Among men, race and age have an important effect on the response to single-drug therapy for hypertension. In addition to cost and quality of life, these factors should be considered in the initial choice of a drug.
The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from -3.5 for placebo, -7.1 to -10.2 for the irbesartan monotherapy groups, -5.1 to -8.3 for the HCTZ monotherapy groups, and -8.1 to -15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.
The effect of vitamin C on blood pressure is not well established. This is a randomized, double-blind control trial. Eligible patients were followed for 8 months. Patients were randomized to 500, 1000, or 2000 mg vitamin C. During each visit, a history including medication change was obtained and standardized blood pressure measurements were performed. A 1-week dietary diary was filled out before each visit. Multiple regression analysis and subsequent multiple comparisons were used for data analysis. Fifty-four patients satisfied our criteria and agreed to participate. Thirty-one patients (mean age, 62 +/- 2 years; 52% men, 90% whites) were randomized to the three doses of vitamin C. Overall compliance was 48 +/- 2%. Both mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased during the vitamin C supplementation phase [mean SBP dropped by 4.5 +/- 1.8 mm Hg (P <.05) and DBP by 2.8 +/- 1.2 mm Hg (P <.05)]. There was no difference between the three vitamin C groups (P =.48). This effect was significant for only 1 month of supplementation, but the trend persisted. There was no reported intolerance to vitamin C. There was no change in lipid levels after 6 months of treatment. Vitamin C supplementation lowers blood pressure in mildly hypertensive patients. There is no additional benefit for a higher dose than 500 mg daily. The effect of vitamin C is most likely to be only short term.
To examine the need for preventive and treatment interventions, a prevalence study was conducted to ascertain the rate of depressive symptomatology and other negative mood states among 112 first-year residents. The participation rate was 54%. Subjects (N = 61) were administered the Beck Depression Inventory and Profile of Mood States in personal interview sessions. The Profile measures five negative mood states, namely, "tension-anxiety," "depression-dejection," "anger-hostility," "fatigue-inertia," "confusion-bewilderment," and one positive state, "vigor-activity." A 15.5% rate of depression was found, which is lower than a rate of 23.5%, also measured by Beck's inventory, among a sample of university undergraduates and 19.9% among an adult sample from the general population. No differences were observed among residency programs or sex on Beck's scale; however, significantly higher scores were found for women on the "depression-dejection" dimension of the Profile. The mean scores on all negative mood dimensions of the Profile were below the mean for university undergraduate norms. Neither sleep nor hours worked over the past week were associated with increased Beck scores. These results indicate that sleep deprivation and long work hours did not contribute to depression among the subjects who participated in the study. Female interns, however, appear to be at increased risk of depression, and adequate support systems need to be provided.
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