Persons with NAFLD are not automatically at high risk of acute MI or stroke
Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults
Introduction and methods
Non-alcoholic fatty liver disease (NAFLD) is a marker of ectopic fat accumulation, and associated with diabetes risk. In addition, it is also thought to be associated with CV outcomes . People with NAFLD are often overweight or obese and have abnormal glucose and lipid levels. Other factors that may give rise to a risk of acute myocardial infarction (AMI) or stroke include increased oxidative stress, deranged adipokine profile and hypercoagulability . Surrogate markers such as subclinical atherosclerosis [3-5], subclinical AMI or stroke  and carotid atherosclerotic plaque [6-7] are also more prevalent in people with NAFLD. Moreover, severity of coronary artery disease was higher in those with NAFLD who underwent coronary angiography, vs those without NAFLD .
Meta-analyses showed an increased risk of CV events in those with NAFLD compared to controls [9,10], approaching the level of risk seen in people with type 2 diabetes. But, these findings are topic of debate, as these results have only been partially corrected for known risk factors such as diabetes and lipid levels.
This study therefore undertook a longitudinal analysis of people with a recorded diagnosis of NAFLD in four European primary care databases (Italian, Dutch, Catalonian/Spanish, UK), to assess the risk of AMI and stroke in those people identified in routine practice. Dependent on the available data, results were sequentially adjusted for known CV risk factors. Data of 120,795 participants with an incident NAFLD diagnosis were used. Each NAFLD subjects was matched with up to 100 participants without a diagnosis of NAFLD or non-alcoholic steatohepatitis (NASH). Matching was done on practice site (proxy for socioeconomic deprivation), age at index/diagnosis date (<5 yrs), sex and a recorded date for visiting a GP (<6 mo).
- Traditional CV risk factors were more prevalent in participants with NAFLD compared with matched controls, namely there were more current smokers, more with history of T2DM or hypertension, and BMI and systolic BP levels were higher in all four databases.
- After adjustment for age, sex and smoking, HR for incident AMI in those with NAFLD ranged from 1.03 (95%CI: 0.90-1.18) in the Italian HSD database to 1.31 (95%CI: 1.16-1.49) in the UK THIN database. The pooled hazard ratio was 1.17 (95%CI: 1.05-1.30, I²=66%, P=0.03 for heterogeneity).
- In a subset of participants for whom data on traditional risk factors was available, the age-, sex- and smoking-adjusted HR for incident AMI was 1.08 (95%CI: 0.96-1.23). After adjustment for SBP, T2DM, total cholesterol level, statin use and hypertension, the relation was no longer statistically significant (HR: 1.01, 95%CI: 0.91-1.12, I²=48.4%, P=0.12 for heterogeneity).
- In the subset with risk factor data available, the pooled risk of stroke in the minimally adjusted model was HR: 1.10 (95%CI: 1.04-1.15). After correction for traditional risk factors, this was attenuated to HR: 1.04 (95%CI: 0.99-1.09, I²=0.0%, P=0.92 for heterogeneity).
- Sensitivity analyses looked into persons with NAFLD without a subsequent diagnosis of NASH. After excluding participants with NASH, associations between NAFLD and AMI or stroke were unchanged.
In a real world primary care study of over 120,000 European participants with NAFLD, a recorded diagnosis of NAFLD was not, after correction for traditional risk factors, significantly associated with AMI and stroke. Thus, these data suggest that risk of CVD in these people can be assessed according to standard CV risk assessment methods, and NAFLD does not seem to be a risk enhancer.