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Etiology

Review: CHD is associated with markers of inflammation

ACP J Club. 1998 Nov-Dec; 129:72. doi:10.7326/ACPJC-1998-129-3-072


Source Citation

Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. Meta-analyses of prospective studies. JAMA. 1998 May 13;279:1477-82.


Abstract

Question

Is coronary heart disease (CHD) associated with markers of inflammation: levels of fibrinogen, C-reactive protein, and albumin and leukocyte count?

Data sources

Studies were identified from MEDLINE using the terms fibrinogen,C-reactive protein, CRP, albumin, leukocyte, leucocyte, white cell count, and acute phase reactants combined with terms related to CHD (coronary heart disease, myocardial infarction, atherosclerosis, and vascular disease). Bibliographies were scanned, relevant journals were hand searched, and authors were contacted.

Study selection

Long-term prospective studies that reported correlations between CHD and levels of fibrinogen, C-reactive protein, and albumin and leukocyte counts.

Data extraction

Data were extracted on size and type of cohort (population-based or patients with previous vascular disease), mean age of participants, duration of follow-up, assay methods, degree of adjustment for potential confounders, and risk factors (fibrinogen, C-reactive protein, and albumin levels and leukocyte counts). Relative risks (RRs) were calculated for the association between the risk for CHD and the level of each risk factor measured at baseline with the population divided into tertiles. The lowest tertile was assigned an RR of 1.0 and was compared with the highest tertile.

Main results

Fibrinogen levels were evaluated in18 studies (12 community-based) that included 4018 patients with CHD.C-reactive protein levels were evaluated in 7 studies (5 community-based) with 1053 patients with CHD. Albumin levels were evaluated in 8 community-based studies of 3770 patients with CHD. Leukocyte counts were evaluated in 19 studies (14 community-based) of 7229 patients with CHD. High baseline levels of fibrinogen and C-reactive protein, low baseline levels of albumin, and high baseline leukocyte counts were associated with an increased risk for CHD (Table) (P < 0.001 for all comparisons).

Conclusion

High baseline levels of fibrinogen and C-reactive protein, low baseline albumin levels, and high baseline leukocyte counts are associated with an increased risk for coronary heart disease.

Source of funding: Not stated.

For correspondence: Dr. J. Danesh, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, University of Oxford, Harkness Building, Oxford OX2 6HE, England, UK. FAX 44-1865-558817.


Table. Risk factors for coronary heart disease with population divided into tertiles according to baseline assessments

Risk factor Usual mean level for lowest-risk tertile Usual mean level for highest-risk tertile Weighted relative risk (95% CI)
Fibrinogen level 7.4 µmol/L (0.25 g/dL) 10.3 µmol/L (0.35 g/dL) 1.8 (1.6 to 2.0)
C-reactive protein level 1.0 mg/L 2.4 mg/L 1.7 (1.4 to 2.1)
Albumin level 42 g/L 38 g/L 1.5 (1.3 to 1.7)
Leukocyte count 5.6 × 109/L 8.4 × 109/L 1.4 (1.3 to 1.5)

Commentary

Nonspecific markers of inflammation are associated with risk for CHD. Danesh and colleagues reviewed prospective studiesthat examined the relation of fibrinogen,C-reactive protein, and albumin levels and leukocyte count to CHD. Other evidence suggests that inflammatory cytokines, such as interleukin-6 and tumor necrosis factor, may also be associated with CHD. Because inflammation (possibly related to chronic subclinical infection with Chlamydia species, Helicobacter species, or cytomegalovirus; oxidized lipoproteins; ischemia-induced endothelial damage; or autoantigens) seems to be involved in CHD pathogenesis, it is not surprising to find markers of inflammation associated with risk for CHD.

It is unknown, however, whether interventions that affect these CHD-related inflammatory markers also affect CHD risk. The Physicians' Health Study, a randomized trial, reported that men with the highest baseline levels of C-reactive protein lowered their risk for myocardial infarction by 56% by taking low-dose aspirin (1). These findings are intriguing but require confirmation. Measurement of inflammatory markers, such as C-reactive protein, may be helpful in specific clinical settings (e.g., unstable angina), but randomized trial data are necessary before recommendations can be made about the usefulness of screening for inflammatory markers and the role of anti-inflammatory therapy for CHD. Efforts to prevent CHD should continue to focus on controlling such established risk factors as hypertension and hypercholesterolemia because of the large segment of population known to be at risk and the existence of clinical proof that treatment saves lives.

Joel A. Simon, MD, MPH
San Francisco Veterans Affairs Medical CenterUniversity of California, San FranciscoSan Francisco, California, USA


Reference

1. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973-9.