Comparison of Incidence and Prognosis of Myocardial Injury in Patients with COVID-19-Related Respiratory Failure and Other Pulmonary Infections: A Contemporary Cohort Study.

Myocardial injury (MI) is frequent in critically ill patients with COVID-19, but its pathogenesis remains unclear. We hypothesized that MI is not solely due to viral infection by SARS-CoV-2 but rather due to the common pathophysiological mechanisms associated with severe pulmonary infections and respiratory failure. This contemporary cohort study was designed to compare the incidence of MI in patients with acute respiratory failure caused by COVID-19 to patients with other pulmonary infections. In addition, we aimed to investigate whether MI was a distinct risk factor for in-hospital mortality in patients with COVID-19 compared to those with non-COVID-19 infections. This study included 1444 patients with COVID-19 (55.5% men; age 58 (46;68) years) and 182 patients with other pulmonary infections (46.9% men; age 62 (44;73) years). The incidence of MI at ICU admission was lower in COVID-19 patients (36.4%) compared to non-COVID-19 patients (56%), and this difference persisted after adjusting for age, sex, coronary artery disease, heart failure, SOFA score, lactate, and C-reactive protein (RR 0.84 (95% CI, 0.71-0.99)). MI at ICU admission was associated with a 59% increase in mortality (RR 1.59 (1.36-1.86); p < 0.001), and there was no significant difference in the mortality between patients with COVID-19 and those with other pulmonary infections (p = 0.271). We concluded that MI is less frequent in patients with critical COVID-19 pneumonia and respiratory failure compared to those with other types of pneumonia. The occurrence of MI is a significant risk factor for in-hospital mortality, regardless of the etiology of the pulmonary infection.

Effects of chlorthalidone plus amiloride compared with amlodipine on short-term blood pressure variability in individuals with hypertension and obstructive sleep apnea: a randomized controlled trial.

OBJECTIVE: To compare the effects of chlortalidone plus amiloride and amlodipine on blood pressure (BP) variability in patients with hypertension and obstructive sleep apnea syndrome (OSA). METHODS: A randomized, controlled, double-blind trial enrolled men and women aged 40 years or older with a diagnosis of OSA (apnea-hypopnea index 10-40 apneas/h of sleep) confirmed by overnight laboratory polysomnography and systolic BP 140-159 mmHg or diastolic BP 90-99 mmHg. Participants were randomized to receive chlortalidone 25 mg plus amiloride 5 mg daily or amlodipine 10 mg daily for 8 weeks. BP variability was calculated from 24-hour ambulatory BP monitoring at baseline and follow-up using the following indices: SD, coefficient of variation, average real variability (ARV), time-rate index, and variability independent of the mean (VIM). RESULTS: The study included 65 patients, with 33 assigned to the chlortalidone plus amiloride group and 32 to the amlodipine group. Participants in both groups had similar baseline characteristics. Short-term BP variability decreased within groups for SD and ARV indexes for 24-hour systolic BP and daytime systolic BP, but statistically significant time*group interactions were found for sleep systolic SD and VIM, with greater reduction in patients treated with amlodipine. CONCLUSION: In brief, our study has shown that the use of chlorthalidone in combination with amiloride and amlodipine produces comparable effects on short-term BP variability in patients with hypertension and OSA. Therefore, our findings suggest that BP variability may not be a significant factor when choosing between these medications for the treatment of hypertension and OSA.

Effects of Antihypertensive Treatment on Left and Right Ventricular Global Longitudinal Strain and Diastolic Parameters in Patients with Hypertension and Obstructive Sleep Apnea: Randomized Clinical Trial of Chlorthalidone plus Amiloride vs. Amlodipine.

Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. METHODS: A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. RESULTS: Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. CONCLUSION: Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

Secondary Pharmacological Prevention of Coronary Artery Disease among Patients Submitted to Clinical Management, Percutaneous Coronary Intervention, or Coronary Artery Bypass Graft Surgery. / Prevenção Farmacológica Secundária da Doença Arterial Coronariana em Pacientes Submetidos ao Manejo Clínico, Intervenção Coronária Percutânea ou Cirurgia de Revascularização Miocárdica.

BACKGROUND: Secondary prevention is recommended for patients with evidence of coronary artery disease (CAD) regardless of the indication for treatment by coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). OBJECTIVES: This study evaluated whether clinical treatment, PCI or CABG had an influence on adherence to the pharmacological secondary prevention in patients with stable CAD. METHODS: This cohort included patients aged ≥40 years with stable CAD confirmed by coronary angiography. The decision for medical treatment alone, or additionally with PCI or CABG, was made by the attending physicians. Adherence to the prescribed drugs recommended by the guidelines for secondary prevention (optimal pharmacological treatment), including antiplatelet agents, lipid-lowering drugs, beta-blockers, and renin-angiotensin-aldosterone system blockers, was assessed at follow-up. Differences were considered significant for p values <0.05. RESULTS: From 928 patients enrolled at baseline, 415 had mild CAD and 66 moderate to severe CAD. The average follow-up was 5.2 ± 1.5 years. Patients submitted to CABG were more likely to receive the optimal pharmacological treatment than those submitted to PCI or treated clinically (63.5% versus 39.1% versus 45.7% respectively, p=0.003). Baseline factors independently associated with greater probability of having a prescription of optimal treatment at follow-up were CABG [39% higher (6% - 83%, p=0.017) and diabetes [25% higher (1% - 56%), p=0.042] than their counterparts treated by other methods and participants without diabetes, respectively. CONCLUSIONS: Patients with CAD submitted to CABG are more commonly treated with optimal pharmacological secondary prevention than patients treated by PCI or exclusively with medical therapy.

FUNDAMENTO: A prevenção secundária é recomendada a pacientes com evidência de doença arterial coronariana (DAC) independentemente da indicação de tratamento por cirurgia de bypass da artéria coronária (CABG) ou intervenção coronária percutânea (ICP). OBJETIVOS: Este estudo avaliou se o tratamento clínico, a ICP ou o CABG teve influência na adesão à prevenção secundária farmacológica em pacientes com DAC estável. MÉTODOS: Esta coorte incluiu pacientes com idade ≥40 anos com DAC estável confirmada por angiografia coronária estável. A decisão por tratamento clínico isolado, ou combinado com ICP ou CABG foi feita por médicos assistentes. A adesão às drogas prescritas recomendadas pelas diretrizes de prevenção secundária (tratamento farmacológico ótimo), incluindo agentes antiplaquetários, drogas hipolipemianetes, betabloqueadores, e bloqueadores do sistema angiotensina aldosterona, foi avaliada no acompanhamento. Diferenças com valores de p < 0,05 foram consideradas estatisticamente significativas. RESULTADOS: Dos 928 pacientes incluídos inicialmente, 415 apresentaram DAC leve e 66 apresentaram DAC leve a moderada. O período médio de seguimento foi 5,2 ± 1,5 anos. Os pacientes submetidos ao CABG apresentaram maior probabilidade de receberem tratamento farmacológico ótimo que aqueles submetidos à ICP ou tratamento clínico (63,5% versus 39,1% versus 45,7% respectivamente, p=0,003). Fatores basais independentemente associados com maior probabilidade de prescrição de tratamento ótimo foram CABG [39% maior (6% - 83%, p=0,017)] em comparação a outros tratamentos e diabetes [25% maior (1% - 56%), p=0,042] em comparação à ausência de diabetes. CONCLUSÕES: Pacientes com DAC submetidos ao CABG são mais frequentemente tratados com prevenção secundária farmacológica ótima que pacientes tratados com ICP ou exclusivamente com tratamento clínico.

Prevenção Farmacológica Secundária da Doença Arterial Coronariana em Pacientes Submetidos ao Manejo Clínico, Intervenção Coronária Percutânea ou Cirurgia de Revascularização Miocárdica / Secondary Pharmacological Prevention of Coronary Artery Disease among Patients Submitted to Clinical Management, Percutaneous Coronary Intervention, or Coronary Artery Bypass Graft Surgery

Resumo Fundamento A prevenção secundária é recomendada a pacientes com evidência de doença arterial coronariana (DAC) independentemente da indicação de tratamento por cirurgia de bypass da artéria coronária (CABG) ou intervenção coronária percutânea (ICP). Objetivos Este estudo avaliou se o tratamento clínico, a ICP ou o CABG teve influência na adesão à prevenção secundária farmacológica em pacientes com DAC estável. Métodos Esta coorte incluiu pacientes com idade ≥40 anos com DAC estável confirmada por angiografia coronária estável. A decisão por tratamento clínico isolado, ou combinado com ICP ou CABG foi feita por médicos assistentes. A adesão às drogas prescritas recomendadas pelas diretrizes de prevenção secundária (tratamento farmacológico ótimo), incluindo agentes antiplaquetários, drogas hipolipemianetes, betabloqueadores, e bloqueadores do sistema angiotensina aldosterona, foi avaliada no acompanhamento. Diferenças com valores de p < 0,05 foram consideradas estatisticamente significativas. Resultados Dos 928 pacientes incluídos inicialmente, 415 apresentaram DAC leve e 66 apresentaram DAC leve a moderada. O período médio de seguimento foi 5,2 ± 1,5 anos. Os pacientes submetidos ao CABG apresentaram maior probabilidade de receberem tratamento farmacológico ótimo que aqueles submetidos à ICP ou tratamento clínico (63,5% versus 39,1% versus 45,7% respectivamente, p=0,003). Fatores basais independentemente associados com maior probabilidade de prescrição de tratamento ótimo foram CABG [39% maior (6% - 83%, p=0,017)] em comparação a outros tratamentos e diabetes [25% maior (1% - 56%), p=0,042] em comparação à ausência de diabetes. Conclusões Pacientes com DAC submetidos ao CABG são mais frequentemente tratados com prevenção secundária farmacológica ótima que pacientes tratados com ICP ou exclusivamente com tratamento clínico.

Abstract Background Secondary prevention is recommended for patients with evidence of coronary artery disease (CAD) regardless of the indication for treatment by coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI). Objectives This study evaluated whether clinical treatment, PCI or CABG had an influence on adherence to the pharmacological secondary prevention in patients with stable CAD. Methods This cohort included patients aged ≥40 years with stable CAD confirmed by coronary angiography. The decision for medical treatment alone, or additionally with PCI or CABG, was made by the attending physicians. Adherence to the prescribed drugs recommended by the guidelines for secondary prevention (optimal pharmacological treatment), including antiplatelet agents, lipid-lowering drugs, beta-blockers, and renin-angiotensin-aldosterone system blockers, was assessed at follow-up. Differences were considered significant for p values <0.05. Results From 928 patients enrolled at baseline, 415 had mild CAD and 66 moderate to severe CAD. The average follow-up was 5.2 ± 1.5 years. Patients submitted to CABG were more likely to receive the optimal pharmacological treatment than those submitted to PCI or treated clinically (63.5% versus 39.1% versus 45.7% respectively, p=0.003). Baseline factors independently associated with greater probability of having a prescription of optimal treatment at follow-up were CABG [39% higher (6% - 83%, p=0.017) and diabetes [25% higher (1% - 56%), p=0.042] than their counterparts treated by other methods and participants without diabetes, respectively. Conclusions Patients with CAD submitted to CABG are more commonly treated with optimal pharmacological secondary prevention than patients treated by PCI or exclusively with medical therapy.

The performance of SYNTAX score versus the coronary angiogram standard evaluation in the prediction of cardiovascular events in a cohort of patients with stable coronary heart disease.

Background: Scores for prediction of cardiovascular events in patients with stable coronary artery disease (CAD) submitted to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) or medical-therapy (MT), such as the SYNTAX score (SXscore), have been proposed, but there is no comparative assessment of their performance with the coronary angiogram standard evaluation (CASE). This study aimed to evaluate the performance of the SXscore versus the CASE in the prediction of major cardiovascular outcomes (MACCE) in patients with chronic CAD who were treated with MT or additionally submitted to CABG or PCI. Methods: Prospective cohort study of 454 patients with CAD referred for elective diagnostic coronary angiography in Hospital de Clínicas de Porto Alegre, Brazil, with 40 years of age or over, which were followed on average for 6±2.0 years. Patients with acute coronary syndromes, valvular heart disease, aortic diseases, previous coronary revascularization, heart failure, chronic renal disease, history of cancer, or severe psychiatric illness were excluded. Agreement between the scores was evaluated by Kappa statistics. The performance of the scores to predict MACCE was evaluated by Cox proportional hazard models. Areas under the ROC curves were compared by the DeLong test. Results: Patients with moderate to high SXscores or with left main or multivessel CAD (LMMCAD) in the CASE evaluation had higher rates of all-cause death and MACCE than those with low SXscore or without LMMCAD. After adjusting for confounding, only LMMCAD remained associated with the incidence of all-cause death in the total sample (HR =2.81;95% CI: 1.17-6.74) and for MACCE in patients undergoing MT (HR =8.72; 95% CI: 1.73-44.10). The ROC curves for all treatments were similar. Kappa statistics was not significant in patients submitted to MT, poor for patients treated by PCI and fair for the whole sample and patients treated with CABG. Conclusions: The severity of CAD defined by CASE or the SXscore provides similar prediction of the occurrence of cardiovascular events in patients submitted to clinical, PCI or CABG therapies. CASE is easier to do and may be the preferential method in the stratification of risk of patients with stable CAD.

Thiazide diuretics alone or in combination with a potassium-sparing diuretic on blood pressure-lowering in patients with primary hypertension: protocol for a systematic review and network meta-analysis.

BACKGROUND: The use of thiazide (T) diuretics for the treatment of hypertension may be associated with adverse metabolic effects, which can be minimized by combining thiazides with potassium-sparing (PS) diuretics. The additional blood pressure (BP)-lowering effect provided by the addition of a PS diuretic is unclear. Due to a large number of drugs in the T diuretics class, and the possible difference between them, there is a need to identify the best available evidence for health decision-making. This systematic review with network meta-analysis aims to compare the antihypertensive efficacy of T diuretics alone or in combination with a PS diuretic in patients with primary hypertension, as well as the safety of such drugs through the measurement of drug-related adverse events. METHODS: A comprehensive electronic search will be conducted in six electronic bibliographic databases (PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, Scopus, Lilacs), a registration database ( ClinicalTrials.gov ), and Educational Resources Information Center (ERIC [ProQuest]), published from inception to the date of the search. The search will be updated towards the end of the review. A hand search of the reference sections of the included studies and cited studies will also be performed. In case of missing data, authors will be contacted by e-mail or academic social networking sites whenever possible. To be included in the review, studies must be double-blind randomized controlled trials evaluating T diuretics alone or in combination with PS diuretics in patients with primary hypertension. The primary outcome measure will be office BP. Ambulatory BP monitoring (ABPM), non-melanoma skin cancer, major adverse cardiovascular events, laboratory parameters, and the number of withdrawals will be included as secondary outcomes. The results will be quantitatively summarized using differences between the mean change from baseline or differences between means for quantitative outcomes and relative risk for dichotomous outcomes. Results will be presented as mean or relative risk with credible intervals through a league table. The treatments will also be ranked using the surface under the cumulative ranking curve method. The risk of bias will be assessed through the RoB 1.0 tool. DISCUSSION: To the best of our knowledge, this review will be the first to synthesize currently available evidence on the antihypertensive efficacy of different T diuretics alone or in combination with PS diuretics in adults with hypertension. The goals of hypertension treatment are to control high BP and to reduce associated cardiovascular morbidity and mortality, using the most appropriate therapy. Thiazides are widely used for pharmacological treatment due to their demonstrated effectiveness in reducing BP, favorable safety profile, and low cost. The results of this study will provide evidence regarding the best therapeutic strategies with T and PS diuretics, evidencing interventions with better antihypertensive efficacy and safety profile. TRIAL REGISTRATION: This systematic review and network meta-analysis was prospectively registered at the PROSPERO database ( CRD42018118492 ).

Quality of life in patients with stable coronary artery disease submitted to percutaneous, surgical, and medical therapies: a cohort study.

BACKGROUND: Clinical, surgical, and percutaneous strategies similarly prevent major cardiovascular events in patients with stable coronary artery disease (CAD). The possibility that these strategies have differential effects on health-related quality of life (HRQoL) has been debated, particularly in patients treated outside clinical trials. METHODS: We assigned 454 patients diagnosed with CAD during an elective diagnostic coronary angiography to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical treatment (OMT), and followed them for an average of 5.2 ± 1.5 years. HRQoL was assessed using a validated Brazilian version of the 12-Item Short-Form Health Survey questionnaire. The association between therapeutic strategies and quality of life scores was tested using variance analysis and adjusted for confounders in a general linear model. RESULTS: There were no differences in the mental component summary scores in the follow-up evaluation by therapeutic strategies: 51.4, 53.7, and 52.3 for OMT, PCI, and CABG, respectively. Physical component summary scores were higher in the PCI group than the CABG and OMT groups (46.4 vs. 42.9 and 43.8, respectively); however, these differences were no longer different after adjustment for confounding variables. CONCLUSION: In a long-term follow-up of patients with stable CAD, HRQoL did not differ in patients treated by medical, percutaneous, or surgical treatments.

Development, Validation, and Reproducibility of Food Group-Based Frequency Questionnaires for Clinical Use in Brazil: A Pre-Hypertension and Hypertension Diet Assessment.

The Blood pressure control diet is well described; however, it has not been implemented in clinical care, possibly due to the impracticability of the diet assessment in these contexts. In order to facilitate the dietary assessment, we developed and assessed the validity and reproducibility of two food group-based food frequency questionnaires (FG-FFQs), with a one-week (7-day FG-FFQ) and a one-month (30-day FG-FFQ) period of coverage for patients with pre-hypertension or hypertension. In 2010, 155 men and women, 30-70 years old, were invited to participate in a prospective study in two outpatient clinics in Porto Alegre, southern Brazil. The participants responded to two 30-day, two 7-day FG-FFQ, four 24-h dietary recalls, and underwent demographic, anthropometric, and blood pressure assessments. The validity and reproducibility were assessed using partial correlation coefficients adjusted for sex and age, and the internal validity was tested using the intra-class correlation coefficient. The participants were aged 61 (±10) years and 60% were women. The validity correlation coefficient was higher than r = 0.80 in the 30-day FG-FFQ for whole bread (r = 0.81) and the 7-day FG-FFQ for diet/light/zero soda and industrialized juices (r = 0.84) in comparison to the 24-h dietary recalls. The global internal validity was α = 0.59, but it increased to α = 0.76 when 19 redundant food groups were excluded. The reproducibility was higher than r = 0.80 for pasta, potatoes and manioc, bakery goods, sugar and cocoa, and beans for both versions. The 30-day had a slightly higher validity, both had good internal validity, and the 7-day FG-FFQ had a higher reproducibility.

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic.

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial.

AIMS: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. METHODS: In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. RESULTS: Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. CONCLUSIONS: Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. TRIAL REGISTRATION: Clinical trials registration number: NCT00971165.

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension - Study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and ≥80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index ≥15 events/hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP.

Effectiveness of Clinical, Surgical and Percutaneous Treatment to Prevent Cardiovascular Events in Patients Referred for Elective Coronary Angiography: An Observational Study.

PURPOSE: To ascertain the most appropriate treatment for chronic, stable, coronary artery disease (CAD) in patients submitted to elective coronary angiography. PATIENTS AND METHODS: A total of 814 patients included in the prospective cohort study were referred for elective coronary angiography and were followed up on average for 6±1.9 years. Main outcomes were all-cause death, cardiovascular death, non-fatal myocardial infarction (MI) and stroke and late revascularization and their combinations as major adverse cardiac and cerebral events (MACCE): MACCE-1 included cardiovascular death, nonfatal MI, and stroke; MACCE-2 was MACCE-1 plus late revascularization. Survival curves and adjusted Cox proportional hazard models were used to explore the association between the type of treatment and outcomes. RESULTS: All-cause death was lower in participants submitted to percutaneous coronary intervention (PCI) (0.41, 0.16-1.03, P=0.057) compared to medical treatment (MT). Coronary-artery bypass grafting (CABG) had an overall trend for poorer outcomes: cardiovascular death 2.53 (0.42-15.10), combined cardiovascular death, nonfatal MI, and stroke 2.15 (0.73-6.31) and these events plus late revascularization (2.17, 0.86-5.49). The corresponding numbers for PCI were 0.27 (0.05-1.43) for cardiovascular death, 0.77 (0.32-1.84) for combined cardiovascular death, nonfatal MI, and stroke and 2.35 (1.16-4.77) with the addition of late revascularization. These trends were not influenced by baseline blood pressure, left ventricular ejection fraction and previous MI. Patients with diabetes mellitus had a significantly higher risk of recurrent revascularization when submitted to PCI than CABG. CONCLUSION: Patients with confirmed CAD in elective coronary angiography do not have a better prognosis when submitted to CABG comparatively to medical treatment. Patients treated with PCI had a trend for the lower incidence of combined cardiovascular events, at the expense of additional revascularization procedures. Patients without significant CAD had a similar prognosis than CAD patients treated with medical therapy.

High Blood Pressure and Cardiovascular Disease.

Fragmented investigation has masked the overall picture for causes of cardiovascular disease (CVD). Among the risk factors for CVD, high blood pressure (BP) is associated with the strongest evidence for causation and it has a high prevalence of exposure. Biologically, normal levels of BP are considerably lower than what has typically been characterized as normal in research and clinical practice. We propose that CVD is primarily caused by a right-sided shift in the population distribution of BP. Our view that BP is the predominant risk factor for CVD is based on conceptual postulates that have been tested in observational investigations and clinical trials. Large cohort studies have demonstrated that high BP is an important risk factor for heart failure, atrial fibrillation, chronic kidney disease, heart valve diseases, aortic syndromes, and dementia, in addition to coronary heart disease and stroke. In multivariate modeling, the presumed attributable risk of high BP for stroke and coronary heart disease has increased steadily with progressive use of lower values for normal BP. Meta-analysis of BP-lowering randomized controlled trials has demonstrated a benefit which is almost identical to that predicted from BP risk relationships in cohort studies. Prevention of age-related increases in BP would, in large part, reduce the vascular consequences usually attributed to aging, and together with intensive treatment of established hypertension would eliminate a large proportion of the population burden of BP-related CVD.

Stage I hypertension is associated with impaired systolic function by strain imaging compared with prehypertension: A report from the prever study.

High blood pressure (BP) is associated with higher rates of cardiovascular events, even in stage I hypertension (HTN) and prehypertension (preHTN). Lower left ventricular (LV) systolic function, assessed by global longitudinal strain (GLS), has been demonstrated in individuals with HTN compared to individuals with normal BP, but a comparison of individuals with preHTN and stage I HTN was not described to date. The PREVER study includes two randomized double-blind controlled trials, performed in volunteers with preHTN (PREVER-prevention trial) or stage I HTN (PREVER-treatment trial), aged 30-70 years. A subsample of patients of both trials had GLS measured from 2D echocardiograms performed at baseline and after 18 months of follow-up. We compared baseline data from both studies and, among stage I HTN patients, clinical and echocardiographic correlates of GLS were determined. Participants with preHTN (n = 91;53% female; 55 ± 9 yo) and stage I HTN (n = 105; 44% female; 55 ± 8 yo) had similar clinical parameters beyond the expected differences in BP levels. Participants with stage I HTN had lower GLS (-17.5 ± 2.5% vs -18.2 ± 2.4%, P = .03) compared with those with preHTN. In stage I HTN, lower GLS was associated with lower e' and lower LV ejection fraction. In conclusion, patients in Stage I HTN may already express changes in GLS compared with individuals with preHTN, suggesting that even mildly difference in BP can be impact in subclinical systolic function.

Self-reported adherence to physical activity recommendations compared to the IPAQ interview in patients with hypertension.

BACKGROUND: Physical activity (PA) is recommended as adjuvant therapy to control blood pressure (BP). The effectiveness of simple recommendations is not clear. We aimed to assess the agreement between self-report of adherence to PA in clinical routine and International Physical Activity Questionnaire (IPAQ) interview and its association with BP control. METHODS: A cross-sectional study was conducted with hypertensive outpatients. Adherence to recommendation to PA was assessed by the physician and IPAQ interview. A cutoff of 150 minutes/week was used to classify active or nonactive patients. High sitting time was considered >4 hours/day. A total of 127 individuals (SBP 144.9±24.4 mmHg/DBP 82.0±12.8 mmHg) were included. RESULTS: A total of 69 subjects (54.3%) reported to be active to their physician, whereas 81 (63.8%) were classified as active by IPAQ (6.3% active in leisure time PA). Kappa test was 0.22 (95% CI, 0.06-0.37). The rate of BP control was 45.7%. There was no association with the reported PA assessed by both methods nor with sitting time. Our results demonstrated poor agreement between self-report adherence and IPAQ interview, and neither evaluation was associated with BP control. CONCLUSION: Our findings underpin evidences that a simple PA recommendation has low association with BP control in clinical settings.

Technologies for Innovative Monitoring to Reduce Blood Pressure and Change Lifestyle Using Mobile Phones in Adult and Elderly Populations (TIM Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Hypertension is a growing problem worldwide, markedly in low- and middle-income countries, where the rate of control slightly decreased. The overall prevalence of hypertension in Brazil is 28.7% among adult individuals and 68.9% in the population aged 60 years and older, and less than a third of patients have controlled blood pressure (BP). The use of technologies-mobile phones and the internet-to implement interventions to reduce blood pressure can minimize costs and diminish cardiovascular risk. Interventions through text messaging and electronic BP monitoring present divergent results. OBJECTIVE: This trial evaluates the effectiveness of interventions-personalized messages and telemonitoring of BP-to reduce systolic BP and improve lifestyle compared to the usual care of patients with hypertension (control group). METHODS: This factorial randomized controlled trial enrolls individuals aged 30 to 75 years who have a mobile phone and internet access with the diagnosis of hypertension under drug treatment with up to 2 medications and uncontrolled BP. Eligible participants should have both increased office BP and 24-hour BP with ambulatory BP monitoring. Participants with severe hypertension (systolic BP ≥180 or diastolic BP ≥110 mm Hg), life threatening conditions, low life expectancy, recent major cardiovascular event (last 6 months), other indications for the use of antihypertensive medication, diagnosis of secondary hypertension, pregnant or lactating women, or those unable to understand the interventions are excluded. Participants are randomly allocate to 1 of 4 experimental arms: (1) Telemonitoring of blood pressure (TELEM) group: receives an automatic oscillometric device to measure BP, (2) telemonitoring by text message (TELEMEV) group: receives personalized, standardized text messages to stimulate lifestyle changes and adhere with BP-lowering medication, (3) TELEM-TELEMEV group: receives both interventions, and (4) control group: receives usual clinical treatment (UCT). Data collection is performed in a clinical research center located in a referent hospital. The primary outcomes are reduction of systolic BP assessed by 24-hour ambulatory BP monitoring (primary outcome) and change of lifestyle (based on dietary approaches to stop hypertension (DASH)-type diet, sodium restriction, weight loss or control, increase of physical activity). RESULTS: This study was funded by two Brazilian agencies: the National Council for Scientific and Technological Development and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul. Enrollment was completed at the end of 2017 (N=231), the follow-up is ongoing, and data analysis is expected to begin in early 2019. A reduction of 24-hour systolic BP of approximately 8.8 [SD 13.1] mm Hg for participants in the BP monitoring group versus 3.4 [SD 11.6] mm Hg in the UCT group is expected. A similar reduction in the text messaging group is expected. CONCLUSIONS: The use of mobile technologies connected to the internet through mobile phones promotes time optimization, cost reduction, and better use of public health resources. However, it has not been established whether simple interventions such as text messaging are superior to electronic BP monitoring and whether both outperform conventional counseling. TRIAL REGISTRATION: ClinicalTrials.gov NCT03005470; https://clinicaltrials.gov/ct2/show/NCT03005470 (Archived by WebCite at http://www.webcitation.org/70AoANESu). Plataforma Brasil CAAE 31423214.0.0000.5327. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9619.