The role of liver fat in coronary heart disease risk

Where an excess of deep body fat has been consistently linked to various cardiovascular diseases, the association between liver fat (LF) and cardiometabolic disorders has remained unclear. To investigate the risk of incident coronary heart disease (CHD) associated with discordant visceral adipose tissue (VAT) level and LF, Ms. Jennifer Linge, AMRA Medical AB, Linkoping, Sweden, and her team have studied the magnetic resonance images of 12,276 individuals in the United Kingdom biobank to measure their VAT and liver proton density fat fraction.

After a mean follow-up period of 1.3 years, 176 CHD events were identified among imaged participants with an average VAT of 2.3% and 4.7% as well as LF of 2.2% and 3.1% observed among female and male participants, respectively. Based on their VAT and LF levels, participants are subdivided into 4 phenotype groups based on the gender-specific average values of VAT and LF: Low VAT/low LF, low VAT/high LF, high VAT/low LF, and high VAT/high LF. Notably, individuals with a combination of high VAT/low LF were found to have the highest risk of CHD with a significantly greater than 2-fold higher odds for incident CHD when compared to the referenced individuals with low VAT/low LF (OR=2.33; 95% CI: 1.50-3.58; p<0.001). Individuals with high VAT/high LF were at the second highest risk of incident CHD when compared to the referenced group with an odds ratio of 1.55 (95% CI: 1.08-2.25; p=0.018). After adjusting for age and body mass index (BMI), the association between high VAT/low LF and CHD was still positive, but the effect size was reduced when compared to the reference group (OR=1.65; 95% CI: 1.03-2.63; p=0.034). Interestingly, participants with high VAT/high LF were no longer at risk of incident CHD after adjusting for age and BMI (OR=1.00; 95% CI: 0.64-1.58; p=0.983), suggesting that a heterogeneous body fat distribution may affect the risk of developing CHD. Contrarily, low VAT/high LF was not associated with the risk of incident CHD before and after adjusting the age and BMI.

From the results of the study, the distribution of body fat, particularly LF, is correlated to the risk of incident CHD. As such, liver triglyceride regulation may play an important role in cardiovascular health among individuals with visceral obesity. In contrast, an earlier study on similar individuals in the United Kingdom biobank has found a nonsignificant association between LF and CHD in females.1 This may be due to a lower prevalence of CHD among females, or females rarely exhibit a skewed fat accumulation that contributes to the positive association between LF and risk of incident CHD in males.1

To confirm the association between high VAT/low LF and the risk of incident CHD, further investigations would be needed to understand whether the high VAT/low LF phenotype is the result of an inability to handle ectopic fat deposition via the liver when the individual is subjected to high CHD risk. Also, the association between CHD risk and liver fat decrease due to liver dysfunction should be investigated.

“First, we have found that visceral fat most effectively identifies individuals at high risk of developing coronary heart disease. Secondly, in the presence of visceral obesity, low liver fat was strongly associated with a higher risk of coronary heart disease,” summarized Ms. Linge. However, as the study implies that a targeted lowering of LF without a resolution of visceral obesity may put the individual at a greater risk of developing CHD, Ms. Linge urged that further investigations should be made before the data is translated into clinical practice.

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