Inflammation is a classical cytokine-mediated phenomenon and is the general subject of research of many scientists. Inflammation has now been brought front and center on the cardiovascular disease research stage as well. Haverkate et al.1 reported that C-reactive protein (CRP), a general marker of inflammation, is a prognostic marker of increased risk of myocardial infarction in patients with either stable or unstable angina pectoris, and Ridker et al.2 reported that in healthy individuals there was a correlation of serum CRP with risk of myocardial infarction up to six year later.
Myocardial infarction is frequently at the end of a long process of atherosclerosis, and it is known that development of atherosclerosis is in part mediated by inflammation. A complicating factor is that atherosclerosis is in turn an inflammation-causing process.
Haverkate et al.1 studied 2121 patients with angina who had coronary angiographic evaluation as part of a complete laboratory analysis, including measurement of CRP, on entry into the study. The patients were followed for two years. The risk of myocardial infarction or sudden coronary death was about two-fold higher for patients in the top quintile of CRP concentrations.
Ridker et al.2 measured CRP in sera from subjects in the The Physicians' Health Study,3 which was begun in 1982. They studied 1086 subjects, half of whom subsequently had a cardiovascular event. Base-line CRP levels were statistically higher in those who subsequently had a myocardial infarct or stroke.
The Physicians' Health Study demonstrated a beneficial effect of aspirin in preventing infarcts. The effect of aspirin is generally attributed to its platelet inhibitory action, but the addition of a CRP measurement revealed that most of the aspirin effect was in subjects with the higher CRP levels. This raises the likelihood that the beneficial effect of aspirin was due to its general anti-inflammatory effect rather than as an inhibitor of platelet activation.
These studies suggest the possibility that a cytokine, adhesion molecule or chemokine might more specifically reflect the inflammatory condition that increases risk for cardiovascular disease. Alternatively, it may be a slightly higher homeostatic regulation of inflammatory/anti-inflammatory cytokines, rather than any particular focal inflammation, that is the risk.
References
- Haverkate, F. et al. (1997) Lancet 349:462.
- Ridker, P.M. et al. (1997) New Engl. J. Med. 336:973.
- Steering Committee (1989) New Engl. J. Med. 321:129.