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Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease

Published:November 01, 2016DOI:https://doi.org/10.1016/j.ejim.2016.10.004

      Highlights

      • This study investigated expression of markers of subclinical atherosclerosis (ATS) in IBD.
      • Both IMT and arterial stiffness parameters (PWV and AIx) are increased in IBD patients.
      • Markers of ATS are significantly increased in patients on 5-ASA therapy only.
      • Therapies able to obtain a full control of inflammation may reverse also ATS risk in IBD.
      • Longitudinal studies are needed to confirm the correlation between ATS markers, inflammation and drug options in IBD.

      Abstract

      Background & Aims

      Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients.

      Methods

      We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45 years old (median age 31.6 ± 8.1 years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed by measurement of carotid-femoral Pulse Wave Velocity (PWV) and Augmentation Index (AIx).

      Results

      Total cholesterol (P< 0.013) and LDL-cholesterol (P< 0.019) levels were significantly lower in IBD patients compared to controls. Carotid IMT was higher in IBD than in controls (P< 0.047), but there was no statistically significant difference among Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Moreover, PWV and AIx were significantly higher in patients as compared to controls (P< 0.006 and P< 0.004 respectively). No medication seemed to affect vascular measurements, though stiffness parameters were significantly higher in patients treated with 5-ASA (11.9 (9.7) vs 18.2 (10.2), P < 0.021), suggesting a lack of efficacy of 5-ASA in protecting IBD patients from early atherogenesis.

      Conclusions

      Young IBD patients show an increase in subclinical markers of atherosclerosis. Future studies need to address whether these markers result in an increased risk of cardiovascular events in these patient.

      Abbreviations:

      IBD (Inflammatory bowel disease), CD (Crohn's Disease), UC (Ulcerative Colitis), IMT (Intima media thickness), PWV (Pulse wave velocity), AIx (Augmentation index), DBP (Diastolic blood pressure), SBP (Systolic blood pressure), FMD (Flow mediated dilation), ESR (Erythrocyte-sedimentation rate), CRP (C-reactive protein)

      Keywords

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      References

        • Baumgart D.C.
        • Carding S.R.
        Inflammatory bowel disease: cause and immunobiology.
        Lancet. 2007; 369: 1627-1640
        • Wakefield A.J.
        • Sawyerr A.M.
        • Dhillon A.P.
        • et al.
        Pathogenesis of Crohn's disease: multifocal gastrointestinal infarction.
        Lancet. 4 1989; 2: 1057-1062
        • Bernstein C.N.
        • Blanchard J.F.
        • Houston D.S.
        • et al.
        The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study.
        ThrombHaemost. 2001; 85: 430-434
        • Ross R.
        Atherosclerosis an inflammatory disease.
        N Engl J Med. 14 1999; 340: 115-126
        • Laroux F.S.
        • Grisham M.B.
        Immunological basis of infiammatory bowel disease: role of microcirculation.
        Microcirculation. 2001; 8: 283-301
        • Libby P.
        • Ridker P.M.
        • Maseri A.
        Inflammation and atherosclerosis.
        Circulation. 5 2002; 105: 1135-1143
        • Paoletti R.
        • Gotto Jr., A.M.
        • Hajjar D.P.
        Inflammation in atherosclerosis and implications for therapy.
        Circulation. 15 2004; 109: III20-III26
        • Hatoum O.A.
        • Binion D.G.
        The vasculature and inflammatory bowel disease: contribution to pathogenesis and clinical pathology.
        Inflamm Bowel Dis. 2005; 11: 304-313
        • Papa A.
        • Danese S.
        • Urgesi R.
        • et al.
        Early atherosclerosis in patients with inflammatory bowel disease.
        Eur Rev Med Pharmacol Sci. Jan-Feb 2006; 10: 7-11
        • Ross R.
        The pathogenesis of atherosclerosis: a perspective for the 1990s.
        Nature. Apr 29 1993; 362: 801-809
        • Libby P.
        • Ridker P.M.
        • Hansson G.K.
        Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice.
        J Am Coll Cardiol. 1 2009; 54: 2129-2138
        • Van Doornum S.
        • McColl G.
        • Wicks I.P.
        Accelerated atherosclerosis: an extra-articular feature of rheumatoid arthritis?.
        Arthritis Rheum. 2002; 46: 862-873
        • Selzer F.
        • Sutton-Tyrrell K.
        • Fitzgerald S.G.
        • et al.
        Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus.
        Arthritis Rheum. 2004; 50: 151-159
        • Södergren A.
        • Karp K.
        • Boman K.
        • et al.
        Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness.
        Arthritis Res Ther. 2010; 12: R158
        • Dorn S.D.
        • Sandler R.S.
        Inflammatory bowel disease is not a risk factor for cardiovascular disease mortality: results from a systematic review and meta-analysis.
        Am J Gastroenterol. 2007; 102: 662-667
        • Yarur A.J.
        • Deshpande A.R.
        • Pechman D.M.
        • et al.
        Inflammatory bowel disease is associated with an increased incidence of cardiovascular events.
        Am J Gastroenterol. 2011; 106: 741-747
        • Rungoe C.
        • Basit S.
        • Ranthe M.F.
        • et al.
        Risk of ischaemic heart disease in patients with inflammatory bowel disease: a nationwide Danish cohort study.
        Gut. 2013; 62: 689-694
        • Osterman M.T.
        • Yang Y.X.
        • Brensinger C.
        • et al.
        No increased risk of myocardial infarction among patients with ulcerative colitis or Crohn's Disease.
        Clin Gastroenterol Hepatol. 2011; 9: 875-880
        • Gandhi S.
        • Narula N.
        • Marshall J.K.
        • et al.
        Are patients with inflammatory bowel disease at increased risk of coronary artery disease?.
        Am J Med. 2012; 125: 956-962
        • Kristensen S.L.
        • Ahlehoff O.
        • Lindhardsen J.
        • et al.
        Disease activity in inflammatory bowel disease is associated with increased risk of myocardial infarction, stroke and cardiovascular death—a Danish nationwide cohort study.
        PLoS One. 2013; 8: e56944
        • Papa A.
        • Santoliquido A.
        • Danese S.
        • et al.
        Increased carotid intima-media thickness in patients with inflammatory bowel disease.
        Aliment Pharmacol Ther. 1 2005; 22: 839-846
        • Broide E.
        • Schopan A.
        • Zaretsky M.
        • et al.
        Intima-media thickness of the common carotid artery is not significantly higher in Crohn's disease patients compared to healthy population.
        Dig Dis Sci. 2011; 56: 197-202
        • Maharshak N.
        • Arbel Y.
        • Bornstein N.M.
        • et al.
        Inflammatory bowel disease is not associated with increased intimal media thickening.
        Am J Gastroenterol. 2007; 102: 1050-1055
        • Dagli N.
        • Poyrazoglu O.K.
        • Dagli A.F.
        • et al.
        Is inflammatory bowel disease a risk factor for early atherosclerosis?.
        Angiology. 2010; 61: 198-204
        • Kayahan H.
        • Sari I.
        • Cullu N.
        • Yuksel F.
        • Demir S.
        • Akarsu M.
        • et al.
        Evaluation of early atherosclerosis in patients with inflammatory bowel disease.
        Dig Dis Sci. Aug 2012; 57: 2137-2143
        • Schinzari F.
        • Armuzzi A.
        • De Pascalis B.
        • Mores N.
        • Tesauro M.
        • Melina D.
        • et al.
        Tumor necrosis factor-alpha antagonism improves endothelial dysfunction in patients with Crohn's disease.
        Clin Pharmacol Ther. Jan 2008; 83: 70-76
        • Aloi M.
        • Tromba L.
        • Di Nardo G.
        • Dilillo A.
        • Del Giudice E.
        • Marocchi E.
        • et al.
        Premature subclinical atherosclerosis in pediatric inflammatory bowel disease.
        J Pediatr. 2012; 161: 589-594
        • Principi M.
        • Mastrolonardo M.
        • Scicchitano P.
        • Gesualdo M.
        • Sassara M.
        • Guida P.
        • et al.
        Endothelial function and cardiovascular risk in active inflammatory bowel diseases.
        J Crohn's Colitis. 1 2013; 7: e427-e433
        • Zanoli L.
        • Cannavò M.
        • Rastelli S.
        • Di Pino L.
        • Monte I.
        • Di Gangi M.
        • et al.
        Arterial stiffness is increased in patients with inflammatory bowel disease.
        J Hypertens. 2012; 30: 1775-1781
        • Zanoli L.
        • Rastelli S.
        • Inserra G.
        • Lentini P.
        • Valvo E.
        • Calcagno E.
        • et al.
        Increased arterial stiffness in inflammatory bowel diseases is dependent upon inflammation and reduced by immunomodulatory drugs.
        Atherosclerosis. Jun 2014; 234: 346-351
        • Ozturk K.
        • Kuler A.M.
        • Cakir M.
        • Ozen A.
        • Demirci H.
        • Turker T.
        • et al.
        Pulse wave velocity, intima media thickness, and flow-mediated dilatation in patients with normotensive normoglycemic inflammatory bowel disease.
        Inflamm Bowel Dis. 2015; 21: 1314-1320
        • Rutgeerts P.
        • Sandborn W.J.
        • Feagan B.G.
        • Reinisch W.
        • Olson A.
        • Johanns J.
        • et al.
        Infliximab for induction and maintenance therapy for ulcerative colitis.
        N Engl J Med. Dec 8 2005; 353: 2462-2476
        • Harvey R.F.
        • Bradshaw M.J.
        Measuring Crohn's disease activity.
        Lancet. May 24 1980; 1: 1134-1135
        • Tuttolomondo A.
        • Di Raimondo D.
        • Di Sciacca R.
        • Pecoraro R.
        • Arnao V.
        • Buttà C.
        • et al.
        Arterial stiffness and ischemic stroke in subjects with and without metabolic syndrome.
        Atherosclerosis. 2012; 225: 216-219
        • Kovaite M.
        • Petrulioniene Z.
        • Ryliskyte L.
        • Badariene J.
        • Dzenkeviciute V.
        • Cypiene A.
        • et al.
        Systemic assessment of arterial wall structure and function in metabolic syndrome.
        Proc West Pharmacol Soc. 2007; 50: 123-130
        • Tuttolomondo A.
        • Pecoraro R.
        • Di Raimondo D.
        • Di Sciacca R.
        • Canino B.
        • Arnao V.
        • et al.
        Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke with and without metabolic syndrome.
        Diabetol Metab Syndr. Feb 27 2014; 6: 28
        • De Silva D.A.
        • Woon F.P.
        • Gan H.Y.
        • Cameron J.
        • Kingwell B.
        • Koh T.H.
        • et al.
        Arterial stiffness, metabolic syndrome and inflammation amongst Asian ischaemic stroke patients.
        Eur J Neurol. 2008; 15: 872-875
        • Kampus R.
        • Kals J.
        • Ristimae T.
        • Fischer K.
        • Zilmer M.
        • Teesalu R.
        High sensitivity C-reactive protein affects central hemodynamics and augmentation index in apparently healthy persons.
        J Hypertens. 2004; 22: 1133-1139
        • Dignass A.
        • Van Assche G.
        • Lindsay J.O.
        • Lémann M.
        • Söderholm J.
        • Colombel J.F.
        • et al.
        The second European evidence-based consensus on the diagnosis and management of Crohn's disease: current management.
        Journal of Crohn's and Colitis. 2010; 4: 28-62
        • Ford A.C.
        • Kane S.V.
        • Khan K.J.
        • Achkar J.P.
        • Talley N.J.
        • Marshall J.K.
        • et al.
        Efficacy of 5-aminosalicylates in Crohn's disease: systematic review and meta-analysis.
        Am J Gastroenterol. 2011; 106: 617-629
        • dos Santos L.C.
        • Costa A.V.
        • Lopes L.G.
        • et al.
        Combination of azathioprine and aminosalicylate treatment prevent risk of cardiovascular disease in women with ulcerative colitis by reducing inflammation.
        Med Sci Monit. 2015; 21: 2305-2315
        • Tuttolomondo A.
        • Pecoraro R.
        • Buttà C.
        • Di Raimondo D.
        • Ferrante A.
        • Della Corte V.
        • et al.
        Arterial stiffness indexes and serum cytokine levels in seronegative spondyloarthritis: relationships between stiffness markers and metabolic and immunoinflammatory variables.
        Scand J Rheumatol. 2015; 14: 1-6
        • Temiz A.
        • Gökmen F.
        • Gazi E.
        • Akbal A.
        • Barutçu A.
        • Bekler A.
        • et al.
        Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and carotid intima–media thickness. Associations in rheumatoid arthritis patients.
        Herz. 2015; 40: 217-224
        • Fan F.
        • Galvin A.
        • Fang L.
        • et al.
        Comparison of inflammation, arterial stiffness and traditional cardiovascular risk factors between rheumatoid arthritis and inflammatory bowel disease.
        J Inflamm. 2014; 11: 29
        • Willum-Hansen T.
        • Staessen J.A.
        • Torp-Pedersen C.
        • Rasmussen S.
        • Thijs L.
        • Ibsen H.
        • et al.
        Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population.
        Circulation. 2006; 113: 664-670
        • Mattace-Raso F.U.
        • van derCammen T.J.
        • Hofman A.
        • van Popele N.M.
        • Bos M.L.
        • Schalekamp M.A.
        • et al.
        Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study.
        Circulation. 2006; 113: 657-663
        • Schicho R.
        • Marsche G.
        • Storr M.
        Cardiovascular complications in inflammatory bowel disease.
        Curr Drug Targets. 2015; 16: 181-188
        • Rungoe C.
        • Andersen N.N.
        • Jess T.
        Inflammatory bowel disease and risk of coronary heart disease.
        Trends in cardiovascular medicine. 2015; : 1050-1738https://doi.org/10.1016/j.tcm.2015.03.010
        • Wu G.C.
        • Leng R.X.
        • Lu Q.
        • Fan Y.G.
        • Wang D.G.
        • Ye D.Q.
        Subclinical atherosclerosis in patients with inflammatory bowel diseases: a systematic review and meta-analysis.
        Angiology. Jun 1 2016; ([pii: 0003319716652031] [Epub ahead of print])
        • Sandborn W.J.
        • Hanauer S.
        • Van Assche G.
        • et al.
        Treating beyond symptoms with a view to improving patient outcomes in inflammatory bowel diseases.
        Journal of Crohn's and Colitis. 2014; 8: 927-935