Background: The triglyceride-glucose index (TyG), a novel marker of insulin resistance, is recognised as a risk factor for multiple cardiovascular diseases. The link between its risk and aortic dissection and aortic aneurysm (AD/AA) is not well-defined. This research seeks to explore the relationship.
Methods: This study analysed 386 063 participants from the UK Biobank, a large prospective cohort, all initially free of AD/AA. The main focus was on the occurrence rate of AD/AA. Multivariate Cox regression models were used to analyse the association between the TyG index, its related parameters, and the risk of AD/AA. Association was further validated using a real-world clinical cohort from Central China Fuwai Hospital. A two-sample Mendelian randomisation (MR) analysis utilising the inverse variance weighting method was conducted to investigate the causal link between TyG and AD/AA.
Result: Among the 386 063 participants in the UK Biobank cohort, 3805 cases of AD/AA were reported. After controlling for covariates, a higher TyG index and its related parameters were associated with an increased incidence of AD/AA. The hazard ratios (HRs) were as follows: TyG (HR = 1.14, 95% CI: 1.07–1.22, p <.001), TyG-WHR (HR = 1.17, 95% CI: 1.12–1.22, p <.001), and TyG-WHtR (HR = 1.11, 95% CI: 1.06–1.16, p <.001). Association between TyG and the risk of aortic diseases was also replicated in the single-centre cohort. Two-sample MR analysis indicated strong evidence of a causal relationship between genetically predicted TyG levels and AA (OR = 1.97, 95% CI: 1.37–2.84, p <.001), while no significant association was observed with AD (OR = 0.79, 95% CI: 0.31–1.99, p = .61).
Conclusion: Through complementary epidemiological, clinical, and genetic approaches, our findings indicate that elevated TyG index represents a robust and potentially causal risk factor for aortic diseases (especially AA). These results highlight the importance of metabolic risk assessment in aortic disease prevention and emphasise the need for further mechanistic studies to understand the differential links between TyG and specific aortic phenotypes.
| [1] |
Zhang Y, Zhang H, Zhao S, et al. S-nitrosylation of Septin2 exacerbates aortic aneurysm and dissection by coupling the TIAM1-RAC1 axis in macrophages. Circulation. 2024; 149(24): 1903-1920.
|
| [2] |
Takada M, Yamagishi K, Tamakoshi A, Iso H. Height and mortality from aortic aneurysm and dissection. J Atheroscler Thromb. 2022; 29(8): 1166-1175.
|
| [3] |
Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease. Jama. 2000; 283(7): 897-903.
|
| [4] |
Chumachenko PV, Postnov AY, Ivanova AG, et al. Thoracic aortic aneurysm and factors affecting aortic dissection. J Pers Med. 2020; 10(4): 153.
|
| [5] |
Hibino M, Otaki Y, Kobeissi E, et al. Blood pressure, hypertension, and the risk of aortic dissection incidence and mortality: results from the J-SCH study, the UK Biobank study, and a meta-analysis of cohort studies. Circulation. 2022; 145(9): 633-644.
|
| [6] |
Milewicz DM, Braverman AC, De Backer J, et al. Marfan syndrome. Nat Rev Dis Primers. 2021; 7(1): 64.
|
| [7] |
Rawshani A, Eliasson B, Boren J, et al. Non-coronary peripheral arterial complications in people with type 2 diabetes: a Swedish retrospective cohort study. Lancet Reg Health Eur. 2024; 39:100888.
|
| [8] |
Sidloff D, Choke E, Stather P, Bown M, Thompson J, Sayers R. Mortality from thoracic aortic diseases and associations with cardiovascular risk factors. Circulation. 2014; 130(25): 2287-2294.
|
| [9] |
Cho IY, Koo HY, Han K, et al. Metabolic syndrome and the risk of abdominal aortic aneurysm: a nationwide cohort study. Atherosclerosis. 2023; 386:117329.
|
| [10] |
Sun X, Du C, Chen Y, Cai Z, Chen L. MS4A1-PTGS2 axis induces taurine metabolic reprogramming to exacerbate abdominal aortic aneurysm progression. Int J Med Sci. 2024; 21(11): 2052-2064.
|
| [11] |
Zhang Y, Li J, Chen L, Liang R, Liu Q, Wang Z. Identification of co-diagnostic effect genes for aortic dissection and metabolic syndrome by multiple machine learning algorithms. Sci Rep. 2023; 13(1):14794.
|
| [12] |
Simental-Mendía LE, Rodríguez-Morán M, Guerrero-Romero F. The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metab Syndr Relat Disord. 2008; 6(4): 299-304.
|
| [13] |
Sánchez-García A, Rodríguez-Gutiérrez R, Mancillas-Adame L, et al. Diagnostic accuracy of the triglyceride and glucose index for insulin resistance: a systematic review. Int J Endocrinol. 2020; 2020:4678526.
|
| [14] |
Nayak SS, Kuriyakose D, Polisetty LD, et al. Diagnostic and prognostic value of triglyceride glucose index: a comprehensive evaluation of meta-analysis. Cardiovasc Diabetol. 2024; 23(1): 310.
|
| [15] |
Vasques AC, Novaes FS, de Oliveira Mda S, et al. TyG index performs better than HOMA in a Brazilian population: a hyperglycemic clamp validated study. Diabetes Res Clin Pract. 2011; 93(3): e98-e100.
|
| [16] |
Zhang X, Zhang T, He S, et al. Association of metabolic syndrome with TyG index and TyG-related parameters in an urban Chinese population: a 15-year prospective study. Diabetol Metab Syndr. 2022; 14(1): 84.
|
| [17] |
Alizargar J, Bai CH, Hsieh NC, Wu SV. Use of the triglyceride-glucose index (TyG) in cardiovascular disease patients. Cardiovasc Diabetol. 2020; 19(1): 8.
|
| [18] |
Liu Z, Fan J, Bu H, et al. Causal associations between frailty and low back pain: a bidirectional two-sample mendelian randomization study. Aging Clin Exp Res. 2024; 36(1): 191.
|
| [19] |
Ma L, Liu Z, Fu L, et al. Bidirectional causal relational between frailty and mental illness: a two-sample Mendelian randomization study. Front Psychiatry. 2024; 15:1397813.
|
| [20] |
Jiang Y, Shen J, Chen P, et al. Association of triglyceride glucose index with stroke: from two large cohort studies and Mendelian randomization analysis. Int j Surg. 2024; 110(9): 5409-5416.
|
| [21] |
Li X, Chan JSK, Guan B, et al. Triglyceride-glucose index and the risk of heart failure: evidence from two large cohorts and a Mendelian randomization analysis. Cardiovasc Diabetol. 2022; 21(1): 229.
|
| [22] |
Wang Y, Liu H, Nie X, et al. L-shaped association of triglyceride glucose index and sensorineural hearing loss: results from a cross-sectional study and Mendelian randomization analysis. Front Endocrinol (Lausanne). 2024; 15:1339731.
|
| [23] |
Si S, Li J, Li Y, et al. Causal effect of the triglyceride-glucose index and the joint exposure of higher glucose and triglyceride with extensive cardio-cerebrovascular metabolic outcomes in the UK Biobank: a Mendelian randomization study. Front Cardiovasc Med. 2020; 7:583473.
|
| [24] |
Lin ZP, He HQ, Aierken Y, Wu Y, Liu Y. Effect of serum uric acid on the risk of aortic aneurysm and dissection: A mendelian randomization analysis. Biochem Biophys Rep. 2024; 38:101743.
|
| [25] |
Howard DP, Banerjee A, Fairhead JF, Perkins J, Silver LE, Rothwell PM. Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study. Circulation. 2013; 127(20): 2031-2037.
|
| [26] |
Golabi S, Ajloo S, Maghsoudi F, Adelipour M, Naghashpour M. Associations between traditional and non-traditional anthropometric indices and cardiometabolic risk factors among inpatients with type 2 diabetes mellitus: a cross-sectional study. J Int Med Res. 2021; 49(10):3000605211049960.
|
| [27] |
Che B, Zhong C, Zhang R, et al. Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio as potential cardiovascular disease risk factors: an analysis of UK biobank data. Cardiovasc Diabetol. 2023; 22(1): 34.
|
| [28] |
Wan Y, Zhang Z, Ling Y, et al. Association of triglyceride-glucose index with cardiovascular disease among a general population: a prospective cohort study. Diabetol Metab Syndr. 2023; 15(1): 204.
|
| [29] |
Chen L, He L, Zheng W, et al. High triglyceride glucose-body mass index correlates with prehypertension and hypertension in east Asian populations: a population-based retrospective study. Front Cardiovasc Med. 2023; 10:1139842.
|
| [30] |
Li F, Wang Y, Shi B, et al. Association between the cumulative average triglyceride glucose-body mass index and cardiovascular disease incidence among the middle-aged and older population: a prospective nationwide cohort study in China. Cardiovasc Diabetol. 2024; 23(1): 16.
|
| [31] |
Miao H, Zhou Z, Yang S, Zhang Y. The association of triglyceride-glucose index and related parameters with hypertension and cardiovascular risk: a cross-sectional study. Hypertens Res. 2024; 47(4): 877-886.
|
| [32] |
Park HM, Han T, Heo SJ, Kwon YJ. Effectiveness of the triglyceride-glucose index and triglyceride-glucose-related indices in predicting cardiovascular disease in middle-aged and older adults: a prospective cohort study. J clin lipidol. 2024; 18(1): e70-e79.
|
| [33] |
Elefteriades JA, Ziganshin BA, Rizzo JA, et al. Indications and imaging for aortic surgery: size and other matters. J Thorac Cardiovasc Surg. 2015; 149(2 Suppl): S10-13.
|
| [34] |
Wanhainen A, Van Herzeele I, Bastos Goncalves F, et al. Editor's Choice – European Society for Vascular Surgery (ESVS) 2024 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysms. Eur J Vasc Endovasc Surg. 2024; 67(2): 192-331.
|
| [35] |
Nienaber CA, Clough RE. Management of acute aortic dissection. Lancet. 2015; 385(9970): 800-811.
|
| [36] |
Pape LA, Awais M, Woznicki EM, et al. Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year trends from the international registry of acute aortic dissection. J Am Coll Cardiol. 2015; 66(4): 350-358.
|
| [37] |
Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010; 47(7): 476-485.
|
| [38] |
Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006; 355(8): 788-798.
|
| [39] |
Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000; 342(10): 673-680.
|
| [40] |
Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008; 27(8): 1133-1163.
|
| [41] |
Smith GD, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol. 2004; 33(1): 30-42.
|
| [42] |
Guo Z, Liu P, Li T, et al. Associations of urinary nicotine metabolites and essential metals with metabolic syndrome in older adults: the mediation effect of insulin resistance. J Hazard Mater. 2024; 480:135969.
|
| [43] |
Ishida M, Sakai C, Kobayashi Y, Ishida T. Cigarette smoking and atherosclerotic cardiovascular disease. J Atheroscler Thromb. 2024; 31(3): 189-200.
|
| [44] |
van der Vaart H, Postma DS, Timens W, ten Hacken NH. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004; 59(8): 713-721.
|
| [45] |
Krüger N, Biwer LA, Good ME, et al. Loss of endothelial FTO antagonizes obesity-induced metabolic and vascular dysfunction. Circ Res. 2020; 126(2): 232-242.
|
| [46] |
Prakash SK, Pedroza C, Khalil YA, Milewicz DM. Diabetes and reduced risk for thoracic aortic aneurysms and dissections: a nationwide case-control study. J Am Heart Assoc. 2012; 1(2): jah3-e000323.
|
| [47] |
Takagi H, Umemoto T. Negative association of diabetes with thoracic aortic dissection and aneurysm. Angiology. 2017; 68(3): 216-224.
|
| [48] |
László KD, Olsen J, Li J, et al. The risk of gestational diabetes mellitus following bereavement: a cohort study from Denmark and Sweden. Paediatr Perinat Epidemiol. 2015; 29(4): 271-280.
|
| [49] |
Wada H, Sakata N, Tashiro T. Clinicopathological study on penetrating atherosclerotic ulcers and aortic dissection: distinct pattern of development of initial event. Heart Vessels. 2016; 31(11): 1855-1861.
|
| [50] |
Akutsu K. Etiology of aortic dissection. Gen Thorac Cardiovasc Surg. 2019; 67(3): 271-276.
|
| [51] |
Li Y, Wang W, Li L, Khalil RA. MMPs and ADAMs/ADAMTS inhibition therapy of abdominal aortic aneurysm. Life Sci. 2020; 253:117659.
|
| [52] |
Picatoste B, Cerro-Pardo I, Blanco-Colio LM, Martín-Ventura JL. Protection of diabetes in aortic abdominal aneurysm: Are antidiabetics the real effectors? Front Cardiovasc Med. 2023; 10:1112430.
|
| [53] |
Hill MA, Yang Y, Zhang L, et al. Insulin resistance, cardiovascular stiffening and cardiovascular disease. Metabolism. 2021; 119:154766.
|
| [54] |
Cheng CI, Lee YH, Chen PH, Lin YC, Chou MH, Kao YH. Free fatty acids induce autophagy and LOX-1 upregulation in cultured aortic vascular smooth muscle cells. J Cell Biochem. 2017; 118(5): 1249-1261.
|
| [55] |
Tian R, Peng R, Yang Z, Peng YY, Lu N. Supplementation of dietary nitrate attenuated oxidative stress and endothelial dysfunction in diabetic vasculature through inhibition of NADPH oxidase. Nitric Oxide. 2020; 96: 54-63.
|
| [56] |
Sena CM, Pereira A, Seiça RM. Cinnamaldehyde Supplementation reverts endothelial dysfunction in rat models of diet-induced obesity: role of NF-E2-related factor-2. Antioxidants (Basel). 2022; 12(1): 82.
|
| [57] |
Schaefer L, Han X, August C, Matzkies F, Lorenz T, Schaefer RM. Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats. Diabetologia. 1997; 40(9): 1035-1043.
|
| [58] |
Lee MP, Sweeney G. Insulin increases gelatinase activity in rat glomerular mesangial cells via ERK- and PI-3 kinase-dependent signalling. Diabetes Obes Metab. 2006; 8(3): 281-288.
|
| [59] |
Juhan-Vague I, Hans M. From fibrinogen to fibrin and its dissolution. Bull Acad Natl Med. 2003; 187(1): 69-82; discussion 83-64.
|
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2026 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
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