Limited data exist on the role of nonalcoholic fatty liver disease (FLD) as a potential independent risk factor in the setting of acute coronary syndromes. The aim of this study was to evaluate the impact of FLD on myocardial perfusion and inhospital major adverse cardiac events (MACE) in the setting of ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). We examined 186 consecutive nondiabetic patients (mean age 58 ± 11 years and 76% men) who underwent primary PCI for STEMI by ultrasound within 72 hours of admission. FLD was graded according to a semiquantitative severity score as mild (score <3) or moderate to severe (score ≥3). Myocardial perfusion was determined by measuring myocardial blush grade (MBG) and ST-segment resolution (STR) analysis. Patients were divided into 2 groups according to FLD score (<3 or ≥3). There were no differences with regard to postprocedural Thrombolysis In Myocardial Infarction 3 flow grade between the 2 groups (89% vs 83%, p = 0.201). Patients with FLD score ≥3 were more likely to have absent myocardial perfusion (MBG 0/1, 37% vs 12%, p <0.0001), absent STR (27% vs 9%, p = 0.001), and higher inhospital MACE rate (31% vs 8%, p <0.0001). By multivariate analysis, FLD ≥3 score was found to be an independent predictor of absent MBG 0/1 (odds ratio [OR] 2.856, 95% confidence interval [CI] 1.214 to 6.225, p = 0.033), absent STR (OR 2.862, 95% CI 1.242 to 6.342, p = 0.031), and inhospital MACE (OR 2.454, 95% CI 1.072 to 4.872, p = 0.048). In conclusion, we found that despite similar high rates of Thrombolysis In Myocardial Infarction 3 after primary PCI, patients with FLD score ≥3 are more likely to have impaired myocardial perfusion which may contribute to adverse inhospital outcome.
Recent data have shown an independent role of nonalcoholic fatty liver disease (FLD) in the development and progression of atherosclerosis. In a review of 27 studies, FLD has been associated with increased carotid intima media thickness, coronary artery calcification, reduced endothelial function and arterial stiffness independent of cardiovascular risk factors, and metabolic syndrome. FLD has been linked to insulin resistance, and thus, its prevalence has been reported high in obese and type 2 diabetic population. The significance of FLD in nondiabetic patients is still to be searched. Moreover, limited data exist on the role of FLD as a potential independent risk factor in the setting of acute coronary syndromes. FLD has been independently associated with increased risk of multivessel coronary disease in nondiabetic patients admitted for ST-segment elevation myocardial infarction (STEMI). However, prospective studies regarding its involvement on treatment outcomes in patients with acute coronary syndromes are still lacking. Myocardial blush grade (MBG) and ST-segment resolution (STR) are 2 validated measurements of myocardial perfusion and have incremental prognostic value beyond Thrombolysis In Myocardial Infarction (TIMI) 3 flow in patients with STEMI. In this study, we investigated the impact of FLD on myocardial perfusion and inhospital prognosis in nondiabetic patients undergoing primary percutaneous coronary intervention (PCI) for STEMI.
Methods
Patients undergoing primary PCI within 12 hours of symptom onset were prospectively and consecutively enrolled for a period of 3 months (October 2012 to December 2012). The study protocol was approved by the institutional review board, and informed consent was obtained from all participants. The inclusion criteria were (1) typical ongoing ischemic chest pain for >30 minutes and (2) ST elevation ≥1 mm in ≥2 contiguous leads (2 mm for leads V 1 to V 3 ). The exclusion criteria were a diagnosis of diabetes mellitus or HbA1c >6.5%, hepatitis B or C infection, alcohol consumption >30 g/day, chronic liver or systemic disease, and conditions associated with FLD (polycystic ovarian syndrome, obstructive sleep apnea syndrome, hypothyroidism, hypogonadism, and duodenopancreatic resection). Patients with conditions confounding STR interpretation on both electrocardiograms (ECGs; left bundle branch block, pacing, preexcitation) were also excluded.
A total of 348 consecutive patients with STEMI were admitted to the intensive care unit during the study period, and 275 primary PCIs were performed. We excluded 62 patients for a history of diabetes mellitus or HbA1c >6.5%, 6 for alcohol consumption >30 g/day, 4 for hepatitis B infection, 1 for hepatitis C infection, 2 for obstructive sleep apnea syndrome, 4 for thyroid disease, and 10 for ECGs confounding STR evaluation. The resulting study population consisted of 186 patients.
All patients received chewable aspirin 300 mg and a loading dose of clopidogrel 300 mg on admission and intravenous standard heparin 70 U/kg before the procedure. The use of glycoprotein IIb/IIIa inhibitor (tirofiban) was left to the primary operator’s decision. All primary PCI procedures were performed through a femoral approach using a 6Fr guiding catheter. The lesions were passed by 0.014-in guidewires. Primary angioplasty was performed with or without stenting according to the operator’s discretion. Only bare metal stents were available for use at our hospital during the study period. Angiographic data were analyzed by 2 independent investigators. Intraobserver and interobserver variabilities for TIMI 0, 1, and 3 were 0%. For TIMI 2, the corresponding values were 1% and 3%. MBG was assessed according to the dye density score described by Van’t Hof et al from 0 (no contrast density or abnormal persistence of contrast medium) to 3 (normal contrast density relative to dye density in uninvolved areas). Intraobserver and interobserver variabilities for MBG 0, 1, and 3 were 0%. For MBG 2, the corresponding values were 1% and 4%.
Electrocardiography was performed on admission and 60 minutes after the procedure. STR was calculated as the ratio of the sum of ST-segment elevation on admission minus the sum of ST segment elevation 60 minutes after primary PCI divided by the sum of ST segment elevation on admission. STR was defined as complete if >70%, partial if 30% to 70%, and absent if <30%.
Creatine kinase-MB isoform (CK-MB) levels were obtained on admission and repeated every 6 hours until peak levels were reached and repeated daily thereafter. The lipid profile, glucose, and HbA1c were investigated in the morning after the procedure, whereas aspartate aminotransferase and alaninetransaminase were measured at the day before discharge.
Liver ultrasound scan was performed within 72 hours of admission to assess the presence and the severity of FLD using 3.5-MHz scanner attached to a high-resolution ultrasound machine (Aplio; Toschiba Corp, Tochigi, Japan). The presence of FLD was diagnosed when the liver–kidney difference was >0. The severity of FLD was graded semiquantitatively according to a scale from 0 to 8 points, on the basis of liver–kidney differences (0 to 3 points), deep attenuation (0 to 1 point), blurring of diaphragm (0 to 1 point) and/or of the hepatic vein (0 to 1 point) and/or of the gallbladder wall (0 to 1 point), and the presence of focal sparing (0 to 1 point). Postprocedural transthoracic echocardiography (Vivid 3 or 5; GE Vingmed Ultrasound AS, Horten, Norway) was performed during inhospital period. The left ventricular ejection fraction (LVEF) was calculated using the biplane Simpson method.
Inhospital major adverse cardiac events (MACE) was defined as nonfatal myocardial infarction (MI), acute heart failure, and death. Nonfatal MI was defined as recurrent chest pain and/or development of new ECG changes with a new rise ≥20% of cardiac biomarkers measured after the recurrent event. Inhospital mortality was defined as death due to MI or other cardiac causes. Heart failure during the index hospitalization was defined as dyspnea, beginning or persisting >24 hours after hospital administration, accompanied by physical signs of heart failure and need for additional/increased heart failure therapy.
Patients were divided into 2 groups according to FLD score (<3 or ≥3) for comparison of clinical, angiographic, procedural, and perfusion findings and inhospital adverse cardiac events. Statistical analysis was performed using SPSS 20.0 (SPSS, Inc, Chicago, Illinois). A 2-tailed p value <0.05 was considered statistically significant. Categorical variables were expressed as frequencies (percentages). Continuous variables were expressed as mean ± standard deviation (tested for normality with Shapiro–Wilk test). Categorical variables were compared using the chi-square or Fisher’s exact tests. Group means for continuous variables were compared using independent sample t test. Multivariate logistic regression analysis was used to identify independent predictors of absent STR (<30%) and absent or minimal blush (MBG 0/1) after primary PCI. Baseline clinical, angiographic, and procedural variables presented in Table 1 were included in the multivariate models with an entry criteria of p <0.10.
| Variable | All patients (n= 186) | Score<3 (n= 111) | Score≥3 (n= 75) | p value |
|---|---|---|---|---|
| Age (years) | 58±11 | 60±11 | 56±10 | 0.010 |
| Male | 142(76%) | 83(75%) | 59(79%) | 0.540 |
| Hypertension | 100(54%) | 56(51%) | 44(59%) | 0.270 |
| Smoker | 103(55%) | 57(51%) | 46(61%) | 0.179 |
| Dyslipidemia | 46(25%) | 24(22%) | 22(29%) | 0.232 |
| Family coronary history | 57(31%) | 37(33%) | 20(27%) | 0.333 |
| Previous coronary disease | 39(21%) | 22(20%) | 17(23%) | 0.640 |
| Anterior wall infarction | 96(52%) | 56(51%) | 40(53%) | 0.700 |
| Killip class ≥ 2 | 36(19%) | 18(16%) | 18(24%) | 0.187 |
| Body mass index (kg/m 2 ) | 26.5±2.4 | 26.0±2.4 | 27.3±2.2 | 0.001 |
| Total cholesterol (mg/dl) | 187±52 | 180±39 | 195±66 | 0.074 |
| LDL cholesterol (mg/dl) | 120±48 | 115±33 | 127±63 | 0.135 |
| HDL cholesterol(mg/dl) | 39±10 | 41±10 | 37±9 | 0.007 |
| Triglyceride (mg/dl) | 144±82 | 127±77 | 161±86 | 0.005 |
| Glucose (mg/dl) | 110±19 | 109±18 | 111±19 | 0.578 |
| Glycated hemoglobin (%) | 5.7±0.5 | 5.6±0.4 | 5.7±0.5 | 0.889 |
| SGPT (mg/dl) | 45±20 | 42±19 | 48±20 | 0.056 |
| SGOT (mg/dl) | 79±35 | 76±35 | 82±35 | 0.235 |
| Creatinine (mg/dl) | 0.8±0.2 | 0.8±0.2 | 0.9±0.2 | 0.805 |
| GFR (ml/min/1.73m 2 ) | 95.4±16.4 | 96.4±14.5 | 94.7±17.6 | 0.488 |
| GpIIbIIIa inhibitor | 30(16%) | 16(14%) | 14(19%) | 0.439 |
| Pain to balloon time (h) | 3.4±1.7 | 3.4±1.8 | 3.4±1.7 | 0.975 |
| Pain to balloon time > 4h | 72 (39%) | 39(35%) | 33(44%) | 0.223 |
| Hospitalization (day) | 5.9±2.3 | 5.3±2.1 | 6.7±2.3 | 0.068 |
| Previous medication | ||||
| ACE inhibitor/ARB | 52(28%) | 33(30%) | 19(25%) | 0.512 |
| Beta blocker | 28(15%) | 18(16%) | 10(13%) | 0.590 |
| Statin | 28(15%) | 20(18%) | 8(11%) | 0.169 |
| Aspirin | 31(17%) | 18(16%) | 13(17%) | 0.841 |
| Multivessel coronary disease | 110(59%) | 56(51%) | 54(72%) | 0.003 |
| Infarct-related artery | ||||
| Left anterior descending | 96(52%) | 56(51%) | 40(53%) | 0.700 |
| Left circumflex | 28(15%) | 13(12%) | 15(20%) | 0.121 |
| Right coronary artery | 56(30%) | 39(35%) | 17(23%) | 0.069 |
| Intermediate/diagonal | 6(3%) | 3(3%) | 3(4%) | 0.623 |
| Baseline TIMI flow | ||||
| 0 | 125(67%) | 77(69%) | 48(64%) | 0.444 |
| 1 | 17(9%) | 9(8%) | 8(11%) | 0.553 |
| 2 | 30(16%) | 15(14%) | 15(20%) | 0.238 |
| 3 | 14(8%) | 10(9%) | 4(5%) | 0.351 |
| Use of stents | 178(96%) | 110(99%) | 68(91%) | 0.256 |
| Stent length (mm) | 21.0±5.6 | 20.4±5.0 | 21.3±5.9 | 0.801 |
| Stent diameter (mm) | 3.03±0.4 | 3.1±0.3 | 3.0±0.5 | 0.867 |
Results
A total of 186 consecutive, nondiabetic patients who underwent primary PCI entered the study (mean age 58 ± 11 years and 76% men). FLD was seen in 149 patients (80%). Patients with FLD had a higher body mass index (27.2 ± 2.4 vs 26.0 ± 2.5 kg/m 2 , p = 0.001), higher triglyceride levels (162 ± 88 vs 126 ± 79 mg/dl, p = 0.004), and higher frequency of multivessel coronary disease (p <0.0001) compared with patients without FLD and were otherwise similar for all parameters.
The distribution of patients according to FLD score is shown in Figure 1 . Baseline clinical, angiographic, and procedural findings according to FLD score (<3 or ≥3) are provided in Table 1 . Patients with FLD ≥3 were younger (p = 0.01). Triglycerides and body mass index were significantly higher (p = 0.005 and p = 0.001, respectively) and HDL cholesterol lower (p = 0.007) in the FLD ≥3 group. Multivessel coronary disease was more common in patients with FLD ≥3 score (p = 0.003).
