Skip to main content

Advertisement

SpringerLink
Log in

Early Predictors of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease: Non-obese Versus Obese Patients

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) is regarded as a risk factor of cardiovascular disease (CVD). However, the association between non-obese NAFLD and CVD has not been well established.

Aim

We aimed to compare the CVD risk between non-obese and obese NAFLD patients, and explored the factors associated with subclinical atherosclerosis.

Method

Consecutive NAFLD patients estimated by magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) were recruited. Liver fat content (LFC) and liver stiffness were measured with MRI-PDFF and shear wave elastography, respectively. CVD risk was estimated by atherosclerosis index (AI), carotid intima-media thickness, carotid plaque, and Framingham risk score (FRS).

Results

This study included 543 NAFLD patients. The presence of carotid intima-media thickening and carotid plaque, FRS, and AI were comparable between non-obese and obese patients. Age increased per 10 years (OR 9.68; P < 0.001) and liver fibrosis (liver stiffness > 6.1 kPa, OR 4.42; P = 0.004) were significant factors associated with carotid intima-media thickening in non-obese patients, while age increased per 10 years (OR 2.02; P < 0.001), liver fibrosis (OR 2.18; P = 0.039), and LFC > 10% (OR 2.29; P = 0.021) were independent predictors in obese patients. Only elevated triglyceride was significantly associated with carotid plaque in non-obese patients (OR 2.42; P = 0.033), while age increased per 10 years (OR 1.77; P = 0.002) and LFC > 10% (OR 2.83; P = 0.019) were significant predictors in obese patients.

Conclusions

Liver stiffness and age were strongly predictive of subclinical atherosclerosis in all NAFLD, while LFC was an additional predictor in obese NAFLD patients. Our findings highlight that early CVD screening strategy should be established for NAFLD patients according to different BMIs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.

    PubMed  Google Scholar 

  2. Lonardo A, Nascimbeni F, Mantovani A, Targher G. Hypertension, diabetes, atherosclerosis and NASH: Cause or consequence? J Hepatol. 2018;68:335–352.

    PubMed  Google Scholar 

  3. Italian Association for the Study of the Liver (AISF). AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions. Dig Liver Dis. 2017;49:471–483.

    Google Scholar 

  4. Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol. 2016;65:589–600.

    PubMed  Google Scholar 

  5. Oni ET, Agatston AS, Blaha MJ, et al. A systematic review: Burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis. 2013;230:258–267.

    CAS  PubMed  Google Scholar 

  6. Jaruvongvanich V, Wirunsawanya K, Sanguankeo A, Upala S. Nonalcoholic fatty liver disease is associated with coronary artery calcification: A systematic review and meta-analysis. Dig Liver Dis. 2016;48:1410–1417.

    PubMed  Google Scholar 

  7. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation. 2016;133:e38–360.

    PubMed  Google Scholar 

  8. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010;56:e50–103.

    PubMed  Google Scholar 

  9. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363:1341–1350.

    CAS  PubMed  Google Scholar 

  10. Ghouri N, Preiss D, Sattar N. Liver enzymes, nonalcoholic fatty liver disease, and incident cardiovascular disease: A narrative review and clinical perspective of prospective data. Hepatology. 2010;52:1156–1161.

    PubMed  Google Scholar 

  11. Leung JC, Loong TC, Wei JL, et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology. 2017;65:54–64.

    CAS  PubMed  Google Scholar 

  12. Wei JL, Leung JC, Loong TC, et al. Prevalence and severity of non-alcoholic fatty liver disease in non-obese patients: A population study using proton-magnetic resonance spectroscopy. Am J Gastroenterol. 2015;110:1306–1314.

    CAS  PubMed  Google Scholar 

  13. Sookoian S, Pirola CJ. Systematic review with meta-analysis: Risk factors for non-alcoholic fatty liver disease suggest a shared altered metabolic and cardiovascular profile between lean and obese patients. Aliment Pharmacol Ther. 2017;46:85–95.

    CAS  PubMed  Google Scholar 

  14. Sookoian S, Pirola CJ. Systematic review with meta-analysis: The significance of histological disease severity in lean patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2018;47:16–25.

    CAS  PubMed  Google Scholar 

  15. Yoshitaka H, Hamaguchi M, Kojima T, Fukuda T, Ohbora A, Fukui M. Non-overweight nonalcoholic fatty liver disease and incident cardiovascular disease: A post hoc analysis of a cohort study. Med (Baltim.). 2017;96:e6712.

    CAS  Google Scholar 

  16. Wong VW, Wong GL, Yeung DK, et al. Fatty pancreas, insulin resistance, and beta-cell function: A population study using fat-water magnetic resonance imaging. Am J Gastroenterol.. 2014;109:589–597.

    CAS  PubMed  Google Scholar 

  17. Heni M, Machann J, Staiger H, et al. Pancreatic fat is negatively associated with insulin secretion in individuals with impaired fasting glucose and/or impaired glucose tolerance: A nuclear magnetic resonance study. Diabetes Metab Res Rev.. 2010;26:200–205.

    CAS  PubMed  Google Scholar 

  18. Mathur A, Marine M, Lu D, et al. Nonalcoholic fatty pancreas disease. HPB. 2007;9:312–328.

    PubMed  PubMed Central  Google Scholar 

  19. Xiao G, Zhu S, Xiao X, Yan L, Yang J, Wu G. Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Hepatology. 2017;66:1486–1501.

    CAS  PubMed  Google Scholar 

  20. Sung KC, Ryan MC, Wilson AM. The severity of nonalcoholic fatty liver disease is associated with increased cardiovascular risk in a large cohort of non-obese Asian subjects. Atherosclerosis. 2009;203:581–586.

    CAS  PubMed  Google Scholar 

  21. Lee SH, Yun SJ, Kim DH, Jo HH, Park YS. Severity of Nonalcoholic Fatty Liver Disease on Sonography and Risk of Coronary Heart Disease. J Clin Ultrasound. 2017;45:391–399.

    PubMed  Google Scholar 

  22. Li R, Liao XH, Ye JZ, et al. Association of keratin 8/18 variants with non-alcoholic fatty liver disease and insulin resistance in Chinese patients: A case-control study. World J Gastroenterol. 2017;23:4047–4053.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Dong Z, Luo Y, Zhang Z, et al. MR quantification of total liver fat in patients with impaired glucose tolerance and healthy subjects. PLoS One. 2014;9:e111283.

    PubMed  PubMed Central  Google Scholar 

  24. Ye J, Hu X, Wu T, et al. Insulin resistance exhibits varied metabolic abnormalities in nonalcoholic fatty liver disease, chronic hepatitis B and the combination of the two: A cross-sectional study. Diabetol Metab Syndr. 2019;11:45.

    PubMed  PubMed Central  Google Scholar 

  25. Caussy C, Alquiraish MH, Nguyen P, et al. Optimal threshold of controlled attenuation parameter with MRI-PDFF as the gold standard for the detection of hepatic steatosis. Hepatology. 2018;67:1348–1359.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Lin SC, Heba E, Wolfson T, et al. Noninvasive Diagnosis of Nonalcoholic Fatty Liver Disease and Quantification of Liver Fat Using a New Quantitative Ultrasound Technique. Clin Gastroenterol Hepatol. 2015;13:1337–1345.

    PubMed  Google Scholar 

  27. Idilman IS, Keskin O, Celik A, et al. A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease. Acta Radiol. 2016;57:271–278.

    PubMed  Google Scholar 

  28. Jayakumar S, Middleton MS, Lawitz EJ, et al. Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib. J Hepatol. 2019;70:133–141.

    PubMed  Google Scholar 

  29. Shao C, Ye J, Li F, Feng S, Wang W, Zhong B. Different predictors of steatosis and fibrosis severity among lean, overweight and obese patients with nonalcoholic fatty liver disease. Dig Liver Dis. 2019; pii: S1590-8658(19)30105-301057.

  30. Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012;34:290–296.

    PubMed  PubMed Central  Google Scholar 

  31. Wang C, Lv G, Zang D. Risk factors of carotid plaque and carotid common artery intima- media thickening in a high- stroke- risk population. Brain Behav. 2017;7:e00847.

    PubMed  PubMed Central  Google Scholar 

  32. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837–1847.

    CAS  PubMed  Google Scholar 

  33. Liu J, Hong Y, D’Agostino RB Sr, et al. Predictive value for the Chinese population of the Framingham CHD risk assessment tool compared with the Chinese Multi-Provincial Cohort Study. JAMA. 2004;291:2591–2599.

    CAS  PubMed  Google Scholar 

  34. Targher G, Bonapace S, Byrne CD. Does high LDL-cholesterol cause cardiovascular disease? Expert Rev Clin Pharmacol. 2019;12:91.

    CAS  PubMed  Google Scholar 

  35. Ravnskov U, De Lorgeril M, Diamond DM, et al. Response letter to ‘does high LDL-cholesterol cause cardiovascular disease?’. Expert Rev Clin Pharmacol. 2019;12:93–94.

    CAS  PubMed  Google Scholar 

  36. Li X, Xia M, Ma H, et al. Liver fat content is associated with increased carotid atherosclerosis in a Chinese middle-aged and elderly population: The Shanghai Changfeng study. Atherosclerosis. 2012;224:480–485.

    CAS  PubMed  Google Scholar 

  37. Dick TJ, Lesser IA, Leipsic JA, Mancini GB, Lear SA. The effect of obesity on the association between liver fat and carotid atherosclerosis in a multi-ethnic cohort. Atherosclerosis. 2013;226:208–213.

    CAS  PubMed  Google Scholar 

  38. Day CP. Non-alcoholic steatohepatitis (NASH): Where are we now and where are we going? Gut. 2002;50:585–588.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. James OF, Day CP. Non-alcoholic steatohepatitis (NASH): A disease of emerging identity and importance. J Hepatol. 1998;29:495–501.

    CAS  PubMed  Google Scholar 

  40. Kawaguchi T, Inokuchi T, Honma T, et al. Factors associated with advanced hepatic fibrosis in patients with various internal diseases: A multicenter community-based survey. Hepatol Res. 2018;48:882–892.

    CAS  PubMed  Google Scholar 

  41. Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology. 2013;57:1357–1365.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a sexual dimorphic disease: Role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent Cardiovascular Risk. Adv Ther. 2017;34:1291–1326.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We are grateful to Professor Aihua Lin in The Public Health School of Sun Yat-sen University for his assistance in statistical analysis of this study.

Funding

This study is funded by Chinese Foundation for Hepatitis Prevention and Control (TQGB20140083), Guangdong Science and Technology Department (2013B021800290, 2014A020212118, 2017A020215015), National Natural Science Foundation of China (81870404, 81670518, 81170392), and Medical Scientific Research Foundation of Guangdong Province (A2019496).

Author information

Author notes

  1. Congxiang Shao and Junzhao Ye have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China

    Congxiang Shao, Junzhao Ye, Fuxi Li, Yansong Lin, Tingfeng Wu & Bihui Zhong

  2. Department of Medical Ultrasonics of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China

    Wei Wang

  3. Department of Radiology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, China

    Shiting Feng

Authors
  1. Congxiang Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Junzhao Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fuxi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yansong Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tingfeng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shiting Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bihui Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bihui Zhong.

Ethics declarations

Conflict of interest

They authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shao, C., Ye, J., Li, F. et al. Early Predictors of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease: Non-obese Versus Obese Patients. Dig Dis Sci 65, 1850–1860 (2020). https://doi.org/10.1007/s10620-019-05926-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-019-05926-7

Keywords

Search

Navigation