MASLD is a rapidly growing pandemic that is expected to affect 40% of the adult population worldwide by 2050 (16). It has been associated with a 2–3 times increased risk of cardiovascular disease mortality, irrespective of other common cardiovascular risk factors including hypertension, dyslipidemia, type 2 diabetes, and gender (2). Studies have suggested that MASLD independently increases the risk of developing critical coronary stenosis and coronary plaques, thus necessitating coronary interventions such as PCI or CABG (17). Although evidence suggests MASLD increases the risk of adverse cardiovascular events such as acute coronary syndrome and ischemic strokes (2, 8–15), not many studies have evaluated the impact of MASLD on adverse PCI outcomes. Because MASLD has been shown to increase the risk of adverse cardiovascular events and is correlated to the severity of coronary artery disease, it is not unexpected that patients living with MASLD have poorer outcomes.

Our systematic review yielded a total of five studies that have investigated the impact of MASLD on PCI in-hospital outcomes and one on CABG outcomes since 2015. One study found MASLD to be independently associated with higher rates of in-hospital mortality following PCI. A 2012 prospective observational study by Keskin et al. (18) found the severity of MASLD (grades 0 through 3) to have increasing rates of in-hospital mortality following PCI (grade 0, 1, 2, and 3 MASLD were 4.7%, 8.3%, 11.3%, and 33.9%, respectively). The authors also concluded that patients with grade 3 MASLD were four times more likely to die in the hospital after PCI compared with those without MASLD (HR 4.0, 95% CI 3.0–8.1). Conversely, a retrospective National Inpatient Sample cross-sectional study by Ali et al. (1.8% vs. 2.2%, p = 0.757) found that comorbid MASLD to not affect in-hospital mortality compared with those without MASLD (4), and a prospective cohort study by Wong et al. (19) even found those with MASLD to have lower rates of mortality (HR 0.53, 95% CI 0.36–0.78, p = 0.001) at 6-year follow-up after discharge. One prospective study by Wang et al. investigated mortality rates following CABG and found no difference in mortality rates between those with and without MASLD (3.2% vs. 0%, p = 0.356) (20).

Additionally, conference abstracts have explored PCI mortality outcomes in patients with MASDLD. An NIS analysis abstract by Aboursheid et al. (21) compared the clinical characteristics and outcomes of patients with MASLD undergoing PCI and found MASLD to be independently associated with an increased risk of in-hospital mortality compared with those without MASLD [11% vs. 2.2%, OR 4.9 (95% CI 4.7–5.2), p < 0.001], after controlling for age, sex, race, Elixhauser comorbidity index, hypertension, chronic obstructive pulmonary disease, chronic kidney disease (CKD), and history of stroke. Another NIS analysis by Khokhlov et al. (22) also supports the association between MASLD and increased in-hospital mortality [8.9% vs. 1.9%, OR 4.91 (95% CI 4.63–5.21), p < 0.001] compared with those without MASLD after comparing for age, sex, race, Charlson comorbidity index, obesity, atrial fibrillation, dyslipidemia, hypertension, peripheral vascular disease, heart failure, CKD, and history of stroke.

Four of our included studies evaluated the effects of MASLD on major adverse cardiovascular events (MACE) following coronary revascularization. A prospective cohort study by Emre et al. (23) found that higher degrees of comorbid MASLD, especially fatty liver disease (FLD) scores ≥3, increase the risk of in-hospital MACE following PCI compared with those without MASLD (31% vs. 8%, p < 0.0001). Furthermore, FLD scores ≥3 were more likely to have absent myocardial perfusion (myocardial blush grade 0/1, 37% vs. 12%, p < 0.0001) and absent ST-segment resolution following PCI (27% vs. 9%, p = 0.001). Another prospective observational study by Liu et al. found that higher degrees of MASLD were associated with higher rates of long-term MACE following PCI, with an average follow-up of 5.0 ± 1.6 years, compared with lesser degrees of MASLD or no MASLD (24). Conversely, the NIS analysis by Ali et al. (25) demonstrated no difference in MACE rate following PCI between those with MASLD and those without (2.7% vs. 2.9%, p = 0.69). Wang et al. also found no statistically significant difference in MACE between those with and without MASLD following CABG (19.4% vs. 13.5%, p = 0.29) (20).

While the studies identified by our literature search did not address other adverse outcomes related to coronary revascularizations, such as cardiogenic shock, cardiac arrest, in-stent thrombosis, gastrointestinal bleeding, or invasive mechanical ventilation, studies published as conference abstracts have investigated these clinical questions. The unadjusted findings from the NIS analysis abstract by Aboursheid et al. (21) suggest that MASLD is associated with higher percentages of in-hospital cardiogenic shock [7.1% vs. 0.9%, OR 5.1 (95% CI 4.8–5.4), p < 0.001], cardiac arrest [4% vs. 0.8%, OR 3.5 (95% CI 3.2–3.8), p < 0.001], in-stent thrombosis [0.26% vs. 0.20%, OR 1.3 (95% CI 1.05–1.8), p = 0.02], gastrointestinal bleeding [10.7% vs. 5%, OR 2.2 (95% CI 2.1–2.3), p < 0.001], and invasive mechanical ventilation [9.5% vs. 2.3%, OR 3.2 (95% CI 3.0–3.4), p < 0.001] following PCI, compared with those without MASLD. The NIS analysis abstract by Khokhlov et al. (22) supports the association between MASLD and higher percentages of in-hospital cardiogenic shock [5.4% vs. 0.9%, OR 5.61 (95% CI 5.21–6.05), p < 0.001], cardiac arrest [3.6% vs. 0.8%, OR 4.08 (95% CI 3.74–4.45), p < 0.001], gastrointestinal bleeding [10.3% vs. 4.5%, OR 2.41 (95% CI 2.29–2.54), p < 0.001], and invasive mechanical ventilation [7.8% vs. 2.3%, OR 3.33 (95% CI 3.13–3.54), p < 0.001] following PCI, compared with those without MASLD. Finally, a nested case–control study by Lee et al. (26) found that higher fatty liver disease fibrosis scores (NFS), specifically >0.67, were more prevalent in patients with left ventricle dysfunction (left ventricular ejection fraction <40% at PCI) compared with those without (81.0% vs. 33.6%, p < 0.001). Baseline higher NFS was significantly associated with LV dysfunction (adjusted OR 1.86, 95% CI 1.36–2.55, p < 0.001), and baseline higher NFS and persistent higher NFS at 1 year after PCI were independent predictor of a 5-year CV death, after adjustment for LVEF (adjusted HR 1.42, 95% CI 1.03–1.95, p = 0.023; adjusted HR 1.52, 95% CI 1.08–2.64, p = 0.033).

MASLD and CAD, though traditionally seen as separate conditions, share core pathophysiological mechanisms rooted in systemic metabolic dysregulation, including insulin resistance, lipotoxicity, chronic inflammation, and atherogenic dyslipidemia. Insulin resistance plays a central role by increasing free fatty acid mobilization and impairing fatty acid oxidation, leading to lipid accumulation in skeletal muscle and liver, which exacerbates hepatic insulin resistance and promotes de novo lipogenesis. This cascade leads to the accumulation of toxic lipid species, mitochondrial dysfunction, oxidative stress, and inflammation, ultimately resulting in hepatocyte injury, fibrosis, and organ failure. Adipocyte dysfunction further contributes by flooding multiple organs with fatty acids and fostering a proinflammatory environment marked by elevated cytokines and altered adipokine levels. These processes impair insulin signaling in skeletal muscle, reduce glucose uptake, and perpetuate hyperglycemia and hepatic lipid overload. Chronic hepatic lipogenesis, driven by excess substrate availability and mitochondrial citrate accumulation, contributes to both MASLD and CAD, with key enzymes in this pathway emerging as therapeutic targets. The extent of inflammation, as reflected in markers such as the neutrophil-to-lymphocyte ratio and mTOR pathway activation, correlates directly with CAD severity, underscoring the intertwined nature of metabolic, hepatic, and cardiovascular dysfunction (2).

Although the direct mechanisms linking MASLD to adverse cardiovascular outcomes after coronary revascularization remain unclear, elevated systemic inflammation following the procedure has been associated with worse outcomes. In a single-center, retrospective observational study of nearly 2,000 patients with ischemic heart failure, elevated Systemic Inflammation Response Index, calculated from monocyte, neutrophil, and lymphocyte counts and recognized as a novel marker of chronic low-grade inflammation, was identified as an independent risk factor for major adverse cardiovascular events (MACE) (27). Another single-center, retrospective study involving approximately 500 post-PCI patients also found that the systemic immune-inflammation index, a different surrogate inflammatory biomarker calculated using platelet, neutrophil, and lymphocyte levels, was independently associated with an increased risk of in-stent restenosis (28). Furthermore, a large retrospective study involving over 22,000 consecutive patients with elevated high-sensitivity C-reactive protein who undergo complex PCI found a significantly higher risk of MACE at 1 year following PCI (29). With extrapolations of this data, it is not unreasonable to suspect that the low level of chronic systemic inflammation imposed by MASLD may hinder tissue recovery and routine healing following revascularization. More studies are needed to correlate and potentially identify direct and indirect mechanisms of elevated systemic inflammation following PCI in patients with MASLD.

The scarcity of studies investigating and comparing coronary revascularization methods, such as PCI and CABG, in patients with MASLD severely hinders claims of superiority or non-inferiority. Previous studies have suggested that MASLD increases the risk of adverse cardiovascular events, and our studies indicate that it may even affect outcomes associated with PCI or CABG, so that risks may be unavoidable with either intervention. Our one included study investigating the mortality associated with CABG found no difference between patients with MASLD and those without MASLD, whereas studies on PCI yielded mixed results. Direct comparisons of PCI and CABG are necessary to determine the preferred intervention methods for individuals with MASLD. Until such studies can be performed, the American Heart Association guidelines recommend that CABG should be preferred over PCI in patients with diabetes and multivessel coronary artery disease involving the left anterior descending artery, who are appropriate surgical candidates, to reduce mortality and the need for repeat revascularizations (30).

Traditional dual antiplatelet therapy (DAPT), which comprises aspirin and a P2Y12 inhibitor, following coronary stenting, largely depends on the type of stent deployed. Bare metal stents should be treated with at least 1 month of DAPT with consideration for continuation longer than 1 month in the absence of high risk or overt bleeding. Drug-eluting stents should be treated with at least 6–12 months of DAPT, depending on bleeding risk or bleeding symptoms. The P2Y12 component of DAPT should be discontinued after 3 months in those with a high risk of bleeding or overt bleeding during DAPT. In patients undergoing CABG, aspirin should be initiated within 6  h postoperatively and continued indefinitely to reduce the risk of saphenous vein graft failure. Select patients may receive DAPT for up to 1 year to improve graft vein patency (30).

Optimal medical management following revascularization has also not been well studied in patients with MASLD. However, clinical recommendations can be extrapolated from studies investigating their safety and efficacy in both MASLD and CAD. Both aspirin and P2Y12 inhibitors are usually safe in patients with MASLD. Aspirin may even ameliorate MASLD and atherosclerosis by inhibiting lipid biosynthesis and elevating catabolic metabolism through the activation of the PPARδ–AMPK–PGC-1α pathway. Regular aspirin use has also been suggested to lower the prevalence and progression of fibrosis in patients with MASLD (2). P2Y12 inhibition may also decrease the activation, accumulation, and adhesion of platelets to the liver endothelium, thereby reducing immune cell recruitment to the liver and protecting against liver damage and the development of fibrosis (31). Unfortunately, the optimal duration of antiplatelet therapy has not been extensively studied; however, it is theoretically expected to mirror the guidelines, given the demonstrated safety and efficacy of these drugs.

Ticagrelor is often the preferred oral P2Y12 inhibitor due to a superior reduced rate of death from vascular causes, myocardial infarction, or stroke without an increased risk of overall major bleeding (32); however, the choice of P2Y12 inhibitor in chronic liver disease, including MASLD, is less well-defined. An in vitro study found the potency of aspirin, cangrelor, and ticagrelor in patients with MASLD cirrhosis to be similar to that of healthy controls (33). A murine model suggested that ticagrelor, not clopidogrel, can attenuate hepatic steatosis and reduce the non-alcoholic fatty liver disease activity score in mice with MASLD by decreasing hepatic lipogenesis and endoplasmic reticulum stress markers, as well as inflammation-related genes (34). However, another murine model suggested that clopidogrel could mitigate hepatic steatosis and downregulate the expression of lipogenic, profibrotic, and proinflammatory genes, while enhancing the phosphorylation of adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase (35). Overall, P2Y12 inhibitors appear to be effective in treating patients with MASLD. More evidence regarding the extracardiac and hepatic benefits is needed to determine the best choice for patients living with MASLD.

Beta-blockers are a core component of post-acute coronary syndrome management. They are generally considered safe in patients with chronic liver disease, as evidenced by non-selective beta-blocker prescription for ascites control in patients with decompensated cirrhosis (36). Some beta-blockers, particularly atenolol and metoprolol, should be avoided in patients with metabolic disorders due to their potential to cause weight gain through decreased energy expenditure. Beta-blockers with additional alpha-receptor antagonism, such as carvedilol and labetalol, may cause less weight gain and are better suited for patients with MASLD (2, 37). Murine models have yielded mixed results regarding the benefits or harms of beta-blockade related to MASLD. One study suggested that beta-blockade may reduce insulin resistance, improve dyslipidemia, and increase the expression of hepatic GLUT4, whereas another study suggested that it may induce MASH in patients with MASLD (2, 38, 39). Overall, beta-blockers are likely safe for use in patients with MASLD; however, further studies are needed to assess their long-term hepatic and metabolic effects.

Statins have been demonstrated to be safe and effective in treating both coronary artery disease and MASLD (2). According to the American College of Cardiology, all patients undergoing PCI or CABG for acute coronary syndrome or coronary artery disease should be initiated on high-dose statin therapy, if not already prescribed, with a target reduction in low-density lipoprotein cholesterol (LDL-C) of at least 50% compared with their baseline level. In very high-risk patients with a history of one or more major cardiovascular disease events or one major atherosclerotic cardiovascular disease event and multiple high-risk conditions, reduction of LDL-C to <55 mg/dl should be targeted (40). The European Society of Cardiology recommends that all patients be targeted to an LDL-C reduction to <55 mg/dl and ≥50% vs. baseline (41). If these targets cannot be reached, adjunctive medications such as ezetimibe or PCSK9 inhibitors can be initiated (40).

The latest European Association for the Study of the Liver–European Association for the Study of Diabetes–European Association for the Study of Obesity (EASL–EASD–EASO) guidelines for the management of MASLD recommend the use of statins for cardiovascular indications, rather than specifically for hepatic benefit, as their safety has been consistently demonstrated in patients with liver disease. A limited number of case–control studies have associated statins with a reduced risk of MASLD, MASH, and liver fibrosis, as well as a reduced risk of hepatic decompensation, mortality, and hepatocellular carcinoma in patients with cirrhosis. However, no large randomized controlled trials with histological evidence exist to probe their effectiveness in MASLD or MASH (2, 42).