Peak oxygen consumption and the minute ventilation/carbon dioxide production relation slope in morbidly obese men and women: influence of subject effort and body mass index.

The authors evaluated the minute ventilation/carbon dioxide production relation (VE/VCO2 slope) as a complementary measure to peak oxygen consumption (peak VO2) in 76 patients (mean +/- SD age = 44.3+/-10.8 years, 69.7% female) with morbid obesity (mean +/- SD body mass index [BMI] = 49.4+/-7.0 kg/m(2)), as it is not limited by effort. Nearly one-half (43%) of the patients achieved a peak respiratory exchange ratio <1.10. Mean peak VO2 and VE/VCO2 slope were 17.0+/-3.7 mL/kg/min and 27.8+/-4.0, respectively. Peak VO2 correlated with BMI (r=-0.45, P<.0001), while VE/VCO2 slope did not (r=-0.04, P=.73). There was a linear trend for declining mean peak VO2 (P=.001) but not for VE /VCO2 slope (P=.59) with increasing BMI quintiles. The VE/VCO2 slope is an effort-independent measure that is also independent of BMI and may serve as an adjunctive cardiorespiratory variable when evaluating morbidly obese men and women.

Caloric expenditure in the morbidly obese using dual energy X-ray absorptiometry.

Total caloric expenditure is the sum of resting energy expenditure (REE) and caloric expenditure during physical activity. In this study, we examined total caloric expenditure in 25 morbidly obese patients (body mass index>or=35 kg/m(2)) using dual energy X-ray absorptiometry (DXA) scanning and cardiorespiratory exercise testing. Our results show average REE for all individuals was 2027+/-276 kcal/d and mean net caloric expenditure during 30 min of exercise was 115+/-16 kcals. Assuming the mean of all input values, a strict 1500 kcal/d diet combined with 150 min per wk of structured physical activity, the projected weight change was -7% (8.8+/-6.2 kg) for 6 mo. We conclude that morbidly obese individuals should be able to achieve only a modest weight loss by following minimal national guidelines. These data suggest that more aggressive energy expenditure and caloric restriction targets for long periods of time are needed to result in significant weight loss in this population.

Cardiorespiratory fitness and short-term complications after bariatric surgery.

BACKGROUND: Morbid obesity is associated with reduced functional capacity, multiple comorbidities, and higher overall mortality. The relationship between complications after bariatric surgery and preoperative cardiorespiratory fitness has not been previously studied. METHODS: We evaluated cardiorespiratory fitness in 109 patients with morbid obesity prior to laparoscopic Roux-en-Y gastric bypass surgery. Charts were abstracted using a case report form by reviewers blinded to the cardiorespiratory evaluation results. RESULTS: The mean age (+/- SD) was 46.0 +/- 10.4 years, and 82 patients (75.2%) were female. The mean body mass index (BMI) was 48.7 +/- 7.2 (range, 36.0 to 90.0 kg/m(2)). The composite complication rate, defined as death, unstable angina, myocardial infarction, venous thromboembolism, renal failure, or stroke, occurred in 6 of 37 patients (16.6%) and 2 of 72 patients (2.8%) with peak oxygen consumption (Vo(2)) levels < 15.8 mL/kg/min or > 15.8 mL/kg/min (lowest tertile), respectively (p = 0.02). Hospital lengths of stay and 30-day readmission rates were highest in the lowest tertile of peak Vo(2) (p = 0.005). There were no complications in those with BMI < 45 kg/m(2) or peak Vo(2) > or= 15.8 mL/kg/min. Multivariate analysis adjusting for age and gender found peak Vo(2) was a significant predictor of complications: odds ratio, 1.61 (per unit decrease); 95% confidence interval, 1.19 to 2.18 (p = 0.002). CONCLUSIONS: Reduced cardiorespiratory fitness levels were associated with increased, short-term complications after bariatric surgery. Cardiorespiratory fitness should be optimized prior to bariatric surgery to potentially reduce postoperative complications.

Substantial weight gain during adulthood: the road to bariatric surgery.

We sought to examine the relationship of body mass index (BMI) at age 18 years with the degree and rate of rise in body weight during adulthood among the morbidly obese. We evaluated 196 patients with a standard medical history form and a structured interview with questions regarding weight at age 18 years. The study included 40 (20.4%) men and 156 (79.6%) women. The mean BMI was 50.2+/-8.0 kg/m2, range 37.0-80.0 kg/m2. Based on self-reported weight, 133 (67.9%) were overweight/obese (BMI >25 kg/m2) and 68 (34.7%) were obese (BMI > or =30 kg/m2) at age 18 years. The distribution of cumulative weight gain was normal with a mean of 60.8+/-23.7 kg. There was a positive relationship (r=0.36, p<0.0001) between BMI at age 18 years and BMI in adulthood at a mean of 44+/-10.6 years. Independent predictors for cumulative adult weight gain were BMI at age 18 years (p<0.0001); women (p<0.0001); African Americans (p=0.05). These data suggest that modestly overweight young adults can have excessive weight gains during adult life, resulting in morbid obesity and high rates of obesity-related comorbidities.

Bundle branch block patterns, age, renal dysfunction, and heart failure mortality.

BACKGROUND: The determinants of bundle block patterns and their relationship to mortality in heart failure patients is not completely understood. METHODS: We evaluated 2907 consecutive patients admitted to an intensive care unit with decompensated heart failure over 8 years. Clinical and echocardiographic factors were analyzed using multivariate techniques. All-cause mortality was available on greater than 99.0% of patients at a median of 23 months after discharge. RESULTS: Right and left bundle branch blocks occurred in 211 (7.3%) and 386 (13.2%), p<0.0001. Older age, decreased left ventricular ejection fraction, and renal dysfunction were all found to be independently associated with bundle branch block patterns. Mortality rates for the subgroups of QRS<120 ms, right bundle branch block and left bundle branch block, over a mean follow-up of 23.4+/-2.6 months were 46.1%, 56.8% and 57.7%, p<0.0001 for comparison of QRS<120 ms versus either bundle pattern. Cox proportional hazards model adjusting for age, sex, ejection fraction, and renal function demonstrated graded decrements in survival in those with QRS<120 ms, right bundle branch block and left bundle branch block, p=0.03. CONCLUSIONS: In patients hospitalized with severe heart failure, age, left ventricular dysfunction, and renal dysfunction are associated with bundle branch block patterns. When controlling for these factors, bundle branch block patterns are independently associated with slightly higher all cause mortality after discharge.

Changes in B-type natriuretic peptide levels in hemodialysis and the effect of depressed left ventricular function.

B-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted by the cardiac ventricles in response to volume expansion, pressure overload, and resultant increased wall tension. Previous research has shown elevated BNP levels in patients with volume overload caused by end-stage renal disease (ESRD). This pilot study was designed to describe the relative reduction in BNP that occurs as a result of hemodialysis (HD) in relation to baseline left ventricular function. Hemodialysis patients (n = 34) with ESRD were enrolled in a prospective manner. All patients had blinded serum BNP levels measured at the initiation and termination of HD. Levels of BNP were also measured in the dialysate and any residual urine, if available. In addition, monthly urea reduction ratio (URR) and Kt/V were obtained. The most recent measurement of left ventricular ejection fraction (LVEF) by any method was obtained from chart review. The BNP reduction ratio (BNPRR) was calculated by the following expression: pre-BNP-post-BNP/pre-BNP. The mean age was 50.8 years, 50.0% were male, and 55.9% were African American. A mean of 3239.4 mL of fluid was removed during HD. The mean pre-BNP, post-BNP, and change in BNP were 556.3 +/- 451.5 pg/mL, 538.6 +/- 488.3 pg/mL, and -17.6 +/-147.0 pg/mL. Of the 27 patients who had both pre-BNP and post-BNP values in the measurable range (< 1,300 pg/mL), BNP rose in 9 (33.3%) and fell in 18 (66.7%). The BNPRR had the following correlations: volume removed, r = -0.33, P = .07; Kt/V, r = -0.51, P = .01; URR, r = -0.34, P = .09; and change in body weight, r = -0.33, P = .07. The BNPRR was not correlated with time on dialysis or change in blood pressure. A total of 20 patients had LVEF recorded and post-BNP levels in the measurable range. For this group, the BNPRR values stratified by lowest to highest LVEF group were 4.6%, 19.1%, and 21.8%; P = .95 for trend. The BNP values were elevated in ESRD patients and decreased slightly during HD. This change was more pronounced in patients with normal or mildly impaired LVEF. The BNPRR correlated with the volume removed, change in body weight, and Kt/V. Future research with the BNPRR as a potential marker of the adequacy of volume removal in HD is warranted.

Outcomes and prognostic factors of systolic as compared with diastolic heart failure in urban America.

We sought to describe a large heart failure (HF) population with respect to systolic and diastolic abnormalities in terms of demographics, echocardiographic parameters, and survival. Using data abstracted from the Resource Utilization Among Congestive Heart Failure (REACH) study, a targeted subpopulation of 3471 patients had electrocardiographic, echocardiographic, and clinical data taken from automated sources during the first year of diagnosis. Among the HF population, 1811 (52.2%) had diastolic HF. Prevalence of diastolic HF trended with age, from 46.4% in those less than 45 years to 58.7% in those 85 years or older (p=0.001 for trend). Patients with diastolic HF had a higher mean ejection fraction (55.7% vs. 28.0%), lower left ventricular end-systolic diameter (3.11 vs. 4.74 cm), and lower left atrium:aortic outlet ratio (1.28 vs. 1.38) (p=0.001 for each comparison). Annualized age, sex, and race-adjusted mortality were 11.2% and 13.0% for those with diastolic and systolic HF, respectively (p=0.001). In a large, racially mixed, urban HF population, those with diastolic HF predominate and enjoy better-adjusted survival than counterparts with systolic HF.

Relationship between obesity and B-type natriuretic peptide levels.

BACKGROUND: The relationships among B-type natriuretic peptide (BNP) levels, body mass index (BMI), and congestive heart failure (CHF) as an emergency diagnosis are unknown. METHODS: Of 1586 participants in the Breathing Not Properly Multinational Study who had acute dyspnea, 1369 (86.3%) had BNP values and self-reported height and weight. Two independent cardiologists masked to the BNP results adjudicated the final diagnosis. RESULTS: Congestive heart failure was found in 46% of participants. Individuals with higher BMIs were younger and had more frequent edema on examination but were equally as likely to have CHF vs noncardiac sources of dyspnea. A nearly 3-fold difference was seen in mean +/- SD BNP values at the low and high extremes of the BMI groupings (516.7 +/- 505.9 vs 176.3 +/- 270.5 pg/mL, respectively; P< .001). The correlations between BMI and log BNP among those with and without CHF were r = -0.34 and r = -0.21, respectively (P< .001 for both). Multivariate analysis for the outcome of log BNP among a small subset with CHF (n = 62) found that Framingham score (P = .002), estimated glomerular filtration rate (P = .007), female sex (P = .03), New York Heart Association functional class (P = .09), and third heart sound (P = .08) were independent predictors. However, BMI was not found to be independently related to log BNP (P = .59). CONCLUSIONS: In patients with and without CHF, BNP levels are inversely related to BMI. When considering demographics, severity of disease, and renal function, BMI is not independently related to BNP levels in a small subgroup when detailed information about CHF severity is known.

Determinants of coronary vascular calcification in patients with chronic kidney disease and end-stage renal disease: a systematic review.

BACKGROUND: Vascular calcification (VC) is a recognized process involved in senescence and atherosclerosis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are conditions associated with metabolic disorders related to soft tissue calcification. METHODS: We performed a systematic review of the literature confined to patients with CKD or ESRD with clinical observations of VC. Case reports of calciphylaxis were excluded. We identified 30 studies over 20 years: 11 prospective cohort, 7 cross-sectional, 11 case-control, and 1 retrospective cohort; n = 2918 subjects, mean age 51 years, 59% men and 41% women. Imaging methods used included: x-ray 43%, computed tomography 30%, ultrasound 17%, and other methods 10%. RESULTS: The most consistent determinants of VC were older age and dialysis vintage. Eight analyses determined a relationship between VC and measures of calcium-phosphate balance while 20 analyses specifically did not find such a relationship. Three studies suggested the degree of calcium loading, treatment with phosphate binders, or treatment with vitamin D analogues were related to VC. When taken into consideration, the lipid profile (primarily low high-density lipoprotein cholesterol, elevated triglycerides, elevated low-density lipoprotein, and elevated total cholesterol) were predictive factors in four analyses. CONCLUSIONS: VC is a common observation in CKD and ESRD and is mainly related to age, length of time on dialysis therapy, and possibly dyslipidemia. The calcium-phosphorus balance and its related treatments are likely not related to this unique form of vascular calcification. Further research into the determinants and potential treatments for vascular calcification is warranted.

Ximelagatran: a novel oral direct thrombin inhibitor for long-term anticoagulation.

The ideal anticoagulant agent would have a fixed oral dose without need for dose adjustment, a wider therapeutic window than that of warfarin, and acceptable bleeding risks without the need for routine coagulation monitoring. Ximelagatran is a new oral agent that, when converted to its active form, melagatran, directly inhibits thrombin, thus blocking its activity and modulating several of its key functions. For the prevention of venous thromboembolism after orthopedic surgery, treatment of venous thromboembolism, and prevention of stroke in patients with atrial fibrillation, clinical trials indicate that ximelagatran meets the criteria for a superior anticoagulant.

Chronic kidney disease and sudden death: strategies for prevention.

The association between chronic kidney disease and cardiovascular death is accounted for, in part, by higher rates of serious arrhythmias. Research shows an independent relationship between worsened renal function and atrial fibrillation, heart block, ventricular tachycardia, ventricular fibrillation, and asystole. These higher rates also associate with underlying structural heart disease including left ventricular hypertrophy, cardiac fibrosis, valvular disease, and left ventricular systolic and diastolic dysfunction. In addition, chronic intermittent ischemia is implicated in the arrhythmias observed during hemodialysis. The superimposed conditions of acidosis and fluxes in both potassium and magnesium also contribute to higher rates of arrhythmias. Baseline estimated glomerular filtration rate is linked to worsened outcomes and increased defibrillation thresholds in patients receiving implantable cardioverter defibrillators. Preventive strategies include meticulous management of electrolytes, baseline treatment for cardiovascular disease, and when indicated, implantable cardioverter defibrillators. Future research into the mechanisms and prevention of sudden cardiac death in patients with chronic kidney disease is warranted.

Epidemiology of contrast-induced nephropathy.

Decreasing levels of renal function act as a major adverse prognostic factor after contrast exposure with or without percutaneous coronary intervention. In chronic kidney disease, the most important risk factor for the development of contrast-induced nephropathy (CIN) is an estimated glomerular filtration rate

B-type natriuretic peptide and renal disease.

B-type natriuretic peptide (BNP) is a cardiac neurohormone which has a principal effect on the kidney to signal both natriuresis and diuresis. Both BNP and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, the relationships between BNP, renal function, and CHF as an emergency diagnosis, are not completely understood. The correlation between BNP and estimated glomerular filtration rate (eGFR) is approximately r = -0.20. At an eGFR < 60 ml/min/1.73 m2, the optimum cutpoint for BNP to diagnose CHF rises to approximately 200 pg/ml. At this cutpoint the area under the receiver operating characteristic curve is 0.81, indicating that BNP is of diagnostic value in this group. Importantly, the precursor molecule N-terminal proBNP has a stronger correlation with eGFR of approximately -0.60, and is influenced by the age-related decline in renal function above the lower bounds of normal of < 60 ml/min/1.73 m2. Because BNP is a principal messenger from the heart to the kidneys, and because it is influenced by renal filtering function, parenchymal mass, and tubular function, BNP can be leveraged in assisting in the diagnosis and management of combined heart and renal failure.

Sorting out the evidence on natriuretic peptides.

B-type natriuretic peptide (BNP) is a cardiac neurohormone released as pre-proBNP and then enzymatically cleaved to the N-terminal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP and NT-proBNP have been used to identify patients with heart failure (HF). Clinical considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, interpretation of their units of measure, and the rapid availability of the test results. The BNP assay is currently used as a diagnostic and prognostic aid in HF and as a prognostic marker in acute coronary syndromes (ACS). In general, a BNP level less than 100 pg/mL excludes acutely decompensated HF. In the absence of renal dysfunction, NT-proBNP has also been shown to be of diagnostic value in HF, related to HF severity, predictive of sudden death, and prognostic for death in ACS. This article will sort out the literature concerning the use of these peptides in a variety of clinical scenarios.

Angiotensin converting enzyme inhibitors and beta-blockers in African Americans with heart failure.

Previous analyses have implied diminished efficacy of angiotensin converting enzyme inhibitors (ACEI), and equivalent or enhanced efficacy of beta-blockers (BB), in African Americans (AA) with congestive heart failure (CHF), when compared to placebo. These results may have been influenced by lead-time bias, in that AA may not have been entered into the older ACEI trials until late in their CHF course. Our goal was to use a prospective cohort study of 29,686 CHF patients within a single health system to examine the impact on AA mortality of administering ACEI and BB within the first year of CHF diagnosis. Pharmacy claims from 1995-1998 were available for 3353 newly diagnosed CHF patients (39.2% AA; N=1317) within the health maintenance organization. Rates of ACEI and BB use were 46.4% and 54.0%; 43.4% and 28.9%; and 40.7% and 18.6%, for Whites, AA, and other races, respectively. The relative risk reductions (RRR) for ACEI were 68.7%, P<.0001; 52.1%, P<.0001; and -36.3%, P=.56, for Whites, AA, and other races, respectively. The RRR for BB were 59.0%, P<.0001; 34.6%, P=.009; and 74.3%, P=.17, for Whites, AA, and other races, respectively. Age- and gender-adjusted survival rates for AA were significantly enhanced in those taking ACEI, BB, or a combination of the two: P<.001, P=.001, and P=.003, respectively. Although we could not control for selection bias, these data suggest that AA benefit from both ACEI and BB when treatment is initiated within the first year of CHF diagnosis. Future, similar analyses other databases should control for the duration of illness to avoid lead-time bias in AA with CHF.

Opportunities for improvement in the diagnosis and treatment of heart failure.

BACKGROUND: Improved treatment of congestive heart failure (CHF) can slow disease progression, promote clinical stability, and prolong survival. HYPOTHESIS: Patterns in diagnostic test utilization and pharmacotherapy among patients with newly diagnosed heart failure may affect outcomes. METHODS: Claims data were analyzed from all diagnostic procedures and prescriptions from 1995 to 1998 in 3,353 patients with heart failure diagnosed within 1 year. Rates of diagnostic testing and categories of drugs prescribed were the main outcome measures. Demographic variables and type of provider were analyzed within a setting whose access to care was controlled. RESULTS: Rates of diagnostic testing with respect to basic, metabolic/endocrine, alternative diagnoses, underlying ischemia, and left ventricular function varied as a function of gender, age, race, and primary versus specialty care provider. Only 4.7% of patients underwent all diagnostics and treatments recommended in current guidelines. However, those patients (27.5%) who underwent an evaluation for ischemic heart disease and were prescribed vasodilators or beta blockers enjoyed the lowest crude mortality. CONCLUSIONS: There are multiple opportunities apparent to improve the initial diagnostic and therapeutic care of patients with heart failure. There appears to be an early survival benefit with respect to use of vasodilators and beta blockers within the first year of treatment.

Performance of multiple cardiac biomarkers measured in the emergency department in patients with chronic kidney disease and chest pain.

OBJECTIVE: To evaluate the individual components of a cardiac multimarker panel in the detection of acute myocardial infarction (AMI) in patients with chest pain across a spectrum of renal dysfunction. METHODS: A total of 817 consecutive patients evaluated for a possible AMI in the emergency department (ED) enrolled in a prospective study of cardiac biomarkers assessed using a point-of-care device with myoglobin (MYO), cardiac troponin I (cTnI), and creatine kinase myocardial band (CK-MB), recorded at 0, 1.5, 3, and 9 hours. This study did not exclude patients on the basis of renal dysfunction. Baseline renal function was available in 808 patients. Patients were stratified by corrected creatinine clearance (CorrCrCl) into quartiles, and those on dialysis (n = 51) were considered as a fifth comparison group. Those patients with advanced renal dysfunction (CorrCrCl < 47/mL/min/72 kg) or on dialysis had higher rates of diabetes, hypertension, and prior coronary disease. Agreement for the diagnosis of AMI was required of two independent cardiologists using criteria based on history, electrocardiogram, and central laboratory assessment of serial cardiac markers. RESULTS: More than 99% of all patients were admitted to a chest pain observation unit or the hospital. Mean MYO levels were elevated in the presence of renal dysfunction in those with and without myocardial infarction. Both MYO and CK-MB were correlated with CorrCrCl, (r = -0.36, p < 0.01, and r = -0.10, p = 0.01, respectively), while cTnI was not (r = -0.10, p = 0.12). Using multiple receiver operating characteristic curve testing, cTnI was found to be the most consistent marker across all strata of renal dysfunction, including end-stage renal disease on dialysis. The authors did not find a trend for false-positive cTnI and renal dysfunction. CONCLUSIONS: A point-of-care, rapid cardiac biomarker strategy utilizing cTnI is applicable and superior to MYO or CK-MB in the evaluation of chest pain in patients with renal dysfunction.

Emergency evaluation of chest pain in patients with advanced kidney disease.

BACKGROUND: Increased rates of myocardial infarction, heart failure, arrhythmias, and death occur in patients with chronic kidney disease. We sought to evaluate the processes of care and outcomes in patients with chronic kidney disease presenting to an emergency department with chest discomfort. METHODS: We enrolled 817 consecutive patients who underwent evaluation for a possible acute myocardial infarction in a prospective study of cardiac biomarkers. Renal dysfunction did not exclude patients from this study, and baseline renal function and 30-day outcomes were available in 808. Patients were stratified by corrected creatinine clearance rate into quartiles, with those undergoing dialysis (n = 51) as a fifth comparison group. RESULTS: Those patients with advanced renal dysfunction (corrected creatinine clearance rate, <47.0 mL/min [<0.8 mL/s] per 72 kg) or who underwent dialysis had higher rates of diabetes, hypertension, and prior coronary disease. More than 99% of all patients were admitted to a chest pain observation unit or to the hospital. Rates of stress testing were lower as renal dysfunction worsened. Rates of revascularization, however, were similar for all groups. The most frequent in-hospital complication was the development of heart failure, which occurred in 36.5% of those with a corrected creatinine clearance rate of less than 47.0 mL/min per 72 kg. At 30 days, this group had the highest rates of cumulative myocardial infarction, development of heart failure, and death (40.2%). CONCLUSION: Chronic kidney disease is a marker for in-hospital and 30-day outcomes in patients presenting to the emergency department with chest discomfort.

Determinants of serum creatinine trajectory in acute contrast nephropathy.

The aim of this study was to describe the trajectory of creatinine (Cr) rise and its determinants after exposure to radiocontrast media. Included were 98 subjects who underwent cardiac catheterization and were randomized to forced diuresis with i.v. crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure was < 20 mmHg), and low dose dopamine versus intravenous crystalloid and matching placebos. Baseline and postcatheterization serum Cr levels were analyzed in a longitudinal fashion, allowing for differences in the time between blood draws, to determine the different critical trajectories of serum Cr. The mean age, baseline serum Cr, and Cr clearance (CrCl) were 69.3 +/- 10.8 years, 2.5 +/- 0.9 mg/dL, and 31.4 +/- 12.1 mL/min, respectively. The clinically driven postprocedural observation time was 5.5 +/- 5.1 days (range 19 hours and one Cr value to 25.7 days and 18 values). The mean maximum Cr was 3.3 +/- 1.4, range 1.7-8.7 mg/dL). Longitudinal models support baseline Cr clearance predictions for the change in Cr at 24 hours, time as the determinant of Cr trajectory, and requisite monitoring. For any given individual, a rise in Cr of < or = 0.5 mg/dL in the first 24 hours after contrast exposure predicted a favorable outcome. Baseline renal function is the major determinant of the rate of rise, height, and duration of Cr trajectory after contrast exposure. Length of observation and frequency of laboratory measures can be anticipated from these models.