The impact of inflammation on the obesity paradox in coronary heart disease.

BACKGROUND: Despite the well-known adverse effects of obesity on almost all aspects of coronary heart disease, many studies of coronary heart disease cohorts have demonstrated an inverse relationship between obesity, as defined by body mass index (BMI), and subsequent prognosis: the 'obesity paradox'. The etiology of this and the potential role of inflammation in this process remain unknown. PATIENTS AND METHODS: We studied 519 patients with coronary heart disease before and after cardiac rehabilitation, dividing them into groups based on C-reactive protein ((CRP)⩾3 mg l-1 and CRP<3 mg l-1 after cardiac rehabilitation). BMI was calculated and body fat was measured using the skin-fold method. Lean mass index (LMI) was calculated as (1-%body fat) × BMI. The population was divided according to age- and gender-adjusted categories based on LMI and body fat and analyzed by total mortality over >3-year follow-up by National Death Index in both CRP groups. RESULTS: During >3-year follow-up, all-cause mortality was higher in the high inflammation and in the low BMI group. In proportional hazard analysis, even after adjusting for ejection fraction and peak O2 consumption, higher BMI was associated with lower mortality in the entire population (hazard ratio (HR) 0.38; confidence interval 0.15-0.97) and a trend to lower mortality in both subgroups (HR 0.45 in low CRP, P=0.24 vs HR 0.32, P=0.06 in high CRP). High body fat, however, was associated with significantly lower mortality in the high CRP group (HR 0.22; P=0.03) but not in the low CRP group (HR 0.73; P=0.64). Conversely, high LMI was associated with markedly lower mortality in the low CRP group (HR 0.04; P=0.04). CONCLUSIONS: The obesity paradox has multiple underlying etiologies. Body composition has a different role in different populations with an obesity paradox by BMI. Especially in the subpopulation with persistently high CRP levels, body fat seems protective.

Obesity and the "obesity paradox" in cardiovascular diseases.

Obesity adversely affects most cardiovascular (CV) risk factors and is strongly associated, probably as an independent risk factor, with most CV diseases. However, substantial evidence points to the existence of an "obesity paradox," in that overweight and obese patients with established CV diseases typically have a better prognosis than leaner patients with the same CV disease. Despite this paradox, we believe that the "weight" of evidence still supports efforts at purposeful weight loss in both primary and secondary CV prevention.

Ventricular-vascular uncoupling increases expression of B-type natriuretic peptide in heart transplantation.

BACKGROUND: Allograft adaptation to a foreign circulation is imperfect as noted from persistent limitations to stress. Effective arterial elastance (Ea), a measure of afterload, provides an estimate of aortic impedance. End systolic elastance (Ees) is a load-independent measure of ventricular performance as well as its interaction in the periphery. The ratio (Ea to Ees) characterizes ventricular-vascular coupling; a value close to unity signifies poor mechanical efficiency. The purpose of this investigation was to correlate mechanical efficiency of work with expression of B-type natriuretic peptide BNP, a specific marker of ventricular stress and strain. METHODS: We measured BNP levels in 40 consecutive stable heart transplant recipients free from rejection. In addition, echocardiography was performed to obtain Ea, Ees, and their ratio (Ea to Ees) by the single-beat method. We examined correlates of BNP expression by assessing Ea to Ees, while correcting for mean arterial pressure, body mass index, left ventricular mass index, ejection fraction, and serum creatinine. RESULTS: BNP levels were significantly and positively correlated (r=0.38, P=.05) with an increased Ea to Ees ratio. By multivariable analysis, this relationship persisted independently (t=2.1, P=.04), while the five other measures were insignificant predictors. CONCLUSION: This investigation indicated that the transplanted heart demonstrates poor contractile efficiency and operates at maximal left ventricular work. This is paralleled by a tandem increase in BNP, suggesting that elevation in this stress peptide is at least partly explained by ventriculo-vascular uncoupling in heart transplantation, independent of alterations in blood pressure.

Comparison of the efficacy and safety of pravastatin and simvastatin in heart transplantation.

AIMS: Data on the safety and efficacy of HMG CoA reductase inhibitors in managing dyslipidemia in heart transplant recipients is inadequate. We undertook this study to evaluate the comparative safety and efficacy of simvastatin and pravastatin in lowering lipids in heart transplant recipients. METHODOLOGY: Forty eight patients (38 males) who received heart transplantation between 1995 and 1997, and who had no contraindications to statin therapy or history of myopathy were randomized to receive either pravastatin (n=24) or simvastatin (n=24) for six months. Detailed fasting lipid profiles, hepatic function tests, and serum creatinine phosphokinase were obtained regularly. Baseline and six month characteristics were compared using the unpaired student t test for continuous variables and Chi-square analysis or Fisher's exact test, as appropriate. RESULTS: Baseline total cholesterol levels, LDL cholesterol levels, HDL cholesterol levels, and triglyceride levels were similar in the two groups. At six months, the total cholesterol, LDL cholesterol, and triglyceride levels were greatly reduced in both groups, with greater reductions in the simvastatin group than in the pravastatin group. Only modest increases were noted in HDL cholesterol levels in the two groups. No significant adverse effects were noted, and no complications with drug withdrawals occurred. Patient compliance exceeded 97%. CONCLUSION: Simvastatin and pravastatin are safe and very effective in total cholesterol and LDL cholesterol lowering in heart transplant recipients, with simvastatin being more efficacious than pravastatin in lipid lowering in this group of patients.

Benefits of cardiac rehabilitation and exercise training programs in elderly coronary patients.

The authors review several studies from the Ochsner Heart and Vascular Institute showing the benefits of formal phase II cardiac rehabilitation and exercise training programs in elderly patients with coronary artery disease, including benefits on plasma lipids, obesity indices, exercise capacity, peak oxygen consumption, behavioral characteristics (especially depression), and quality of life. Marked benefits were noted in elderly women and all elderly patients over the age of 75 years. The authors conclude that the therapy has proved to be safe and effective for elderly coronary patients, and that these individuals should be routinely referred to, and vigorously encouraged to attend, cardiac rehabilitation programs following major coronary events.

Exercise and the heart: risks, benefits, and recommendations for providing exercise prescriptions.

Considerable research from the Ochsner Heart and Vascular Institute has focused on the effects of exercise training in patients with coronary heart disease. In this review, the authors discuss the risks and benefits of exercise training in general patients, as well as those with known vascular disease, and provide suggestions for exercise prescriptions for these patients, including modes of exercise and intensity, duration, and frequency of exercise sessions.

The incremental prognostic importance of body fat adjusted peak oxygen consumption in chronic heart failure.

OBJECTIVES: We sought to assess whether the adjustment of peak oxygen consumption (PkVO2) to lean body mass would yield a more accurate discriminator of outcomes in the chronic heart failure population. BACKGROUND: Peak oxygen consumption is traditionally used to risk stratify patients with congestive heart failure (CHF) and to time cardiac transplantation. There is, however, considerable variability in body fat content, which represents metabolically inactive mass. METHODS: In 225 consecutive patients with CHF, the percentage of body fat was determined by the sum of skinfolds technique. All underwent CPX using a ramping treadmill protocol. Mean follow-up duration was 18.9+/-11.3 months. RESULTS: There were 14 cardiovascular deaths and 15 transplants. Peak oxygen consumption lean, both as a continuous variable and using a cutoff of < or =19 ml/kg/min, was a better predictor of outcome than unadjusted PkVO2 (p = 0.003 vs. 0.027 for the continuous variables and p = 0.0006 vs. 0.055 for < or =19 ml/kg/min and < or =14 ml/kg/min unadjusted body weight, respectively). Using partial correlation index R statistics, the Cox model using PkVO2 lean < or =19 ml/kg/min, in addition to age and etiology of CHF as covariates, yielded the strongest predictive relationship to the combined end point (chi-square value 24.32). Especially in the obese patients and in women, there was considerably better correlation of PkVO2 lean with outcome than the unadjusted PkVO2. CONCLUSIONS: The adjustment of PkVO2 to lean body mass increases the prognostic value of cardiopulmonary stress testing in the evaluation of patients with chronic heart failure. The use of <19 ml O2/kg of lean body mass/min as a cutoff in PkVO2 should be used for timing transplantation, particularly in women and the obese.

Disparate effects of improving aerobic exercise capacity and quality of life after cardiac rehabilitation in young and elderly coronary patients.

PURPOSE: Although cardiopulmonary exercise variables predict prognosis, functional capacity, and quality of life (QoL) in patients with coronary artery disease (CAD), these variables have not been assessed fully before and after exercise training in elderly with CAD. Therefore, the purpose of this study was to determine the impact of formal Phase II cardiac rehabilitation and exercise training programs on cardiopulmonary variables and QoL in elderly and younger CAD patients. METHODS: The authors analyzed consecutive patients before and after Phase II cardiac rehabilitation and exercise training programs, and compared exercise cardiopulmonary data and data from validated questionnaires assessing QoL (MOS SF-36) and function in 125 younger patients (< 55 years; mean 48 +/- 6 years) and 57 elderly (> 70 years; mean 78 +/- 3 years). RESULTS: At baseline, elderly patients had lower estimated aerobic exercise capacity (-27%; P < 0.001), peak oxygen consumption (VO2) (-19%; P < 0.01), and anaerobic threshold (-10%; P < 0.05), as well as total function scores (-11%; P < 0.01) and total QoL scores (-5%; P = 0.06). Commonly used prediction equations greatly overestimated aerobic exercise capacity compared with precise measurements using cardiopulmonary testing both before (+23% and +12% in younger and elderly patients, respectively) and after the exercise training programs (+51% and +31% in younger and elderly patients, respectively), and more so in younger compared with older patients. After rehabilitation, the elderly had significant improvements in estimated aerobic exercise capacity (+32%; P < 0.0001), peak VO2 (+13%; P < 0.0001), anaerobic threshold (+11%; P = 0.03), total function scores (+27%; P < 0.0001), and total QoL scores (+20%; P < 0.0001). Although younger patients had greater improvements in estimated aerobic exercise capacity (+44% versus +32%; P = 0.08), peak VO2 (+18% versus +13%; P < 0.01), and anaerobic threshold (+17% versus +11%; P = 0.07), the elderly had statistically greater improvements in both function scores (+27% versus +20%; P = 0.02), and total QoL scores (+20% versus +14%; P = 0.03). CONCLUSIONS: These data confirm the benefits of precisely determining aerobic exercise capacity by cardiopulmonary function, especially to determine the benefits of an exercise training program. In addition, these data using cardiopulmonary exercise tests and validated assessments of quality of life demonstrate the disparate effects of cardiac rehabilitation programs on improvements in aerobic exercise capacity and QoL in young and elderly with CAD.

Study of arterial and autonomic effects of cyclosporine in humans.

Altered sympathetic activity and peripheral vascular function are suspected as a mechanism of the development of arterial hypertension in organ transplantation recipients treated with cyclosporine. We assessed whether cyclosporine might alter peripheral vascular properties or autonomic modulation of the sinus node and the vasculature during rest and standing. We examined 17 orthotopic heart transplantation recipients, 8 solid organ transplantation recipients, 17 patients with essential hypertension, and 42 normotensive control subjects. All except the normotensive control subjects were treated with a long-acting dihydropyridine calcium entry blocker; transplantation recipients also received cyclosporine-based immunosuppression. Radial artery compliance was reduced in patients with essential hypertension and in patients with heart and solid organ transplantation as compared with normotensive control subjects, with this reduction being more marked in heart transplantation recipients. At rest, R-R variance was lowest in heart transplantation recipients, denoting denervation. The spectral profile of both R-R and systolic blood pressure variability as well as the index of baroreflex gain was normal at rest in patients with solid organ transplantation. On standing, both transplantation groups demonstrated reduced responsiveness in markers of autonomic modulation. The decrease in arterial compliance in cyclosporine-induced hypertension seems to imply a degree of ventricular vascular uncoupling more apparent in heart transplantation recipients. These changes are associated with alterations in autonomic modulation that are evidenced by an orthostatic stimulus.

Effects of aerobic exercise training on indices of ventricular repolarization in patients with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have a markedly increased incidence of malignant ventricular arrhythmias. QT dispersion (QTd), defined as the difference between maximal and minimal QT intervals, reflects the regional inhomogeneity of ventricular repolarization dispersion and may mark the presence of malignant ventricular arrhythmias. PURPOSE: To determine the effects of exercise training on QTd in patients with CHF. PATIENTS: Fifteen patients with CHF and ejection fractions < 40% (mean, 28+/-9%) who were on a stable medical regimen. DESIGN AND INTERVENTION: Standardized 12-lead surface ECGs were obtained at the beginning and end of the exercise training program, and QT and JT intervals were measured manually and corrected for heart rate by using Bazett's formula. QTd, heart rate-corrected QTd (QTc-d), JT dispersion (JTd), and heart rate-corrected JTd (JTc-d) were measured in at least eight ECG leads in each patient. RESULTS: Following the cardiac rehabilitation and exercise training programs, patients with CHF had only slight improvements in exercise capacity (results were not significant). However, these patients had marked improvements in QTd (71+/-11 to 59+/-17 ms; p < 0.02), QTc-d (82+/-28 to 63+/-17 ms; p < 0.01), JTd (76+/-19 to 57+/-18 ms; p < 0.002), and JTc-d (84+/-23 to 61+/-18 ms; p < 0.001) following the exercise training programs. CONCLUSION: These data indicate that aerobic exercise training significantly reduces the indices of ventricular repolarization dispersion in patients with CHF. Further studies are needed to evaluate how effectively this reduction in ventricular repolarization dispersion decreases the risk of malignant ventricular arrhythmias and sudden death in patients with CHF.

Effects of cardiac rehabilitation and exercise training on peak aerobic capacity and work efficiency in obese patients with coronary artery disease.

Using cardiopulmonary stress testing in 76 lean and 99 obese coronary patients, we demonstrated significant improvements in both groups for anaerobic threshold, peak aerobic capacity (VO2), peak VO2 corrected for lean body mass, and work efficiency. Although anaerobic threshold and peak VO2 are adequate to describe exercise capacity in lean patients, baseline and post-training data are best exemplified by peak VO2 corrected for lean body mass and work efficiency in obese coronary patients.

Effects of cardiac rehabilitation and exercise training programs in women with depression.

Depression is prevalent in women with coronary artery disease, and increases morbidity and mortality following major coronary events. We demonstrated that women with depression had markedly abnormal overall cardiovascular risk profiles and have marked benefits in exercise capacity, obesity indexes, behavioral characteristics (including depression), and quality of life following formal, outpatient phase II cardiac rehabilitation and exercise training programs.

Cardiac rehabilitation and preventive cardiology in the elderly.

This article reviews data demonstrating the benefits of cardiac rehabilitation and exercise training programs in the elderly. Other risk factor interventions, including cessation of smoking, treatment of diabetes, and lipid therapy, are very beneficial for the elderly with coronary heart disease or strong risk of coronary heart disease. Also briefly reviewed are current data suggesting the benefits of antioxidant vitamins, and folic acid to reduce levels of homocysteine for the primary and secondary prevention of coronary heart disease in the elderly.

Effects of cardiac rehabilitation and exercise training programs on coronary patients with high levels of hostility.

OBJECTIVE: To determine the effects of cardiac rehabilitation interventions on patients with hostility, or unexpressed anger, a coronary heart disease risk factor that adversely affects morbidity and mortality after major coronary heart disease events. METHODS: Using validated questionnaires to evaluate behavioral characteristics and quality of life, we studied 500 consecutive patients before and after cardiac rehabilitation and compared a group of 65 patients with high levels of hostility with 435 patients with low levels of hostility. RESULTS: After rehabilitation, statistically significant improvements occurred in the total cohort in scores for anxiety, depression, and somatization, as well as total quality of life, but not in hostility score (-20%; P = .07). Patients with high levels of hostility had significant improvements in hostility scores as well as other behavioral characteristics (anxiety, depression, and somatization) and all quality-of-life components. These patients also improved exercise capacity, percent body fat, body mass index, and total cholesterol and high-density lipoprotein cholesterol levels. Compared with patients with low levels of hostility, those with high levels of hostility had greater relative improvements in hostility scores, as well as anxiety, general health, energy, mental health, and total quality-of-life scores, and had similar improvements in exercise capacity, obesity indexes, lipid levels, and other behavioral characteristics and quality-of-life measurements. After cardiac rehabilitation, the prevalence of high levels of hostility decreased by 40%, from 13% to 8% (P < .01). CONCLUSIONS: These data suggest that cardiac rehabilitation reduces hostility and significantly improves quality of life and other behavioral characteristics in patients with high levels of hostility. We believe that greater attention should be directed at behavioral characteristics, including hostility, to enhance the primary and particularly the secondary prevention of coronary heart disease.