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

doi:10.1210/jc.2003-030967

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

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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Observational studies have reported inconsistent associations between IGF-1 and mortality.
“a series of observational studies have reported inconsistent associations (37-41)”
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“…diseases (Rosen and Bengtsson, 1990; Bates et al., 1996; Spallarossa et al., 1996; Bulow et al., 1997; Tomlinson et al., 2001; Juul et al., 2002; Roubenoff et al., 2003; van den Beld et al., 2003; Vasan et al., 2003; Conti et al., 2004; Laughlin et al., 2004; Ungvari and Csiszar, 2012).”
Insulin-Like Growth Factor-1 (IGF-1) and Its Monitoring in Medical Diagnostic and in Sports
Bailes, J., & Soloviev, M. (2021) · Biomolecules · doi:10.3390/biom11020217 · Cited by 134 · see citing works
Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?
Giannoulis, M. G., Martin, F. C., Nair, K. S., Umpleby, A. M., & Sonksen, P. (2012) · Endocrine Reviews · doi:10.1210/er.2012-1002 · Cited by 132 · see citing works
Insulin-Like Growth Factor I as a Biomarker of Health, Fitness, and Training Status
Nindl, B. C., & Pierce, J. R. (2009) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181b07c4d · Cited by 131 · see citing works
The Neurotoxic Effects of Estrogen on Ischemic Stroke in Older Female Rats Is Associated with Age-Dependent Loss of Insulin-Like Growth Factor-1
Selvamani, A., & Sohrabji, F. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0761-10.2010 · Cited by 130 · see citing works
“Low normal levels of IGF-1 are associated with increased morbidity and mortality in ischemic heart disease and stroke (Schwab et al., 1997; Laughlin et al., 2004; Johnsen et al., 2005).”
Background
IGF-1, oxidative stress and atheroprotection
Higashi, Y., Sukhanov, S., Anwar, A., Shai, S., & Delafontaine, P. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.12.005 · Cited by 128 · see citing works
“Others [45,114–122] found that low IGF-1 is a predictor of ischemic heart disease and ischemic heart disease mortality consistent with the potential anti-apoptotic, antioxidant and plaque stabilization actions of IGF-1.”
Background
IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population
Andreassen, M., Raymond, I. E., Kistorp, C., Hildebrandt, P. R., Faber, J. O., & Kristensen, L. Ø. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0452 · Cited by 124 · see citing works
“The authors concluded that the side effects outweigh beneficial effects mainly due to soft tissue oedema, arthralgias and insulin resistance (28) .B y contrast to our results, two previous published studies in American background populations have not found any influence of IGF1 levels on all cause mortality ( 8 , 29)…”
Result
Insulin-Like Growth Factor-1 Receptor Deficiency in Macrophages Accelerates Atherosclerosis and Induces an Unstable Plaque Phenotype in Apolipoprotein E–Deficient Mice
Higashi, Y., Sukhanov, S., Shai, S., Danchuk, S. D., Tang, R., Snarski, P., Li, Z., Lobelle‐Rich, P., Wang, M., Wang, D. D., et al. (2016) · Circulation · doi:10.1161/circulationaha.116.021805 · Cited by 122 · see citing works
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, R. C., McGinn, A. P., Pollak, M., Kuller, L. H., Strickler, H. D., Rohan, T. E., Cappola, A. R., Xue, X., & Psaty, B. M. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1631 · Cited by 121 · see citing works
“Moreover, some previous studies have had small sample sizes and have oftenidentifiedCVDeventsthroughdatabaseswithoutmedicalrecordreview( 12 ).Becauseoftheincreasingoff-labeluse of GH for the prevention of age-related conditions, it is critical to have an accurate assessment of the association betweenlowcirculatingIGF-…”
BackgroundInfluential
Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease
Ichikawa, T., Nakao, K., Hamasaki, K., FURUKAWA, R., Tsuruta, S., Ueda, Y., Taura, N., Shibata, H., Fujimoto, M., Toriyama, K., et al. (2007) · Hepatology International · doi:10.1007/s12072-007-9007-4 · Cited by 120 · see citing works
Mortality and Serum Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein 3 Concentrations
Friedrich, N., Haring, R., Nauck, M. A., Lüdemann, J., Rosskopf, D., Spilcke-Liss, E., Felix, S. B., Dörr, M., Brabant, G. E., Völzke, H., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2138 · Cited by 116 · see citing works
“The Rancho Bernardo Study, which followed up 1185 subjects (633 men) aged 51–98 yr for 9–13 yr, found that a 40-ng/ml decrease in IGF-I level caused a significant increase of 38% in risk of IHD mortality but not all-cause and non-IHD CVD mortality risk (13).”
BackgroundMethod
PCOS and Depression: Common Links and Potential Targets
Kolhe, J. V., Chhipa, A. S., Butani, S., Chavda, V. K., & Patel, S. S. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00765-2 · Cited by 108 · see citing works
Predictive Value of Circulating Insulin-Like Growth Factor I Levels in Ischemic Stroke Outcome
Bondanelli, M., Ambrosio, M. R., Onofri, A., Bergonzoni, A., Lavezzi, S., Zatelli, M. C., Valle, D., Basaglia, N., & Uberti, E. C. D. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1040 · Cited by 108 · see citing works
“IGF-I concentrations in the low normal range have been reported to be associated with increased risk of carotid atherosclerosis (36), ischemic heart disease (6), and stroke (8, 9).”
Background
The insulin-like growth factor I system: Physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome
Ren, J. T., & Anversa, P. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.12.006 · Cited by 100 · see citing works
Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects
Colao, A., Somma, C. D., Cascella, T., Pivonello, R., Vitale, G., Grasso, L. F. S., Lombardi, G., & Savastano, S. (2008) · European Journal of Endocrinology · doi:10.1530/eje-08-0201 · Cited by 101 · see citing works
Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men
LEWITT, M. S., Hilding, A., Östenson, C., Efendić, S., Brismar, K., & Hall, K. E. (2008) · Diabetologia · doi:10.1007/s00125-008-1016-x · Cited by 98 · see citing works
“Low IGF-I is also associated with cardiovascular risk factors [45, 47], independently of low IGFBP-1 [12, 15].”
Background
Age-dependent impairment of number and angiogenic potential of adipose tissue-derived progenitor cells
Madonna, R., Renna, F. V., Cellini, C., Cotellese, R., Picardi, N., Francomano, F., Innocenti, P., & Caterina, R. D. (2010) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2010.02384.x · Cited by 97 · see citing works
Heart Failure as a Multiple Hormonal Deficiency Syndrome
Saccà, L. (2009) · Circulation Heart Failure · doi:10.1161/circheartfailure.108.821892 · Cited by 94 · see citing works
The Association of Serum Insulin-Like Growth Factor-I with Mortality, Cardiovascular Disease, and Cancer in the Elderly: A Population-Based Study
van Bunderen, C. C., van Nieuwpoort, I. C., van Schoor, N. M., Deeg, D. J. H., Lips, P. T. A. M., & Drent, M. L. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0940 · Cited by 95 · see citing works
“and Nutrition Examination Survey and Rancho Bernardo Study) did not find a significant association between serum IGF-1 level and all-cause mortality.(26;27) A possible explanation might be the difference”
Background
The role of IGF‐I and its binding proteins in the development of type 2 diabetes and cardiovascular disease
Ezzat, V., Duncan, E. R., Wheatcroft, S. B., & Kearney, M. T. (2007) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2007.00709.x · Cited by 91 · see citing works
The heart: an end-organ of GH action
Colao, A., Vitale, G., Pivonello, R., Ciccarelli, A., Somma, C. D., & Lombardi, G. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.151s093 · Cited by 91 · see citing works
Circulating Insulin-Like Growth Factor-1 and Its Binding Protein-3
Lam, C. S. P., Chen, M., Lacey, S. M., Yang, Q., SULLIVAN, L. M., Xanthakis, V., Safa, R., Smith, H., Peng, X., Sawyer, D. B., et al. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.203943 · Cited by 89 · see citing works
New insights on the cardiovascular effects of IGF-1
Mačvanin, M., Gluvic, Z. M., Radovanović, J., Essack, M., Gao, X., & Isenović, E. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1142644 · Cited by 91 · see citing works
“Accordingly, the risk of developing acute coronary syndrome has also been linked to low IGF1 levels (53, 133, 134).”
Background
Lack of Evidence of Premature Atherosclerosis in Untreated Severe Isolated Growth Hormone (GH) Deficiency due to a GH-Releasing Hormone Receptor Mutation
Oliveira, J. L. M., Marques-Santos, C., Barreto‐Filho, J. A., Ximenes, R., Britto, A. V. D. O., Souza, A. H. O., Prado, C. M., Oliveira, C. R. P., Pereira, R. M. C., Vicente, T. A. R., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2571 · Cited by 88 · see citing works
“Epidemiological studies have suggested that reduced levels of IGF-I are associated with increased risk of cardiovascular mortality and ischemic heart disease in the general population (15, 16).”
Association between hepatic steatosis and serum IGF1 and IGFBP-3 levels in a population-based sample
Völzke, H., Nauck, M. A., Rettig, R., Dörr, M., Higham, C. E., Brabant, G. E., & Wallaschofski, H. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0374 · Cited by 84 · see citing works
Adult height in relation to mortality from 14 cancer sites in men in London (UK): evidence from the original Whitehall study
Batty, G. D., Shipley, M. J., Langenberg, C., Marmot, M. G., & Smith, G. D. (2005) · Annals of Oncology · doi:10.1093/annonc/mdj018 · Cited by 83 · see citing works
“IGF levels [56] and height [5, 12] are also inversely related to coronary heart disease in some studies.”
Background
Beginning to end: Cardiovascular implications of growth hormone (GH) deficiency and GH therapy
Colao, A., Somma, C. D., Savanelli, M. C., Leo, M. D., & Lombardi, G. (2006) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2006.03.006 · Cited by 82 · see citing works
IGF-binding protein 1 and abdominal obesity in the development of type 2 diabetes in women
LEWITT, M. S., Hilding, A., Brismar, K., Efendić, S., Östenson, C., & Hall, K. E. (2010) · European Journal of Endocrinology · doi:10.1530/eje-10-0301 · Cited by 82 · see citing works
Age at puberty and adult blood pressure and body size in a British birth cohort study
Hardy, R., Kuh, D. J., Whincup, P. H., & Wadsworth, M. E. J. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000198033.14848.93 · Cited by 81 · see citing works
Associations of insulin‐like growth factors, insulin‐like growth factor binding proteins and acid‐labile subunit with coronary heart disease
Fischer, F., Schulte, H., Mohan, S., Tataru, M., Köhler, E., Assmann, G., & von Eckardstein, A. (2004) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2004.02136.x · Cited by 80 · see citing works
“It has to be emphasized that two recent prospective population studies made the opposite observation on IGF-I, namely low rather than high IGF-I levels were associated with an increased risk of myocardial infarction (Juul et al., 2002; Laughlin et al., 2004).”
BackgroundResultInfluential
Opposite associations of age-dependent insulin-like growth factor-I standard deviation scores with nutritional state in normal weight and obese subjects
Schneider, H. J., Saller, B., Klotsche, J., März, W., Erwa, W., Wïttchen, H., & Stalla, G. K. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02131 · Cited by 78 · see citing works
Genes, ageing and longevity in humans: Problems, advantages and perspectives
Salvioli, S., Olivieri, F., Marchegiani, F., Cardelli, M., Santoro, A., Bellavista, E., Mishto, M., Invidia, L., Capri, M., Valensin, S., et al. (2006) · Free Radical Research · doi:10.1080/10715760600917136 · Cited by 77 · see citing works
The Role of Insulin-Like Growth Factor (IGF) Binding Protein-2 in the Insulin-Mediated Decrease in IGF-I Bioactivity
Arafat, A. M., Weickert, M. O., Frystyk, J., Spranger, J., Schöfl, C., Möhlig, M., & Pfeiffer, A. F. H. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0875 · Cited by 77 · see citing works
Normal levels of serum IGF-I: determinants and validity of current reference ranges
Brabant, G. E., & Wallaschofski, H. (2007) · Pituitary · doi:10.1007/s11102-007-0035-9 · Cited by 76 · see citing works
“Lower IGF-I levels were associated with an increased risk of cardiovascular disease such as congestive heart failure, ischemic heart disease, and an increased cardiovascular mortality [34, 35].”
Background
Apoptosis and the cardiac action of insulin-like growth factor I.
Suleiman, M., Singh, R., & Stewart, C. (2007) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2007.03.001 · Cited by 82 · see citing works
Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome?
Ruan, W., & Lai, M. (2010) · Acta Diabetologica · doi:10.1007/s00592-009-0142-3 · Cited by 96 · see citing works
Serum Insulin‐Like Growth Factor‐1 Binding Proteins 1 and 2 and Mortality in Older Adults: The Health, Aging, and Body Composition Study
Hu, D., Pawlikowska, L., Kanaya, A. M., Hsueh, W., Colbert, L. H., Newman, A. B., Satterfield, S., Rosen, C. J., Cummings, S. R., Harris, T. B., et al. (2009) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02318.x · Cited by 74 · see citing works
Association between Serum Interleukin-6 Concentrations and Mortality in Older Adults: The Rancho Bernardo Study
Lee, J. K., Bettencourt, R., Brenner, D. A., Le, T., Barrett-Connor, E. L., & Loomba, R. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034218 · Cited by 74 · see citing works
“. Lastly, we performed all models examining the association between serum IL-6 and CVD, cancer, and liver-related mortality by excluding participants with prevalent CVD, cancer, or liver disease at baseline. Information on prevalent CVD (including angina, myocardial infarction, cardiac revascularization, stroke or tra…”
MethodSelf-citation
Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: Results of the Study of Health in Pomerania (SHIP)
Friedrich, N., Alte, D., Völzke, H., Spilcke-Liss, E., Lüdemann, J., Lerch, M. M., Kohlmann, T., Nauck, M. A., & Wallaschofski, H. (2007) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2007.09.005 · Cited by 74 · see citing works
“During the last decade, several studies investigated the potential role of IGF-1 in different diseases, including cardiovascular disease [7– 9], cancer [10], or osteoporosis [11].”
Background
Probiotics: Protecting Our Health from the Gut
Varela-Trinidad, G. U., Domínguez-Díaz, C., Solórzano-Castanedo, K., Íñiguez-Gutiérrez, L., Hernández-Flores, T. D. J., & Fafutis‐Morris, M. (2022) · Microorganisms · doi:10.3390/microorganisms10071428 · Cited by 77 · see citing works
“Through the gut microbiota and heart communication axis, ID may trigger or exacerbate heart diseases, such as hypertension, atherosclerosis, CAD, and even heart failure.”
BackgroundInfluential
Insulin-like growth factors and subsequent risk of mortality in the United States
Saydah, S., Graubard, B., Ballard-Barbash, R., & Berrigan, D. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm124 · Cited by 71 · see citing works
“In contrast to our study, a prospective study from the Rancho Bernardo cohort (22) found that lower levels of IGF-I were associated with an increased risk of cardiovascular disease mortality.”
BackgroundResult
Association of diet with serum insulin-like growth factor I in middle-aged and elderly men
Larsson, S. C., Wolk, K., Brismar, K., & Wolk, A. (2005) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.5.1163 · Cited by 84 · see citing works
GH and ageing: Pitfalls and new insights
Bartke, A., & Darcy, J. (2017) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2017.02.005 · Cited by 70 · see citing works
Growth Hormone and IGF-1 Deficiency Exacerbate High-Fat Diet-Induced Endothelial Impairment in Obese Lewis Dwarf Rats: Implications for Vascular Aging
Bailey‐Downs, L. C., Sosnowska, D., Tóth, P., Mitschelen, M. C., Gautam, T., Henthorn, J., Ballabh, P., Koller, Á., Farley, J. A., Sonntag, W. E., et al. (2011) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr197 · Cited by 69 · see citing works
Insulin-like growth factor-1 signaling in cardiac aging
Lee, W. S., & Kim, J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.08.029 · Cited by 68 · see citing works
“This result was supported by another prospective study of 1185 adults who were followed up for over a decade, showing that circulating IGF-1 levels are a predictor of fatal ischemic heart disease [129].”
Result
Control of aging and longevity by IGF-I signaling
Yang, J., Anzo, M., & Cohen, P. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.08.001 · Cited by 66 · see citing works
Congenital Growth Hormone (GH) Deficiency and Atherosclerosis: Effects of GH Replacement in GH-Naive Adults
Oliveira, J. L. M., Aguiar-Oliveira, M. H., D’Oliveira, A., Pereira, R. M. C., Oliveira, C. R. P., Farias, C. T., Barreto‐Filho, J. A., Anjos-Andrade, F. D., Marques-Santos, C., Nascimento-Junior, A. C., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1636 · Cited by 67 · see citing works
Effects of gastric bypass on the GH/IGF-I axis in severe obesity – and a comparison with GH deficiency
Engström, B. E., Burman, P., Holdstock, C., Öhrvall, M., Sundbom, M., & Karlsson, F. A. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.02069 · Cited by 67 · see citing works
A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3
Kaplan, R. C., Petersen, A.-K., Chen, M., Teumer, A., Glazer, N. L., Döring, A., Lam, C. S. P., Friedrich, N., Newman, A. B., Müller‐Nurasyid, M., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddq560 · Cited by 67 · see citing works
Circulating insulin-like growth factor-I levels are correlated with the atherosclerotic profile in healthy subjects independently of age
Colao, A., Spiezia, S., Somma, C. D., Pivonello, R., Marzullo, P., Rota, F., Musella, T., Auriemma, R. S., Martino, M. C. D., & Lombardi, G. (2005) · Journal of Endocrinological Investigation · doi:10.1007/bf03347225 · Cited by 67 · see citing works
Insulin-like Growth Factor-1 and IGF Binding Proteins Predict All-Cause Mortality and Morbidity in Older Adults
Zhang, W. B., Aleksić, S., Gao, T., Weiss, E. F., Demetriou, E., Verghese, J., Holtzer, R., Barzilai, N., & Milman, S. (2020) · Cells · doi:10.3390/cells9061368 · Cited by 63 · see citing works
“This was particularly relevant for the interpretation of IGFBP-1 levels, which normally fluctuate in relation to prandial status; yet, not all prior studies have been able to establish these conditions [39].”
BackgroundResult
IGF-I/IGFBP-3 ratio: a mechanistic insight into the metabolic syndrome
Sierra‐Johnson, J., Romero‐Corral, A., Somers, V. K., López-Jiménez, F. A., Mälarstig, A., Brismar, K., Hamsten, A., Fisher, R. M., & Hellénius, M.-L. (2008) · Clinical Science · doi:10.1042/cs20080382 · Cited by 63 · see citing works
Short-Term Effects of Growth Hormone (GH) Treatment or Deprivation on Cardiovascular Risk Parameters and Intima-Media Thickness at Carotid Arteries in Patients with Severe GH Deficiency
Colao, A., Somma, C. D., Rota, F., Pivonello, R., Savanelli, M. C., Spiezia, S., & Lombardi, G. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2247 · Cited by 62 · see citing works
Growth Hormone Treatment on Atherosclerosis: Results of a 5-Year Open, Prospective, Controlled Study in Male Patients with Severe Growth Hormone Deficiency
Colao, A., Somma, C. D., Spiezia, S., Savastano, S., Rota, F., Savanelli, M. C., & Lombardi, G. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2810 · Cited by 61 · see citing works
IGF-1 and atherothrombosis: relevance to pathophysiology and therapy
Conti, E., Musumeci, B., Giusti, M., Dito, E., Mastromarino, V., Autore, C., & Volpe, M. (2011) · Clinical Science · doi:10.1042/cs20100400 · Cited by 61 · see citing works
Current IGFBP-Related Biomarker Research in Cardiovascular Disease—We Need More Structural and Functional Information in Clinical Studies
Hoeflich, A., David, R., & Hjortebjerg, R. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00388 · Cited by 60 · see citing works
Role of IGF-1 in glucose regulation and cardiovascular disease
Abbas, A., Grant, P. J., & Kearney, M. T. (2008) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.6.8.1135 · Cited by 59 · see citing works
The role of exercise in the reversal of IGF-1 deficiencies in microvascular rarefaction and hypertension
Norling, A. M., Gerstenecker, A. T., Buford, T. W., Khan, B., Oparil, S., & Lazar, R. M. (2019) · GeroScience · doi:10.1007/s11357-019-00139-2 · Cited by 59 · see citing works
“These findings corroborate other studies that showed a reduced level of IGF-1 to be a strong predictor of cardiovascular disease (Juul et al. 2002; Laughlin et al. 2004).”
Result
Cardiovascular risk in adult hypopituitaric patients with growth hormone deficiency: is there a role for vitamin D?
Savanelli, M. C., Scarano, E., Muscogiuri, G., Barrea, L., Vuolo, L., Rubino, M., Savastano, S., Colao, A., & Di Somma, C. (2016) · Endocrine · doi:10.1007/s12020-015-0779-3 · Cited by 59 · see citing works
Growth Hormone and the Cardiovascular System
Palmeiro, C., Anand, R. G., Dardi, I. K., Balasubramaniyam, N., Schwarcz, M., & Weiss, I. A. (2012) · Cardiology in Review · doi:10.1097/crd.0b013e318248a3e1 · Cited by 57 · see citing works
Metformin stimulates IGFBP-2 gene expression through PPARalpha in diabetic states
Kang, H. S., Cho, H., Lee, J., Oh, G. T., Koo, S., Park, B., Lee, I., Choi, H., Song, D., & Im, S. (2016) · Scientific Reports · doi:10.1038/srep23665 · Cited by 56 · see citing works
The serum proteome of nonalcoholic fatty liver disease: A multimodal approach to discovery of biomarkers of nonalcoholic steatohepatitis
Miller, M. H., Walsh, S. V., Atrih, A., Huang, J. T.-J., Ferguson, M. A. J., & Dillon, J. F. (2014) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12614 · Cited by 55 · see citing works
Associations of insulin‐like growth factor‐I and its binding proteins and testosterone with frailty in older men
Yeap, B. B., Paul Chubb, S. A., Lopez, D., Ho, K. K. Y., Hankey, G. J., & Flicker, L. (2013) · Clinical Endocrinology · doi:10.1111/cen.12052 · Cited by 53 · see citing works
Associations of Adiposity from Childhood into Adulthood with Insulin Resistance and the Insulin-Like Growth Factor System: 65-Year Follow-Up of the Boyd Orr Cohort
Martin, R. M., Holly, J. M. P., Smith, G. D., & Gunnell, D. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0745 · Cited by 54 · see citing works
Vascular Insulin-Like Growth Factor-I Resistance and Diet-Induced Obesity
Imrie, H., Abbas, A., Viswambharan, H., Rajwani, A., Cubbon, R. M., Gage, M., Kahn, M., Ezzat, V., Duncan, E. R., Grant, P. J., et al. (2009) · Endocrinology · doi:10.1210/en.2008-1641 · Cited by 54 · see citing works
Total Insulinlike Growth Factor 1 and Insulinlike Growth Factor Binding Protein Levels, Functional Status, and Mortality in Older Adults
Kaplan, R. C., McGinn, A. P., Pollak, M., Kuller, L. H., Strickler, H. D., Rohan, T. E., Xue, X., Kritchevsky, S. B., Newman, A. B., & Psaty, B. M. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01637.x · Cited by 53 · see citing works
“In the Rancho Bernardo cohort, high IGFBP-1 levels were associated with lower risk of ischemic heart disease mortality, although results for nonischemic heart disease or all-cause mortality were null.(26) IGFBP-1 levels in the Rancho Bernardo study were nonfasting, which makes interpretation of these results uncertain…”
Background
Growth hormone/insulin-like growth factor-I axis in obstructive sleep apnea syndrome: An update
Lanfranco, F., Motta, G., Minetto, M. A., Ghigo, E., & Maccario, M. (2010) · Journal of Endocrinological Investigation · doi:10.1007/bf03346580 · Cited by 52 · see citing works
Revisiting the Relationship Between Blood Pressure and Insulin-Like Growth Factor-1
Schutte, A. E., Volpe, M., Tocci, G., & Conti, E. (2014) · Hypertension · doi:10.1161/hypertensionaha.113.03057 · Cited by 52 · see citing works
“8±15 y; cross-sectional analysis of controls at study entry (n=200)20; (29) men and women from the general population aged 40±9 y (n=3496); cross-sectional analysis of first examination of prospective study, adjusted for sex and age.”
Background
Endothelial IGF-1 Receptor Signalling in Diabetes and Insulin Resistance
Cubbon, R. M., Kearney, M. T., & Wheatcroft, S. B. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.11.009 · Cited by 51 · see citing works
“In the Rancho Bernardo study, every 40-ng/ml decrement in IGF-1 was associated with a 38% increase in risk of death from coronary artery disease [23].”
Background
Insulin-like growth factor (IGF)-I and IGF binding proteins axis in diabetes mellitus
Kim, M. S., & Lee, D. (2015) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2015.20.2.69 · Cited by 51 · see citing works
Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor–Binding Protein 3 in Relation to the Risk of Type 2 Diabetes Mellitus: Results From the EPIC–Potsdam Study
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High Serum Insulin-Like Growth Factor Binding Protein-1 is Associated with Increased Cardiovascular Mortality in Elderly Men
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Decline in circulating insulin-like growth factors and mortality in older adults: cardiovascular health study all-stars study
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IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population
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The Association of Serum Insulin-Like Growth Factor-I with Mortality, Cardiovascular Disease, and Cancer in the Elderly: A Population-Based Study
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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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