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

ABSTRACT: 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.

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.

Association between anxiety or depressive symptoms and arterial hypertension, and their impact on the quality of life.

OBJECTIVE: Despite all progress made in understanding and treating systemic arterial hypertension (SAH), the study of the impact of psychological disorders in SAH is still controversial and is not well understood. Our aim was to test the hypothesis that SAH can be associated with anxiety and depressive symptoms and to verify its effect on the quality of life. METHOD: A controlled cross-sectional study included 302 patients (152 hypertensive and 150 normotensive) outpatients at Hospital São Lucas of PUC-RS. Measurements were made in individual interviews and included data collection and application of general scales such as State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Medical Outcome Study Short Form, General Health Survey (SF-36). RESULTS: Anxiety was significantly associated with SAH only after adjusted for relevant risk factors (odds ratio (OR) = 2.83, 95% confidence interval (CI) = 1.55 to 5.18). Depressive symptoms were significantly associated with SAH (OR) = 4.34 (95% CI: 2.34 to 8.06). A significant association between quality of life and SAH were also found. However, this association diminished after adjusted for BDI and STAI. This shows the effect of depressive symptoms, in particular, and anxiety, in the worsening of quality of life. CONCLUSIONS: This study suggested that anxiety, especially depressive symptoms, are significantly associated with SAH and had a significant effect on hypertensive patients' worse quality of life.

Anticorpos contra LDL-ox e síndrome coronariana aguda / Antibodies against OxLDL and acute coronary syndrome

FUNDAMENTO: A oxidação da lipoproteína de baixa densidade (LDL-ox) induz à formação de epítopos imunogênicos na molécula. A presença de autoanticorpos contra a LDL-ox tem sido demonstrada no soro de pacientes com doença arterial coronariana (DAC). Contudo, o papel desses autoanticorpos na fisiopatologia das síndromes coronarianas agudas (SCA) e o seu significado clínico permanecem indefinidos. OBJETIVO: Avaliar a associação entre autoanticorpos contra a LDL-ox e SCA. MÉTODOS: Os títulos de imunoglobulina G autoanticorpos contra a LDL-ox por cobre (antiLDL-ox) e contra o peptídeo sintético D derivado da apolipoproteína B (antipeptD) foram determinados por ensaio imunoenzimático (ELISA) em 90 pacientes, nas primeiras 12h de SCA (casos) e em 90 pacientes com DAC crônica (controles). RESULTADOS: Os resultados mostraram que os títulos de antiLDL-ox foram significativamente mais elevados (p = 0,017) nos casos (0,40 ± 0,22), do que nos controles (0,33 ± 0,23). Por outro lado, os títulos de antipeptD foram significativamente menores (p < 0,01) nos casos (0,28 ± 0,23) do que nos controles (0,45 ± 0,30). A diferença dos títulos de ambos anticorpos entre os dois grupos estudados foi independente de idade, sexo, hipertensão arterial, diabete melito, dislipidemia, índice de massa corporal, tabagismo, perfil lipídico, uso de estatinas e história familiar de DAC. CONCLUSÃO: Os resultados mostraram que os títulos de antiLDL-ox foram significativamente mais elevados nos pacientes com síndrome coronariana aguda quando comparados aos pacientes com doença arterial coronariana e podem estar associados à instabilidade da placa aterosclerótica.

BACKGROUND: The oxidation of low-density lipoprotein (oxLDL) induces the formation of immunogenic epitopes in molecules. The presence of autoantibodies against oxLDL has been demonstrated in the serum of patients with coronary artery disease (CAD). However, the role of these autoantibodies in the pathophysiology of acute coronary syndromes (ACS) and their clinical significance remain undefined. OBJECTIVE: To evaluate the association between antibodies against oxLDL and ACS. METHODS: Titers of IgG autoantibodies against oxLDL by copper (anti-oxLDL) and anti-D synthetic peptide derived from apolipoprotein B (antipeptD) were determined by Enzyme-linked immunosorbent assay (ELISA) in 90 patients, in the first 12 hours of ACS (cases) and in 90 patients with chronic CAD (controls). RESULTS: The results showed that the titers of anti-oxLDL were significantly higher (p = 0.017) in cases (0.40 ± 0.22) than in controls (0.33 ± 0.23). On the other hand, the titers of antipeptD were significantly lower (p < 0.01) in cases (0.28 ± 0.23) than in controls (0.45 ± 0.30). The difference in the titers of both antibodies between the two groups was independent of age, sex, hypertension, diabetes mellitus, dyslipidemia, body mass index, smoking, lipid profile, statin use and family history of CAD. CONCLUSION: The results showed that the titers of anti-oxLDL were significantly higher in patients with acute coronary syndrome as compared to patients with coronary artery disease and may be associated with atherosclerotic plaque instability.

Antibodies against oxLDL and acute coronary syndrome.

BACKGROUND: The oxidation of low-density lipoprotein (oxLDL) induces the formation of immunogenic epitopes in molecules. The presence of autoantibodies against oxLDL has been demonstrated in the serum of patients with coronary artery disease (CAD). However, the role of these autoantibodies in the pathophysiology of acute coronary syndromes (ACS) and their clinical significance remain undefined. OBJECTIVE: To evaluate the association between antibodies against oxLDL and ACS. METHODS: Titers of IgG autoantibodies against oxLDL by copper (anti-oxLDL) and anti-D synthetic peptide derived from apolipoprotein B (antipeptD) were determined by Enzyme-linked immunosorbent assay (ELISA) in 90 patients, in the first 12 hours of ACS (cases) and in 90 patients with chronic CAD (controls). RESULTS: The results showed that the titers of anti-oxLDL were significantly higher (p = 0.017) in cases (0.40 +/- 0.22) than in controls (0.33 +/- 0.23). On the other hand, the titers of antipeptD were significantly lower (p < 0.01) in cases (0.28 +/- 0.23) than in controls (0.45 +/- 0.30). The difference in the titers of both antibodies between the two groups was independent of age, sex, hypertension, diabetes mellitus, dyslipidemia, body mass index, smoking, lipid profile, statin use and family history of CAD. CONCLUSION: The results showed that the titers of anti-oxLDL were significantly higher in patients with acute coronary syndrome as compared to patients with coronary artery disease and may be associated with atherosclerotic plaque instability.

Associação do polimorfismo do gene da enzima conversora de angiotensina com doença arterial coronariana: um estudo controlado por angiografia / Association of the angiotensin converting enzyme gene polymorphism and coronary artery disease: an angiographically controlled study

O trabalho teve como objetivo investigar a associação do polimorfismo de inserção/ delegação do gene da enzima conversora de angiotensina (ECA) com a presença de infarto do miocárdio e a extensão da doença arterial coronariana (DAC). Na literatura o alelo D da ECA tem sido relacionado com o desenvolvimento de doenças cardiovasculares, porém os resultados dos estudos publicados permanecem controversos. A associação do genótipo DD da ECA com infarto do miocárdio tem sido inconstante e atualmente sugere-se que esta associação estaria limitada a certos grupos raciais. A população do estudo consistiu de pacientes masculinos com idade entre 35 e 70 anos e que foram submetidos a cateterismo cardíaco para investigação de DAC. Definiu-se como grupo caso os indivíduos com diagnóstico de DAC e como grupo controle os pacientes com coronárias normais ao exame. A extensão do envolvimento caronariano foi classificado de acordo com o número de artérias coronarianas que apresentavam estenoses moderada ou severa. A genotipagem foi realizada através da técnica de reação em cadeia da polimerase (PCR) e os fatores de risco clássicos para DAC avaliados através de questionário, exame físico e exames laboratoriais. Participaram do estudo 34 pacientes, sendo 19 casos e 15 controles. A média de idade foi de 56 anos, sem diferença significativa entre os grupos. Na amostra estudada o genótipo da ECA não esteve associado à idade, índice de massa corporal, dislipidemia, níveis de glicemia em jejum elevados, tabagismo e história de hipertensão ou tratamento anti-hipertensivo. Não houve associação significativa entre o genótipo DD da ECA e a presença de infarto do miocárdio (P = 0,257). Também não se evidenciou associação entre o genótipo DD da ECA e o grau de extensão da DAC (P = 0,355). A maior prevalência do Genótipo DD no grupo de pacientes com DAC, levanta a hipótese de que com o aumento do número da amostra poderemos obter dados mais consistentes.