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

Kaplan, Robert C.; McGinn, Aileen P.; Pollak, Michael; Kuller, Lewis H.; Strickler, Howard D.; Rohan, Tomáš; Cappola, Anne R.; Xue, Xiao Nan; Psaty, Bruce M.

doi:10.1210/jc.2006-1631

Cited by 109 publications

(97 citation statements)

References 36 publications

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“…Circulating concentrations of IGF‐I and IGFBP‐3 have been associated with risk of type 2 diabetes, cardiovascular diseases, cancer, and mortality in epidemiological studies (Juul et al ., 2002; Vasan et al ., 2003; Renehan et al ., 2004; Kaplan et al ., 2007; Friedrich et al ., 2009; Burgers et al ., 2011; Rajpathak et al ., 2012). In animal models, diminished IGF‐I/insulin signaling has been associated with extended lifespans (Ziv & Hu, 2011), although the role of the IGF axis in human longevity remains inconclusive.…”

Section: Introductionmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

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SummaryThe growth hormone/insulin‐like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF‐related proteins including IGF‐I and IGF‐binding protein‐3 (IGFBP‐3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF‐I and IGFBP‐3 concentrations (IGF1, IGFBP3,GCKR,TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP‐3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF‐I and IGFBP‐3 concentrations. The IGF‐I‐decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity‐associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF‐I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF‐I‐ and IGFBP‐3‐associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF‐I and IGFBP‐3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity‐associated loci.

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Section: Introductionmentioning

confidence: 99%

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Teumer¹,

Qi²,

Nethander³

et al. 2016

Aging Cell

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“…However, the GH/IGF-1 axis declines with age with a large variability between individuals, emphasizing the need for prospective studies. Several such studies have been conducted, particularly among elderly people, showing that low IGF-1 is predictive of all-cause and cardiovascular mortality [2,19]. Recently, a bioassay was devised to specifically measure unbound bioactive IGF-1 and elevated IGF-1 bioactivity was found predictive of extended survival among elderly [6].…”

Section: Discussionmentioning

confidence: 99%

Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: The PRIME study

et al. 2011

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a b s t r a c tObjective: Insulin-like growth factor-1 (IGF-1) has been associated with cardiovascular risk factors and atherosclerosis. The aim of the present study was to evaluate the prognostic value of IGF-1 concentrations with respect to occurrence of well-defined coronary syndromes. Methods: The PRIME study is a prospective cohort having included 10,600 subjects from Northern Ireland and France. Detailed information on cardiovascular risk factors, socioeconomic and behavioural variables were collected and a cardiologic examination was performed. At 5-year follow-up, 317 incident cases of coronary events were recorded according to strict protocols. They were matched to 634 age-and centre-paired controls from the same cohort, free of coronary disease. Baseline IGF-1 concentrations were measured, together with variables of lipid and glucose metabolism and markers of vascular and systemic inflammation. Results: Baseline IGF-1 concentration was lower in subjects developing an acute coronary syndrome than in unaffected controls. IGF-1 levels correlated negatively with age, waist circumference, tobacco consumption and markers of inflammation. Subjects in the highest quartile of IGF-1 distribution had a 55% reduction in the relative risk of developing myocardial infarction and a 45% decrease for all-combined acute coronary syndromes. A similar trend, although non-significant, was noted for angina pectoris. Multiple adjustments on classical risk factors and inflammation markers did not affect IGF-1 results. Elevated levels of both IGF-1 and apo A-I conferred a significantly greater risk reduction than either one alone. However, interaction between the two markers was not significant. Conclusion: Like HDL markers, high levels of IGF-1 confer protection against coronary artery disease.

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“…IGF-I, the main effector peptide of the IGF system and the principal mediator of growth hormone (GH) effects, may influence the development of agerelated cardiovascular diseases (7)(8)(9)(10)(11). A report from the Framingham Heart Study identified low IGF-I as a risk factor for incident congestive heart failure (CHF) in the elderly (7).…”

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confidence: 99%

High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly

Kaplan¹,

McGinn²,

Pollak³

et al. 2008

American Heart Journal

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Background-Low insulin-like growth factor-1 (IGF-I) may influence the development of agerelated cardiovascular diseases including congestive heart failure (CHF). Insulin-like growth factor binding protein-1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in CHF patients and has been associated prospectively with increased mortality among older adults and myocardial infarction survivors. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study (CHS).

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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: 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.

Cited by 109 publications

References 36 publications

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Genomewide meta‐analysis identifies loci associated with IGF ‐I and IGFBP ‐3 levels with impact on age‐related traits

Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: The PRIME study

High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly

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