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Relationship between homocysteine and chronic total coronary occlusion: a cross-sectional study from southwest China

Published online by Cambridge University Press:  09 October 2023

Kaiyong Xiao*
Department of Cardiology, Guangyuan Central Hospital, Guangyuan, SC, China
Zhe Xv
Department of Pediatric Medicine, Guangyuan Central Hospital, Guangyuan, SC, China
Liang Liu
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, SX, China
Bin Yang
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, SX, China
Huili Cao
Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, SX, China
Jianping Wang
Department of Cardiology, Guangyuan Central Hospital, Guangyuan, SC, China
Yuling Xv
Sterilization Supply Center, Guangyuan Central Hospital, Guangyuan, SC, China
Qingrui Li
Department of Cardiology, Guangyuan Central Hospital, Guangyuan, SC, China
Yulin Hou
Department of Cardiology, Guangyuan Central Hospital, Guangyuan, SC, China
Feifei Feng
Department of Cardiology, Guangyuan Central Hospital, Guangyuan, SC, China
Jie Wang
Department of Cardiology, Guangyuan Central Hospital, Guangyuan, SC, China
Hui Feng
Medical Laboratory Center, Guangyuan Central Hospital, Guangyuan, SC, China
Corresponding author: K. Xiao; Email:



Chronic total coronary occlusion is among the most complex coronary artery diseases. Elevated homocysteine is a risk factor for coronary artery diseases. However, few studies have assessed the relationship between homocysteine and chronic total coronary occlusion.


1295 individuals from Southwest China were enrolled in the study. Chronic total coronary occlusion was defined as complete occlusion of coronary artery for more than three months. Homocysteine was divided into quartiles according to its level. Univariate and multivariate logistic regression models, receiver operating characteristic curves, and subgroup analysis were applied to assess the relationship between homocysteine and chronic total coronary occlusion.


Subjects in the higher homocysteine quartile had a higher rate of chronic total coronary occlusion (P < 0.001). After adjustment, the odds ratio for chronic total coronary occlusion in the highest quartile of homocysteine compared with the lowest was 1.918 (95% confidence interval 1.237–2.972). Homocysteine ≥ 15.2 μmol/L was considered an independent indicator of chronic total coronary occlusion (odds ratio 1.53, 95% confidence interval 1.05–2.23; P = 0.0265). The area under the receiver operating characteristic curve was 0.659 (95% confidence interval, 0.618–0.701; P < 0.001). Stronger associations were observed in elderly and in those with hypertension and diabetes.


Elevated homocysteine is significantly associated with chronic total coronary occlusion, particularly in elderly and those with hypertension and diabetes.

Original Article
© The Author(s), 2023. Published by Cambridge University Press

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Ambrose, JA, Singh, M. Pathophysiology of coronary artery disease leading to acute coronary syndromes. F1000Prime Rep 2015; 7: 08.CrossRefGoogle ScholarPubMed
Ybarra, LF, Rinfret, S, Brilakis, ES, et al. Definitions and clinical trial design principles for coronary artery chronic total occlusion therapies: CTO-ARC consensus recommendations. Circulation 2021; 143: 479500.CrossRefGoogle ScholarPubMed
Tsai, TT, Stanislawski, MA, Shunk, KA, et al. Contemporary incidence, management, and long-term outcomes of percutaneous coronary interventions for chronic coronary artery total occlusions: insights from the VA CART program. JACC Cardiovasc Interv 2017; 10: 866875.CrossRefGoogle ScholarPubMed
Galassi, AR, Werner, GS, Boukhris, M, et al. Percutaneous recanalisation of chronic total occlusions: 2019 consensus document from the EuroCTO club. EuroIntervention 2019; 15: 198208.CrossRefGoogle ScholarPubMed
Gao, A, Liu, J, Hu, C, et al. Association between the triglyceride glucose index and coronary collateralization in coronary artery disease patients with chronic total occlusion lesions. Lipids Health Dis 2021; 20: 140.CrossRefGoogle ScholarPubMed
Škovierová, H, Vidomanová, E, Mahmood, S, et al. The molecular and cellular effect of homocysteine metabolism imbalance on human health. Int J Mol Sci 2016; 17: 1733.CrossRefGoogle ScholarPubMed
Tu, W, Yan, F, Chao, B, Ji, X, Wang, L. Status of hyperhomocysteinemia in China: results from the China stroke high-risk population screening program, 2018. Front Med 2021; 15: 903912.CrossRefGoogle Scholar
Qujeq, D, Omran, TS, Hosini, L. Correlation between total homocysteine, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in the serum of patients with myocardial infarction. Clin Biochem 2001; 34: 97101.CrossRefGoogle ScholarPubMed
Woodward, M, Rumley, A, Rumley, A, et al. The association between homocysteine and myocardial infarction is independent of age, sex, blood pressure, cholesterol, smoking and markers of inflammation: the glasgow myocardial infarction study. Blood Coagul Fibrinolysis 2006; 17: 15.CrossRefGoogle Scholar
Akyürek, Ö., Akbal, E, Güneş, F. Increase in the risk of ST elevation myocardial infarction is associated with homocysteine level. Arch Med Res 2014; 45: 501506.CrossRefGoogle ScholarPubMed
Shenoy, V, Mehendale, V, Prabhu, K, Shetty, R, Rao, P. Correlation of serum homocysteine levels with the severity of coronary artery disease. Indian J Clin Biochem 2014; 29: 339344.CrossRefGoogle ScholarPubMed
Kobori, Y, Tanaka, N, Matsuoka, O, et al. [Influence of serum homocysteine level on coronary atherosclerosis in Japanese]. J Cardiol 2004; 43: 223229.Google ScholarPubMed
Schaffer, A, Verdoia, M, Cassetti, E, Marino, P, Suryapranata, H, De Luca, G. Relationship between homocysteine and coronary artery disease. Results from a large prospective cohort study. Thromb Res 2014; 134: 288293.CrossRefGoogle ScholarPubMed
Agoşton-Coldea, L, Mocan, T, Seicean, A, Gatfossé, M, Rosenstingl, S. The plasma homocysteine concentrations and prior myocardial infarction. Rom J Intern Med 2010; 48: 6572.Google ScholarPubMed
Pang, X, Liu, J, Zhao, J, et al. Homocysteine induces the expression of C-reactive protein via NMDAr-ROS-MAPK-NF-κB signal pathway in rat vascular smooth muscle cells. Atherosclerosis 2014; 236: 7381.CrossRefGoogle ScholarPubMed
Guthikonda, S, Haynes, WG. Homocysteine: role and implications in atherosclerosis. Curr Atheroscler Rep 2006; 8: 100106.CrossRefGoogle ScholarPubMed
McCully, KS. Homocysteine and the pathogenesis of atherosclerosis. Expert Rev Clin Pharmacol 2015; 8: 211219.CrossRefGoogle ScholarPubMed
Sreckovic, B, Sreckovic, VD, Soldatovic, I, et al. Homocysteine is a marker for metabolic syndrome and atherosclerosis. Diabetes Metab Syndr 2017; 11: 179182.CrossRefGoogle ScholarPubMed
Zhang, S, Bai, YY, Luo, LM, Xiao, WK, Wu, HM, Ye, P. Association between serum homocysteine and arterial stiffness in elderly: a community-based study. J Geriatr Cardiol 2014; 11: 3238.Google ScholarPubMed
Zhao, J, Chen, H, Liu, N, et al. Role of hyperhomocysteinemia and Hyperuricemia in pathogenesis of atherosclerosis. J Stroke Cerebrovasc Dis 2017; 26: 26952699.CrossRefGoogle ScholarPubMed
Liu, Y, Wang, X, Wang, T, et al. Relationship between coronary VH-IVUS plaque characteristics and CTRP9, SAA, and Hcy in patients with coronary heart disease. J Healthc Eng 2022; 2022: 1635446–6.Google ScholarPubMed
McCully, KS. Homocysteine metabolism, atherosclerosis, and diseases of aging. Compr Physiol 2015; 6: 471505.CrossRefGoogle ScholarPubMed
Sayar, N, Terzi, S, Bilsel, T, et al. Plasma homocysteine concentration in patients with poor or good coronary collaterals. Circ J 2007; 71: 266270.CrossRefGoogle ScholarPubMed
Basu, A, Jenkins, AJ, Stoner, JA, et al. Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: a prospective study. Atherosclerosis 2014; 236: 188195.CrossRefGoogle ScholarPubMed
Esse, R, Barroso, M, Tavares de Almeida, I, Castro, R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art. Int J Mol Sci 2019; 20: 867.CrossRefGoogle ScholarPubMed
Ganguly, P, Alam, SF. Role of homocysteine in the development of cardiovascular disease. Nutr J 2015; 14: 6.CrossRefGoogle ScholarPubMed
Hankey, GJ, Eikelboom, JW. Homocysteine and vascular disease. Lancet 1999; 354: 407413.CrossRefGoogle ScholarPubMed
Guo, W, Zhang, H, Yang, A, et al. Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway. J Mol Cell Cardiol 2020; 138: 3448.CrossRefGoogle Scholar
Jin, P, Bian, Y, Wang, K, et al. Homocysteine accelerates atherosclerosis via inhibiting LXRα-mediated ABCA1/ABCG1-dependent cholesterol efflux from macrophages. Life Sci 2018; 214: 4150.CrossRefGoogle ScholarPubMed
Xie, L, Ding, N, Zhang, H, et al. SNF5 promotes IL-1β expression via H3K4me1 in atherosclerosis induced by homocysteine. Int J Biochem Cell Biol 2021; 135: 105974.CrossRefGoogle ScholarPubMed
Hai, Z, Zuo, W. Aberrant DNA methylation in the pathogenesis of atherosclerosis. Clin Chim Acta 2016; 456: 6974.CrossRefGoogle ScholarPubMed
Wei, LH, Chao, NX, Gao, S, et al. Homocysteine induces vascular inflammatory response via SMAD7 hypermethylation in human umbilical vein smooth muscle cells. Microvasc Res 2018; 120: 812.CrossRefGoogle ScholarPubMed
Dimitrova, KR, DeGroot, K, Myers, AK, Kim, YD. Estrogen and homocysteine. Cardiovasc Res 2002; 53: 577588.CrossRefGoogle ScholarPubMed
Obersby, D, Chappell, DC, Dunnett, A, Tsiami, AA. Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis. Br J Nutr 2013; 109: 785794.CrossRefGoogle ScholarPubMed
Ostrakhovitch, EA, Tabibzadeh, S. Homocysteine and age-associated disorders. Ageing Res Rev 2019; 49: 144164.CrossRefGoogle ScholarPubMed
Nygård, O, Vollset, SE, Refsum, H, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland homocysteine study. JAMA 1995; 274: 15261533.CrossRefGoogle ScholarPubMed
Nordström, M, Kjellström, T. Age dependency of cystathionine beta-synthase activity in human fibroblasts in homocyst(e)inemia and atherosclerotic vascular disease. Atherosclerosis 1992; 94: 213221.CrossRefGoogle ScholarPubMed
Wang, H, Sun, Q, Zhou, Y, et al. Nitration-mediated deficiency of cystathionine β-synthase activity accelerates the progression of hyperhomocysteinemia. Free Radic Biol Med 2017; 113: 519529.CrossRefGoogle ScholarPubMed
Mangge, H, Becker, K, Fuchs, D, Gostner, JM. Antioxidants, inflammation and cardiovascular disease. World J Cardiol 2014; 6: 462477.CrossRefGoogle ScholarPubMed
Pessina, AC, Pauletto, P, Rossi, GP, Valle, R. [Hypertension and arteriosclerosis]. Ann Ital Med Int 1992; 7: 112S118S.Google ScholarPubMed
Boutouyrie, P, Tropeano, AI, Asmar, R, et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39: 1015.CrossRefGoogle ScholarPubMed
Gupta, M, Sharma, P, Garg, G, Kaur, K, Bedi, GK, Vij, A. Plasma homocysteine: an independent or an interactive risk factor for coronary artery disease. Clin Chim Acta 2005; 352: 121125.CrossRefGoogle ScholarPubMed
Lim, U, Cassano, PA. Homocysteine and blood pressure in the third national health and nutrition examination survey, 1988-1994. Am J Epidemiol 2002; 156: 11051113.CrossRefGoogle ScholarPubMed
Montalescot, G, Ankri, A, Chadefaux-Vekemans, B, et al. Plasma homocysteine and the extent of atherosclerosis in patients with coronary artery disease. Int J Cardiol 1997; 60: 295300.CrossRefGoogle ScholarPubMed
Ghassibe-Sabbagh, M, Platt, DE, Youhanna, S, et al. Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk. Atherosclerosis 2012; 222: 180186.CrossRefGoogle ScholarPubMed
Parissis, JT, Korovesis, S, Giazitzoglou, E, Kalivas, P, Katritsis, D. Plasma profiles of peripheral monocyte-related inflammatory markers in patients with arterial hypertension. Correlations with plasma endothelin-1. Int J Cardiol 2002; 83: 1321.CrossRefGoogle ScholarPubMed
Pockley, AG, De Faire, U, Kiessling, R, Lemne, C, Thulin, T, Frostegård, J. Circulating heat shock protein and heat shock protein antibody levels in established hypertension. J Hypertens 2002; 20: 18151820.CrossRefGoogle ScholarPubMed
Hu, Y, Xu, Y, Wang, G. Homocysteine levels are associated with endothelial function in newly diagnosed Type 2 Diabetes mellitus patients. Metab Syndr Relat Disord 2019; 17: 323327.CrossRefGoogle ScholarPubMed
Janus, A, Szahidewicz-Krupska, E, Mazur, G, Doroszko, A. Insulin resistance and endothelial dysfunction constitute a common therapeutic target in cardiometabolic disorders. Mediators Inflamm 2016; 2016: 3634948.CrossRefGoogle ScholarPubMed
Sethi, AS, Lees, DM, Douthwaite, JA, Dawnay, AB, Corder, R. Homocysteine-induced endothelin-1 release is dependent on hyperglycaemia and reactive oxygen species production in bovine aortic endothelial cells. J Vasc Res 2006; 43: 175183.CrossRefGoogle ScholarPubMed
Hermida, N, Balligand, JL. Low-density lipoprotein-cholesterol-induced endothelial dysfunction and oxidative stress: the role of statins. Antioxid Redox Signal 2014; 20: 12161237.CrossRefGoogle ScholarPubMed
Begum, N, Hockman, S, Manganiello, VC. Phosphodiesterase 3A (PDE3A) deletion suppresses proliferation of cultured murine vascular smooth muscle cells (VSMCs) via inhibition of mitogen-activated protein kinase (MAPK) signaling and alterations in critical cell cycle regulatory proteins. J Biol Chem 2011; 286: 2623826249.CrossRefGoogle ScholarPubMed