Abstract 3766: Determinants of Platelet Activation in Heart Failure
Background: Thromboembolism is a critical and relatively common complication of chronic heart failure (HF). We designed a study to assess the determinants of platelet activation in HF.
Methods: We performed a cross-sectional study in 84 HF patients [33 M; 81±8 yr; 24 in I, 25 in II, 19 in III and 16 in IV NYHA class] and 42 age- and gender-matched healthy subjects, using urinary 8-iso-prostaglandin (PG) F2α and 11-dehydro-thromboxane (TX) B2 as non-invasive indexes of oxidative stress and platelet activation, respectively. B-type natriuretic peptide (BNP) as a biomarker of cardiac function and prognosis, plasma asymmetric dimethylarginine (ADMA) as an index of endothelial dysfunction, plasma C-reactive protein (CRP) and sCD40 ligand (sCD40L) as markers of inflammation were also measured.
Results: Forty-two aspirin-free HF patients had significantly higher urinary 11-dehydro-TXB2 excretion [Median (IQR): 1488 (824–2130) vs 440 (313– 611) pg/mg cr, p<0.0001], 8-iso-PG F2α [528 (430–702) vs. 304 (228–364) pg/mg cr, p<0.0001], BNP [363 (196 – 659) vs 78 (56–98) pg/mL, p<0.0001], ADMA (1.6±0.5 vs 0.5±0.2 μmol/L, p<0.0001), CRP [1.7 (0.9–2.7) vs 0.5 (0.4 – 0.7) mg/L, p<0.0001] and sCD40L levels [1342 (653–2320) vs 432 (322– 840) pg/mL, p<0.0001] than controls. Forty-two HF patients on low-dose aspirin showed significantly lower 11-dehydro-TXB2 [343 (227– 455) pg/mg cr, p<0.007] and sCD40L levels [820 (535–1160) pg/mL, p<0.02] than aspirin-free HF patients, with no significant differences in the other parameters. Patients in NYHA classes III-IV showed significantly higher urinary 11-dehydro-TXB2 as compared to patients in I-II classes, independently of aspirin treatment (p<0.05). In the 42 aspirin-free HF patients, 11-dehydro-TXB2 was linearly correlated with BNP (Rs=0.59, p<0.0001), 8-iso-PGF2α (Rs=0.58, p<0.0001), and CD40L (Rs=0.61, p<0.0001). Multiple regression analysis showed that higher BNP levels (Beta Coefficient=0.74, p<0.0001), no aspirin therapy (−0.41, p<0.0001) and sCD40L levels (0.32, p<0.0001) independently predicted 11-dehydro-TXB2 excretion rate.
Conclusions: Persistent platelet activation characterizes patients with HF. This phenomenon is related to disease severity and is largely suppressable by low-dose aspirin.