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Cardiovascular diseases in grandparents and the risk of congenital heart diseases in grandchildren

Published online by Cambridge University Press:  19 February 2014

K. P. J. Wijnands
Affiliation:
Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
S. A. Obermann-Borst
Affiliation:
Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
E. J. G. Sijbrands
Affiliation:
Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
M. F. Wildhagen
Affiliation:
Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands Department of Urology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
W. A. Helbing
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
R. P. M. Steegers-Theunissen*
Affiliation:
Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands Department of Clinical Genetics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
*
*Address for correspondence: Dr Régine P. M. Steegers-Theunissen, Professor in Periconception Epidemiology, Department of Obstetrics and Gynecology, University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. (Email [email protected])

Abstract

Hyperglycemia, dyslipidemia and hyperhomocysteinemia are associated with both adult cardiovascular disease (CVD) and having a child with a congenital heart disease (CHD). We investigated associations between CVD in grandparents and the risk of CHD in grandchildren. In a case–control family study, we obtained detailed questionnaire information on CVD and CHD in 247 families with a CHD child and 203 families without a CHD child. Grandparents with CVD or intermittent claudication (IC) were significantly associated with an increased risk for CHD in grandchildren [OR 1.39 (95% CI 1.03–1.89) and OR 2.77 (95% CI 1.02–7.56), respectively]. The risk of CHD grandchildren was particularly increased in paternal grandfathers with CVD [OR 1.85 (95% CI 1.01–3.37)]. Overall, having a grandparent with CVD increased the risk for CHD in the grandchild by 1.65 (95% CI 1.12–2.41). After adjustment for potential maternal confounders, this risk was 1.44 (95% CI 0.94–2.21). Having two or more grandparents with CVD was associated with an approximately threefold risk for CHD grandchildren [OR adjusted 2.72 (95% CI 1.08–6.89)]. Our data suggest that CVD and IC in grandparents are associated with an increased risk of having a CHD grandchild. These first findings may be explained by shared causality of derangements in metabolic pathways and are in line with the fetal origins of health and disease.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2014 

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References

1. World Health Organization. Fact sheet No. 317 Cardiovascular Diseases, March 2013. Retrieved July 2, 2013 from http://www.who.int/mediacentre/factsheets/fs317/en/.Google Scholar
2. March of Dimes Birth Defects Foundation. Global Report on Birth Defects. The Hidden Toll of Dying and Disabled Children. White Plains, NY: March of Dimes Birth Defects Foundation. 2006.Google Scholar
3. Jenkins, KJ, Correa, A, Feinstein, JA, et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007; 115, 29953014.CrossRefGoogle Scholar
4. Steegers-Theunissen, RP, Steegers, EA. Nutrient-gene interactions in early pregnancy: a vascular hypothesis. Eur J Obstet Gynecol Reprod Biol. 2003; 106, 115117.Google Scholar
5. Smedts, HP, van Uitert, EM, Valkenburg, O, et al. A derangement of the maternal lipid profile is associated with an elevated risk of congenital heart disease in the offspring. Nutr Metab Cardiovasc Dis. 2012; 22, 477485.Google Scholar
6. Hobbs, CA, Cleves, MA, Melnyk, S, Zhao, W, James, SJ. Congenital heart defects and abnormal maternal biomarkers of methionine and homocysteine metabolism. Am J Clin Nutr. 2005; 81, 147153.Google Scholar
7. Verkleij-Hagoort, AC, Verlinde, M, Ursem, NT, et al. Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease. BJOG. 2006; 113, 14121418.Google Scholar
8. Fruchart, JC, Nierman, MC, Stroes, ES, Kastelein, JJ, Duriez, P. New risk factors for atherosclerosis and patient risk assessment. Circulation. 2004; 109(Suppl. 1), III15III19.Google Scholar
9. Ingelsson, E, Schaefer, EJ, Contois, JH, et al. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA. 2007; 298, 776785.Google Scholar
10. Kaati, G, Bygren, LO, Edvinsson, S. Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet. 2002; 10, 682688.Google Scholar
11. Kaati, G, Bygren, LO, Pembrey, M, Sjostrom, M. Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet. 2007; 15, 784790.Google Scholar
12. Pembrey, ME. Male-line transgenerational responses in humans. Hum Fertil (Camb). 2010; 13, 268271.Google Scholar
13. Roseboom, TJ, van der Meulen, JH, Osmond, C, et al. Coronary heart disease after prenatal exposure to the Dutch famine, 1944–45. Heart. 2000; 84, 595598.Google Scholar
14. Roseboom, TJ, van der Meulen, JH, Osmond, C, et al. Plasma lipid profiles in adults after prenatal exposure to the Dutch famine. Am J Clin Nutr. 2000; 72, 11011106.Google Scholar
15. Jansen, AC, van Aalst-Cohen, ES, Tanck, MW, et al. The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. J Intern Med. 2004; 256, 482490.Google Scholar
16. Centers for Disease Control and Prevention. National Health Interview Survey. Retrieved July 2, 2013 from http://www.cdc.gov/nchs/nhis/quest_data_related_1997_forward.htm.Google Scholar
17. Verkleij-Hagoort, AC, de Vries, JH, Ursem, NT, et al. Dietary intake of B-vitamins in mothers born a child with a congenital heart defect. Eur J Nutr. 2006; 45, 478486.Google Scholar
18. Steegers-Theunissen, RP. Inaugural lecture: 'New life in a changing environment'. 2010; ISBN 978-90-779-0672-9.Google Scholar
19. van der Bom, T, Zomer, AC, Zwinderman, AH, et al. The changing epidemiology of congenital heart disease. Nat Rev Cardiol. 2011; 8, 5060.Google Scholar
20. Pierpont, ME, Basson, CT, Benson, DW Jr, et al. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007; 115, 30153038.Google Scholar
21. Carone, BR, Fauquier, L, Habib, N, et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell. 2010; 143, 10841096.Google Scholar
22. Nafee, TM, Farrell, WE, Carroll, WD, Fryer, AA, Ismail, KM. Epigenetic control of fetal gene expression. BJOG. 2008; 115, 158168.Google Scholar
23. Hanson, MA, Gluckman, PD. Developmental origins of health and disease: new insights. Basic Clin Pharmacol Toxicol. 2008; 102, 9093.Google Scholar
24. Moons, P, Van Deyk, K, Dedroog, D, Troost, E, Budts, W. Prevalence of cardiovascular risk factors in adults with congenital heart disease. Eur J Cardiovasc Prev Rehabil. 2006; 13, 612616.Google Scholar
25. Hopper, JL, Bishop, DT, Easton, DF. Population-based family studies in genetic epidemiology. Lancet. 2005; 366, 13971406.CrossRefGoogle ScholarPubMed
26. Li, X, Li, S, Mu, D, et al. The association between periconceptional folic acid supplementation and congenital heart defects: A case-control study in China. Prev Med. 2013; 56, 385389.Google Scholar
27. Cresci, M, Foffa, I, Ait-Ali, L, et al. Maternal and paternal environmental risk factors, metabolizing GSTM1 and GSTT1 polymorphisms, and congenital heart disease. Am J Cardiol. 2011; 108, 16251631.Google Scholar
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