Original Article

Prevalence and Prediction of Coronary Artery Disease in Patients With Liver CirrhosisCLINICAL PERSPECTIVE

A Registry-Based Matched Case–Control Study

Jihyun An, Ju Hyun Shim, Seon-Ok Kim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung Sang Lee
https://doi.org/10.1161/CIRCULATIONAHA.114.009278
Circulation. 2014;130:1353-1362
Originally published August 5, 2014

Jump to

Abstract

Background—There is conflict regarding the prevalence of coronary artery disease (CAD) in patients with liver cirrhosis. This study aimed to investigate the prevalence of silent CAD in comparison with the general population, and to identify the relevant risk factors in patients with liver cirrhosis.

Methods and Results—This retrospective study included 1045 prospectively registered consecutive patients with liver cirrhosis without any history of chest pain or CAD, who underwent computerized coronary angiography as a pretransplant workup. These were matched with 6283 controls with healthy livers, based on propensity scores according to established cardiovascular risk factors. Obstructive CAD was defined as ≥50% luminal narrowing in any artery. A matched analysis of 853 pairs showed that the proportion of subjects with obstructive CAD did not differ significantly between the cirrhotic and control groups (7.2% versus 7.9%, P=0.646), in agreement with the outcome of multivariate analysis for its predictors, with an adjusted odds ratio for liver cirrhosis of 1.06 (P=0.690). Nonobstructive CAD was more prevalent in the matched cirrhotic cases (30.6% versus 23.4%, P=0.001). In the pooled cirrhotic cohort, older age, male sex, hypertension, diabetes mellitus, and alcoholic cirrhosis were independently associated with obstructive CAD (adjusted odds ratios, 1.07, 2.74, 1.69, 2.37, and 2.17, respectively; P<0.05 for all), whereas liver function and coagulation parameters were not.

Conclusions—Asymptomatic cirrhotic patients and nonhepatic subjects are similar in terms of the prevalence of occult obstructive CAD. Traditional cardiovascular risk factors are related to critical coronary stenosis in cirrhotic patients, and thus may be helpful indicators for more careful preoperative evaluation of coronary risk.

Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide.1 It is widely accepted that high blood pressure, smoking, obesity, hyperlipidemia, and diabetes mellitus are the major risk factors for developing cardiovascular disease.2 However, causality between liver cirrhosis (LC) and CAD is uncertain, although it has been reported that the heart and the liver interact and affect each other.3

Editorial see p 1337

Clinical Perspective on p 1362

It was originally believed that liver diseases might have a protective effect against CAD.4,5 In the mid-20th century, early autopsy studies provoked this speculation, providing evidence of reduced incidences of cardiovascular atherosclerosis and myocardial infarction in cadavers with portal cirrhosis.5,6 In contrast, the more recent literature reports a prevalence of CAD varying between 2.5% and 27.0% in patients who have cirrhosis being considered for liver transplantation (LT).7–10 However, these studies differed in their definitions of CAD and in their diagnostic parameters, and the controls were inadequate, and they involved different individuals in terms of cardiac symptoms and history, as well. Reliable knowledge of the prevalence of occult CAD, particularly of anatomically confirmed CAD, in patients with LC is limited.

Underlying CAD has a marked unfavorable effect on mortality and morbidity in cirrhotic patients, especially following major surgery such as LT, and cardiovascular complications are the leading cause of non–graft-related posttransplant death.11–13 It is therefore crucial to assess cardiovascular risk and to prevent CAD and associated death under normal conditions and especially perioperatively in patients with LC. Because there is no reliable information on the cardiovascular risk of cirrhotic patients in comparison with individuals who have normal livers, there are currently no specific guidelines for assessing cardiovascular risk in such patients.

We therefore aimed to assess the prevalence of silent CAD in cirrhotic patients by examining asymptomatic LC participants in an ongoing prospective registry of patients who underwent coronary computed tomography (CT) angiography as part of pre-LT cardiac evaluation, and to compare the result with matched individuals in the nonhepatic population. We also sought to identify clinical risk factors related to critical coronary artery stenosis in the LC subset.

Methods

Study Population and Matched Controls

A registry-based retrospective cohort study was conducted with 1183 consecutive prospectively registered patients who underwent computerized angiography as part of a pre-LT cardiac workup from October 2007 to December 2012.14 Patients with acute liver failure (n=32), chronic hepatitis (n=41), idiopathic portal hypertension (n=6), or other liver diseases such as polycystic liver disease (n=14) not accompanied by underlying cirrhosis were excluded, as were subjects with any clinical symptoms of typical chest pain at the time of evaluation, or with a previous history of CAD, including acute myocardial infarction, angina, and congestive heart failure (n=45). Finally, 1045 asymptomatic patients with LC were included in the main analyses of this study. LT was actually performed in 759 (72.6%) of these patients. LC was diagnosed based on clinical features of portal hypertension together with compatible imaging (CT scan or ultrasound) or histological findings, in addition to laboratory test features of hepatic dysfunction and the existence of major complications of liver cirrhosis such as ascites, hepatic encephalopathy, and gastroesophageal varices. The severity of liver disease was calculated from Child-Turcott-Pugh (CTP) and Model for End-Stage Liver Disease scores. Data on the etiology of the liver disease including viral and alcoholic causes were historically and serologically collected. All patients who were classified as having alcoholic cirrhosis had ingested >80 g daily of alcohol for a decade or more. The diagnosis of hepatocellular carcinoma (HCC) was established based on both American and European guidelines.15,16

To obtain individuals as nearly as possible representative of the healthy population, we used as the source of matched controls 8032 subjects in the general population in whom coronary CT scanning was performed as part of a comprehensive health evaluation at the health promotion center of our institution during the study period. Of these, 1749 were excluded because of previous or current histories of liver disease including nonalcoholic fatty liver disease (NAFLD; n=1147), CAD (n=304), and noncoronary cardiac disorders (n=298), as well, based on laboratory and imaging examinations in addition to an assessment by questionnaire. Altogether 6283 healthy subjects were selected, of whom 853 were matched 1:1 with LC cases for age, sex, smoking status, family history of cardiovascular disease, hyperlipidemia, hypertension, diabetes mellitus, and body mass index (BMI) by using the propensity score–based method.17 The study was undertaken with the approval of the local research ethics committee and in accordance with the Declaration of Helsinki (1989) of the World Medical Association.

Cardiovascular Risk Factors

Demographic and clinical parameters, including age, sex, BMI, the presence of hypertension, diabetes mellitus, and hyperlipidemia, and other laboratory test scores were collected from all enrolled subjects. (1) Arterial hypertension was diagnosed according to the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in which arterial hypertension is defined as having a blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic or current use of antihypertensive medication.18 In patients with cirrhosis, the use of diuretics for the management of ascites, or nonselective β-blockers to prevent variceal hemorrhage, was not considered an indicator of hypertension, provided that the patient was not diagnosed as hypertensive before starting on these drugs. (2) Patients were considered to have diabetes mellitus if they were already receiving antidiabetic treatment (oral hypoglycemic agents or insulin), or had elevated fasting plasma glucose levels (≥126 mg/dL) on the first test and on at least 1 further test on a later day.19 (3) Hyperlipidemia was defined if patients were undergoing antilipidemic treatment or had elevated fasting low-density lipoprotein (≥190 mg/dL).20 Relevant information was sought from patients’ medical records on smoking habits, and also family history of cardiovascular disease, which was defined as positive if a diagnosis of CAD or sudden cardiac death had involved a male first-degree relative ≤55 years of age or a female first-degree relative ≤65 years of age.21

Pretransplant Cardiac Workup

All patients being considered for LT at our institution underwent a standard pretransplant cardiac workup including a detailed clinical history, physical examination, standard 12-lead ECG, chest x-ray, and 2-dimensional transthoracic echocardiogram. Coronary CT angiography was also included as a further pretransplant heart evaluation for all these prospectively registered patients. Patients with significant coronary artery stenosis on coronary CT images before LT underwent elective coronary angiography performed in multiple projections by standard techniques, if a reversible defect was observed on myocardial perfusion single-photon emission CT images, or if its need was confirmed by an interventional cardiologist based on the severity and location of the stenotic lesion(s). All major cardiovascular events after LT, including acute coronary syndrome (defined as an ST or a non-ST elevation myocardial infarct or unstable angina),22 congestive heart failure, and arrhythmias, were retrospectively reviewed in detail.

Data Acquisition and Analysis of CT Angiography Images

Coronary CT angiographic examinations were performed by either single-source, 64-section CT (VCT XT; General Electric, Milwaukee, WI) or dual-source CT (Somatom Definition or Definition FLASH; Siemens, Erlangen, Germany). Subjects with no contraindication to β-adrenergic blocker therapy, and heart rates >70 beats/min, were given β-blocking agents 1 hour before coronary CT imaging. All patients except for those with contraindications were also given a nitroglycerin spray 5 minutes before the CT scan. A standard scanning protocol was used, with 240–400 mAs per rotation (dual-source CT), and 400-800-mA tube current (64-section CT), 100-120-kVp tube voltage according to each subjects’ body habitus. CT scanning was performed in the prospective ECG triggering mode or the retrospective ECG-gating mode, with ECG-based tube current modulation to reduce radiation dose.23,24 A bolus of contrast dye was intravenously injected, followed by a saline flush of 50mL. The region of interest on the descending thoracic aorta was defined, and image acquisition was automatically initiated, once a selected threshold (150 Housefield units) was reached, with bolus tracking. Each subject’s ECG was simultaneously recorded to allow for retrospective segmental data reconstruction. Images were initially reconstructed at middiastolic phase (75% of the R-R interval) of the cardiac cycle. The average radiation dose for coronary CT was 9.5 ± 5.5 mSv for dual-source CT and 12.0 ± 6.7 mSv for 64-section CT.

All data were evaluated on a remote workstation. Each lesion was identified by using a multiplanar reconstruction technique and the maximum intensity projections of short-axis, 2-chamber, and 4-chamber views. CT image data were acquired by careful review of the cardiovascular radiologists’ reports. All of the coronary segments were visually analyzed in accordance with a 16-segment coronary artery model.25 The contrast-enhanced portion of the coronary lumen was semiautomatically traced at the maximally stenotic site and compared with the mean value of proximal and distal reference sites. The severity of CAD (classified as normal [no atherosclerosis], mild [nonobstructive; <50% narrowing of the luminal diameter in at least 1 major coronary artery], moderate [50%–70%], or severe [>70%]),26 and number of coronary vessels involved, were recorded. Obstructive CAD was defined as 50% or more narrowing of the luminal diameter in ≥1 coronary arteries.25,27–30 In total, 246 artery segments could not be evaluated on coronary CT angiography owing to motion or stair-step artifacts, or severe calcifications. Altogether 30 (2.9%) of the 1045 LC patients included, and 151 (2.4%) of the 6283 nonhepatic subjects, had at least 1 segment that could not be assessed (P=0.388). For any coronary artery segments considered to be nonevaluable, stenosis severity was assigned based on the outcome of the most adjacent proximal and evaluable segment, as previously described.31

Statistical Analysis

Demographic and laboratory data are presented as means and standard deviations for continuous variables, and as number of subjects (percentages) for categorical variables, unless otherwise stated. Student t test was used to analyze differences between groups, and the χ2 test for comparisons between categorical variables. We used a propensity score–matching method to adjust for potential confounding by using a Greedy algorithm in which randomly selected individuals in the cirrhotic group were paired with comparable individuals in the control group who fulfilled a matching criterion. Using the SAS macro, gmatch,17 we matched cirrhotic patients with controls based on a difference of ±0.2 standard deviations in linear propensity scores, and completed the statistical inference with Cox regression models, with robust standard errors that accounted for the clustering of matched pairs. Patients with LC were subsequently compared with matched controls with regard to the prevalence of obstructive or nonobstructive CAD. To identify significant cardiovascular risk factors, we included all clinically relevant variables with P<0.1 in the univariate analysis in a multivariate logistic regression model, where the presence of liver cirrhosis was also considered a covariate, to explore an association between cirrhosis and obstructive CAD in the pooled analysis. A P value of <0.05 was considered significant, and all statistical tests were 2-sided. Statistical analyses were performed with SPSS software version 20.0 (SPSS, Chicago, IL) or SAS version 9.3 (SAS Institute, Cary, NC).

Results

Baseline Characteristics of the Cirrhotic and Control Cohorts

In terms of clinical factors specific for the disease group (Table 1), 805 (77.0%) of the 1045 cirrhotic patients were male, 820 (78.5%) had LC caused by viruses, predominantly hepatitis B virus, and 585 (56.0%) had untreated or treated HCC(s) at the time of evaluation; mean age was 53.5±8.2 years. The severities of liver disease according to the CTP classification were as follows: 313 (30.0%) cases of CTP A class; 410 (39.2%) of CTP B; and 322 (30.8%) of CTP C. The mean Model for End-Stage Liver Disease score was 14.7±6.7. The frequencies of major cardiovascular risk factors in the entire LC cohort are presented in Table 2: 2.7% had a family history of cardiovascular disease, 33.5% hypertension, 24.2% diabetes mellitus, and 1.1% hyperlipidemia. The proportion of subjects with pathologically elevated blood pressure was greater in the cirrhotic group than the control group (33.5% versus 28.5%; P=0.001), and the cirrhotic patients were less hyperlipidemic (1.1% versus 16.9%; P<0.001; Table 2). Diabetes mellitus was more common in the cirrhotic cases (24.2% versus 10.6%; P<0.001), whereas mean BMI was lower (21.5 kg/m2 versus 24.0 kg/m2; P<0.001; Table 2). After performing propensity score matching, we created 853 matched pairs of subjects with no longer any significant differences with respect to clinically relevant nonhepatic covariates (Table 2).

View this table:
Table 1.

Baseline Cirrhotic Parameters of the Entire Patient Cohort

View this table:
Table 2.

Baseline Characteristics of the Pooled and Matched Cohorts

Coronary Parameters of the Cirrhotic and Control Cohorts

The coronary factors scored by CT scans in the pooled and matched cohorts are presented in Table 2 and Figures 1 and 2. The distribution of grades of coronary artery stenosis among all the LC cases (Figure 1) was as follows: no stenosis in 646 (61.8%) patients, mild nonobstructive lesion in 316 (30.2%) patients, and significant obstructive lesion in 83 (7.9%) patients, of whom 39 (3.7%) had severe stenosis. A single coronary artery was involved in approximately two-thirds (65.1%) of all the cases with obstructive CAD, and the remaining 34.9% had multivessel disease. The frequency of obstructive CAD on coronary images among the controls (486 of the 6283 [7.7%]; P=0.803) was similar to that among the cirrhotic patients, whereas nonobstructive CAD was significantly less frequent (1532 of the 6283 [24.4%]; P<0.001). A propensity score–matching analysis yielded the same findings in terms of the prevalence of obstructive and nonobstructive CAD in the corresponding groups (7.2% versus 7.9%; P=0.646; and 30.6% versus 23.4%; P=0.001, respectively; Table 2 and Figure 2). When we compared the number of epicardial arteries involved in the subsets with obstructive and nonobstructive CAD in the pooled and matched cohorts, multivessel atherosclerosis was more frequent in the cirrhotic patients in the pooled set (34.9% versus 22.2%, P=0.018; and 49.7% versus 40.0%, P=0.002, respectively), but the same was not true in the case of obstructive CAD in the matched set (32.8% versus 23.8%, P=0.326 for obstructive CAD; and 49.4% versus 38.5%, P=0.023 for nonobstructive CAD; Table 2). These findings on the prevalence of CAD and numbers of affected vessels were replicated in the extended cohort (n=7677) containing the cirrhotic patients and controls with prior CAD (Table I and Figure I in the online-only Data Supplement).

Figure 1.
Figure 1.

Distribution of coronary artery stenosis on coronary CT angiography among all cirrhotics (n=1045) and controls (n=6283). The prevalence of significant obstructive CAD was similar in the 2 groups (7.9% [83/1045] vs 7.7% [486/6283]; P=0.803), in contrast to that of mild nonobstructive CAD (30.2% [316/1045] vs 24.4% [1532/6283]; P<0.001). CAD indicates coronary artery disease; and CT, computed tomography.

Figure 2.
Figure 2.

Distribution of coronary artery stenosis on coronary CT angiography in the propensity score–matched cohort (n=853 for cirrhotic cases and n=853 for matched controls). Although the prevalence of mild nonobstructive CAD was greater in the cirrhotic patients than in the matched nonhepatic population (30.6% [261/853] vs 23.4% [200/853]; P=0.001), the 2 matched samples were similar in terms of the prevalence of obstructive CAD (7.2% [61/853] vs 7.9% [67/853]; P=0.646). CAD indicates coronary artery disease; and CT, computed tomography.

Association Between Cirrhosis and CAD in the Pooled Cohort

After adjusting for all relevant covariates such as age, sex, smoking, and family history of cardiovascular disease, BMI, hypertension, diabetes mellitus, and hyperlipidemia, together with presence of cirrhosis, in the pooled sample (n=7328), only the conventional cardiovascular risk factors of hypertension (odds ratio [OR] 1.64; 95% confidence interval [CI], 1.37–1.96; P<0.001), diabetes mellitus (OR, 1.70; 95% CI, 1.37–2.11; P<0.001), and hyperlipidemia (OR, 1.41; 95% CI, 1.12–1.78; P=0.004), along with age (OR, 1.08; 95% CI, 1.07–1.10; P<0.001), and male sex (OR, 2.46; 95% CI, 1.95–3.10; P<0.001), were independent risk factors for obstructive CAD, and cirrhosis continued not to be a significant risk factor (OR, 1.06; 95% CI, 0.81–1.39; P=0.690; Table 3).

View this table:
Table 3.

Clinical Factors Related to Obstructive CAD in the Pooled Cohort (n=7328)

Risk Factors Related to CAD in the Entire Cirrhotic Cohort

In univariate analyses involving all the included LC patients (n=1045), the traditional cardiovascular risk factors, older age (57.8±7.2 versus 53.2±8.1; P<0.001), male sex (90.4% versus 75.9%; P=0.002), hypertension (45.8% versus 32.4%, P=0.015), and diabetes mellitus (48.2% versus 22.1%; P<0.001), were significantly more common in patients with obstructive CAD than in those without obstructive CAD (Table 4). In addition, alcohol-related cirrhosis was associated with obstructive disease (25.3% versus 12.4%; P=0.002). Platelet count was higher in the patients with obstructive disease (88.1±42.1 versus 75.9±47.3, P=0.024), but not the international normalized ratio (1.45±0.49 versus 1.48±0.44; P=0.551), another coagulation indicator. The severity of liver function measured by CTP or Model for End-Stage Liver Disease score and the presence of HCC did not differ between patients with and without obstructive CAD. Multivariate analysis indicated that age (OR, 1.07; 95% CI, 1.04–1.10; P<0.001), male sex (OR, 2.74; 95% CI, 1.28–5.88; P=0.009), the presence of hypertension (OR, 1.69; 95% CI, 1.04–2.75; P=0.034), and the presence of diabetes mellitus (OR, 2.37; 95% CI, 1.47–3.84; P<0.001), along with alcohol-related cirrhosis (OR, 2.17; 95% CI 1.22–3.87; P=0.008), were clinical parameters independently related to obstructive disease. A similar trend was noted in the data obtained from further analyses based on patients with any CAD including nonobstructive plaque (n=1045; Table II in the online-only Data Supplement).

View this table:
Table 4.

Clinical Factors Related to Obstructive CAD in the Entire Cirrhotic Cohort (n=1045)

Cardiovascular Outcomes of Cirrhotic Patients With Pretransplant CAD

Transplantation was not abandoned in any of the included LC patients on account of the severity of the results of coronary CT scans. Of a total of 83 cirrhotic patients with obstructive CAD on CT angiography, 24 underwent coronary catheterization. Percutaneous (n=5) and surgical revascularization (n=1) were subsequently performed before LT in only 6 of the latter patients, all of whom had multivessel disease, and the remaining subjects were medically treated. LT was performed in 57 of the patients with obstructive CAD, and 1 case each of non-ST elevation myocardial infarct, atrial fibrillation, and ventricular tachycardia occurred during the early post-LT hospitalized periods among the patients with multivessel atherosclerosis. None of these 3 patients were indicated for revascularization interventions pre-LT, and all improved after medical treatment. During a mean follow-up of 2.1±0.5 years (median, 2.3 years; interquartile range, 1.5–3.5 years), only 2 late revascularizations occurred, at ≈1 year post-LT, without any cardiovascular deaths among the patients with pre-LT obstructive plaque. None of the transplant recipients with nonobstructive CAD were ultimately indicated for coronary catheterization before LT, and only one of the recipients experienced reversible paroxysmal atrial fibrillation early after surgery. No other cardiac events or deaths occurred during the observation period in any of the patients with or without obstructive CAD who ultimately underwent LT.

Discussion

Whether cirrhotic conditions confer protection against, or accelerate, coronary atherosclerosis has been an unresolved controversy.7–10 However, the prevalence of CAD in patients with LC is only now being assessed and is still disputed. The present study is the largest to date assessing coronary disease states in asymptomatic cirrhotic patients with the use of noninvasive angiographic testing. We found that the prevalence of obstructive CAD among cirrhotic patients without symptoms or histories of heart attack did not differ significantly from that among a propensity score–matched nonhepatic control group. In a multivariable analysis, the prevalence was completely independent of clinical parameters that can be affected by the severity of liver cirrhosis, such as hyperlipidemia, arterial hypertension, diabetes mellitus, and BMI32–36 although the cirrhotic cases were at higher risk of nonobstructive lesions, which have a more favorable course.25,27–30 The prevalence of obstructive disease in both sets was ≈8%, and the traditional clinical predictors such as age, sex, hypertension, and diabetes mellitus contributed substantially to coronary narrowing in the hepatic patients. It is noteworthy that, regardless of atherosclerotic severity, all our subjects with LC had more extensive involvement of the coronary vessels than those without LC, although this effect did not reach statistical significance for obstructive CAD in the matched sample. In fact, a previous study by Yong et al reported that multivessel disease, a well-established predictor of adverse cardiovascular events in both obstructive and nonobstructive disease,28,30 was associated with higher mortality post-LT, which was independent of the severity of coronary stenosis.37

A protective role of cirrhosis against atherosclerotic events has occasionally been reported in postmortem studies.5,6 This might in principle be supported by the favorable cardiovascular risk profiles of cirrhosis per se in terms of the hemostatic defects such as impaired coagulation, thrombocytopenia, and platelet dysfunction, low blood pressure and cholesterol levels, and high levels of circulating estrogens, as well, seen in previous and, in part, also in the current series.7,35,38 However, because we did not find these factors to be significantly prognostic, this argument may be fallacious. On the other hand, some recent studies have suggested that cirrhotic conditions promote CAD because moderate to severe coronary stenotic disorders seemed to be relatively prevalent in LT candidates, accounting for up to 27% of the candidates.7,8,10 The authors based their explanation of these findings on the following epidemiological notions: (1) the growing incidence of chronic liver disease specifically related to NAFLD, including silent or burnt-out steatohepatitis in which approximately half of the patients with NAFLD meet the diagnostic criteria for metabolic syndrome and consequently have an increased risk of ischemic heart disease;9,33 and (2) the prolonged survival of LC patients owing to the advances in medical care.9,33 The present study seems useful in this regard in that the effect of LC on its own could be evaluated because our cohort included only a small proportion of NAFLD-related patients (<5%), and clearly excluded the confounding bias of age by using the matching method at the design stage. More importantly, in contrast to the present study, few previous workers obtained well-matched control data and used only functional cardiac tests (ie, single-photon emission CT or stress echocardiography), along with different enrollment criteria and definition of CAD. In fact, the 2 studies, from Italy and Sweden, that used control groups—albeit not matched controls—did not yield consistent results in terms of whether cirrhosis had a preventative or aggravating effect on cardiovascular pathology; they also did not use a sufficiently quantitative diagnostic tool or an adequately powered sample size.8,39

Consistent with previous data from cirrhotic patients, putative cardiopathological predictors such as age, sex, hypertension, and diabetes mellitus were strongly associated with meaningful CAD in our set of patients. Diabetes mellitus is an atherosclerogenic factor that has been repeatedly identified in different hepatopathy populations.7,8,10,39 Moreover, overt diabetes mellitus seems to be followed by cirrhosis in many cases, as observed in our series, possibly because of the effects of common pathogenic factors such as alcohol and defects of carbohydrate metabolism, although it remains debatable whether diabetes mellitus is more atherogenic in cirrhotic patients.39 Assiduous control of blood glucose and screening for occult CAD especially before surgery should be considered in patients with cirrhosis and diabetes mellitus.

Interestingly, our findings showed that, unlike the hepatitis virus–related disease, alcoholic cirrhosis was of independent significance as a CAD risk factor in cirrhotic patients. Evidence has been accumulating that unlike light-to-moderate drinking, heavy and binge-like alcohol consumption confers an increased risk of CAD and associated death in noncirrhotic subjects.40 Our study, together with a previous study by Kalaitzakis et al,8 extends these findings to cirrhotic patients. However, because studies of coronary narrowing assessed by cardiac catheterization or autopsy have suggested that alcohol can protect against coronary narrowing,5,41 more studies are required to address the complex relation between alcohol intake and coronary blockage.

In terms of the diagnostic value of the coronary risk assessment tool used in our study, multiple reviews have demonstrated that 64-slice CT coronary angiography, which is surely superior to 16-slice CT, is almost as good as conventional coronary angiography for detecting true negatives, although somewhat poorer in its rate of false positives.31,42–44 This ability to noninvasively rule out significant CAD may make it useful for avoiding unnecessary invasive coronary angiography and saving overall cost in the diagnostic pathway, particularly in subjects, like our asymptomatic patients, without chest pain, whose diagnosis remains uncertain despite clinical evaluation and simple cardiac testing.45 Although the relatively high false-positive rate of 64-slice CT invites caution against overestimating the prevalence of occult CAD in the present series, our conclusion seems likely to be reliable, given the similarity of our matched control data to angiographic analyses of previous normal populations in terms of CAD prevalence, in addition to our appropriate use of case and control samples.46,47

At present, the optimal cardiovascular risk stratification and assessment strategy for perioperative patients with cirrhosis is limited in terms of practice guidelines. It is most important to predict cardiac outcomes in adult patients who are undergoing LT, because cardiovascular disease has been found to be one of the most common causes of complications, and even death, in LT patients with functional grafts, particularly in cases with preexisting cardiac histories.13,48 Our data indicate that multivessel CAD, which is thought to be a powerful predictor of post-LT mortality,37 may be more common in cirrhotic patients, despite the fact that the prevalence of obstructive lesions in the cirrhotic patients was equivalent to that in the noncirrhotic individuals. Furthermore, LC patients were also at higher risk of nonobstructive CAD with more unfavorable course than normal coronary arteries, especially in extensive disease, although it remains to be seen whether management of such patients might improve outcomes.25,28–30 Based on these and previous observations, our comprehensive findings emphasize that a rigorous cardiac workup should be considered in the presurgical period of cirrhotic patients, in place of the universal screening procedure for subjects with normal hepatic function currently available, particularly for individuals with cirrhosis due to alcoholic abuse, along with hypertensive patients, diabetic patients, and older patients. The best method of objectively measuring cardiovascular risk in these patients is an area in need of further research.

In addition to the above-mentioned shortcomings regarding the diagnostic performance of coronary CT angiography, certain limitations should be taken into consideration when interpreting the results of the current study. First, because this study was conducted in a hepatitis B virus–endemic area, it is likely that the prevalence of CAD would be somewhat lower than in other geographical regions, especially the Western region where alcohol and NAFLD are more significant causes of cirrhosis, and could affect cardiovascular profiles.7,8,10 However, our cohort in which chronic hepatitis B, which was repeatedly been found not to be associated with the risk of atherosclerosis,49,50 was the main cause of cirrhosis, might be preferable for investigating the effect of LC per se on coronary stenotic end points. Second, considering that the current study included pretransplant cases in a tertiary LT center, our results may be applicable only to patients with more severe cirrhosis referred for LT. However, given the absence of any influence of liver function on the presence of CAD in our cirrhotic series, it is likely that our results can be extrapolated to noncandidates for LT. Third, whether the thrombogenic property of HCC that accompanied over half of our cases has an atherogenic effect should be clarified in future studies, although the prevalence of occult CAD was the same in our pooled cirrhotic patients with and without HCC. Fourth, we used subjects undergoing a general health check as controls, and medical information on any prior CAD history gathered from their direct reports, as well, which may have introduced a selection bias. However, additional data based on the extended sample including individuals with and without documented or reported prior history of CAD yielded similar results in relation to the current prevalence of both nonobstructive and obstructive disease.

In conclusion, this matched case–control study, with propensity score balancing using an imaging modality that can visualize coronary anatomy, showed that the prevalence of subclinical but obstructive CAD with half or more luminal narrowing was not higher, and also not lower, in patients with cirrhosis than in asymptomatic individuals without liver disease, although the prevalence of the more benign nonobstructive CAD was higher. Traditional cardiovascular factors such as age, male sex, hypertension, and diabetes mellitus, lack of impairment of hepatic function and coagulation, which are specific for LC itself, also predicted critical obstructive atherosclerotic plaque, along with alcohol-related disease in the cirrhotic patients. These findings suggest that detailed preoperative evaluation of coronary risk is warranted in cirrhotic patients displaying the above factor(s).

Disclosures

None.

Footnotes

  • Received February 7, 2014.
  • Accepted June 24, 2014.

References

  1. 1.↵
    1. Roger VL,
    2. Go AS,
    3. Lloyd-Jones DM,
    4. Benjamin EJ,
    5. Berry JD,
    6. Borden WB,
    7. Bravata DM,
    8. Dai S,
    9. Ford ES,
    10. Fox CS,
    11. Fullerton HJ,
    12. Gillespie C,
    13. Hailpern SM,
    14. Heit JA,
    15. Howard VJ,
    16. Kissela BM,
    17. Kittner SJ,
    18. Lackland DT,
    19. Lichtman JH,
    20. Lisabeth LD,
    21. Makuc DM,
    22. Marcus GM,
    23. Marelli A,
    24. Matchar DB,
    25. Moy CS,
    26. Mozaffarian D,
    27. Mussolino ME,
    28. Nichol G,
    29. Paynter NP,
    30. Soliman EZ,
    31. Sorlie PD,
    32. Sotoodehnia N,
    33. Turan TN,
    34. Virani SS,
    35. Wong ND,
    36. Woo D,
    37. Turner MB
    ; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–e220.
    OpenUrlFREE Full Text
  2. 2.↵
    1. D’Agostino RB Sr.,
    2. Vasan RS,
    3. Pencina MJ,
    4. Wolf PA,
    5. Cobain M,
    6. Massaro JM,
    7. Kannel WB
    . General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117:743–753.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Møller S,
    2. Bernardi M
    . Interactions of the heart and the liver. Eur Heart J. 2013;34:2804–2811.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Vaněcek R
    . Atherosclerosis and cirrhosis of the liver. Bull World Health Organ. 1976;53:567–570.
    OpenUrlPubMed
  5. 5.↵
    1. Howell WL,
    2. Manion WC
    . 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;60:341–344.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Creed DL,
    2. Baird WF,
    3. Fisher ER
    . The severity of aortic arteriosclerosis in certain diseases; a necropsy study. Am J Med Sci. 1955;230:385–391.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Carey WD,
    2. Dumot JA,
    3. Pimentel RR,
    4. Barnes DS,
    5. Hobbs RE,
    6. Henderson JM,
    7. Vogt DP,
    8. Mayes JT,
    9. Westveer MK,
    10. Easley KA
    . The prevalence of coronary artery disease in liver transplant candidates over age 50. Transplantation. 1995;59:859–864.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Kalaitzakis E,
    2. Rosengren A,
    3. Skommevik T,
    4. Björnsson E
    . Coronary artery disease in patients with liver cirrhosis. Dig Dis Sci. 2010;55:467–475.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Keeffe BG,
    2. Valantine H,
    3. Keeffe EB
    . Detection and treatment of coronary artery disease in liver transplant candidates. Liver Transpl. 2001;7:755–761.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Tiukinhoy-Laing SD,
    2. Rossi JS,
    3. Bayram M,
    4. De Luca L,
    5. Gafoor S,
    6. Blei A,
    7. Flamm S,
    8. Davidson CJ,
    9. Gheorghiade M
    . Cardiac hemodynamic and coronary angiographic characteristics of patients being evaluated for liver transplantation. Am J Cardiol. 2006;98:178–181.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Mandell MS,
    2. Lindenfeld J,
    3. Tsou MY,
    4. Zimmerman M
    . Cardiac evaluation of liver transplant candidates. World J Gastroenterol. 2008;14:3445–3451.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Therapondos G,
    2. Flapan AD,
    3. Plevris JN,
    4. Hayes PC
    . Cardiac morbidity and mortality related to orthotopic liver transplantation. Liver Transpl. 2004;10:1441–1453.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Fouad TR,
    2. Abdel-Razek WM,
    3. Burak KW,
    4. Bain VG,
    5. Lee SS
    . Prediction of cardiac complications after liver transplantation. Transplantation. 2009;87:763–770.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Chae WY,
    2. Hwang S,
    3. Yoon YI,
    4. Kang MC,
    5. Moon DB,
    6. Song GW,
    7. Park GC,
    8. Jung DH,
    9. Namgoong JM,
    10. Jung SW,
    11. Yoon SY,
    12. Kim JJ,
    13. Hwang GS,
    14. Lee SG
    . Clinical value of preoperative coronary risk assessment by computed tomographic arteriography prior to adult living donor liver transplantation. Transplant Proc. 2012;44:415–417.
    OpenUrlCrossRefPubMed
  15. 15.↵
    European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–93.
    OpenUrlPubMed
  16. 16.↵
    1. Bruix J,
    2. Sherman M
    ; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.
    OpenUrlCrossRefPubMed
  17. 17.↵
    1. Bergstralh EJ,
    2. Kosanke JL
    . Computerized matching of cases to controls. Technical Report No 56. Rochester: Mn: Section of Biostatistics, Mayo Clinic; 1995:17–20.
  18. 18.↵
    1. Chobanian AV,
    2. Bakris GL,
    3. Black HR,
    4. Cushman WC,
    5. Green LA,
    6. Izzo JL Jr.,
    7. Jones DW,
    8. Materson BJ,
    9. Oparil S,
    10. Wright JT Jr.,
    11. Roccella EJ
    ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560–2572.
    OpenUrlCrossRefPubMed
  19. 19.↵
    American Diabetes Association. Standards of medical care in diabetes–2013. Diabetes Care. 2013;36(suppl 1):S11–S66.
    OpenUrlFREE Full Text
  20. 20.↵
    1. Jellinger PS,
    2. Smith DA,
    3. Mehta AE,
    4. Ganda O,
    5. Handelsman Y,
    6. Rodbard HW,
    7. Shepherd MD,
    8. Seibel JA
    ; AACE Task Force for Management of Dyslipidemia and Prevention of Atherosclerosis. American Association of Clinical Endocrinologists’ Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis: executive summary. Endocr Pract. 2012;18:269–293.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Myers RH,
    2. Kiely DK,
    3. Cupples LA,
    4. Kannel WB
    . Parental history is an independent risk factor for coronary artery disease: the Framingham Study. Am Heart J. 1990;120:963–969.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Cannon CP,
    2. Brindis RG,
    3. Chaitman BR,
    4. Cohen DJ,
    5. Cross JT Jr.,
    6. Drozda JP Jr.,
    7. Fesmire FM,
    8. Fintel DJ,
    9. Fonarow GC,
    10. Fox KA,
    11. Gray DT,
    12. Harrington RA,
    13. Hicks KA,
    14. Hollander JE,
    15. Krumholz H,
    16. Labarthe DR,
    17. Long JB,
    18. Mascette AM,
    19. Meyer C,
    20. Peterson ED,
    21. Radford MJ,
    22. Roe MT,
    23. Richmann JB,
    24. Selker HP,
    25. Shahian DM,
    26. Shaw RE,
    27. Sprenger S,
    28. Swor R,
    29. Underberg JA,
    30. Van de Werf F,
    31. Weiner BH,
    32. Weintraub WS
    . 2013 ACCF/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes and coronary artery disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on clinical data standards (writing committee to develop acute coronary syndromes and coronary artery disease clinical data standards). J Am Coll Cardiol. 2013;61:992–1025.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Raff GL,
    2. Chinnaiyan KM,
    3. Share DA,
    4. Goraya TY,
    5. Kazerooni EA,
    6. Moscucci M,
    7. Gentry RE,
    8. Abidov A
    ; Advanced Cardiovascular Imaging Consortium Co-Investigators. Radiation dose from cardiac computed tomography before and after implementation of radiation dose-reduction techniques. JAMA. 2009;301:2340–2348.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Hausleiter J,
    2. Martinoff S,
    3. Hadamitzky M,
    4. Martuscelli E,
    5. Pschierer I,
    6. Feuchtner GM,
    7. Catalán-Sanz P,
    8. Czermak B,
    9. Meyer TS,
    10. Hein F,
    11. Bischoff B,
    12. Kuse M,
    13. Schömig A,
    14. Achenbach S
    . Image quality and radiation exposure with a low tube voltage protocol for coronary CT angiography results of the PROTECTION II Trial. JACC Cardiovasc Imaging. 2010;3:1113–1123.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Lin FY,
    2. Shaw LJ,
    3. Dunning AM,
    4. Labounty TM,
    5. Choi JH,
    6. Weinsaft JW,
    7. Koduru S,
    8. Gomez MJ,
    9. Delago AJ,
    10. Callister TQ,
    11. Berman DS,
    12. Min JK
    . Mortality risk in symptomatic patients with nonobstructive coronary artery disease: a prospective 2-center study of 2,583 patients undergoing 64-detector row coronary computed tomographic angiography. J Am Coll Cardiol. 2011;58:510–519.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Raff GL,
    2. Abidov A,
    3. Achenbach S,
    4. Berman DS,
    5. Boxt LM,
    6. Budoff MJ,
    7. Cheng V,
    8. DeFrance T,
    9. Hellinger JC,
    10. Karlsberg RP
    ; Society of Cardiovascular Computed Tomography. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr. 2009;3:122–136.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Leipsic J,
    2. Taylor CM,
    3. Grunau G,
    4. Heilbron BG,
    5. Mancini GB,
    6. Achenbach S,
    7. Al-Mallah M,
    8. Berman DS,
    9. Budoff MJ,
    10. Cademartiri F,
    11. Callister TQ,
    12. Chang HJ,
    13. Cheng VY,
    14. Chinnaiyan K,
    15. Chow BJ,
    16. Delago A,
    17. Hadamitzky M,
    18. Hausleiter J,
    19. Cury R,
    20. Feuchtner G,
    21. Kim YJ,
    22. Kaufmann PA,
    23. Lin FY,
    24. Maffei E,
    25. Raff G,
    26. Shaw LJ,
    27. Villines TC,
    28. Min JK
    . Cardiovascular risk among stable individuals suspected of having coronary artery disease with no modifiable risk factors: results from an international multicenter study of 5262 patients. Radiology. 2013;267:718–726.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Bittencourt MS,
    2. Hulten E,
    3. Ghoshhajra B,
    4. O’Leary D,
    5. Christman MP,
    6. Montana P,
    7. Truong QA,
    8. Steigner M,
    9. Murthy VL,
    10. Rybicki FJ,
    11. Nasir K,
    12. Gowdak LH,
    13. Hainer J,
    14. Brady TJ,
    15. Di Carli MF,
    16. Hoffmann U,
    17. Abbara S,
    18. Blankstein R
    . Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ Cardiovasc Imaging. 2014;7:282–291.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Min JK,
    2. Shaw LJ,
    3. Devereux RB,
    4. Okin PM,
    5. Weinsaft JW,
    6. Russo DJ,
    7. Lippolis NJ,
    8. Berman DS,
    9. Callister TQ
    . Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. J Am Coll Cardiol. 2007;50:1161–1170.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Ostrom MP,
    2. Gopal A,
    3. Ahmadi N,
    4. Nasir K,
    5. Yang E,
    6. Kakadiaris I,
    7. Flores F,
    8. Mao SS,
    9. Budoff MJ
    . Mortality incidence and the severity of coronary atherosclerosis assessed by computed tomography angiography. J Am Coll Cardiol. 2008;52:1335–1343.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Budoff MJ,
    2. Dowe D,
    3. Jollis JG,
    4. Gitter M,
    5. Sutherland J,
    6. Halamert E,
    7. Scherer M,
    8. Bellinger R,
    9. Martin A,
    10. Benton R,
    11. Delago A,
    12. Min JK
    . Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52:1724–1732.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Campillo B,
    2. Richardet JP,
    3. Bories PN
    . Validation of body mass index for the diagnosis of malnutrition in patients with liver cirrhosis. Gastroenterol Clin Biol. 2006;30:1137–1143.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Targher G,
    2. Day CP,
    3. Bonora E
    . Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363:1341–1350.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Dumitraşcu DL,
    2. Stanciu L,
    3. Dumitraşcu D,
    4. Simon B
    . The prognostic significance of arterial blood pressure in liver cirrhosis. Rom J Intern Med. 1995;33:155–159.
    OpenUrlPubMed
  35. 35.↵
    1. Minuk GY,
    2. MacCannell KL
    . Is the hypotension of cirrhosis a GABA-mediated process? Hepatology. 1988;8:73–77.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Wlazlo N,
    2. Beijers HJ,
    3. Schoon EJ,
    4. Sauerwein HP,
    5. Stehouwer CD,
    6. Bravenboer B
    . High prevalence of diabetes mellitus in patients with liver cirrhosis. Diabet Med. 2010;27:1308–1311.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Yong CM,
    2. Sharma M,
    3. Ochoa V,
    4. Abnousi F,
    5. Roberts J,
    6. Bass NM,
    7. Niemann CU,
    8. Shiboski S,
    9. Prasad M,
    10. Tavakol M,
    11. Ports TA,
    12. Gregoratos G,
    13. Yeghiazarians Y,
    14. Boyle AJ
    . Multivessel coronary artery disease predicts mortality, length of stay, and pressor requirements after liver transplantation. Liver Transpl. 2010;16:1242–1248.
    OpenUrlCrossRefPubMed
  38. 38.↵
    1. Kujovich JL
    . Hemostatic defects in end stage liver disease. Crit Care Clin. 2005;21:563–587.
    OpenUrlCrossRefPubMed
  39. 39.↵
    1. Marchesini G,
    2. Ronchi M,
    3. Forlani G,
    4. Bugianesi E,
    5. Bianchi G,
    6. Fabbri A,
    7. Zoli M,
    8. Melchionda N
    . Cardiovascular disease in cirrhosis–a point-prevalence study in relation to glucose tolerance. Am J Gastroenterol. 1999;94:655–662.
    OpenUrlPubMed
  40. 40.↵
    1. Malyutina S,
    2. Bobak M,
    3. Kurilovitch S,
    4. Gafarov V,
    5. Simonova G,
    6. Nikitin Y,
    7. Marmot M
    . Relation between heavy and binge drinking and all-cause and cardiovascular mortality in Novosibirsk, Russia: a prospective cohort study. Lancet. 2002;360:1448–1454.
    OpenUrlCrossRefPubMed
  41. 41.↵
    1. Pearson TA
    . Alcohol and heart disease. Circulation. 1996;94:3023–3025.
    OpenUrlFREE Full Text
  42. 42.↵
    1. Meijboom WB,
    2. Meijs MF,
    3. Schuijf JD,
    4. Cramer MJ,
    5. Mollet NR,
    6. van Mieghem CA,
    7. Nieman K,
    8. van Werkhoven JM,
    9. Pundziute G,
    10. Weustink AC,
    11. de Vos AM,
    12. Pugliese F,
    13. Rensing B,
    14. Jukema JW,
    15. Bax JJ,
    16. Prokop M,
    17. Doevendans PA,
    18. Hunink MG,
    19. Krestin GP,
    20. de Feyter PJ
    . Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am Coll Cardiol. 2008;52:2135–2144.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Bamberg F,
    2. Sommer WH,
    3. Hoffmann V,
    4. Achenbach S,
    5. Nikolaou K,
    6. Conen D,
    7. Reiser MF,
    8. Hoffmann U,
    9. Becker CR
    . Meta-analysis and systematic review of the long-term predictive value of assessment of coronary atherosclerosis by contrast-enhanced coronary computed tomography angiography. J Am Coll Cardiol. 2011;57:2426–2436.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Min JK,
    2. Shaw LJ,
    3. Berman DS
    . The present state of coronary computed tomography angiography a process in evolution. J Am Coll Cardiol. 2010;55:957–965.
    OpenUrlCrossRefPubMed
  45. 45.↵
    1. Hamon M,
    2. Biondi-Zoccai GG,
    3. Malagutti P,
    4. Agostoni P,
    5. Morello R,
    6. Valgimigli M,
    7. Hamon M
    . Diagnostic performance of multislice spiral computed tomography of coronary arteries as compared with conventional invasive coronary angiography: a meta-analysis. J Am Coll Cardiol. 2006;48:1896–1910.
    OpenUrlCrossRefPubMed
  46. 46.↵
    1. Enbergs A,
    2. Bürger R,
    3. Reinecke H,
    4. Borggrefe M,
    5. Breithardt G,
    6. Kerber S
    . Prevalence of coronary artery disease in a general population without suspicion of coronary artery disease: angiographic analysis of subjects aged 40 to 70 years referred for catheter ablation therapy. Eur Heart J. 2000;21:45–52.
    OpenUrlAbstract/FREE Full Text
  47. 47.↵
    1. Choi EK,
    2. Choi SI,
    3. Rivera JJ,
    4. Nasir K,
    5. Chang SA,
    6. Chun EJ,
    7. Kim HK,
    8. Choi DJ,
    9. Blumenthal RS,
    10. Chang HJ
    . Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol. 2008;52:357–365.
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Desai S,
    2. Hong JC,
    3. Saab S
    . Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management. Liver Int. 2010;30:948–957.
    OpenUrlPubMed
  49. 49.↵
    1. Kiechl S,
    2. Egger G,
    3. Mayr M,
    4. Wiedermann CJ,
    5. Bonora E,
    6. Oberhollenzer F,
    7. Muggeo M,
    8. Xu Q,
    9. Wick G,
    10. Poewe W,
    11. Willeit J
    . Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation. 2001;103:1064–1070.
    OpenUrlAbstract/FREE Full Text
  50. 50.↵
    1. Yang KC,
    2. Chen MF,
    3. Su TC,
    4. Jeng JS,
    5. Hwang BS,
    6. Lin LY,
    7. Liau CS,
    8. Lee YT
    . Hepatitis B virus seropositivity is not associated with increased risk of carotid atherosclerosis in Taiwanese. Atherosclerosis. 2007;195:392–397.
    OpenUrlCrossRefPubMed

CLINICAL PERSPECTIVE

There has been controversy over whether liver cirrhosis confers protection against coronary atherosclerosis or aggravates it. Because coronary artery disease (CAD) has a crucial impact on clinical prognosis in cirrhotic patients, especially after major surgery such as liver transplantation, it is very important to assess cardiovascular risk and prevent serious cardiac outcomes in these patients, especially during perioperative periods. In this large, registry-based, matched case–control study, we investigated the prevalence of silent CAD in asymptomatic patients with liver cirrhosis and matched controls with healthy livers, based on noninvasive computerized coronary angiographic images. We found that the prevalence of obstructive CAD was ≈8% in both cirrhotics and controls, although the former were at higher risk of nonobstructive CAD, which has a more benign course. In addition, obstructive or nonobstructive CAD was not related to liver function and coagulation parameters in the cirrhotic patients but to presumptive cardiovascular risk factors such as older age, male sex, hypertension, and diabetes mellitus, along with alcohol-related cirrhosis. Our comprehensive findings could provide important practical information relevant to cardiac workup specific for CAD, where a more rigorous type of workup should be considered in the presurgical period of cirrhotic patients displaying the above risk factor(s), in place of the current universal screening guidelines for individuals with normal livers, especially in the case of potential candidates for liver transplantation.

View Abstract

This Issue

Circulation
October 14, 2014, Volume 130, Issue 16

Jump to

Article Tools

Share this Article

  • Email
  • Prevalence and Prediction of Coronary Artery Disease in Patients With Liver CirrhosisCLINICAL PERSPECTIVE
    Jihyun An, Ju Hyun Shim, Seon-Ok Kim, Danbi Lee, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung and Yung Sang Lee
    Circulation. 2014;130:1353-1362, originally published August 5, 2014
    https://doi.org/10.1161/CIRCULATIONAHA.114.009278
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Related Articles

Cited By...

Subjects