Coronary artery disease in liver cirrhosis: Does the aetiology of liver disease matter?
Authors: Evangelos Kalaitzakis, Einar Björnsson
Journal: Journal of Hepatology (2009)

We read with great interest the paper by Kadayifci et al. [[1]Kadayifci A. Tan V. Ursell P.C. Merriman R.B. Bass N.M. Clinical and pathologic risk factors for atherosclerosis in cirrhosis: a comparison between NASH-related cirrhosis and cirrhosis due to other aetiologies.J Hepatol. 2008; 49: 595-599Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar] regarding the prevalence of coronary artery disease (CAD) and risk factors for atherosclerosis in liver cirrhosis. The authors reviewed retrospectively the patient notes of 60 subjects with non-alcoholic steatohepatitis (NASH)-related cirrhosis and 60 age- and sex-matched controls with cirrhosis of other aetiologies who underwent liver transplantation. The two groups were compared regarding the prevalence of CAD and that of risk factors for atherosclerosis. The prevalence of CAD was found to be higher in NASH-cirrhosis than in cirrhosis due to other aetiologies (21.6% vs. 3.3%, p < 0.05). Also, patients with NASH-cirrhosis were found to have higher prevalence of arterial hypertension (51.6% vs. 20%), diabetes mellitus (65% vs. 31.6%), obesity (28.3% vs. 6.6%), and the metabolic syndrome (48.3% vs. 10%) compared to those with cirrhosis of other aetiologies (p < 0.05 for all). The two groups did not differ significantly in smoking habits or the presence of atherosclerosis in hepatic arteries of explanted livers [[1]Kadayifci A. Tan V. Ursell P.C. Merriman R.B. Bass N.M. Clinical and pathologic risk factors for atherosclerosis in cirrhosis: a comparison between NASH-related cirrhosis and cirrhosis due to other aetiologies.J Hepatol. 2008; 49: 595-599Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar]. The authors concluded that CAD and major risk factors for atherosclerosis are significantly more prevalent in subjects with NASH-cirrhosis compared to cirrhosis of other aetiologies. The prevalence of CAD has been considered to be low among patients with liver cirrhosis compared to the general population. This notion is based mainly on autopsy studies since the 1960s and 1970s [2Howell W.L. Manion W.C. The low incidence of myocardial infarction in patients with portal cirrhosis of the liver: a review of 639 cases of cirrhosis of the liver from 17,731 autopsies.Am Heart J. 1960; 60: 341-344Abstract Full Text PDF PubMed Scopus (70) Google Scholar, 3Kane W.C. Aronson S.M. Cerebrovascular disease in an autopsy population. Reduced frequency of stroke in patients with liver cirrhosis.Trans Am Neurol Assoc. 1971; 96: 259-260PubMed Google Scholar] as well as on studies from the South of Europe in which the majority of included patients had cirrhosis due to hepatitis C [4Marchesini G. Ronchi M. Forlani G. Bugianesi E. Bianchi G. Fabbri A. et al.Cardiovascular disease in cirrhosis – a point-prevalence study in relation to glucose tolerance.Am J Gastroenterol. 1999; 94: 655-662PubMed Google Scholar, 5Berzigotti A. Bonfiglioli A. Muscari A. Bianchi G. Libassi S. Bernardi M. et al.Reduced prevalence of ischemic events and abnormal supraortic flow patterns in patients with liver cirrhosis.Liver Int. 2005; 25: 331-336Crossref PubMed Scopus (47) Google Scholar]. Although no formal comparison with a control population was performed, the study of Kadayifci et al. suggests that patients with NASH-cirrhosis do not have a low prevalence of CAD. However, the most common cause of cirrhosis in Western countries is alcoholic liver disease (ALD) and, unfortunately, no patients with ALD-cirrhosis were included in the study by Kadayifci et al. [[1]Kadayifci A. Tan V. Ursell P.C. Merriman R.B. Bass N.M. Clinical and pathologic risk factors for atherosclerosis in cirrhosis: a comparison between NASH-related cirrhosis and cirrhosis due to other aetiologies.J Hepatol. 2008; 49: 595-599Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar]. Comparative data on the prevalence of CAD and its risk factors in patients with cirrhosis of different aetiologies are largely lacking. We recently conducted a prospective study on the prevalence of CAD and its risk factors in 127 consecutive patients with liver cirrhosis compared to a sample of subjects from the general population (n = 203) [[6]Kalaitzakis E, Rosengren A, Skommevik T, Björnsson E. Coronary artery disease in patients with liver cirrhosis. Dig Dis Sci 2009; Feb 26. [Epub ahead of print].Google Scholar]. A total of 55/127 patients (43%) had ALD-cirrhosis, 22 (17%) had NASH (or cryptogenic) cirrhosis, and 50 (40%) had cirrhosis of other aetiologies. CAD was found to be more common in cirrhotic patients compared to controls (20% vs. 12%, p = 0.001). In regression analysis, CAD was independently related to diabetes (odds ratio (OR) 5.47, 95% confidence interval (CI) 2.44–12.28), but not to liver cirrhosis. In the liver cirrhosis group only ALD-cirrhosis (OR 9.5, 95% CI 1.08–83.4) and age (OR 1.23 per year, 95% CI 1.06–1.43) were independently related to CAD [[2]Howell W.L. Manion W.C. The low incidence of myocardial infarction in patients with portal cirrhosis of the liver: a review of 639 cases of cirrhosis of the liver from 17,731 autopsies.Am Heart J. 1960; 60: 341-344Abstract Full Text PDF PubMed Scopus (70) Google Scholar]. In this study, although ALD-cirrhosis was more common among cirrhotic patients with CAD than in those without CAD (65% vs. 38%, p = 0.01), the prevalence of NASH-cirrhosis did not differ significantly between the two groups (23% vs. 16%, p > 0.05) and, thus, the latter was not entered in the regression analysis [[6]Kalaitzakis E, Rosengren A, Skommevik T, Björnsson E. Coronary artery disease in patients with liver cirrhosis. Dig Dis Sci 2009; Feb 26. [Epub ahead of print].Google Scholar]. We have now stratified our cohort according to etiology of liver cirrhosis, thus dividing it into three groups: the ALD-cirrhosis group (n = 55), the NASH-cirrhosis group (n = 22), and the groups of cirrhosis due to other aetiologies (n = 50). The prevalence of CAD did not differ significantly between NASH- and ALD-cirrhosis but was lower in cirrhosis of other aetiologies compared to both groups (p < 0.05) (Fig. 1). The prevalence of CAD risk factors is shown in Table 1. Patients with NASH-cirrhosis were older and had diabetes and history of arterial hypertension more often than patients in the other two cirrhosis groups (p < 0.05). ALD-cirrhotic patients were more often male and smokers than patients in the other two groups (p < 0.05). The three cirrhosis groups did not differ significantly in the prevalence of obesity, hereditary predisposition to CAD, cirrhosis complications or severity, or serum cholesterol (p > 0.05 for all). In multivariate analysis, CAD was found to be independently related to age (OR 1.1 per yr, 95% CI 1.04–1.2), ALD-cirrhosis (3.5, 95% CI 1.2–10.1), and history of arterial hypertension (2.9, 95% CI 1.04–8.2).Table 1Clinical characteristics and risk factors for coronary artery disease in patients with ALD-cirrhosis, NASH-cirrhosis, and those with cirrhosis of other etiologies.NASH-cirrhosis (n = 22)Alcoholic cirrhosis (n = 55)Cirrhosis of other etiologies (n = 50)p-ValueAge (years)63 (11)58 (9)53 (13)0.001Males41%75%54%0.011Smoking59%80%54%0.014Diabetes41%29%16%0.067History of arterial hypertension52%28%12%0.002Obesity (BMI > 30)32%13%14%0.104Hereditary predisposition for CAD17%7%3%0.214Data are presented as mean (standard deviation) or percentage as appropriate.The p-value for ANOVA (age) or for chi-square testing (nominal variables) for all three groups are reported.SD, standard deviation; CAD, coronary artery disease. Open table in a new tab Data are presented as mean (standard deviation) or percentage as appropriate. The p-value for ANOVA (age) or for chi-square testing (nominal variables) for all three groups are reported. SD, standard deviation; CAD, coronary artery disease. Taken together, the findings of Kadayifci et al. [[1]Kadayifci A. Tan V. Ursell P.C. Merriman R.B. Bass N.M. Clinical and pathologic risk factors for atherosclerosis in cirrhosis: a comparison between NASH-related cirrhosis and cirrhosis due to other aetiologies.J Hepatol. 2008; 49: 595-599Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar] and our results indicate that the prevalence of CAD is higher in ALD- and NASH-cirrhosis compared to cirrhosis of other aetiologies. Both studies show that CAD risk factors are more common in NASH-cirrhosis than in cirrhosis of other aetiologies. These results suggest that a more rigorous work-up for the diagnosis of CAD may be indicated in patients with ALD- and NASH-cirrhosis.