Insulinlike Growth Factor Binding Protein-1 and Ghrelin Predict Health Outcomes Among Older Adults: Cardiovascular Health Study Cohort.
Multiple diseases may explain the association of the growth hormone/insulinlike growth factor-I (GH/IGF-I) axis with longevity.



To relate circulating GH/IGF-I system protein levels with major health events.



This is a cohort study set in 4 US communities.



Adults (N = 2268) 65 years and older free of diabetes and cardiovascular disease.



We assessed insulinlike growth factor binding protein-1 (IGFBP-1) and ghrelin in fasting and 2-hour oral glucose tolerance test (OGTT) blood samples, as well as fasting IGF-I and IGFBP-3. Hazard ratios for mortality and a composite outcome for first incident myocardial infarction, stroke, heart failure, hip fracture, or death were adjusted for sociodemographic, behavioral, and physiological covariates.



During 13,930 person-years of follow-up, 48.1% of individuals sustained one or more components of the composite outcome and 31.8% died. Versus the lowest quartiles, the highest quartiles of fasting and 2-hour ghrelin were associated with 27% higher (95% confidence interval [CI]: 6%, 53%) and 39% higher (95% CI: 14%, 71%) risks of the composite outcome, respectively. The highest quartile of 2-hour IGFBP-1 was associated with 35% higher (95% CI: 1%, 52%) risk of the composite end point. Similarly, higher mortality was significantly associated with higher fasting and 2-hour ghrelin levels and with 2-hour IGFBP-1 level. When examined together, 2-hour post-OGTT levels of IGFBP-1 and ghrelin tended to predict outcomes better than fasting levels.



Circulating IGFBP-1 and ghrelin measured during an OGTT predicted major health events and death in older adults, which may explain the influence of the GH/IGF-I axis on lifespan and health.
Department of Epidemiology and Population Health and.
Robert C
RC
Kaplan
Department of Epidemiology and Population Health and.
Garrett
G
Strizich
Department of Epidemiology and Population Health and.
Chino
C
Aneke-Nash
Department of Biostatistics and.
Clara
C
Dominguez-Islas
Department of Biostatistics and.
Petra
P
Bužková
Department of Epidemiology and Population Health and.
Howard
H
Strickler
Department of Epidemiology and Population Health and.
Thomas
T
Rohan
Department of Medicine and Oncology, McGill University, Montreal, Quebec, Canada H4A 3J1.
Michael
M
Pollak
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Lewis
L
Kuller
Division of Cardiology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
Jorge R
JR
Kizer
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
Anne
A
Cappola
Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington 98195.|Epidemiology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109; and.
Christopher I
CI
Li
Cardiovascular Health Research Unit, Departments of Epidemiology and Health Services, University of Washington & Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101.
Bruce M
BM
Psaty
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261.
Anne
A
Newman
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D005215:Fasting / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D054439:Ghrelin / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies
D015415:Biomarkers; D054439:Ghrelin; C032231:IGFBP1 protein, human; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I