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Interactions between plasma homocysteine and arterial stiffness in chronic kidney disease in community-dwelling individuals: The Maine-Syracuse Study

Journal of Human Hypertension volume 29, pages 726–731 (2015)Cite this article

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Abstract

Plasma homocysteine (tHcy) is associated with kidney disease. However, few, if any, studies have examined homocysteine in relation to arterial stiffness, with stratification by the presence or absence of early-stage chronic kidney disease (CKD). The aim of this study was to examine prospective associations between tHcy and carotid–femoral pulse wave velocity (PWV) in persons with and without early-stage CKD in a sample of community-living individuals free from end-stage renal disease, dialysis, stroke and dementia. We conducted a prospective study with 498 participants of the Maine-Syracuse Longitudinal Study (mean age 61 years). Levels of tHcy were positively related to PWV measured 4–5 years later for participants with early-stage CKD (estimated glomerular filtration rate <60 ml min−1 per 1.73 m2). Statistical adjustment was made for multiple confounders, including demographic factors, PWV-related variables and cardiovascular risk factors (b=4.27, 95% confidence interval: 0.23–8.31, P=0.04). These associations were not observed in persons free from CKD. Plasma tHcy is an important predictor of arterial stiffness, as indexed by PWV, in community-living individuals with modest CKD.

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References

  1. Whitworth JA . Progression of renal failure — the role of hypertension. Ann Acad Med Singapore 2005; 34 (1): 8–15.

    CAS  PubMed  Google Scholar 

  2. Upadhyay A, Hwang SJ, Mitchell GF, Vasan RS, Vita JA, Stantchev PI et al. Arterial stiffness in mild-to-moderate CKD. J Am Soc Nephrol 2009; 20 (9): 2044–2053.

    Article  CAS  Google Scholar 

  3. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298 (17): 2038–2047.

    Article  CAS  Google Scholar 

  4. Friedman AN, Bostom AG, Selhub J, Levey AS, Rosenberg IH . The kidney and homocysteine metabolism. J Am Soc Nephrol 2001; 12 (10): 2181–2189.

    CAS  PubMed  Google Scholar 

  5. Blacher J, Demuth K, Guerin AP, Safar ME, Moatti N, London GM . Influence of biochemical alterations on arterial stiffness in patients with end-stage renal disease. Arterioscler Thromb Vasc Biol 1998; 18 (4): 535–541.

    Article  CAS  Google Scholar 

  6. Bostom AG, Shemin D, Lapane KL, Miller JW, Sutherland P, Nadeau M et al. Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study. Atherosclerosis 1995; 114 (1): 93–103.

    Article  CAS  Google Scholar 

  7. Townsend RR, Wimmer NJ, Chirinos JA, Parsa A, Weir M, Perumal K et al. Aortic PWV in chronic kidney disease: a CRIC ancillary study. Am J Hypertens 2010; 23 (3): 282–289.

    Article  Google Scholar 

  8. Safar ME, London GM, Plante GE . Arterial stiffness and kidney function. Hypertension 2004; 43 (2): 163–168.

    Article  CAS  Google Scholar 

  9. Elias MF, Davey A, Dore GA, Gillespie A, Abhayaratna WP, Robbins MA . Deterioration in renal function is associated with increased arterial stiffness. Am J Hypertens 2014; 27 (2): 207–214.

    Article  CAS  Google Scholar 

  10. Bortolotto LA, Safar ME, Billaud E, Lacroix C, Asmar R, London GM et al. Plasma homocysteine, aortic stiffness, and renal function in hypertensive patients. Hypertension 1999; 34 (4 Pt 2): 837–842.

    Article  CAS  Google Scholar 

  11. Brattstrom L, Wilcken DE . Homocysteine and cardiovascular disease: cause or effect? Am J Clin Nutr 2000; 72 (2): 315–323.

    Article  CAS  Google Scholar 

  12. McCully KS . Hyperhomocysteinemia and arteriosclerosis: historical perspectives. Clin Chem Lab Med 2005; 43 (10): 980–986.

    Article  CAS  Google Scholar 

  13. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG . A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274 (13): 1049–1057.

    Article  CAS  Google Scholar 

  14. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE . Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337 (4): 230–236.

    Article  CAS  Google Scholar 

  15. Van Guelpen B, Hultdin J, Johansson I, Witthoft C, Weinehall L, Eliasson M et al. Plasma folate and total homocysteine levels are associated with the risk of myocardial infarction, independently of each other and of renal function. J Intern Med 2009; 266 (2): 182–195.

    Article  CAS  Google Scholar 

  16. Vollset SE, Refsum H, Tverdal A, Nygard O, Nordrehaug JE, Tell GS et al. Plasma total homocysteine and cardiovascular and noncardiovascular mortality: the Hordaland Homocysteine Study. Am J Clin Nutr 2001; 74 (1): 130–136.

    Article  CAS  Google Scholar 

  17. Hultberg B, Andersson A, Sterner G . Plasma homocysteine in renal failure. Clin Nephrol 1993; 40 (4): 230–235.

    CAS  PubMed  Google Scholar 

  18. Anan F, Masaki T, Umeno Y, Yonemochi H, Eshima N, Saikawa T et al. Correlations between homocysteine levels and atherosclerosis in Japanese type 2 diabetic patients. Metabolism 2007; 56 (10): 1390–1395.

    Article  CAS  Google Scholar 

  19. Shargorodsky M, Boaz M, Pasternak S, Hanah R, Matas Z, Fux A et al. Serum homocysteine, folate, vitamin B12 levels and arterial stiffness in diabetic patients: which of them is really important in atherogenesis? Diabetes-Metabolism Research and Reviews 2009; 25 (1): 70–75.

    Article  CAS  Google Scholar 

  20. Xiao W, Bai Y, Ye P, Luo L, Liu D, Wu H et al. Plasma homocysteine is associated with aortic arterial stiffness but not wave reflection in Chinese hypertensive subjects. PLoS One 2014; 9 (1): e85938.

    Article  Google Scholar 

  21. Vyssoulis G, Karpanou E, Kyvelou SM, Adamopoulos D, Gialernios T, Gymnopoulou E et al. Associations between plasma homocysteine levels, aortic stiffness and wave reflection in patients with arterial hypertension, isolated office hypertension and normotensive controls. J Hum Hypertens 2010; 24 (3): 183–189.

    Article  CAS  Google Scholar 

  22. Kim BJ, Seo M, Huh JK, Kwon CH, Kim JT, Sung KC et al. Associations of plasma homocysteine levels with arterial stiffness in prehypertensive individuals. Clin Exp Hypertens 2011; 33 (6): 411–417.

    Article  CAS  Google Scholar 

  23. Dore GA, Elias MF, Robbins MA, Budge MM, Elias PK . Relation between central adiposity and cognitive function in the Maine-Syracuse Study: attenuation by physical activity. Ann Behav Med 2008; 35 (3): 341–350.

    Article  Google Scholar 

  24. Elias MF, Robbins MA, Budge MM, Abhayaratna WP, Dore GA, Elias PK . Arterial pulse wave velocity and cognition with advancing age. Hypertension 2009; 53 (4):668–673.

    Article  CAS  Google Scholar 

  25. Elias MF, Robbins MA, Budge MM, Elias PK, Brennan SL, Johnston C et al. Homocysteine, folate, and vitamins B6 and B12 blood levels in relation to cognitive performance: the Maine-Syracuse study. Psychosom Med 2006; 68 (4): 547–554.

    Article  CAS  Google Scholar 

  26. Robbins MA, Elias MF, Elias PK, Budge MM . Blood pressure and cognitive function in an African-American and a Caucasian-American sample: the Maine-Syracuse Study. Psychosom Med 2005; 67 (5): 707–714.

    Article  Google Scholar 

  27. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM . Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34 (7): 939–944.

    Article  CAS  Google Scholar 

  28. Elias MF, Robbins MA, Budge MM, Elias PK, Dore GA, Brennan SL et al. Homocysteine and cognitive performance: modification by the ApoE genotype. Neurosci Lett 2008; 430 (1): 64–69.

    Article  CAS  Google Scholar 

  29. Weber T, Ammer M, Rammer M, Adji A, O'Rourke MF, Wassertheurer S et al. Noninvasive determination of carotid-femoral pulse wave velocity depends critically on assessment of travel distance: a comparison with invasive measurement. J Hypertens 2009; 27 (8): 1624–1630.

    Article  CAS  Google Scholar 

  30. Handler J . The importance of accurate blood pressure measurement. The Permanente journal 2009; 13 (3): 51–54.

    Article  Google Scholar 

  31. Wolf AM, Hunter DJ, Colditz GA, Manson JE, Stampfer MJ, Corsano KA et al. Reproducibility and validity of a self-administered physical-activity quesionnaire. Int J Epidemiol 1994; 23 (5): 991–999.

    Article  CAS  Google Scholar 

  32. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006; 27 (21): 2588–2605.

    Article  Google Scholar 

  33. O'Rourke MF, Pauca A, Jiang XJ . Pulse wave analysis. Br J Clin Pharmacol 2001; 51 (6): 507–522.

    Article  CAS  Google Scholar 

  34. Millasseau SC, Stewart AD, Patel SJ, Redwood SR, Chowienczyk PJ . Evaluation of carotid-femoral pulse wave velocity: influence of timing algorithm and heart rate. Hypertension 2005; 45 (2): 222–226.

    Article  CAS  Google Scholar 

  35. Seliger SL, Siscovick DS, Stehman-Breen CO, Gillen DL, Fitzpatrick A, Bleyer A et al. Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study. J Am Soc Nephrol 2004; 15 (7): 1904–1911.

    Article  Google Scholar 

  36. Vlachopoulos C, Aznaouridis K, Stefanadis C . Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 2010; 55 (13): 1318–1327.

    Article  Google Scholar 

  37. Mourad JJ, Pannier B, Blacher J, Rudnichi A, Benetos A, London GM et al. Creatinine clearance, pulse wave velocity, carotid compliance and essential hypertension. Kidney Int 2001; 59 (5): 1834–1841.

    Article  CAS  Google Scholar 

  38. Kerr PG, Guerin AP . Arterial calcification and stiffness in chronic kidney disease. Clin Exp Pharmacol Physiol 2007; 34 (7): 683–687.

    Article  CAS  Google Scholar 

  39. Moody WE, Edwards NC, Chue CD, Ferro CJ, Townend JN . Arterial disease in chronic kidney disease. Heart 2013; 99 (6): 365–372.

    Article  CAS  Google Scholar 

  40. Crichton GE, Robbins MA, Elias MF . Homocysteine, Folic Acid, B Vitamins and Cognitive Functioning: a Review of the Literature. Edited by Waldstein SR, Elias MF. In: Neuropsychology of Cardiovascular Disease 2nd edn.Taylor and Francis: New York, 2014.

    Google Scholar 

  41. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O'Rourke MF . Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation 1983; 68 (1): 50–58.

    Article  CAS  Google Scholar 

  42. Smulders YM, Blom HJ . The homocysteine controversy. J Inherit Metab Dis 2011; 34 (1): 93–99.

    Article  CAS  Google Scholar 

  43. van Dijk SC, Enneman AW, van Meurs J, Swart KMA, Ham AH, van Wijngaarden JP et al. B-vitamin levels and genetics of hyperhomocysteinemia are not associated with arterial stiffness. Nutrition, metabolism, and cardiovascular diseases: NMCD 2014; 24 (7): 760–766.

    Article  CAS  Google Scholar 

  44. Clarke R, Halsey J, Lewington S, Lonn E, Armitage J, Manson JE et al. Effects of Lowering Homocysteine Levels With B Vitamins on Cardiovascular Disease, Cancer, and Cause-Specific Mortality Meta-analysis of 8 Randomized Trials Involving 37 485 Individuals. Arch Intern Med 2010; 170 (18): 1622–1631.

    Article  CAS  Google Scholar 

  45. Huang T, Chen Y, Yang B, Yang J, Wahlqvist ML, Li D . Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. Clin Nutr 2012; 31 (4): 448–454.

    Article  CAS  Google Scholar 

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Acknowledgements

The Maine-Syracuse Longitudinal Study was supported by Grants R01HL067358 and R01HL081290 from the National Heart, Lung and Blood Institute, National Institutes of Health (USA) and research grant R01AG03055 from the National Institute on Aging, National Institutes of Health (USA). GEC is supported by a National Health and Medical Research Council (NHMRC) Sidney Sax Research Fellowship (GNT1054567) (Australia).

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Authors and Affiliations

  1. Department of Psychology, University of Maine, Orono, ME, USA

    M F Elias

  2. Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, USA

    M F Elias

  3. Nutritional Physiology Research Centre, University of South Australia, Adelaide, SA, Australia

    G E Crichton

  4. Centre de Recherche Public Santé, Centre d’Etudes en Santé, Grand-Duchy of Luxembourg, Luxembourg

    G E Crichton

  5. College of Medicine, Biology, and Environment, Australian National University, Canberra, ACT, Australia

    W P Abhayaratna

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Correspondence to G E Crichton.

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Elias, M., Crichton, G. & Abhayaratna, W. Interactions between plasma homocysteine and arterial stiffness in chronic kidney disease in community-dwelling individuals: The Maine-Syracuse Study. J Hum Hypertens 29, 726–731 (2015). https://doi.org/10.1038/jhh.2015.17

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