Introduction
Nearly seven million patients worldwide are affected by inflammatory bowel disease (IBD), with the United States (US) leading all countries in disease prevalence.¹ IBD includes both Crohn's disease (CD) and ulcerative colitis (UC), and is characterized by chronic inflammation of the intestinal tract with extraintestinal manifestations that can involve nearly any organ system. IBD patients can experience flares, but the goal of treatment is to maintain remission.

Chronic inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis predispose patients to atherosclerotic cardiovascular disease (ASCVD).² However, the mechanisms through which IBD increases ASCVD risk remain to be elucidated. This article summarizes studies looking at the association between IBD and ASCVD, potential mechanisms, current guidelines and strategies, and future directions based on a recent review.³

Association between IBD and ASCVD
Several meta-analyses have shown an independent association between IBD and ASCVD. A 2017 meta-analysis including ten cohort studies found a multivariate-adjusted independent association between IBD and coronary heart disease (pooled relative risk (RR) 1.24; 95% CI 1.14-1.36). This association was also present in subgroup analyses of CD and UC.⁴

Another meta-analysis noted similar associations between IBD and coronary heart disease (RR 1.17, CI 1.07-1.27), as well as myocardial infarction (MI) (RR 1.12, CI 1.05-1.21) and incident cerebrovascular disease (RR 1.25, CI 1.08-1.44); these associations were more pronounced in women.⁵ These findings were consistent with a nationwide Danish retrospective cohort study, which included IBD patients followed for up to 13 years and a 2019 US study based on cross-sectional data from 26 nationwide health care systems.^6,7 The US study found a stronger association among younger patients.

There is also an association between periods of active disease in IBD with increased risk for cardiovascular events. A prospective study in Denmark found that the risks of MI, cerebrovascular disease, and cardiovascular death were significantly higher during IBD flares and periods of persistent IBD activity, especially in the first year after IBD diagnosis. During remission, the risks were like those of the controls.⁸ Although there is an association between IBD and ASCVD, the relationship between IBD and ASCVD-related mortality has not always been observed.^5,9,10 Potential explanations include the younger ages of the IBD population and low case-fatality rates of ASCVD events in this age group.

Potential Mechanisms between IBD and ASCVD
Several processes in IBD likely contribute to increased ASCVD risk including local and systemic inflammation, gut microbiome abnormalities, endothelial dysfunction, thrombosis, lipid dysfunction, and corticosteroids, which are used in IBD treatment and are known to increase ASCVD risk.³ Patients with IBD have elevated levels of inflammatory markers, such as C-reactive protein, IL-6, and TNF-a, that can lead to endothelial dysfunction.^3,11

Additionally, IBD promotes a hypercoagulable state, especially during periods of active flare, and patients have an increased risk of venous and arterial thromboembolic events.^3,12 Furthermore, changes in nutrition and absorption, along with inflammation can lead to lipid alterations.^3,13 However, the exact mechanisms of these associations require further investigation.

Current Guidelines
The guidelines for primary prevention of ASCVD from the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) consider chronic inflammatory conditions as a risk enhancer or modifier that should lead clinicians to more strongly consider statin therapy in borderline- or intermediate-risk patients.^2,14 However, cardiovascular risk stratification of IBD patients is complicated by the overall younger age of this patient population, typically resulting in low 10-year ASCVD risk assessments.

Additionally, these tools have not been validated in adults with IBD and do not incorporate specific IBD-risk mechanisms, which can lead to underestimating risk. Also, the 2019 ACC/AHA guidelines acknowledges that the prognostic significance of a coronary artery calcium (CAC) score of zero in patients with chronic inflammatory disorders does not necessarily represent very low 10–15-year risk.²

Proposed Strategies
Although current guidelines provide limited recommendations, the following strategies may reduce ASCVD risk in patients with IBD.³

1) Initiation of a Multi-disciplinary, Team-Based Approach
It is important to start preventive care soon after diagnosis of IBD because there is an increased ASCVD risk at initial diagnosis. Gastroenterologists and preventive cardiologists should work together to develop patient-centered approaches focused on shared decision-making.

2) Remission of Disease
Increased disease activity is an important risk enhancer for ASCVD. Therefore, optimization of IBD management, especially during active flares, is necessary.¹⁰ IBD treatment consists of a stepwise approach consisting of steroids, 5-aminosalicylates, immunosuppressives, and biologics; 5-aminosalicylates and anti-TNF agents may decrease ASCVD risk.^6,15

3) Aggressive Reduction in Cardiovascular Risk Factors
All patients with IBD should be screened for established risk factors at initial diagnosis and aggressively managed. Screening includes blood pressure, glucose, lipid panel, and lifestyle habits. Careful consideration of blood pressure management is needed given the propensity for volume depletion secondary to gastrointestinal losses during flares. Additionally, complete tobacco cessation is key.

4) Implementation of ACC/AHA Guidelines
Systematic implementation of current ACC/AHA guideline recommendations for risk assessment and management in patients with chronic inflammatory conditions should be followed.

Future Directions
Further research to better elucidate the mechanisms involved in ASCVD development in patients with IBD is needed. The identification of these mechanisms will hopefully allow for the development of novel therapeutic targets in IBD patients and inform the development of tailored risk estimation tools in this patient population.

A better understanding of the potential role of the CAC score and of more advanced coronary imaging techniques is also needed in people with IBD. Future studies should focus on characterizing the effects of disease-modifying therapies in IBD on ASCVD risk and developing adapted risk estimators for this patient population.

Conclusion
The management of IBD patients should focus on a multidisciplinary, team-based approach to preventive care, remission of IBD disease activity, and aggressive reduction of cardiovascular risk factors. Systematic implementation of current ACC/AHA guidance for patients with chronic inflammatory conditions may increase the proportion of patients with IBD treated with statin therapy.

References

1. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017. Lancet Gastroenterol Hepatol 2020;5:17–30.
2. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;140:e596-e646.
3. Cainzos-Achirica M, Glassner K, Zawahir HS, et al. Inflammatory bowel disease and atherosclerotic cardiovascular disease: JACC Review Topic of the Week. J Am Coll Cardiol 2020;76:2895-2905.
4. Feng W, Chen G, Cai D, Zhao S, Cheng J, Shen H. Inflammatory bowel disease and risk of ischemic heart disease: an updated meta-analysis of cohort studies. J Am Heart Assoc 2017;6:e005892.
5. Sun HH, Tian F. Inflammatory bowel disease and cardiovascular disease incidence and mortality: a meta-analysis. Eur J Prev Cardiol 2018;25:1623-31.
6. Rungoe C, Basit S, Ranthe MF, Wohlfahrt J, Langholz E, Jess T. Risk of ischaemic heart disease in patients with inflammatory bowel disease: a nationwide Danish cohort study. Gut 2013;62:689-94.
7. Panhwar MS, Mansoor E, Al-Kindi SG, et al. Risk of myocardial infarction in inflammatory bowel disease: a population-based national study. Inflamm Bowel Dis 2019;25:1080-87.
8. Kristensen SL, 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.
9. Fumery M, Xiaocang C, Dauchet L, Gower-Rousseau C, Peyrin-Biroulet L, Colombel JF. Thromboembolic events and cardiovascular mortality in inflammatory bowel diseases: a meta-analysis of observational studies. J Crohns Colitis 2014;8:469-79.
10. Dorn SD, Sandler RS. Inflammatory bowel disease is not a risk factor for cardiovascular disease mortality: results from a systematic review and meta-analysis. Am J Gastroenterol 2007;102:662-67.
11. Principi M, Mastrolonardo M, Scicchitano P, et al. Endothelial function and cardiovascular risk in active inflammatory bowel diseases. J Crohns Colitis 2013;7:e427-e433.
12. Senchenkova E, Seifert H, Granger DN. Hypercoagulability and platelet abnormalities in inflammatory bowel disease. Semin Thromb Hemost 2015;41:582-89.
13. Agouridis AP, Elisaf M, Milionis HJ. An overview of lipid abnormalities in patients with inflammatory bowel disease. Ann Gastroenterol 2011;24:181-87.
14. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88.
15. Kirchgesner J, Nyboe Andersen N, Carrat F, Jess T, Beaugerie L. Risk of acute arterial events associated with treatment of inflammatory bowel diseases: nationwide French cohort study. Gut 2020;69:852-58.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Dyslipidemias, Prospective Studies, C-Reactive Protein, Cardiovascular Diseases, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Interleukin-6, Mesalamine, American Heart Association, Cross-Sectional Studies, Colitis, Ulcerative, Blood Pressure, Tumor Necrosis Factor-alpha, Biological Products, Retrospective Studies, Coronary Vessels, Decision Making, Risk Factors, Primary Prevention, Risk Assessment, Coronary Disease, Inflammation, Arthritis, Rheumatoid, Thrombosis, Myocardial Infarction, Cerebrovascular Disorders, Delivery of Health Care, Lipids, Adrenal Cortex Hormones, Patient Care Team, Patient-Centered Care, Inflammatory Bowel Diseases

< Back to Listings