Dawn Stewart

Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) trials and registry

Diabetes is an independent predictor of morbidity and mortality in patients with symptomatic heart failure, patients with asymptomatic left ventricular dysfunction (defined as an ejection fraction of 35% or less), and in a broader registry population with less stringent entry criteria. Although the SOLVD Trials made a major clinical contribution by proving the value of enalapril, diabetes remains a significant predictor of outcome even after adjusting for treatment with enalapril.

Effects of periodontal therapy on rate of preterm delivery: A randomized controlled trial

OBJECTIVE: To test the effects of maternal periodontal disease treatment on the incidence of preterm birth (delivery before 37 weeks of gestation). METHODS: The Maternal Oral Therapy to Reduce Obstetric Risk Study was a randomized, treatment-masked, controlled clinical trial of pregnant women with periodontal disease who were receiving standard obstetric care. Participants were assigned to either a periodontal treatment arm, consisting of scaling and root planing early in the second trimester, or a delayed treatment arm that provided periodontal care after delivery. Pregnancy and maternal periodontal status were followed to delivery and neonatal outcomes until discharge. The primary outcome (gestational age less than 37 weeks) and the secondary outcome (gestational age less than 35 weeks) were analyzed using a χ2 test of equality of two proportions. RESULTS: The study randomized 1,806 patients at three performance sites and completed 1,760 evaluable patients. At baseline, there were no differences comparing the treatment and control arms for any of the periodontal or obstetric measures. The rate of preterm delivery for the treatment group was 13.1% and 11.5% for the control group (P=.316). There were no significant differences when comparing women in the treatment group with those in the control group with regard to the adverse event rate or the major obstetric and neonatal outcomes. CONCLUSION: Periodontal therapy did not reduce the incidence of preterm delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00097656. LEVEL OF EVIDENCE: I

Clinical characteristics of patients in studies of left ventricular dysfunction (SOLVD).

The Studies of Left Ventricular Dysfunction (SOLVD) trials were designed to evaluate the effects of enalapril on long-term mortality in patients with severe left ventricular (LV) dysfunction. Patients with LV ejection fractions less than or equal to 0.35 and symptoms of congestive heart failure (CHF) were enrolled in the treatment trial, whereas those with no history of overt CHF and taking no treatment directed for LV dysfunction were enrolled in the prevention trial. The baseline clinical characteristics of SOLVD patients were compared to characterize differences between patients in these 2 separate but concurrent trials. From over 70,000 patients screened with LV dysfunction, 4,228 patients were enrolled in the prevention trial and 2,569 patients in the treatment trial. Ischemic heart disease was the primary cause of LV dysfunction in both prevention (83%) and treatment (71%) trial patients. Prior myocardial infarction was present in 80% of the prevention and 66% of the treatment trial patients (p less than 0.001). In the prevention trial, infarction was recent (less than or equal to 6 months) in 27% patients and remote (greater than 6 months) in 57% patients. Treatment trial patients had proportionately more women (20 vs 13%; p less than 0.001) and non-Caucasians (20 vs 14%; p less than 0.001), as well as the coexisting risk factors of hypertension (42 vs 37%; p less than 0.001) and diabetes (26 vs 15%; p less than 0.001) than did prevention trial patients. Clinical characteristics of patients in both trials were influenced by the gender and race of enrolled patients. Similarly, coronary artery bypass surgery was performed less often in women and non-Caucasians.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical activity assessment in American Indian schoolchildren in the Pathways study

The objective of the Pathways physical activity feasibility study was to develop methods for comparing type and amount of activity between intervention and control schools participating in a school-based obesity prevention program. Two methods proved feasible: 1) a specially designed 24-h physical activity recall questionnaire for assessing the frequency and type of activities and 2) use of a triaxial accelerometer for assessing amount of activity. Results from pilot studies supporting the use of these methods are described. Analyses of activity during different segments of the day showed that children were most active after school. The activities reported most frequently (e.g., basketball and mixed walking and running) were also the ones found to be most popular in the study population on the basis of formative assessment surveys. Both the physical activity recall questionnaire and the triaxial accelerometer methods will be used to assess the effects of the full-scale intervention on physical activity.

Metformin for Weight Loss and Metabolic Control in Overweight Outpatients With Schizophrenia and Schizoaffective Disorder

OBJECTIVE The purpose of this study was to determine whether metformin promotes weight loss in overweight outpatients with chronic schizophrenia or schizoaffective disorder. METHOD In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were randomly assigned to receive 16 weeks of metformin or placebo. Metformin was titrated up to 1,000 mg twice daily, as tolerated. All patients continued to receive their prestudy medications, and all received weekly diet and exercise counseling. The primary outcome measure was change in body weight from baseline to week 16. RESULTS Fifty-eight (77.3%) patients who received metformin and 58 (81.7%) who received placebo completed 16 weeks of treatment. Mean change in body weight was -3.0 kg (95% CI=-4.0 to -2.0) for the metformin group and -1.0 kg (95% CI=-2.0 to 0.0) for the placebo group, with a between-group difference of -2.0 kg (95% CI=-3.4 to -0.6). Metformin also demonstrated a significant between-group advantage for BMI (-0.7; 95% CI=-1.1 to -0.2), triglyceride level (-20.2 mg/dL; 95% CI=-39.2 to -1.3), and hemoglobin A1c level (-0.07%; 95% CI=-0.14 to -0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation. CONCLUSIONS Metformin was modestly effective in reducing weight and other risk factors for cardiovascular disease in clinically stable, overweight outpatients with chronic schizophrenia or schizoaffective disorder over 16 weeks. A significant time-by-treatment interaction suggests that benefits of metformin may continue to accrue with longer treatment. Metformin may have an important role in diminishing the adverse consequences of obesity and metabolic impairments in patients with schizophrenia.

Baseline Characteristics of the Study Population in the Diabetes Atherosclerosis Intervention Study (DAIS)

The Diabetes Atherosclerosis Intervention Study (DAIS) is the first study designed a priori to determine whether correcting dyslipoproteinemia in type II diabetes will alter coronary atherosclerosis. It is a multinational randomized double-blind, placebo-controlled trial using micronized fenofibrate. Its primary end point is a change in the average mean segment diameter determined on coronary angiograms taken at the beginning and end of the treatment period. This study describes the population baseline characteristics. Four hundred eighteen individuals (305 men and 113 women) were randomized; 168 patients were from Canadian clinics and 250 from those in Europe. Because the patients in both regions were very similar, it was possible to pool their data. All had > or = 1 minimally visible lesion on coronary angiography. Their average (+/-SD) lipid levels were: triglycerides 2.42 +/- 1.00 mmol/L, total cholesterol 5.57 +/- 0.70 mmol/L, low-density lipoprotein cholesterol 3.43 +/- 0.70 mmol/L, and high-density lipoprotein cholesterol 1.03 +/- 0.20 mmol/L. They were in very good glycemic control (hemoglobin A1c [HbA1c] 7.51 +/- 1.20%). The remainder of the coronary risk factors and demographic characteristics are described in the following. The characteristics of the DAIS population should determine whether correcting the dyslipoproteinemia seen in type II diabetes alters the progression and/or regression of angiographically determined coronary disease, to ascertain whether there is a difference between those with previous coronary intervention and those without, and to determine whether there is a gender effect.

Acute and long-term effects of the angiotensin-converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction

Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of Left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 1 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular ejection fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy.

Factors influencing exercise performance in patients with left ventricular dysfunction

BACKGROUND The determinants of exercise performance are multifactorial and incompletely understood in patients with symptomatic left ventricular (LV) dysfunction, with much less information regarding asymptomatic LV dysfunction. This study assessed the hemodynamics and neurohormonal factors influencing exercise performance in patients with LV ejection fractions > or =0.35, both symptomatic and asymptomatic, enrolled in Studies of LV Dysfunction. METHODS AND RESULTS We studied 103 patients enrolled prospectively in Studies of LV Dysfunction before randomized therapy; 38 were symptomatic and 65 had no or minimal symptoms. By using rest-exercise gated equilibrium radionuclide ventriculography and cuff blood pressure, we assessed the heart rate, LV and right ventricular (RV) volumes and ejection fractions, total peripheral resistance, the LV peak systolic pressure/end systolic volume ratio as an index of contractility, and plasma renin and norepinephrine at rest and during maximal graded supine bicycle ergometer exercise. Changes between rest and exercise were evaluated as indices of cardiovascular reserve. The cumulative workload ranged from 120 to 2,100 watt-min. At rest, the LV ejection fraction was 0.30 in asymptomatic patients and 0.25 in symptomatic patients, respectively (P < .0004). During exercise, asymptomatic patients had greater increases in heart rate, systolic blood pressure, LV ejection fraction, and cardiac output than symptomatic patients (P > or = .05). Combining all patients, the strongest univariate correlates of exercise workload were the ability to increase heart rate (r = 0.70), the pressure/volume ratio (r = 0.63), and systolic blood pressure (r = 0.55), and to decrease the total peripheral resistance (r = -0.47) with moderate correlations for the ability to increase LV and RV ejection fractions (r = 0.33 and 0.35, respectively) (P < .0008). By multivariate analysis, workload was modeled best by the changes in four factors: heart rate, systolic blood pressure, and the LV and RV ejection fractions (R2 = 0.54, P < .001). CONCLUSION Exercise performance and its hemodynamics differed in patients with symptomatic and asymptomatic LV dysfunction. Rather than features at rest, the reserve capacities for increasing heart rate, systolic blood pressure, and the LV and RV ejection fractions were the predominant cardiac mechanisms related to greater exercise performance.