Kidney tubule health scores and their associations with incident CKD in women living with HIV.

OBJECTIVES: Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. METHODS: We measured eight urine biomarkers of kidney tubule health at two visits over a 3-year period in 647 women living with HIV in the Women's Interagency Health Study. We integrated biomarkers into factor scores using exploratory factor analysis. We evaluated associations between CKD risk factors and factor scores, and used generalized estimating equations to determine associations between factor scores and risk of incident CKD. RESULTS: Factor analysis identified two unique factor scores: a tubule reabsorption score comprising alpha-1-microglobulin, beta-2-microglobulin and trefoil factor-3; and a tubule injury score comprising interleukin-18 and kidney injury molecule-1. We modelled the two factor scores in combination with urine epidermal growth factor (EGF) and urine albumin. Predominantly HIV-related CKD risk factors were independently associated with worsening tubule reabsorption scores and tubule injury scores. During a median follow-up of 7 years, 9.7% (63/647) developed CKD. In multivariable time-updated models that adjusted for other factor scores and biomarkers simultaneously, higher tubule reabsorption scores [risk ratio (RR) = 1.27, 95% confidence interval (CI): 1.01-1.59 per 1 SD higher time-updated score], higher tubule injury scores (RR = 1.36, 95% CI: 1.05-1.76), lower urine EGF (RR = 0.75, 95% CI: 0.64-0.87), and higher urine albumin (RR = 1.20, 95% CI: 1.02-1.40) were jointly associated with risk of incident CKD. CONCLUSIONS: We identified two novel and distinct dimensions of kidney tubule health that appear to quantify informative metrics of CKD risk in PLWH.

Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial.

Cardiovascular risk remains high in kidney transplant recipients (KTRs) despite improved kidney function after transplant. Urinary markers of kidney fibrosis and injury may help to reveal mechanisms of this risk. In a case-cohort study among stable KTRs who participated in the FAVORIT trial, we measured four urinary proteins known to correlate with kidney tubulointerstitial fibrosis on biopsy (urine alpha 1 microglobulin [α1m], monocyte chemoattractant protein-1 [MCP-1], procollagen type I [PINP] and type III [PIIINP] N-terminal amino peptide) and evaluated associations with cardiovascular disease (CVD) events (n = 300) and death (n = 371). In adjusted models, higher urine α1m (hazard ratio [HR] per doubling of biomarker 1.40 [95% confidence interval [CI] 1.21, 1.62]), MCP-1 (HR 1.18 [1.03, 1.36]), and PINP (HR 1.13 [95% CI 1.03, 1.23]) were associated with CVD events. These three markers were also associated with death (HR per doubling α1m 1.51 [95% CI 1.32, 1.72]; MCP-1 1.31 [95% CI 1.13, 1.51]; PINP 1.11 [95% CI 1.03, 1.20]). Higher concentrations of urine α1m, MCP-1, and PINP may identify KTRs at higher risk for CVD events and death. These markers may identify a systemic process of fibrosis involving both the kidney and cardiovascular system, and give new insights into mechanisms linking the kidney with CVD.

The association of adiposity with kidney function decline among HIV-infected adults: findings from the Fat Redistribution and Metabolic Changes in HIV Infection (FRAM) study.

OBJECTIVES: The aim of the study was to investigate the association of adiposity with longitudinal kidney function change in 544 HIV-infected persons in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) cohort over 5 years of follow-up. METHODS: The regional distribution of muscle and adipose tissue was quantified by whole-body magnetic resonance imaging (MRI), and total adiponectin and leptin levels were measured in serum. Kidney function was assessed using the estimated glomerular filtration rate from serum cystatin C (eGFRCys), obtained at baseline and follow-up. Rapid kidney function decline was defined as annual loss of eGFRCys ≥ 3 mL/min/1.73 m(2) , and incident chronic kidney disease (CKD) was defined as eGFRCys <60 mL/min/1.73 m(2) . Multivariate regression analysis was adjusted for age, race, gender, glucose, antihypertensive use, serum albumin, baseline and change in HIV viral load. RESULTS: At baseline, mean age was 43 years, mean eGFRCys was 86 mL/min/1.73 m(2) , and 21% of patients had albuminuria. The mean (± standard deviation) eGFRCys decline was -0.11 ± 4.87 mL/min/1.73 m(2) per year; 23% of participants had rapid kidney function decline, and 10% developed incident CKD. The lowest tertile of visceral adipose tissue and the highest tertile of adiponectin were both marginally associated with annual kidney function decline of -0.5 mL/min/1.73 m(2) each, but these associations were not statistically significant after adjustment. We found no statistically significant associations of MRI-measured regional adiposity or serum adipokines with rapid kidney function decline or incident CKD (all P-values>0.1 in adjusted models). CONCLUSIONS: Contrary to findings in the general population, adiposity did not have a substantial association with longitudinal change in kidney function among HIV-infected persons.

Blood pressure and chronic kidney disease progression in a multi-racial cohort: the Multi-Ethnic Study of Atherosclerosis.

The relationship between blood pressure (BP) and kidney function among individuals with chronic kidney disease (CKD) remains controversial. This study evaluated the association between BP and estimated glomerular filtration rate (eGFR) decline among adults with nondiabetic stage 3 CKD. The Multi-Ethnic Study of Atherosclerosis participants with an eGFR 30-59 ml min(-1) per 1.73 m2 at baseline without diabetes were included. Participants were followed over a 5-year period. Kidney function change was determined by annualizing the change in eGFR using cystatin C, creatinine and a combined equation. Risk factors for progression of CKD (defined as a decrease in annualized eGFR>2.5 ml min(-1) per 1.73 m2) were identified using univariate analyses and sequential logistic regression models. There were 220 participants with stage 3 CKD at baseline using cystatin C, 483 participants using creatinine and 381 participants using the combined equation. The median (interquartile range) age of the sample was 74 (68-79) years. The incidence of progression of CKD was 16.8% using cystatin C and 8.9% using creatinine (P=0.002). Systolic BP>140 mm Hg or diastolic BP>90 mm Hg was significantly associated with progression using a cystatin C-based (odds ratio (OR), 2.49; 95% confidence interval (CI), 1.12-5.52) or the combined equation (OR, 2.07; 95% CI, 1.16-3.69), but not when using creatinine after adjustment for covariates. In conclusion, with the inclusion of cystatin C in the eGFR assessment hypertension was an important predictor of CKD progression in a multi-ethnic cohort with stage 3 CKD.

Albuminuria and the risk of incident stroke and stroke types in older adults.

BACKGROUND: The kidney biomarker that best reflects risk of stroke is unknown. We sought to evaluate the association of stroke with 3 kidney biomarkers: albuminuria, cystatin C, and glomerular filtration rate. METHODS: These 3 biomarkers were determined in 3,287 participants without history of stroke from the Cardiovascular Health Study, a longitudinal cohort study of men and women age 65 years and older from 4 US communities. The biomarkers were albuminuria ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up between 1996 and 2006. RESULTS: A total of 390 participants had an incident stroke: 81% ischemic, 12% hemorrhagic, and 7% unclassified. In adjusted Cox regression models, UACR was more strongly related to any stroke, ischemic stroke, and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any stroke comparing the top to bottom quintile of UACR was 2.10 (95% confidence interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95% CI 0.91-1.84) and for cystatin C was 1.22 (95% CI 0.85-1.74). When considering clinically relevant categories, elevated UACR was associated with increased hazard of any stroke and ischemic stroke regardless of eGFR or cystatin C categories. CONCLUSIONS: UACR was the kidney biomarker most strongly associated with risk of incident stroke. Results in this elderly cohort may not be applicable to younger populations. These findings suggest that measures of glomerular filtration and permeability have differential effects on stroke risk.

Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults. METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (< or =5.6%), tertile 2 (5.61-6.20%) and tertile 3 (> or =6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest). CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

Fetuin-A is not associated with mortality in chronic kidney disease.

Fetuin-A is a serum protein that inhibits vascular calcification such that lower levels are associated with a higher prevalence of vascular calcification and mortality risk among end-stage renal disease populations. We analyzed data of 822 persons in the Modification of Diet in Renal Disease study, a randomized, controlled trial of persons with predominantly non-diabetic stage 3-4 chronic kidney disease (CKD). Serum fetuin-A levels were measured in baseline serum. Survival status and cause of death were determined by the National Death Index. Cox proportional hazard models evaluated the association of fetuin-A levels with all-cause and cardiovascular mortality. Glomerular filtration ranged from 13 to 55 ml per min per 1.73 m(2). During a median follow-up of 9.5 years, 25% of persons died from any cause and 12% died from a cardiovascular cause. Compared to the lowest tertile, no association was found between the highest fetuin-A tertile and all-cause or cardiovascular mortality. Similarly, no association was found between fetuin-A as a continuous variable and all-cause or cardiovascular mortality. Our study shows that serum fetuin-A levels are not related to all-cause or cardiovascular mortality among persons with predominantly non-diabetic stage 3 or 4 CKD.

Kidney function and markers of inflammation in elderly persons without chronic kidney disease: the health, aging, and body composition study.

Inflammatory markers are elevated in persons with estimated glomerular filtration rates less than 60 ml/min/1.73 m2. As cystatin C may detect small changes in kidney function not detected by estimated glomerular filtration rate, we evaluated the association between cystatin C and serum markers of inflammation in older adults with estimated glomerular filtration rate >or=60. This is an analysis using measures from the Health, Aging, and Body Composition Study, a cohort of well-functioning adults aged 70-79 years. Cystatin C correlated with all five inflammatory biomarkers: C-reactive protein (r=0.08), interleukin-6 (r=0.19), tumor necrosis factor alpha (TNF-alpha) (r=0.41), soluble TNF receptor 1 (STNF-R1) (r=0.61), and soluble TNF receptor 2 (STNF-R2) (r=0.54); P<0.0005 for all. In adjusted analyses, cystatin C concentrations appeared to have stronger associations with each biomarker compared with estimated glomerular filtration rate or serum creatinine. Participants with a cystatin C>or=1.0 mg/l had significantly higher levels of all five biomarkers compared to those with a cystatin C<1.0 (mean differences ranging 16-29%, all P<0.05). Cystatin C has a linear association with inflammatory biomarkers in an ambulatory elderly cohort with estimated glomerular filtration rates >or=60; associations are particularly strong with TNF-alpha and the STNF-R.

The PRIME curriculum. Clinical research training during residency.

AIM: The Primary Medical Education (PRIME) program is an outpatient-based, internal medicine residency track nested within the University of California, San Francisco (UCSF) categorical medicine program. Primary Medical Education is based at the San Francisco Veteran's Affairs Medical Center (VAMC), 1 of 3 teaching hospitals at UCSF. The program accepts 8 UCSF medicine residents annually, who differentiate into PRIME after internship. In 2000, we implemented a novel research methods curriculum with the dual purposes of teaching basic epidemiology skills and providing mentored opportunities for clinical research projects during residency. SETTING: Single academic internal medicine program. PROGRAM DESCRIPTION: The PRIME curriculum utilizes didactic lecture, frequent journal clubs, work-in-progress sessions, and active mentoring to enable residents to "try out" a clinical research project during residency. PROGRAM EVALUATION: Among 32 residents in 4 years, 22 residents have produced 20 papers in peer-reviewed journals, 1 paper under review, and 2 book chapters. Their clinical evaluations are equivalent to other UCSF medicine residents. DISCUSSION: While learning skills in evidence-based medicine, residents can conduct high-quality research. Utilizing a collaboration of General Internal Medicine researchers and educators, our curriculum affords residents the opportunity to "try-out" clinical research as a potential future career choice.

Evaluating provider adherence in a trial of a guideline-based decision support system for hypertension.

Measurement of provider adherence to a guideline-based decision support system (DSS) presents a number of important challenges. Establishing a causal relationship between the DSS and change in concordance requires consideration of both the primary intention of the guideline and different ways providers attempt to satisfy the guideline. During our work with a guideline-based decision support system for hypertension, ATHENA DSS, we document a number of subtle deviations from the strict hypertension guideline recommendations that ultimately demonstrate provider adherence. We believe that understanding these complexities is crucial to any valid evaluation of provider adherence. We also describe the development of an advisory evaluation engine that automates the interpretation of clinician adherence with the DSS on multiple levels, facilitating the high volume of complex data analysis that is created in a clinical trial of a guideline-based DSS.

Hormone therapy and in-hospital survival after myocardial infarction in postmenopausal women.

BACKGROUND: Although postmenopausal hormone therapy (HRT) commonly is used in hope of preventing coronary heart disease, the effect of HRT on case fatality of myocardial infarction has never been studied. We evaluated HRT as a predictor of survival after MI in postmenopausal women. METHODS AND RESULTS: The present study was performed with 114 724 women of age >/=55 years with confirmed myocardial infarction who presented between April 1998 and January 2000 to 1 of 1674 hospitals participating in the National Registry of Myocardial Infarction-3. Presenting characteristics, treatment, and clinical outcome data were obtained by chart review. At time of hospitalization, 7353 (6.4%) women reported current use of HRT, defined as use of estrogen, progestin, or estrogen/progestin for reasons other than contraception. Unadjusted mortality was 7.4% in users of HRT and 16.2% in nonusers (odds ratio 0.41, 95% confidence interval 0.36 to 0.43). After adjustments were made for prior medical history, clinical characteristics, treatments received in-hospital, and likelihood of receiving HRT, HRT remained associated with an improved rate of survival (odds ratio 0.65, 95% confidence interval 0.59 to 0.72). Significant association of HRT with decreased mortality after myocardial infarction was observed in all age strata. CONCLUSIONS: Postmenopausal HRT appears to be associated with reduced mortality after myocardial infarction. This finding could be caused by therapeutic effect of HRT, selection and adherence bias, or some combination of both.

Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women.

OBJECTIVES: We examined the association of hormone therapy (HRT) with hemorrhagic and ischemic stroke among postmenopausal women with acute myocardial infarction (AMI). BACKGROUND: Hemorrhagic and ischemic strokes are common complications of AMI, and women are at increased risk for hemorrhagic stroke after thrombolytic therapy. This risk may be related to female hormones. METHODS: Using data from the National Registry of Myocardial Infarction-3, we studied 114,724 women age 55 years or older admitted to the hospital for AMI, of whom 7,353 reported HRT use on admission. We determined rates of in-hospital hemorrhagic and ischemic stroke stratified by HRT use and estimated the independent association of HRT with each stroke type using multivariable logistic regression. RESULTS: The HRT users were younger than non-users, had fewer risk factors for stroke including diabetes and prior stroke, and received more pharmacologic and invasive therapy including cardiac catheterization. A total of 2,152 (1.9%) in-hospital strokes occurred, with 442 (0.4%) hemorrhagic, 1,017 (0.9%) ischemic and 693 (0.6%) unspecified. Among HRT users and non-users, the rates of hemorrhagic stroke (0.40% vs. 0.42%, p = 1.00) and ischemic stroke (0.80% vs. 0.96%, p = 0.11) were similar. Among 13,328 women who received thrombolytic therapy, the rate of hemorrhagic stroke was not significantly different for users and non-users (1.6% vs. 2.1%, p = 0.22). After adjustment for baseline and treatment differences, HRT was not associated with hemorrhagic (odds ratio [OR], 0.88; 95% confidence intervals [CI], 0.58 to 1.35) or ischemic stroke (OR, 0.89; CI, 0.66 to 1.18). CONCLUSIONS: Acute myocardial infarction is a high-risk setting for stroke among postmenopausal women, but HRT does not appear to modify that risk. Clinicians should not alter their approach to thrombolytic therapy based on HRT use.

Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease.

OBJECTIVES: This study sought to determine the independent association of renal insufficiency with cardiovascular risk among women with known coronary heart disease (CHD). BACKGROUND: Although patients with end-stage renal disease and proteinuria are at high risk for cardiovascular events, little is known about the cardiovascular risk associated with moderate renal insufficiency. METHODS: The Heart and Estrogen/progestin Replacement Study (HERS) was a clinical trial among 2,763 women with coronary disease who were randomized to conjugated estrogen plus progestins or identical placebo and followed for a mean of 4.1 years. Women were categorized as having normal renal function (creatinine < 1.2 mg/dl; n = 2,012), mild renal insufficiency (1.2 mg/dl to 1.4 mg/dl; n = 567) and moderate renal insufficiency (>1.4 mg/dl; n = 182). We examined the independent association of renal function with incident cardiovascular events including CHD death, nonfatal myocardial infarction, hospitalization for unstable angina, stroke and transient ischemic attacks. RESULTS: Compared with women with normal renal function, those with mild and moderate renal insufficiency were older, more likely to be black, have a history of hypertension and diabetes and have higher serum levels of triglycerides and lipoprotein(a). After multivariate adjustment, both mild (relative hazards [RH] = 1.24; 95% confidence interval [CI]: 1.0 to 1.5) and moderate renal insufficiency (RH = 1.57; 95% CI: 1.2 to 2.1) were independently associated with increased risk for cardiovascular events compared with women with normal renal function. CONCLUSIONS: Renal insufficiency is an independent risk factor for cardiovascular events in postmenopausal women with known coronary artery disease. Renal function may add helpful information to CHD risk stratification.

The incidence of unrecognized myocardial infarction in women with coronary heart disease.

BACKGROUND: Several cohort studies in populations without coronary heart disease have demonstrated that up to 40% of incident myocardial infarctions are clinically unrecognized. OBJECTIVE: To determine the incidence of unrecognized myocardial infarction in women with coronary heart disease in the Heart and Estrogen/progestin Replacement Study (HERS). DESIGN: Randomized, double-blind, placebo-controlled trial of conjugated estrogens plus medroxyprogesterone or identical placebo with 4.1 years of follow-up. SETTINGS: Outpatient and community settings at 20 U.S. clinical centers. PATIENTS: 2763 postmenopausal women younger than 80 years of age with coronary heart disease and an intact uterus. MEASUREMENTS: Annual electrocardiograms were obtained for all participants during follow-up (mean, 4.1 years) and were evaluated by using the NOVACODE computer algorithm and visual confirmation. A total of 13 715 electrocardiograms were obtained. Suspected unrecognized myocardial infarctions were investigated by comparing a participant's previous surveillance electrocardiograms with the electrocardiograms obtained from all of her intervening hospitalizations. Characteristics of patients with recognized and unrecognized myocardial infarction were compared. RESULTS: Among the 256 nonfatal myocardial infarctions, 11 were unrecognized (4.3% [95% CI, 2.2% to 7.6%]). Seven occurred in women assigned to placebo and 4 occurred in women assigned to hormone therapy (P > 0.2). Women with unrecognized myocardial infarction were less likely to have diabetes mellitus or previous angina and were more likely to have had previous bypass surgery compared with women who had clinically recognized myocardial infarction. CONCLUSION: The incidence of unrecognized myocardial infarction in women with coronary disease was far lower than that observed in previous studies of populations without coronary heart disease.

Of principles and pens: attitudes and practices of medicine housestaff toward pharmaceutical industry promotions.

PURPOSE: Little is known about the factors that influence housestaff attitudes toward pharmaceutical industry promotions or, how such attitudes correlate with physician behaviors. We studied these attitudes and practices among internal medicine housestaff. SUBJECTS AND METHODS: Confidential surveys about attitudes and behaviors toward industry gifts were distributed to 1st- and 2nd-year residents at a university-based internal medicine residency program. RESULTS: Ninety percent of the residents (105 of 117) completed the survey. A majority of respondents considered seven of nine types of promotions appropriate. Residents judged the appropriateness of promotions on the basis of their cost (median percentage of items considered appropriate 100% for inexpensive items vs. 60% for expensive ones) more than on the basis of their educational value (80% for educational items vs.75% for noneducational ones; P < .001 for comparison of appropriateness based on cost vs. educational value). Behaviors were often inconsistent with attitudes; every resident who considered conference lunches (n = 13) and pens (n = 18) inappropriate had accepted these gifts. Most respondents (61%)stated that industry promotions and contacts did not influence their own prescribing, but only 16% believed other physicians were similarly unaffected (P< .0001). Nonetheless, more than two thirds of residents agreed that it is appropriate for a medical institution to have rules on industry interactions with residents and faculty. CONCLUSIONS: Residents hold generally positive attitudes toward gifts from industry, believe they are not influenced by them, and report behaviors that are often inconsistent with their attitudes. Thoughtful education and policy programs may help residents learn to critically appraise these gifts.

Comparison of the effects of angiotensin converting-enzyme inhibitors and beta blockers on survival in elderly patients with reduced left ventricular function after myocardial infarction.

PURPOSE: Angiotensin converting-enzyme (ACE) inhibitors decrease mortality after myocardial infarction among patients with depressed left ventricular function. Beta blockers may also improve survival in these patients. We compared the relative effects of these agents on the survival of elderly patients with a left ventricular ejection fraction less than 40% after myocardial infarction. SUBJECTS AND METHODS: The Cooperative Cardiovascular Project collected data on patients aged 65 years and older who were admitted with myocardial infarction from April 1994 to July 1995, including 20,902 with a measured left ventricular ejection fraction less than 40% before discharge. Using proportional hazard regression models that adjusted for patient characteristics and in-hospital treatments, we compared survival among patients discharged on ACE inhibitors, beta blockers, both medications, or neither medication. RESULTS: Among patients surviving hospitalization with reduced left ventricular function, 9,108 (44%) were discharged on ACE inhibitors, 2,613 (13%) on beta blockers, 3,309 (16%) on both medications, and 5,872 (28%) on neither medication. Patients treated with ACE inhibitors were more likely to have a prior diagnosis of heart failure and less likely to have undergone revascularization, whereas those treated with beta blockers were more often treated with thrombolytic therapy and aspirin. Patients treated with ACE inhibitors [hazard ratio (HR = 0.80), 0.80; 95% confidence interval (CI), 0.73 to 0.87] or beta blockers (HR = 0.76, 0.76; 95% CI, 0.64 to 0.90) had lower adjusted 1-year mortality than those who were not treated with either medication. The combination of both medications was associated with additional benefit (HR = 0.68, 0.68; 95% CI, 0.59 to 0.80). The relative benefit of each medication was greatest among patients with an ejection fraction less than 30%, a serum creatinine level 2.0 mg/dL or greater, or both. To prevent a death within a year, the number of patients who needed to be treated with both medications varied from 5 to 15, depending on ejection fraction and renal function. CONCLUSION: ACE inhibitors and beta blockers were associated with similar improvements in survival among elderly patients with reduced left ventricular ejection fraction after myocardial infarction. Our results suggest that patients who can tolerate both medications gain additional benefit from the combination.

Racial differences in mortality among men hospitalized in the Veterans Affairs health care system.

CONTEXT: Racial disparities in health care delivery and outcomes may be due to differences in health care access and, therefore, may be mitigated in an equal-access health care system. Few studies have examined racial differences in health outcomes in such a system. OBJECTIVE: To study racial differences in mortality among patients admitted to hospitals in the Veterans Affairs (VA) system, a health care system that potentially offers equal access to care. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 28 934 white and 7575 black men admitted to 147 VA hospitals for 1 of 6 common medical diagnoses (pneumonia, angina, congestive heart failure, chronic obstructive pulmonary disease, diabetes, and chronic renal failure) between October 1, 1995, and September 30, 1996. MAIN OUTCOME MEASURES: The primary outcome measure was 30-day mortality among black compared with white patients. Secondary outcome measures were in-hospital mortality and 6-month mortality. RESULTS: Overall mortality at 30 days was 4.5% in black patients and 5.8% in white patients (relative risk [RR], 0.77; 95% confidence interval [CI], 0.69-0.87; P =.001). Mortality was lower among blacks for each of the 6 medical diagnoses. Multivariate adjustment for patient and hospital characteristics had a small effect (RR, 0.75; 95% CI, 0.66-0.85; P<.001). Black patients also had lower adjusted in-hospital and 6-month mortality. These findings were consistent among all subgroups evaluated. CONCLUSIONS: Black patients admitted to VA hospitals with common medical diagnoses have lower mortality rates than white patients. The survival advantage of black patients is not readily explained; however, the absence of a survival disadvantage for blacks may reflect the benefits of equal access to health care and the quality of inpatient treatment at VA medical centers.

Health and economic benefits of increased beta-blocker use following myocardial infarction.

CONTEXT: beta-blockers are underused in patients who have myocardial infarction (MI), despite the proven efficacy of these agents. New evidence indicates that beta-blockers can have benefit in patients with conditions that have been considered relative contraindications. Understanding the consequences of underuse of beta-blockers is important because of the implications for current policy debates over quality-of-care measures and Medicare prescription drug coverage. OBJECTIVE: To examine the potential health and economic impact of increased use of beta-blockers in patients who have had MI. DESIGN AND SETTING: We used the Coronary Heart Disease (CHD) Policy Model, a computer-simulation Markov model of CHD in the US population, to estimate the epidemiological impact and cost-effectiveness of increased beta-blocker use from current to target levels among survivors of MI aged 35 to 84 years. Simulations included 1 cohort of MI survivors in 2000 followed up for 20 years and 20 successive annual cohorts of all first-MI survivors in 2000-2020. Mortality and morbidity from CHD were derived from published meta-analyses and recent studies. This analysis used a societal perspective. MAIN OUTCOME MEASURES: Prevented MIs, CHD mortality, life-years gained, and cost per quality-adjusted life-year (QALY) gained in 2000-2020. RESULTS: Initiating beta-blocker use for all MI survivors except those with absolute contraindications in 2000 and continuing treatment for 20 years would result in 4300 fewer CHD deaths, 3500 MIs prevented, and 45,000 life-years gained compared with current use. The incremental cost per QALY gained would be $4500. If this increase in beta-blocker use were implemented in all first-MI survivors annually over 20 years, beta-blockers would save $18 million and result in 72,000 fewer CHD deaths, 62,000 MIs prevented, and 447,000 life-years gained. Sensitivity analyses demonstrated that the cost-effectiveness of beta-blocker therapy would always be less than $11,000 per QALY gained, even under unfavorable assumptions, and may even be cost saving. Restricting beta-blockers only to ideal patients (those without absolute or relative contraindications) would reduce the epidemiological impact of beta-blocker therapy by about 60%. CONCLUSIONS: Our simulation indicates that increased use of beta-blockers after MI would lead to impressive gains in health and would be potentially cost saving. JAMA. 2000;284:2748-2754.

Does physician specialty affect the survival of elderly patients with myocardial infarction?

OBJECTIVE: To determine the effect of treatment by a cardiologist on mortality of elderly patients with acute myocardial infarction (AMI, heart attack), accounting for both measured confounding using risk-adjustment techniques and residual unmeasured confounding with instrumental variables (IV) methods. DATA SOURCES/STUDY SETTING: Medical chart data and longitudinal administrative hospital records and death records were obtained for 161,558 patients aged > or =65 admitted to a nonfederal acute care hospital with AMI from April 1994 to July 1995. Our principal measure of significant cardiologist treatment was whether a patient was admitted by a cardiologist. We use supplemental data to explore whether our analysis would differ substantially using alternative definitions of significant cardiologist treatment. STUDY DESIGN: This retrospective cohort study compared results using least squares (LS) multivariate regression with results from IV methods that accounted for additional unmeasured patient characteristics. Primary outcomes were 30-day and one-year mortality, and secondary outcomes included treatment with medications and revascularization procedures. DATA COLLECTION/EXTRACTION METHODS: Medical charts for the initial hospital stay of each AMI patient underwent a comprehensive abstraction, including dates of hospitalization, admitting physician, demographic characteristics, comorbid conditions, severity of clinical presentation, electrocardiographic and other diagnostic test results, contraindications to therapy, and treatments before and after AMI. PRINCIPAL FINDINGS: Patients admitted by cardiologists had fewer comorbid conditions and less severe AMIs. These patients had a 10 percent (95 percent CI: 9.5-10.8 percent) lower absolute mortality rate at one year. After multivariate adjustment with LS regression, the adjusted mortality difference was 2 percent (95 percent CI: 1.4-2.6 percent). Using IV methods to provide additional adjustment for unmeasured differences in risk, we found an even smaller, statistically insignificant association between physician specialty and one-year mortality, relative risk (RR) 0.96 (0.88-1.04). Patients admitted by a cardiologist were also significantly more likely to have a cardiologist consultation within the first day of admission and during the initial hospital stay, and also had a significantly larger share of their physician bills for inpatient treatment from cardiologists. IV analysis of treatments showed that patients treated by cardiologists were more likely to undergo revascularization procedures and to receive thrombolytic therapy, aspirin, and calcium channel-blockers, but less likely to receive beta-blockers. CONCLUSIONS: In a large population of elderly patients with AMI, we found significant treatment differences but no significant incremental mortality benefit associated with treatment by cardiologists.