{
  "abstract": "Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with elevated risk of incident cardiovascular disease (CVD) 1, the leading cause of mortality in people with MASLD2. However, it is unclear whether liver disease is an independent risk factor (RF) for CVD or whether cardiometabolic RFs common to MASLD and CVD fully explain this risk. Equipoise exists in the literature, with studies conducted in liver centres suggesting MASLD confers higher CVD risk regardless of metabolic RFs3, but large epidemiological studies suggesting the converse.4 Mendelian epidemiology cannot resolve this discrepancy. A systematic review and meta-analysis was conducted to delineate the relationship between MASLD and CVD.Methods Medline, Embase, and Cochrane databases were interrogated from database inception to December 2024. Exclusion criteria incorporated: method of MASLD diagnosis (imaging, elastography or biopsy), alcohol intake (<30g/20g daily for males/females), pre-existing CVD, and follow-up period. Cross-sectional studies were excluded. The primary outcome was overall incident CVD. Secondary endpoints were fatal/non-fatal CVD events (CVEs), atrial fibrillation (AF), acute coronary syndrome (ACS), CVD mortality, and stroke. Raw outcome data were extracted from studies and meta-regression analyses performed using random-effects models to derive pooled odds ratios (ORs) with 95% confidence intervals (CIs).Results Nineteen longitudinal cohort studies reporting cardiovascular endpoints were identified, with aggregate data on 1,250,661 individuals (median follow-up 8.4 years [IQR 5.7–10.0]). MASLD was associated with increased risk of any incident CVD (OR 1.90 [1.27–2.84]; p=0.004). After adjustment for age, sex and cardiometabolic RFs, this association remained but with CIs spanning 1.0 (OR 1.62 [0.06–3.18]; p=0.043). Further adjustment for follow-up duration yielded similar results (OR 1.83 [0.03–3.63; p=0.048). MASLD was associated with CVEs (OR 1.52 [0.12–2.91]; p=0.037) and CVD mortality (OR 1.51 [0.03–2.99]; p=0.049) in covariate-adjusted models, but CIs again spanned 1.0. MASLD was associated with elevated incidence of ACS, AF, and stroke, but eligible study numbers precluded full adjustment for all cardiometabolic RFs.Abstract P3 Figure 1Forest plot depicting the risk of any incident CVD in the MASLD group as compared to non-MASLD controls. Unadjusted odds ratios (ORs) are given for each of the individual studies (dark blue squares) included in the meta-analysis (n=16), with the pooled OR presented at the base of the plot (purple diamond) alongside heterogeneity statisticsConclusion MASLD is associated with a nearly twofold increase in risk of incident CVD. After adjusting for common cardiometabolic RFs, this association is equivocal due to the relatively wide CIs for ORs calculated in fully adjusted models. Thus, these data demonstrate no irrefutable evidence that there exists an association between MASLD and CVD independent of common cardiometabolic RFs. As such, further high-quality studies are needed to resolve the discrepancy between hepatological and epidemiological studies. Regardless, the association between MASLD and CVD highlights the importance of effective CVD risk management for people with MASLDP10References Targher G, Byrne CD, Tilg H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2020;69:1691–1705.Mellemkjær A, Kjaer MB, Haldrup D, et al. Management of cardiovascular risk in patients with metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med. 2024;122:28–34. Fracanzani AL, Tiraboschi S, Pisano G, et al. Progression of carotid vascular damage and cardiovascular events in non-alcoholic fatty liver disease patients compared to the general population during 10 years of follow-up. Atherosclerosis. 2016;246:208–213.Alexander M, Loomis AK, van der Lei J, et al. Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ. 2019;367:l5367.",
  "authors": [
    {
      "affiliations": [
        "Department of Hepatology, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK",
        "Institute for Liver and Digestive Health, Division of Medicine, UCL, London, UK"
      ],
      "name": "Alexander Hung"
    },
    {
      "affiliations": [
        "Odense Liver Research Centre, Odense University Hospital, Jacob Benignus Winsløws Vej 4, 5000 Odense C, Odense, Denmark"
      ],
      "name": "Ida Katharina Ziegler Spedtsberg"
    },
    {
      "affiliations": [
        "Institute for Liver and Digestive Health, Division of Medicine, UCL, London, UK"
      ],
      "name": "David Etoori"
    },
    {
      "affiliations": [
        "Odense Liver Research Centre, Odense University Hospital, Jacob Benignus Winsløws Vej 4, 5000 Odense C, Odense, Denmark"
      ],
      "name": "Maja Thiele"
    },
    {
      "affiliations": [
        "Department of Hepatology, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK",
        "Institute for Liver and Digestive Health, Division of Medicine, UCL, London, UK"
      ],
      "name": "William Rosenberg"
    }
  ],
  "title": "P3 A systematic review and meta-analysis: does metabolic dysfunction-associated steatotic liver disease increase the risk of cardiovascular disease above and beyond shared risk factors?",
  "uid": "6530ce55-ba1e-5c39-9042-6764d89424b4"
}