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.

Benefits of cardiac rehabilitation and exercise training in secondary coronary prevention in the elderly.

OBJECTIVES: The aim of this study was to determine the effects of cardiac rehabilitation and exercise training on plasma lipids, indexes of obesity and exercise capacity in the elderly and to compare the benefits in elderly patients with coronary heart disease with benefits in a younger cohort. BACKGROUND: Despite the well proved benefits of cardiac rehabilitation and exercise training, elderly patients with coronary heart disease are frequently not referred or vigorously encouraged to pursue this therapy. In addition, only limited data are available for these elderly patients on the benefits of cardiac rehabilitation on plasma lipids, indexes of obesity and exercise capacity. METHODS: At two large multispecialty teaching institutions, baseline and post-rehabilitation data including plasma lipids, indexes of obesity and exercise capacity were compared in 92 elderly patients (> or = 65 years, mean age 70.1 +/- 4.1 years) and 182 younger patients (< 65 years, mean 53.9 +/- 7.4 years) enrolled in phase II cardiac rehabilitation and exercise programs after a major cardiac event. RESULTS: At baseline, body mass index (26.0 +/- 3.9 vs. 27.8 +/- 4.2 kg/m2, p < 0.001), triglycerides (141 +/- 55 vs. 178 +/- 105 mg/dl, p < 0.01) and estimated metabolic equivalents (METs) (5.6 +/- 1.6 vs. 7.7 +/- 3.0, p < 0.0001) were lower and high density lipoprotein cholesterol was greater (40.4 +/- 12.1 vs. 37.5 +/- 10.4 mg/dl, p < 0.05) in the elderly than in younger patients. After rehabilitation, the elderly demonstrated significant improvements in METs (5.6 +/- 1.6 vs. 7.5 +/- 2.3, p < 0.0001), body mass index (26.0 +/- 3.9 vs. 25.6 +/- 3.8 kg/m2, p < 0.01), percent body fat (24.4 +/- 7.0 vs. 22.9 +/- 7.2%, p < 0.0001), high density lipoprotein cholesterol (40.4 +/- 12.1 vs. 43.0 +/- 11.4 mg/dl, p < 0.001) and the ratio of low density to high density lipoprotein cholesterol (3.6 +/- 1.3 vs. 3.3 +/- 1.0, p < 0.01) and a decrease in triglycerides that approached statistical significance (141 +/- 55 vs. 130 +/- 76 mg/dl, p = 0.14) but not in total cholesterol or low density lipoprotein cholesterol. Improvements in functional capacity, percent body fat and body mass index, as well as lipids, were statistically similar in the older and younger patients. CONCLUSIONS: Despite baseline differences, improvements in exercise capacity, obesity indexes and lipids were very similar in older and younger patients enrolled in cardiac rehabilitation and exercise training. These data emphasize that elderly patients should not be categorically denied the psychosocial, physical and risk factor benefits of secondary coronary prevention including formal cardiac rehabilitation and supervised exercise training.

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.

Factors predicting improvements in lipid values following cardiac rehabilitation and exercise training.

BACKGROUND: Cardiac rehabilitation and exercise training improve prognosis following major cardiac events, partly by improving coronary risk factors, including plasma lipids. Only limited data are available to define predictors of lipid improvements following aggressive nonpharmacologic therapy with cardiac rehabilitation. METHODS: We studied 237 consecutive patients from two institutions who were enrolled in outpatient phase 2 cardiac rehabilitation and exercise programs. By univariable and multivariable analyses, we assessed the impact of numerous clinical variables, including indexes of obesity, age, gender, lipid concentrations, exercise capacity, and psychological factors, on improvements in plasma lipid values with cardiac rehabilitation. RESULTS: Coronary risk factors improved following cardiac rehabilitation, including levels of low-density lipoprotein cholesterol (-4%; P < .05), high-density lipoprotein cholesterol (7%; P < .0001), and triglycerides (-13%; P < .0001); body mass index (-2%; P < .0001); percentage of body fat (-5%; P < .0001); and exercise capacity (26%; P < .0001). By both univariable and multivariable analyses, corresponding dyslipidemic baseline values were the strongest predictors of improvements in levels of low-density lipoprotein cholesterol (univariable: r = .51, P < .0001; multivariable: t = 8.5, P < .0001), high-density lipoprotein cholesterol (univariable: r = .37, P < .0001; multivariable: t = 6.6, P < .0001), and triglycerides (univariable: r = .36, P < .0001; multivariable: t = 6.8, P < .0001). By multivariable analyses, reductions in body mass index (t = 4.6, P < .0001) and older age (t = 4.0, P < .0001) were strong independent predictors of reduction in triglyceride values following cardiac rehabilitation. However, low baseline triglyceride values were independently associated with improvements in both low-density and high-density lipoprotein cholesterol levels. Using a model incorporating 13 clinical variables, improvements in lipid values with cardiac rehabilitation were only modestly predictable with the variables assessed, accounting for only 30% to 40% of the improvements in lipid values. CONCLUSIONS: (1) Coronary risk factors markedly improved following cardiac rehabilitation and exercise training. (2) Improvements in lipid values are modestly predictable. (3) Those patients with the worst baseline lipid values had the most improvements in lipid values following cardiac rehabilitation. However, patients with combined hyperlipidemia and low levels of high-density lipoprotein cholesterol are likely to require drug treatment.

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.

Behavioral differences and effects of cardiac rehabilitation in diabetic patients following cardiac events.

PURPOSE: To describe the incidence of depression and other behavioral disorders in diabetic coronary patients following major cardiac events and to assess the impact of cardiac rehabilitation. PATIENTS: 291 consecutive coronary patients (70 with diabetes mellitus). METHODS: Patients were prospectively enrolled in comprehensive phase II cardiac rehabilitation 4 to 6 weeks following a major cardiac event. Depressive symptoms and other behavioral characteristics (anxiety, somatization, hostility), as well as parameters of quality of life, were assessed by validated questionnaires at entry and upon completion (12 weeks, 36 sessions) of cardiac rehabilitation. RESULTS: Diabetic patients made up 24% of the cohort and were more likely to be female (P = 0.08), hypertensive (P = 0.05), and obese (P = 0.08). Additionally, diabetic patients had a reduced exercise capacity (P = 0.008), lower high-density lipoprotein cholesterol (P = 0.008), lower low-density lipoprotein cholesterol (P = 0.02), and increased triglyceride (P = 0.04) levels. Diabetic patients had a higher incidence of depression (26% versus 14%; P < 0.03), demonstrated more symptoms of somatization (P < 0.06), and exhibited lower scores for components of quality of life. Following cardiac rehabilitation, the incidence of depression was reduced in diabetic patients by 67% (P = 0.01) and ultimately equaled the 9% prevalence found in the non-diabetic group. CONCLUSIONS: Diabetic coronary patients demonstrate a higher incidence of depression than non-diabetic patients following major cardiac events. In addition to improving traditional cardiac risk factors, cardiac rehabilitation reduces depression in this high-risk group.

Effects of cardiac rehabilitation and exercise training on low-density lipoprotein cholesterol in patients with hypertriglyceridemia and coronary artery disease.

Substantial data suggest that elevated triglycerides are associated with increased coronary risk, and may be an independent coronary risk factor. Although it is generally accepted that patients with hypertriglyceridemia can have marked improvement in lipids after vigorous nonpharmacologic therapy, data to support this belief are lacking. This study assessed 313 consecutive patients before and after outpatient phase II cardiac rehabilitation and exercise programs to compare the response of patients with elevated triglycerides (> or = 250 mg/dl; n = 39) to vigorous nonpharmacologic therapy with the response of patients with "normal" triglyceride levels (< 150 mg/dl; n = 157). The independent effects that baseline triglycerides, as well as other variables, had on improving lipids after nonpharmacologic therapy were also determined. After cardiac rehabilitation and exercise training, patients had improvement in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol levels, low-density lipoprotein (LDL) cholesterol levels, LDL/HDL ratios, body mass index, percent body fat, and METs. Patients with hypertriglyceridemia were younger (p = 0.05) and had higher baseline body mass index (p < 0.001) and LDL/HDL ratios (p < 0.0001) but lower HDL cholesterol levels (p < 0.0001) than patients with low baseline triglycerides. Both groups had improvement in lipids, obesity indexes, and exercise capacity. However, patients with hypertriglyceridemia had significantly greater reductions in triglycerides (-31% vs +3%; p < 0.0001), but had less improvement in both LDL cholesterol levels (0% vs -4%; p < 0.01) and LDL/HDL ratios (-5% vs -9%; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cardiac rehabilitation, exercise training, and weight reduction on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in obese coronary patients.

Obesity is strongly associated with coronary artery disease (CAD) and may be an independent risk factor; however, limited data are available on obesity intervention in patients with CAD. We studied 588 consecutive patients, including 235 (40%) who were obese by body mass index criteria (body mass index > or = 27.3 kg/m2 in women and > or = 27.8 kg/m2 in men) before and after out-patient phase II cardiac rehabilitation to determine the effects of this therapy and weight reduction on exercise capacity, CAD risk factors, behavioral characteristics, and quality of life in obese patients with CAD. At baseline, obese patients were younger (p < 0.0001) and had more systemic hypertension (p < 0.01), and diabetes mellitus (p < 0.05) and higher percent body fat (p < 0.0001), total cholesterol (p = 0.02), triglycerides (p < 0.0001), fasting glucose (p = 0.04), and low-density lipoprotein (LDL)-high-density lipoprotein (HDL) cholesterol (p < 0.0001), but had lower HDL cholesterol (p < 0.01) and exercise capacity (p = 0.07) than patients not classified as obese. After rehabilitation, obese patients had significant improvements in body mass index (-2%; p < 0.0001), percent body fat (-5%; p < 0.0001), exercise capacity (+27%; p < 0.0001), HDL cholesterol (+4%; p < 0.01), LDL/HDL ratio (-6%; p < 0.01), as well as scores for anxiety (p < 0.0001), depression (p < 0.01), somatization (p < 0.0001) and quality of life (p < 0.0001); nonobese patients, however, had significantly greater improvements in exercise capacity (+39% vs +27%; p < 0.001). In a subgroup of 45 obese patients with > or = 5% weight reduction, improvements in exercise capacity (p < 0.001), total cholesterol (p = 0.03), triglycerides (p < 0.01), HDL cholesterol (p < 0.001), LDL cholesterol (p = 0.02), and LDL/HDL ratio (p < 0.0001) were greater than improvements in 81 obese patients who did not lose weight. These data indicate that greater emphasis on more successful weight reduction programs is needed to further enhance CAD risk reduction in the 40% CAD patients with obesity.

Benefits of cardiac rehabilitation and exercise training in elderly women.

Elderly women are frequently not referred to cardiac rehabilitation programs. The data provided in this study, which demonstrate the benefits on exercise capacity, obesity indexes, behavioral characteristics, quality of life, and plasma lipids, support the idea that elderly women should be routinely referred to and vigorously encouraged to attend these programs following major coronary artery disease events.

Effects of cardiac rehabilitation and exercise training programs in patients > or = 75 years of age.

Even elderly patients > or = 75 years of age with coronary artery disease have modest improvements in lipid levels and marked improvements in exercise capacity, behavioral characteristics, and quality-of-life parameters after cardiac rehabilitation and exercise training programs. These data support that even very elderly patients with coronary artery disease should be routinely referred to and vigorously encouraged to pursue formal outpatient cardiac rehabilitation and exercise training programs following major coronary events.

Effects of nonpharmacologic therapy with cardiac rehabilitation and exercise training in patients with low levels of high-density lipoprotein cholesterol.

In a study of 591 consecutive coronary patients, we identified 243 (41%) with low high-density lipoprotein (HDL) cholesterol <35 mg/dl and demonstrated the benefits of vigorous nonpharmacologic therapy with cardiac rehabilitation and exercise training in this subgroup. However, patients with low HDL and "normal" triglycerides have significantly greater improvements in low-density lipoprotein (LDL) cholesterol and LDL/HDL ratio than patients with low HDL cholesterol and hypertriglyceridemia who are more likely to require drug treatment.

Effects of cardiac rehabilitation programs on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in a large elderly cohort.

Despite the limitations of our study, we believe the current data support the beneficial effects of cardiac rehabilitation and exercise training in the elderly, including modest improvements in lipids, obesity indexes, behavioral characteristics, and quality-of-life parameters, and marked improvements in exercise capacity. In fact, elderly patients had greater improvements than younger patients in both exercise capacity and mental health after cardiac rehabilitation. These data indicate that elderly patients with CAD should be routinely referred to and vigorously encouraged to pursue formal outpatient cardiac rehabilitation and exercise training programs after major CAD events.

Effects of cardiac rehabilitation and exercise training on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in women.

Despite the known benefits of cardiac rehabilitation, limited data are available on the outcome of this treatment in women, and this secondary prevention strategy may be underutilized. To assess the gender differences in baseline exercise capacity, indexes of obesity, lipid profiles, behavior characteristics, and components of quality of life, as well as the improvements in these components after a secondary prevention program, we retrospectively reviewed data from 458 patients (83 women and 375 men) enrolled in a phase II cardiac rehabilitation and exercise program after a major cardiac event. At baseline (6 weeks after the cardiac event and before rehabilitation), exercise capacity (-9%, p = 0.08) and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (-14%, p < 0.01) were lower, but total cholesterol (+7%, p < 0.01), high-density lipoprotein cholesterol (+25%, p < 0.0001), low-density lipoprotein cholesterol (+8%, p < 0.01), and percent body fat (+15%, p < 0.0001) were higher in women than in men with coronary artery disease. In addition, with regard to quality of life, women had lower scores for energy (p = 0.06), function (p < 0.01), and total quality of life (p < 0.05) than men. After cardiac rehabilitation and exercise training, women had significant improvements in exercise capacity (+33%, p < 0.0001) and percent body fat (-7%, p < 0.001), which compared favorably with the improvements (+40% and -5%, respectively) seen in men, but improvements in body mass index and lipids were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Prevalence and effects of cardiac rehabilitation on depression in the elderly with coronary heart disease.

Depression is a prevalent condition in coronary patients and is associated with increased morbidity and mortality following major coronary events. We measured the prevalence of depressive symptoms in 268 elderly coronary patients 4 to 6 weeks following a major coronary event and assessed its modulation by outpatient cardiac rehabilitation and found that cardiac rehabilitation resulted in a significant reduction in the prevalence and severity of this disorder.

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.

Lipid-lowering therapy and long-term survival in heart transplantation.

The influence of lipid-lowering therapy employing a historic cohort study design was assessed following heart transplantation. Lipid-lowering therapy appears to confer a survival benefit in cardiac transplant recipients who survive beyond the first year.

Usefulness of peak oxygen consumption in predicting outcome of heart failure in women versus men.

This investigation finds that percent of predicted maximum oxygen consumption, an age- and gender-adjusted measurement of exercise, capacity, describes the degree of functional impairment in women more accurately than peak oxygen consumption. This evidence must be considered when cardiopulmonary metabolic parameters are used for prognostic stratification of women with heart failure.