Background and Purpose This study aimed to explore the possible association of plasma total homocysteine with carotid plaque stability. Methods A cross-sectional study was conducted from 2010 to 2011. A stratified random sample of 2,919 Chinese participants aged 40 years or older was enrolled. Plasma total homocysteine levels were measured and carotid plaques were evaluated by ultrasonography. Logistic regression model was used to analyze the association of homocysteine levels to the progression of carotid plaque development, while adjusting for demographics and vascular risk factors. Results The mean level of plasma homocysteine in the subjects was 14.9 μmol/l. Along with increase in homocysteine level, the risk of advanced carotid plaque elevated (odds ratio = 1.28; 95% confidence interval = 1.09–1.51) after adjusting for age, sex, and other potential confounders. Stratified by sex, higher homocysteine level was strongly associated with advanced carotid plaque in men (OR = 1.41; 95% confidence interval = 1.17–1.70), but not in women. Conclusion The findings suggest that plasma level of homocysteine may be associated with advanced carotid plaque, which constitutes high risks of stroke, in male Chinese adults.
References
[1]
WHO (2004) The Global Burden Of Disease:2004 Update. Switzerland: WHO Press. 11–12P.
[2]
Yang GH, Wang Y, Zeng YX, George FG, Liang XF, et al. (2013) Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. The lancet 381: 1987–2015. doi: 10.1016/s0140-6736(13)61097-1
[3]
Wang YL, Wu D, Liao XL, Zhang W, Zhao XQ, et al. (2007) Burden of stroke in China. Stroke 2: 211–213. doi: 10.1111/j.1747-4949.2007.00142.x
[4]
Spagnoli LG, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, et al. (2004) Extracranial Thrombotically Active Carotid Plaque as a Risk Factor for Ischemic. Stroke JAMA 292: 1845–1852. doi: 10.1001/jama.292.15.1845
[5]
Casscells W, Naghavi M, Janes T (2003) Willerson (2003) Vulnerable Atherosclerotic Plaque A Multifocal Disease. Circulation 107: 2072–2075. doi: 10.1161/01.cir.0000069329.70061.68
[6]
Wald DS, Malcolm L, Morris JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325: 1202. doi: 10.1136/bmj.325.7374.1202
[7]
Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288: 2015–22. doi: 10.1001/jama.288.16.2015
[8]
Ralph LS, Kishlay A, Lee HS, Albala BB, Sally S, et al. (2004) Homocysteine and the Risk of Ischemic Stroke in a Triethnic Cohort: The Northern Manhattan Study. Stroke 35: 2263–2269. doi: 10.1161/01.str.0000142374.33919.92
[9]
Giles WH, Macko RF, Amytis T, Daniela M, Bruce O (1999) Homocyst(e)ine and Risk of Cerebral Infarction in a Biracial Population: The Stroke Prevention in Young Women Study. Stroke 30: 1554–1560. doi: 10.1161/01.str.30.8.1554
[10]
Bosts ML, Launer LJ, Lindemans J, Hoes AW, Hofman A, et al. (1999) Homocysteine and Short-term Risk of Myocardial Infarction and Stroke in the Elderly: The Rotterdam Study. Arch Intern Med 159: 38–44. doi: 10.1001/archinte.159.1.38
[11]
Bostom AG, Rosenberg IH, Slibershatz H, Jacques PF, Selhub J, et al. (1999) Nonfasting Plasma Total Homocysteine Levels and Stroke Incidence in Elderly Persons: The Framingham Study. Ann Intern Med 131: 352–355. doi: 10.7326/0003-4819-131-5-199909070-00006
[12]
Towfighi A, Markovic D, Ovbiagele B (2010) Pronounced association of elevated serum homocysteine with stroke in subgroups of individuals: A nationwide study. Neurological 298: 153–157. doi: 10.1016/j.jns.2010.07.013
[13]
Alsulaimani S, Gardener H, Elkind MS, Cheung K, Sacco R, et al. (2013) Elevated Homocysteine and Carotid Plaque Area and Densitometry in the Northern Manhattan Study. Stroke 44: 457–461. doi: 10.1161/strokeaha.112.676155
[14]
Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, et al. (2003) From Vulnerable Plaque to Vulnerable Patient A Call for New Definitions and Risk Assessment Strategies. Circulation 108: 1664–1672. doi: 10.1161/01.cir.0000087480.94275.97
[15]
Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ (2005) Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol 46: 937–54. doi: 10.1016/j.jacc.2005.03.074
[16]
Wang AX, Wu JW, Zhou Y, Guo XH, Luo YX, et al. (2013) Measures of Adiposity and Risk of Stroke in China: A Result from the Kailuan Study. PLOS One 17 8: e61665 doi:10.1371/journal.pone.0061665.
[17]
Wang CH, Gao X, Zhou Y, Zhou H, Wang AN, et al. (2013) Cardiovascular Health Metrics on the Prevalence of Asymptomatic Intracranial Artery Stenosis: A Cross-Sectional Study. PLoS One 8: e58923 doi:10.1371/journal.pone.0058923.
[18]
Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH (1993) Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 39: 1764–79.
[19]
Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG (1995) Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 346: 1395–8. doi: 10.1016/s0140-6736(95)92407-8
[20]
Pelisek J, Eckstein HH, Zernecke A (2012) Pathophysiological mechanisms of carotid plaque vulnerability: impact on ischemic stroke. Arch Immunol Ther Exp (Warsz) 60: 431–42. doi: 10.1007/s00005-012-0192-z
[21]
Coppola A, Davi G, De Stefano V, Mancini FP, Cerbone AM, et al. (2000) Homocysteine, coagulation, platelet function, and thrombosis. Semin Thromb Hemost 26: 243–54. doi: 10.1055/s-2000-8469
[22]
Lentz SR (2005) Mechanisms of homocysteine-induced atherothrombosis. J Thromb Haemost 3: 1646–54. doi: 10.1111/j.1538-7836.2005.01364.x
[23]
Werstuck GH, Lentz SR, Dayal S, Hossain GS, Sood SK, et al. (2001) Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J Clin Invest 107: 1263–73. doi: 10.1172/jci11596
[24]
Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, et al. (2001) Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 107: 675–83. doi: 10.1172/jci10588
[25]
Tsai JC, Perrella MA, Yoshizumi M, Hsieh CM, Haber E, et al. (1994) Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc Natl Acad Sci U S A 91: 6369–73. doi: 10.1073/pnas.91.14.6369
[26]
Upchurch GR Jr, Welch GN, Fabian AJ, Freedman JE, Johnson JL, et al. (1997) Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 272: 17012–7. doi: 10.1074/jbc.272.27.17012
[27]
Moat SJ, Bonham JR, Cragg RA, Powers HJ (2000) Elevated plasma homocysteine elicits an increase in antioxidant enzyme activity. Free Radic Res 32: 171–9. doi: 10.1080/10715760000300171
[28]
Ferretti G, Bacchetti T, Moroni C, Vignini A, Nanetti L, et al. (2004) Effect of homocysteilation of low density lipoproteins on lipid peroxidation of human endothelial cells. J Cell Biochem 2: 351–60. doi: 10.1002/jcb.20069
[29]
Alsulaimani S, Gardener H, Elkind MS, Cheung K, Sacco RL, et al. (2013) Elevated homocysteine and carotid plaque area and densitometry in the Northern Manhattan Study. Stroke 44: 457–61. doi: 10.1161/strokeaha.112.676155
[30]
Adachi H, Hirai Y, Fujiura Y, Matsuoka H, Satoh A, et al. (2002) Plasma homocysteine levels and atherosclerosis in Japan: epidemiological study by use of carotid ultrasonography. Stroke 33: 2177–81. doi: 10.1161/01.str.0000026861.18199.89
[31]
Kamdi SP, Palkar P (2013) Prevalence of hyperhomocysteinemia in healthy Indian doctors. Bioinformation 9: 193–6. doi: 10.6026/97320630009193
[32]
Fukagawa NK, Martin JM, Wurthmann A, Prue AH, Ebenstein D, et al. (2000) Sex-related differences in methionine metabolism and plasma homocysteine concentrations. Am J Clin Nutr 72: 22–9.
[33]
VITATOPS Trial Study Group (2010) B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol 9: 855–65. doi: 10.1016/s1474-4422(10)70187-3
[34]
Pettigrew LC, Bang H, Chambless LE, Howard VJ, Toole JF (2008) Assessment of pre- and post-methionine load homocysteine for prediction of recurrent stroke and coronary artery disease in the Vitamin Intervention for Stroke Prevention Trial. Atherosclerosis 200: 345–9. doi: 10.1016/j.atherosclerosis.2007.11.014