Cited by 374Growth Hormone and Insulin-like Growth FactorsHormonal and reproductive studiesDiabetes, Cardiovascular Risks, and Lipoproteins

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The Prospective Association of Serum Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-1 Levels with All Cause and Cardiovascular Disease Mortality in Older Adults: The Rancho Bernardo Study

Laughlin, Gail A., Barrett-Connor, Elizabeth, Criqui, Michael H., Kritz-Silverstein, Donna·2004·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2003-030967

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Abstract

The IGF system has been implicated in cardiovascular disease (CVD) development. The prospective association of serum IGF-I and IGF-binding protein-1 (IGFBP-1) with all cause, ischemic heart disease (IHD), and non-IHD CVD mortality was examined in 633 men and 552 nonestrogen-using postmenopausal women, aged 51-98 yr (mean, 74 yr) in 1988-1992, who were followed through July 2001 (96% follow-up). During the 9- to 13-yr follow-up, there were 522 deaths; 224 were attributed to CVD, and 105 were caused by IHD. IGF-I and IGFBP-1 were independently and jointly related to risk of IHD mortality. In a proportional hazards model including both IGF-I and IGFBP-1 and adjusting for CVD risk factors, the relative risk of IHD mortality was 38% higher for every 40 ng/ml (1 SD) decrease in IGF-I (95% confidence interval, 1.09-1.76; P = 0.005) and 3.11 times greater for those in the lowest quintile of IGFBP-1 (95% confidence interval, 1.74-5.56; P < 0.001) compared with those with higher IGFBP-1 levels. IGF-I and IGFBP-1 (alone or in combination) were not related to risk of all cause or non-IHD CVD mortality. We conclude that low baseline levels of IGF-I and IGFBP-1 increase the risk of fatal IHD among elderly men and women independent of prevalent IHD and CVD risk factors.

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Effects of IGF-1 on the Cardiovascular System
Obradovic, M. M., Zafirovic, S. S., Šoškić, S., Stanimirović, J., Trpković, A., Jevremović, D., & Isenović, E. R. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191106091507 · Cited by 51
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“Interestingly, the IGF system has recently been implicated in cardiovascular disease development [38] with lower levels of IGF-1 specifically linked to increased risk of ischemic heart disease.”
Background
Both Low and High Serum IGF-1 Levels Associate With Increased Risk of Cardiovascular Events in Elderly Men
Carlzon, D., Svensson, J., Petzold, M., Karlsson, M. K., Ljunggren, Ö., Tivesten, Å., Mellström, D., & Ohlsson, C. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-1575 · Cited by 49
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The Insulin-Like Growth Factor System, Metabolic Syndrome, and Cardiovascular Disease Risk
Akanji, A. O., & Smith, R. J. (2011) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2011.0083 · Cited by 47
The role of IGF-1 in obesity, cardiovascular disease, and cancer.
Hanjani, N. A., & Vafa, M. (2019) · PubMed Central · doi:10.34171/mjiri.33.56 · Cited by 47
“It is hypothesized that low IGF1 is correlated with, obesity, low physical activity, and IF(24, 25).”
Background
Age-specific variations in hematological and biochemical parameters in middle- and large-sized of dogs
Lee, S. H., Kim, J. W., Lee, B. C., & Oh, H. J. (2019) · Journal of Veterinary Science · doi:10.4142/jvs.2020.21.e7 · Cited by 52
“Interestingly, previous epidemiological studies have indicated that a higher concentration of IGF-1 can decrease the risk of cognitive decline and dementia [11,12], which is intimately linked with age-related process.”
Serum concentrations of human insulin-like growth factor-1 and levels of insulin-like growth factor-binding protein-5 in patients with nonalcoholic fatty liver disease
Çolak, Y., Şenateş, E., Öztürk, O., Yilmaz, Y. N., Zemheri, E. I., Enc, F. Y., Ulaşoğlu, C., Aksaray, S., Bozbeyoğlu, S. G., KIZILTAŞ, Ş., et al. (2011) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e32834e8041 · Cited by 46
Both Low and High Serum IGF-I Levels Associate with Cancer Mortality in Older Men
Svensson, J., Carlzon, D., Petzold, M., Karlsson, M. K., Ljunggren, Ö., Tivesten, Å., Mellström, D., & Ohlsson, C. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2329 · Cited by 46
Vasoprotective Effects of Life Span-Extending Peripubertal GH Replacement in Lewis Dwarf Rats
Ungvari, Z. I., Gautam, T., Koncz, P., Henthorn, J., Pinto, J. T., Ballabh, P., Yan, H., Mitschelen, M. C., Farley, J. A., Sonntag, W. E., et al. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq147 · Cited by 46
The age-related down-regulation of the growth hormone/insulin-like growth factor-1 axis in the elderly male is reversed considerably by donepezil, a drug for Alzheimer's disease
Obermayr, R. P., Mayerhofer, L., Knechtelsdorfer, M., Mersich, N., Huber, E. R., Geyer, G., & Tragl, K. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.11.001 · Cited by 45
Development of the Monoclonal Antibody Figitumumab, Targeting the Insulin-like Growth Factor-1 Receptor, for the Treatment of Patients with Non–Small-Cell Lung Cancer
Gualberto, A., & Karp, D. D. (2009) · Clinical Lung Cancer · doi:10.3816/clc.2009.n.038 · Cited by 45
Free Radical Production, Antioxidant Capacity, and Oxidative Stress Response Signatures in Fibroblasts From Lewis Dwarf Rats: Effects of Life Span-Extending Peripubertal GH Treatment
Ungvari, Z. I., Sosnowska, D., Podlutsky, A. J., Koncz, P., Sonntag, W. E., & Csiszár, A. (2011) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr004 · Cited by 44
Low-Plasma Insulin-Like Growth Factor-I Levels Are Associated with Impaired Endothelium-Dependent Vasodilatation in a Cohort of Untreated, Hypertensive Caucasian Subjects
Perticone, F., Sciacqua, A., Perticone, M., Laino, I., Miceli, S., Carè, I., Leone, G. G., Andreozzi, F., Maio, R., & Sesti, G. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0646 · Cited by 44
Effects of the route of oestrogen administration on IGF‐1 and IGFBP‐3 in healthy postmenopausal women: results from a randomized placebo‐controlled study
Sonnet, E., Lacut, K., Roudaut, N., Mottier, D., Kerlan, V., & Oger, E. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02783.x · Cited by 44
Associations of Insulin-Like Growth Factor (IGF)-I, IGF-II, IGF Binding Protein (IGFBP)-2 and IGFBP-3 with Ultrasound Measures of Atherosclerosis and Plaque Stability in an Older Adult Population
Martin, R. M., Gunnell, D., Whitley, E., Nicolaides, A. N., GRIFFIN, M. B., Georgiou, N., Smith, G. D., Ebrahim, S. B. J., & Holly, J. M. P. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2295 · Cited by 44
“The association of IGF-I with plaque stability was strengthened in models controlling for IGFBP-3, in line with the results of prospective studies showing inverse associations of IGF-I with IHD only after controlling for IGFBP-3 (5) or IGFBP-1 (6).”
Result
Associations of age-dependent IGF-I SDS with cardiovascular diseases and risk conditions: cross-sectional study in 6773 primary care patients
Schneider, H. J., Klotsche, J., Saller, B., Böhler, S., Sievers, C., Pittrow, D. B., Ruf, G., März, W., Erwa, W., Zeiher, A. M., et al. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0600 · Cited by 44
Low Level of IGF-1 in Obesity May Be Related to Obstructive Sleep Apnea Syndrome
Ursavaş, A., Karadağ, M., İlçöl, Y. Ö., Ercan, İ., BURGAZLIOĞLU, B., Çoşkun, F., & Gözü, R. O. (2007) · Lung · doi:10.1007/s00408-007-9026-x · Cited by 43
“Laughlin et al. [ 31 ] investigated the relationship between serum IGF-1 level and ischemic heart disease mortality in 633 men and 552 women during 9‐13 years of follow-up.”
Background
IGF-1 and Survival in ESRD
Jia, T., Axelsson, T. G., Heimbürger, O., Barany, P. F., Lindholm, B., Stenvinkel, P., & Qureshi, A. R. (2013) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.02470213 · Cited by 43
“Low IGF-1 levels did not relate to allcause mortality among elderly Finish men (10), whereas low levels of IGF-I were independently associated with increased risk of ischemic heart disease mortality in elderly subjects (11).”
Common Carotid Intima-Media Thickness in Growth Hormone (GH)-Deficient Adolescents: A Prospective Study after GH Withdrawal and Restarting GH Replacement
Colao, A., Somma, C. D., Rota, F., Maio, S. D., Salerno, M., Klain, A., Spiezia, S., & Lombardi, G. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1844 · Cited by 43
IGF-I levels and depressive disorders: Results from the Study of Health in Pomerania (SHIP)
Sievers, C., Auer, M. K., Klotsche, J., Athanasoulia, A. P., Schneider, H. J., Nauck, M. A., Völzke, H., John, U., Schulz, A., Freyberger, H. J., et al. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.01.008 · Cited by 43
“After the termination of growth, GH and IGF-I play a pivotal role in the optimization of body composition, and the perpetuation of a metabolic balance (Laughlin et al., 2004) by influencing risk factors such as glucose metabolism and lipid profiles (Janssen et al.”
Background
Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model
Aryankalayil, M. J., Martello, S. E., Bylicky, M. A., Chopra, S., May, J. M., Shankardass, A., MacMillan, L., Sun, L. T., Sanjak, J. S., Vanpouille‐Box, C., et al. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02998-w · Cited by 42
Insulin-Like Growth Factor I and Impaired Glucose Tolerance
Dunger, D. B., Yuen, K. C. J., & Ong, K. K. (2004) · Hormone Research in Paediatrics · doi:10.1159/000080767 · Cited by 41
Interactions between ghrelin, leptin and IGF-I affect metabolic syndrome and early atherosclerosis
Ukkola, O. H., Pöykkö, S. M., Päivänsalo, M. J., & Kesäniemi, Y. A. (2008) · Annals of Medicine · doi:10.1080/07853890802084860 · Cited by 41
“IGF-I deficiency has been shown to increase the cardiovascular risk in some studies (14,15).”
Background
IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men
Yeap, B. B., Chubb, S. A. P., Ho, K. K. Y., Setoh, J. W. S., McCaul, K. A., Norman, P. E., Jamrozik, K. D., & Flicker, L. A. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0852 · Cited by 41
Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?
Rensing, K. L., Bloemendaal, F. M., Weijers, E. M., Richel, D. J., Buller, H. R., Koolwijk, P., van der Loos, C. M., Twickler, T. B., & von der Thüsen, J. H. (2010) · Diabetologia · doi:10.1007/s00125-010-1687-y · Cited by 40
Sex Differences in the Impact of Shift Work Schedules on Pathological Outcomes in an Animal Model of Ischemic Stroke
Earnest, D. J., Neuendorff, N., Coffman, J., Selvamani, A., & Sohrabji, F. (2016) · Endocrinology · doi:10.1210/en.2016-1130 · Cited by 40
Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens
Alehagen, U., Johansson, P., Aaseth, J., Alexander, J., & Brismar, K. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178614 · Cited by 40
Correlation of serum IGF‐I and IGFBP‐1 and ‐3 to cardiovascular risk indicators and early carotid atherosclerosis in healthy middle‐aged men
Boquist, S., Ruotolo, G., Skoglund-Andersson, C., Tang, R., Björkegren, J., Bond, M. G., Fairé, U. D., Brismar, K., & Hamsten, A. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02998.x · Cited by 40
Recombinant Human Insulin-Like Growth Factor I (IGF-I): Risks and Benefits of Normalizing Blood IGF-I Concentrations
CLARK, R. G. (2004) · Hormone Research in Paediatrics · doi:10.1159/000080766 · Cited by 40
DECLINE IN INSULIN-LIKE GROWTH FACTOR-I LEVELS ACROSS ADULT LIFE SPAN IN TWO LARGE POPULATION STUDIES
Maggio, M. G., Blè, A., Ceda, G. P., & Metter, E. J. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.2.182 · Cited by 39
“Recent studies suggest that, in older persons, lower IGF-I levels are associated with an increased risk of disability and all-cause (1) and cardiovascular mortality (2).”
Background
Total Serum Insulin-like Growth Factor-1 and C-Reactive Protein in Metabolic Syndrome With or Without Diabetes
Efstratiadis, G., Tsiaousis, G. Z., Athyros, V. G., Karagianni, D., Pavlitou, A., Giannakou-Darda, A., & Manes, C. (2006) · Angiology · doi:10.1177/000331970605700306 · Cited by 39
Associations of IGF1 and IGFBPs 1 and 3 with all-cause and cardiovascular mortality in older men: the Health In Men Study
Yeap, B. B., Chubb, S. A. P., McCaul, K. A., Ho, K. K. Y., Hankey, G. J., Norman, P. E., & Flicker, L. A. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0059 · Cited by 38
Figitumumab (CP-751,871) for cancer therapy
Gualberto, A. (2010) · Expert Opinion on Biological Therapy · doi:10.1517/14712591003689980 · Cited by 39
“Low IGF-I levels have been associated with increased cardiovascular events in long-term follow up studies, supporting a role of this factor as a vascular protector [14,15].”
Background
Leptin a new biological marker for evaluating malnutrition in elderly patients
Bouillanne, O., Golmard, J. L., Coussieu, C., Noël, M., Durand, D., Piette, F., & Nivet‐Antoine, V. (2006) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602572 · Cited by 38
Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake
Heald, A. H., Sharma, R., Anderson, S. G., Vyas, A., Siddals, K. W., Patel, J. V., Bhatnagar, D., Prabharkaran, D., Rudenski, A. S., Hughes, E. A., et al. (2005) · Public Health Nutrition · doi:10.1079/phn2005729 · Cited by 37
GH/IGF-I/insulin system in centenarians
Vitale, G., Barbieri, M., Kamenetskaya, M., & Paolisso, G. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.12.001 · Cited by 36
The IGF system in patients with type 2 diabetes: associations with markers of cardiovascular target organ damage
Hjortebjerg, R., Laugesen, E., Høyem, P., Oxvig, C., Stausbøl‐Grøn, B., Knudsen, S. T., Kim, W. Y., Poulsen, P. L., Hansen, T. K., Bjerre, M., et al. (2017) · European Journal of Endocrinology · doi:10.1530/eje-16-0940 · Cited by 36
Insulin-Like Growth Factor-I and Risk of Type 2 Diabetes and Coronary Heart Disease: Molecular Epidemiology
Sandhu, M. S. (2005) · KARGER eBooks · doi:10.1159/000085755 · Cited by 36
Turning anti-ageing genes against cancer
Longo, V. D., Lieber, M. R., & Vijg, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2526 · Cited by 36
“Conclusions and future perspectives A therapy aimed at reducing GH and IGF-I to prevent cancer is not straightforward because GH and/or IGF-I deficiencies are associated with dwarfism, increased obesity and heart diseas”
Background
Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]
Mehta, K., Gala, J., Bhasale, S., Naik, S., Modak, M., Thakur, H. P., Deo, N., & Miller, M. J. S. (2007) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-7-34 · Cited by 36
Metabolic and cardiovascular risk factors in subjects with impaired fasting glucose: the 100 versus 110 mg/dL threshold
Andreozzi, F., Succurro, E., Mancuso, M. R., Perticone, M., Sciacqua, A., Perticone, F., & Sesti, G. (2007) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.724 · Cited by 37
Markers of arterial health could serve as accurate non-invasive predictors of human biological and chronological age
Fedintsev, A., Kashtanova, D. A., Ткачева, О. Н., Strazhesko, I. D., Kudryavtseva, A. V., Baranova, A. V., & Moskalev, A. (2017) · Aging · doi:10.18632/aging.101227 · Cited by 34
“In our study, patients with more than five years of extra ageing implied by higher scores of Arterial Index also demonstrated significant elevation of CVD Prediction Scores [9] and lowered levels of serum IGF-1, the primary mediator of growth hormone (GH) effects, which is known to influence probability to develop maj…”
Result
Impact of Age-Adjusted Insulin-Like Growth Factor 1 on Major Cardiovascular Events After Acute Myocardial Infarction: Results From the Fast-MI Registry
Bourron, O., Bouc, Y. L., Berard, L., Kotti, S., Brunel, N., Ritz, B., Leclercq, F., Tabone, X., Drouet, É., Mulak, G., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3968 · Cited by 34
Rat models of caloric intake and activity: relationships to animal physiology and human health
Young, G. S., & Kirkland, J. B. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h06-082 · Cited by 35
“High levels of IGF-1 have been linked with the development of certain cancers, including breast, colon, and lung cancers, although low levels of IGF-1 have been linked with the development of cardiovascular disease and diabetes (Laughlin et al. 2004).”
Background
Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile
Giovannini, S., Cesari, M., Marzetti, E., Leeuwenburgh, C., Maggio, M. G., & Pahor, M. (2010) · The journal of nutrition health & aging · doi:10.1007/s12603-010-0036-7 · Cited by 34
“Previous studies have suggested that larger increases of total IGF-1 (19) and IGFBP-3 (20) compared to our results were associated to a significant reduction in the risk of adverse cardiovascular events.”
Result
Characterisation of receptors for IGF-I and insulin; evidence for hybrid insulin/IGF-I receptor in human coronary artery endothelial cells
Chisalita, S. I., Nitert, M. D., & Arnqvist, H. J. (2006) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2006.06.003 · Cited by 34
“We can only speculate about the clinical consequences of our observation, but dysregulation of the IGF system is associated with cardiovascular disease [12,46–52].”
Background
The Role of Osteokines in Sarcopenia: Therapeutic Directions and Application Prospects
Lu, W., Xiao, W., Xie, W., Fu, X., Pan, L., Jin, H., Yu, Y., Zhang, Y., & Li, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.735374 · Cited by 36
“, 2016), heart disease (Laughlin et al., 2004), non-alcoholic fatty liver disease (NAFLD) (Brea et al.”
Background
High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly
Kaplan, R. C., McGinn, A. P., Pollak, M., Kuller, L. H., Strickler, H. D., Rohan, T. E., Cappola, A. R., Xue, X. N., & Psaty, B. M. (2008) · American Heart Journal · doi:10.1016/j.ahj.2007.12.031 · Cited by 33
Positive association between plasma IGF1 and high-density lipoprotein cholesterol levels in adult nondiabetic subjects
Succurro, E., Arturi, F., Grembiale, A., Iorio, F., Laino, I., Andreozzi, F., Sciacqua, A., Hribal, M. L., Perticone, F., & Sesti, G. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0113 · Cited by 32
The role of IGF-1 resistance in obesity and type 2 diabetes-mellitus-related insulin resistance and vascular disease
Gatenby, V. K., & Kearney, M. T. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.528930 · Cited by 32
“The Rancho Bernardo Study showed that in older adults every 40 ng/ml decrement in IGF-1 was associated with an increase of 38% in the risk of coronary artery disease mortality [54].”
Background
IGF-I and Longevity
Janssen, J. A. M. J. L., & Lamberts, S. W. J. (2004) · Hormone Research in Paediatrics · doi:10.1159/000080508 · Cited by 32
Insulin-Like Growth Factors and Leukocyte Telomere Length: The Cardiovascular Health Study
Kaplan, R. C., Fitzpatrick, A. L., Pollak, M., Gardner, J. P., Jenny, N. S., McGinn, A. P., Kuller, L. H., Strickler, H. D., Kimura, M., Psaty, B. M., et al. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp036 · Cited by 31
Novel biomolecules of ageing, sex differences and potential underlying mechanisms of telomere shortening in coronary artery disease
Opstad, T. B., Kalstad, A. A., Pettersen, A. R., Arnesen, H., & Seljeflot, I. (2019) · Experimental Gerontology · doi:10.1016/j.exger.2019.01.020 · Cited by 32
“higher in subjects affected by age-related diseases or obesity than in healthy and lean subjects, however, low circulating IGF1 levels have also been associated with increased all-cause mortality in several population studies [14].”
Background
Sex-steroid control of the aging somatotropic axis
Veldhuis, J. D., Erickson, D., Iranmanesh, A., Miles, J. M., & Bowers, C. Y. (2005) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2005.07.006 · Cited by 30
Incremental Effects of Endocrine and Metabolic Biomarkers and Abdominal Obesity on Cardiovascular Mortality Prediction
Schneider, H. J., Wallaschofski, H., Völzke, H., Markus, M. R. P., Dörr, M., Felix, S. B., Nauck, M. A., & Friedrich, N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033084 · Cited by 30
“. Low levels of insulin-like growth factor-1 (IGF-1), a metabolic and anabolic hormone as well as a mediator of growth hormone action, have been associated with increased cardiovascular mortality in some studies”
Background
PAPP-A and the IGF system in atherosclerosis: what’s up, what’s down?
Steffensen, L. B., Conover, C. A., & Oxvig, C. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00395.2019 · Cited by 30
Telomere Dynamics and Telomerase in the Biology of Hair Follicles and their Stem Cells as a Model for Aging Research
Stone, R. C., Aviv, A., & Paus, R. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.12.006 · Cited by 30
Chapter 3 Diseases Associated with Growth Hormone‐Releasing Hormone Receptor (GHRHR) Mutations
Martari, M., & Salvatori, R. (2009) · Progress in molecular biology and translational science · doi:10.1016/s1877-1173(09)88003-4 · Cited by 30
Effects of hormone replacement therapy on insulin-like growth factor (IGF)-I, IGF-II and IGF binding protein (IGFBP)-1 to IGFBP-4: Implications for cardiovascular risk
Heald, A. H., Kaushal, K., Anderson, S. G., Redpath, M., Durrington, P. N., Selby, P. L., & Gibson, M. (2005) · Gynecological Endocrinology · doi:10.1080/09513590400027406 · Cited by 30
“In the Rancho Bernado Study, low baseline levels of IGF-I and IGFBP-1 were associated with an increased risk of fatal IHD among elderly men and women, independent of prevalent IHD risk factors [19].”
BackgroundResult
Association of Biomarker and Physiologic Indices With Mortality in Older Adults: Cardiovascular Health Study
Sanders, J. L., Arnold, A. M., Boudreau, R. M., Hirsch, C. H., Kizer, J. R., Kaplan, R. C., Cappola, A. R., Cushman, M., Jacob, M. E., Kritchevsky, S. B., et al. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly075 · Cited by 29
Relationship Between Serum IGF-1 and BMI Differs by Age
Sherlala, R. A., Kammerer, C. M., Kuipers, A. L., Wojczynski, M. K., Ukraintseva, S. V., Feitosa, M. F., Mengel‐From, J., Zmuda, J. M., & Minster, R. L. (2020) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaa282 · Cited by 29
“In contrast, studies that reported a positive relationship were often performed with older individuals with ages ranging from 45 to 90 years (21).”
BackgroundResult
Expression and function of receptors for insulin-like growth factor-I and insulin in human coronary artery smooth muscle cells
Chisalita, S. I., & Arnqvist, H. J. (2005) · Diabetologia · doi:10.1007/s00125-005-1890-4 · Cited by 29
“deficiency [48, 49] and normal ageing [50].”
Comparative Endocrinology of Aging and Longevity Regulation
Allard, J. B., & Duan, C. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00075 · Cited by 30
“The underlying cause of most CVD is atherosclerosis, a disease of the arteries in which complex lipid-containing inflammatory lesions called atheromatous plaques form beneath the endothelial cell lining.”
BackgroundResultInfluential
IGF‐I concentrations are positively associated with carotid artery atherosclerosis in women
Hietaniemi, M., Pöykkö, S. M., Ukkola, O. H., Päivänsalo, M. J., & Kesäniemi, Y. A. (2005) · Annals of Medicine · doi:10.1080/07853890510011967 · Cited by 29
“Low IGF-I levels have been associated with an increased incidence of ischaemic heart disease (IHD) (5) and IHD mortality (6), but IGF-I levels have also been shown to correlate positively with coronary artery disease progression”
Background
Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments
Gulej, R., Patai, R., Ungvari, A., Kállai, A., Tarantini, S., Yabluchanskiy, A., Huffman, D. M., Conboy, M. J., Conboy, I. M., Mika Kivimaki, B., et al. (2025) · GeroScience · doi:10.1007/s11357-025-01657-y · Cited by 29
Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population: impact of ACE inhibitors
Chisalita, S. I., Dahlström, U., Arnqvist, H. J., & Alehagen, U. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0584 · Cited by 28
The concept of multiple hormonal dysregulation.
Maggio, M., Cattabiani, C., Lauretani, F., Ferrucci, L., Luci, M., Valenti, G., & Ceda, G. P. (2010) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · Cited by 28
Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases
Strazhesko, I. D., Ткачева, О. Н., Akasheva, D. U., Dudinskaya, Е. N., Владимировна, П. Е., Pykhtina, V. S., Сергеевна, К. А., Brailova, N. V., Шарашкина, Н. В., Kashtanova, D. A., et al. (2017) · Frontiers in Genetics · doi:10.3389/fgene.2017.00198 · Cited by 27
“Our studies are consistent with others indicating that patients with GH deficiency and low circulating IGF-1 had an increased risk of CVD (Vasan et al., 2003; Conti et al., 2004; Laughlin et al., 2004).”
BackgroundResult
Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis
Erlandsson, M. C., Lyngfelt, L., Åberg, N. D., Wasén, C., Espino, R. A., Silfverswärd, S. T., Nadali, M., Jood, K., Andersson, K., Pullerits, R., et al. (2019) · BMC Medicine · doi:10.1186/s12916-019-1374-x · Cited by 27
Associations of IGF1 and its binding proteins with abdominal aortic aneurysm and aortic diameter in older men
Yeap, B. B., Chubb, S. A. P., McCaul, K. A., Flicker, L. A., Ho, K. K. Y., Golledge, J., Hankey, G. J., & Norman, P. E. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0725 · Cited by 27
Obesity and endometrial cancer: biological mechanisms, nutritional strategies, and clinical perspectives
Simancas‐Racines, D., Campuzano-Donoso, M., Román-Galeano, N. M., Zambrano-Villacres, R., Memoli, P., Verde, L., Reytor-González, C., & Carbone, L. (2025) · Food and Agricultural Immunology · doi:10.1080/09540105.2025.2510961 · Cited by 29
“Long-term CR has been shown to lower serum IGF-1 levels by approximately 30–40% in rodent models, playing a key role in cancer protection and aging deceleration (Laughlin et al., 2004; Sonntag et al., 1999).”
Insulin-like growth factor I: a predictor of long-term glucose abnormalities in patients with acute myocardial infarction
Wallander, M., Brismar, K., Öhrvik, J., Rydén, L., & Norhammar, A. (2006) · Diabetologia · doi:10.1007/s00125-006-0386-1 · Cited by 26
“Furthermore, clinical studies have shown that low levels of IGF-I and IGF binding proteins 1 and 3 (IGFBP-1 and IGFBP-3) are related to AMI or angiographically assessed coronary heart disease [7–10].”
Background
The association of insulin-like-growth factor 1 (IGF-1) with incident coronary heart disease in women: Findings from the prospective British Women's Heart and Health Study
Lawlor, D. A., Ebrahim, S. B. J., Smith, G. D., Cherry, L., Watt, P., & Sattar, N. A. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.12.061 · Cited by 26
Insulin-like growth factor-1 in plasma and brain: regulation in health and disease
Sievers, C. (2007) · Frontiers in bioscience · doi:10.2741/2662 · Cited by 26
Getting old through the blood: circulating molecules in aging and senescence of cardiovascular regenerative cells
Angelini, F., Pagano, F., Bordin, A., Picchio, V., De Falco, E., & Chimenti, I. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00062 · Cited by 25
“Several population studies have correlated an increased risk for all-cause mortality (including cardiovascular) to the presence of low circulating IGF-1 levels (47, 48).”
Background
Adiponectin, body mass index and hepatic steatosis are independently associated with IGF-I status in obese non-diabetic women
Sîrbu, A. M., Gologan, S., Arbănaş, T., Copăescu, C., Martin, S. C., Albu, A. I., Barbu, C. G., Pîrvulescu, I., & Fica, S. V. (2012) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2012.10.001 · Cited by 25
“Furthermore, in Rancho Bernardo Study, low IGF-I concentrations have been shown to predict cardiovascular mortality [6].”
Background
A polymorphism at IGF1 locus is associated with carotid intima media thickness and endothelium-dependent vasodilatation
Sesti, G., Mannino, G. C., Andreozzi, F., Greco, A., Perticone, M., Sciacqua, A., Marini, M. A., & Perticone, F. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.10.024 · Cited by 25
Social Differences in Insulin-like Growth Factor-1: Findings from a British Birth Cohort
Meena Kumari, B., Tabassum, F., Clark, C., Strachan, D. P., Stansfeld, S. A., & Power, C. (2008) · Annals of Epidemiology · doi:10.1016/j.annepidem.2008.03.001 · Cited by 25
The molecular mechanisms of skeletal muscle wasting: Implications for therapy
Skipworth, R. J. E., Stewart, G. D., Ross, J. A., Guttridge, D. C., & Fearon, K. C. H. (2006) · The Surgeon · doi:10.1016/s1479-666x(06)80004-1 · Cited by 25
The relation between adiposity throughout the life course and variation in IGFs and IGFBPs: evidence from the ProtecT (Prostate testing for cancer and Treatment) study
Rowlands, M., Holly, J. M. P., Gunnell, D., Gilbert, R., Donovan, J., Lane, J. A., Marsden, G. L., Collin, S. M., Hamdy, F. C., Neal, D. E., et al. (2010) · Cancer Causes & Control · doi:10.1007/s10552-010-9610-x · Cited by 25
“There are reports of inverse [22, 23, 40, 45–47], positive [48] and null [19, 21, 24, 25, 35, 49–53] associations for IGF-I; inverse [23], positive [19], and null [24, 25, 46] associations for IGF-II; and inverse [48] positive [19, 53], and null [22–25, 35, 49, 54] associations for IGFBP-3.”
Telomeres and endocrine dysfunction of the adrenal and GH / IGF ‐1 axes
Aulinas, A., Barahona, M. J., Barahona, M. J., Mato, E., Bell, O. L., Surrallés, J., & Webb, S. M. (2013) · Clinical Endocrinology · doi:10.1111/cen.12310 · Cited by 26
Association between Serum Insulin-Like Growth Factor (IGF) I and IGF Binding Protein-3 and Lung Function
Gläser, S., Friedrich, N., Ewert, R., Schäper, C., Nauck, M. A., Dörr, M., Völzke, H., Felix, S. B., Krebs, A., Wallaschofski, H., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2662 · Cited by 25
Insulin-Like Growth Factor I and the Pathogenesis of Delirium: A Review of Current Evidence
Adamis, D., & Meagher, D. J. (2011) · Journal of Aging Research · doi:10.4061/2011/951403 · Cited by 25
“In contrast, two more studies reported no relationship between IGF-I levels and all-cause mortality [66, 67].”
Trajectories of IGF-I Predict Mortality in Older Adults: The Cardiovascular Health Study
Sanders, J. L., Guo, W., O’Meara, E. S., Kaplan, R. C., Pollak, M., Bartz, T. M., Newman, A. B., Fried, L. P., & Cappola, A. R. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx143 · Cited by 25
Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins
González-Guerra, J. L., Castilla‐Cortázar, I., Aguirre, G. A., Muñoz, Ú., Martín‐Estal, I., Ávila-Gallego, E., Granado, M., Puche, J. E., & Garcı́a-Villalón, Á. L. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181760 · Cited by 25
Insulin-Like Growth Factor 1 in the Cardiovascular System
Aguirre, G. A., González-Guerra, J. L., Espinosa, L., & Castilla‐Cortázar, I. (2018) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2017_8 · Cited by 25
Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study
Kaplan, R. C., Bùžková, P., Cappola, A. R., Strickler, H. D., McGinn, A. P., Mercer, L. D., Arnold, A. M., Pollak, M. N., & Newman, A. B. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2967 · Cited by 24
Increased insulin-like growth factor-1 in relation to cardiovascular function in polycystic ovary syndrome: friend or foe?
Desai, N. A., & Patel, S. S. (2015) · Gynecological Endocrinology · doi:10.3109/09513590.2015.1075497 · Cited by 23
“The Rancho Bernardo Study showed prospective relation of serum insulin-like growth factor-1 levels with all cause and cardiovascular disease mortality [15].”
Background
The relationship between insulin-like growth factor-1 and metabolic syndrome, independent of adiponectin
Oh, J., Kim, J., Park, S., Youn, J., Son, N., Shin, D.-J., Lee, S., Kang, S., Jee, S. H., & Jang, Y. (2011) · Clinica Chimica Acta · doi:10.1016/j.cca.2011.11.015 · Cited by 24
“Several large cohort studies reported that there is an inverse correlation between IGF-1 level and mortality, especially cardiovascular mortality [13,14].”
Background
Macrophage-Specific IGF-1 Overexpression Reduces CXCL12 Chemokine Levels and Suppresses Atherosclerotic Burden in Apoe-Deficient Mice
Snarski, P., Sukhanov, S., Yoshida, T., Higashi, Y., Danchuk, S., Chandrasekar, B., Tian, D., Rivera-Lopez, V., & Delafontaine, P. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.121.316090 · Cited by 22
Low IGF-1 levels are associated with cardiovascular risk factors in haemodialysis patients
Abdulle, A. M., Gillett, M. P. T., Abouchacra, S., Sabri, S. M., Rukhaimi, M. A., Obineche, E. N., & Singh, J. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9441-6 · Cited by 23
Plasma Insulinlike Growth Factor 1 and Binding-Protein 3 and Risk of Myocardial Infarction in Women: A Prospective Study
Page, J. H., Ma, J., Pollak, M., Manson, J. E., & Hankinson, S. E. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2008.105825 · Cited by 23
“tionship of IGF1 concentrations with ischemic heart disease mortality ( 23 ).”
Relation of insulin-like growth factor (IGF) I and IGF-binding protein 3 concentrations with intakes of fruit, vegetables, and antioxidants
Tran, C. D., Diorio, C., Bérubé, S., Pollak, M., & Brisson, J. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.6.1518 · Cited by 23
“For instance, prospective epidemiologic studies showed that higher IGF-I concentrations, lower IGF-binding protein 3 (IGFBP-3) concentrations, or both were associated with a reduced risk of ischemic heart disease (13), heart failure (14), and of ischemic heart disease mortality (15).”
Background
Evidence for distinct effects of GH and IGF‐I in the metabolic syndrome
Maison, P., Balkau, B., Souberbielle, J., Cunin, P., Vol, S., Macquin‐Mavier, I., Eschwège, É., & the D. E. S. I. R. Study Group (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02195.x · Cited by 23
Association of serum IGF1 with endothelial function: results from the population-based study of health in Pomerania
Empen, K., Lorbeer, R., Völzke, H., Robinson, D. M., Friedrich, N., Krebs, A., Nauck, M. A., Reffelmann, T., Ewert, R., Felix, S. B., et al. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0563 · Cited by 22
IGF-I and IGFBP2 in peripheral artery disease: results of a prospective study
Urbonavičienė, G., Frystyk, J., Urbonavičius, S., & Lindholt, J. S. (2014) · Scandinavian Cardiovascular Journal · doi:10.3109/14017431.2014.891760 · Cited by 21
“Previous studies identifi ed association between lower IGF-1 and increased risk for CVD mortality among elderly men and women, but no association was found with all-cause mortality (7).”
BackgroundResult
Hepatocytes respond differently to major dietary trans fatty acid isomers, elaidic acid and trans-vaccenic acid
Krogager, T. P., Nielsen, L. V., Kahveci, D., Dyrlund, T. F., Scavenius, C., Sanggaard, K. W., & Enghild, J. J. (2015) · Proteome Science · doi:10.1186/s12953-015-0084-3 · Cited by 21

Authors: Laughlin, G. A., Barrett-Connor, E., Criqui, M. H., & Kritz-Silverstein, D.
Affiliations: University of California San Diego (US)
Corresponding author: Barrett-Connor, Elizabeth
ORCID: Barrett-Connor, Elizabeth
Criqui, Michael H.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2004-01
Volume: 89
Issue: 1
Pages: 114-120
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2003-030967
OpenAlex: W2115525455
Cited by: 374
References: 40
Citations by year: 2026: 7 · 2025: 9 · 2024: 9 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 13 · 2019: 17 · 2018: 8 · 2017: 19 · 2016: 13 · 2015: 10 · 2014: 13 · 2013: 12 · 2012: 26
FWCI: 15.14
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG07181)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK031801, DK-31801)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: insulin-like growth factor I, IGF-binding protein-1, cardiovascular mortality, ischemic heart disease mortality, all-cause mortality, older adults, postmenopausal women, IGF system, cardiovascular risk markers
MeSH terms: Age Factors, Aged, Blood Pressure, Cardiovascular Diseases, Cholesterol, Female, Humans, Insulin-Like Growth Factor I, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Pregnancy Proteins, Prospective Studies, Risk Factors, Sex Factors, Triglycerides, Body Mass Index, Myocardial Ischemia, Insulin-Like Growth Factor Binding Proteins, Insulin-Like Growth Factor Binding Protein 1

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The Prospective Association of Serum Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-1 Levels with All Cause and Cardiovascular Disease Mortality in Older Adults: The Rancho Bernardo Study

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