Showing papers in "Acc Current Journal Review in 2004"

Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

Abstract: Background End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. Methods We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. Results The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1....

Surgeon volume and operative mortality in the United States

Abstract: Background Although the relation between hospital volume and surgical mortality is well established, for most procedures, the relative importance of the experience of the operating surgeon is uncertain. Methods Using information from the national Medicare claims data base for 1998 through 1999, we examined mortality among all 474,108 patients who underwent one of eight cardiovascular procedures or cancer resections. Using nested regression models, we examined the relations between operative mortality and surgeon volume and hospital volume (each in terms of total procedures performed per year), with adjustment for characteristics of the patients and other characteristics of the providers. Results Surgeon volume was inversely related to operative mortality for all eight procedures (P=0.003 for lung resection, P<0.001 for all other procedures). The adjusted odds ratio for operative death (for patients with a low-volume surgeon vs. those with a high-volume surgeon) varied widely according to the procedure — f...

Plasma adiponectin levels and risk of myocardial infarction in men

Abstract: ContextAdiponectin, a recently discovered adipocyte-derived peptide, is involved in the regulation of insulin sensitivity and lipid oxidation and, purportedly, in the development of atherosclerosis and coronary heart disease in humans.ObjectiveTo assess prospectively whether plasma adiponectin concentrations are associated with risk of myocardial infarction (MI).Design, Setting, and ParticipantsNested case-control study among 18 225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw (1993-1995). During 6 years of follow-up through January 31, 2000, 266 men subsequently developed nonfatal MI or fatal coronary heart disease. Using risk set sampling, controls were selected in a 2:1 ratio matched for age, date of blood draw, and smoking status (n = 532).Main Outcome MeasureIncidence of nonfatal MI and fatal coronary heart disease by adiponectin level.ResultsAfter adjustment for matched variables, participants in the highest compared with the lowest quintile of adiponectin levels had a significantly decreased risk of MI (relative risk [RR], 0.39; 95% confidence interval [CI], 0.23-0.64; P for trend <.001). Additional adjustment for family history of MI, body mass index, alcohol consumption, physical activity, and history of diabetes and hypertension did not substantively affect this relationship (RR, 0.41; 95% CI, 0.24-0.70; P for trend <.001). Further adjustment for hemoglobin A1c or C-reactive protein levels also had little impact, but additional adjustment for low- and high-density lipoprotein cholesterol levels modestly attenuated this association (RR, 0.56; 95% CI, 0.32-0.99; P for trend = .02).ConclusionsHigh plasma adiponectin concentrations are associated with lower risk of MI in men. This relationship can be only partly explained by differences in blood lipids and is independent of inflammation and glycemic status.

C-reactive protein and the risk of developing hypertension

Abstract: tein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.951.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.361.69) (linear trend P.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP. Conclusion C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.

Childhood cardiovascular risk factors and carotid vascular changes in adulthood. The Bogalusa heart study

Abstract: CONTEXT Carotid artery intima-media thickness (IMT) is associated with cardiovascular risk factors and is recognized as an important predictive measure of clinical coronary atherosclerosis events in middle-aged and elderly populations. However, information on the association of carotid IMT in young adults with different risk factors measured in childhood, adulthood, or as a cumulative burden of each of the risk factors measured serially from childhood to adulthood is limited. OBJECTIVE To examine the association between carotid IMT in young adults and traditional cardiovascular risk factors measured since childhood. DESIGN, SETTING, AND PARTICIPANTS A cohort study of 486 adults aged 25 to 37 years from a semirural black and white community in Bogalusa, La (71% white, 39% men), who had at least 3 measurements of traditional risk factors since childhood, conducted between September 1973 and December 1996. MAIN OUTCOME MEASURE Association of carotid IMT with risk factors, including systolic blood pressure, lipoprotein levels, and body mass index. RESULTS Male vs female (0.757 mm vs 0.719 mm) and black vs white (0.760 mm vs 0.723 mm) participants had increased carotid IMT (P<.001 for both). In multivariable analyses, significant predictors for being in top vs lower 3 quartiles of carotid IMT in young adults were childhood measures of low-density lipoprotein cholesterol (LDL-C) level (odds ratio [OR], 1.42, corresponding to 1-SD change specific for age, race, and sex; 95% confidence interval [CI], 1.14-1.78) and body mass index (BMI; OR, 1.25; 95% CI, 1.01-1.54); adulthood measures of LDL-C level (OR, 1.46; 95% CI, 1.16-1.82), high-density lipoprotein cholesterol (HDL-C) level (OR, 0.67; 95% CI, 0.51-0.88), and systolic blood pressure (OR, 1.36; 95% CI, 1.08-1.72); and long-term cumulative burden of LDL-C (OR, 1.58; 95% CI, 1.24-2.01) and HDL-C (OR, 0.75; 95% CI, 0.58-0.97) levels measured serially from childhood to adulthood. An increasing trend in carotid IMT across quartiles of LDL-C level measured in childhood was observed, with a mean value of 0.761 mm (95% CI, 0.743-0.780 mm) for those at the top quartile vs 0.724 mm (95% CI, 0.715-0.734 mm) for those in the lower 3 quartiles (P<.001). CONCLUSIONS Childhood measures of LDL-C level and BMI predict carotid IMT in young adults. The prevention implications of these findings remains to be explored.

A multicenter risk index for atrial fibrillation after cardiac surgery

Abstract: CONTEXT Atrial fibrillation is a common, but potentially preventable, complication following coronary artery bypass graft (CABG) surgery. OBJECTIVES To assess the nature and consequences of atrial fibrillation after CABG surgery and to develop a comprehensive risk index that can better identify patients at risk for atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Prospective observational study of 4657 patients undergoing CABG surgery between November 1996 and June 2000 at 70 centers located within 17 countries, selected using a systematic sampling technique. From a derivation cohort of 3093 patients, associations between predictor variables and postoperative atrial fibrillation were identified to develop a risk model, which was assessed in a validation cohort of 1564 patients. MAIN OUTCOME MEASURE New-onset atrial fibrillation after CABG surgery. RESULTS A total of 1503 patients (32.3%) developed atrial fibrillation after CABG surgery. Postoperative atrial fibrillation was associated with subsequent greater resource use as well as with cognitive changes, renal dysfunction, and infection. Among patients in the derivation cohort, risk factors associated with atrial fibrillation were advanced age (odds ratio [OR] for 10-year increase, 1.75; 95% confidence interval [CI], 1.59-1.93); history of atrial fibrillation (OR, 2.11; 95% CI, 1.57-2.85) or chronic obstructive pulmonary disease (OR, 1.43; 95% CI, 1.09-1.87); valve surgery (OR, 1.74; 95% CI, 1.31-2.32); and postoperative withdrawal of a beta-blocker (OR, 1.91; 95% CI, 1.52-2.40) or an angiotensin-converting enzyme (ACE) inhibitor (OR 1.69; 95% CI, 1.38-2.08). Conversely, reduced risk was associated with postoperative administration of beta-blockers (OR, 0.32; 95% CI, 0.22-0.46), ACE inhibitors (OR, 0.62; 95% CI, 0.48-0.79), potassium supplementation (OR, 0.53; 95% CI, 0.42-0.68), and nonsteroidal anti-inflammatory drugs (OR, 0.49; 95% CI, 0.40-0.60). The resulting multivariable risk index had adequate discriminative power with an area under the receiver operating characteristic (ROC) curve of 0.77 in the validation sample. Forty-three percent (640/1503) of patients who had atrial fibrillation after CABG surgery experienced more than 1 episode of atrial fibrillation. Predictors of recurrent atrial fibrillation included older age, history of congestive heart failure, left ventricular hypertrophy, aortic atherosclerosis, bicaval venous cannulation, withdrawal of ACE inhibitor or beta-blocker therapy, and use of amiodarone or digoxin (area under the ROC curve of 0.66). Patients with recurrent atrial fibrillation had longer hospital stays and experienced greater infectious, renal, and neurological complications than those with a single episode. CONCLUSIONS We have developed and validated models predicting the occurrence of atrial fibrillation after CABG surgery based on an analysis of a large multicenter international cohort. Our findings suggest that treatment with beta-blockers, ACE inhibitors, and/or nonsteroidal anti-inflammatory drugs may offer protection. Atrial fibrillation after CABG surgery is associated with important complications.

Predicting mortality among patients hospitalized for heart failure. Derivation and validation of a clinical model

Abstract: ContextA predictive model of mortality in heart failure may be useful for clinicians to improve communication with and care of hospitalized patients.ObjectivesTo identify predictors of mortality and to develop and to validate a model using information available at hospital presentation.Design, Setting, and ParticipantsRetrospective study of 4031 community-based patients presenting with heart failure at multiple hospitals in Ontario, Canada (2624 patients in the derivation cohort from 1999-2001 and 1407 patients in the validation cohort from 1997-1999), who had been identitifed as part of the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study.Main Outcome MeasuresAll-cause 30-day and 1-year mortality.ResultsThe mortality rates for the derivation cohort and validation cohort, respectively, were 8.9% and 8.2% in hospital, 10.7% and 10.4% at 30 days, and 32.9% and 30.5% at 1 year. Multivariable predictors of mortality at both 30 days and 1 year included older age, lower systolic blood pressure, higher respiratory rate, higher urea nitrogen level (all P<.001), and hyponatremia (P<.01). Comorbid conditions associated with mortality included cerebrovascular disease (30-day mortality odds ratio [OR], 1.43; 95% confidence interval [CI], 1.03-1.98; P = .03), chronic obstructive pulmonary disease (OR, 1.66; 95% CI, 1.22-2.27; P = .002), hepatic cirrhosis (OR, 3.22; 95% CI, 1.08-9.65; P = .04), dementia (OR, 2.54; 95% CI, 1.77-3.65; P<.001), and cancer (OR, 1.86; 95% CI, 1.28-2.70; P = .001). A risk index stratified the risk of death and identified low- and high-risk individuals. Patients with very low-risk scores (≤60) had a mortality rate of 0.4% at 30 days and 7.8% at 1 year. Patients with very high-risk scores (>150) had a mortality rate of 59.0% at 30 days and 78.8% at 1 year. Patients with higher 1-year risk scores had reduced survival at all times up to 1 year (log-rank, P<.001). For the derivation cohort, the area under the receiver operating characteristic curve for the model was 0.80 for 30-day mortality and 0.77 for 1-year mortality. Predicted mortality rates in the validation cohort closely matched observed rates across the entire spectrum of risk.ConclusionsAmong community-based heart failure patients, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The externally validated predictive index may assist clinicians in estimating heart failure mortality risk and in providing quantitative guidance for decision making in heart failure care.

Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea

Abstract: BACKGROUND B-type natriuretic peptide levels are higher in patients with congestive heart failure than in patients with dyspnea from other causes. METHODS We conducted a prospective, randomized, controlled study of 452 patients who presented to the emergency department with acute dyspnea: 225 patients were randomly assigned to a diagnostic strategy involving the measurement of B-type natriuretic peptide levels with the use of a rapid bedside assay, and 227 were assessed in a standard manner. The time to discharge and the total cost of treatment were the primary end points. RESULTS Base-line demographic and clinical characteristics were well matched between the two groups. The use of B-type natriuretic peptide levels reduced the need for hospitalization and intensive care; 75 percent of patients in the B-type natriuretic peptide group were hospitalized, as compared with 85 percent of patients in the control group (P=0.008), and 15 percent of those in the B-type natriuretic peptide group required intensive care, as compared with 24 percent of those in the control group (P=0.01). The median time to discharge was 8.0 days in the B-type natriuretic peptide group and 11.0 days in the control group (P=0.001). The mean total cost of treatment was 5,410 dollars (95 percent confidence interval, 4,516 dollars to 6,304 dollars) in the B-type natriuretic peptide group, as compared with 7,264 dollars (95 percent confidence interval, 6,301 dollars to 8,227 dollars) in the control group (P=0.006). The respective 30-day mortality rates were 10 percent and 12 percent (P=0.45). CONCLUSIONS Used in conjunction with other clinical information, rapid measurement of B-type natriuretic peptide in the emergency department improved the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment.

General Cardiology AbstractsPredictors of major bleeding in acute coronary syndromes: the global registry of acute coronary events (GRACE)

Abstract: AIMS There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding. METHODS AND RESULTS Data from 24045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28). CONCLUSIONS In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding.

Anticoagulation therapy for stroke prevention in atrial fibrillation. how well do randomized trials translate into clinical practice

Abstract: CONTEXT Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. OBJECTIVE To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. DESIGN Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999. SETTING Large integrated health care system in Northern California. PATIENTS Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. MAIN OUTCOMES Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. RESULTS Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage. The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications (total cohort of 13,559). CONCLUSIONS Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small. Results of randomized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation.

Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease

Abstract: BACKGROUND Liposuction has been proposed as a potential treatment for the metabolic complications of obesity. We evaluated the effect of large-volume abdominal liposuction on metabolic risk factors for coronary heart disease in women with abdominal obesity. METHODS We evaluated the insulin sensitivity of liver, skeletal muscle, and adipose tissue (with a euglycemic-hyperinsulinemic clamp procedure and isotope-tracer infusions) as well as levels of inflammatory mediators and other risk factors for coronary heart disease in 15 obese women before and 10 to 12 weeks after abdominal liposuction. Eight of the women had normal glucose tolerance (mean [+/-SD] body-mass index, 35.1+/-2.4), and seven had type 2 diabetes (body-mass index, 39.9+/-5.6). RESULTS Liposuction decreased the volume of subcutaneous abdominal adipose tissue by 44 percent in the subjects with normal glucose tolerance and 28 percent in those with diabetes; those with normal oral glucose tolerance lost 9.1+/-3.7 kg of fat (18+/-3 percent decrease in total fat, P=0.002), and those with type 2 diabetes lost 10.5+/-3.3 kg of fat (19+/-2 percent decrease in total fat, P<0.001). Liposuction did not significantly alter the insulin sensitivity of muscle, liver, or adipose tissue (assessed by the stimulation of glucose disposal, the suppression of glucose production, and the suppression of lipolysis, respectively); did not significantly alter plasma concentrations of C-reactive protein, interleukin-6, tumor necrosis factor alpha, and adiponectin; and did not significantly affect other risk factors for coronary heart disease (blood pressure and plasma glucose, insulin, and lipid concentrations) in either group. CONCLUSIONS Abdominal liposuction does not significantly improve obesity-associated metabolic abnormalities. Decreasing adipose tissue mass alone will not achieve the metabolic benefits of weight loss.

Association between cholesterol level and mortality in dialysis patients

Abstract: CONTEXT Total cholesterol level is inversely associated with mortality in dialysis patients, a group at high risk of cardiovascular disease (CVD). This paradox may be explained by systemic inflammation and/or malnutrition, which are associated with lower cholesterol levels and higher mortality. OBJECTIVE To determine the relationship between cholesterol level and outcome in patients undergoing dialysis, accounting for inflammation and malnutrition. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 823 patients enrolled from October 1995 to June 1998 who recently initiated dialysis, from 79 clinics, classified by absence or presence of inflammation and/or malnutrition (defined as serum albumin levels <3.6 mg/dL, C-reactive protein > or =10 mg/L, or interleukin 6 > or =3.09 pg/mL). MAIN OUTCOME MEASURES All-cause and cardiovascular disease mortality. RESULTS During a median follow-up of 2.4 years, 324 deaths (159 CVD deaths), 153 renal transplantations, and 10 losses to follow-up occurred. Average serum cholesterol level was lower in the presence of inflammation/malnutrition than in its absence. In a Cox model adjusted for age, race, and sex, a 40-mg/dL (1.0-mmol/L) increment in baseline total serum cholesterol level was associated with a decreased risk of all-cause mortality overall (relative hazard [RH], 0.92; 95% confidence interval [CI], 0.87-0.98) and in the presence of inflammation/malnutrition (RH, 0.89; CI, 0.84-0.95). In contrast, serum cholesterol level was associated with an increased risk in the absence of inflammation/malnutrition (RH, 1.32; 95% CI, 1.07-1.63). For CVD mortality, an inverse trend was not statistically significant in the presence of inflammation/malnutrition, and a positive association was evident in the absence of inflammation/malnutrition (RH, 1.41; 95% CI, 1.04-1.89). Further adjustment for traditional CVD risk factors, dialysis modality, comorbidity, and inflammatory markers attenuated the inverse association but strengthened the positive association. CONCLUSIONS The inverse association of total cholesterol level with mortality in dialysis patients is likely due to the cholesterol-lowering effect of systemic inflammation and malnutrition, not to a protective effect of high cholesterol concentrations. These findings support treatment of hypercholesterolemia in this population.

Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes

Abstract: ContextControl of blood glucose levels, blood pressure, and cholesterol levels is proven to reduce the risk of vascular disease among individuals with diabetes mellitus; however, the current state of control of these risk factors among individuals in the United States is uncertain.ObjectivesTo examine 1999-2000 national data on control of risk factors for vascular disease among adults with previously diagnosed diabetes and to assess trends during the past decade.Design, Setting, and ParticipantsReview of data from the Third National Health and Nutrition Examination Survey (NHANES III, conducted 1988-1994) and NHANES 1999-2000, cross-sectional surveys of a nationally representative sample of the noninstitutionalized civilian US population. Participants were adults aged 20 years and older with previously diagnosed diabetes who participated in both the interview and examination in either NHANES III (n = 1265) or NHANES 1999-2000 (n = 441).Main Outcome MeasuresLevels of glycosylated hemoglobin (HbA1c), blood pressure, and total serum cholesterol in reference to target goals.ResultsCompared with NHANES III, participants with previously diagnosed diabetes in NHANES 1999-2000 were similar by age and sex, were less likely to be non-Hispanic white, were diagnosed at an earlier age, had a higher body mass index, and were more likely to use insulin in combination with oral agents. In NHANES 1999-2000, only 37.0% of participants achieved the target goal of HbA1c level less than 7.0% and 37.2% of participants were above the recommended "take action" HbA1c level of greater than 8.0%; these percentages did not change significantly from NHANES III (P = .11 and P = .87, respectively). Only 35.8% of participants achieved the target of systolic blood pressure (SBP) less than 130 mm Hg and diastolic blood pressure (DBP) less than 80 mm Hg, and 40.4% had hypertensive blood pressure levels (SBP ≥140 or DBP ≥90 mm Hg). These percentages did not change significantly from NHANES III (P = .10 and P = .56, respectively). Over half (51.8%) of the participants in NHANES 1999-2000 had total cholesterol levels of 200 mg/dL or greater (vs 66.1% in NHANES III; P<.001). In total, only 7.3% (95% confidence interval, 2.8%-11.9%) of adults with diabetes in NHANES 1999-2000 attained recommended goals of HbA1c level less than 7%, blood pressure less than 130/80 mm Hg, and total cholesterol level less than 200 mg/dL (5.18 mmol/L).ConclusionFurther public health efforts are needed to control risk factors for vascular disease among individuals with diagnosed diabetes.

Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial

Abstract: CONTEXT Nearly 1 million hospitalizations for chronic heart failure occur yearly in the United States, with most related to worsening systemic congestion. Diuretic use, the mainstay therapy for congestion, is associated with electrolyte abnormalities and worsening renal function. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function. OBJECTIVE To evaluate the short- and intermediate-term effects of tolvaptan in patients hospitalized with heart failure. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2 trial conducted at 45 centers in the United States and Argentina and enrolling 319 patients with left ventricular ejection fraction of less than 40% and hospitalized for heart failure with persistent signs and symptoms of systemic congestion despite standard therapy. INTERVENTION After admission, patients were randomized to receive 30, 60, or 90 mg/d of oral tolvaptan or placebo in addition to standard therapy, including diuretics. The study drug was continued for up to 60 days. MAIN OUTCOME MEASURES In-hospital outcome was change in body weight at 24 hours after randomization; outpatient outcome was worsening heart failure (defined as death, hospitalization, or unscheduled visits for heart failure) at 60 days after randomization. RESULTS Median (interquartile range) body weight at 24 hours after randomization decreased by -1.80 (-3.85 to -0.50), -2.10 (-3.10 to -0.85), -2.05 (-2.80 to -0.60), and -0.60 (-1.60 to 0.00) kg in the groups receiving tolvaptan 30, 60, and 90 mg/d, and placebo, respectively (P< or =.008 for all tolvaptan groups vs placebo). The decrease in body weight with tolvaptan was not associated with changes in heart rate or blood pressure, nor did it result in hypokalemia or worsening renal function. There were no differences in worsening heart failure at 60 days between the tolvaptan and placebo groups (P =.88 for trend). In post hoc analysis, 60-day mortality was lower in tolvaptan-treated patients with renal dysfunction or severe systemic congestion. CONCLUSION Tolvaptan administered in addition to standard therapy may hold promise for management of systemic congestion in patients hospitalized for heart failure.

Prevalence of congenital heart disease

Abstract: Background Today most patients with congenital heart disease survive childhood to be cared for by adult cardiologists. The number of physicians that should be trained to manage these lesions is unknown because we do not know the number of patients. Methods To answer this question, the expected numbers of infants with each major type of congenital heart defect born in each 5-year period since 1940 were estimated from birth rates and incidence. The numbers expected to survive with or without treatment were estimated from data on natural history and the results of treatment. Finally, lesions were categorized as simple, moderate, or complex, based on the amount of expertise in management needed for optimal patient care. Results From 1940 to 2002, about 1 million patients with simple lesions, and half that number each with moderate and complex lesions, were born in the United States. If all were treated, there would be 750,000 survivors with simple lesions, 400,000 with moderate lesions, and 180,000 with complex lesions; in addition, there would be 3,000,000 subjects alive with bicuspid aortic valves. Without treatment, the survival in each group would be 400,000, 220,000, and 30,000, respectively. The actual numbers surviving will be between these 2 sets of estimates. Conclusions Survival of patients with congenital heart disease, treated or untreated, is expected to produce large numbers of adults with congenital disease, and it is likely that many more adult cardiologists will need to be trained to manage moderate and complex congenital lesions.

Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis

Abstract: ContextArterial puncture closing devices (APCDs) were developed to replace standard compression at the puncture site and to shorten bed rest following percutaneous coronary intervention.ObjectiveTo assess the safety and efficacy of APCDs (Angioseal, Vasoseal, Duett, Perclose, Techstar, Prostar) compared with standard manual compression in patients undergoing coronary angiography or percutaneous vascular interventions.Data SourcesA systematic literature search of MEDLINE (1966-January 2003), EMBASE (1989-January 2003), PASCAL (1996-January 2003), BIOSIS (1990-January 2003), and CINHAL (1982-January 2003) databases and the Cochrane Central Register of Controlled Trials for relevant articles in any language.Study SelectionIncluded randomized controlled trials reporting vascular complications at the puncture site (hematoma, bleeding, arteriovenous fistula, pseudoaneurysm) and efficacy (time to hemostasis, time to ambulation, time to discharge from hospital).Data ExtractionTwo reviewers abstracted the data independently and in duplicate. Disagreements were resolved by discussion among at least 3 reviewers. The most important criteria were adequacy of allocation concealment, whether the analysis was according to the intention-to-treat principle, and if person assessing the outcome was blinded to intervention group. Random-effects models were used to pool the data.Data SynthesisThirty trials met the selection criteria and included up to 4000 patients. When comparing any APCD with standard compression, the relative risk (RR) of groin hematoma was 1.14 (95% confidence interval [CI], 0.86-1.51; P = .35); bleeding, 1.48 (95% CI, 0.88-2.48; P = .14); developing an arteriovenous fistula, 0.83 (95% CI, 0.23-2.94; P = .77); and developing a pseudoaneurysm at the puncture site, 1.19 (95% CI, 0.75-1.88; P = .46). Time to hemostasis was shorter in the group with APCD compared with standard compression (mean difference, 17 minutes; range, 14-19 minutes), but there was a high degree of heterogeneity among studies. Only 2 studies explicitly reported allocation concealment, blinded outcome assessment, and intention-to-treat analysis. When limiting analyses to only trials that used explicit intention-to-treat approaches, APCDs were associated with a higher risk of hematoma (RR, 1.89; 95% CI, 1.13-3.15) and a higher risk of pseudoaneurysm (RR, 5.40; 95% CI, 1.21-24.5).ConclusionsBased on this meta-analysis of 30 randomized trials, many of poor methodological quality, there is only marginal evidence that APCDs are effective and there is reason for concern that these devices may increase the risk of hematoma and pseudoaneurysm.

General cardiology: abstractValvular dysfunction and carotid, subclavian, and coronary artery disease in survivors of hodgkin lymphoma treated with radiation therapy

Abstract: CONTEXT The majority of patients with Hodgkin lymphoma are young and highly curable. This necessitates concern for prevention, diagnosis, and optimal management of potential treatment-related complications. OBJECTIVE To identify and quantify the incidence of and factors contributing to long-term cardiac and vascular complications after radiation therapy for Hodgkin lymphoma. DESIGN AND SETTING Retrospective study comparing patients treated from 1962 to 1998 at a university-based referral center with a matched general population. PATIENTS Four hundred fifteen consecutive patients who fulfilled the inclusion criteria of a minimum 2-year follow-up (median, 11.2 years) and whose radiation fields included the heart or carotid or subclavian arteries. MAIN OUTCOME MEASURES Multivariable analyses of potential risk factors and observed-to-expected ratios for cardiac valve surgery, coronary artery bypass graft surgery, percutaneous coronary intervention, or both based on Surveillance, Epidemiology, and End Results (SEER) and National Hospital Discharge Survey (NHDS) data. RESULTS Forty-two patients (10.4%) developed coronary artery disease at a median of 9 years after treatment, 30 patients (7.4%) developed carotid and/or subclavian artery disease at a median of 17 years after treatment, and 25 patients (6.2%) developed clinically significant valvular dysfunction at a median of 22 years. The most common valve lesion was aortic stenosis, which occurred in 14 valves. The observed-to-expected ratio for valve surgery was 8.42 (95% confidence interval [CI], 3.20-13.65) and the observed-to-expected ratio for coronary artery bypass graft surgery or percutaneous coronary intervention was 1.63 (95% CI, 0.98-2.28). At least 1 cardiac risk factor was present in all patients who developed coronary artery disease. The only treatment-related factor associated with the development of coronary artery disease was utilization of a radiation technique that resulted in a higher total dose to a portion of the heart (relative risk, 7.8; 95% CI, 1.1-53.2; P =.04). No specific treatment-related factor was associated with carotid or subclavian artery disease or valvular dysfunction. Freedom from any cardiovascular morbidity was 88% at 15 years and 84% at 20 years. CONCLUSIONS Among patients treated with radiation therapy for Hodgkin lymphoma, there are statistically higher than expected rates of valve surgery and coronary revascularization procedures over the next 10 to 20 years. Coronary vascular disease is associated with higher radiation doses and traditional coronary heart disease risk factors. Noncoronary vascular disease and clinically important valvular dysfunction are less well understood complications at 15 to 20 years after radiation, requiring surveillance and further study.

Procedural volume as a marker of quality for cabg surgery

Abstract: THE ASSOCIATION BETWEEN HOSpitals’ coronary artery bypass graft (CABG) surgery volume and outcome has been the subject of multiple investigations. Based on these studies, the Center for Medicare & Medicaid Services (CMS) and the Leapfrog Group have proposed using hospital volume as an indicator of CABG quality. Prior studies of the association between volume and outcome, however, generally have been based on administrative data sources, have reflected selected patient populations, and often have not adequately accounted for patient case mix, patient clustering, and other methodological concerns. Before hospital surgery volume is accepted as a standard quality metric, further research into issues related to both analysis and policy implication is warranted. We undertook a contemporary examination of the association between hospital CABG procedural volume and outcome using clinical data available from the Society of Thoracic Surgeons (STS) National Cardiac Database. Specifically, we considered whether hospital CABG volume was associated with operative mortality after accounting for patient case mix. Second, we examined the extent to which patient clustering within centers and site variance issues affected this association. Third, we determined how the association varied as a function of patient age and predicted surgical risk. Fourth, we determined whether the association between hospital volume and outcome was influenced by individual surgeon volume. Finally, we investigated the potential health policy implications of using hospital volume as a quality indicator. This included determining the ability of hospital volume to discriminate high-mortality outliers, as well as investigating the potential number of lives saved if low-volume centers were systematically closed. METHODS Data Source The STS National Cardiac Database was established in 1989 to report surgical outcomes following cardiothoracic surgical procedures. The database cur-

Effects of the amount of exercise on body weight, body composition and measures of central obesity

Abstract: BACKGROUND Obesity is a major health problem due, in part, to physical inactivity. The amount of activity needed to prevent weight gain is unknown. OBJECTIVE To determine the effects of different amounts and intensities of exercise training. DESIGN Randomized controlled trial (February 1999-July 2002). SETTING AND PARTICIPANTS Sedentary, overweight men and women (aged 40-65 years) with mild to moderate dyslipidemia were recruited from Durham, NC, and surrounding communities. INTERVENTIONS Eight-month exercise program with 3 groups: (1) high amount/vigorous intensity (calorically equivalent to approximately 20 miles [32.0 km] of jogging per week at 65%-80% peak oxygen consumption); (2) low amount/vigorous intensity (equivalent to approximately 12 miles [19.2 km] of jogging per week at 65%-80%), and (3) low amount/moderate intensity (equivalent to approximately 12 miles [19.2 km] of walking per week at 40%-55%). Subjects were counseled not to change their diet and were encouraged to maintain body weight. MAIN OUTCOME MEASURES Body weight, body composition (via skinfolds), and waist circumference. RESULTS Of 302 subjects screened, 182 met criteria and were randomized and 120 completed the study. There was a significant (P<.05) dose-response relationship between amount of exercise and amount of weight loss and fat mass loss. The high-amount/vigorous-intensity group lost significantly more body mass (in mean [SD] kilograms) and fat mass (in mean [SD] kilograms) (-2.9 [2.8] and -4.8 [3.0], respectively) than the low-amount/moderate-intensity group (-0.9 [1.8] and -2.0 [2.6], respectively), the low-amount/vigorous-intensity group (-0.6 [2.0] and -2.5 [3.4], respectively), and the controls (+1.0 [2.1] and +0.4 [3.0], respectively). Both low-amount groups had significantly greater improvements than controls but were not different from each other. Compared with controls, all exercise groups significantly decreased abdominal, minimal waist, and hip circumference measurements. There were no significant changes in dietary intake for any group. CONCLUSIONS In nondieting, overweight subjects, the controls gained weight, both low-amount exercise groups lost weight and fat, and the high-amount group lost more of each in a dose-response manner. These findings strongly suggest that, absent changes in diet, a higher amount of activity is necessary for weight maintenance and that the positive caloric imbalance observed in the overweight controls is small and can be reversed by a modest amount of exercise. Most individuals can accomplish this by walking 30 minutes every day.

Association of long QT syndrome loci and cardiac events among patients treated with β-blockers

Abstract: CONTEXT Data on the efficacy of beta-blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited. OBJECTIVE To describe and assess outcome in a large systematically genotyped population of beta-blocker-treated LQTS patients. DESIGN, SETTING, AND PATIENTS Consecutive LQTS-genotyped patients (n = 335) in Italy treated with beta-blockers for an average of 5 years. MAIN OUTCOME MEASURES Cardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received beta-blocker therapy according to genotype. RESULTS Cardiac events among patients receiving beta-blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P =.001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from beta-blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P =.01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001). CONCLUSION Among patients with genetic LQTS treated with beta-blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.

A calcium antagonist vs. a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease: the international verapamil-trandolapril study (INVEST): a randomized controlled trial

Abstract: THE PREVALENCE OF CORONARY artery disease (CAD) is increasing, as are major CAD risk factors (hypertension, aging, diabetes, obesity, and inactivity). Blood pressure is important in the progression of CAD, yet no large trials have evaluated blood pressure management in only patients with CAD. Thus, blood pressure management in CAD patients must be guided by data from relatively small subsets of high-risk patients from other trials. Current trends in hypertension management emphasize multidrug regimens rather than monotherapy. Combinations of antihypertensive drugs with Author Affiliations and Financial Disclosures are listed at the end of this article. Corresponding Author and Reprints: Carl J. Pepine, MD, University of Florida College of Medicine, 1600 SW Archer Rd, Gainesville, FL 32610. Context Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. Objective To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non–calcium antagonist strategy (NCAS). Design, Setting, and Participants Randomized, open label, blinded end point study of 22576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. Interventions PatientswererandomlyassignedtoeitherCAS(verapamil sustainedrelease) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. Main Outcome Measures Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. Results At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. Conclusion The verapamil-trandolapril–based strategy was as clinically effective as the atenolol-hydrochlorothiazide–based strategy in hypertensive CAD patients.

Relationship of physical fitness vs. body mass index with coronary artery disease and cardiovascular events in women

Abstract: CONTEXT Individual contributions of obesity and physical fitness (physical activity and functional capacity) to risk of coronary heart disease in women remain unclear. OBJECTIVE To investigate the relationships of measures of obesity (body mass index [BMI], waist circumference, waist-hip ratio, and waist-height ratio) and physical fitness (self-reported Duke Activity Status Index [DASI] and Postmenopausal Estrogen-Progestin Intervention questionnaire [PEPI-Q] scores) with coronary artery disease (CAD) risk factors, angiographic CAD, and adverse cardiovascular (CV) events in women evaluated for suspected myocardial ischemia. DESIGN, SETTING, AND PARTICIPANTS The National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) is a multicenter prospective cohort study. From 1996-2000, 936 women were enrolled at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (mean follow-up, 3.9 [SD, 1.8] years) for adverse outcomes. MAIN OUTCOME MEASURES Prevalence of obstructive CAD (any angiographic stenosis >or=50%) and incidence of adverse CV events (all-cause death or hospitalization for nonfatal myocardial infarction, stroke, congestive heart failure, unstable angina, or other vascular events) during follow-up. RESULTS Of 906 women (mean age, 58 [SD, 12] years) with complete data, 19% were of nonwhite race, 76% were overweight (BMI >or=25), 70% had low functional capacity (DASI scores <25, equivalent to