113 Blood thrombogenicity is inversely related to coronary lesion severity in patients with non ST-elevation acute coronary syndrome and type 2 diabetes mellitus
In patients with type 2 diabetes mellitus (T2DM), non-ST elevation–acute coronary syndrome (NSTE-ACS) occurs frequently secondary to non-obstructive coronary lesions than those without T2DM. Pathophysiological events leading to acute myocardial infarction in these individuals remain largely unknown, and subsequently demonstrate a poorer prognosis than those without T2DM.
Methods We evaluated blood thrombogenicity (BT) in 80 patients with and without T2DM 7–10 days after troponin positive NSTE-ACS. In accordance to AHA/ESC recommendations all patients received secondary prevention therapy including aspirin and clopidogrel (300 mg loading and 75 mg maintenance doses respectively). Coronary artery disease (CAD) was quantified by coronary angiography through an independent investigator blinded to clinical and laboratory data. Lesions were classified as either obstructive (plaque >75% of the luminal diameter) or non-obstructive (plaque 25%–75% of luminal diameter). We excluded those with minor plaques (<25% of the luminal diameter) and systemic inflammation (eg, sepsis). The subjects were divided: (i) T2DM and obstructive CAD (n=26), (ii) T2DM and non-obstructive CAD (n=14), (iii) non-diabetic and obstructive CAD (n=30) and (iv) non-diabetic and non-obstructive CAD (n=10). BT was measured by the ex-vivo Badimon chamber as total thrombus area. Cytokines and platelet activation markers were measured.
Results All baseline cardiovascular risk factors were similar between groups (p>0.05). BT was higher in T2DM than in those without (22 481±12 336 vs 14 650±8074, p=0.024). When stratified according to CAD status, BT was highest in those with T2DM and non-obstructive CAD (p=0.002, ANOVA F=5.26) (Abstract 113 figure 1). Inflammatory cytokines TNF α (p=0.018, ANOVA F=3.15) and interleukin 6 (p=0.031, ANOVA F=5.0) and platelet activation as measured by P selectin were highest in this group. (p=0.022, ANOVA F=3.422) (Abstract 113 figure 2). Interleukin 1, interferon γ and soluble CD40 ligand levels were similar between the groups.
Conclusion Patients with T2DM and non-obstructive CAD had highest BT and markers of platelet activation and inflammation. These findings suggest biochemical changes also play a significant role in evolution of NSTE-ACS in T2DM. A causal link, if confirmed by large-scale studies may offer us an opportunity to identify therapeutic targets like individualised anti thrombotic therapy and anti inflammatory therapy in this high risk population.