Table 2.
Summary of studies that evaluated the association between NAFLD and subclinical CAD.
| Author, Year, Ref. | Country | Study Type | NAFLD Diagnosis |
CAD Diagnosis | Patients Characteristics | Impact of NAFLD on CAD/Results |
|---|---|---|---|---|---|---|
| Carter et al., 2022 [61] | Scotland | Post-hoc analysis of Prospective Scottish Computed Tomography of HEART trial | CT | CT (CACS) | 1726 155 hepatic steatosis |
Hepatic steatosis associated with increased prevalence of CAD No difference in MI in those with and without steatosis (1.9% vs. 2.4%, p = 0.92) |
| Ichikawa et al., 2022 [62] | Japan | Prospective | CT | CCTA | 1148 247 hepatic steatosis 977 suspected CAD |
High association between hepatic steatosis and increased risk of MACE in suspected stable CAD |
| Wang X et al., 2022 [63] | China | Retrospective | FIB-4 score | Coronary angiography Gensini score |
342 105 NAFLD |
NAFLD severity—associated with CAS High FIB-4 score—high CAC |
| Chen et al., 2021 [25] | Taiwan | Prospective | US | CACS (CT) | 545 437 NAFLD 242 CAC |
1.36-fold greater risk of developing CAC in patients with different severity of NAFLD vs. those without NAFLD (OR: 1.36, 95% CI: 1.07–1.77, p = 0.016) |
| Ichikawa et al., 2021 [64] | Japan | Prospective | CT | CACS FRS |
529 T2DM | NAFLD, CACS, and FRS-associated with CVE (HR and 95% CI: 5.43, 2.82–10.44, p < 0.001; 1.56, 1.32–1.86, p < 0.001; 1.23, 1.08–1.39, p = 0.001, respectively) |
| Meyersohn NM et al., 2021 [33] | North America | Nested cohort study | CT | CCTA | 3756 | Hepatic steatosis associated with MACE (4.4% vs 2.6% in those without steatosis) indepently of other CV RF/extent of CAD |
| Saraya et al., 2021 [65] | Egypt | Prospective | CT | CCTA | 800 440 CAD |
NAFLD and high-risk plaque features: Napkin ring sign, Positive remodeling, Low HU, and Spotty calcium (OR: 7.88, 95% CI (4.39–14.12), p < 0.001, OR: 5.84, 95% (3.85–8.85), p < 0.001, OR: 7.25, 95% CI (3.31–15.90), p < 0.001 and OR: 6.66, 95% CI (3.75–11.82), p < 0.001) |
| Bae YS et al., 2020 [66] | South Korea | Retrospective | US NFS, FIB-4 index |
CCTA | 3693 244 CAS 1588 NAFLD |
NAFLD associated with CAS (≥50% stenosis) stronger in women, but absolute risk higher in men |
| Ismael H et al., 2020 [19] | Egypt | Prospective | FibroScan | Coronary angiography Gensini score |
100 42 NAFLD |
S2-S3 NAFLD and CVD (OR: 24, 95% CI: 17–31) |
| Koo BK et al., 2020 [67] | USA | Retrospective | CT | CCTA | 719 NAFLD 443 CHD |
NAFLD significantly associated with coronary calcification (OR: 1.28; 95% CI: 1.07–1.53) |
| Chang Y et al., 2019 [68] | South Korea | Retrospective | US FIB-4 score, APRI |
CACS | 105328 34382 NAFLD 5249 CAD |
NAFLD, AFLD associated with CAC |
| Oni E et al., 2019 [69] | USA | Retrospective | CT | CACS CIMT |
4123 729 NAFLD 386 CHD |
NAFLD—independently associated with CAC> 0 and CIMT > 1 mm |
| Pais et al., 2019 [70] | France | Retrospective | FLI | FRS CACS (CT) |
2617 930 NAFLD |
High prevalence of CAC (183 ± 425 vs 117 ± 288, p < 0.001) in those with hepatic steatosis vs without |
| Park HE et al., 2019 [71] | South Korea | Retrospective | CAP | CCTA Coronary plaque >1.5 mm2 |
330 NAFLD 186 CAD 147 NCP |
CAP-defined NAFLD significantly associated with NCP, independent with cardiometabolic RF (adjusted OR: 3.528, 95% CI: 1.463–8.511, p = 0.005), no significant correlation with CP (p = 0.171) |
| Sinn DH et al., 2019 [51] | South Korea | Retrospective | US NFS |
Hospitalization for MI | 111492 37263 NAFLD 183 MI |
NAFLD associated with increased incidence of MI independent of RF |
| Gummesson et al., 2018 [72] | Sweden | Retrospective | CT | CACS (CT) | 106 NAFLD 73 CHD |
NAFLD and CACS association in subjects with few other metabolic risk factors (60% subjects of the total cohort) with 0 or 1 of the 7 predefined RF; OR: 5.94, 95% CI: 2.13 ± 16.6 |
| Lee SB et al., 2018 [36] | South Korea | Retrospective | US, FLI, NFS | CCTA | 5121 38.6% NAFLD |
NAFLD associated with NCP; significant association of FLI ≥30 with NCP (1.37, 95% CI: 1.14–1.65, p = 0.001) and NFS ≥ −1.455 with NCP (1.20, 95% CI: 1.08–1.42, p = 0.030) |
| Wu R et al., 2017 [73] | China | Retrospective | US | CACS (CT) | 2345 1272 NAFLD 237 CHD |
NAFLD—significantly associated with the development of coronary artery calcifications (adjusted OR: 1.348, 95% CI: 1.030–1.765) |
| Jacobs K et al., 2016 [74] | USA | Retrospective | US | CACS (CT) (VAT) |
250 71 NAFLD 52 CHD |
NAFLD and CAC—no clear association Increased CAC, VAT with age, but no increased NAFLD |
| Kim JB et al., 2016 [75] | South Korea | Retrospective | US | CT EFV | 1472 677 NAFLD 147 CHD |
Higher EFV levels and NAFLD prevalence in individuals with MS than those without MS (81.0 cm3 vs 57.3 cm3, p < 0.001; 75.6% vs 36.5%, p < 0.001) |
| Park HE et al., 2016 [76] | South Korea | Retrospective | US | CCTA (CAC) |
1732 846 NAFLD 413 CAC |
NAFLD associated with CAC development independent of other metabolic RF in those without CAC at baseline, but not with CAC progression in those with CAC at baseline DM risk factor for CAC progression |
| Al Rifai M et al., 2015 [18] | USA | Retrospective | CT | CACS (CT) | 3976 670 NAFLD 362 CAC |
NAFLD—associated with inflammation and CAC |
| Kim MK et al., 2015 [77] | South Korea | Retrospective | US | CACS (CT) | 919 Postmenopausal women 294 NAFLD 81 CAC |
OR for prevalence of CAC: no NAFLD, 1.0; mild NAFLD, 1.34 (95% CI: 0.92–2.16); moderate to severe NAFLD, 1.83 (95% CI: 1.06–3.16) NAFLD—not independent factor for CAD in postmenopausal women |
| Kang MK et al., 2015 [78] | South Korea | Retrospective | US | CT | 346 NAFLD 173 CHD |
NAFLD—associated with coronary plaques OR: 1.48; 95% CI: 1.05–2.08, p = 0.025 |
| Lee M-K et al., 2015 [79] | South Korea | Retrospective | US | CACS (CT) | 10063 NAFLD 1843 CAD 340 CACS>100 |
NAFLD relatively increased risk for CAC vs non-NAFLD; higher OR than that in subjects with abdominal obesity [1.360; 95% CI: 1.253–1.476) vs (1.220; 95% CI: 1.122–1.326)] |
| Efe D et al., 2014 [80] | Turkey | Retrospective | CT | CT | 372 204 NAFLD 107 CAD |
Higher prevalence of CAD in NAFLD than non-NAFLD |
| VanWagner et al., 2014 [81] | USA | Retrospective | CT | CACS (CT) | 2424 232 NAFLD 88 CAD |
Increased CAC (37.9% vs 26.0%, p < 0.001) in NAFLD cases Obesity attenuates NAFLD-ATS relation |
| Chhabra et al., 2013 [82] | USA | Retrospective | CT | CACS (CT) | 400 43 NAFLD 15 CAD |
Hepatic steatosis—independent predictor of CACS |
| Juarez-Rojas et al., 2013 [83] | Mexico | Retrospective | CT | CACS (CT) | 765 163 NAFLD 64 CHD |
Fatty liver associated with T2DM and MS |
| Khashper et al., 2013 [84] | Israel | Retrospective | CT | CACS (CT) | 318 93 NAFLD 70 CAD |
Increased VAT in patients with coronary artery plaques, p < 0.001 |
| Sung KC et al., 2013 [85] | South Korea | Retrospective | US | CACS (CT) | 7371 39.5% NAFLD 4.5% CACS > 0 |
Steatosis and baPWV are independently associated with the presence of CAC |
| Arslan et al., 2012 [86] | Turkey | Prospective | US | Coronary angiography | 151 98 NAFLD |
64.9% patients with NAFLD NAFLD associated with poor coronary collateral development |
| Kim D et al., 2012 [26] | South Korea | Prospective | US | CACS (CT) | 4023 1617 NAFLD 649 CAD |
High CACS significantly associated with the presence of NAFLD (OR: 1.28, 95% CI: 1.04–1.59, p = 0.023) independent of visceral adiposity |
| Sung KC et al., 2012 [87] | South Korea | Retrospective | US | CACS (CT) | 3784 NAFLD 510 CAD |
Steatosis (OR: 1.21, 95% CI: 1.01–1.45, p = 0.04) and HOMA-IR (1.10; 1.02–1.18, p = 0.02) associated with CACS > 0 |
| Agarwal et al., 2011 [88] | India | Prospective | US | CIMT | 124 T2DM 71 NAFLD 43 CAD |
60.5% CAD of the patients with NAFLD; 45.2% of the ones without NAFLD NAFLD—risk marker for CAD in T2DM |
Abbreviations: NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; CAD, coronary artery disease; CHD, coronary heart disease; CCTA, coronary computed tomography angiography; CAC, coronary artery calcification; CACS, coronary artery calcium score; CT, computed tomography; FLI, Fatty Liver Index; NFS, NAFLD Fibrosis Score; US, ultrasonography; ECG, electrocardiogram; T2DM, type 2 diabetes; MS, metabolic syndrome; CP, calcified plaques; NCP, non-calcified plaques; ATS, atherosclerosis; CAS, coronary artery stenosis; CV, cardiovascular; CVE, cardiovascular events; CVD, cardiovascular disease; MI, myocardial infarction; RF, risk factor; LSM, liver stiffness measurement; APRI, AST to platelet ratio index; baPWV, brachial-ankle pulse wave velocity; CIMT, carotid intima-media tissue; VAT, visceral abdominal adipose tissue; EFV, epicardial fat volume; FRS, Framingham score; VAT, visceral adipose tissue; CRP, C-reactive protein; HOMA-IR, homeostatic model assessment for insulin resistance; HR, hazard ratio; OR, odd ratio; CI, confidence interval.