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Prevalence of Colorectal (cancer) Neoplasm Among Patients With Newly Diagnosed Coronary Artery Disease, and the Metabolic Syndrome
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JAMA. Sept 26, 2007;298:1412-1419.
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 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).
"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"
ABSTRACT
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 2 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.
INTRODUCTION
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. 4-6 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.10-12 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.
COMMENT
Previous studies have reported the association between colorectal neoplasm and CAD,21-23 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 others21-24 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 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.
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