hypertension Optimal Treatment Trial: A Randomized Controlled Trial

The prevalence of resistant hypertension (ReHy) is not well established. Furthermore, diuretics, angiotensin‐converting enzyme inhibitors or angiotensin‐receptor blockers, and calcium channel blockers are largely used as the first 3‐drug combinations for treating ReHy. However, the fourth drug to be added to the triple regimen is still controversial and guided by empirical choices. We sought (1) to determine the prevalence of ReHy in patients with stage II hypertension; (2) to compare the effects of spironolactone vs clonidine, when added to the triple regimen; and (3) to evaluate the role of measuring sympathetic and renin‐angiotensin‐aldosterone activities in predicting blood pressure response to spironolactone or clonidine. The Resistant Hypertension Optimal Treatment (ReHOT) study (ClinicalTrials.gov NCT01643434) is a prospective, multicenter, randomized trial comprising 26 sites in Brazil. In step 1, 2000 patients will be treated according to hypertension guidelines for 12 weeks, to detect the prevalence of ReHy. Medical therapy adherence will be checked by pill count monitoring. In step 2, patients with confirmed ReHy will be randomized to an open label 3‐month treatment with spironolactone (titrating dose, 12.5–50 mg once daily) or clonidine (titrating dose, 0.1–0.3 mg twice daily). The primary endpoint is the effective control of blood pressure after a 12‐week randomized period of treatment. The ReHOT study will disseminate results about the prevalence of ReHy in stage II hypertension and the comparison of spironolactone vs clonidine for blood pressure control in patients with ReHy under 3‐drug standard regimen.

Ambulatory blood pressure monitoring and cardiovascular risk in resistant hypertensive women

FUNDAMENTO: Pocos estudios exploraron el valor pronostico del monitoreo ambulatorio de presion arterial (MAPA) en pacientes hipertensos resistentes, un grupo que presenta alto riesgo. OBJETIVO: Investigar el valor pronostico de la presion arterial (PA) diurna, en mujeres hipertensas resistentes. METODOS: Se siguieron por hasta 8,9 anos (promedio 3,9), a 382 mujeres hipertensas resistentes con edad entre 24 y 92 anos, atendidas en una unidad de hipertension de un hospital universitario. Se clasificaron a las pacientes como controladas (PA de consultorio>140/90 mmHg y PA diurna 140/90 mmHg y PA diurna>135/85 mmHg). Se analizo una combinacion de mortalidad cardiovascular, cardiopatia isquemica, accidente vascular encefalico y nefropatia. Se utilizo el modelo proporcional de Cox para estimarse el riesgo de eventos cardiovasculares ajustado para potenciales confundidores. RESULTADOS: La tasa total de eventos fue de 5,0 por 100 mujeres-ano. En el grupo de controladas ese valor fue de 3,7 y entre las no-controladas, de 5,8, con p=0.06. Los riesgos relativos asociados al aumento de 10 mmHg en la PA sistolica, ajustando para edad y tabaquismo actual, fueron mayores que los asociados a aumentos de 5 mmHg en la PA diastolica. Pacientes con descenso nocturno 10%, aunque esa asociacion no haya sido estadisticamente significante. La presion diurna no controlada (si/no) fue un fuerte factor de riesgo independiente, 1,67 (1,00-2,78). CONCLUSION: El aumento del 67% en el riesgo de evento cardiovascular cuando la PA diurna no estaba controlada es un indicador de que el empleo del MAPA es esencial en la evaluacion del control y como guia de las decisiones terapeuticas en la hipertension resistente.BACKGROUND Few studies have explored the prognostic value of ambulatory blood pressure (ABP) in resistant hypertensive patients, a high-risk group. OBJECTIVE To investigate the prognostic value of uncontrolled daytime ABP in resistant hypertensive women. METHODS We followed 382 resistant hypertensive women, aged 24-92 years, from a hypertension unit of a university hospital, for up to 8.9 years (mean 3.9). Patients were classified as controlled (office BP>140/90 mmHg and daytime ABP<135/85 mmHg) or uncontrolled (office BP>140/90 mmHg and daytime ABP >135/85 mmHg). We analyzed a combined endpoint, consisting of cardiovascular mortality, ischemic heart disease, stroke and nephropathy. Cox proportional hazard models were used to estimate the risk for cardiovascular events, adjusting for potential confounders. RESULTS The total event rate was 5.0 per 100 women-years. In the controlled and uncontrolled groups, the rates were 3.7 vs. 5.8 events respectively, p=0.06. The relative risks adjusted for age and current smoking status associated with a 10 mmHg increment in systolic ABP were greater than the ones associated with a 5 mmHg increment in diastolic ABP. Non-dipper patients had a higher risk for cardiovascular events than dipper patients (RR = 1.42 (0.87-2.32)), although this association had no statistical significance. Uncontrolled daytime blood pressure (yes/no) was a stronger independent risk factor, 1.67 (1.00-2.78). CONCLUSIONS There was a 67% increase in the risk of a cardiovascular event if daytime ambulatory blood pressure was uncontrolled in women with resistant hypertension. Therefore, it is mandatory to use ABP to evaluate control and to guide therapeutic strategies in resistant hypertensive patients.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5–50 mg QD) or clonidine (0.1–0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55–1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.

The association of ACE gene D/I polymorphism with cardiovascular risk factors in a population from Rio de Janeiro

Our aim was to determine the frequencies of the angiotensin-converting enzyme (ACE) gene alleles D and I and any associations to cardiovascular risk factors in a population sample from Rio de Janeiro, Brazil. Eighty-four adults were selected consecutively during a 6-month period from a cohort subgroup of a previous large cross-sectional survey in Rio de Janeiro. Anthropometric data and blood pressure measurements, echocardiogram, albuminuria, glycemia, lipid profile, and ACE genotype and serum enzyme activity were determined. The frequency of the ACE*D and I alleles in the population under study, determined by PCR, was 0.59 and 0.41, respectively, and the frequencies of the DD, DI, and II genotypes were 0.33, 0.51, and 0.16, respectively. No association between hypertension and genotype was detected using the Kruskal-Wallis method. Mean plasma ACE activity (U/mL) in the DD (N = 28), DI (N = 45) and II (N = 13) groups was 43 (in males) and 52 (in females), 37 and 39, and 22 and 27, respectively; mean microalbuminuria (mg/dL) was 1.41 and 1.6, 0.85 and 0.9, and 0.6 and 0.63, respectively; mean HDL cholesterol (mg/dL) was 40 and 43, 37 and 45, and 41 and 49, respectively, and mean glucose (mg/dL) was 93 and 108, 107 and 98, and 85 and 124, respectively. A high level of ACE activity and albuminuria, and a low level of HDL cholesterol and glucose, were found to be associated with the DD genotype. Finally, the II genotype was found to be associated with variables related to glucose intolerance.

Office blood pressure and 24-hour ambulatory blood pressure measurements: high proportion of disagreement in resistant hypertension

OBJECTIVE To evaluate the accuracy and quantify the agreement between office blood pressure (BP) and daytime ambulatory BP monitoring in the assessment of BP control of patients with a clinical diagnosis of resistant hypertension. STUDY DESIGN AND SETTING Office BP measurements were done in a cohort of 228 true resistant (TR) or white-coat resistant (WCR) hypertensives classified by ambulatory BP in a hypertension clinic in Rio de Janeiro in this validity study. The agreement between the daytime ambulatory BP and office BP was analyzed using the graphic methods of Altman -- Bland and survival -- agreement plots. RESULTS The likelihood ratio of a positive test result of office BP was 1.99 for the assessment of uncontrolled BP in TR patients and 1.05 for the WCR hypertensive patients. The Altman and Bland plot showed a significant difference between the two methods, and the presence of a fixed and a proportional bias. The survival-agreement plot showed that a tolerance limit of 20 mm Hg of difference between systolic office BP and systolic daytime ambulatory BP would generate a proportion of disagreement equal to 57.5%. CONCLUSION The office BP is still an important tool to monitor BP control of patients with TR hypertension, whereas the monitoring of patients with WCR hypertension requires ambulatory BP.

Hipertensão arterial na Ilha do Governador, Rio de Janeiro, Brasil: I. Metodologia

The aim of this paper (first of a series of two) is to present the main methodological aspects used in a cross-sectional study whose proposals were to establish the prevalence of arterial hypertension in adults in Ilha do Governador (a district of the city of Rio de Janeiro, Brazil), and to examine its relationship to other risk factors, including those for cardiovascular diseases, so as to establish its control status. Sampling design (of clusters in strata, according to mean household income) is described in detail, in addition to measurement methods, and training of observers. Indicators of performance in field work and quality control are also presented as results of the application of the metodology of study.