Elsevier

American Heart Journal

Volume 163, Issue 4, April 2012, Pages 666-676.e3
American Heart Journal

Clinical Investigation
Coronary Artery Disease
Exercise intervention and inflammatory markers in coronary artery disease: A meta-analysis

https://doi.org/10.1016/j.ahj.2011.12.017Get rights and content

Background

Inflammatory activity plays a role in the development and progression of coronary artery disease (CAD), and exercise confers survival benefit. We performed a meta-analysis of changes in inflammatory biomarkers over the course of exercise interventions in patients with CAD.

Methods

We searched MEDLINE, Embase, the Cochrane Collaboration, AMED, and CINAHL for studies reporting peripheral inflammatory biomarker concentrations before and after exercise interventions of ≥2 weeks in patients with CAD. Data were summarized using standard mean differences (SMD) and 95% CIs.

Results

Twenty-three studies were included. Concentrations of C-reactive protein (CRP; SMD −0.345, 95% CI −0.444 to −0.246, n = 1,466, P < .001), interleukin 6 (SMD −0.546, 95% CI −0.739 to −0.353, n = 280, P < .001), fibrinogen (SMD −0.638, 95% CI −0.953 to −0.323, n = 247, P < .001), and vascular cell adhesion molecule 1 (SMD −0.413, 95% CI −0.778 to −0.048, n = 187, P = .027) were lower postintervention. Higher total cholesterol (B = −0.328, 95% CI −0.612 to −0.043, P = .026) and higher total/high-density lipoprotein cholesterol ratios (B = −0.250, 95% CI −0.425 to −0.076, P = .008) at baseline were associated with greater reductions in CRP. In controlled studies, follow-up concentrations of CRP (SMD −0.500, 95% CI −0.844 to −0.157, nexercise/control = 485/284, P = .004), and fibrinogen (SMD −0.544, 95% CI −1.058 to −0.030, nexercise/control = 148/100, P = .038) were lower in subjects who exercised compared with controls.

Conclusion

Exercise training is associated with reduced inflammatory activity in patients with CAD. C-reactive protein and fibrinogen have provided the strongest evidence. Higher baseline CRP and adverse baseline lipid profiles predicted greater reductions in CRP.

Section snippets

Background

In patients with coronary artery disease (CAD), exercise interventions confer long-term survival benefit and reduce the risk of recurrent events.1 Roles of immune activity in the development and progression of atherosclerosis are now appreciated.2, 3 Monocytes recruited by vascular endothelial cell signals (eg, vascular cell adhesion molecule 1 [VCAM-1]) are activated during plaque formation to produce metalloproteinases, nitric oxide, and the proinflammatory cytokines tumor necrosis factor α

Data sources

Methodology followed PRISMA guidelines.21 English-language literature was searched using MEDLINE, Embase, the Cochrane Collaboration, AMED, and CINAHL up to June 2011 for original reports of inflammatory biomarker changes after exercise in patients with CAD (see online Appendix A).

Study selection

Inclusion criteria were (1) inflammatory biomarkers measured before and after aerobic exercise intervention; (2) intervention ≥2 weeks; (3) diagnosis of CAD by history of myocardial infarction, percutaneous coronary

Population characteristics

Twenty-three studies met inclusion criteria (Figure 1) ranging in size from 12 to 393 subjects (Table I). Subjects (73.0% male, mean age 63.1 ± 7.6 years) had a 20.1% prevalence of diabetes (antidiabetic use inconsistently reported), and 73.1% were prescribed a cholesterol-lowering medication. Mean exercise prescriptions were 41.5 ± 15.8 (20-80) minutes, 3.9 ± 1.7 (2-7) sessions per week, for 11.3 ± 5.3 (2-24) weeks with estimated energy expenditures ranging from 1,918 to 14,654 kJ per week (

Discussion

Collectively, the evidence supports a reduction in inflammatory activity associated with exercise training in patients with CAD as indicated by lower CRP, fibrinogen, IL-6, and VCAM-1 after intervention. Associations between these biomarkers and risk of mortality10, 11, 12,14, 15 emphasize the potential significance of these findings. Controlled studies strengthened this evidence, showing lower final concentrations of CRP and fibrinogen in those who undertook exercise compared with controls.

The

Acknowledgements

The authors thank Drs Anita Shumacher, Sanja Balen, and Kari Peersen for their valued correspondence and Maureen Pakosh, BA, MISt, for information resources support.

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