Top

European Journal of Medical Research

Published in:

Open Access 01-12-2024 | Stroke | Research

A non-linear connection between the total cholesterol to high-density lipoprotein cholesterol ratio and stroke risk: a retrospective cohort study from the China Health and Retirement Longitudinal Study

Authors: Binhui Xiao, Changchun Cao, Yong Han, Fangju Yang, Haofei Hu, Jiao Luo

Published in: European Journal of Medical Research | Issue 1/2024

Abstract

Objective

The connection between total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio and stroke risk is controversial. This study aims to examine the connection between the TC/HDL-C ratio and stroke in middle-aged and older individuals who are part of the China Health and Retirement Longitudinal Study (CHARLS).

Methods

This study conducted a retrospective cohort analysis, enrolling a total of 10,184 participants who met the designated criteria from CHARLS between 2011 and 2012. We then used the Cox proportional-hazards regression model to analyze the relationship between the TC/HDL-C ratio and stroke risk. Using a Cox proportional hazards regression model with cubic spline functions and smooth curve fitting, we were able to identify the non-linear relationship between the TC/HDL-C ratio and stroke occurrence. The sensitivity and subgroup analyses were also performed to investigate the connection between TC/HDL-C ratio and stroke.

Results

This study revealed a statistically significant association between the TC/HDL-C ratio and stroke risk in subjects aged 45 years or older after adjusting for risk factors (HR: 1.05, 95%CI 1.00–1.10, P = 0.0410). Furthermore, a non-linear connection between the TC/HDL-C ratio and stroke risk was detected, with a TC/HDL-C ratio inflection point of 3.71. We identified a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71 (HR: 1.25, 95%CI 1.07–1.45, P = 0.0039). However, their connection was not significant when the TC/HDL-C ratio exceeded 3.71 (HR: 1.00, 95%CI 0.94–1.06, P = 0.9232). The sensitivity analysis and subgroup analyses revealed that our findings were well-robust.

Conclusion

Our study demonstrated a positive, non-linear connection between the TC/HDL-C ratio and stroke risk in middle-aged and older individuals. There was a significant positive connection between the TC/HDL-C ratio and stroke risk, when the TC/HDL-C ratio was less than 3.71. The current research can be used as a guideline to support clinician consultation and optimize stroke prevention measures for middle-aged and older adults.

Available only for authorised users

Feigin VL, Stark BA, Johnson CO, Roth GA, Bisignano C, Abady GG, Abbasifard M, Abbasi-Kangevari M, Abd-Allah F, Abedi V, Abualhasan A. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795–820. https://doi.org/10.1016/S1474-4422(21)00252-0.CrossRef

Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, Chugh S, Mensah GA, Norrving B, Shiue I, Ng M, Estep K, Cercy K, Murray C, Forouzanfar MH. Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol. 2016;15(9):913–24. https://doi.org/10.1016/S1474-4422(16)30073-4.CrossRefPubMed

Millan J, Pinto X, Munoz A, Zuniga M, Rubies-Prat J, Pallardo LF, Masana L, Mangas A, Hernandez-Mijares A, Gonzalez-Santos P, Ascaso JF, Pedro-Botet J. Lipoprotein ratios: physiological significance and clinical usefulness in cardiovascular prevention. Vasc Health Risk Manag. 2009;5:757–65.PubMedPubMedCentral

Chu SY, Jung JH, Park MJ, Kim SH. Risk assessment of metabolic syndrome in adolescents using the triglyceride/high-density lipoprotein cholesterol ratio and the total cholesterol/high-density lipoprotein cholesterol ratio. Ann Pediatr Endocrinol Metab. 2019;24(1):41–8. https://doi.org/10.6065/apem.2019.24.1.41.CrossRefPubMedPubMedCentral

Zheng J, Sun Z, Zhang X, Li Z, Guo X, Xie Y, Sun Y, Zheng L. Non-traditional lipid profiles associated with ischemic stroke not hemorrhagic stroke in hypertensive patients: results from an 8.4 years follow-up study. Lipids Health Dis. 2019;18(1):9. https://doi.org/10.1186/s12944-019-0958-y.CrossRefPubMedPubMedCentral

Tang M, Zhao Q, Yi K, Wu Y, Xiang Y, Cui S, Su X, Yu Y, Zhao G, Jiang Y. Association between four nontraditional lipids and ischemic stroke: a cohort study in Shanghai, China. Lipids Health Dis. 2022;21(1):72. https://doi.org/10.1186/s12944-022-01683-1.CrossRefPubMedPubMedCentral

Liu Y, Jin X, Fu K, Li J, Xue W, Tian L, Teng W. Non-traditional lipid profiles and the risk of stroke: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis. 2023;33(4):698–714. https://doi.org/10.1016/j.numecd.2023.01.003.CrossRefPubMed

Zhang Y, Tuomilehto J, Jousilahti P, Wang Y, Antikainen R, Hu G. Total and high-density lipoprotein cholesterol and stroke risk. Stroke. 2012;43(7):1768–74. https://doi.org/10.1161/STROKEAHA.111.646778.CrossRefPubMed

Yokokawa H, Yasumura S, Tanno K, Ohsawa M, Onoda T, Itai K, Sakata K, Kawamura K, Tanaka F, Yoshida Y, Nakamura M, Terayama Y, Ogawa A, Okayama A. Serum low-density lipoprotein to high-density lipoprotein ratio as a predictor of future acute myocardial infarction among men in a 2.7-year cohort study of a Japanese northern rural population. J Atheroscler Thromb. 2011;18(2):89–98. https://doi.org/10.5551/jat.5215.CrossRefPubMed

10.

Canoui-Poitrine F, Luc G, Bard JM, Ferrieres J, Yarnell J, Arveiler D, Morange P, Kee F, Evans A, Amouyel P, Ducimetiere P, Empana JP. Relative contribution of lipids and apolipoproteins to incident coronary heart disease and ischemic stroke: the PRIME Study. Cerebrovasc Dis. 2010;30(3):252–9. https://doi.org/10.1159/000319067.CrossRefPubMed

11.

Zhao Y, Hu Y, Smith JP, Strauss J, Yang G. Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS). Int J Epidemiol. 2014;43(1):61–8. https://doi.org/10.1093/ije/dys203.CrossRefPubMed

12.

Chen X, Liu S, Chu J, Hu W, Sun N, Shen Y. Joint effect of elevated-c-reactive protein level and hypertension on new-onset stroke: a nationwide prospective cohort study of CHARLS. Front Public Health. 2022;10: 919506. https://doi.org/10.3389/fpubh.2022.919506.CrossRefPubMedPubMedCentral

13.

Wang Y, Zha F, Han Y, Cai Y, Chen M, Yang C, Cai X, Hu H, Cao C, Luo J. Nonlinear connection between remnant cholesterol and stroke risk: evidence from the China health and retirement longitudinal study. Lipids Health Dis. 2023;22(1):181. https://doi.org/10.1186/s12944-023-01943-8.CrossRefPubMedPubMedCentral

14.

Wei G, Lin F, Cao C, Hu H, Han Y. Non-linear dose-response relationship between body mass index and stroke risk in middle-aged and elderly Chinese men: a nationwide Longitudinal Cohort Study from CHARLS. Front Endocrinol (Lausanne). 2023;14:1203896. https://doi.org/10.3389/fendo.2023.1203896.CrossRefPubMed

15.

Piercy KL, Troiano RP, Ballard RM, Carlson SA, Fulton JE, Galuska DA, George SM, Olson RD. The physical activity guidelines for Americans. JAMA. 2018;320(19):2020–8. https://doi.org/10.1001/jama.2018.14854.CrossRefPubMedPubMedCentral

16.

Groenwold RH, White IR, Donders AR, Carpenter JR, Altman DG, Moons KG. Missing covariate data in clinical research: when and when not to use the missing-indicator method for analysis. CMAJ. 2012;184(11):1265–9. https://doi.org/10.1503/cmaj.110977.CrossRefPubMedPubMedCentral

17.

White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30(4):377–99. https://doi.org/10.1002/sim.4067.MathSciNetCrossRefPubMed

18.

von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg. 2014;12(12):1495–9. https://doi.org/10.1016/j.ijsu.2014.07.013.CrossRef

19.

Burne RM, Abrahamowicz M. Adjustment for time-dependent unmeasured confounders in marginal structural Cox models using validation sample data. Stat Methods Med Res. 2019;28(2):357–71. https://doi.org/10.1177/0962280217726800.MathSciNetCrossRefPubMed

20.

Wang W, Jiang B, Sun H, Ru X, Sun D, Wang L, Wang L, Jiang Y, Li Y, Wang Y, Chen Z, Wu S, Zhang Y, Wang D, Wang Y, Feigin VL. Prevalence, incidence, and mortality of stroke in china: results from a nationwide population-based survey of 480 687 adults. Circulation. 2017;135(8):759–71. https://doi.org/10.1161/CIRCULATIONAHA.116.025250.CrossRefPubMed

21.

Hindy G, Engstrom G, Larsson SC, Traylor M, Markus HS, Melander O, Orho-Melander M. Role of blood lipids in the development of ischemic stroke and its subtypes: a Mendelian randomization study. Stroke. 2018;49(4):820–7. https://doi.org/10.1161/STROKEAHA.117.019653.CrossRefPubMedPubMedCentral

22.

Elshazly MB, Quispe R, Michos ED, Sniderman AD, Toth PP, Banach M, Kulkarni KR, Coresh J, Blumenthal RS, Jones SR, Martin SS. Patient-level discordance in population percentiles of the total cholesterol to high-density lipoprotein cholesterol ratio in comparison with low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol: The Very Large Database of Lipids Study (VLDL-2B). Circulation. 2015;132(8):667–76. https://doi.org/10.1161/CIRCULATIONAHA.115.016163.CrossRefPubMedPubMedCentral

23.

Zemel PC, Sowers JR. Relation between lipids and atherosclerosis: epidemiologic evidence and clinical implications. Am J Cardiol. 1990;66(21):7I-12I. https://doi.org/10.1016/0002-9149(90)91257-7.CrossRefPubMed

24.

Koba S, Hirano T. Dyslipidemia and atherosclerosis. Nihon Rinsho. 2011;69(1):138–43.PubMed

25.

Alemzadeh R, Kichler J. Comparison of apolipoprotein (ApoB/ApoA-1) and lipoprotein (total cholesterol/HDL) ratios in obese adolescents. Metab Syndr Relat Disord. 2018;16(1):40–5. https://doi.org/10.1089/met.2017.0135.CrossRefPubMed

26.

Badimon L, Storey RF, Vilahur G. Update on lipids, inflammation and atherothrombosis. Thromb Haemost. 2011;105(Suppl 1):S34-42. https://doi.org/10.1160/THS10-11-0717.CrossRefPubMed

27.

Koutsaliaris IK, Moschonas IC, Pechlivani LM, Tsouka AN, Tselepis AD. Inflammation, oxidative stress, vascular aging and atherosclerotic ischemic stroke. Curr Med Chem. 2022;29(34):5496–509. https://doi.org/10.2174/0929867328666210921161711.CrossRefPubMed

28.

Thorand B, Baumert J, Doring A, Schneider A, Chambless L, Lowel H, Kolb H, Koenig W. Association of cardiovascular risk factors with markers of endothelial dysfunction in middle-aged men and women. Results from the MONICA/KORA Augsburg Study. Thromb Haemost. 2006;95(1):134–41.CrossRefPubMed

29.

Gimbrone MJ, Garcia-Cardena G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. 2016;118(4):620–36. https://doi.org/10.1161/CIRCRESAHA.115.306301.CrossRefPubMedPubMedCentral

30.

Simpson CF, Boyd CM, Carlson MC, Griswold ME, Guralnik JM, Fried LP. Agreement between self-report of disease diagnoses and medical record validation in disabled older women: factors that modify agreement. J Am Geriatr Soc. 2004;52(1):123–7. https://doi.org/10.1111/j.1532-5415.2004.52021.x.CrossRefPubMed

31.

Engstad T, Bonaa KH, Viitanen M. Validity of self-reported stroke: the Tromso Study. Stroke. 2000;31(7):1602–7. https://doi.org/10.1161/01.str.31.7.1602.CrossRefPubMed

32.

O’Mahony PG, Dobson R, Rodgers H, James OF, Thomson RG. Validation of a population screening questionnaire to assess prevalence of stroke. Stroke. 1995;26(8):1334–7. https://doi.org/10.1161/01.str.26.8.1334.CrossRefPubMed

Title: A non-linear connection between the total cholesterol to high-density lipoprotein cholesterol ratio and stroke risk: a retrospective cohort study from the China Health and Retirement Longitudinal Study
Authors: Binhui Xiao
Changchun Cao
Yong Han
Fangju Yang
Haofei Hu
Jiao Luo
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Stroke
Coronary Heart Disease
Published in: European Journal of Medical Research / Issue 1/2024
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/s40001-024-01769-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A non-linear connection between the total cholesterol to high-density lipoprotein cholesterol ratio and stroke risk: a retrospective cohort study from the China Health and Retirement Longitudinal Study

Abstract

Objective

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2024

Human pan-cancer analysis of the predictive biomarker for the CDKN3

Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea

Changes of Mycobacterium tuberculosis specific antigen-stimulated CD27−CD38+IFN-γ+CD4+ T cells before and after anti-tuberculosis treatment

Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study

Identification of the prognostic value of LACTB2 and its correlation with immune infiltrates in ovarian cancer by integrated bioinformatics analyses

Associations between Life’s Essential 8 and post-stroke depression and all-cause mortality among US adults