Abstract Body (Do not enter title and authors here):
Background:
Non-alcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the global population. Significant epidemiological data links NAFLD to an increased risk of coronary artery disease. Both, coronary artery disease and NAFLD are linked to underlying insulin resistance and inflammation as drivers of the disease. Coronary flow reserve parameters including coronary flow reserve velocity (CFRV), baseline diastolic peak flow velocity (DPFV), and hyperemic DPFV are non-invasive markers of coronary microvascular circulation. The existing literature contains conflicting findings for these parameters in NAFLD patients.

Aim: This meta-analysis aimed to compare CFRV, baseline DPFV, and hyperemic DPFV in between NAFLD patients and healthy controls.

Methods:
A comprehensive systematic search was conducted on PubMed, Embase, Cochrane Library, and Google Scholar from inception until 8th May 2024 to identify relevant studies. We pooled the standardized mean differences (SMD) with the 95% confidence intervals (CI) using the inverse variance random-effects model. A p-value of less than 0.05 was considered statistically significant.

Results:
We included 4 studies with 1139 participants (226: NAFLD and 913: controls). The mean age in the NAFLD group was 54.55 ± 7.62 years and in the control group was 54.2 ± 7.6 years. NAFLD was associated with a significantly lower CFRV [SMD: -0.77; 95% CI: -1.19, -0.36; p<0.0002] and hyperemic DPFV [SMD: -0.73; 95% CI: -1.03, -0.44; p<0.00001] compared to the controls. NAFLD demonstrated a statistically insignificant trend towards reduction in the baseline DPFV [SMD: -0.09; 95% CI: -0.38, 0.19; p=0.52] as compared to healthy controls.

Conclusion:
NAFLD patients are at a higher risk of coronary microvascular dysfunction as demonstrated by reduced CFRV and hyperemic DPFV. The presence of abnormal coronary flow reserve in NAFLD patients provides insights into the higher rates of cardiovascular disease in these patients. Early aggressive targeted interventions towards impaired coronary flow reserve in NAFLD subjects may lead to improvement in clinical outcomes.