Aims Diabetes mellitus (DM) is associated with high incidence of first and recurrent cardiovascular events, especially acute coronary syndromes (ACSs); however, the mechanisms involved are still unknown. We sought to investigate the role of CD4+CD28nullT-lymphocytes, a rare long-lived subset of T-lymphocytes with proatherogenic and plaque-destabilizing properties, in the increased cardiovascular risk associated with DM.
Methods and results CD4+CD28nullT-cell frequency was analysed by flow-cytometry in 60 DM patients without overt cardiovascular disease (cDM), in 166 ACS patients with or without DM (ACS/DM+, n= 51 and ACS/DM−, n= 115), and in 60 healthy individuals. The incidence of cardiovascular events (death, myocardial infarction, unstable angina) was assessed at 36 months follow-up. CD4+CD28nullT-cell frequency (median, range) was higher in ACS/DM+ (12.7%, 0.1–48) vs. ACS/DM− (3.9%, 0.2–35), cDM (3.1%, 0.3–22.4), and controls (1.5%, 0.1–9.1) (P< 0.001 for all comparisons). Notably, cDM patients had significantly higher CD4+CD28nullT-cell frequency than controls (P= 0.001). Glycosylated haemoglobin A1c was the only parameter independently associated with CD4+CD28nullT-cells in cDM. The 36-month event-free survival was significantly lower in cDM patients with CD4+CD28nullT-cells ≥4% (90th percentile of normal distribution) than in those with CD4+CD28nullT-cells <4% (P= 0.039). Among ACS patients, the 36-month event-free survival was the lowest in those with DM and CD4+CD28nullT-cells ≥4% and highest in those without DM and CD4+CD28nullT-cells <4% (P< 0.001), being intermediate in those with only one of these features.
Conclusions In DM patients, CD4+CD28nullT-cells are expanded and are associated with poor glycaemic control; they also correlate with the occurrence of a first cardiovascular event and with a worse outcome after an ACS.
- acute coronary syndromes
- diabetes mellitus