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CLINICAL RESEARCH: HEART FAILURE

Novel Metabolic Risk Factors for Incident Heart Failure and Their Relationship With Obesity

The MESA (Multi-Ethnic Study of Atherosclerosis) Study

Hossein Bahrami, MD, MPH, PhD^_*,, David A. Bluemke, MD, PhD^_*,, Richard Kronmal, PhD^,||, Alain G. Bertoni, MD, MPH^¶, Donald M. Lloyd-Jones, MD, ScM^#, Eyal Shahar, MD, MPH^_**, Moyses Szklo, MD, DrPH and João A.C. Lima, MD^_*,,,_*

^_* Cardiology Division, Department of Medicine, Baltimore, Maryland
Department of Epidemiology, School of Public Health, Baltimore, Maryland
Department of Radiology, Johns Hopkins University, Baltimore, Maryland
Department of Biostatistics, University of Washington, Seattle, Washington
^|| Collaborative Health Studies Coordinating Center, University of Washington, Seattle, Washington
^¶ Department of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina
^# Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois
^_** Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona.

Manuscript received July 25, 2007; revised manuscript received December 17, 2007, accepted December 19, 2007.

^_* Reprint request and correspondence: Dr. João A. C. Lima, Johns Hopkins University, Department of Cardiology, 600 North Wolfe Street, Block 524, Baltimore, Maryland 21205. (Email: jlima{at}jhmi.edu).

Objectives: The objectives of this study were to determine the associations of the metabolic syndrome, inflammatory markers, and insulin resistance with incident congestive heart failure (CHF), beyond established risk factors, and to examine whether these risk factors may provide the link between obesity and CHF.

Background: Recently, increasing interest has emerged on the potential role of novel risk factors such as systemic inflammation, insulin resistance, and albuminuria in the pathophysiology of CHF and their relationship with obesity.

Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) study is a community-based multicenter cohort study of 6,814 participants (age 45 to 84 years, 3,601 women) of 4 ethnicities: Caucasians, African Americans, Hispanics, and Chinese Americans. Participants were recruited between 2000 and 2002 from 6 U.S. communities. Median follow-up time was 4 years. Participants with history of symptomatic cardiovascular disease were excluded. Cox proportional hazards models were used to analyze the associations of the metabolic syndrome, inflammatory markers, insulin resistance, and albuminuria with incident CHF, independent of established risk factors (age, gender, hypertension, diabetes mellitus, left ventricular hypertrophy, obesity, serum total cholesterol, and smoking), an interim myocardial infarction, and baseline magnetic resonance imaging parameters of left ventricular structure and function.

Results: A total of 79 participants developed CHF during follow-up, and 26 participants (32.9%) had a myocardial infarction prior to CHF and 65% of the cases had CHF with preserved function (left ventricular ejection fraction 40%). In multivariable analyses, serum interleukin-6 (hazard ratio [HR] for 1 standard deviation 1.50, 95% confidence interval [CI] 1.10 to 2.03) or C-reactive protein (HR for 1 standard deviation 1.38; 95% CI 1.01 to 1.86) and macroalbuminuria (HR 4.31, 95% CI 1.58 to 11.76) were predictors of CHF, independent of obesity and the other established risk factors. Although obesity was significantly associated with incident CHF, this association was no longer significant after adding inflammatory markers (interleukin-6 or C-reactive protein) to the model.

Conclusions: Inflammatory markers and albuminuria are independent predictors of CHF. The association of obesity and CHF may be related to pathophysiologic pathways associated with inflammation.

Abbreviations and Acronyms   BMI = body mass index   CHF = congestive heart failure   CI = confidence interval   CPH = Cox proportional hazards   CRP = C-reactive protein   ECG = electrocardiography   HOMA = homeostasis model assessment   HR = hazard ratio   IL = interleukin   IR = Insulin resistance   LV = left ventricle/ventricular   LVEF = left ventricular ejection fraction   LVH = left ventricular hypertrophy   MI = myocardial infarction   MRI = magnetic resonance imaging   UACR = urinary albumin-to-creatinine ratio

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