Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events, thus a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in NAFLD patients.
Methods A total of 718 NAFLD participants from Multi-Ethnic Study of Atherosclerosis (MESA) without previous cardiovascular events were followed for the occurrence of incident ASCVD. NAFLD was defined using non-enhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistic and net reclassification improvement were used to compare incremental contributions of CAC score when added to the clinical risk factors.
Results In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR = 1.33, 95% CI = 1.22–1.44, p < 0.001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (p < 0.001) and the net reclassification index was 0.721 (95% CI = 0.494–0.977). In subgroup analyses, the incremental prognostic value of CAC score was more significant in NAFLD participants with low/borderline- (<7.5%) and intermediate- (7.5–20%) 10–year ASCVD risk score.
Conclusions The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with NAFLD, indicating a potential role for CAC screening in risk assessment.
Clinical Perspective With the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) individuals, there is an unmet need for a diagnostic approach to identify NAFLD individuals who are at higher risk for atherosclerotic cardiovascular disease (ASCVD) events. This study showed that higher coronary artery calcium (CAC) score was associated with ASCVD events during follow-up and improved the discriminative ability for future events in NAFLD individuals. Our study suggests routine CAC screening can be useful in assessing the risk of future ASCVD events. Future studies are needed to explore the therapeutic implications of CAC screening in this population.
Competing Interest Statement
KI is supported in parts by Takeda Science Foundation, Fukuda Foundation for Medical Technology, Wesco Scientific Promotion Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research. MB has received National Institutes of Health grant and research support from General Electric Company. All other authors have reported that they have no relationships relevant to the contents of this study to disclose.
Funding Statement
KI is supported in parts by Takeda Science Foundation, Fukuda Foundation for Medical Technology, Wesco Scientific Promotion Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research. MB has received National Institutes of Health grant and research support from General Electric Company. All other authors have reported that they have no relationships relevant to the contents of this study to disclose.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Not Applicable
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The MESA Steering Committee
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Footnotes
Email addresses Keishi Ichikawa: keishi.ichikawa{at}lundquist.org; Spencer Hansen: hanses6{at}uw.edu; Venkat S. Manubolu: venkat.manubolu{at}lundquist.org; Leili Pourafkari: leili.pourafkari{at}lundquist.org; Hooman Fazlalizadeh: hooman.fazlalizadeh{at}lundquist.org; Jairo Aldana-Bitar: jairo.aldana{at}lundquist.org; Lisa B VanWagner: lisa.vanwagner{at}utsouthwestern.edu; Srikanth Krishnan: srikanthkrishnan{at}mednet.ucla.edu; Matthew J. Budoff: mbudoff{at}lundquist.org
Data Availability
The MESA data are available to qualifying investigators directly from the study and also through dbGaP (http://www.ncbi.nlm.nih.gov/gap) and BioLINCC (https://biolincc.nhlbi.nih.gov).