Nonalcoholic Fatty Liver Disease May Contribute to Arterial Stiffness

Researchers sought to determine whether NAFLD had a causal effect on cardiovascular diseases, such as coronary artery disease, stroke, and more.

Nonalcoholic fatty liver disease (NAFLD) has a causal effect on arterial stiffness, according to study results published in Metabolism.

While evidence suggests that NAFLD is associated with cardiovascular disease (CVD), the reasons for the association are unclear. To investigate the potential causal relationship between NAFLD and CVD, such as heart failure (HF), coronary artery disease (CAD), stroke, and arterial stiffness, researchers conducted a Mendelian randomization analysis using summary-level data from established cohort studies, including the UK Biobank, the CARDIoGRAMplusC4D Consortium, and the MEGASTROKE Consortium.

Researchers extracted single nucleotide polymorphisms (SNPs) strongly associated with NAFLD in European ancestry as candidate variables from existing cohorts. Outcomes of interest were arterial stiffness index, HF, CAD, stroke, and ischemic stroke and its subtypes. The primary analysis used the inverse variance weighted method (IVW) to estimate the causal effect of NAFLD-associated SNPs on CVD.

Per the results of the IVW method, genetically determined NAFLD was strongly associated with arterial stiffness index (β=0.04; 95% CI, 0.02-0.06, P =5.53-04). In this primary analysis, NAFLD was also associated with increased risk for HF (odds ratio [OR], 1.08; 95% CI, 1.02-1.14; P =.005). However, this relationship did not persist in sensitivity analyses or analyses using other Mendelian randomization methods. No causal association was detected between NAFLD and the other primary outcomes.

The mechanisms underlying the association between NAFLD and arterial stiffness warrant further investigation, the study authors noted.

Study limitations included the small genetic variance in NAFLD phenotypes and the lack of data on patient demographics and clinical severity.

“[W]e found solid evidence that NAFLD was significantly associated with [arterial stiffness index],” the study authors wrote. “It hints that improvement of NAFLD patients and preventing the CVD risk in NAFLD are necessary. In addition, CVDs and NAFLD might share common cardio-metabolic risk factors, such as obesity and chronic inflammation.”


Peng H, Wang S, Wang M, et al. Nonalcoholic fatty liver disease and cardiovascular diseases: a Mendelian randomization study. Metabolism. Published online May 22, 2022. doi:10.1016/j.metabol.2022