Candesartan and hydrochlorothiazide in isolated systolic hypertension

Aim: We investigated the efficacy and safety of daily candesartan 8/16 mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension. Methods: The study used a double-blind randomized placebo-controlle

Candesartan and hydrochlorothiazide in isolated systolic hypertension

Aim: We investigated the efficacy and safety of daily candesartan 8/16 mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension. Methods: The study used a double-blind randomized placebo-controlled crossover design. Treatment phases were of 6 weeks duration. For inclusion, patients were aged 55-84 years with sitting systolic blood pressure (SBP) 160-210 mmHg and diastolic blood pressure (DBP) \u3c95 mmHg. Nineteen patients (11 male, eight female, median age 68 years) completed the study. Major findings: Compared with the placebo phase, clinic and ambulatory SBP was significantly reduced with both dose-adjusted candesartan and fixed-dose hydrochlorothiazide as monotherapy, the effect of candesartan being greater than that of hydrochlorothiazide. In combination, the effects of the two drugs were additive. Both drugs were well tolerated either as monotherapy or in combination. Conclusion: Both candesartan and a low dose of hydrochlorothiazide are effective and well-tolerated antihypertensive agents in isolated systolic hypertension with additive effects in combination. Candesartan was more effective than hydrochlorothiazide, although it is possible that dose adjustment only of candesartan could have enhanced its relative effectiveness

Association of depression with mortality in an elderly treated hypertensive population

Background:Both elevated blood pressure and/or depression increase the risk of cardiovascular disease and mortality. This study in treated elderly hypertensive patients explored the incidence of depression, its association (pre-existing and incident) with mortality and predictors of incident depression.Methods:Data from 6,083 hypertensive patients aged =65 years enrolled in the Second Australian National Blood Pressure study were used. Participants were followed for a median of 10.8 years (including 4.1 years in-trial) and classified into: "no depression," "pre-existing" and "incident" depression groups based on either being "diagnosed with depressive disorders" and/or "treated with an anti-depressant drug" at baseline or during in-trial period. Further, we redefined "depression" restricted to presence of both conditions for sensitivity analyses. For the current study, end-points were all-cause and any cardiovascular mortality.Results:313 (5%) participants had pre-existing depression and a further 916 (15%) participants developed depression during the trial period (incidence 4% per annum). Increased (hazard-ratio, 95% confidence-interval) all-cause mortality was observed among those with either pre-existing (1.23, 1.01-1.50; p = 0.03) or incident (1.26, 1.12-1.41; p < 0.001) depression compared to those without. For cardiovascular mortality, a 24% increased risk (1.24, 1.05-1.47; p = 0.01) was observed among those with incident depression. The sensitivity analyses, using the restricted depression definition showed similar associations. Incident depression was associated with being female, aged =75 years, being an active smoker at study entry, and developing new diabetes during the study period.Conclusions:This elderly cohort had a high incidence of depression irrespective of their randomised antihypertensive regimen. Both pre-existing and incident depression were associated with increased mortality

Lacidipine, hydrochlorothiazide and their combination in systolic hypertension in the elderly

Objective. To compare with placebo the efficacies of once-daily administrations of lacidipine and hydrochlorothiazide separately and in combination to elderly patients with systolic hypertension. Design and methods. Nineteen elderly subjects (five men and 14 women, median age 71 years, range 62-79 years) participated in the study, which had a randomized double-blind crossover design. For each subject there were four treatment phases, each of duration 4 weeks. The initial treatments in each phase were 2 mg lacidipine once a day and 25 mg hydrochlorothiazide once a day, separately and in combination, and placebo. Doses of each agent could be doubled after 2 weeks in each phase if the patient\u27s goal systolic blood pressure had not been achieved. The numbers of subjects administered the higher dose of each treatment were 13 for placebo, 14 for lacidipine, 11 for hydrochlorothiazide and eight for lacidipine plus hydrochlorothiazide. Results. End-of-phase mean clinic blood pressures were 164/85 mmHg with placebo, 159/82 mmHg with lacidipine, 157/84 mmHg with hydrochlorothiazide and 152/82 mmHg with lacidipine plus hydrochlorothiazide. Systolic blood pressure was significantly reduced during all active treatment phases compared with placebo and that for the lacidipine plus hydrochlorothiazide phase was also significantly less than those for both of the other active treatment phases. There was no difference between sitting and standing blood pressure for any phase. Factorial analysis of the main effects of treatment indicated that the effects of lacidipine and hydrochlorothiazide on clinic blood pressure were additive and also that heart rate was higher when hydrochlorothiazide had been administered. Ambulatory blood pressure monitoring confirmed the pattern of the responses of blood pressure and showed that administration of hydrochlorothiazide had a significantly greater effect on systolic blood pressure and a longer duration of action than did administration of lacidipine. There was no difference in the frequency of adverse effects among any of the phases. Conclusions. In treating elderly systolic hypertensives the diuretic hydrochlorothiazide is a more effective antihypertensive agent with a longer duration of action than is the calcium channel antagonist lacidipine. In combination the effects of these two drugs on blood pressure are additive

Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor

Aim: To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (\u3c 100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. Design and Methods: Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. Results: 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mmHg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p \u3c 0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. Conclusions: In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP

Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives

© 2006 American Heart Association, Inc.Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study (untreated blood pressure 169/88±12/8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival (hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure 81 versus <81 mm Hg; P=0.01), no such relation was found for carotid augmentation index (HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance (HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.Anthony M. Dart, Christoph D. Gatzka, Bronwyn A. Kingwell, Kristyn Willson, James D. Cameron, Yu-Lu Liang, Karen L. Berry, Lindon M.H. Wing, Christopher M. Reid, Philip Ryan, Lawrence J. Beilin, Garry L.R. Jennings, Colin I. Johnston, John J. McNeil, Graham J. MacDonald, Trefor O. Morgan and Malcolm J. Wes

Genetic and environmental transmission of body mass index fluctuation

This study sought to determine the relationship between body mass index (BMI) fluctuation and cardiovascular disease phenotypes, diabetes, and depression and the role of genetic and environmental factors in individual differences in BMI fluctuation using the extended twin-family model (ETFM). This study included 14,763 twins and their relatives. Health and Lifestyle Questionnaires were obtained from 28,492 individuals from the Virginia 30,000 dataset including twins, parents, siblings, spouses, and children of twins. Self-report cardiovascular disease, diabetes, and depression data were available. From self-reported height and weight, BMI fluctuation was calculated as the difference between highest and lowest BMI after age 18, for individuals 18–80 years. Logistic regression analyses were used to determine the relationship between BMI fluctuation and disease status. The ETFM was used to estimate the significance and contribution of genetic and environmental factors, cultural transmission, and assortative mating components to BMI fluctuation, while controlling for age. We tested sex differences in additive and dominant genetic effects, parental, non-parental, twin, and unique environmental effects. BMI fluctuation was highly associated with disease status, independent of BMI. Genetic effects accounted for ~34 % of variance in BMI fluctuation in males and ~43 % of variance in females. The majority of the variance was accounted for by environmental factors, about a third of which were shared among twins. Assortative mating, and cultural transmission accounted for only a small proportion of variance in this phenotype. Since there are substantial health risks associated with BMI fluctuation and environmental components of BMI fluctuation account for over 60 % of variance in males and over 50 % of variance in females, environmental risk factors may be appropriate targets to reduce BMI fluctuation