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W B Applegate

Publications and source records attributed to W B Applegate.

At least 37 records · Page 2Linked to original sources
PubMed1999

Does syndrome X exist in hypertensive elderly persons with impaired glycemic control?

BACKGROUND: This report focuses on the glycemic state in relation to insulin and lipid levels of a cohort of elderly hypertensive persons to estimate the prevalence of syndrome X. METHODS: A cross-sectional study was performed at the University of Tennessee, Memphis, and the General Clinical Research Center (GCRC) on 95 participants in the Trial of Nonpharmacologic Interventions in the Elderly (TONE) study who agreed to participate in an ancillary study. A standard oral glucose tolerance test (OGTT) with insulin and C-peptide levels and a fasting lipid profile were obtained. RESULTS: In this sample of healthy elderly participants with hypertension who were taking an antihypertensive medication, 43 (45.3%) had normal glucose tolerance (NGT), 41 (43.2%) had impaired glucose tolerance (IGT), and 11 (11.6%) had undiagnosed non-insulin-dependent diabetes mellitus (NIDDM). Fasting hyperinsulinemia occurred in only one participant, who was in the IGT group. Hypertriglyceridemia and low high density lipoprotein (HDL) occurred in four persons, none of whom had hyperinsulinemia. Persons in the NIDDM and IGT groups had decreased beta cell function compared to persons in the NGT group, but did not have increased peripheral insulin resistance as estimated from the OGTT data. CONCLUSIONS: Our data demonstrated that in this cohort of elderly hypertensive participants with a high prevalence of central obesity, impaired glycemic control was common, but was not associated with fasting hyperinsulinemia or peripheral insulin resistance. Furthermore, we conclude that syndrome X essentially did not occur in these participants and postulate that the primary etiology for their impaired glycemic control is beta cell dysfunction. Further research is needed to elucidate these relationships.

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PubMed1998

Diuretic-based treatment and cardiovascular events in patients with mild renal dysfunction enrolled in the systolic hypertension in the elderly program.

BACKGROUND: It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events, but the evidence in these patients is lacking. OBJECTIVE: To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction. METHODS: A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were randomly assigned to receive either placebo or chlorthalidone (12.5-25.0 mg/d), with the addition of atenolol (25-50 mg/d) or reserpine (0.05-0.10 mg/d) if needed, and observed for 5 years. The risk of first-occurring cardiovascular events, including stroke, transient ischemic attack, myocardial infarction, heart failure, coronary artery bypass surgery, angioplasty, aneurysm, endarterectomy, sudden death, or rapid death, was stratified according to baseline serum creatinine levels (35.4-84.0, 84.1-101.6, 101.7-119.3, and 119.4-212.2 micromol/L [0.4-0.9, 1.0-1.1, 1.2-1.3, and 1.4-2.4 mg/dL]). RESULTS: Systolic blood pressure reduction was not affected by baseline serum creatinine levels. Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up. The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels. In the 4 baseline serum creatinine groups, the relative risk (95% confidence interval) of cardiovascular events developing with active treatment was 0.73 (0.54-0.97), 0.63 (0.49-0.82), 0.62 (0.44-0.87), and 0.59 (0.38-0.91). The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age. CONCLUSION: Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction.

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PubMed1998

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group.

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.

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PubMed1998

Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group.

CONTEXT: Nonpharmacologic interventions are frequently recommended for treatment of hypertension in the elderly, but there is a paucity of evidence from randomized controlled trials in support of this recommendation. OBJECTIVE: To determine whether weight loss or reduced sodium intake is effective in the treatment of older persons with hypertension. DESIGN: Randomized controlled trial. PARTICIPANTS: A total of 975 [corrected] men and women aged 60 to 80 years with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure lower than 85 mm Hg while receiving treatment with a single antihypertensive medication. SETTING: Four academic health centers. INTERVENTION: The 585 obese participants were randomized to reduced sodium intake, weight loss, both, or usual care, and the 390 nonobese participants were randomized to reduced sodium intake or usual care. Withdrawal of antihypertensive medication was attempted after 3 months of intervention. MAIN OUTCOME MEASURE: Diagnosis of high blood pressure at 1 or more follow-up visits, or treatment with antihypertensive medication, or a cardiovascular event during follow-up (range, 15-36 months; median, 29 months). RESULTS: The combined outcome measure was less frequent among those assigned vs not assigned to reduced sodium intake (relative hazard ratio, 0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese participants, among those assigned vs not assigned to weight loss (relative hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight loss combined. The frequency of cardiovascular events during follow-up was similar in each of the 6 treatment groups. CONCLUSION: Reduced sodium intake and weight loss constitute a feasible, effective, and safe nonpharmacologic therapy of hypertension in older persons.

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PubMed1998

Tennessee's failed managed care program for mental health and substance abuse services.

In July 1996, Tennessee initiated a managed mental health and substance abuse program called TennCare Partners. This publicly funded "carve-out" experiment started chaotically and soon deteriorated into a crisis. Many patients did not receive care or lost continuity of care, and the traditional "safety net" mental health system nearly disintegrated. This qualitative case study sought to ascertain the impact of the TennCare Partners program. It points out that the program's difficulties stemmed directly from a flawed design that spread funds previously earmarked for severely mentally ill patients across the entire Medicaid population. States contemplating similar reforms should strive to protect vulnerable patients by risk-adjusting capitation payments and by focusing resources on care for severely mentally ill persons. States should also minimize program complexity and ensure the accountability of managed care networks for their patients' behavioral health care needs.

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PubMed1998

The prognostic significance of asymptomatic carotid bruits in the elderly.

OBJECTIVE: To determine the association between asymptomatic carotid bruits and the development of subsequent stroke in older adults with isolated systolic hypertension. DESIGN: Retrospective cohort study. SETTING: The Systolic Hypertension in the Elderly Program (SHEP), a 5-year randomized trial testing the efficacy of treating systolic hypertension in noninstitutionalized persons aged 60 years or older. From the original 4,736 SHEP participants, we identified a cohort of 4,442 persons who had no prior history of stroke, transient ischemic attack, or myocardial infarction at randomization. MEASUREMENTS AND MAIN RESULTS: The end point for this ancillary study was the development of a stroke. The average follow-up was 4.2 years. Carotid bruits were found in 284 (6.4%) of the participants at baseline. Strokes developed in 21 (7.4%) of those with carotid bruits and in 210 (5.0%) of those without carotid bruits. The unadjusted risk of stroke among persons with carotid bruits was 1.53 (95% confidence interval [CI] 0.98, 2.40). Adjusting for age, gender, race, blood pressure, smoking, lipid levels, self-reported aspirin use, and treatment group assignment, the relative risk of stroke among persons with asymptomatic carotid bruits was 1.29 (95% CI 0.80, 2.06). Among SHEP enrollees aged 60 to 69 years, there was a trend (p = .08) toward increased risk (relative risk [RR] 2.05; 95% CI 0.92, 4.68) of subsequent stroke in persons with, compared to those without, carotid bruits. However, among enrollees aged 70 years or over, there was no relation between carotid bruit and subsequent stroke (RR 0.98; 95% CI 0.55, 1.76). In no other subgroup of SHEP enrollees did the presence of carotid bruit independently predict stroke. CONCLUSIONS: Although we cannot rule out a small increased risk of stroke associated with bruits in asymptomatic SHEP enrollees aged 60 to 69 years, the utility of carotid bruits as a marker for increased risk of stroke among asymptomatic elderly with isolated systolic hypertension aged 70 years or older is limited.

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PubMed1998

Activity Counseling Trial (ACT): rationale, design, and methods. Activity Counseling Trial Research Group.

The Activity Counseling Trial (ACT) is a multicenter, randomized controlled trial to evaluate the effectiveness of interventions to promote physical activity in the primary health care setting. ACT has recruited, evaluated, and randomized 874 men and women 35-75 yr of age who are patients of primary care physicians. Participants were assigned to one of three educational interventions that differ in amount of interpersonal contact and resources required: standard care control, staff-assisted intervention, or staff-counseling intervention. The study is designed to provide 90% power in both men and women to detect a 1.1 kcal.kg-1.day-1 difference in total daily energy expenditure between any two treatment groups, and over 90% power to detect a 7% increase in maximal oxygen uptake, the two primary outcomes. Primary analyses will compare study groups on mean outcome measures at 24 months post-randomization, be adjusted for the baseline value of the outcome measure and for multiple comparisons, and be conducted separately for men and women. Secondary outcomes include comparisons between interventions at 24 months of factors related to cardiovascular disease (blood lipids/lipoproteins, blood pressure, body composition, plasma insulin, fibrinogen, dietary intake, smoking, heart rate variability), psychosocial effect, and cost-effectiveness, and at 6 months for primary outcome measures. ACT is the first large-scale behavioral intervention study of physical activity counseling in a clinical setting, includes a generalizable sample of adult men and women and of clinical setting, and examines long-term (24 months) effects. ACT has the potential to make substantial contributions to the understanding of how to promote physical activity in the primary health care setting.

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PubMed1997

Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group.

CONTEXT: Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. OBJECTIVE: To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. DESIGN: Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). INTERVENTION: Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. MAIN OUTCOME MEASURES: Fatal and nonfatal heart failure. RESULTS: During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure. CONCLUSION: In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.

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PubMed1997

Effect of pharmacologic lipid lowering on health-related quality of life in older persons: results from the Cholesterol Reduction in Seniors Program (CRISP) Pilot Study.

OBJECTIVE: To determine the effect of lovastatin therapy on health-related quality of life in older persons. DESIGN: A prospective, randomized, double blind clinical trial. SETTING: Four university medical center research clinics. PARTICIPANTS: There were 431 men and women, primarily 65 years of age or older, with low density lipoprotein levels greater than 159 mg/dL and less than 221 mg/dL. Exclusion criteria included a Mini-Mental state score less than 24 or presence of recent cardiovascular events or other serious chronic disease likely to shorten survival. INTERVENTION: All participants were administered the National Cholesterol Education Program step one diet and were then randomized to placebo, 20 mg lovastatin, or 40 mg lovastatin. MEASUREMENTS: Areas of health-related quality of life assessed in the Cholesterol Reduction in Seniors Program (CRISP) included: (1) physical functioning, (2) sleep behavior, (3) social support, (4) depression, (5) cognitive function, and (6) health perception. Three global change questions asked the patients to judge change in general health since starting the study diet or the study medication and change in ability to function or care for self. Although some patients were followed for a total of 12 months, all participants were followed for 6 months, and 6-month data have been used for the primary analysis in this paper. RESULTS: Patients treated with 20 mg of lovastatin had a 17% and 24% reduction in total cholesterol and LDL-cholesterol, respectively. Patients treated with the 40-mg lovastatin dose achieved reductions of 20% for total cholesterol and 28% for LDL-cholesterol. Complaints of possible adverse events were remarkably similar in the two active treatment groups and the placebo group. At 6 months of follow-up there were no statistically significant differences found in mean change scores from baseline between treatment groups on the health-related quality of life measures (physical functioning, sleep, social support, depression, cognitive function scales, health perception) or global questions. CONCLUSIONS: This study demonstrates that lovastatin was extremely well tolerated in an older cohort, both with regard to symptoms and to health-related quality of life.

Activities of Daily Living↗
PubMed1997

Prevalence of undiagnosed non-insulin-dependent diabetes mellitus and impaired glucose tolerance in a cohort of older persons with hypertension.

OBJECTIVE: To determine the prevalence of undiagnosed non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in a cohort of older persons with hypertension. To examine the usefulness of screening for NIDDM in this study population. DESIGN: Cross-sectional study. SETTING: University of Tennessee, Memphis and the General Clinical Research Center (GCRC). PATIENTS: Ninety-five participants in the Trial of Nonpharmacologic Interventions in the Elderly (TONE) study who agreed to participate in an ancillary study. MEASUREMENTS: A standard oral glucose tolerance test (OGTT) with insulin and C-peptide levels was performed before the beginning of the TONE intervention. RESULTS: In this cohort, 43 participants (45.3%) had normal glucose tolerance (NGT), 41 (43.2%) had IGT, and 11 (11.6%) had undiagnosed NIDDM. The positive predictive value for NIDDM of a fasting glucose > or = 115 mg/dL in our participants was 57%. Hyperinsulinemia occurred in only one participant, a subject in the IGT group. CONCLUSIONS: Our data demonstrate that undiagnosed NIDDM is common in our cohort of older persons who are being treated for essential hypertension and that impaired glucose tolerance may be more common than in the general population of the same age. Further, our data show that the vast majority of this older, obese, hypertensive cohort did not have fasting hyperinsulinemia. We also infer that a fasting glucose alone has a low positive predictive value for screening of NIDDM in our older cohort. As the prevalence of NIDDM and impaired glucose tolerance in older hypertensive patients in the general population is unknown, we believe that further investigation is needed to characterize the relationship of hypertension, glycemic status, and hyperinsulinemia in the general population.

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