Thromb Haemost 2011; 105(02): 365-370
DOI: 10.1160/TH10-06-0379
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Low insulin-like growth factor-1 levels are associated with anaemia in adult non-diabetic subjects

Elena Succurro
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Franco Arturi
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Vittoria Caruso
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Stefania Rudi
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Angela Sciacqua
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Francesco Andreozzi
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Marta L. Hribal
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Francesco Perticone
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
,
Giorgio Sesti
1   Department of Experimental and Clinical Medicine, University Magna-Græcia of Catanzaro, Cantanzaro, Italy
› Author Affiliations
Further Information

Publication History

Received: 18 June 2010

Accepted after major revision: 30 October 2010

Publication Date:
25 November 2017 (online)

Summary

Anaemia is a risk factor for cardiovascular morbidity and mortality. Among factors responsible for anaemia, insulin-like growth factor-1 (IGF-1) is a plausible candidate. We evaluated the association of IGF-1 with haemoglobin (Hb) concentration and anaemia in a cohort of 1,039 Caucasians subjects. Subjects with anaemia exhibited lower IGF-1 (p=0.006), and higher hsCRP levels (p=0.003). To estimate the independent contribution of variables to Hb concentration, a multivariable regression analysis was modeled including age, gender, body mass index (BMI), waist circumference, blood pressure, fasting glucose, fasting insulin, IGF-1, fibrinogen, hsCRP, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), serum iron, estimated glomerular filtration rate (eGFR), and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The variables significantly associated with Hb concentration were gender (p<0.0001), IGF-1 (p<0.0001), waist circumference (p=0.02), hsCRP (p<0.04), MCH (p<0.0001), MCV (p<0.0001), serum iron (p=0.001), IGF-1 (p=0.003), hsCRP (p=0.008), and waist circumference (p=0.01), accounting for 54.0% of its variation. Hb concentration was significant lower in subjects in the lowest IGF-1 quartile as compared with those in the third (p=0.02) and fourth (p=0.001). In a logistic regression model adjusted for age, gender, BMI, waist circumference, blood pressure, fasting glucose, fasting insulin, fibrinogen, hsCRP, MCH, MCV, serum iron, eGFR, and treatment with ACE inhibitors or ARBs, subjects in the first quartile of IGF-1 had a 2.49-fold higher risk of having anaemia as compared with those in the fourth (odds ratio 2.70, 95% confidence interval 1.02–7.16). Our data suggest that low IGF-1 may be an important contributor to mild anaemia.

 
  • References

  • 1 Kosiborod M, Smith GL, Radford MJ. et al. The prognostic importance of anemia in patients with heart failure. Am J Med 2003; 114: 112-119.
  • 2 Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation 2003; 107: 223-225.
  • 3 Anand I, McMurray JJ, Whitmore J. et al. Anemia and its relationship to clinical outcome in heart failure. Circulation 2004; 110: 149-154.
  • 4 Foley RN, Parfrey PS, Harnett JD. et al. The impact of anemia on cardiomyopathy, morbidity, and mortality in end-stage renal disease. Am J Kidney Dis 1996; 28: 53-61.
  • 5 Keith DS, Nichols GA, Gullion CM. et al. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004; 164: 659-663.
  • 6 Thomas MC, MacIsaac RJ, Tsalamandris C. et al. The burden of anaemia in type 2 diabetes and the role of nephropathy: A cross-sectional audit. Nephrol Dial Transplant 2004; 19: 1792-1797.
  • 7 Tong PC, Kong AP, So WY. et al. Hematocrit, independent of chronic kidney disease, predicts adverse cardiovascular outcomes in Chinese patients with type 2 diabetes. Diabetes Care 2006; 29: 2439-2444.
  • 8 Beghe C, Wilson A, Ershler WB. Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature. Am J Med 2004; 116: 3S-10S.
  • 9 Zakai NA, Katz R, Hirsch C. et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med 2005; 165: 2214-2220.
  • 10 Sarnak MJ, Tighiouart H, Manjunath G. et al. Anemia as a risk factor for cardiovascular disease in The Atherosclerosis Risk in Communities (ARIC) study. J Am Coll Cardiol 2002; 40: 27-33.
  • 11 Claustres M, Chatelain P, Sultan C. Insulin-like growth factor I stimulates human erythroid colony formation in vitro. J Clin Endocrinol Metab 1987; 65: 78-82.
  • 12 Correa PN, Axelrad AA. Production of erythropoietic bursts by progenitor cells from adult human peripheral blood in an improved serum-free medium: role of insulin-like growth factor 1. Blood 1991; 78: 2823-2833.
  • 13 Merchav S, Tatarsky I, Hochberg Z. Enhancement of erythropoiesis in vitro by human growth hormone is mediated by insulin-like growth factor I. Br J Haematol 1988; 70: 267-271.
  • 14 Powell DR, Rosenfeld RG, Baker BK. et al. Serum somatomedin levels in adults with chronic renal failure: the importance of measuring insulin-like growth factor-I (IGF-I) and IGF-II in acid-chromatographed uremic serum. J Clin Endocrinol Metab 1986; 63: 1186-1192.
  • 15 Christ ER, Cummings MH, Westwood NB. et al. The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency. J Clin Endocrinol Metabol 1997; 82: 2985-2990.
  • 16 Nilsson-Ehle H, Bengtsson BA, Lindstedt G. et al. Insulin-like growth factor-1 is a predictor of blood haemoglobin concentration in 70-yr-old subjects. Eur J Haematol 2005; 74: 111-116.
  • 17 Chu LW, Lam KS, Tam SC. et al. A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients. J Clin Endocrinol Metab 2001; 86: 1913-1920.
  • 18 Succurro E, Andreozzi F, Sciaqua A. et al. Reciprocal association of plasma IGF-1 and interleukin-6 levels with cardiometabolic risk factors in nondiabetic subjects. Diabetes Care 2008; 31: 1886-1888.
  • 19 Succurro E, Marini MA, Arturi F. et al.. Elevated one-hour post-load plasma glucose levels identifies subjects with normal glucose tolerance but early carotid atherosclerosis. Atherosclerosis 2009; 207: 245-249.
  • 20 National Kidney Foundation.. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39: S1-S266.
  • 21 World Health Organization.. Nutritional anaemias: report of a WHO scientific group. World Health Organ Tech Rep Ser 1968; 405: 3-37.
  • 22 Jiménez D, Escobar C, Martí D. et al. Association of anaemia and mortality in patients with acute pulmonary embolism. Thromb Haemost 2009; 102: 153-158.
  • 23 Auernhammer CJ, Strasburger CJ. Effects of growth hormone and insulin-like growth factor I on the immune system. Eur J Endocrinol 1995; 133: 635-645.
  • 24 Sukhanov S, Higashi Y, Shai SY. et al. IGF-1 reduces inflammatory responses, suppresses oxidative stress, and decreases atherosclerosis progression in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 2007; 27: 2684-2690.
  • 25 Means Jr RT, Krantz SB. Progress in understanding the pathogenesis of the anemia of chronic disease. Blood 1992; 80: 1639-1647.
  • 26 Bhatia V, Chaudhuri A, Tomar R. et al. Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabetes Care 2006; 29: 2289-2294.
  • 27 Dallman PR, Yip R, Johnson C. Prevalence and causes of anemia in the United States, 1976 to 1980. Am J Clin Nut 1984; 39: 437-445.
  • 28 Meyers LD, Habicht JP, Johnson CL. et al. Prevalence of anemia and iron deficiency anemia in black and white women in the United States estimated by two methods. Am J Public Health 1983; 73: 1042-1049.
  • 29 Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?. Blood 2006; 107: 1747-1750.
  • 30 Kaaks R, Toniolo P, Akhmedkhanov A. et al. Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst 2000; 92: 1592-1600.