Many chronic inflammatory disorders associated with higher risk of CHD and diabetes

Dregan A, Charlton J, Chowienczyk P, et al.
Circulation. 2014 Jun 26. pii: CIRCULATIONAHA.114.009990. [Epub ahead of print]

Background

Recent insights that chronic inflammation may be associated with increased risk of atheromatous disease, including coronary heart disease (CHD) and stroke, and insulin resistance, may affect management of patients with chronic inflammatory disorders. Clinical disorders affecting the skin, the gastrointestinal tract and joints may be considered, as well as multi-system inflammatory disorders.
Attempts have been made to link the rates of CVD and T2DM in patients with individual inflammatory diseases [1-5], but due to great heterogeneity in study design, general conclusions concerning the CV risk associated with chronic inflammatory cannot be drawn as yet.
This study tested the hypothesis that risks of CHD, stroke and T2DM are consistently elevated across a range of inflammatory diseases affecting either single systems or involving multiple systems. To that extent, electronic health records of a large prospective primary care database (Clinical Practice Research Datalink (CPRD)) were employed. Levels of C-reactive protein (CRP) were considered a biomarker for inflammation. Outcome events were CHD (myocardial infarction, angina, CABG and PCI), stroke, diabetes or multimorbidity.

Main results

• Diagnosis of multiple inflammatory disorders was seen in less than 3% of patients in the cohort.
• Outcome events were most common in patients with systemic vasculitis (13%), bullous skin disorders (9%) and inflammatory arthritis (9%), and least common in Crohn’s disease (4%). Overall, more participants with chronic inflammatory disorders experienced outcome events than the control cohort, with absolute risk per 1000 persons in the cohort of chronic inflammation of 7.42 for T2DM, 5.12 for CHD and 2.67 for stroke, as compared with 5.32, 4.06 and 2.15 respectively in the control group.
• Overall, the pooled estimate hazard ratio for multiple outcomes was 1.20 (95%CI: 1.15-1.26). Heterogeneity was seen between the different conditions, with the highest adjusted HR in systemic autoimmune disorders (HR: 1.32, 95%CI: 1.16-1.50) and systemic vasculitis (HR: 1.29, 95%CI: 1.16-1.44). The highest hazards for organ-specific chronic inflammatory disorders were seen for severe psoriasis (HR: 1.29, 95%CI: 1.12-1.47) and ulcerative colitis (HR: 1.26, 95%CI: 1.14-1.40).
• Based on tertiles of CRP values, patients in the highest tertile had a HR for multiple outcomes of 1.52 (95%CI: 1.37-1.68) as compared to the bottom tertile. HR for the middle tertile was 1.27 (95%CI: 1.14-1.41). Similar, but lower associations were seen in the control group.

Conclusion

This population-based study gives insight into the risk of CVD and T2DM associated with a wide range of chronic inflammatory disorders. Five out of eight of the inflammatory conditions considered were associated with increased risk of T2DM, three with incident stroke and four with elevated CHD risk. Except in Crohn’s disease and systemic autoimmune disorders, an increased risk of at least two of the outcomes was seen. These observations suggests that similar mechanisms may be responsible for the increased risk of CVD and T2DM events across diverse inflammatory conditions. Severity of psoriasis, as well as CRP levels suggested a dose-response effect  for the association between chronic inflammation and outcomes.
These findings suggest that prevention of CVD and T2DM merits higher priority in the management of persons with chronic inflammatory disorders. More research is needed to determine an appropriate CRP-threshold for starting preventive interventions.

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