CLINICAL RESEARCH
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 ,
* Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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.
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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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