CHAI Jason (1,2), CHAI Jason (1,2), LEES Charlotte (3), BERRETTA Antonio (1), JANG Injung (1), HAYDER Nawshad (3), BODEN Katherine (1), LUCKING Andrew (2), JEREMY Tomlinson (4), SUSAN Shapiro (5), MEAD Adam (3), ROBIN Choudhury (1,2)
(1) Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UNITED KINGDOM; (2) Oxford Heart Centre, Oxford, UNITED KINGDOM; (3) MRC Weatherall Institute of Molecular Medicine (Oxford University & John Radcliffe Hospital), Oxford, UNITED KINGDOM; (4) Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UNITED KINGDOM; (5) Oxford Haemophilia and Thrombosis Centre, Churchill Hospital, Oxford, UNITED KINGDOM
AIMS
Complex coronary artery disease (CAD) in diabetes associates with adverse cardiovascular outcomes. In a collaborative analysis of lipid-lowering therapy trials, in which 76% of participants had diabetes, high-sensitivity CRP (hsCRP) was a stronger predictor of cardiovascular risk than low-density lipoprotein (LDL) cholesterol. We aimed to explore the relationship between inflammation and CAD extent in type 2 diabetes (T2D).
METHODS AND RESULTS
116 patients (mean ± SD age of 66±10.2) presenting to Oxford University Hospital with acute coronary syndrome (ACS) were consented to the INFLAMED study; 62 (53.4%) had T2D or pre-diabetes. hsCRP (Abbott) was performed clinically; median 0 (IQR: 0-1) days from admission (n=99). Plasma was isolated at follow-up to measure hsCRP, IL-6 and IL-18 using the Ella apparatus (Protein Simple) as per manufacturer; median 57 (44-72) days from discharge (n=86). CAD extent was stratified by SYNTAX score (low ≤22, high >22).
SYNTAX scores were similar between patients with and without T2D or pre-diabetes (mean 24±11.9 vs 22±11.9; p = 0.513). At admission, patients with T2D or pre-diabetes had higher hsCRP (median 3.9 (1.4-8.0) vs 2.35 (1.1-4.4) mg/L; p = 0.09). hsCRP was significantly higher in patients with high SYNTAX scores (3.9 (1.6-8.7) vs 1.9 (1.0-4.5) mg/L; p = 0.01), more so in diabetes (5.1 (2.6-11.0) vs 2.5 (1.6-5.8) mg/L, p = 0.052). In multivariable linear regression adjusted for age, sex and BMI, high SYNTAX score (β = 0.32, p = 0.002) and diabetes status (β = 0.25, p = 0.01) were independently associated with higher hsCRP.
At follow-up, hsCRP were similar between groups (median 1.5(0.9-3.6) vs 1.2(0.5-5.0) mg/L, p = 0.223). IL-6 and IL-18 were higher in patients with T2D or pre-diabetes; median 4.64 (2.8-6.35) vs 3.38 (2.03-4.76) pg/mL; p = 0.051 and 340 (266-422) vs 274 (224-369) pg/mL; p = 0.032. After adjustment for age, sex, BMI and patients who had CABG, high SYNTAX score was not associated with hsCRP, IL-6 or IL-18 and diabetes was only independently associated with IL-18 (β = 0.08, p = 0.044).
CONCLUSIONS
Consistent with literature, IL-6 and IL-18 were elevated in diabetes at follow-up. However, inflammation measured by CRP acutely, but not at follow-up, associated significantly with extensive CAD and diabetes, suggesting that acute measurement of CRP characterises a patient’s inflammatory status in CAD.
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