Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Feb 13;23(1):69.
doi: 10.1186/s12933-024-02161-x.

Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts

Damien Denimal  1   2 , Maharajah Ponnaiah  3 , Anne-Caroline Jeannin  4   5 , Franck Phan  4   6   5 , Agnès Hartemann  6   5 , Samia Boussouar  3   7   8 , Etienne Charpentier  3   7   8 , Alban Redheuil  3   7   8 , Fabienne Foufelle  6 , Olivier Bourron  9   10   11
Affiliations

Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts

Damien Denimal et al. Cardiovasc Diabetol. .

Abstract

Background: Studies have demonstrated that coronary artery calcification on one hand and non-alcoholic fatty liver disease (NAFLD) on the other hand are strongly associated with cardiovascular events. However, it remains unclear whether NAFLD biomarkers could help estimate cardiovascular risk in individuals with type 2 diabetes (T2D). The primary objective of the present study was to investigate whether the biomarkers of NAFLD included in the FibroMax® panels are associated with the degree of coronary artery calcification in patients with T2D.

Methods: A total of 157 and 460 patients with T2D were included from the DIACART and ACCoDiab cohorts, respectively. The coronary artery calcium score (CACS) was measured in both cohorts using computed tomography. FibroMax® panels (i.e., SteatoTest®, FibroTest®, NashTest®, and ActiTest®) were determined from blood samples as scores and stages in the DIACART cohort and as stages in the ACCoDiab cohort.

Results: CACS significantly increased with the FibroTest® stages in both the DIACART and ACCoDiab cohorts (p-value for trend = 0.0009 and 0.0001, respectively). In DIACART, the FibroTest® score was positively correlated with CACS in univariate analysis (r = 0.293, p = 0.0002) and remained associated with CACS independently of the traditional cardiovascular risk factors included in the SCORE2-Diabetes model [β = 941 ± 425 (estimate ± standard error), p = 0.028]. In the ACCoDiab cohort, the FibroTest® F3-F4 stage was positively correlated with CACS in point-biserial analysis (rpbi = 0.104, p = 0.024) and remained associated with CACS after adjustment for the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (β = 234 ± 97, p = 0.016). Finally, the prediction of CACS was improved by adding FibroTest® to the traditional cardiovascular risk factors included in the SCORE2-Diabetes model (goodness-of-fit of prediction models multiplied by 4.1 and 6.7 in the DIACART and ACCoDiab cohorts, respectively). In contrast, no significant relationship was found between FibroMax® panels other than FibroTest® and CACS in either cohort.

Conclusions: FibroTest® is independently and positively associated with the degree of coronary artery calcification in patients with T2D, suggesting that FibroTest® could be a relevant biomarker of coronary calcification and cardiovascular risk.

Trial registration: ClinicalTrials.gov identifiers NCT02431234 and NCT03920683.

Keywords: Coronary artery calcium score; FibroMax®; FibroTest®; Type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Univariate correlations between coronary artery calcium score and clinical or biological characteristics shown as a heatmap. The figure reports the values of Pearson (r) or point-biserial (rpbi) correlation coefficients, as appropriate. Colored boxes indicate instances where the correlation coefficient retained significance following Benjamini–Hochberg correction to control the false discovery rate. CACS values were log10 transformed in the ACCoDiab cohort to improve normality. ALT alanine aminotransferase, AST aspartate aminotransferase, BMI body mass index, CACS coronary artery calcium score, CRP C-reactive protein, DBP diastolic blood pressure, eGFR estimated glomerular filtration rate, GGT gamma glutamyltransferase, HDL high-density lipoprotein, LDL low-density lipoprotein, N.A. not applicable, SBP systolic blood pressure, TyG index triglyceride-glucose index
Fig. 2
Fig. 2
Random forest variable importance plot for predicting CACS > 100 (A) and > 400 AU (B) in the DIACART cohort. Mean decrease accuracy indicates the importance of each variable in predicting elevated CACS. BMI body mass index, CACS coronary artery calcium score, LDL low-density lipoprotein, SBP systolic blood pressure
Fig. 3
Fig. 3
Bootstrapping ROC curves for predicting CACS > 400 AU in the DIACART (A) and ACCoDiab (B) cohorts. The blue zone represents the 95% confidence interval. AUROC area under the receiver operating characteristic curve, CACS coronary artery calcium score, CI confidence interval
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. The Emerging Risk Factors Collaboration Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–2222. doi: 10.1016/S0140-6736(10)60484-9. - DOI - PMC - PubMed
    1. Young LH, Wackers FJT, Chyun DA, Davey JA, Barrett EJ, Taillefer R, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301(15):1547–1555. doi: 10.1001/jama.2009.476. - DOI - PMC - PubMed
    1. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849–1861. doi: 10.1016/S0140-6736(05)67667-2. - DOI - PubMed
    1. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HAW, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364(9435):685–696. doi: 10.1016/S0140-6736(04)16895-5. - DOI - PubMed
    1. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, ADVANCE Collaborative Group et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–2572. doi: 10.1056/NEJMoa0802987. - DOI - PubMed

Publication types

MeSH terms

Associated data