Fatty Liver and CAD

Ramon F. Abarquez, Jr., MD

Dr. Ramon F. Abarquez, Jr. has been one of the most prolific consultant writers of H&L and its sister publication, Vital Signs. Highly esteemed in the medical community, he is the founding president of Philippine Society of Hypertension and a past president of the Philippine College of Physicians

For comments, ramonfabarquezjr@yahoo.com.ph

A meta-analysis of 34 studies (164,494 participants, 21 crosssectional studies, and 13 cohort studies) showed that nonalcoholic fatty liver disease (NAFLD) was associated with an increased risk of prevalent and incident coronary artery disease (CAD), prevalent and incident hypertension, and prevalent atherosclerosis.

NAFLD is associated with an increased risk of major adverse cardiovascular events (CVEs), but not related to mortality from all causes or cardiovascular disease (CVD) [Wu, Sci Rep. 2016 Sep 16;6:33386)

Although conventional risk factors were stronger predictors of coronary calcification and plaque formation, the severity of hepatic steatosis remained an independent risk factor for obstructive CAD. Coronary CT angiography may play a potential role in risk stratification for patients with hepatic steatosis. (Tomizawa, Int J Cardiovasc Imaging. 2016 Jan 30)

Fatty Liver and CAD 2The association remained consistent for subgroups with clinical CAD (RR: 2.26;1.04-4.92, p<0.001) and ischemic stroke (RR: 2.09; 1.46-2.98, p<0.001). The risk of CV mortality was also increased in the NAFLD group (RR 1.46,1.31-1.64, p<0.001).

NAFLD patients have a significantly higher risk for clinical CVE. (Mahfood Haddad, Diabetes Metab Syndr. 2016 Dec 15. pii: S1871-4021[16]30276-4)

Metabolic syndrome and ACS

Metabolic syndrome (MetS), as a syndrome which is also linked with NAFLD or its individual risk factor components, is associated with atherosclerotic disease progression with high lipid content, positive remodeling, and plaque rupture. MetS is regarded as a pre-diabetic state, hence central adiposity, is essential to prevent cardiovascular disease progression from the development of frank type 2 diabetes mellitus (DM). Obesity is linked with increased atherosclerotic plaque burden and progression, with attenuated response to therapies, increased plaque vulnerability and events.

In women with DM, stable angina pectoris, and higher baseline LDL-C and CRP levels, the reduction was irrespective of HDL-C levels. But, in the REVERSAL trial, HDL-C levels were significantly associated with plaque regression. [Nissen, JAMA 2004;291:1071-80. 10.1001/jama.291.9.1071]

However, treatment CRP levels and not the absolute LDL-C change was associated with plaque reduction and MACE, [Puri, Circulation 2013;128:2395-403] highlighting the complex interaction between female sex, cardiovascular risk factors, CRP and HDL-C with plaque regression or different response to therapy and events.

Fatty Liver and CAD 3

No statistically significant correlation between BP reduction and plaque progression rate [Hirohata, Atherosclerosis 2012;220:134-8] , but optimization of BP is important in patients with CAD and with benefit in treating pre-HT.

Fatty Liver and CAD 4

Smoking and ACS

An association between smoking and degree of coronary atherosclerosis was present in patients undergoing coronary angiography who presented with acute coronary syndrome (ACS) with higher fibro-fatty percentage, but without associations with percentage necrotic core, nor with virtual histology intravascular ultrasound (VH-IVUS) derived thin-cap fibroatheroma (TCFA) lesions.

Despite the modest magnitude of the differences in the degree and composition of atherosclerosis, clinical relevance of the findings may be questioned. (Buljubasic, PLoS One. 2015 Oct 22;10(10):e0141093)

Cigarette smokers had a higher burden of necrotic core (20.7 percent vs 17.2 percent; P=.04), with 58 percent fibrous plaques, 19 percent fibro-fatty, 18.3 percent with necrotic core, and 5.4 percent with dense calcium. On multivariate analysis, cigarette smoking was independently associated, as well as older age (>80 years) as predictors of higher necrotic core burden (P=.02). Hence, cigarette smoking is associated with a higher burden of necrotic core in coronary atherosclerotic plaques. (Bolorunduro, J Invasive Cardiol. 2015 Aug;27(8):354-8. Epub 2015 May 15.)

Fatty Liver and CAD 5

Fibroatheroma in the renally impaired

In both stable angina and ACS patients, with glomerular filtration rate (GFR) reduction, a significantly increased volume of dense calcification and necrotic core with the highest values in ACS patients. [Kono, Kidney Int 2012;82:344-51] Interestingly, a meta-analysis, stratified patients by GFR >60 and <60 concluded that there was no difference in progression rates of atheroma volume despite preventive therapies. Understanding the phenotype of plaques in various susceptible groups may allow potential development of personalised therapies. (Munnur, Cardiovasc Diagn Ther. 2016 Aug;6 [4] 382-95)