Different outcome of six homozygotes for prothrombin A20210A gene variant

Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk

Impact of them, elevation of biochemical markers of myocardial damage on long-term mortality after percutaneous coronary intervention: results of the CK-MB and PCI study

AIMS: Retrospective studies and post hoc analyses have suggested that mild elevations in the creatine kinase-MB (CK-MB) isoenzyme following percutaneous coronary intervention (PCI) may be associated with an increased risk of death in the long term. However, this finding is still controversial, and the prognostic significance of elevations of more sensitive markers of myocardial damage, such as the cardiac troponins, has not been established. In this multicentre prospective cohort study, we evaluated the influence of post-procedural elevations of CK-MB and troponin I (cTnI) on long-term mortality. METHODS AND RESULTS: The CK-MB and PCI study included 3494 consecutive patients undergoing PCI from February 2000 to October 2000 in 16 Italian tertiary centres. Blood samples were collected at baseline, and at 8-12 and 18-24 h after the procedure, and were analysed in a core biochemistry laboratory. CK-MB elevation was detected in 16% of the patients, and was associated with increased 2-year mortality [7.2 vs. 3.8%; odds ratio (OR): 1.9; 95% confidence interval (CI): 1.3-2.8; P<0.001). The degree of CK-MB elevation (peak CK-MB ratio) independently predicted the risk of death (adjusted OR per unit: 1.04; 95% CI: 1.01-1.07; P=0.009). A cTnI elevation was detected in 44.2% of the cases and was not associated with a significant increase in mortality (4.9 vs. 4.0%; OR: 1.2; 95% CI: 0.9-1.7; P=0.2). CONCLUSION: Post-procedural elevations of CK-MB, but not cTnI, influence 2-year mortality

Prognostic value of isolated troponin I elevation after percutaneous coronary intervention.

BACKGROUND: Mild elevations of cardiac troponin are frequent after percutaneous coronary intervention (PCI). Their prognostic value is uncertain in the absence of changes in creatine kinase-MB (CK-MB). METHODS AND RESULTS: We evaluated the relation between isolated elevations of cardiac troponin I (cTnI) and all-cause mortality. We studied 3494 consecutive patients who underwent PCI in 16 Italian tertiary cardiology centers. CK-MB and cTnI were analyzed in a central laboratory. Duration of follow-up was 2 years. The present analysis was restricted to 2362 patients with normal CK-MB and cTnI values at baseline and no CK-MB elevation after PCI. A rise in cTnI after PCI >0.15 ng/mL, the upper reference limit, was found in 932 patients (39.4%). A rise >0.45 ng/mL (>3 7upper reference limit) was found in 467 patients (19.7%). Compared with patients with normal cTnI, those with cTnI elevation >0.15 ng/mL showed a slightly increased mortality (3.8% versus 2.6%; hazard ratio, 1.53; 95% confidence interval, 0.97 to 2.42; P=0.069). A cTnI elevation >0.45 ng/mL was associated with a higher risk of mortality (4.5% versus 2.7%; hazard ratio, 1.68; 95% confidence interval, 1.01 to 2.80; P=0.044), which, however, did not remain significant after adjustment for concomitant risk factors (hazard ratio, 1.45; 95% confidence interval, 0.86 to 2.46; P=0.162). Postprocedural cTnI elevation was associated with coronary and clinical features consistent with a worse risk profile. CONCLUSIONS: In the absence of a rise in CK-MB, elevated cTnI levels after PCI are associated with a modest increased risk of death. However, this is not independent of the concomitant adverse baseline clinical characteristics of these patients