Does Non-alcoholic Fatty Liver Disease Have an Impact on Contrast Induced Nephropathy and Adverse Events in Non-ST-elevation?

Abstract

Objectives: The primary aim of this study was to investigate the potential relationship between non-alcoholic fatty liver disease (NAFLD) and contrast-induced nephropathy (CIN) in patients with non-ST-elevation myocardial infarction (NSTEMI). As a secondary goal, we aimed to explore the impact of NAFLD on short-term adverse events and coronary artery disease (CAD) severity in patients with NSTEMI.

Methods: Three hundred and seven NSTEMI patients were included in this study. Laboratory analyses of these patients were performed before the procedure and 48–72 h after the procedure, and all patients underwent pre-procedure 2-dimensional transthoracic echocardiography and pre-discharge abdominal ultrasonography. The NAFLD (-) and (+) groups were compared statistically in terms of CIN, major cardiovascular-cerebrovascular adverse events (MACCE), and coronary artery severity (assessed by syntax score).

Results: The mean age of the 307 consecutive patients included in the study was 61.58±12.39 (min-max: 26–94). The rates of CIN (primary objective) and MACCE and syntax scores (secondary objective) were comparable in both groups.

Conclusion: In patients with NSTEMI, there was no relationship between NAFLD and CIN and short-term MACCE. Furthermore, NAFLD may not have an impact on the CAD severity in such patients. Based on these results, NAFLD is not a risk factor for CIN, short-term mortality, or CAD severity in NSTEMI patients.

Introduction

Liver steatosis that does not arise from excessive alcohol consumption is termed non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common cause of chronic liver disease, is associated with metabolic syndrome and obesity. The global increase in these diseases has inflated the prevalence of NAFLD, currently estimated at 24%.[1,2]

Chronic kidney disease (CKD) is a prominent risk factor for cardiovascular disease (CVD).[3] There is plentiful evidence revealing an independent relationship between NAFLD and CKD.[4–8] The pathophysiological mechanisms that trigger NAFLD and CKD seem similar.[9] NAFLD is also associated with other metabolism-related diseases such as CVDs and diabetes mellitus. The newly proposed “cross-talk” concept may explain the relationship between all these diseases. Disrupted crosstalk can lead to loss of homeostatic balance and, hence, engendering organ damage. Contrast-induced nephropathy (CIN) is one of the most widespread causes of acute kidney damage in the hospital setting.[10]

In addition to studies displaying the presence and severity of coronary artery disease (CAD) in patients with NAFLD,[11,12] a limited number of studies have investigated the relationship between NAFLD and mortality in acute coronary syndrome.[13] However, the potential relationship between NAFLD and CIN remains unknown. The primary aim of this study was to investigate the possible relationship between NAFLD and CIN in patients with non-ST-elevation myocardial infarction (NSTEMI). Second, we aimed to explore the impact of NAFLD on shortterm adverse events and CAD severity in patients with NSTEMI.

Materials and Methods

Study Population

This prospective and cross-sectional study was approved by the University of Health Sciences Bursa Yuksek Ihtisas Training and Research Hospital Ethics Committee (date: 16.11.2022; no: 2011-KAEK-25 2022/11-10). The exclusion criteria were as follows: non-NAFLD liver fat or chronic liver disease such as hepatitis cirrhosis and patients with chronic renal failure whose estimated GFR was below 30 mL/min. The study population comprised patients with NSTEMI admitted to our coronary care unit between December 2022 and July 2023. NSTEMI is defined as acute myocardial injury evidenced by abnormal cardiac biomarkers of acute myocardial ischemia without persistent ST elevation. Out of 355 consecutive patients, eight did not agree to participate in the study. Written consent was obtained from the remaining 347 patients who were included in the study. Of these patients, 23 were excluded from the study because they could not undergo angiography or refused angiography within the last minute. In addition, 17 patients were excluded from the study because their 1-month control examinations could not be performed; finally, 307 patients were included in the statistical analysis (Fig. 1). Patients were monitored for CIN and major adverse cardiovascular and cerebrovascular events (MACCE: cardiovascular death, unstable angina, myocardial infarction, stroke, unplanned revascularization, cardiovascular hospitalizations, and hemodialysis) during the in-hospital and post-discharge 1-month periods.

Figure 1. Study flowchart. NSTMI: Non-ST segment myocardial infarction; NAFLD: Non-alcoholic fatty liver disease.

Laboratory Analysis

Fasting blood samples were collected from all patients before the procedure and were sent to the central laboratory of our hospital. The patients’ fasting blood tests were repeated between 48 and 72 h after angiography and interventional procedures. CIN was defined as an increase in serum creatinine level by ≥0.5 mg/dL or more than 25% from the baseline within 48–72 h following the invasive procedure.

Echocardiographic and Ultrasonographic Evaluation

All patients underwent 2-dimensional (2D) transthoracic echocardiography before coronary angiography. Echocardiography was performed by a single echocardiographer blinded to the patient’s data, and a Vivid E95 platform with a 3.5 Mhz transducer was used for the procedure software (GE Vingmed Ultrasound AS, Horten, Norway). Echocardiographic parameters were evaluated according to the recommendations of the American Society of Echocardiography guidelines.[14] Standard 2D, color, pulse, and continuous Doppler data were recorded while the patient was lying supine in the left decubitus position and during patient expiration. The modified Simpson method was used for the volumetric chamber and ejection fraction measurements.

All patients underwent abdominal ultrasonography by a radiologist blinded to the patients’ data before discharge and after 8 h of fasting (3.5 MHz convex transducer, Toshiba USDI-790A, Otawara, Japan). Liver echogenicity was determined by comparison with the echogenicity of the right kidney. If the echogenicity of the kidney and liver was the same, this condition was considered normal and considered no NAFLD (grade 0). Liver steatosis was ultrasonographically divided into three groups as follows: mild (grade 1) with a slight diffuse increase in liver echogenicity, hepatic vessels, and diaphragm contours. Moderate (grade 2): moderate increase in liver echogenicity with slight distortions in the hepatic vessels and diaphragm boundaries. Advanced (grade 3): A significant increase in liver echogenicity, and hepatic vessels and diaphragm are not visible.[15,16]

Angiography and Interventional Procedure

All patients included in the study underwent coronary angiography within 72 h of hospital admission, and if deemed necessary, percutaneous coronary intervention was performed in the same session. The decision for interventional procedure was left to the discretion of the invasive cardiologist performing the procedure. In these procedures, iopromide (Ultravist® 370 mg/mL, Berlin, Germany) was used as contrast agent. The syntax scores of the patients were obtained by two experienced invasive cardiologists who were unaware of the patients’ clinical features, using a webbased online calculator (www.syntaxscore.com, version 2.1).

Statistical Analysis

All statistical analyses were performed using IBM SPSS Statistics (version 26.0; IBM Corp., Armonk, NY, USA). Patients were divided into two groups according to the presence or absence of NAFLD: NAFLD (-) and NAFLD (+). Continuous variables showing normal distribution according to the Kolmogorov–Smirnov test were expressed as mean±standard deviation, and those not showing normal distribution were expressed as median (interquartile range 25–75). Categorical variables were presented as numbers (n) and percentages (%). The independent Samples t-test was used to compare demographic, clinical, and procedure-related variables between the NAFLD (-) and NAFLD (+) groups for continuous variables showing normal distribution, the Mann–Whitney U-test was used for continuous variables not showing normal distribution, and the chi-square test was used to compare categorical variables. A p<0.05 was considered at significant.

Results

The mean age of the 307 consecutive patients included in the study was 61.58±12.39 years old (min-max: 26–94). NAFLD was observed in 127 (41.4%) patients. Of the 127 patients in the NAFLD (+) group, 88 (69%) had grade 1, 33 (26%) had grade 2, and 5 (3%) had Grade 3 hepatosteatosis. Demographic, drug, and echocardiographic variables of the two groups with and without NAFLD are shown in Table 1. MI, diabetes percentage, and metformin and insulin usage rates were statistically higher in the NAFLD (+) group (p<0.05).

Table 1. Demographic, medication, and echocardiographic variables of NAFLD (-) and (+) groups

On examination of the pre-procedure blood tests, HDL cholesterol was lower in the NAFLD (+) group, whereas ALT, triglycerides, HbA1C, albumin, and lymphocyte levels were significantly higher in this group (p<0.05). A comparison of the laboratory analysis results of the groups is presented in Table 2. The rates of CIN (primary goal) and MACCE and syntax scores (secondary goal) were comparable in both study groups. Comparisons of patient angiographic and follow-up data between the groups are presented in Table 3.

Table 2. Laboratory analysis results of NAFLD (-) and (+) groups before and after the procedure

Table 3. Angiographic variables and follow-up results of NAFLD (-) and (+) groups

Discussion

Regarding the relationship between NAFLD and CIN and short-term MACCE in patients with NSTEMI, no statistically significant difference was observed between subjects with and without NAFLD in terms of CIN and MACCE. To the best of our knowledge, this study is the first to explore the probable relationship between NAFLD and CIN in NSTEMI patients.

Despite higher BMI and diabetes rates, the CIN rates in the NAFLD (+) group were comparable to those in the NAFLD (-) group. The rate of NAFLD found in 41.4% of all patients appears to be higher than that in epidemiological studies examining the entire population worldwide.[2,17] However, it is lower than the 48.3% rate detected in a study using ultrasonography on 113,239 patients who were healthy but applied to the hospital for check-ups in Turkey between 2007 and 2016, conducted by Değertekin et al.[18]

In 120 acute coronary syndrome patients, the 6-month mortality was higher in subjects with NAFLD, had a lower number of patients compared to our study, and also included patients with ST-segment elevation myocardial infarction (STEMI). During the literature review, we could not encounter any other study investigating the prognostic relationship between acute coronary syndrome and NAFLD.

Contrary to previous studies, in our study, no significant difference was detected between the groups with and without NAFLD, in terms of CAD severity, assessed using the syntax scoring in patients with NSTEMI. In a study conducted by Yılmaz et al.,[11] the rate of Grade 2 NAFLD in the CAD group, which is approximately twice (48.2%) that in our study (26%), may explain the difference in such outcomes. In that study, unlike ours, the severity of CAD was evaluated using the Gensini score. In another study with a limited number of patients with acute coronary syndrome (n=80), the syntax score was statistically higher in the NAFLD (+) group. [NAFLD (+) group: 18±8 vs. NAFLD (−) group: 11±5 (p<0.001)]. In that study, nearly half of the patients had STEMI, which was different from our study population, and the NAFLD (+) group included only 15 patients. Inci et al.[19] reported that in patients with chronic coronary syndrome, there was a meaningful correlation between moderate and advanced NAFLD and the severity of CAD using the Gensini score. Again, that was conducted on a limited number of patients (n=136) in a different study population, which may explain the differences from the results of our current study.

In a study by Boddi et al.,[20] in patients with non-diabetic STEMI, the prevalence of NAFLD was found to be considerably higher. NAFLD was found in 87% of all patients, which was about twice the prevalence rates in all epidemiological studies conducted so far, and it was revealed that those with more severe NAFLD in STEMI patients were younger and had more severe CAD.

In a study conducted by Gholoobi et al.[21] on 296 patients with chronic coronary syndrome, an independent relationship was found between the prevalence and severity of NAFLD and CAD. In that study, the rate of more severe NAFLD in the CAD group was higher than that in the non-CAD group. The results may differ from those of our current study since the study was conducted on a different population.

In almost all of the studies mentioned above, the severity of CAD has been found to increase with advanced NAFLD degrees. Our study may differ from the above studies due to the high proportion of subjects with grade 1 NAFLD (69%). These results suggest that Grades 2 and 3 hepatosteatosis may be more influential for CRD, CVD, CIN, and MACCE. Therefore, further research with larger patient numbers, specifically those with higher Grade 2 and 3 NAFLD, may reveal any potential relationship between these diseases.

Study Limitations

The present study has some limitations. The biggest limitation is that patients were diagnosed with NAFLD, not by gold standard liver biopsy, but solely by ultrasound. In addition, the low prevalence of subjects with Grade 2 and 3 NAFLD compared to those with Grade 1 NAFLD is another noteworthy limitation. It would be better for our study if the follow-up periods of the patients were longer, like 1-year instead of 1-month. Therefore, we plan to publish long-term (≥1-year) results in the near future.

Conclusion

In patients with NSTEMI, there seems to be no relationship between NAFLD, CIN, and short-term MACCE. Furthermore, NAFLD may not have an impact on the CAD severity in such patients. Based on these results, NAFLD is not a risk factor for CIN, short-term mortality, or CAD severity in NSTEMI patients. Further studies are required to confirm these results.

Cite This Article: Koca F, Demir ÖF, Şensoy NÖ, Şensoy B, Kat N, Levent F, et al. Does Non-alcoholic Fatty Liver Disease Have an Impact on Contrast Induced Nephropathy and Adverse Events in Non-ST-elevation? Koşuyolu Heart J 2024;27(3):97–102

The study was approved by the University of Health Sciences Bursa Yuksek Ihtisas Training and Research Hospital Ethics Committee (no: 2011-KAEK-25 2022/11-10, date: 16/11/2022).

Externally peer-reviewed.

Concept – F.K., B.Ş., N.Ö.Ş., N.K.; Design – F.K., B.Ş., Ö.F.D.; Supervision – E.T., M.D.; Funding – F.K., F.L.; Data collection and/ or processing – F.K., Ö.F.D., E.T., G.Ö., N.K.; Data analysis and/or interpretation – F.K., Ö.F.D., E.T.; Literature search – F.K., Ö.F.D., B.Ş., N.Ö.Ş., N.K.; Writing – F.K., B.Ş., Ö.F.D.; Critical review – M.D., E.T., B.Ş.

All authors declared no conflict of interest.

No AI technologies utilized.

The authors declared that this study received no financial support.

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Figure and Tables

Figure 1. Study flowchart. NSTMI: Non-ST segment myocardial infarction; NAFLD: Non-alcoholic fatty liver disease.

Table 1. Demographic, medication, and echocardiographic variables of NAFLD (-) and (+) groups

Table 2. Laboratory analysis results of NAFLD (-) and (+) groups before and after the procedure

Table 3. Angiographic variables and follow-up results of NAFLD (-) and (+) groups