Relationship between non-alcoholic fatty liver disease and coronary heart disease

Table 1 Clinical studies examining the relationship between non-alcoholic fatty liver disease and the presence and severity of clinical coronary heart disease

Ref.	Study characteristics	NAFLD diagnosis	CHD diagnosis	Main findings
NAFLD and cardiac CT studies
Santos et al[43], 2007	Data were analyzed from a Brazil occupational cohort of 505 people	US	Cardiac CT, CAC score	Hepatic steatosis associated with CAC
Sung et al[41], 2012	Data were analyzed from a South Korean occupational cohort of 10153 people	US	Cardiac CT, CAC score	NAFLD associated with a CAC score > 0
Kim et al[44], 2012	Out of 5648 subjects who visited one of our health screening centers between 2003 and 2008, 4023 subjects	CT	Cardiac CT, CAC score	Patients with NAFLD are at increased risk for coronary atherosclerosis independent of classical coronary risk factors
Vanwagner et al[45], 2014	Participants from the Coronary Artery Risk Development in Young Adults study (n = 2424)	CT	Cardiac CT, CAC and AAC score	NAFLD associated with a subclinic atherosclerosis (CAC and AAC score > 0)
Rifai et al[46], 2015	Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 3976)	CT	Cardiac CT, CAC score	NAFLD is associated with increased inflammation and CAC
Mellinger et al[42], 2015	Analysis of the Framingham Heart Study, 3529 participants	CT	Cardiac CT, CAC and AAC score	NAFLD associated with a subclinic atherosclerosis (CAC and AAC score)
Park et al[47], 2016	1732 subjects who underwent serial CAC evaluation	US	Cardiac CT, CAC score	NAFLD plays a role in the early development of CAC
Ishiba et al[48], 2016	698 patients with chest pain or ECG abnormalities who underwent coronary computed tomography	CT	Cardiac CT, CAC score	The progression of arteriosclerosis and that of liver fibrosis may be associated in NAFLD patients
Kim et al[49], 2017	Participants in a health screening program (n = 1575)	CT	Cardiac CT, CAC score	The concomitant presence of NAFLD and systemic inflammation as assessed by hs-CRP increases the risk of CAC
Sinn et al[50], 2017	This retrospective cohort study included 4731 adult men and women with no history of cardiovascular disease (CVD)	US	Cardiac CT, CAC score	NAFLD was significantly associated with the development of CAC
Wu et al[51], 2017	A total of 2345 participants aged ≥ 40 (1035 men and 1310 women)	US	Cardiac CT, CAC score	NAFLD was significantly associated with the development of CAC
NAFLD and stable CHD
Lin et al[58], 2005	2088 male worker undergoing health surveillence	US	Patient history, ECG	NAFLD associated with higher prevalence of CHD, independently of obesity and other traditional CVD risk factors
Arslan et al[55], 2007	Turkish patients admitted with stable CHD (n = 92)	US	CAG (elective)	NAFLD was an independent predictor of CHD (> 50% stenosis of ≥ 1 major coronary artery)
Mirbagheri et al[59], 2007	Iranian patients admitted with ACS and CHD (n = 317)	US	CAG (elective)	NAFLD was an independent predictor of clinically relevant CHD (> 30% stenosis of ≥ 1 major coronary artery)
Akabame et al[60], 2008	Japanese patients with suspected CHD (n = 298)	CT	CT (elective)	NAFLD was independently associatedwith lipid core ofcoronary plaques
Alper et al[56], 2008	Turkish patients with suspected CHD (n = 80)	US	CAG (elective)	NAFLD is associated with more severe CAD
Açikel et al[61] (2009)	Turkish patients admitted for stable CHD and ACS (n = 355)	US	CAG (elective and acute)	NAFLD was an independent predictor of CHD (> 50% stenosis of ≥ 1 major or CHD suspicion
Targher et al[62], 2010	250 consecutive type 1 diabetes mellitus patients	US	Patient history, ECG	NAFLD was associated with higher prevalence of CHD
Sun et al[63], 2011	Hospitalized Chinese patients with high suspicion of CHD (n = 542)	CT	CAG (elective)	NAFLD was associated with severity of CHD
Wong et al[54], 2011	Chinese patients with suspicion of CHD (n = 612)	US	CAG (elective)	NAFLD was associated with CHD, independently of established CVD risk factors
Agac et al[64], 2013	Turkish patients with ACS (n = 80)	US	CAG (elective)	NAFLD was independently associated with a greater severity of CHD (syntax score)
Puchner et al[65], 2014	445 patients randomized to coronary CT angiography arm in ROMICAT II study	CT	Coronary CT angiography	NAFLD is associated with advanced high-risk coronary plaque, independent of traditional CV risk factors and the extent and severity of CHD
NAFLD and ACS
Boddi et al[57], 2013	Nondiabetic Italian patients admitted for ACS (n = 95)	US	CAG (acute)	NAFLD was independently associated with higher risk of multi-vessel CHD
Emre et al[69], 2015	186 consecutive nondiabetic patients who underwent primary PCI for STEMI	US	CAG (acute)	High rates of TIMI 3 after primary PCI, patients with Fatty liver disease score ≥ 3 are more likely to have impaired myocardial perfusion which may contribute to adverse in hospital outcome
Wong et al[70], 2016	612 prospective patients undergoing CAG for stable CHD and ACS	US	CAG (acute, elective)	In patients with clinical indications for coronary angiogram, the presence of NAFLD is associated with coronary artery stenosis and need for coronary intervention
Perera et al[67], 2016	The study group including patients with non-fatal ACS (n = 120)	US	CAG (acute, elective)	Patients with NAFLD have a higher predicted mortality from ACS and thus require aggressive treatment of CAD
Keskin et al[68], 2017	The study group consisted of 360 patients with STEMI	US	CAG (acute)	In STEMI patients, presence of NAFLD is associated with unfavorable clinical outcomes. Grade 3 NAFLD had the highest mortality rates

ACS: Acute coronary syndrome; AAC: Abdominal aortic calcification; CAC: Coronary artery calcification; CAG: Coronary angiography; CHD: Coronary heart disease; CT: Computed tomography; DM: Diabetes mellitus; ECG: Electrocardiogram; NAFLD: Non-alcoholic fatty liver disease; PCI: Percutane coronary investigation STEMI: ST segment elevation miyocardial infarction; TIMI: Thrombolysis In myocardial infarction; US: Ultrasonography.