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Original Contribution |

Prevalence of Colorectal Neoplasm Among Patients With Newly Diagnosed Coronary Artery Disease FREE

Annie On On Chan, MD, PhD; Man Hong Jim, MD; Kwok Fai Lam, PhD; Jeffrey S. Morris, PhD; David Chun Wah Siu, MD; Teresa Tong, BSc; Fook Hong Ng, MD; Siu Yin Wong, MD; Wai Mo Hui, MD; Chi Kuen Chan, MD; Kam Chuen Lai, MD; Ting Kin Cheung, MD; Pierre Chan, MD; Grace Wong, MD; Man Fung Yuen, MD, PhD; Yuk Kong Lau, MD; Stephen Lee, MD; Ming Leung Szeto, MD; Benjamin C. Y. Wong, MD, PhD; Shiu Kum Lam, MD
[+] Author Affiliations

Author Affiliations: Departments of Medicine (Drs A. O. O. Chan, Jim, Siu, Hui, C. K. Chan, Lai, Cheung, P. Chan, Yuen, Lee, B. C. Y. Wong, and S. K. Lam and Ms Tong) and Statistics and Actuarial Science (Dr K. F. Lam), University of Hong Kong, Department of Medicine, Ruttonjee Hospital (Drs Ng, S. Y. Wong, and Lau), and Department of Medicine, Tuen Mun Hospital (Drs G. Wong and Szeto), Hong Kong, China; Department of Biostatistics, M. D. Anderson Cancer Center, Houston, Texas (Dr Morris).

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JAMA. 2007;298(12):1412-1419. doi:10.1001/jama.298.12.1412.
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Published online

Context Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated.

Objectives To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases.

Design, Setting, and Participants Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years.

Main Outcome Measures The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex.

Results The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by χ2 test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the association of advanced colonic lesions and CAD.

Conclusions In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.

Figures in this Article

Colorectal cancer is the second most prevalent cancer worldwide.1 There were about 1 million new cases and 500 000 deaths due to colorectal cancer in 2002.1 It has been estimated that 1 in 20 healthy individuals will eventually develop colorectal cancer. Coronary artery disease (CAD) is the single leading cause of death in the United States and other industrialized countries.2 We previously published a retrospective study that reported a strong association between colorectal cancer/adenoma and CAD, possibly due to the sharing of common environmental risk factors.3

Colorectal cancer and CAD share similar environmental risks factors, such as diabetes mellitus; smoking; hyperlipidemia; sedentary lifestyle; high-fat, low-fiber diet; obesity; and hypertension.46 The metabolic syndrome is being increasingly recognized as a significant health hazard worldwide.7 It comprises a constellation of metabolic risk factors, including most of the underlying risk factors for both colorectal cancer and CAD: diabetes or impaired glucose tolerance, hypertriglyceridemia, low high-density lipoprotein cholesterol level, central obesity, and hypertension. Persons with the metabolic syndrome have been reported to have increased risk of developing CAD.8,9 We postulated that the metabolic syndrome might also be an important risk factor for the development of both colorectal cancer and CAD.

Hong Kong is an industrialized region with incidences of and mortality due to colorectal cancer and CAD similar to that in western countries.1012 Although we observed an association between colorectal cancer and CAD in our previous study,3 we were not able to identify the risk factors involved because of its retrospective nature.3 We thus designed and conducted the current cross-sectional study, the primary aim of which was to investigate the prevalence of colorectal cancer and adenoma (colorectal neoplasms) in patients with newly diagnosed CAD. A secondary aim was to identify the underlying risk factors, after adjusting for age and sex, that predisposed to the 2 conditions. The results have important implications in prevention of both colorectal neoplasm and CAD, as well as for the screening strategy of colorectal cancer.

Patient Recruitment

The study period encompassed November 2004 to June 2006. Participating hospitals include the cardiac divisions of Queen Mary Hospital, Grantham Hospital, and Ruttonjee Hospital. These are regional hospitals serving patients with heart disease in the Hong Kong West cluster.

The study was approved by the institutional review boards of the University of Hong Kong/Queen Mary Hospital, Grantham Hospital, and Ruttonjee Hospital, all in Hong Kong. All participants provided written informed consent.

Consecutive patients with suspected CAD (ie, those with angina or abnormal exercise stress test results) who presented for the first time for coronary angiography were invited to participate in the study. Because we aimed at studying the prevalence of colorectal neoplasm in patients with newly diagnosed CAD, and to avoid the potential protective effect of aspirin and statins on colorectal neoplasm, patients with a history of CAD for more than 1 year or who had been taking aspirin or a statin for more than 1 year were excluded. In addition, those presenting for coronary angiography for reasons other than suspected CAD (eg, congestive heart failure, cardiomyopathy) were also excluded. Additional exclusion criteria were history of colonic disease, such as colorectal cancer, polyp, and inflammatory bowel disease, and history of colorectal surgery or colonoscopy within the previous 10 years.

Consecutive patients with coronary angiogram were invited for colonoscopy regardless of hemoglobin status to avoid preselection in the CAD-positive group of patients with gastrointestinal tract bleeding due to aspirin or clopidogrel therapy. In accordance with American College of Cardiology/American Heart Association guidelines, patients were defined as CAD-positive if at least 50% diameter stenosis in any 1 of the major coronary arteries was found on coronary angiography; otherwise, patients were defined as CAD-negative.

Because age and sex matching was not available in the CAD-negative group, a second control group from the general population was recruited. They were healthy participants who were asymptomatic other than having functional epigastric pain but with a normal result on upper endoscopy performed in our unit. They were age- and sex-matched to the CAD-positive group within 5 years on a nearly case-to-case basis. This group did not undergo coronary angiogram. The same exclusion criteria were also applied in this second control group.

All individuals in the 3 groups were invited to participate. Information on age, sex, history of smoking, diabetes mellitus, hypertension, family history of colorectal cancer, and use and duration of aspirin and statins was recorded. Waist circumference was measured. Blood was drawn and fasting glucose level and complete lipid profile were measured. The metabolic syndrome was defined as at least 3 of the following criteria set forth by the National Cholesterol Education Program's modified Adult Treatment Panel III (Asian Pacific Region criteria)13: (1) abdominal obesity: waist circumference of at least 36 in (91 cm) for men and 32 in (81 cm) for women; (2) low high-density lipoprotein cholesterol level: 40 mg/dL (1.03 mmol/L) or lower for men and 50 mg/dL (1.3 mmol/L) or lower for women; (3) hypertriglyceridemia: 150 mg/dL (1.7 mmol/L) or higher; (4) hypertension: blood pressure 130/85 mm Hg or higher; and (5) impaired glucose tolerance: fasting glucose 110 mg/dL (6.1 mmol/L) or higher.

Colonoscopy

Colonoscopy was scheduled within 8 weeks after assessing for eligibility or after revascularization for critical patients. All patients received the same bowel preparation. Colonoscopies were repeated the next day for those with poor bowel preparation. Patients taking clopidogrel had their treatment changed to subcutaneous heparin 2 days before colonoscopy. Endoscopists were blinded to the CAD status of the patients. The withdrawal time of the colonoscopy procedure was more than 6 min to minimize the chance of lesions being missed.14 Incomplete examination was excluded from analysis.

Advanced colonic lesion was defined as presence of cancer or adenomas with villous component, with high-grade dysplasia, or 1 cm or larger. The size of a polyp was assessed by comparing it with an open colonoscope biopsy forcep (Bard, Murray Hill, NJ). The site of colorectal neoplasm was defined as right-sided if proximal to splenic flexure. The size, site, histologic findings, and number of polyps were recorded.

Statistical Analysis

The polyp prevalence in Hong Kong was assumed to be 24% (including hyperplastic polyps).15 Assuming an unadjusted odds ratio of 2.0,3 the sample size required to achieve a 2-tailed α level of significance of .05 with a power of 1−β = .9 was 207 in the CAD-positive, CAD-negative, and general population groups.

The Pearson χ2 test or the Fisher exact test (for small prevalences) was carried out to perform simple comparisons of prevalence based on various demographic and clinical characteristics among participants in the CAD-positive, CAD-negative, and general population groups. F tests based on a 1-way analysis of variance model was used to compare the ages of the patients in the 3 groups. Descriptive statistics and simple analyses were carried out using JMP software, release 6.0.2 (SAS Institute Inc, Cary, North Carolina).

A bivariate logistic regression analysis16,17 was carried out to examine the association between colorectal neoplasm and CAD, adjusted accordingly for potential risk factors χ1, . . . , χk. In the current application, we let Y = 1 denote presence of CAD and W = 1 denote presence of colorectal neoplasm, while Y = 0 and W = 0 denote the absence of CAD and colorectal neoplasm, respectively. The marginal probabilities of Y and W were modeled by the usual logistic regression analysis with models

logit[P(Yi = 1)] = α1 + α2x1i +  . . .  + αk+1xk,i

and

logit[P(Wi = 1)] = β1 + β2x1i +  . . .  +βk+1xk,i for i = 1, . . . ,  n.

The odds ratio [OR] is defined as

This OR measures the association of CAD and colorectal neoplasm. An OR of γi = 1 corresponds to no association between CAD and colorectal neoplasm, and γi>1 means that a patient with CAD is also more likely to have colorectal neoplasm, with larger values of γi indicating a stronger association. While it is possible to model this OR γi as a constant γ, forcing it to be the same for all participants in the population, we chose to also let it depend on covariates, thus allowing patients with certain characteristics to have a stronger association between CAD and colorectal neoplasm than others. This relationship is mitigated through the equation

log(γi) = θ1 + θ2x1i +  . . .  + θk+1xk,i

With this specification, the joint probabilities of Y and W are given by

where

δi = 1 + (γi − 1){γi[P(Yi = 1) − P(Wi = 1)]2 − [P(Yi = 1)+P(Wi = 1)]2 + 2[P(Yi = 1) + P(Wi = 1)]}

and

P(Yi = 1,Wi = 0) = P(Yi = 1) − P(Yi = 1,Wi = 1),

P(Yi = 0,Wi = 1) = P(Wi = 1) − P(Yi = 1,Wi = 1),

P(Yi = 0,Wi = 0) = 1 − P(Yi = 1) − P(Wi = 1) + P(Yi = 1,Wi = 1).

Maximum likelihood estimates of the regression coefficients, namely α, β, and θ, were computed using a tailor-made computer program in FORTRAN language. The 95% confidence intervals (CIs) were computed based on the asymptotic χ2 distributed properties of the log-likelihood ratio. The CAD-negative and general population groups were pooled together as the control group in the bivariate logistic regression analysis because they were not statistically significantly different in terms of sex and age distribution, family history of colorectal cancer, smoking history, metabolic syndrome, or diabetes (Table 1). Our aim was to (1) assess if any association existed between CAD and colorectal neoplasm and (2) identify the risk factors that predispose to both diseases simultaneously.

Table Graphic Jump LocationTable 1. Key Risk Factors and Assessment of Heterogeneity of the CAD-Negative and General Population Groups

There are a number of potential covariates, but not all of them are useful predictors in the marginal probabilities of Y or W or the ORs of the 2 events. The effects of age and sex were included in the modeling of the marginal probabilities P(Y = 1) and P(W = 1) since they are well known to be the risk factors that predispose to the development of both CAD and colonic lesions. We did not consider other factors in the marginal models because our primary objective was to investigate the effect of factors on the association between CAD and colorectal neoplasm or advanced lesions, and the inclusion of too many simultaneous factors in the model could result in colinearity or other difficulties fitting the model.

In the first phase of our analysis, we simply assumed that the OR γ was a constant that, thus, was not affected by any covariates. We tested the null hypothesis of no association between CAD and colorectal neoplasm using a Wald test. In the second phase of the bivariate logistic regression analysis, we allowed the OR γ to depend on some explanatory variable that may play an important role in mitigating the association of the 2 diseases. The factors of age, sex, metabolic syndrome, smoking history, and family history of colon cancer were included in the regression model for the log OR, log(γi); while the effects of age and sex were adjusted in the modeling of P(Yi = 1) and P(Wi = 1). A backward-elimination procedure was adopted to remove the most insignificant variable in the regression model for log(γi) at each step until the P values for the variables remained in the working model were all less than .10.

The P values reported are based on 2-tailed alternatives in the cases in which comparisons were made between 2 groups and for the regression coefficients of the log OR in the bivariate logistic regression analyses. The method of Holm18 was used to adjust the P values in multiple testing, where appropriate, particularly on the demographic variables and prevalence of colonic lesions of the 3 groups. For example, when reporting KP values for K distinct tests, the Holm method is to compare the rth smallest P value (for r = 1, . . . , K) among the KP values with .05/(K − r + 1), and the test result is considered statistically significant after adjustment for the multiple tests if the rth smallest P value is less than .05/(K − r + 1). However, if the rth smallest P value is the first that exceeds .05/(K − r + 1), then the test results associated with the (K − r + 1) largest P values are considered statistically nonsignificant according to the Holm method. To make the presentation simpler, we let the adjusted P value be (K − r + 1) times the original P value and simply compare the adjusted P value with .05 to determine whether a particular test result is statistically significant after adjustment.

Baseline Characteristics

There were 706 participants assessed for eligibility in the 3 groups. The response rates are summarized in the Figure. The final numbers of participants for analysis were 206, 208, and 207 in the CAD-positive, CAD-negative, and general population groups, respectively.

Figure. Study Recruitment and Participant Flow
Graphic Jump Location

CAD indicates coronary artery disease.

The baseline demographic and clinical characteristics in each group are summarized in Table 2. The CAD-positive and general population group were age- and sex-matched. According to the Holm adjustment, we concluded that the mean age and distributions of family history of colorectal cancer were insignificantly different among the 3 groups, but there were differences in the distributions of sex, smoking history, the metabolic syndrome, and the individual factors of the metabolic syndrome among the 3 groups (Table 2). Eighty-five percent of the patients in the CAD-positive group underwent revascularization and 10% underwent coronary artery bypass graft surgery; the remaining 5% were treated noninvasively. None of the participants in the CAD-negative and general population groups underwent revascularization or coronary artery bypass graft surgery. The prevalence of the metabolic syndrome in the CAD-positive patients in our study is similar to that reported in the Asia/Pacific region.19,20

Table Graphic Jump LocationTable 2. Baseline Demographic and Clinical Characteristics of the CAD-Positive, CAD-Negative, and General Population Groups
Prevalence and Characteristics of Colorectal Neoplasms

The characteristics and prevalence of colonic lesions in the 3 groups are summarized in Table 3 together with the original and Holm-adjusted P values. Colorectal neoplasm and advanced lesion were more prevalent (34.0% and 18.4%, respectively) in the CAD-positive group than in the CAD-negative (18.8% and 8.7%) and general population (20.8% and 5.8%) groups (P < .001 for both by Pearson χ2 test and adjusted P = .002 and P = .001, respectively). In addition, using the Holm method, there was no difference in the prevalence of endoscopic polyps (40.8% vs 28.4% vs 33.3%; adjusted P = .055 by Pearson χ2 test), hyperplastic polyps (8.3% vs 4.8% vs 7.2%; adjusted P = .33 by Fisher exact test), and adenocarcinoma (4.4% vs 0.5% vs 1.4%; adjusted P = .06 by Fisher exact test). Differences in the prevalence of colorectal neoplasm (34.0% vs 20.8%; adjusted P = .01 by Pearson χ2 test) and advanced lesions (18.4% vs 5.8%; adjusted P<.001 by Pearson χ2 test) were still observed when comparing only the CAD-positive and general population groups, which were age- and sex-matched.

Table Graphic Jump LocationTable 3. Type and Prevalence of Colonic Lesions in the CAD-Positive, CAD-Negative, and General Population Groups

Of the 9 adenocarcinomas (4.4%) detected in the CAD-positive group, 8 were asymptomatic. Five (55%) of the 9 cancers detected were at an early stage (Dukes A or B) and were small (<3 cm). In contrast, only 1 cancer (0.5%) and 3 cancers (1.4%) were detected in the CAD-negative and general population groups, respectively. All were asymptomatic and 75% (3/4) were of small size (1-2 cm) and early stage (Dukes A).

Bivariate Logistic Regression Analysis

The 2 control groups were merged for the bivariate logistic regression analysis because no significant differences between them were found for any demographic or clinical characteristics (age, sex, family history of colorectal cancer, smoking status, presence of the metabolic syndrome, and high fasting glucose level) and the 2 groups appeared to be reasonably homogeneous (Table 1).

Assuming that the OR of the association of the 2 diseases was constant (ie, not affected by any independent variables) when adjusting only for the marginal probabilities for age and sex, we observed evidence of a strong association between colorectal neoplasm and CAD (OR, 1.88; 95% CI, 1.25-2.70; 2-tailed P = .002; Table 4), and between advanced lesions and CAD (OR, 2.51; 95% CI, 1.43-4.35; 2-tailed P = .001; Table 5). If all explanatory variables (age, sex, smoking status, family history of colon cancer, and the metabolic syndrome) were included in the estimate of the marginal probabilities P(Yi = 1) and P(Wi = 1) and assuming the OR did not depend on any explanatory variables, the constant OR for CAD and colorectal neoplasm is estimated to be 1.54 (95% CI, 1.04-2.30; 2-tailed P = .048).

Table Graphic Jump LocationTable 4. Results of the Bivariate Logistic Regression Analysis on CAD and Colorectal Neoplasm Assuming a Constant Odds Ratio γ
Table Graphic Jump LocationTable 5. Results of Bivariate Logistic Regression Analysis on CAD and Advanced Lesions Assuming a Constant Odds Ratio γ

In the second part of the bivariate logistic regression analysis, we allowed the OR for the association of the 2 diseases to depend on explanatory variables like age, sex, smoking status, metabolic syndrome, and family history of colorectal cancer. To identify the risk factors and/or predictors that predispose to the development of both CAD and colorectal neoplasm, the variables of age, sex, smoking history, metabolic syndrome, and family history of colorectal cancer were included as the explanatory variables for the log of the OR while adjusted for the variables of age and sex in the marginal probabilities P(Yi = 1) and P(Wi = 1). A backward-elimination procedure was adopted to remove the most nonsignificant variable in the regression of the log of the OR at each step. The final model indicated that the association between CAD and colorectal neoplasm did not depend on any of the aforementioned explanatory variables (P > .05) and that the OR (estimated to be 1.88; Table 4) was constant across all participants.

However, we found that both the metabolic syndrome and history of smoking were strong independent predictive factors for the positive association between advanced lesions and CAD (for metabolic syndrome, OR, 5.99; 95% CI, 1.43-28.0; 2-tailed P = .02; for smoking, OR, 4.74; 95% CI, 1.38-19.0; 2-tailed P = .02; Table 6). This indicates that participants who were smokers and/or who had the metabolic syndrome were much more likely to develop both CAD and advanced lesions. The OR of the metabolic syndrome in predicting the positive association of the 2 diseases was higher than the OR of the individual components of the metabolic syndrome (Table 7) after adjustment for age and sex. The wide CI for this OR was because the OR was larger in magnitude and fewer participants had the metabolic syndrome than had its individual components.

Table Graphic Jump LocationTable 6. Final Results of the Bivariate Logistic Regression Analysis on CAD and Advanced Lesions Allowing the Odds Ratio γ to Depend on Some Explanatory Variables
Table Graphic Jump LocationTable 7. Age- and Sex-Adjusted Odds Ratios for Independent Predictive Factors for Association of Advanced Colonic Lesions and CAD
Complications

One patient from the CAD-positive group developed colonic perforation during polypectomy for a 2-cm sessile villous adenoma. She recovered after operation. Another patient in the CAD-positive group developed congestive heart failure after bowel preparation for colonoscopy and was treated conservatively.

Previous studies have reported the association between colorectal neoplasm and CAD,2123 and some have refuted the association.24 The current study confirms the association between the 2 diseases and our previous retrospective study observation.3 The design of the current study is robust compared to others2124 in that CAD was defined by coronary angiogram, which is the criterion standard for diagnosing CAD, and that patients were recruited prospectively for colonoscopy. We observed that there was a strong association between colorectal neoplasm and CAD (OR, 1.88) and between advanced colonic lesion and CAD (OR, 2.51). The prevalence of colorectal neoplasm (34%) was much higher in the CAD-positive group than in the CAD-negative group (18.8%) or in the age- and sex-matched general population group (20.8%), as well as that reported by Sung et al15 (21%). Moreover, the prevalence of advanced lesions (18.4%) and adenocarcinoma (4.4%) was also observed to be much higher in the CAD-positive group.

The high prevalence of advanced lesions in CAD-positive patients in the study is remarkable. This is much higher than the 12.5% reported in the general population in Hong Kong by Sung et al15 and the 10.5% in the US general population.25 Importantly, we observed that the metabolic syndrome and smoking, after adjusting for age and sex, were important predictive factors for the association of advanced colonic lesions and CAD. It has been well documented that old age and male sex are important risk factors for CAD and colorectal neoplasm. However, these 2 factors are not modifiable. But the metabolic syndrome and smoking are environmental factors that can be reversed. Smoking has been demonstrated as a major risk factor in the development of the 2 diseases.26,27 There are also reports on insulin resistance syndrome and colorectal cancer,28,29 as well as metabolic syndrome, predisposing to colorectal adenomas.30,31

Both colorectal neoplasm and CAD probably develop through the mechanism of chronic inflammation. Inflammation is now recognized as being pivotal in the pathogenesis of atherosclerosis and, hence, CAD.32,33 Colorectal cancer is also thought to progress through the pathway of inflammation.34 This is evidenced by the development of colorectal cancer in patients with ulcerative colitis. Inflammation, which may result from underlying risk factors, may be the culprit for the simultaneous development of the 2 conditions. In addition, insulin resistance is recognized as an important metabolic defect linking the components of the metabolic syndrome. The direct proliferative/antiapoptotic effects of insulin and related insulinlike growth factor 1 on both colorectal neoplasm and CAD has gained support recently.35,36 Peroxisome proliferator–activated receptor γ may play an important role in metabolic syndrome to regulate metabolic and vascular pathways. These may be important potential mechanisms for the simultaneous evolution of the 2 diseases. Interestingly, statins have been shown to have beneficial effects in both colorectal cancer and CAD, probably through an anti-inflammatory mechanism.37 Aspirin has long been proven to be beneficial in both conditions, albeit through different mechanisms.

It would be ideal to perform an age- and sex-matched study in both the CAD-positive and CAD-negative groups to study the association of the 2 diseases. However, in reality, this is nearly impossible. Asymptomatic men with healthy coronary arteries (the control group) would rarely undergo a coronary angiogram. Similarly, few young women have CAD (the study group). Therefore, we have included the age- and sex-matched general population as another control group. In addition, the factors of age and sex were further adjusted in the marginal logistic regression part of the analysis. We chose coronary angiogram to be the diagnostic criterion for the presence of CAD because diagnosis based on symptoms alone is not reliable and coronary angiogram has the highest sensitivity among the tests (treadmill, thallium scan, or computed tomography angiogram). However, the current design might have potential bias in that we were only assessing the prevalence of colorectal neoplasm in CAD patients who presented for coronary angiogram. The study might not be able to estimate the true magnitude of association between CAD and colorectal neoplasm because there might be a percentage of patients in the general population with CAD who have not had a coronary angiogram. However, the study highlights the important point that, at least in those with CAD presenting for coronary angiogram, a high prevalence of colorectal neoplasm was observed. The predictive value of the metabolic syndrome and smoking on predisposing the positive association of colorectal neoplasm and CAD is limited by the nature of the cross-sectional study. A prospective study evaluating the role of the metabolic syndrome and smoking on the 2 conditions is desirable.

In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.

Corresponding Author: Annie On On Chan, MD, PhD, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China (aoochan@hku.hk).

Author Contributions: Dr Chan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: A. O. O. Chan, Jim, Morris, Lai, S. K. Lam.

Acquisition of data: A. O. O. Chan, Jim, Siu, Tong, Ng, S. Y. Wong, C. K. Chan, Cheung, P. Chan, G. Wong, Yuen, Lau, Lee, B. C. Y. Wong.

Analysis and interpretation of data: A. O. O. Chan, K. F. Lam, Morris, Hui.

Drafting of the manuscript:A. O. O. Chan, Tong, C. K. Chan, Lai, P. Chan, Lau, Szeto, S. K. Lam.

Critical revision of the manuscript for important intellectual content: A. O. O. Chan, Jim, K. F. Lam, Morris, Siu, Ng, S. Y. Wong, Hui, Cheung, Yuen, Lee.

Statistical analysis: A. O. O. Chan, K. F. Lam, Morris.

Obtained funding: A. O. O. Chan, S. K. Lam.

Administrative, technical, or material support: A. O. O. Chan.

Study supervision: A. O. O. Chan.

Financial Disclosures: None reported.

Funding/Support: The study was partially sponsored by the Gastrointestinal Cancer Research Fund, University of Hong Kong.

Role of the Sponsor: The Gastrointestinal Cancer Research Fund had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

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Sung JJ, Chan FK, Leung WK.  et al.  Screening for colorectal cancer in Chinese: comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy.  Gastroenterology. 2003;124(3):608-614
PubMed   |  Link to Article
Chan JS, Kuk AY, Bell J. A likelihood approach to analyzing longitudinal bivariate binary data.  Biom J. 1997;4:409-421
Link to Article
Ananth CV, Preisser JS. Bivariate logistic regression: modelling the association of small for gestational age births in twin gestations.  Stat Med. 1999;18(15):2011-2023
PubMed   |  Link to Article
Holm S. A simple sequentially rejective multiple test procedure.  Scand J Stat. 1979;6:65-70
Kwon HS, Prak YM, Lee HJ.  et al.  Prevalence and clinical characteristics of the metabolic syndrome in middle-aged Korean adults.  Korean J Intern Med. 2005;20(4):310-316
PubMed   |  Link to Article
Lin RT, Lee WJ, Jeng CY, Sheu WH, Chen YT. Metabolic syndrome and its contribution to CAD in non-DM participants.  J Formos Med Assoc. 2004;103(4):317-320
PubMed
Correa P, Strong JP, Johnson WD.  et al.  Atherosclerosis and polyps of the colon: quantification of precursors of coronary heart disease and colon cancer.  J Chronic Dis. 1982;35(5):313-320
PubMed   |  Link to Article
Neugut AI, Jacobson JS, Sherif G.  et al.  Coronary artery disease and colorectal neoplasia.  Dis Colon Rectum. 1995;38(8):873-877
PubMed   |  Link to Article
Reicher-Reiss H, Jonas M, Goldbourt U, Boyko V, Modan B. Selectively increased risk of cancer in men with coronary heart disease.  Am J Cardiol. 2001;87(4):459-462, A6
PubMed   |  Link to Article
Neugut AI, Rosenberg DJ, Ahsan H.  et al.  Association between coronary heart disease and cancers of the breast, prostate, and colon.  Cancer Epidemiol Biomarkers Prev. 1998;7(10):869-873
PubMed
Lieberman DA, Prindiville S, Weiss DG, Willett W.VA Cooperative Study Group 380.  Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals.  JAMA. 2003;290(22):2959-2967
PubMed   |  Link to Article
Lakier JB. Smoking and cardiovascular disease.  Am J Med. 1992;93(1A):8S-12S
PubMed   |  Link to Article
Giovannucci E. An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer.  Cancer Epidemiol Biomarkers Prev. 2001;10(7):725-731
PubMed
Bowers K, Albanes D, Limburg P.  et al.  A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers.  Am J Epidemiol. 2006;164(7):652-664
PubMed   |  Link to Article
Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR. The metabolic syndrome and risk of incident colorectal cancer.  Cancer. 2006;107(1):28-36
PubMed   |  Link to Article
Morita T, Tabata S, Mineshita M, Mizoue T, Moore MA, Kono S. The metabolic syndrome is associated with increased risk of colorectal adenoma development: the Self-Defense Forces health study.  Asian Pac J Cancer Prev. 2005;6(4):485-489
PubMed
Wang YY, Lin SY, Lai WA, Liu PH, Sheu WH. Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population.  J Gastroenterol Hepatol. 2005;20(9):1410-1415
PubMed   |  Link to Article
Tiong AY, Brieger D. Inflammation and coronary artery disease.  Am Heart J. 2005;150(1):11-18
PubMed   |  Link to Article
Sepulveda JL, Mehta JL. C-reactive protein and cardiovascular disease: a critical appraisal.  Curr Opin Cardiol. 2005;20(5):407-416
PubMed
Clevers H. At the crossroads of inflammation and cancer.  Cell. 2004;118(6):671-674
PubMed   |  Link to Article
Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis.  Lancet. 2004;363(9418):1346-1353
PubMed   |  Link to Article
McEwen JE, Zimniak P, Mehta JL, Reis RJ. Molecular pathology of aging and its implications for senescent coronary atherosclerosis.  Curr Opin Cardiol. 2005;20(5):399-406
PubMed   |  Link to Article
Demierre MF, Higgins PD, Gruber SB.  et al.  Statins and cancer prevention.  Nat Rev Cancer. 2005;5(12):930-942
PubMed   |  Link to Article

Figures

Figure. Study Recruitment and Participant Flow
Graphic Jump Location

CAD indicates coronary artery disease.

Tables

Table Graphic Jump LocationTable 1. Key Risk Factors and Assessment of Heterogeneity of the CAD-Negative and General Population Groups
Table Graphic Jump LocationTable 2. Baseline Demographic and Clinical Characteristics of the CAD-Positive, CAD-Negative, and General Population Groups
Table Graphic Jump LocationTable 3. Type and Prevalence of Colonic Lesions in the CAD-Positive, CAD-Negative, and General Population Groups
Table Graphic Jump LocationTable 4. Results of the Bivariate Logistic Regression Analysis on CAD and Colorectal Neoplasm Assuming a Constant Odds Ratio γ
Table Graphic Jump LocationTable 5. Results of Bivariate Logistic Regression Analysis on CAD and Advanced Lesions Assuming a Constant Odds Ratio γ
Table Graphic Jump LocationTable 6. Final Results of the Bivariate Logistic Regression Analysis on CAD and Advanced Lesions Allowing the Odds Ratio γ to Depend on Some Explanatory Variables
Table Graphic Jump LocationTable 7. Age- and Sex-Adjusted Odds Ratios for Independent Predictive Factors for Association of Advanced Colonic Lesions and CAD

References

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Simmons DT, Harewood GC, Baron TH.  et al.  Impact of endoscopist withdrawal speed on polyp yield: implications for optimal colonoscopy withdrawal time.  Aliment Pharmacol Ther. 2006;24(6):965-971
PubMed   |  Link to Article
Sung JJ, Chan FK, Leung WK.  et al.  Screening for colorectal cancer in Chinese: comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy.  Gastroenterology. 2003;124(3):608-614
PubMed   |  Link to Article
Chan JS, Kuk AY, Bell J. A likelihood approach to analyzing longitudinal bivariate binary data.  Biom J. 1997;4:409-421
Link to Article
Ananth CV, Preisser JS. Bivariate logistic regression: modelling the association of small for gestational age births in twin gestations.  Stat Med. 1999;18(15):2011-2023
PubMed   |  Link to Article
Holm S. A simple sequentially rejective multiple test procedure.  Scand J Stat. 1979;6:65-70
Kwon HS, Prak YM, Lee HJ.  et al.  Prevalence and clinical characteristics of the metabolic syndrome in middle-aged Korean adults.  Korean J Intern Med. 2005;20(4):310-316
PubMed   |  Link to Article
Lin RT, Lee WJ, Jeng CY, Sheu WH, Chen YT. Metabolic syndrome and its contribution to CAD in non-DM participants.  J Formos Med Assoc. 2004;103(4):317-320
PubMed
Correa P, Strong JP, Johnson WD.  et al.  Atherosclerosis and polyps of the colon: quantification of precursors of coronary heart disease and colon cancer.  J Chronic Dis. 1982;35(5):313-320
PubMed   |  Link to Article
Neugut AI, Jacobson JS, Sherif G.  et al.  Coronary artery disease and colorectal neoplasia.  Dis Colon Rectum. 1995;38(8):873-877
PubMed   |  Link to Article
Reicher-Reiss H, Jonas M, Goldbourt U, Boyko V, Modan B. Selectively increased risk of cancer in men with coronary heart disease.  Am J Cardiol. 2001;87(4):459-462, A6
PubMed   |  Link to Article
Neugut AI, Rosenberg DJ, Ahsan H.  et al.  Association between coronary heart disease and cancers of the breast, prostate, and colon.  Cancer Epidemiol Biomarkers Prev. 1998;7(10):869-873
PubMed
Lieberman DA, Prindiville S, Weiss DG, Willett W.VA Cooperative Study Group 380.  Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals.  JAMA. 2003;290(22):2959-2967
PubMed   |  Link to Article
Lakier JB. Smoking and cardiovascular disease.  Am J Med. 1992;93(1A):8S-12S
PubMed   |  Link to Article
Giovannucci E. An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer.  Cancer Epidemiol Biomarkers Prev. 2001;10(7):725-731
PubMed
Bowers K, Albanes D, Limburg P.  et al.  A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers.  Am J Epidemiol. 2006;164(7):652-664
PubMed   |  Link to Article
Ahmed RL, Schmitz KH, Anderson KE, Rosamond WD, Folsom AR. The metabolic syndrome and risk of incident colorectal cancer.  Cancer. 2006;107(1):28-36
PubMed   |  Link to Article
Morita T, Tabata S, Mineshita M, Mizoue T, Moore MA, Kono S. The metabolic syndrome is associated with increased risk of colorectal adenoma development: the Self-Defense Forces health study.  Asian Pac J Cancer Prev. 2005;6(4):485-489
PubMed
Wang YY, Lin SY, Lai WA, Liu PH, Sheu WH. Association between adenomas of rectosigmoid colon and metabolic syndrome features in a Chinese population.  J Gastroenterol Hepatol. 2005;20(9):1410-1415
PubMed   |  Link to Article
Tiong AY, Brieger D. Inflammation and coronary artery disease.  Am Heart J. 2005;150(1):11-18
PubMed   |  Link to Article
Sepulveda JL, Mehta JL. C-reactive protein and cardiovascular disease: a critical appraisal.  Curr Opin Cardiol. 2005;20(5):407-416
PubMed
Clevers H. At the crossroads of inflammation and cancer.  Cell. 2004;118(6):671-674
PubMed   |  Link to Article
Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis.  Lancet. 2004;363(9418):1346-1353
PubMed   |  Link to Article
McEwen JE, Zimniak P, Mehta JL, Reis RJ. Molecular pathology of aging and its implications for senescent coronary atherosclerosis.  Curr Opin Cardiol. 2005;20(5):399-406
PubMed   |  Link to Article
Demierre MF, Higgins PD, Gruber SB.  et al.  Statins and cancer prevention.  Nat Rev Cancer. 2005;5(12):930-942
PubMed   |  Link to Article
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