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Ballestri et al. Metab Target Organ Damage 2023;3:1     https://dx.doi.org/10.20517/mtod.2022.23                                                                              Page 13 of 22



                          Table 4. Association between liver fibrosis assessed by elastographic techniques and cardiovascular outcomes/mortality

                          Author                                    F-up                                          CVD/mortality                                                      Clinical variables
                          (ref.)       Study characteristics        (year)   NAFLD (%) Fibrosis (%)               Outcomes (%)           Main findings at MVA                        for adjustment/covariates
                                       Cross-sectional

                          Friedrich-   505 consecutive patients     -        71.5% (CAP ≥  11.2% NAFLD with       70.5%                  High-grade CAD is independently predicted by   Sex, hypertension, and hip-waist-
                                   [94]
                          Rust et al.  undergoing elective coronary          234 dB/m)     advanced LF (VCTE      CHD 3 (stenosis  ≥     NAFLD but not NAFLD with advanced LF        ratio
                                       angiography for various                             LSM ≥ 7.9kPa)          75%)
                                       indications, 78.2% men, mean
                                       age 65.7 years
                                   [95]
                          Song et al.  120 consecutive patients with   -     67% in non-   2DSWE-SSI (kPa) 4.82  50%                     LSM (by 2D-SWE SSI), age, male sex, total   T2D, hypertension, smoking, HDL-C,
                                       suspect CHD submitted to              CHD,          ± 0.92 in non-CHD vs.   CHD                   cholesterol, and visceral fat thickness were   LDL-C, HbA1c,
                                       coronary angiography or CTA           95% in CHD    6.37 ± 1.39 in CHD                            determinants of CHD                         NAFLD
                                       (n.60 CHD and n.60 non-CHD)
                          Lombardi     394 T2D outpatients from 5   -        89% (US)      21% significant LF     19% CVD (prior MI      Significant LF was independently associated with  Age, sex, smoking, cardiometabolic
                              [96]
                          et al.       diabetes centers, 52% men,            72% (CAP ≥    (VCTE LSM ≥ 7.0/6.2    and/or IS), 33%        prior CVD (OR 3.3) and the presence of      risk factors, diabetes-related
                                       mean age 68 ± 10 years                248 dB/m)     kPa by M/XL probe)     microvascular          microvascular complications (OR 4.2), mainly   variables, severe US steatosis
                                                                                                                  complications          CKD (OR 3.6) and retinopathy (OR 3.7)
                          Mantovani    137 consecutive patients with   -     73.7% (US)    17.5% (VCTE LSM ≥ 7    20.4% CV               CV complications (previous CHD, IS, permanent  Age, sex, cardiometabolic risk
                              [97]
                          et al.       non-insulin-treated T2D,                            kPa) or 10.2%          complications (medical  AF) increased across LSM tertiles (from around   factors, diabetes-related variables,
                                       52.8% women, mean age 69.9                          (LSM ≥ 8.7 kPa)        history)               15% to 30%). At MVA, LSM tertile 3 remained   CRP levels
                                       ± 7 years                                           significant LF                                significantly associated with an increased risk of
                                                                                                                                         prevalent CKD but not with cardiovascular
                                                                                                                                         complications

                          Mikolasevic  442 outpatients with         -        84.2% (CAP  46.6% significant LF     25% macrovascular      Significant LF but not steatosis was        Age, sex, cardiometabolic risk
                              [98]
                          et al.       established T2D, 52.7%                ≥ 238 dB/m)   (VCTE LSM ≥ 7.0/6.2    complications (MI, IS)   independently associated with MI (OR 6.61),   factors, diabetes-related variables,
                                       women, median (IQR) age 62                          kPa by M/XL probe)     (at least one) (medical   peripheral polyneuropathy (OR 4.55), CKD (OR   CRP levels
                                       (53-68) years                                                              history)               4.54), and retinopathy (OR 1.81)
                                   [99]
                          Long et al.  3276 Framingham Heart Study  -        28.8%         8.8% significant LF    -                      LF was associated with multiple CVD risk factors  Age, sex, smoking, alcohol, physical
                                       adult participants, 54%               (CAP ≥ 290    (VCTE LSM ≥ 8.2 kPa)                          (obesity: OR 1.82; MetS: OR 1.49; diabetes: OR   activity, aminotransferases, and CAP
                                       women, mean age 54 ± 9 years          dB/m)                                                       2.67, hypertension: OR 1.52; low HDL-C: OR
                                                                                                                                         1.47)
                          Pennisi      542 subjects from a          -        31.7% (CAP >  4.8% severe LF (VCTE   22.2% high-risk ASCVD  Both steatosis (OR 1.62, 95%CI: 1.13-2.33) and   Age, BMI
                              [100]
                          et al.       community-based study, 59%            288 dB/m)     LSM ≥ 9.6/9.3 kPa by   score                  severity of
                                       women, mean age of 58 ± 10                          M/XL probe)                                   fibrosis (OR 1.67, 95%CI: 1.18-2.36) were
                                       years                                                                                             independently associated with higher ASCVD
                                   [101]
                          Park et al.  105 patients with NAFLD, 52%  -       100% (MRI-    35.2% significant LF   49.5% CAC > 0          LS was independently associated with the    Age, sex, smoking, total cholesterol,
                                       women, mean age of 55 years           PDFF ≥ 5%)    (MRE ≥ 2.97 kPa)                              presence of CAC in a sex and age-adjusted   HDL-C, SBP, medication for
                                                                                                                                         model (OR 2.23; 95%CI: 1.31-4.34) as well as in   hypertension, T2D, and history of
                                                                                                                                         an FRS-adjusted model (OR 2.16, 95%CI: 1.29-  CVD
                                                                                                                                         4.09)
                          Ciardullo    2734 subjects from NHANES    -        48.6% (CAP  9.7% significant LF      12%                    Neither steatosis nor significant fibrosis was   Age, sex, race-ethnicity, BMI, T2D,
                              [102]
                          et al.       2017-2018, 53% women, mean            ≥ 274 dB/m) (VCTE LSM ≥ 8 kPa)       (9% CHD)               independently associated with CVD           smoking, CKD
                                       age 59 years
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