Interleukin-6 and C-reactive protein prognostic value following acute coronary syndrome.

BACKGROUND AND AIMS: After acute coronary syndrome (ACS), high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels have been associated with risk of major adverse cardiovascular events (MACE). Whether the prognostic information provided by hsCRP and IL-6 is independent and complementary after ACS is unclear.

METHODS

The ODYSSEY OUTCOMES trial compared alirocumab with placebo in post-ACS patients on optimized statin therapy. In post hoc analyses, the relation between log-transformed hsCRP and IL-6 levels and risk of MACE and all-cause death was assessed in proportional hazards models.

RESULTS

A total of 11 817 patients had baseline hsCRP and IL-6 data; 1306 had a MACE primary endpoint and 458 died. Median hsCRP, IL-6, and low-density lipoprotein cholesterol (LDL-C) were 1.54 mg/L, 5.00 pg/ml, and 86 mg/dl, respectively. hsCRP and IL-6 had moderate correlation (r = 0.52). In models for one biomarker adjusted for the other biomarker, treatment assignment, age, sex, diabetes, LDL-C, and time since index ACS, hsCRP was a significant independent predictor of MACE (P < .0001) and IL-6 was not (P = .21); both independently predicted death (P < .0001 for hsCRP and P = .0003 for IL-6). Relationships did not depend on treatment (all Pinteraction > .25). When dichotomized at 2 mg/L (hsCRP) and 5 pg/ml (IL-6), risks of MACE and death were significantly elevated when both, but not when one marker was elevated.

CONCLUSIONS

In patients with recent ACS, hsCRP independently predicted MACE, while both hsCRP and IL-6 predicted death. Together, the two markers provided complementary prognostic information. hsCRP conveys independent information on inflammatory risk beyond that provided by IL-6.