Treating acute exacerbations of COPD with Chinese herbal medicine to aid antibiotic use reduction (Excalibur): a randomised double-blind, placebo-controlled feasibility trial.

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine "Shufeng Jiedu" (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD. Aims: To assess the feasibility of conducting a randomised placebo-controlled clinical trial of SFJD for AECOPD in UK primary care. Methods: GPs opportunistically recruited patients experiencing an AECOPD. Participants were randomised 1:1 to usual care plus SFJD or placebo for 14 days. Participants, GPs and research nurses were blinded to treatment allocation. GPs could prescribe immediate, delayed or no antibiotics, with delayed prescribing encouraged where appropriate. Participants were asked to complete a participant diary, including EXACT-PRO and CAT™ questionnaires for up to 4 weeks. Outcomes included recruitment rate and other measures of study feasibility described using only descriptive statistics and with no formal comparisons between groups. We also conducted qualitative interviews with recruited and non-recruited COPD patients and clinicians, analysed using framework analysis. Results: Over 6 months, 19 participants (6 SFJD, 13 placebo) were recruited. Sixteen (84%) participants returned diaries or provided a diary by recall. Overall, 1.3 participants were recruited per 1,000 patients on the COPD register per month open. Median duration of treatment was 9.8 days in the intervention group vs 13.3 days in the placebo group. The main reason for discontinuation in both groups was perceived side-effects. in both groups. Point estimates for both the EXACT-PRO and CAT™ outcomes suggested possible small benefits of SFJD. Most patients and clinicians were happy to try SFJD as an alternative to antibiotics for AECOPD. Recruitment was lower than expected because of the short recruitment period, the lower incidence of AECOPD during the COVID-19 pandemic, patients starting antibiotics from "rescue packs" before seeing their GP, and workforce challenges in primary care. Conclusion: Recruitment was impaired by the COVID-19 pandemic. Nevertheless, we were able to demonstrate the feasibility of recruiting and randomising participants and identified approaches to address recruitment challenges such as including the trial medication in COPD patients' "rescue packs" and delegating recruitment to a central trials team. Clinical Trial Registration: Identifier, ISRCTN26614726.

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.

Repurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high-dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin ) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID-19.

Independent prognostic value of echocardiography and N-terminal pro-B-type natriuretic peptide in patients with heart failure.

BACKGROUND: Echocardiographic indices of cardiac structure and function and natriuretic peptide levels are strong predictors of mortality in patients with heart failure. Whether cardiac ultrasound and natriuretic peptides provide independent prognostic information is uncertain. METHODS: Echocardiograms and measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) were prospectively performed in 211 patients with left ventricular systolic dysfunction who were followed for a median of 4 years. Echocardiographic variables and NT-proBNP were examined as predictors of all-cause mortality in univariable and multivariable proportional hazards models. RESULTS: Participants averaged 57 years old (SD 12 years) and had a mean left ventricular ejection fraction of 32% (SD 11%). A total of 71 patients (34%) died during the follow-up period. N-terminal pro-brain natriuretic peptide was a strong predictor of mortality (P < .001) as were multiple echocardiographic measures. In models that included age and NT-proBNP, with other clinical variables eligible for entry by stepwise selection, significant predictors of death included left ventricular ejection fraction (P = .013) and end-diastolic volume (P < .001), left atrial volume index (P = .005), right atrial volume index (P = .003), and tricuspid regurgitation area (P = .015). In models that also included left ventricular ejection fraction, end-diastolic volume of the left ventricle (P = .019), left atrial volume (P = .026), and right atrial volume (P = .020) remained significant predictors of mortality. CONCLUSIONS: Left ventricular size and function and left atrial and right atrial sizes are significant predictors of all-cause mortality in patients with heart failure, independent of NT-proBNP levels and other clinical variables.

Relationship of depression to death or hospitalization in patients with heart failure.

BACKGROUND: Depression is widely recognized as a risk factor in patients with coronary heart disease. However, patients with heart failure (HF) have been less frequently studied, and the effect of depression on prognosis, independent of disease severity, is uncertain. METHODS: Two hundred four outpatients having a diagnosis of HF, with a ventricular ejection fraction of 40% or less, underwent baseline assessments including evaluation of depressive symptoms using the Beck Depression Inventory and of HF severity determined by plasma N-terminal pro-B-type natriuretic peptide. Cox proportional hazards regression analyses were used to examine the effects of depressive symptoms on a combined primary end point of death and hospitalizations because of cardiovascular disease (hereafter referred to as cardiovascular hospitalization) during a median follow-up of 3 years. RESULTS: Symptoms of depression (Beck Depression Inventory score) were associated with risk of death or cardiovascular hospitalization (P<.001) after controlling for established risk factors including HF disease severity, ejection fraction, HF etiology, age, and medications. Clinically significant symptoms of depression (Beck Depression Inventory score >/=10) were associated with a hazard ratio of 1.56 (95% confidence interval, 1.07-2.29) for the combined end point of death or cardiovascular hospitalization. Contrary to our expectation, antidepressant medication use was associated with increased likelihood of death or cardiovascular hospitalization (hazard ratio, 1.75; 95% confidence interval,1.14-2.68, P =.01) after controlling for severity of depressive symptoms and for established risk factors. CONCLUSIONS: Symptoms of depression were associated with an adverse prognosis in patients with HF after controlling for HF severity. The unexpected association of antidepressant medications with worse clinical outcome suggests that patients with HF requiring an antidepressant medication may need to be monitored more closely.

Cerebrovascular risk factors, vascular disease, and neuropsychological outcomes in adults with major depression.

OBJECTIVE: To investigate the relationship of cerebrovascular risk factors (CVRFs), endothelial function, carotid artery intima medial thickness (IMT), and neuropsychological performance in a sample of 198 middle-aged and older individuals with major depressive disorder (MDD). Neuropsychological deficits are common among adults with MDD, particularly among those with CVRFs and potentially persons with subclinical vascular disease. METHODS: CVRFs were indexed by the Framingham Stroke Risk Profile (FSRP) and serum cholesterol levels obtained by medical history and physical examination. Patients completed a neuropsychological test battery including measures of executive functioning, working memory, and verbal recall. Vascular function was indexed by carotid artery IMT and brachial artery flow mediated dilation (FMD). Hierarchical multiple regression analyses were used to investigate the association between CVRFs, vascular disease, and neurocognitive performance. RESULTS: Greater FSRP scores were associated with poorer executive functioning (b = -0.86; p = .041) and working memory (b = -0.90; p = .024). Lower high-density lipoprotein levels also were associated with poorer executive functioning (b = 1.03; p = .035). Higher IMT (b = -0.83; p = .028) and lower FMD (b = 1.29; p = .032) were associated with poorer executive functioning after controlling for CVRFs. Lower FMD was also associated with poorer working memory (b = 1.58; p = .015). CONCLUSIONS: Greater CVRFs were associated with poorer neuropsychological performance. Vascular dysfunction also was associated with neuropsychological decrements independent of traditional CVRFs.

Exercise and pharmacotherapy in the treatment of major depressive disorder.

OBJECTIVE: To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. METHODS: Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50-200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). RESULTS: After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). CONCLUSIONS: The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors.

Ulnar tunnel syndrome.

As our understanding of the anatomy of the ulnar tunnel has increased, so too has our ability to clinically predict the specific sites of compression in ulnar tunnel syndrome. Anatomic studies have described in detail the course of the ulnar nerve as it passes through the ulnar tunnel and have helped correlate symptoms with anatomic location. Although the most common cause of compression is from a ganglion, other space-occupying lesions, such as tumors, anomalous muscles, or a thrombosed ulnar artery, are important to consider in the initial evaluation of the patient. While conservative management can sometimes be successful, the mainstay of treatment of this condition remains meticulous surgical exploration and decompression.

In situ decompression of the ulnar nerve at the cubital tunnel.

Cubital tunnel syndrome is a clinical entity that has been described for more than a century. Numerous conservative and surgical treatments have evolved to address this condition, but a consensus has yet to emerge regarding optimal treatment. Evidence suggests a limited but potentially valuable role for in situ decompression of the ulnar nerve at the cubital tunnel. Future research will undoubtedly clarify this role and contribute to the development of a standard treatment protocol.

Impaired endothelial function in coronary heart disease patients with depressive symptomatology.

OBJECTIVES: The purpose of this study was to assess whether depressive symptomatology was associated with vascular endothelial dysfunction in patients with coronary heart disease (CHD). BACKGROUND: In patients with CHD, the presence of depression is associated with a two to four times increased risk of mortality, but the disease pathways involved are uncertain. Endothelial dysfunction is an established risk factor for cardiovascular events in patients with CHD. METHODS: Flow-mediated dilation (FMD) of the brachial artery, a measure of endothelial function, was assessed in 143 patients (99 men, 44 women), ages 40 to 84 years (mean age, 63 +/- 10 years), with documented CHD. RESULTS: Patients with significant depressive symptomatology, as indicated by a Beck Depression Inventory (BDI) score > or = 10 (n = 47) showed attenuated FMD (p = 0.001) compared with patients that were not depressed (BDI < 10; n = 96). The use of antidepressant medication was associated with improved FMD (p < 0.05). CONCLUSIONS: The increased risk of cardiovascular events in CHD patients with elevated symptoms of depression may be mediated, in part, by endothelial dysfunction.

Changes in plasma volume associated with mental stress ischemia in patients with coronary artery disease.

Psychological stress has been shown to trigger angina and myocardial ischemia in patients with coronary artery disease. However, the mechanisms by which stress may trigger cardiac events has yet to be fully elucidated. Twenty five patients underwent radionuclide ventriculography during a multiple stress challenge. Plasma volume was assessed during rest and at the end of the stress task. Flow-mediated dilatation was also measured. Controlling for endothelial function and medications, patients with ischemia had greater reductions in plasma volume than non-ischemic patients. Reduced plasma volume may be one mechanism by which mental stress may increase the risk for acute coronary events.

Effects of exercise and weight loss on cardiac risk factors associated with syndrome X.

BACKGROUND: Patients with high blood pressure (BP) often exhibit syndrome X, an aggregation of abnormalities in carbohydrate and lipoprotein metabolism associated with increased risk of coronary heart disease (CHD). The present study evaluated the effects of a 6-month intervention involving either aerobic exercise training alone (EX only) or exercise combined with a structured weight loss program (EX + WL) on CHD risk factors associated with syndrome X. METHODS: A total of 53 men and women were selected from a larger behavioral intervention trial, who showed the hyperinsulinemia, dyslipidemia, and high BP characteristic of syndrome X. Participants were randomly assigned to EX only (n = 21), EX + WL (n = 21), or a waiting list control group (n = 11). Before and following treatment, participants underwent measurement of glucose tolerance, lipid levels, and clinical BP. RESULTS: Hyperinsulinemic responses to glucose challenge were significantly reduced in both the EX + WL group (P<.001) and the EX-only group (P =.003). Participants who showed the largest amount of weight loss showed the most robust improvements in abnormal insulin responses (EX + WL group, 47% reduction; EX-only group, 27% reduction). Diastolic BP was significantly reduced in the EX + WL group (96 +/- 4 to 87 +/- 5 mm Hg [mean +/- SD]; P =.01), but not in the EX-only group (93 +/- 4 to 89 +/- 5 mm Hg [mean +/- SD]; P =.08). Lipid profile was not significantly improved by either intervention. CONCLUSION: These results suggest that EX + WL is an effective treatment for hyperinsulinemia and lowering of diastolic BP in patients with the syndrome X.

Reduction of left ventricular hypertrophy after exercise and weight loss in overweight patients with mild hypertension.

BACKGROUND: Hypertrophy and concentric remodeling of the left ventricle are important manifestations of hypertension that are associated with increased morbidity and mortality. Although lifestyle interventions are efficacious in lowering blood pressure, evidence that they have a beneficial effect on target organs has been lacking. OBJECTIVE: To assess the effects of regular aerobic exercise or exercise plus weight management counseling on left ventricular mass and geometry in overweight, sedentary men and women with high-normal or mildly elevated blood pressure. METHODS: Eighty-two participants in a randomized, controlled trial were assigned to supervised aerobic exercise only, a behavioral weight management program that included exercise, or a waiting-list control group for 6 months. Blood pressure and echocardiographic measures of left ventricular structure were measured at baseline and at the conclusion of the treatment phase. RESULTS: The 45 women and 37 men had a mean +/- SD age of 47 +/- 9 years and had a mean +/- SD blood pressure of 140 +/- 10/93 +/- 5 mm Hg. Blood pressure fell by 7/6 mm Hg in the weight management group and by 3/4 mm Hg in the aerobic exercise group. In association with these decreases in blood pressure, participants in the intervention groups exhibited significant decreases in left ventricular relative wall thickness (P =.003), posterior wall thickness (P =.05), and septal thickness (P =.004) and a trend toward a decrease in indexed left ventricular mass (P =.08) relative to the control group. CONCLUSIONS: In a cohort of overweight, sedentary men and women, exercise and weight loss reduced blood pressure and induced favorable changes in left ventricular structure.

Effects of exercise and stress management training on markers of cardiovascular risk in patients with ischemic heart disease: a randomized controlled trial.

CONTEXT: Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality, but the effects of behavioral interventions on psychosocial and medical end points remain uncertain. OBJECTIVE: To determine the effect of 2 behavioral programs, aerobic exercise training and stress management training, with routine medical care on psychosocial functioning and markers of cardiovascular risk. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial of 134 patients (92 male and 42 female; aged 40-84 years) with stable ischemic heart disease (IHD) and exercise-induced myocardial ischemia. Conducted from January 1999 to February 2003. INTERVENTIONS: Routine medical care (usual care); usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks; usual care plus weekly 1.5-hour stress management training for 16 weeks. MAIN OUTCOME MEASURES: Self-reported measures of general distress (General Health Questionnaire [GHQ]) and depression (Beck Depression Inventory [BDI]); left ventricular ejection fraction (LVEF) and wall motion abnormalities (WMA); flow-mediated dilation; and cardiac autonomic control (heart rate variability during deep breathing and baroreflex sensitivity). RESULTS: Patients in the exercise and stress management groups had lower mean (SE) BDI scores (exercise: 8.2 [0.6]; stress management: 8.2 [0.6]) vs usual care (10.1 [0.6]; P = .02); reduced distress by GHQ scores (exercise: 56.3 [0.9]; stress management: 56.8 [0.9]) vs usual care (53.6 [0.9]; P = .02); and smaller reductions in LVEF during mental stress testing (exercise: -0.54% [0.44%]; stress management: -0.34% [0.45%]) vs usual care (-1.69% [0.46%]; P = .03). Exercise and stress management were associated with lower mean (SE) WMA rating scores (exercise: 0.20 [0.07]; stress management: 0.10 [0.07]) in a subset of patients with significant stress-induced WMA at baseline vs usual care (0.36 [0.07]; P = .02). Patients in the exercise and stress management groups had greater mean (SE) improvements in flow-mediated dilation (exercise: mean [SD], 5.6% [0.45%]; stress management: 5.2% [0.47%]) vs usual care patients (4.1% [0.48%]; P = .03). In a subgroup, those receiving stress management showed improved mean (SE) baroreflex sensitivity (8.2 [0.8] ms/mm Hg) vs usual care (5.1 [0.9] ms/mm Hg; P = .02) and significant increases in heart rate variability (193.7 [19.6] ms) vs usual care (132.1 [21.5] ms; P = .04). CONCLUSION: For patients with stable IHD, exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone.

Effects of spouse-assisted coping skills training and exercise training in patients with osteoarthritic knee pain: a randomized controlled study.

This study tested the separate and combined effects of spouse-assisted pain coping skills training (SA-CST) and exercise training (ET) in a sample of patients having persistent osteoarthritic knee pain. Seventy-two married osteoarthritis (OA) patients with persistent knee pain and their spouses were randomly assigned to: SA-CST alone, SA-CST plus ET, ET alone, or standard care (SC). Patients in SA-CST alone, together with their spouses, attended 12 weekly, 2-h group sessions for training in pain coping and couples skills. Patients in SA-CST + ET received spouse-assisted coping skills training and attended 12-weeks supervised ET. Patients in the ET alone condition received just an exercise program. Data analyses revealed: (1) physical fitness and strength: the SA-CST + ET and ET alone groups had significant improvements in physical fitness compared to SA-CST alone and patients in SA-CST + ET and ET alone had significant improvements in leg flexion and extension compared to SA-CST alone and SC, (2) pain coping: patients in SA-CST + ET and SA-CST alone groups had significant improvements in coping attempts compared to ET alone or SC and spouses in SA-CST + ET rated their partners as showing significant improvements in coping attempts compared to ET alone or SC, and (3) self-efficacy: patients in SA-CST + ET reported significant improvements in self-efficacy and their spouses rated them as showing significant improvements in self-efficacy compared to ET alone or SC. Patients receiving SA-CST + ET who showed increased self-efficacy were more likely to have improvements in psychological disability. An intervention that combines spouse-assisted coping skills training and exercise training can improve physical fitness, strength, pain coping, and self-efficacy in patients suffering from pain due to osteoarthritis.

Depression and increased myocardial ischemic activity in patients with ischemic heart disease.

BACKGROUND: Depression is relatively common in patients with ischemic heart disease (IHD) and is associated with increased risk of mortality and morbidity. However, the mechanisms by which depression adversely affects clinical outcomes of patients with IHD are unknown. This study examined the relationship between depression and myocardial ischemia during mental stress testing and during daily living in patients with stable IHD.Methods and results The Center for Epidemiological Studies-Depression scale (CES-D) was administered to 135 patients with IHD to evaluate depressive symptoms. Radionuclide ventriculography was used to evaluate the occurrence of left ventricular wall motion abnormality (WMA) during mental stress and exercise testing. Forty-eight-hour ambulatory electrocardiography was used to assess myocardial ischemia during daily living. The mean CES-D score was 8.2 (SD 7.4, range 0-47) with a median of 7. Logistic regression models using restricted cubic splines revealed a curvilinear relation among CES-D scores and the probability of ischemia. For patients with CES-D scores 19, the relation among scores and ischemia during mental stress tended to be inversely related, but the portion of the sample is very small. Similar patterns of results were noted for CES-D scores and ischemia during daily life. CONCLUSIONS: Patients with mild to moderate depressive symptoms (CES-D scores

Relationship between exercise systolic blood pressure and left ventricular geometry in overweight, mildly hypertensive patients.

OBJECTIVE: To examine the association between the graded exercise systolic blood pressure (SBP) response and left ventricular (LV) geometric structure in patients with untreated mild hypertension. PARTICIPANTS: The study included 80 sedentary, overweight patients (43 female and 37 male) with unmedicated high normal blood pressure or stage 1-2 hypertension. METHODS: An echocardiogram was used to determine LV mass and the relative wall thickness (RWT) in relation to the chamber dimension. Participants performed a maximal graded exercise test, and the SBP was recorded at workloads of 2, 4 and 6 metabolic equivalents and at peak exercise. Separate statistical models were used to determine the influence of LV mass indexed for height(2.7) (LVMIh) and RWT on submaximal exercise SBP and peak exercise SBP, controlling for resting SBP, age, gender, ethnicity and body mass index. RESULTS: A greater RWT was associated with a higher submaximal SBP level (P = 0.038). Neither LVMIh (P = 0.989) nor the interaction of RWT and LVMIh (P = 0.787) were related to the submaximal SBP. None of the main or interaction effects of RWT and LVMIh were associated with the peak exercise SBP level. CONCLUSION: Increases in RWT were associated with higher submaximal exercise SBP responses in a sample of overweight, unmedicated hypertensives. These results suggest that RWT is an important determinant of the association between cardiac mass and exercise SBP response.

Association between exercise capacity and left ventricular geometry in overweight patients with mild systemic hypertension.

The purpose of this study was to determine the relation between left ventricular (LV) geometry and exercise capacity in unmedicated, hypertensive patients. Analysis of the data revealed peak oxygen consumption (ml kg(-1) min(-1)) for concentric hypertrophy (corrected mean +/- SE 23.5 +/- 1.2) was significantly less (F = 3.68, p <0.02) than the concentric remodeling (28.1 +/- 1.2) and normal (27.3 +/- 0.6) geometries. The LV geometric pattern was found to be associated with exercise capacity in unmedicated, hypertensive patients, such that patients with concentric hypertrophy showed reduced capacity.

Changes in hemodynamics and left ventricular structure after menopause.

To evaluate the cardiovascular changes associated with menopause, we studied hemodynamics at rest, ambulatory blood pressure, and left ventricular structure in a biracial cohort of pre- and postmenopausal women of similar age, race, weight, and blood pressure. Despite similar levels of blood pressure, postmenopausal women had a higher indexed peripheral resistance (2,722 +/- 757 vs 2,262 +/- 661 dynes.s.m(2)/cm(5), p <0.01) and a lower cardiac index (2.64 +/- 0.73 vs 3.10 +/- 0.71 L/min.m(2), p <0.01) than premenopausal women. Postmenopausal women also had less nocturnal decreases in both systolic (15 +/- 8 vs 19 +/- 8 mm Hg, p <0.01) and diastolic (12 +/- 6 vs 15 +/- 6 mm Hg, p = 0.05) pressures during ambulatory monitoring and higher levels of hematocrit (40 +/- 2% vs 38 +/- 3%, p <0.01). In association with this greater hemodynamic load, postmenopausal women had evidence of early concentric left ventricular remodeling, manifested by a greater relative wall thickness (0.38 +/- 0.06 vs 0.35 +/- 0.06, p <0.01) than that observed in premenopausal women. Differences between pre- and postmenopausal women in hemodynamics, diurnal blood pressure variation, and left ventricular structure were observed in white and African-American subjects. These results suggest that menopause is associated with hemodynamic changes and left ventricular remodeling, which may contribute to the enhanced cardiovascular risk observed in postmenopausal women.

Effects of daily stress on autonomic cardiac control in patients with coronary artery disease.

Emotional stress has been implicated in the development and progression of coronary artery disease, with 1 proposed causal pathway being changes in cardiac autonomic tone. One hundred thirty-five patients with coronary artery disease underwent 48 hours of ambulatory electrocardiographic monitoring and completed activity and mood diaries every 20 minutes while awake. Random-effects model analyses associated higher levels of negative emotions (e.g., anger, stress, sadness) with decreases in high- and low-frequency power, whereas higher levels of positive emotion were related to an increase in low-frequency power, independent of age, posture, and medications.

Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in men.

This study examined the effects of exercise and stress management training on clinical outcomes and medical expenditures over a 5-year follow-up period in 94 male patients with established coronary artery disease (CAD) and evidence of ambulatory or mental stress-induced myocardial ischemia. Patients were randomly assigned to 4 months of aerobic exercise 3 times per week or to a 1.5-hour weekly class on stress management; patients who lived too far from Duke to participate in the weekly treatments formed the usual care control group. Follow-up was performed at the end of treatment and annually thereafter for 5 years. Stress management was associated with a significant reduction in clinical CAD events relative to usual care over each of the first 2 years of follow-up and after 5 years. Economic analyses revealed that stress management was associated with lower medical costs than usual care and exercise in the first 2 years, and that the cumulative cost over 5 years was also lower for stress management relative to usual care. These results suggest that there may be clinical and economic benefit to offering the type of preventive stress management and exercise interventions provided to patients with myocardial ischemia. Moreover, these findings suggest that the financial benefits that accrue from an appropriately targeted intervention may be substantial and immediate.