Atherogenic index of plasma is associated with major adverse cardiovascular events in patients with type 2 diabetes mellitus

Liyao Fu, Ying Zhou, Jiaxing Sun, Zhaowei Zhu, Zhenhua Xing, Shenghua Zhou, Yongjun Wang, Shi Tai, Liyao Fu, Ying Zhou, Jiaxing Sun, Zhaowei Zhu, Zhenhua Xing, Shenghua Zhou, Yongjun Wang, Shi Tai

Abstract

Background: Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM).

Methods: This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors.

Results: AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084-1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205-1.474, P < 0.001; Model 2: HR = 1.171, 95% CI 1.030-1.333, P = 0.016; Model 3: HR = 1.194, 95% CI 1.049-1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077-1.303, P < 0.001), cardiovascular death (Model 1: HR = 1.422, 95% CI 1.201-1.683, P < 0.001; Model 3: HR = 1.264, 95% CI 1.015-1.573, P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255-1.669, P < 0.001; Model 2: HR = 1.252, 95% CI 1.045-1.499, P = 0.015; Model 3: HR = 1.284, 95% CI 1.071-1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events.

Conclusions: This study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM.

Trial registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.

Keywords: Atherogenic index of plasma; Atherosclerosis; Cardiovascular disease; Major adverse cardiovascular events; Prognosis; Type 2 diabetes mellitus.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves for the primary and secondary outcomes. Low AIP vs. High AIP in A Primary outcome, B CVD mortality, C Nonfatal myocardial infarction, D Nonfatal stroke, E Total mortality, F Total Stroke, and G Heart failure

References

    1. American Diabetes A 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2019. Diabetes Care. 2019;42(Suppl 1):S103–S123. doi: 10.2337/dc19-S010.
    1. Beckman JA, Paneni F, Cosentino F, Creager MA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Eur Heart J. 2013;34(31):2444–2452. doi: 10.1093/eurheartj/eht142.
    1. Booth GL, Kapral MK, Fung K, Tu JV. Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study. Lancet. 2006;368(9529):29–36. doi: 10.1016/S0140-6736(06)68967-8.
    1. Kumar A, Singh V. Atherogenic dyslipidemia and diabetes mellitus: what’s new in the management arena? Vasc Health Risk Manag. 2010;6:665–669. doi: 10.2147/VHRM.S5686.
    1. Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137–149. doi: 10.1016/j.diabres.2013.11.002.
    1. Leong DP, Joseph PG, McKee M, Anand SS, Teo KK, Schwalm JD, Yusuf S. Reducing the global burden of cardiovascular disease, part 2: prevention and treatment of cardiovascular disease. Circ Res. 2017;121(6):695–710. doi: 10.1161/CIRCRESAHA.117.311849.
    1. Qin Z, Zhou K, Li Y, Cheng W, Wang Z, Wang J, Gao F, Yang L, Xu Y, Wu Y, et al. The atherogenic index of plasma plays an important role in predicting the prognosis of type 2 diabetic subjects undergoing percutaneous coronary intervention: results from an observational cohort study in China. Cardiovasc Diabetol. 2020;19(1):23. doi: 10.1186/s12933-020-0989-8.
    1. Dobiásová M, Frohlich J. The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate in apoB-lipoprotein-depleted plasma (FER(HDL)) Clin Biochem. 2001;34(7):583–588. doi: 10.1016/S0009-9120(01)00263-6.
    1. Fernandez-Macias JC, Ochoa-Martinez AC, Varela-Silva JA, Perez-Maldonado IN. Atherogenic index of plasma: novel predictive biomarker for cardiovascular illnesses. Arch Med Res. 2019;50(5):285–294. doi: 10.1016/j.arcmed.2019.08.009.
    1. Tan MHJD, Glazer NB. Pioglitazone reduces atherogenic index of plasma in patients with type 2 diabetes. Clin Chem. 2004;50(7):1184–1188. doi: 10.1373/clinchem.2004.031757.
    1. Wang L, Chen F, Xiaoqi C, Yujun C, Zijie L. Atherogenic index of plasma is an independent risk factor for coronary artery disease and a higher SYNTAX score. Angiology. 2021;72(2):181–186. doi: 10.1177/0003319720949804.
    1. Won KB, Jang MH, Park EJ, Park HB, Heo R, Han D, Chang HJ. Atherogenic index of plasma and the risk of advanced subclinical coronary artery disease beyond traditional risk factors: an observational cohort study. Clin Cardiol. 2020;43(12):1398–1404. doi: 10.1002/clc.23450.
    1. Wu TT, Gao Y, Zheng YY, Ma YT, Xie X. Atherogenic index of plasma (AIP): a novel predictive indicator for the coronary artery disease in postmenopausal women. Lipids Health Dis. 2018;17(1):197. doi: 10.1186/s12944-018-0828-z.
    1. Nam JS, Kim MK, Nam JY, Park K, Kang S, Ahn CW, Park JS. Association between atherogenic index of plasma and coronary artery calcification progression in Korean adults. Lipids Health Dis. 2020;19(1):157. doi: 10.1186/s12944-020-01317-4.
    1. Won KB, Han D, Lee JH, Choi SY, Chun EJ, Park SH, Han HW, Sung J, Jung HO, Chang HJ. Atherogenic index of plasma and coronary artery calcification progression beyond traditional risk factors according to baseline coronary artery calcium score. Sci Rep. 2020;10(1):21324. doi: 10.1038/s41598-020-78350-x.
    1. Choudhary MK, Eräranta A, Koskela J, Tikkakoski AJ, Nevalainen PI, Kähönen M, Mustonen J, Pörsti I. Atherogenic index of plasma is related to arterial stiffness but not to blood pressure in normotensive and never-treated hypertensive subjects. Blood Press. 2019;28(3):157–167. doi: 10.1080/08037051.2019.1583060.
    1. Li Z, Huang Q, Sun L, Bao T, Dai Z. Atherogenic index in type 2 diabetes and its relationship with chronic microvascular complications. Int J Endocrinol. 2018;2018:1765835.
    1. Shimizu Y, Nakazato M, Sekita T, Kadota K, Yamasaki H, Takamura N, Aoyagi K, Maeda T. Association of arterial stiffness and diabetes with triglycerides-to-HDL cholesterol ratio for Japanese men: the Nagasaki Islands Study. Atherosclerosis. 2013;228(2):491–495. doi: 10.1016/j.atherosclerosis.2013.03.021.
    1. Ma X, Sun Y, Cheng Y, Shen H, Gao F, Qi J, Yang L, Wang Z, Shi D, Liu Y, et al. Prognostic impact of the atherogenic index of plasma in type 2 diabetes mellitus patients with acute coronary syndrome undergoing percutaneous coronary intervention. Lipids Health Dis. 2020;19(1):240. doi: 10.1186/s12944-020-01418-0.
    1. Zhu XW, Deng FY, Lei SF. Meta-analysis of Atherogenic Index of Plasma and other lipid parameters in relation to risk of type 2 diabetes mellitus. Prim Care Diabetes. 2015;9(1):60–67. doi: 10.1016/j.pcd.2014.03.007.
    1. Elam MB, Ginsberg HN, Lovato LC, Corson M, Largay J, Leiter LA, Lopez C, O’Connor PJ, Sweeney ME, Weiss D, et al. Association of fenofibrate therapy with long-term cardiovascular risk in statin-treated patients with type 2 diabetes. JAMA Cardiol. 2017;2(4):370–380. doi: 10.1001/jamacardio.2016.4828.
    1. Elam MB, Ginsberg HN, Lovato LC, Corson M, Largay J, Leiter LA, Lopez C, O’Connor PJ, Sweeney ME, Weiss D, et al. Association of fenofibrate therapy with long-term cardiovascular risk in statin-treated patients with type 2 diabetes. JAMA Cardiol. 2017;2(4):370–380. doi: 10.1001/jamacardio.2016.4828.
    1. Gerstein HC, Riddle MC, Kendall DM, Cohen RM, Goland R, Feinglos MN, Kirk JK, Hamilton BP, Ismail-Beigi F, Feeney P. Glycemia treatment strategies in the Action to control cardiovascular risk in diabetes (ACCORD) trial. Am J Cardiol. 2007;99(12a):34i–43i. doi: 10.1016/j.amjcard.2007.03.004.
    1. Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, Genuth S, Gerstein HC, Ginsberg HN, Goff DC, Jr, et al. Action to control cardiovascular risk in diabetes (ACCORD) trial: design and methods. Am J Cardiol. 2007;99(12a):21i–33i. doi: 10.1016/j.amjcard.2007.03.003.
    1. Sullivan MD, O’Connor P, Feeney P, Hire D, Simmons DL, Raisch DW, Fine LJ, Narayan KM, Ali MK, Katon WJ. Depression predicts all-cause mortality: epidemiological evaluation from the ACCORD HRQL substudy. Diabetes Care. 2012;35(8):1708–1715. doi: 10.2337/dc11-1791.
    1. Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC, Jr, Probstfield JL, Cushman WC, Ginsberg HN, Bigger JT, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364(9):818–828. doi: 10.1056/NEJMoa1006524.
    1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843. doi: 10.1016/j.diabres.2019.107843.
    1. Song P, Xu L, Xu J, Zhang HQ, Yu CX, Guan QB, Zhao M, Zhang X. Atherogenic index of plasma is associated with body fat level in type 2 diabetes mellitus patients. Curr Vasc Pharmacol. 2018;16(6):589–595. doi: 10.2174/1570161116666180103125456.
    1. Qin Z, Zhou K, Li YP, Wang JL, Cheng WJ, Hu CP, Shi C, He H, Zhou YJ. Remnant lipoproteins play an important role of in-stent restenosis in type 2 diabetes undergoing percutaneous coronary intervention: a single-centre observational cohort study. Cardiovasc Diabetol. 2019;18(1):11. doi: 10.1186/s12933-019-0819-z.
    1. Onat A, Can G, Kaya H, Hergenç G. “Atherogenic index of plasma” (log10 triglyceride/high-density lipoprotein-cholesterol) predicts high blood pressure, diabetes, and vascular events. J Clin Lipidol. 2010;4(2):89–98. doi: 10.1016/j.jacl.2010.02.005.
    1. Nogay NH. Assessment of the correlation between the atherogenic index of plasma and cardiometabolic risk factors in children and adolescents: might it be superior to the TG/HDL-C ratio? J Pediatr Endocrinol Metab. 2017;30(9):947–955. doi: 10.1515/jpem-2016-0479.
    1. Murguia-Romero M, Jimenez-Flores JR, Sigrist-Flores SC, Espinoza-Camacho MA, Jimenez-Morales M, Pina E, Mendez-Cruz AR, Villalobos-Molina R, Reaven GM. Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults. J Lipid Res. 2013;54(10):2795–2799. doi: 10.1194/jlr.M040584.
    1. Salazar MR, Carbajal HA, Espeche WG, Aizpurua M, Maciel PM, Reaven GM. Identification of cardiometabolic risk: visceral adiposity index versus triglyceride/HDL cholesterol ratio. Am J Med. 2014;127(2):152–157. doi: 10.1016/j.amjmed.2013.10.012.
    1. Dobiásová M. AIP—atherogenic index of plasma as a significant predictor of cardiovascular risk: from research to practice. Vnitr Lek. 2006;52(1):64–71.
    1. Salazar MR, Carbajal HA, Espeche WG, Aizpurua M, Leiva Sisnieguez CE, March CE, Balbin E, Stavile RN, Reaven GM. Identifying cardiovascular disease risk and outcome: use of the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio versus metabolic syndrome criteria. J Intern Med. 2013;273(6):595–601. doi: 10.1111/joim.12036.

Source: PubMed

3
구독하다