Nonalcoholic Fatty Liver Disease in Lean Patients Linked With CVD Risk

Lean patients with nonalcoholic fatty liver disease (NAFLD) were more likely to have cardiovascular disease (CVD) than those overweight or obese, a researcher reported.

Among over 18,000 such patients, logistic regression analysis — adjusting for demographics and clinical risk factors — showed patients with overweight or obesity with NAFLD were associated with a significantly lower prevalence of any CVD compared to lean patients, according to Karn Wijarnpreecha, MD, MPH, of the University of Michigan in Ann Arbor. Specifically:

• Overweight: odds ratio 0.8, 95% CI 0.6-0.9
• Obesity class 1: OR 0.7, 95% CI 0.6-0.9
• Obesity class 2-3: OR 0.7, 95% CI 0.6-0.8

While lean patients had a lower prevalence of cirrhosis, diabetes, dyslipidemia, hypertension, chronic kidney disease (CKD), and other metabolic diseases, they had a greater prevalence of cerebrovascular accident and peripheral arterial disease, Wijarnpreecha said during a press briefing ahead of Digestive Disease Week.

“We think that could be from a difference in lifestyle, diet, exercise, genetics, or even microbiota,” he stated. “These are the factors that we did not capture in this current study and this could be the explanation why the lean group has the higher association or prevalence of CVD.”

The multisystem NAFLD more commonly develops in patients with obesity and often presents without symptoms. NAFLD can lead to non-liver related conditions such as metabolic diseases, CKD, and CVD. However, about 10%-20% of individuals with a normal BMI can still develop NAFLD. There remains a lack of data on whether those with a normal BMI who develop NAFLD experience any less severe liver disease, CKD, or CVD than those with obesity, according to Wijarnpreecha and colleagues.

“Our team had expected to see that those with a normal BMI would have a lower prevalence of any metabolic or cardiovascular conditions, so we were very surprised to find this link to CVD,” said Wijarnpreecha. “Too often, we overlook NAFLD patients with a normal BMI because we assume their risk for more serious conditions is lower than those who are overweight. But this way of thinking may be putting these patients at risk.”

The authors retrospectively examined electronic health records data on 18,594 adults diagnosed with NAFLD at the University of Michigan hospital (n= 10,220) from Jan. 1, 2012 to Feb. 28, 2021 and a Michigan NAFLD cohort (n= 8,374; Wijarnpreecha did not specify the source of this data). Of those, 2,137 were lean (BMI 18.5-24.9), 4,692 were overweight (BMI 25-29.9), 5,234 had class 1 obesity (BMI 30-34.9), and 6,531 had class 2-3 obesity (BMI 35-<40), based on BMI cutoff recommendations for Asians and non-Asians that were provided by the World Health Organization.

NAFLD diagnoses were confirmed by liver biopsy, the presence of hepatic steatosis on imaging, or having a controlled attenuation parameter of over 250 db/m on vibration-controlled transient elastography. Patients with excessive alcohol consumption, alcohol-related disease, and cancer, among others were excluded. Multivariate analysis adjusted for age, gender, race, smoking, diabetes, dyslipidemia, and hypertension.

Overall, more than half of patients in all of the weight categories were women, white (78%-82%), and never smokers, (56%-57%) with the most common comorbidities being hypertension (42%-60%), dyslipidemia (34%-52%), and any CVD (29%-33%). Patients with obesity tended to have a greater prevalence of cirrhosis (4.7%).

The current study was retrospective and done at a single medical center. The authors concluded that “NAFLD in lean people is not a benign disease, and that “attention to cardiac risk stratification and intervention is warranted for lean patients with NAFLD.”

“The results are interesting because the authors found a significantly increased prevalence of CVD compared to overweight/obese individuals even though the prevalence of risk factors for atherosclerotic disease and metabolic diseases were lower,” Andrew Talal, MD, of the University at Buffalo in New York told MedPage Today. “Primary care physicians, endocrinologists, hepatologists and public health officials should consider screening for CVD in lean individuals with NAFLD.”

“Future work is warranted to investigate the effect of CVD risk factor modification in lean individuals with NAFLD,” said Talal, who was not involved in this study.