PubMed Health⌕ Search

Biomedical subjects

Jeffrey A Cutler

Publications and source records attributed to Jeffrey A Cutler.

At least 19 recordsLinked to original sources

Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

BACKGROUND: Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension. The significance of this finding is uncertain. Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic, calcium-channel blocker, or angiotensin-converting enzyme inhibitor on fasting glucose (FG) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus (DM) in 3 treatment groups. METHODS: We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) among nondiabetic participants who were randomized to receive treatment with chlorthalidone (n = 8419), amlodipine (n = 4958), or lisinopril (n = 5034) and observed for a mean of 4.9 years. RESULTS: Mean FG levels increased during follow-up in all treatment groups. At year 2, those randomized to the chlorthalidone group had the greatest increase (+8.5 mg/dL [0.47 mmol/L] vs +5.5 mg/dL [0.31 mmol/L] for amlodipine and +3.5 mg/dL [0.19 mmol/L] for lisinopril). The odds ratios for developing DM with lisinopril (0.55 [95% confidence interval, 0.43-0.70]) or amlodipine (0.73 [95% confidence interval, 0.58-0.91]) vs chlorthalidone at 2 years were significantly lower than 1.0 (P<.01). There was no significant association of FG level change at 2 years with subsequent coronary heart disease, stroke, cardiovascular disease, total mortality, or end-stage renal disease. There was no significant association of incident DM at 2 years with clinical outcomes, except for coronary heart disease (risk ratio, 1.64; P = .006), but the risk ratio was lower and nonsignificant in the chlorthalidone group (risk ratio, 1.46; P = .14). CONCLUSIONS: Fasting glucose levels increase in older adults with hypertension regardless of treatment type. For those taking chlorthalidone vs other medications, the risk of developing FG levels higher than 125 mg/dL (6.9 mmol/L) is modestly greater, but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events.

Aged↗

Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

BACKGROUND: Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. METHODS AND RESULTS: ALLHAT was a double-blind, randomized, clinical trial in 33,357 high-risk hypertensive patients aged > or =55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. CONCLUSIONS: HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.

Adrenergic beta-Antagonists↗

Clinical research in primary stroke prevention: needs, opportunities, and challenges.

Most ( approximately 70%) of strokes are first-ever strokes, and hence to substantially reduce the neurological burden, primary prevention is crucial. Here, highlights of the National Institute of Neurological Disorders and Stroke workshop "Stroke Risk Assessment and Future Stroke Primary Prevention Trials" held January 12-13, 2004 are summarized. The Workshop discussions focused on stroke risk assessment; the high-risk vs. population-based approaches to primary prevention; desirable characteristics of candidate treatments and potential novel treatments, such as the 'polypill'; subclinical disease as risk assessment tool and as surrogate outcome, and methodological issues in stroke primary prevention trials. The importance of assessing cognitive decline as an important consequence of covert and overt vascular injury of the brain was emphasized. The scientific or logistic barriers to stroke primary prevention trials are challenging, but are not insurmountable.

Cardiovascular Diseases↗

Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril.

CONTEXT: Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs). OBJECTIVE: To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease (CVD) incidence in racial subgroups. DESIGN, SETTING, AND PARTICIPANTS: Prespecified subgroup analysis of ALLHAT, a randomized, double-blind, active-controlled, clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older (35% black) with at least 1 other cardiovascular risk factor. INTERVENTIONS: Antihypertensive regimens initiated with a CCB (amlodipine) or an ACE inhibitor (lisinopril) vs a thiazide-type diuretic (chlorthalidone). Other medications were added to achieve goal blood pressures (BPs) less than 140/90 mm Hg. MAIN OUTCOME MEASURES: The primary outcome was combined fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined CVD (CHD death, nonfatal MI, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. RESULTS: No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup. For amlodipine vs chlorthalidone only, HF was the only prespecified clinical outcome that differed significantly (overall: relative risk [RR], 1.37; 95% confidence interval [CI], 1.24-1.51; blacks: RR, 1.46; 95% CI, 1.24-1.73; nonblacks: RR, 1.32; 95% CI, 1.17-1.49; P<.001 for each comparison) with no difference in treatment effects by race (P = .38 for interaction). For lisinopril vs chlorthalidone, results differed by race for systolic BP (greater decrease in blacks with chlorthalidone), stroke, and combined CVD outcomes (P<.001, P = .01, and P = .04, respectively, for interactions). In blacks 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) and for combined CVD were 1.19 (95% CI, 1.09-1.30) and 1.06 (95% CI, 1.00-1.13). For HF, the RRs were 1.30 (95% CI, 1.10-1.54) and 1.13 (95% CI, 1.00-1.28), with no significant interaction by race. Time-dependent BP adjustment did not significantly 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.

Aged↗

ALLHAT: setting the record straight.

The findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) have generated worldwide reaction from clinicians and researchers, including a recent commentary in this journal. Such response was expected for a trial of ALLHAT's size and scope, especially since its results challenged some widely held beliefs. This paper reviews key aspects of the ALLHAT design, analyses, findings, and conclusions to provide a perspective on the commentary about the trial's results and implications for clinical practice. Several of the most frequent comments regarding the study's results are addressed, particularly with respect to heart failure and diabetes outcomes. Responses to these comments reinforce the investigators' original conclusion that thiazide-type diuretics should remain the preferred first-step drug class for treating hypertension and should generally be a part of any multidrug regimen.

Antihypertensive Agents↗

Trends in blood pressure among children and adolescents.

CONTEXT: The prevalence of overweight among children and adolescents increased between 1988 and 2000. The change in blood pressure among children and adolescents over that time and the role of overweight is unknown. OBJECTIVE: To examine trends in systolic and diastolic blood pressure among children and adolescents between 1988 and 2000. DESIGN, SETTING, AND POPULATION: Two serially conducted cross-sectional studies using nationally representative samples of children and adolescents, aged 8 to 17 years, from the third National Health and Nutrition Examination Survey (NHANES III) conducted in 1988-1994 (n = 3496) and NHANES 1999-2000 (n = 2086). MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure levels. RESULTS: In 1999-2000, the mean (SE) systolic blood pressure was 106.0 (0.3) mm Hg and diastolic blood pressure was 61.7 (0.5) mm Hg. After adjustment for age, mean systolic blood pressure was 1.6 mm Hg higher among non-Hispanic black girls (P =.11) and 2.9 mm Hg higher among non-Hispanic black boys (P<.001) compared with non-Hispanic whites. Among Mexican Americans, girls' systolic blood pressure was 1.0 mm Hg higher (P =.21) and boys' was 2.7 mm Hg higher (P<.001) compared with non-Hispanic whites (P<.001). With further adjustment for body mass index, these differences were attenuated. After age, race/ethnicity, and sex standardization, systolic blood pressure was 1.4 (95% confidence interval [CI], 0.6-2.2) mm Hg higher (P<.001) and diastolic blood pressure was 3.3 (95% CI, 2.1-4.5) mm Hg higher in 1999-2000 (P<.001) compared with 1988-1994. With further adjustment for differences in the body mass index distribution in 1988-1994 and 1999-2000, the increase in systolic blood pressure was reduced by 29% and diastolic blood pressure was reduced by 12%. CONCLUSIONS: Blood pressure has increased over the past decade among children and adolescents. This increase is partially attributable to an increased prevalence of overweight.

Adolescent↗

Individual blood pressure responses to changes in salt intake: results from the DASH-Sodium trial.

Although group characteristics are known to influence average blood pressure response to changes in salt intake, predictability of individual responses is less clear. We examined variability and consistency of individual systolic blood pressure responses to changes in salt intake in 188 participants who ate the same diet at higher, medium, and lower (140, 104, 62 mmol/d) sodium levels for 30 days each, in random order, after 2 weeks of run-in at the higher sodium level. Regarding variability in systolic blood pressure changes over time, changes from run-in to higher sodium (no sodium level change) ranged from -24 to +25 mm Hg; 8.0% of participants decreased > or =10 mm Hg. Regarding variability in systolic blood pressure response to change in sodium intake, with higher versus lower sodium levels (78-mmol sodium difference), the range of systolic blood pressure change was -32 to +17 mm Hg; 33.5% decreased > or =10 mm Hg. Regarding consistency of response, systolic blood pressure change with run-in versus lower sodium was modestly correlated with systolic blood pressure change with higher versus medium sodium; systolic blood pressure change with higher versus lower sodium was similarly correlated with run-in versus medium sodium (combined Spearman r=0.27, P=0.002). These results show low-order consistency of response and confirm that identifying individuals as sodium responders is difficult. They support current recommendations for lower salt intake directed at the general public rather than "susceptible" individuals as one of several strategies to prevent and control adverse blood pressures widely prevalent in the adult population.

Adult↗

Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy.

A Working Group on Research in Hypertension in Pregnancy was recently convened by the National Heart Lung and Blood Institute to determine the state of knowledge in this area and suggest appropriate directions for research. Hypertensive disorders in pregnancy, especially preeclampsia, are a leading cause of maternal mortality worldwide and even in developed countries increase perinatal mortality five-fold. Much has been learned about preeclampsia but gaps in the knowledge necessary to direct therapeutic strategies remain. Oxidative stress is a biologically plausible contributor to the disorder that may be amenable to intervention. Hypertension that antedates pregnancy (chronic hypertension) bears many similarities to hypertension in nonpregnant women but the special setting of pregnancy demands information to guide evidence based therapy. The recommendations of the Working Group are to attempt a clinical trial of antioxidant therapy to prevent preeclampsia that is be complemented by mechanistic research to increase understanding of the genetics and pathogenesis of the disorder. For chronic hypertension clinical trials are recommended to direct choice of drugs, evaluate degree of control and assess implications to the mother and fetus. Recommendations to increase participation in this research are also presented.

Adult↗

Low-fat diet: effect on anthropometrics, blood pressure, glucose, and insulin in older women.

OBJECTIVE: The Women's Health Trial: Feasibility Study in Minority Populations (WHT: FSMP) documented that a low-fat diet was associated with a reduced fat intake in older women of diverse ethnic backgrounds. The purpose of the current study was to examine the effect of the low-fat diet on anthropometric and biochemical variables. DESIGN: Randomized clinical trial in 2,208 postmenopausal women, 50 to 79 years of age. RESULTS: The decrease in fat intake correlated directly with a decrease in body weight (r=.22, P<.001). After 6 months, the intervention group had an average weight loss of 1.8 kg. Body mass index decreased 0.7 kg/m2. Waist circumference decreased 1.8 cm. All of these changes were statistically significant, compared to changes in the control group (P<.01). Changes in systolic (-3.1 mm Hg) and diastolic (-1.1 mm Hg) blood pressures (BP) occurred in the intervention group. The decrease in systolic BP reached statistical significance (P=.02), relative to the control group. Decreases in plasma glucose were small (-0.2 mmol/L) in the intervention group, although there was a trend for difference from the control group (P=.11). Decreases in serum insulin levels were small (-0.5 microIU/mL) in the intervention group, although there was, again, a trend for difference from the control group. CONCLUSIONS: In older White, Black, and Hispanic women, a long-term low-fat dietary intervention was accompanied by modest, but statistically significant, decreases in body weight and anthropometric indices, without any particular attempt being made to reduce calories. Changes in glucose and insulin were small. The long-term biological significance of the glucose and insulin changes is unknown.

Aged↗