Association of total insulin-like growth factor-I, insulin-like growth factor binding protein-1 (IGFBP-1), and IGFBP-3 levels with incident coronary events and ischemic stroke

J Clin Endocrinol Metab. 2007 Apr;92(4):1319-25. doi: 10.1210/jc.2006-1631. Epub 2007 Jan 30.

Abstract

Context: Prior observational studies have demonstrated that the GH/IGF axis is associated with cardiovascular disease. However, this association has not been extensively studied among older adults.

Objective: The objective of this study was to assess the association between levels of total IGF-I and IGF binding proteins (IGFBP-1, IGFBP-3) and risk of incident coronary events and ischemic stroke.

Design and participants: A case-cohort analysis was conducted among adults 65 yr and older in the Cardiovascular Health Study.

Main outcome measures: A total of 534 coronary events [316 nonfatal myocardial infarctions (MIs), 48 fatal MIs, and 170 fatal coronary heart disease events] and 370 ischemic strokes were identified on follow-up. Comparison subjects were 1122 randomly selected participants from the Cardiovascular Health Study.

Results: Mean follow-up time was 6.7 yr for coronary events, 5.6 yr for strokes, and 9.3 yr for comparison subjects. Hazard ratios (95% confidence intervals) associated with baseline levels of total IGF-I and IGFBPs were estimated using multivariate adjusted Cox proportional hazards models. Neither IGF-I nor IGFBP-1 levels predicted risk of incident coronary events or stroke. IGFBP-3 had an inverse association with risk of coronary events [adjusted hazard ratio per sd=0.88 (0.78-1.00), P=0.05] but was not associated with stroke. Exploratory analyses suggested that low IGF-I and low IGFBP-3 levels were significantly associated with higher risk of nonfatal MI (P<0.05) but not with risk of fatal MI or fatal coronary heart disease.

Conclusion: Circulating levels of total IGF-I or IGFBP-1 were not associated with risk of total coronary events or ischemic stroke among older adults, whereas low IGFBP-3 level was associated with increased risk of incident coronary events.

Publication types

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

MeSH terms

  • Aged
  • Cardiovascular Diseases / epidemiology
  • Case-Control Studies
  • Cohort Studies
  • Coronary Disease / epidemiology*
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / blood*
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Multivariate Analysis
  • Risk Factors
  • Stroke / epidemiology*

Substances

  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I