Novel metabolic risk factors for incident heart failure and their relationship with obesity: the MESA (Multi-Ethnic Study of Atherosclerosis) study

J Am Coll Cardiol. 2008 May 6;51(18):1775-83. doi: 10.1016/j.jacc.2007.12.048.


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 >or=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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Albuminuria / complications*
  • Arteriosclerosis / blood
  • Arteriosclerosis / complications*
  • Arteriosclerosis / physiopathology
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Ethnicity / statistics & numerical data
  • Female
  • Heart Failure / blood
  • Heart Failure / epidemiology
  • Heart Failure / etiology*
  • Heart Failure / physiopathology*
  • Humans
  • Incidence
  • Inflammation / blood
  • Inflammation / complications*
  • Inflammation / physiopathology
  • Insulin Resistance*
  • Interleukin-6 / blood
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / physiopathology
  • Middle Aged
  • Obesity / blood
  • Obesity / complications*
  • Obesity / physiopathology
  • Prospective Studies
  • Risk Factors
  • Surveys and Questionnaires
  • United States / epidemiology
  • Ventricular Dysfunction, Left / etiology


  • Biomarkers
  • Interleukin-6
  • C-Reactive Protein