Showing papers by "Barry R. Davis published in 2005"

Outcomes in Hypertensive Black and Nonblack Patients Treated With Chlorthalidone, Amlodipine, and Lisinopril

Abstract: and nonblacks, respectively, the RRs for stroke were 1.40 (95% CI, 1.17-1.68) and 1.00 (95%CI,0.85-1.17)andforcombinedCVDwere1.19(95%CI,1.09-1.30)and1.06(95% CI, 1.00-1.13). For HF, the RRs were 1.30 (95% CI, 1.10-1.54) and 1.13 (95% CI, 1.001.28),withnosignificantinteractionbyrace.Time-dependentBPadjustmentdidnotsignificantly alter differences in outcome for lisinopril vs chlorthalidone in blacks. Conclusions In blacks and nonblack subgroups, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome, and diuretic-based treatment resulted in the lowest risk of heart failure. While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks, thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients.

Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Abstract: Background This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. Methods We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (≥90 mL /min per 1.73m 2 , n = 8126), mild reduction (60-89 mL /min per 1.73 m 2 , n = 18 109), or moderate-severe reduction ( 2 , n = 5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. Results In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR, 0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR, 0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [ P = .74] and 0.85 [ P = .23], respectively) and lisinopril (odds ratios, 1.13 [ P = .31] and 1.00 [ P = .98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL /min per 1.73 m 2 higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. Conclusions In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups.

Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes

Abstract: Diuretic-based antihypertensive therapy is associated with the development of diabetes but with improved clinical outcomes. It has been proposed that the duration of clinical trials has been too short to detect the adverse effects of diabetes. We assessed the long-term mortality rate of subjects in the Systolic Hypertension in the Elderly Program (n = 4,732) who were randomized to stepped-care therapy with 12.5 to 25.0 mg/day of chlorthalidone or matching placebo. If blood pressure remained above the goal, atenolol or matching placebo was added. At a mean follow-up of 14.3 years, cardiovascular (CV) mortality rate was significantly lower in the chlorthalidone group (19%) than in the placebo group (22%; adjusted hazard ratio [HR] 0.854, 95% confidence interval [CI] 0.751 to 0.972). Diabetes at baseline (n = 799) was associated with increased CV mortality rate (adjusted HR 1.659, 95% CI 1.413 to 1.949) and total mortality rate (adjusted HR 1.510, 95% CI 1.347 to 1.693). Diabetes that developed during the trial among subjects on placebo (n = 169) was also associated with increased CV adverse outcome (adjusted HR 1.562, 95% CI 1.117 to 2.184) and total mortality rate (adjusted HR 1.348, 95% CI 1.051 to 1.727). However, diabetes that developed among subjects during diuretic therapy (n = 258) did not have significant associations with CV mortality rate (adjusted HR 1.043, 95% CI 0.745 to 1.459) or total mortality rate (adjusted HR 1.151, 95% CI 0.925 to 1.433). Diuretic treatment in subjects who had diabetes was strongly associated with lower long-term CV mortality rate (adjusted HR 0.688, 95% CI 0.526 to 0.848) and total mortality rate (adjusted HR 0.805, 95% CI 0.680 to 0.952). Thus, chlorthalidone-based treatment improved long-term outcomes, especially among subjects who had diabetes. Subjects who had diabetes associated with chlorthalidone had no significant increase in CV events and had a better prognosis than did those who had preexisting diabetes.

Clinical Outcomes in Antihypertensive Treatment of Type 2 Diabetes, Impaired Fasting Glucose Concentration, and Normoglycemia: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Abstract: Background Optimal first-step antihypertensive drug therapy in type 2 diabetes mellitus (DM) or impaired fasting glucose levels (IFG) is uncertain. We wished to determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor decreases clinical complications compared with treatment with a thiazide-type diuretic in DM, IFG, and normoglycemia (NG). Methods Active-controlled trial in 31 512 adults, 55 years or older, with hypertension and at least 1 other risk factor for coronary heart disease, stratified into DM (n = 13 101), IFG (n = 1399), and NG (n = 17 012) groups on the basis of national guidelines. Participants were randomly assigned to double-blind first-step treatment with chlorthalidone, 12.5 to 25 mg/d, amlodipine besylate, 2.5 to 10 mg/d, or lisinopril, 10 to 40 mg/d. We conducted an intention-to-treat analysis of fatal coronary heart disease or nonfatal myocardial infarction (primary outcome), total mortality, and other clinical complications. Results There was no significant difference in relative risk (RR) for the primary outcome in DM or NG participants assigned to amlodipine or lisinopril vs chlorthalidone or in IFG participants assigned to lisinopril vs chlorthalidone. A significantly higher RR (95% confidence interval) was noted for the primary outcome in IFG participants assigned to amlodipine vs chlorthalidone (1.73 [1.10-2.72]). Stroke was more common in NG participants assigned to lisinopril vs chlorthalidone (1.31 [1.10-1.57]). Heart failure was more common in DM and NG participants assigned to amlodipine (1.39 [1.22-1.59] and 1.30 [1.12-1.51], respectively) or lisinopril (1.15 [1.00-1.32] and 1.19 [1.02-1.39], respectively) vs chlorthalidone. Conclusion Our results provide no evidence of superiority for treatment with calcium channel blockers or angiotensin-converting enzyme inhibitors compared with a thiazide-type diuretic during first-step antihypertensive therapy in DM, IFG, or NG.

Ethnic differences in the relationships between obesity and glucose-metabolic abnormalities: a cross-sectional population-based study.

Abstract: To evaluate whether body mass index (BMI) and other anthropometric indices of visceral obesity vary by ethnic group in their distribution and their relationship to metabolic abnormalities. Cross-sectional study. Canadian men and women, aged 35–75 years, of South Asian (n=342), Chinese (n=317), European (n=326) and Aboriginal (n=301) descent were recruited using stratified random sampling. Anthropometric indices (BMI, waist to hip ratio (WHR) and waist circumference (WC)), metabolic markers (fasting glucose, HbA1c, the ratio of total cholesterol/HDL) and clinical markers (systolic blood pressure) were assessed. In subjects with BMI 88 cm in women, >102 cm in men) vs people with normal WC were 6.16 vs 5.34 mmol/l for fasting glucose, 6.05 vs 5.66% for HbA1c and 5.46 vs 4.68 for the ratio of total cholesterol to HDL (P<0.001 in each case). At nearly every given level of BMI, non-European ethnic groups displayed significantly higher marker levels than Europeans. For example, for a given BMI, age and sex, the difference between European and non-European groups in HbA1c levels was 0.53% (95% confidence interval (CI): 0.37–0.69) for South Asians, 0.37% (95% CI: 0.2–0.54) for Chinese and 0.95% (95% CI: 0.78–1.12) for Aboriginal People. Uniform cut-points for the classification of obesity using BMI, WHR or WC result in marked variation in the levels of glucose-metabolic abnormalities between ethnic groups. Existing action thresholds for these anthropometric indices do not apply to non-European ethnic groups and warrant revision.

Pharmacogenetic Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Antihypertensive Treatment The Genetics of Hypertension-Associated Treatment (GenHAT) Study

Abstract: Background— Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system, but no clinical trails have tested whether the ACE insertion/deletion (I/D) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes. Methods and Results— We used a double-blind, active-controlled randomized trial of antihypertensive treatment that included hypertensives ≥55 years of age with ≥1 risk factor for cardiovascular disease. ACE I/D genotypes were determined in 37 939 participants randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatments and followed up for 4 to 8 years. Primary outcomes included fatal coronary heart disease (CHD) and/or nonfatal myocardial infarction. Secondary outcomes included stroke, all-cause mortality, combined CHD, and combined cardiovascular disease. Fatal and nonfatal CHD occurred in 3096 individuals during fo...

Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a Diuretic A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Abstract: Background: This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. Methods: We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (90 mL /min per 1.73 m 2 , n=8126), mild reduction (60-89 mL/min per 1.73 m 2 , n=18 109), or moderate-severe reduction (60 mL/min per 1.73 m 2 , n=5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. Results: In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR,0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR,0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P=.23], respectively) and lisinopril (odds ratios, 1.13 [P=.31] and 1.00 [P=.98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL/min per 1.73 m 2 higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. Conclusions: In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups. Arch Intern Med. 2005;165:936-946

Diabetes mellitus, smoking, and the risk for asymptomatic peripheral arterial disease: Whom should we screen?

Abstract: Objective: To describe coexisting medical conditions and lifestyle factors associated with asymptomatic peripheral arterial disease (PAD) in a population of white, African American, and Hispanic patients. Study Design and Setting: White, African American, and Hispanic patients 50 years or older were recruited for this cross-sectional study from 4 primary care clinics in Houston, TX. Patients with an ankle-brachial index (ABI) Results: 403 patients were screened for PAD. Of these, 25 (6.2%) had asymptomatic PAD. Compared with patients without PAD, diabetes mellitus ([OR] 3.8; 95% CI 1.6, 9.0) and a history of smoking at least 1 pack of cigarettes per day ([OR] 2.5; 95% CI 1.1, 6.0) were significantly associated with asymptomatic PAD. An interaction effect existed between diabetes mellitus and smoking at least 1 pack of cigarettes per day. Diabetes mellitus combined with heavy smoking showed the highest predicted value positive (15%) and the highest specificity (92%). A lack of both demonstrated low rates for predicting asymptomatic PAD (predicted value positive, 1%). Conclusion: The ankle-brachial index could become routine screening among patients with diabetes mellitus and/or who smoke.