Effect of Chronic Kidney Disease and Supplemental Polyunsaturated Fatty Acid Use on Exercise Levels During Cardiac Rehabilitation in Patients With Coronary Artery Disease.

PURPOSE: The correlation between chronic kidney disease (CKD) and increased cardiovascular disease-related mortality is well established. Cardiac rehabilitation (CR) improves exercise capacity, quality of life, and risk factors in patients with coronary artery disease (CAD). Data on the benefits of CR in patients with CKD are sparse. The purpose of this study was to compare outcomes after CR in patients with CAD but normal renal function, versus those with CAD and CKD. METHODS: We studied 804 patients with CAD entering an exercise-based CR program. Demographics, risk factors, exercise capacity in metabolic equivalent levels (METs), and estimated glomerular filtration rate (GFR) were recorded before and after the 3-month CR program. Use of polyunsaturated fatty acid (PUFA) was determined by medical records review. Stage III-V CKD (GFR <60 mL/min/1.73 m) was present in 170 patients at baseline. RESULTS: After CR, METs improved in all patients, although increases in patients with a GFR 30 to 59 mL/min/1.73 m (Δ1.6) and a GFR <30 (Δ1.2) were smaller than those in patients with a GFR ≥60 (Δ2.6, P < .05 vs GFR 30-59 and GFR <30). In patients with a GFR ≥60 mL/min/1.73 m, PUFA use was associated with a 20% greater increase in MET levels compared with nonusers (Δ3.0 vs Δ2.5, P = .02); and in patients with a GFR 30 to 59, PUFA use was associated with 30% increase in MET level compared with nonusers (Δ2.0 vs Δ1.4, P = .03). These observations persisted after multivariable adjustment for baseline MET level, demographics, and risk factors. CONCLUSIONS: Potential mitigation by PUFA of the smaller improvement in exercise capacity with decreasing GFR requires confirmation in prospective randomized trials.

Degree and Direction of Change of Body Weight in Cardiac Rehabilitation and Impact on Exercise Capacity and Cardiac Risk Factors.

Cardiac rehabilitation (CR) improves functional capacity and reduces mortality in patients with cardiovascular disease. It also improves cardiovascular risk factors and aids in weight reduction. Because of the increase in morbidly obese patients with cardiovascular disease, the prevalence of obesity and patterns of weight change in those undergoing CR merit fresh study. We studied 1,320 participants in a 12-week CR program at our academic medical center. We compared 5 categories: 69 class III obese (body mass index [BMI] ≥40) patients, 128 class II obese patients (BMI 35.0 to 39.9), 318 class I obese patients (BMI 30.0 to 34.9), 487 overweight patients (BMI 25.0 to 29.9), and 318 normal weight patients (BMI 18.5 to 24.9). Exercise capacity in METs, weight, blood pressure, and fasting lipid profile were measured before and after CR. Overall, 131 patients gained weight, 827 had no significant weight change, and 363 lost weight (176 lost 3% to 5% of their baseline weight, 161 lost 5% to 10%, and 26 lost >10%). Exercise capacity, blood pressure, and low-density lipoprotein cholesterol improved in all patients. Class III obese patients had the smallest improvement in peak METs (p <0.001), but the greatest weight loss. Patients who lost >10% of their baseline weight had the greatest improvements in exercise capacity, low-density lipoprotein, and triglycerides. In conclusion, after CR, a minority of patients lost weight. Most patients had no significant weight change and some even gained weight. The greatest loss was seen in class III obese patients. All patient groups showed improvements in exercise capacity and risk factors, regardless of the direction or degree of weight change.

Cardiac rehabilitation in African Americans: evidence for poorer outcomes compared with whites, especially in women and diabetic participants.

BACKGROUND: Cardiac rehabilitation (CR) improves coronary artery disease risk factors and mortality. Outcomes after CR in African Americans (AAs) compared with whites have not been studied extensively. METHODS: A total of 1,096 patients (169 AAs, 927 whites) were enrolled in a 36-session CR program for ischemic heart disease or postcardiac surgery. The program consisted of exercise, lifestyle modification, and pharmacotherapy. RESULTS: After CR, quality of life, blood pressure, and low-density lipoprotein cholesterol improved significantly in both AAs and whites, although to a lesser degree in AAs. Whites also had significant improvements in weight and triglyceride concentrations. Overall, mean peak exercise capacity, measured in metabolic equivalents (METs), improved by only 1.6 (95% CI 1.3-1.8) in AAs compared with 2.4 (2.3-2.6) in CCs (P< .001 for AAs vs CCs). African American women had the least improvement in METs, but changes were still significant (1.1 [CI 0.9-1.4]). The subgroup with the least improvement in METs was AA diabetic patients (1.4 (CI 1.1-1.7]). CONCLUSION: African Americans derive a significant benefit from CR, but not to the same degree as whites, based on changes in risk factors and in exercise capacity. Within both ethnic groups, both women and diabetic patients appeared to have markedly less improvement.

Effect of early enrollment on outcomes in cardiac rehabilitation.

Outpatient cardiac rehabilitation (CR) is most beneficial when delivered 1 to 3 weeks after the index cardiac event. The effects of delayed enrollment on subsequent outcomes are unclear. A total of 1,241 patients were enrolled in CR after recent (<1 year) treatment of cardiac events or postcardiac surgery. Risk factors and metabolic equivalent levels (METs) during aerobic exercise were calculated before and after CR. The mean CR delay time was 34 days (maximum of 327). Delay time >30 days was associated with older age, female gender, nonwhite race, being unemployed, and increased length of hospital stay before CR after index cardiac event (p <0.05 vs 0 to 15 and 16 to 30 days for all comparisons). Patients with delay time >30 days had significant improvements in all CR metrics, but peak METs and weight improvements were lesser in magnitude compared with patients with CR delay times 0 to 15 and 16 to 30 days. After multivariate adjustment, delay time >30 days remained an independent predictor of decreased MET improvement compared with delay time 0 to 15 days (ß = -0.59, p <0.001). In conclusion, time to enrollment in CR varies substantially and is independently linked to demographics and length of index hospital stay. Delayed enrollment in CR is directly related to patient outcomes. Although all patients showed improvements in key metrics regardless of delay time, CR was of greatest benefit, particularly for weight and exercise capacity, when initiated within 15 days of the index event.

Small, short-duration, dobutamine-induced perfusion defects are not associated with adverse prognosis in intermediate-risk individuals receiving cardiovascular magnetic resonance stress imaging.

OBJECTIVE: The objective of this study was to assess the frequency and prognostic utility of small, short-duration left ventricular myocardial perfusion defects during dobutamine cardiovascular magnetic resonance (DCMR) stress imaging. METHODS: We performed first-pass contrast-enhanced DCMR at peak stress in 331 consecutively recruited individuals (aged 68 ± 8 years, 50% men) at intermediate risk for a future cardiac event. Size, location, and persistence of low-signal intensity perfusion defects were recorded. Cardiac events were assessed by personnel blinded to imaging results for a median of 24 months after the DCMR. RESULTS: Among the 55 individuals (16.6%) who exhibited small (<25% myocardial thickness) and short-duration (<5 frames in persistence) perfusion defects, diabetes was more prevalent (P = 0.019) and no cardiac events were observed. Large, persistent perfusion defects were associated with coronary artery disease, prior myocardial infarction, and decreased left ventricular function (P < 0.001 for all) and increased 2-year risk for a cardiac event (hazard ratio, 10.3; P < 0.001; confidence interval, 3.3-33.0). CONCLUSIONS: In individuals with diabetes, hypertension, or coronary artery disease at intermediate risk for a future cardiac event, small, short-duration DCMR perfusion defects are not associated with increased 2-year risk for a subsequent cardiac event.

Effects of cardiac rehabilitation in diabetic patients: both cardiac and noncardiac factors determine improvement in exercise capacity.

BACKGROUND: Diabetic patients have a worse prognosis than nondiabetic patients after myocardial infarction. Although exercise improves risk factors, exercise capacity, and mortality, it is still unclear if these benefits are the same as in nondiabetics. Furthermore, although exercise tolerance is predicted by systolic and diastolic dysfunction in nondiabetics, its role as a predictor of exercise capacity in diabetics remains unclear. HYPOTHESIS: Diabetics and nondiabetics see a similar improvement in their cardiac risk factors and exercise parameters from exercise-based cardiac rehabilitation (CR). METHODS: A series of 370 diabetics and 942 nondiabetics entered a 36-session outpatient CR program after interventions for coronary heart disease or after bypass or cardiac valve surgery. The program consisted of physical exercise, lifestyle modification, and pharmacotherapy. RESULTS: Quality of life, weight, blood pressure, and lipid profiles improved significantly in both groups during the 12-week program. Baseline metabolic equivalents (METs) were lower in diabetics vs nondiabetics at the start of CR (2.4 vs 2.7, P < 0.001). Although both groups increased their exercise capacity, diabetics had less improvement (change in METs 1.7 vs 2.6, P < 0.001). Significant predictors for improvement after CR included age, sex, and weight, as well as both systolic and diastolic function. After adjustment for these, diabetes remained a significant predictor of reduced improvement in exercise capacity. CONCLUSIONS: Diabetics saw a significant benefit in quality of life, weight, exercise tolerance, and cardiac risk factors, but to a lesser extent when compared with nondiabetics. The mechanisms for poorer improvement in diabetics following CR also include noncardiac factors and require further study.

Comparison of usefulness of secondary prevention of coronary disease in patients <80 versus ≥80 years of age.

The population older than 80 years is increasing but data on prevention of coronary disease in this age group are sparse. The present study compared the improvement in quality of life, lipid profile, blood pressure, weight, and physical performance after cardiac rehabilitation in patients <80 versus ≥80 years of age. A total of 1,112 patients, of whom 79 were older than 80 years, entered a 36-session outpatient cardiac rehabilitation program after interventions for coronary heart disease. The program consisted of physical exercise, lifestyle modification, and pharmacotherapy. Quality of life improved by 1.3 (95% confidence interval [CI] 0.6 to 2.0) in octogenarians and 1.8 (95% CI 1.5 to 2.1) in younger patients (p = 0.21), whereas weight decreased by 1.7 lbs (95% CI -2.9 to -0.4) and 3.1 lbs (95% CI -3.6 to -2.5, p = 0.04), respectively. In hypertensive patients, systolic blood pressure decreased from 155 ± 11 to 133 ± 20 mm Hg in octogenarians versus 155 ± 13 to 130 ± 20 mm Hg in younger patients, reducing the prevalence of hypertension to approximately 10% in both groups. Low-density lipoprotein cholesterol decreased by 16 mg/dl (95% CI -27 to -5) versus 19 mg/dl (95% CI -22 to -16), increasing the percentage of patients at recommended goals from 32% to 46% in the elderly (p = 0.04) and from 18% to 30% in younger patients (p <0.001). Metabolic equivalent levels increased by 1.0 (95% CI 0.7 to 1.3) in octogenarians versus 2.4 (95% CI 2.2 to 2.5) in younger patients (p <0.001). In conclusion, patients ≥80 years of age in an active secondary prevention program derive a significant benefit in well being, risk factors, and exercise capacity and should not be denied such treatment because of age.

Left ventricular hypertrophy influences cardiac prognosis in patients undergoing dobutamine cardiac stress testing.

BACKGROUND: This study was performed to determine the utility of dobutamine stress test results for predicting myocardial infarction (MI) and cardiac death in patients with chest pain and left ventricular hypertrophy (LVH). METHODS AND RESULTS: Three hundred fifty-three participants with a mean+/-SD age of 64+/-12 years (54%men) underwent dobutamine cardiovascular magnetic resonance stress testing and then were followed up for 6+/-2 years (mean+/-SD; range, 0.5-11.5) to assess the post-dobutamine cardiovascular magnetic resonance stress test occurrence of MI or cardiac death. LV mass and the presence or absence of ischemia were determined; LVH was defined as an LV mass index >96 g/m(2) in men and >77 g/m(2) in women. LVH was present in 62 participants (18% of the men and 17% of the women, P=0.90). Seventy-one (20%) participants experienced an MI or cardiac death during follow-up. The MI and cardiac death rate was more frequent in those with versus without LVH (32% vs 17%, P=0.009). In multivariable analysis that accounted for the presence of preexisting coronary artery disease, hypertension, diabetes, stress-induced ischemia, and reduced LV ejection fraction, LVH was an independent predictor of MI and cardiac death (hazard ratio=1.99; 95% CI, 1.13-3.50; P=0.02). CONCLUSIONS: LVH is predictive of future MI and cardiac death in patients with or without inducible ischemia during dobutamine cardiac stress testing. As a result, LVH should be reported in those referred for dobutamine cardiac stress tests, particularly in those without inducible ischemia, in whom one would otherwise assume a favorable cardiac prognosis.

Relation of homocysteine and C-reactive protein to urinary albumin loss.

This study shows that elevated high-sensitivity C-reactive protein and plasma total homocysteine contribute independently to the likelihood of an increased urinary albumin:creatinine ratio. This result suggests that total homocysteine and C-reactive protein may be acting by separate mechanistic pathways.

Design and statistical issues in the homocysteinemia in kidney and end stage renal disease (HOST) study.

The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No. 453, is a prospective, randomized, two arm, double blind study of patients with end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined as an estimated creatinine clearance of 30 ml/min or less). Its primary objective is to determine whether administration of high doses of three vitamins, folic acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels, will reduce all cause mortality. The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infarction, stroke, amputation of a lower extremity, a composite of death and the foregoing three events, the plasma homocysteine level, and, in ESRD patients undergoing hemodialysis, thrombosis of the vascular access. A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone (or, if necessary, by mail). The subject is contacted every three months throughout the duration of the study from a central location. The study drug is shipped to the patient from a central location rather supplied locally. In a two year enrollment period, 2006 patients are to be enrolled. The duration of the observation period is four to six years. Data will be stored and analyzed at a coordinating center. The study design has the power to detect a reduction in all cause mortality rate of 17%. Issues related to the unique features of the design of this study are discussed.

Association between hyperhomocysteinemia and primary pulmonary hypertension.

STUDY OBJECTIVE: This case-control study was conducted to test the hypothesis that fasting homocysteine levels are higher in PPH patients than in healthy controls. DESIGN: Levels of plasma total homocysteine, serum folate, vitamin B-12, and serum creatinine in 18 consecutive patients with PPH were compared with data from 36 age- and sex-matched controls. RESULTS: Eight of the 18 patients (44.4%) and three of the 36 controls (8.3%) had elevated plasma total homocysteine (tHcy) levels (> or = 15 mol/l, odds ratio 8.8; 95% CI: 2.0-39.6; P = 0.005). There was an inverse correlation between tHcy levels and creatinine clearance in patients with PPH (P = 0.036). CONCLUSION: PPH patients are significantly more likely to have hyperhomocysteinemia, and higher mean plasma total homocysteine levels than in controls. Plasma total homocysteine may be an important factor in the pathogenesis of PPH.

Usefulness of plasma vitamin B(6), B(12), folate, homocysteine, and creatinine in predicting outcomes in heart transplant recipients.

Atherothrombotic complications are frequently seen in patients undergoing heart transplantation. These patients have high plasma total homocysteine concentrations associated with lower folate and vitamin B(6) levels. The relation between these metabolic abnormalities and the development of vascular complications, however, remains unclear. Fasting plasma total homocysteine, folate, vitamin B(12), vitamin B(6), and creatinine were measured in 160 cardiac transplant recipients who were followed for a mean duration of 28 +/- 9 months after blood draw (mean 59 +/- 28 months after transplant). Cardiovascular events and causes of mortality were determined and Cox proportional-hazards regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Twenty-five patients developed cardiovascular events and 17 died (11 cardiovascular deaths). Mean +/- SD total homocysteine value was 18.4 +/- 8.5 (range 4.3 to 63.5 micromol/L). Hyperhomocysteinemia (> or =15 micromol/L) was seen in 99 patients (62%). Levels were no different in patients with or without cardiovascular complications/death (16.8 +/- 6.2 vs 18.9 +/- 9 micromol/L, p = 0.4). However, vitamin B(6) deficiency was seen in 21% of recipients with and in 9% without cardiovascular complications/death (p = 0.05). The relative risk for cardiovascular events, including cardiovascular death, increased 2.7 times (confidence interval 1.2 to 5.9) for B(6) levels < or =20 nmol/L compared with those with normal B(6) levels (p = 0.02). Thus, hyperhomocysteinemia is common in transplant recipients but may have no causal role in the atherothrombotic vascular complications of transplantation. Deficiency of vitamin B(6), however, may predict adverse outcomes, suggesting a possible role for supplementation with this vitamin.