Dataset Information

Non-alcoholic fatty liver disease and outcomes in persons with acute coronary syndromes: insights from the GRACE-ALT analysis.

ABSTRACT:

Objective

Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of cardiovascular disease, but no data exist about the relation between NAFLD and adverse outcomes in persons with acute coronary syndromes (ACS). We evaluated elevated serum alanine aminotransferase (ALT) as a marker of NAFLD, in association adverse outcomes following ACS.

Methods

We conducted a retrospective cohort study of participants enrolled in the Global Registry of Acute Coronary Events (GRACE) admitted for ACS to St Michael's Hospital, Toronto, between 1999 and 2007. Multivariable linear regression was used to determine the change in maximum measured cardiac troponin I (cTnI) per each 1?IU/l increase in serum ALT concentration. The association between an elevated ALT >90th centile, and adverse outcomes in-hospital and at 6?months were calculated using multiple logistic regression analyses, adjusting for age, sex, body mass index, serum creatinine, glucose, triglycerides and LDL-C, as well as chronic statin or other lipid-lowering agent use.

Results

528 participants were included. Each 1?IU/l increase in ALT was associated with an increase in maximum measured cTnI of 0.16?µg/l (95% CI 0.10 to 0.22). An elevated ALT concentration >90th percentile was associated with a maximum measured cTnI in the highest quartile (adjusted OR 7.07, 95% CI 1.83 to 27.37). An elevated ALT >90th percentile was also significantly associated with all-cause mortality in-hospital, and up to 6?months after discharge (adjusted OR 8.96, 95% CI 3.28 to 24.49).

Conclusions

NAFLD, determined by an elevated serum ALT, is associated with a higher risk of adverse outcomes in persons with ACS. Whether ALT is a valid and independent prognostic marker in ACS remains to be determined.

SUBMITTER: Ravichandran L

PROVIDER: S-EPMC4832624 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Non-alcoholic fatty liver disease and outcomes in persons with acute coronary syndromes: insights from the GRACE-ALT analysis.

Ravichandran Lavanya L Goodman Shaun G SG Yan Andrew T AT Mendelsohn Aurora A Ray Joel G JG

Heart Asia 20121012 1

<h4>Objective</h4>Non-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of cardiovascular disease, but no data exist about the relation between NAFLD and adverse outcomes in persons with acute coronary syndromes (ACS). We evaluated elevated serum alanine aminotransferase (ALT) as a marker of NAFLD, in association adverse outcomes following ACS.<h4>Methods</h4>We conducted a retrospective cohort study of participants enrolled in the Global Registry of Acute Coronary Events (G ...[more]

PMID: 27326050

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Project description:BACKGROUND & AIMS:Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans. METHODS:MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts. RESULTS:Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis. CONCLUSIONS:We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.

Project description:One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease (NAFLD), which is the most common form of liver disease in children. NAFLD is defined by hepatic fat infiltration > 5% hepatocytes, as assessed by liver biopsy, in the absence of excessive alcohol intake, viral, autoimmune and drug-induced liver disease. It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis, which, in turn, can evolve into cirrhosis and end stage liver disease. Obesity and insulin resistance are the main risk factors for pediatric NAFLD. In fact, NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome, prediabetes and type 2 diabetes mellitus (T2D). In particular, it has been clearly shown in obese youth that the prevalence of metabolic syndrome, pre-diabetes and type 2 diabetes increases with NAFLD severity progression. Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition. Recently, a non-synonymous SNP (rs738409), characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene (PNPLA3), has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children. Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein. The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes, is aimed at acting upon specific targets involved in the pathogenesis. There are some therapeutic approaches that are being studied in children. This article reviews the current knowledge regarding the pediatric fatty liver disease, the new insights and the future directions.

Dataset Information

Non-alcoholic fatty liver disease and outcomes in persons with acute coronary syndromes: insights from the GRACE-ALT analysis.

Objective

Methods

Results

Conclusions

Publications

Non-alcoholic fatty liver disease and outcomes in persons with acute coronary syndromes: insights from the GRACE-ALT analysis.

Similar Datasets

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