Clinical Gastroenterology and Hepatology 2014;-:-–-

LETTER TO THE EDITOR Readers are encouraged to write letters to the editor concerning articles that have been published in Clinical Gastroenterology and Hepatology. Short, general comments are also considered, but use of the Letters to the Editor section for publication of original data in preliminary form is not encouraged. Letters should be typewritten and submitted electronically to http://www. editorialmanager.com/cgh.

Are Patients With Inflammatory Bowel Diseases at Increased Risk for Cardiovascular Disease? Dear Editor: The debate as to whether patients with inflammatory bowel diseases (IBDs) are at increased risk for cardiovascular disease (CVD) remains open. Epidemiologic studies, mainly retrospective with contradictory results, have been inconclusive. Thus, the systematic review and meta-analysis published recently in this journal contributes greatly to this debate.1 The authors included 9 studies, 6 case-control and 3 cohort studies, that assessed risk of cardiovascular accidents (CVAs), ischemic heart disease, and/or peripheral arterial disease in patients with IBD compared with non-IBD populations. They found 18% increased risk of CVA and ischemic heart disease in IBD patients, with the risk being significantly increased only in female patients, and no difference in the risk of peripheral arterial disease. The CVD risk was similar in patients with Crohn’s disease (CD) and ulcerative colitis (UC). We strongly believe that these results should be interpreted with caution. To assess CVD risk in IBD patients, comparisons should be made against populations with similar traditional CVD risk factors, ie, smoking, diabetes mellitus, dyslipidemia, hypertension, and obesity. This is particularly important considering that IBD patients exhibit distinctive CVD risk profile compared with non-IBD populations. It is well known that smoking has a beneficial effect on UC, and cessation has been associated with disease exacerbations, whereas smoking has a detrimental effect on intestinal inflammation in CD. Smoking patterns in IBD have been studied in a cohort of 820 patients, with 52% of CD patients vs only 9% of UC patients being active smokers.2 Only 3 of the included studies in the present meta-analysis controlled for smoking,3–5 and in one of them smoking rates were significantly higher in the CD group when compared with both UC patients and controls (37%, 23%, and 28%, respectively).4 Dyslipidemia, in particular high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol levels, and obesity are major risk factors for CVD. IBD patients exhibit lower LDL-C levels compared with controls matched for body mass index (BMI),6 and commonly low BMI. Five of the included studies adjusted for hyperlipidemia3–5,7,8 and 3 for BMI.3–5 In 2 of these studies, hyperlipidemia was more common among IBD

patients,7,8 and in 1 study IBD patients had significantly lower total cholesterol and LDL-C levels.5 With regard to the rest of traditional CVD risk factors, 3 studies did not control for either diabetes or hypertension.9–11 In 3 studies hypertension was more common among IBD patients,4,7,8 in 1 study diabetes was more common in the same group,8 whereas in another study both hypertension and diabetes were less common in IBD patients.5 It is worth mentioning that 3 studies did not assess any of the traditional CVD risk factors, and in another study IBD patients had significantly higher rates of heart failure and cardiac dysrhythmias.8 IBD patients might be predisposed to accelerated atherosclerosis secondary to chronic systemic inflammation leading to endothelial dysfunction. The inflammatory burden in IBD entails several factors such as disease duration, extent of intestinal involvement, disease activity, ie, frequency and severity of flares, as well as the effect of anti-inflammatory therapy. It is evident that there is great heterogeneity within the IBD population with regard to the inflammatory burden, which likely translates into different degree of endothelial damage and, thus, different CVD risk. Patients with longer disease duration, extensive bowel involvement, and severe persistent disease would be expected to be at the greatest risk for CVD. Kristensen et al8 demonstrated increased risk of myocardial infarction, CVA, and CV death in IBD patients during flares or periods of persistent activity, whereas the risk was not increased in patients in remission when compared with the reference population. Before making the hasty conclusion that this difference highlights the role of chronic inflammation in the atherogenesis process in these patients, we should consider that acute illness is associated with increased short-term risk of CV events even in non-IBD populations.12 In summary, we believe that the evidence so far does not suffice to conclude definitively as to whether IBD patients are at increased risk for CVD. Prospective studies are needed not only with large number of patients and long-term follow-up, but importantly with control groups that have similar CVD risk profile with the IBD population studied. Stratification of the IBD population according to inflammatory burden is also required. Composite scoring systems should be generated to stratify/classify inflammatory burden in IBD patients. Finally, the use of potent anti-inflammatory agents should also be taken into consideration, because they

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Letter to the Editor

may effectively lower the inflammatory burden and subsequently lower CVD risk. ELENI THEOCHARIDOU, MD 2nd Propaedeutic Department of Internal Medicine Hippokration General Hospital Aristotle University of Thessaloniki Thessaloniki, Greece THOMAS D. GOSSIOS, MD Department of Cardiology AHEPA General Hospital Aristotle University of Thessaloniki Thessaloniki, Greece ASTERIOS KARAGIANNIS, MD, PhD 2nd Propaedeutic Department of Internal Medicine Hippokration General Hospital Aristotle University of Thessaloniki Thessaloniki, Greece

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References 1. Singh S, et al. Clin Gastroenterol Hepatol 2014;12:382–393. 2. van der Heide F, et al. J Crohns Colitis 2010;4:125–131. 3. Andersohn F, et al. Inflamm Bowel Dis 2010;16:1387–1392. 4. Osterman MT, et al. Clin Gastroenterol Hepatol 2011;9:875–880. 5. Yarur AJ, et al. Am J Gastroenterol 2011;106:741–747. 6. Theocharidou E, et al. J Crohns Colitis 2014 Feb 11. Epub ahead of print. 7. Ha C, et al. Am J Gastroenterol 2009;104:1445–1451. 8. Kristensen SL, et al. PLoS One 2013;8:e56944. 9. Zoller B, et al. BMC Neurol 2012;12:41. 10. Zoller B, et al. PLoS One 2012;7:e33442. 11. Bernstein CN, et al. Clin Gastroenterol Hepatol 2008;6:41–45. 12. Dalager-Pedersen M, et al. Circulation 2014;129:1387–1396.

Conflicts of interest The authors disclose no conflicts. http://dx.doi.org/10.1016/j.cgh.2014.04.004

Are patients with inflammatory bowel diseases at increased risk for cardiovascular disease?

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