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

Robert C. Kaplan, Aileen P. McGinn, Michael N. Pollak, Lewis H. Kuller, Howard Strickler, Thomas E. Rohan, Anne R. Cappola, Xiaonan (Nan) Xue, Bruce M. Psaty

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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.

Original languageEnglish (US)
Pages (from-to)1319-1325
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number4
DOIs
StatePublished - Apr 2007

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Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Stroke
Myocardial Infarction
Insulin-Like Growth Factor Binding Proteins
Hazards
Coronary Disease
Health
Proportional Hazards Models
Observational Studies
Cohort Studies
Cardiovascular Diseases
Outcome Assessment (Health Care)
Confidence Intervals

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{cd45b4dddf7c4264951d629bc6ab39e1,
title = "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",
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.",
author = "Kaplan, {Robert C.} and McGinn, {Aileen P.} and Pollak, {Michael N.} and Kuller, {Lewis H.} and Howard Strickler and Rohan, {Thomas E.} and Cappola, {Anne R.} and Xue, {Xiaonan (Nan)} and Psaty, {Bruce M.}",
year = "2007",
month = "4",
doi = "10.1210/jc.2006-1631",
language = "English (US)",
volume = "92",
pages = "1319--1325",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "4",

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TY - JOUR

T1 - 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

AU - Kaplan, Robert C.

AU - McGinn, Aileen P.

AU - Pollak, Michael N.

AU - Kuller, Lewis H.

AU - Strickler, Howard

AU - Rohan, Thomas E.

AU - Cappola, Anne R.

AU - Xue, Xiaonan (Nan)

AU - Psaty, Bruce M.

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

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U2 - 10.1210/jc.2006-1631

DO - 10.1210/jc.2006-1631

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