Biomedical subjects
Publications and source records attributed to Mark A Hlatky.
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CONTEXT: Leptin is associated with adiposity and insulin resistance and may play a direct role in vascular calcification. It is unclear, however, whether leptin is an independent predictor of atherosclerotic burden. OBJECTIVE: The aim of this study was to examine the association between plasma leptin and coronary artery calcification (CAC) in an ethnically diverse cohort of older adult men and women free of clinical cardiovascular disease. DESIGN: This was a cross-sectional study with data collection between January 2002 and February 2004 as part of the ADVANCE Study. SETTING: The study was conducted at an integrated health care delivery system in Northern California. PARTICIPANTS: Participants included 949 men and women aged 60-69 yr old. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURE: The main outcome measure was CAC by multidetector row computed tomography. RESULTS: In ordinal logistic regression, plasma leptin levels were positively associated with extent of CAC independently of age, race/ethnicity, and smoking status in women (odds ratio of higher CAC for the sex-specific upper tertile vs. lower tertile = 1.81; 95% confidence interval, 1.10-3.00) but not in men (odds ratio = 1.29; 95% confidence interval = 0.89-1.86). However, this association was explained by metabolic risk factors and adiposity measures. CONCLUSIONS: Our findings support a role of leptin on vascular calcification in women but, in our sample of older adults, the association between leptin and CAC was not independent of other cardiac risk factors.
OBJECTIVES: We sought to examine the association between the metabolic syndrome (MetS) (defined both by the 2001 National Cholesterol Educational Program Adult Treatment Panel III [ATP-III] definition and the American Heart Association/National Heart, Lung and Blood Institute [AHA/NHLBI] revision incorporating the lower threshold for impaired fasting glucose [IFG]) and early-onset coronary artery disease (CAD). BACKGROUND: The impact of MetS on premature CAD has not been studied extensively. Lowering the threshold to define the IFG component (from 110 to 100 mg/dl) and the value of the syndrome as a whole versus its individual components are subjects of intense debate. METHODS: We performed a case-control study with 393 early-onset CAD subjects (acute myocardial infarction, angina with > or =50% stenosis, or coronary revascularization) in men under age 46 years or women under age 56 years and 393 control subjects individually matched for gender, age, and race/ethnicity. RESULTS: By conditional logistic regression, presence of ATP-III MetS without diabetes (adjusted odds ratio [adj-OR] 4.9; 95% confidence interval [CI] 3.4 to 8.0) and with diabetes (adj-OR 8.0, 95% CI 4.39 to 14.6) was a strong independent determinant of early-onset CAD. Using the AHA/NHLBI revision, these ORs became slightly stronger. However, neither definition of MetS remained significantly associated with early-onset CAD in multivariate models adjusting for individual components. CONCLUSIONS: The presence of MetS imparts a high risk of early-onset clinical CAD, but the prognostic information associated with the syndrome is not greater than the sum of its parts.
Increased use of ICDs in patients with cardiac disease has the potential to strain national health care budgets because of the large numbers of eligible patients and the high cost of the ICDs. Randomized trials show ICDs increase life-expectancy in some groups of patients and also increase total medical costs significantly. ICDs exemplify the role of new technology as the main force behind rising health care costs. ICDs have not been used in all eligible patients, in part because of cost, but also because of patient resistance and a shortage of specialists able to implant and manage complex ICDs. The cost-effectiveness of ICDs would be improved by development of simpler and cheaper devices, and by better tools to identify patients who benefit from an ICD.
BACKGROUND: A Department of Veterans Affairs Cooperative Study randomized high-risk patients with medically refractory myocardial ischemia, a group largely excluded from previous trials, to urgent revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The present study examined the cost-effectiveness of PCI versus CABG for these high-risk patients. METHODS AND RESULTS: Of 454 patients at 16 Department of Veterans Affairs medical centers, 445 were available for the economic analysis (218 PCI and 227 CABG patients). Total costs were assessed at 3 and 5 years from the third-party payer's perspective, and effectiveness was measured by survival. After 3 years, average total costs were 63,896 dollars for PCI versus 84,364 dollars for CABG patients, a difference of 20,468 dollars (95% confidence interval [CI] 13,918 dollars to 27,569 dollars). CIs were estimated by bootstrapping. Survival at 3 years was 0.82 for PCI versus 0.79 for CABG patients (P=0.34). Precision of the cost-effectiveness estimates were assessed by bootstrapping. PCI was less costly and more effective at 3 years in 92.6% of the bootstrap replications. After 5 years, average total costs were 81,790 dollars for PCI versus 100,522 dollars for CABG patients, a difference of 18,732 dollars (95% CI 9873 dollars to 27,831 dollars), whereas survival at 5 years was 0.75 for PCI patients versus 0.70 for CABG patients (P=0.21). At 5 years, PCI remained less costly and more effective in 89.4% of the bootstrap replications. CONCLUSIONS: PCI was less costly and at least as effective for the urgent revascularization of medically refractory, high-risk patients over 5 years.
The Stanford Brief Activity Survey (SBAS), a new two-item physical activity survey, and the Stanford Seven-Day Physical Activity Recall (PAR) questionnaire were administered to men and women, aged 60-69 years, in the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology (ADVANCE) Study. Frequency distributions of SBAS activity levels, as well as a receiver operating curve, were calculated to determine if the SBAS can detect recommended physical activity levels of 150 or more minutes/week at moderate or greater intensity, with PAR minutes/week. Data were collected between December 2001 and January 2004 from 1,010 participants (38% women) and recorded. Subjects were 65.8 (standard deviation: 2.8) years of age, 77% were married, 55% were retired, 23% were college graduates, and 68% were Caucasian. SBAS scores related significantly in an expected manner to PAR minutes/week (p < 0.01), energy expenditure (kcal/kg per day) (p < 0.01), and selected cardiovascular disease risk biomarkers (p < 0.01). The SBAS of physical activity at moderate intensity had a sensitivity of 0.73 and a specificity of 0.61. The SBAS is a quick assessment of the usual amount and intensity of physical activity that a person performs throughout the day. The SBAS needs further validation in other populations but demonstrated the potential of being a reasonably valid and inexpensive tool for quickly assessing habitual physical activity in large-scale epidemiology studies and clinical practice.
Diabetes mellitus and coronary artery disease (CAD) commonly coexist, and thus effective, cost-effective management strategies are needed. Intensive management of diabetes has been shown to increase medical costs while yielding better outcomes, with an acceptable cost-effectiveness ratio of <50,000 dollars per life-year added. On the basis of clinical trial findings in the 1970s and 1980s, coronary bypass surgery was cost-effective compared with medical therapy in the treatment of extensive CAD. Few trials have compared angioplasty with medical therapy, and its cost-effectiveness is not well established. The economic outcomes of contemporary coronary revascularization, especially angioplasty, compared with contemporary medical therapy must be evaluated. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial will collect extensive economic data and examine the cost-effectiveness of alternative strategies to manage diabetes and CAD in patients with both disorders.
BACKGROUND: Coronary atherosclerosis develops slowly over decades but is frequently characterized clinically by sudden unstable episodes. Patients who present with unstable coronary disease, such as acute myocardial infarction, may systematically differ from patients who present with relatively stable coronary disease, such as exertional angina. OBJECTIVE: To examine whether medication use or patient characteristics influence the mode of initial clinical presentation of coronary disease. DESIGN: Case-control study. SETTING: Large integrated health care delivery system in northern California. PATIENTS: Adults whose first clinical presentation of coronary disease was either acute myocardial infarction (n = 916) or stable exertional angina (n = 468). MEASUREMENTS: Use of cardiac medications before the event from pharmacy databases and demographic, lifestyle, and clinical characteristics from self-report and clinical and administrative databases. RESULTS: Compared with patients with incident stable exertional angina, patients with incident acute myocardial infarction were more likely to be men, smokers, physically inactive, and hypertensive but were less likely to have a parental history of coronary disease. Patients presenting with myocardial infarction were much less likely to have received statins (19.3% vs. 40.4%; P < 0.001) and beta-blockers (19.0% vs. 47.7%; P < 0.001) than patients presenting with exertional angina. After adjustment for potential confounders, recent use of statins (adjusted odds ratio, 0.45 [95% CI, 0.32 to 0.62]) and beta-blockers (adjusted odds ratio, 0.26 [CI, 0.19 to 0.35]) was associated with lower likelihoods of presenting with an acute myocardial infarction than with stable angina. LIMITATIONS: This observational study did not have information on all possible confounding factors, including use of aspirin therapy. CONCLUSION: Statin and beta-blocker use was associated with lower odds of presenting with an acute myocardial infarction than with stable angina. Additional studies are needed to confirm that these therapies protect against unstable, higher-risk clinical presentations of coronary disease.
BACKGROUND: Prior studies have shown an association between depression and self-rated health among patients with coronary disease. However, the magnitude of the effect of depression on self-rated health compared with that of major clinical events is unknown. Our main objective was to clarify the association between depression and self-rated health using longitudinal data. METHODS: We performed a prospective cohort study of 2675 postmenopausal women with coronary disease. The primary predictor variable was a 4-state categorical depression variable based on the Burnam depression screen assessed at sequential visits. The outcome variable was self-rated overall health (excellent, very good, or good vs fair or poor). RESULTS: After adjustment for age, comorbidities, prior self-rated health, and interim events, women with depression at both current and prior annual visits had a >5-fold increased odds of fair/poor self-rated health (odds ratio [OR] 5.1, 95% CI 3.8-6.8). New depression was associated with a >2-fold increased odds of fair/poor self-rated health (OR 2.6, 95% CI 2.0-3.4). Having a history of depression at the preceding annual visit but not at the current visit was associated with a slight increased odds of fair/poor self-rated health (OR 1.3, 95% CI 1.0-1.7). The magnitude of the impact of persistent or new depression was comparable to that of recent angina, myocardial infarction, angioplasty, heart failure, or bypass surgery. CONCLUSIONS: Women with persistent or new depression are more likely to report fair/poor self-rated health. The magnitude of the impact of persistent or new depression is comparable to that of major cardiac events.
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BACKGROUND: Economic outcomes are now included in many contemporary randomized trials and provide an additional dimension to the assessment of interventions. Economic data collection and analysis pose several methodologic challenges, however. PURPOSE: This paper reviews methods of incorporating economic outcomes in clinical trials. RESULTS: Data on medical resource utilization and cost can readily be collected along with data on clinical outcomes. The cost of planned interventions can be measured with reasonable accuracy, but costs due to unplanned clinical events are more difficult to measure reliably. The total cost depends critically on these relatively infrequent, yet costly, adverse outcomes, which may partially, or even completely, offset any difference between the planned costs of the randomized therapies. Newer therapies are typically more expensive than older therapies, so the most important question is whether patient outcomes are improved sufficiently to justify the added expense. Cost-effectiveness analysis helps gauge the value provided by a new therapy. The cost-effectiveness of an intervention compared with an alternative is defined as the ratio of the incremental costs and the incremental clinical benefits, measured as dollars per quality-adjusted life-year added. The follow-up period in most clinical trials is generally long enough to measure the added cost of therapy, but may not capture the full benefits of treatment. The limited time horizon of clinical trials makes it necessary to use a model to extrapolate the observed effect of treatment and project the increase in life expectancy. The resulting cost-effectiveness ratio is sensitive to assumptions about the long-term efficacy of treatment, particularly whether the treatment effect will continue or dissipate over time. CONCLUSION: Economic outcomes can be measured alongside clinical outcomes in randomized trial. While the use of cost-effectiveness models falls outside the strictly empirical, within-trial analysis framework that is embraced by most clinical trialists, it provides an explicit approach to assessing whether the intervention under study provides a clinically meaningful improvement in outcome that is worthwhile.
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BACKGROUND: Eight randomized trials have evaluated whether the prophylactic use of an implantable cardioverter-defibrillator (ICD) improves survival among patients who are at risk for sudden death due to left ventricular systolic dysfunction but who have not had a life-threatening ventricular arrhythmia. We assessed the cost-effectiveness of the ICD in the populations represented in these primary-prevention trials. METHODS: We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of the prophylactic implantation of an ICD, as compared with control therapy, among patients with survival and mortality rates similar to those in each of the clinical trials. We modeled the efficacy of the ICD as a reduction in the relative risk of death on the basis of the hazard ratios reported in the individual clinical trials. RESULTS: Use of the ICD increased lifetime costs in every trial. Two trials--the Coronary Artery Bypass Graft (CABG) Patch Trial and the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)--found that the prophylactic implantation of an ICD did not reduce the risk of death and thus was both more expensive and less effective than control therapy. For the other six trials--the Multicenter Automatic Defibrillator Implantation Trial (MADIT) I, MADIT II, the Multicenter Unsustained Tachycardia Trial (MUSTT), the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)--the use of an ICD was projected to add between 1.01 and 2.99 quality-adjusted life-years (QALY) and between 68,300 dollars and 101,500 dollars in cost. Using base-case assumptions, we found that the cost-effectiveness of the ICD as compared with control therapy in these six populations ranged from 34,000 dollars to 70,200 dollars per QALY gained. Sensitivity analyses showed that this cost-effectiveness ratio would remain below 100,000 dollars per QALY as long as the ICD reduced mortality for seven or more years. CONCLUSIONS: Prophylactic implantation of an ICD has a cost-effectiveness ratio below 100,000 dollars per QALY gained in populations in which a significant device-related reduction in mortality has been demonstrated.
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Demand for economic evaluations in multinational clinical trials is increasing, but there is little consensus about how such studies should be conducted and reported. At a workshop in Durham, North Carolina, we sought to identify areas of agreement about how the primary findings of economic evaluations in multinational clinical trials should be generated and presented. In this paper, we propose a framework for classifying multinational economic evaluations according to (a) the sources of an analyst's estimates of resource use and clinical effectiveness and (b) the analyst's method of estimating costs. We review existing studies in the cardiology literature in the context of the proposed framework. We then describe important methodological and practical considerations in conducting multinational economic evaluations and summarize the advantages and disadvantages of each approach. Finally, we describe opportunities for future research. Delineation of the various approaches to multinational economic evaluation may assist researchers, peer reviewers, journal editors, and decision makers in evaluating the strengths and limitations of particular studies.
BACKGROUND: Coronary bypass surgery (CABG) and angioplasty (PTCA) have been compared in several randomized trials, but data about long-term economic and quality-of-life outcomes are limited. METHODS AND RESULTS: Cost and quality-of-life data were collected prospectively from 934 patients who were randomized in the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for 10 to 12 years. CABG had 53% higher costs initially, but the gap closed to <5% during the first 2 years; after 12 years, the mean cumulative cost of CABG patients was 123,000 dollars versus 120,750 dollars for PTCA, yielding a cost-effectiveness ratio of 14,300 dollars/life-year added. CABG patients experienced significantly greater improvement in their physical functioning for the first 3 years but not in later follow-up. Recurrent angina substantially reduced all quality-of-life measures throughout follow-up. Cumulative costs were significantly higher among patients with diabetes, heart failure, and comorbid conditions and among women; costs also were increased by angina, by the number of revascularization procedures, and among patients who died. CONCLUSIONS: Early differences between CABG and PTCA in costs and quality of life were no longer significant at 10 to 12 years of follow-up. CABG was cost-effective as compared with PTCA for multivessel disease.