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J Am Coll Cardiol, 2005; 46:2054-2060, doi:10.1016/j.jacc.2005.07.059 (Published online 8 November 2005).
© 2005 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: HEART FAILURE

Novel Metabolic Risk Factors for Heart Failure

Erik Ingelsson, MD, PhD*,*, Johan Ärnlöv, MD, PhD*, Johan Sundström, MD, PhD*, Björn Zethelius, MD, PhD*, Bengt Vessby, MD, PhD* and Lars Lind, MD, PhD{dagger},{ddagger}

* Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden
{dagger} Department of Medical Sciences, Uppsala University, Uppsala, Sweden
{ddagger} Astra Zeneca R and D, Mölndal, Sweden.

Manuscript received March 29, 2005; revised manuscript received July 11, 2005, accepted July 25, 2005.

* Reprint requests and correspondence: Dr. Erik Ingelsson, Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala Science Park, SE-75185 Uppsala, Sweden; Visiting address: Dag Hammarskjölds väg 14B, Uppsala, Sweden. (Email: erik.ingelsson{at}pubcare.uu.se).

OBJECTIVES: Our objectives were to explore novel metabolic risk factors for development of heart failure (HF).

BACKGROUND: In the past decade, considerable knowledge has been gained from limited samples regarding novel risk factors for HF, but the importance of these in the general population is largely unexplored.

METHODS: In a community-based prospective study of 2,321 middle-aged men free from HF and valvular disease at baseline, variables reflecting glucose and lipid metabolism and variables involved in oxidative processes were compared with established risk factors for HF (prior myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, obesity, and serum cholesterol) using Cox proportional hazards analyses.

RESULTS: During a median follow-up time of 29 years, 259 subjects developed HF. In a multivariable Cox proportional hazards backward stepwise model, a 1-SD increase of fasting proinsulin (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.15 to 1.66) and apolipoprotein B/A-I-ratio (HR 1.27, 95% CI 1.09 to 1.48) increased the risk, whereas a 1-SD increase in serum beta-carotene (HR 0.79, 95% CI 0.66 to 0.94) decreased the risk of HF. These variables also remained significant when adjusting for acute myocardial infarction during follow-up.

CONCLUSIONS: Novel variables reflecting insulin resistance and dyslipidemia, together with a low beta-carotene level, were found to predict HF independently of established risk factors. If confirmed, our observations could have large clinical implications, as they may offer new approaches in the prevention of HF.

Abbreviations and Acronyms
  BMI = body mass index
  CHD = coronary heart disease
  CI = confidence interval
  ECG-LVH = electrocardiographic left ventricular hypertrophy
  HDL = high-density lipoprotein
  HF = heart failure
  HOMA = homeostasis model assessment
  HR = hazard ratio
  ICD = International Classification of Diseases
  IVGTT = intravenous glucose tolerance test
  LDL = low-density lipoprotein
  LV = left ventricular
  MI = myocardial infarction
  ULSAM = Uppsala Longitudinal Study of Adult Men




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