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Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults

BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5367 (Published 08 October 2019) Cite this as: BMJ 2019;367:l5367

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Re: Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults

We thank Drs McKenna-Barry and Ryan, for their interest in our article. While there are studies that have reported associations between stage of liver disease and surrogate markers of CVD, we agree more work is needed to examine whether the existence and/or stage of NASH provides a meaningful independent risk for cardiovascular disease over and above the traditional risk factors. The nature of real-world data that we studied is such that we are unable to determine the stage of liver disease with any degree of accuracy. As per our recent publications (1, 2), the proportion of individuals with a diagnosis of NAFLD in whom we could calculate the Fib-4 score ranged from 11% to 54% in the different databases, of whom 29.8% - 35.7% had indeterminate or high risk scores. Therefore we did not have sufficient power to study this aspect.

Whilst the overlap of some processes highlighted by McKenna-Barry and Ryan may lead some to conjecture this ought to be the case, only by doing properly powered analyses will robust answers emerge. In this respect, it is worth remembering those some risk factors for more advanced liver disease e.g. diabetes, continued weight gain, are also risk factors for cardiovascular disease. Thus, whilst cardiovascular risk may be higher in those with NASH versus simple steatosis, a higher prevalence of usual risk factors (which also lead to the occurrence of greater systemic inflammation, etc.) might adequately capture such risk. Clearly more work is needed to answer this important question.

Naveed Sattar and William Alazawi on behalf of co-authors

References

1: Alexander M, Loomis AK, van der Lei J, Duarte-Salles T, Prieto-Alhambra D, Ansell D, Pasqua A, Lapi F, Rijnbeek P, Mosseveld M, Waterworth DM, Kendrick S, Sattar N, Alazawi W. Risks and clinical predictors of cirrhosis and
hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts. BMC Med. 2019 May 20;17(1):95.

2: Alexander M, Loomis AK, van der Lei J, Duarte-Salles T, Prieto-Alhambra D, Ansell D, Pasqua A, Lapi F, Rijnbeek P, Mosseveld M, Avillach P, Egger P, Dhalwani NN, Kendrick S, Celis-Morales C, Waterworth DM, Alazawi W, Sattar N.
Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ. 2019 Oct 8;367:l5367.

Competing interests: No competing interests

01 November 2019
Naveed Sattar
Professor of Metabolic Medicine
William Alazawi, (w.alazawi@qmul.ac.uk)
University of Glasgow
University of Glasgow