Raised Concentrations of Macrophage Colony Stimulating Factor in Severe Unstable Angina Beyond the Acute Phase Are Strongly Predictive of Long Term Outcome

Objective: To evaluate the long term prognostic value of macrophage colony stimulating factor (MCSF), interleukin-6 (IL-6), and tumour necrosis factor alpha (TNFalpha) measured in serum six weeks after the occurrence of unstable angina.

Subjects: 119 consecutive patients, mean (SD) age 58 (10) years, with severe unstable angina (Braunwald class IIIb); controls were 96 subjects of similar age and sex distribution.

Design: MCSF, IL-6, and TNFalpha were measured on admission, at discharge, and six weeks later, and the patients were followed for two years. Clinical end points were: cardiac death, readmission for acute coronary syndromes, and revascularisation.

Setting: District general hospital.

Results: 113 patients completed follow up, during which two died of non-cardiac causes. Of the remaining 111 patients, 39 (35.1%) had a cardiac event (two deaths, 15 revascularisations, and 22 readmissions for acute coronary syndromes). MCSF and IL-6 concentrations at six weeks were higher in patients with cardiac events than in those without (424 v 306 pg/ml, p = 0.0008, and 6.6 v 4.5 pg/ml, p = 0.01, respectively). Cytokine concentrations at six weeks were also significantly higher than in the control group. Logistic regression analysis showed that MCSF concentrations were the only independent predictors of future events, with an adjusted odds ratio for events of 4.1 (95% confidence interval 1.1 to 14.8; p = 0.03). The two year survival free of cardiac events was significantly lower in patients with MCSF concentrations in the highest tertile (values > or = 468 pg/ml) than in those with values < 468 pg/ml.

Conclusions: Increased MCSF concentrations beyond the acute phase are strongly predictive of long term outcome in patients with severe unstable angina.