NAFLD, Myocardial Infarction Linked to Cardiovascular Disease Mortality

Johanna Geleijnse, PhD

Credit: Wageningen University

Patients with nonalcoholic fatty liver disease (NAFLD) and a history of myocardial infarction are at increased risk of cardiovascular disease mortality and all-cause mortality compared to patients without NAFLD, according to findings from a recent study.

The results, which remained consistent after excluding patients with obesity and diabetes, showed a stronger adverse association of Fatty Liver Index with cardiovascular disease mortality in female post-myocardial infarction patients than in their male counterparts.¹

“Little is known on the association of NAFLD and [cardiovascular disease] mortality in post-MI patients. Associations in this group may differ due to cardiometabolic alterations, medication use, and older age,” wrote investigators.¹

Risk factors for NAFLD include being overweight, having obesity, metabolic syndrome, and high levels of triglycerides in the blood.² High blood pressure, unhealthy blood cholesterol levels, diabetes, and obesity are associated with an increased risk of cardiovascular disease.³ Patients with a history of myocardial infarction, also known as a heart attack, may experience various health complications, including arrhythmias, heart failure, heart valve problems, and sudden cardiac arrest.⁴

Senior investigator Johanna Geleijnse, PhD, professor in the division of human nutrition and health at Wageningen University in Wageningen, Netherlands, and a team of investigators examined the relationship between Fatty Liver Index and risk of cardiovascular disease and all-cause mortality in patients with a history of myocardial infarction. Participants included patients from the Alpha Omega Cohort aged 60–80 years who had a myocardial infarction ≤10 years prior to study enrollment. Investigators excluded patients who were missing data on Fatty Liver Index components and alcohol consumption. After applying the same exclusion criteria in a random subset of the cohort which was re-examined after 40 months, 1678 patients were eligible for the analysis of 40-month change in Fatty Liver Index and mortality risk.¹

From the Alpha Omega Cohort, investigators collected data on demographics, smoking status, alcohol consumption, and medication use at baseline and after 40 months of follow-up. Among all participants, the median Fatty Liver Index was 68 (interquartile range [IQR], 48-84) and 60% of patients had Fatty Liver Index ≥ 60, which was the threshold for having hepatic steatosis. Patients had a mean age of 69.1 (Standard Deviation [SD], 5.7 years), 23% were female, 85% used statins, and the mean BMI was 27.8 (SD, 3.9) kg/m2.¹

Investigators followed participants for cause-specific mortality from enrollment, between 2002–2006, through December 2018 and used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular disease mortality, CHD mortality, and all-cause mortality. In the main models, Fatty Liver Index at baseline was analyzed in categories, using Fatty Liver Index <30 as the reference category.¹

Investigators adjusted HRs for age and sex in model 2. Model 3 also included systolic blood pressure, smoking status, alcohol consumption, statin use, time since last myocardial infarction, fasting, and the type of intervention during the Alpha Omega Trial. Restricted cubic splines (RCS) analyses were performed to assess the continuous association of Fatty Liver Index with cardiovascular disease and all-cause mortality.¹

A total of 1934 deaths were recorded among the cohort during 12 years follow-up (IQR 8.5–14.0), including 795 deaths from cardiovascular disease. A Fatty Liver Index ≥ 60 was associated with a higher risk of cardiovascular disease mortality (HR, 1.34; 95% CI, 1.02-1.75) compared to a Fatty Liver Index <30, which grew in magnitude after adjustment for potential confounders (HR, 1.58; 95% CI, 1.19-2.09).¹

Further analysis suggested risk of all-cause mortality was also greater with Fatty Liver Index ≥60 (HR, 1.18; 95% CI, 1.00-1.39). RCS analyses showed Fatty Liver Index was nonlinearly associated with cardiovascular disease mortality with a lower risk for Fatty Liver Index <30 and a gradual increase from Fatty Liver Index >75 (P = .036). Additionally, results for all-cause mortality showed no association with Fatty Liver Index up to 75, with a slight increase in mortality risk in Fatty Liver Index >75.¹

Investigators pointed out multivariable HRs differed substantially between males and females for categorical analyses, showing an increased risk of cardiovascular disease mortality for females with a Fatty Liver Index ≥60 compared to Fatty Liver Index <30 (HR, 2.66; 95% CI, 1.55-4.56). HRs for cardiovascular disease mortality were slightly lower in patients ≤70 years (HR, 1.30; 95% CI, 0.83-2.05) than in patients aged >70 years with FLI ≥60 (HR, 1.48; 95% CI, 1.07-2.05). HRs did not change when excluding patients with obesity (HR, 1.50; 95% CI, 1.13-1.99) or diabetes (HR, 1.54; 95% CI, 1.12-2.13).¹

In 1678 patients with repeated measurements, investigators noted a 10.5 (SD 9.3) mean absolute change in Fatty Liver Index after 40 months of follow-up. Among these patients, 142 progressed into Fatty Liver Index ≥60 after 40 months of follow-up and 177 regressed from Fatty Liver Index ≥60. RCS analyses showed change of Fatty Liver Index was not associated with cardiovascular disease mortality.¹

After stratification of baseline Fatty Liver Index, a decrease in Fatty Liver Index was associated with a lower risk of cardiovascular disease mortality for patients with a baseline Fatty Liver Index ≥60, but not in those with baseline Fatty Liver Index <60. Change of Fatty Liver Index was not associated with all-cause mortality risk in the total study population, but an increase of Fatty Liver Index was associated with a higher all-cause mortality risk for patients with a baseline Fatty Liver Index ≥60.¹

“FLI was highly predictive for premature [cardiovascular disease] mortality and all-cause mortality, but FLI cut-off points might differ between males and females regarding [cardiovascular disease] mortality. Further studies are warranted to investigate if FLI cut-off points truly predict NAFLD, taking into account the likelihood of deteriorating health in this post-MI patient population,” concluded investigators.¹

References:

1. Heerkens L, van Kleef LA, de Knegt RJ, et al. Fatty Liver Index and mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort. PLoS One. 2023;18(9):e0287467. Published 2023 Sep 8. doi:10.1371/journal.pone.0287467
2. Mayo Clinic. Nonalcoholic fatty liver disease. Diseases & conditions. Accessed September 14, 2023. https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567
3. Centers for Disease Control and Prevention. Heart Disease. CDC. Accessed September 14, 2023. https://www.cdc.gov/heartdisease/risk_factors.htm
4. Cleveland Clinic. Heart Attack (Myocardial Infarction). Diseases & Conditions. Accessed September 14, 2023. https://my.clevelandclinic.org/health/diseases/16818-heart-attack-myocardial-infarction