Faculty Bibliography

BACKGROUND: Albuminuria has been associated with cardiovascular risk, but the relationship of high-normal albuminuria to subsequent heart failure has not been well established. STUDY DESIGN: Prospective observational study, the Atherosclerosis Risk in Communities (ARIC) Study. SETTING & PARTICIPANTS: 10,975 individuals free from heart failure were followed up from the fourth ARIC Study visit (1996-1998) through January 2006. PREDICTOR: Urinary albumin-creatinine ratio (UACR), analyzed continuously and categorically as optimal (<5 mg/g), intermediate-normal (5-9 mg/g), high-normal (10-29 mg/g), microalbuminuria (30-299 mg/g), and macroalbuminuria (>/=300 mg/g). OUTCOMES & MEASUREMENTS: Incident heart failure was defined as a heart failure-related hospitalization or death. Cox proportional hazard models were used to calculate the HR of heart failure after adjustment for age, race, sex, estimated glomerular filtration rate (eGFR), and other cardiovascular risk factors. RESULTS: Individuals were followed up for a median of 8.3 years and experienced 344 heart failure events. Compared with normal UACR, albuminuria was associated with a progressively increased risk of heart failure from intermediate-normal (adjusted HR, 1.54; 95% CI, 1.12-2.11) and high-normal UACR (adjusted HR, 1.91; 95% CI, 1.38-2.66) to microalbuminuria (adjusted HR, 2.49; 95% CI, 1.77-3.50) and macroalbuminuria (adjusted HR, 3.47; 95% CI, 2.10-5.72). Results were similar in secondary analyses of participants censored at the time of coronary heart disease event and along a range of eGFRs. LIMITATIONS: UACR was measured as a single random sample. CONCLUSIONS: Albuminuria is associated with subsequent heart failure, even in individuals with few cardiovascular risk factors and UACR within the normal range. Our results suggest that the association between albuminuria and heart failure may not be mediated fully by ischemic heart disease or kidney disease, measured using eGFR.

BACKGROUND: A substantial portion of the public health burden of heart failure is due to hospitalizations, many of which are for causes other than cardiovascular disease. We assessed whether left ventricular (LV) systolic dysfunction was associated with increased risk of both cardiovascular and noncardiovascular hospitalizations in a community sample of African Americans. METHODS: African American participants from the Jackson, MS, site of the Atherosclerosis Risk in Communities (ARIC) study who underwent echocardiography were followed for 12 years. Hospitalization rates among individuals with and without LV systolic dysfunction were compared using negative binomial regression. RESULTS: Among 2,416 participants with echocardiograms, LV systolic dysfunction was found in 61 (2.5%). Participants with LV dysfunction experienced 366 hospitalizations, a rate of 1.27 per person-year, compared with 0.25 per person-year among individuals without LV dysfunction. The incidence rate ratio adjusted for demographics, comorbidities, and other risk factors was 3.11 (95% CI 2.22-4.35). The adjusted rate ratios were 4.76 (95% CI 2.90-7.20) for cardiovascular and 2.67 (95% CI 1.82-3.90) for noncardiovascular diagnoses, with similar findings in the subset of individuals with asymptomatic LV dysfunction. The percentage attributable risks for hospitalizations were 87% and 74% for cardiovascular and noncardiovascular causes (79% and 63% after adjustment). CONCLUSIONS: African American individuals with LV dysfunction are at an increased risk of hospitalization due to a wide range of causes, with noncardiovascular hospitalizations accounting for nearly half the increased risk. To the extent that estimates of risk focus on cardiovascular morbidity, they may underestimate the true health burden of LV dysfunction.

OBJECTIVE: This study sought to investigate an association of HbA1c (A1C) with incident heart failure among individuals without diabetes and compare it to fasting glucose. RESEARCH DESIGN AND METHODS: We studied 11,057 participants of the Atherosclerosis Risk in Communities (ARIC) Study without heart failure or diabetes at baseline and estimated hazard ratios of incident heart failure by categories of A1C (<5.0, 5.0-5.4 [reference], 5.5-5.9, and 6.0-6.4%) and fasting glucose (<90, 90-99 [reference], 100-109, and 110-125 mg/dl) using Cox proportional hazards models. RESULTS: A total of 841 cases of incident heart failure hospitalization or deaths (International Classification of Disease, 9th/10th Revision, 428/I50) occurred during a median follow-up of 14.1 years (incidence rate 5.7 per 1,000 person-years). After the adjustment for covariates including fasting glucose, the hazard ratio of incident heart failure was higher in individuals with A1C 6.0-6.4% (1.40 [95% CI, 1.09-1.79]) and 5.5-6.0% (1.16 [0.98-1.37]) as compared with the reference group. Similar results were observed when adjusting for insulin level or limiting to heart failure cases without preceding coronary events or developed diabetes during follow-up. In contrast, elevated fasting glucose was not associated with heart failure after adjustment for covariates and A1C. Similar findings were observed when the top quartile (A1C, 5.7-6.4%, and fasting glucose, 108-125 mg/dl) was compared with the lowest quartile (<5.2% and <95 mg/dl, respectively). CONCLUSIONS: Elevated A1C (> or =5.5-6.0%) was associated with incident heart failure in a middle-aged population without diabetes, suggesting that chronic hyperglycemia prior to the development of diabetes contributes to development of heart failure.

OBJECTIVE: To examine the association between severe mental illness (SMI) and quality of care in heart failure. METHODS: We conducted a cohort study between 2001 and 2004 of disabled Maryland Medicaid participants with heart failure. Quality measures and clinical outcomes were compared for individuals with and without SMI. RESULTS: Of 1801 individuals identified with heart failure, 341 had comorbid SMI. SMI was not associated with differences in quality measures, including left ventricular assessment [adjusted relative risk (aRR) 0.99; 95% CI 0.91-1.07], utilization of angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) (aRR 1.04; 95% CI 0.92-1.17), or beta-blocker use (aRR 1.13; 95% CI 0.99-1.29). During the study period, 52.2% of individuals in the cohort filled a prescription for an ACE inhibitor or ARB and 45.5% filled a beta-blocker prescription. Individuals with and without SMI had similar rates of clinical outcomes, including hospitalizations, readmissions, and mortality. Both medication interventions were associated with improved mortality. CONCLUSIONS: In this sample of disabled Medicaid recipients with heart failure, persons with SMI received similar quality of care as those without SMI. Both groups had low rates of beneficial medical treatments. Quality improvement programs should consider how best to target these vulnerable populations.

In the era of "comparative effectiveness" research, each of the major stakeholders in healthcare-payors, patients, providers, and government-face a similar challenge. When making a decision about whether a new device, drug, or a diagnostic modality should be considered for use or coverage, what choices are best supported by the evidence? Medical evidence is defined by randomized controlled trials and by observational studies that vary greatly in their design, the accuracy of their analyses, and the relevance of their conclusions and recommendations. Hence, key decision makers increasingly rely on systematic reviews and meta-analyses to facilitate the interpretation and application of research evidence. Knowing how to evaluate meta-analyses and understanding the potential pitfalls of the method are crucial for those involved in designing drug benefits. The authors highlight the process, strengths, and weaknesses of meta-analysis and explain how to judge the value of the results.