Cardiovascular Disease Risk Elevated in Children and Young Adults With NAFLD
Key findings
- This analysis of a Swedish population–based cohort study examined the incidence of major adverse cardiovascular events (MACE) and arrhythmias in children and young adults according to the presence of non-alcoholic fatty liver disease (NAFLD)
- 699 individuals with biopsy-confirmed NAFLD who were ≤25 years old (38% with non-alcoholic steatohepatitis [NASH]) were matched with up to five controls from the general population and followed for a median of 16 years
- Compared with controls, patients with NAFLD had a significant 2.33-fold greater rate of MACE, including both ischemic heart disease and congestive heart failure, and the subgroup with NASH had a 5.27-fold higher rate
- The findings were consistent regardless of age, sex, duration of follow-up or underlying cardiometabolic comorbidities, and they persisted when patients with NAFLD were compared to their siblings
- This study, the first to estimate cardiovascular disease risk in pediatric and young adult NAFLD on a nationwide scale, suggests the need for more attention to screening and early intervention in this patient population
Evidence shows that non-alcoholic fatty liver disease (NAFLD) is particularly aggressive in pediatric patients. For example, rapid progression to non-alcoholic steatohepatitis (NASH) or fibrosis has been reported, including development of cirrhosis in early adulthood.
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Massachusetts General Hospital researchers recently conducted the first longitudinal study that shows pediatric NAFLD, like NAFLD in adults, is linked to higher risk of major adverse cardiovascular events (MACE) and arrhythmia. Tracey G. Simon, MD, MPH, hepatologist in the Division of Gastroenterology and assistant professor of Medicine at Harvard Medical School, and colleagues published the findings in Gut.
Methods
The ESPRESSO cohort study in Sweden resulted in a database of prospectively recorded liver histopathology data from all 28 pathology departments nationwide, collected from 1966 to 2017. Subjects who provided specimens were matched with up to five controls from the general population according to age, sex, county, and year that follow-up started.
For this analysis, the researchers identified 699 individuals with NAFLD ≤25 years old at the time of index biopsy. 62% had simple steatosis, and the others had NASH. 40% were diagnosed at age <18 years, and the mean age at index biopsy was 17.
Risk of Major Adverse Cardiovascular Events
The median duration of follow-up among patients with NAFLD was 16 years. The primary study outcome was the composite of new-onset ischemic heart disease (including acute myocardial infarction), congestive heart failure, stroke and/or cardiovascular disease–related mortality.
After multivariable adjustment, the rate of MACE compared with controls was:
- All patients with NAFLD—adjusted HR (aHR), 2.33 (95% CI, 1.43–3.78)
- Patients with NASH—aHR, 5.27 (95% CI, 1.96–14.19)
The findings were consistent regardless of age, sex, duration of follow-up, and underlying cardiometabolic comorbidities. Positive associations with NAFLD were also observed for the individual MACE outcomes, although the numbers of events in each subgroup was small.
Sibling Analyses
The research team rematched 414 patients with NAFLD to 639 full-sibling comparators. After multivariable adjustment, the patients had a 5.97-fold greater rate of MACE than their sibling controls (95% CI, 1.48–24.07). This finding implies genetic or early-life factors cannot fully explain the excess CVD risk in young patients with NAFLD.
Risk of Arrhythmia
The secondary outcome was the composite of new-onset atrial fibrillation, bradyarrhythmias, other supraventricular arrhythmias and/or ventricular arrhythmias, including cardiac arrest and sudden cardiac death.
After multivariable adjustment, patients with NAFLD had a 3.16-fold greater rate of arrhythmia than controls (95% CI, 1.49–6.68).
Risk Stratification Needed
Clinicians and public health officials should focus more on identifying and modifying early CVD risk factors in children and young adults with NAFLD.
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