SummaryWe have demonstrated previously that carriers of a genotype called C4B*Q0 (silent allele of the C4B gene) have a substantially increased risk to suffer from myocardial infarction or stroke, and are selected out from the healthy elderly population. Because smoking carries a major risk for cardiovascular disease (CVD), it seemed worthwhile to study if these two factors interact. Study 1 involved 74 patients with angina pectoris (AP), 85 patients with recent acute myocardial infarction (AMI) and 112 survivors of a previous AMI and 382 controls from Iceland. Study 2 involved 233 patients with severe CVD and 274 controls from Hungary. Smoking habits were registered for each subject. The number of C4A and C4B genes was determined by phenotyping or genotyping. Compared to controls, C4B*Q0 carrier frequency was significantly higher at diagnosis in Icelandic smokers with AP (P = 0·005) and AMI (P = 0·0003) and Hungarian smokers with severe coronary artery disease (P = 0·023), while no such difference was observed in non-smoking subjects. Age-associated decrease in C4B*Q0 observed previously in two remote Caucasian populations was found, in the present study, to be associated strongly with smoking, and to already occur in smokers after age 50 years both in Iceland and Hungary. Our findings indicate that the C4B*Q0 genotype can be considered as a major covariate of smoking in precipitating the risk for AMI and associated deaths.
P e r f o r m a n c e o f P r o t h r o m b i n -P r o c o n v e r t i n T i m e a s a M o n i t o r i n g T e s t o f O r a l A n t i c o a g u l a t i o nT h e r a p y Oral anticoagulation therapy (OAT) with vitamin K antagonists (VKA) is most commonly monitored with the prothrombin clotting time (PT), which is sensitive to decreases in activity of any of the v i t a m i n K-dependent coagulation factors (F), II, VII, or X, as well as to decreases in fibrinogen or coagulation factor V (FV). 1 In the past, the PT was usually reported as a ratio of patient to control plasma clotting times (PT-ratio), but a system of international standardization was developed because of variability in clotting times obtained with different thromboplastins and variability in the methods of reporting the results. Accordingly, for the purpose of OAT control, PT results are now generally reported as international normalized ratios (INRs), 2 ' 3 ie, PT ratios are transformed to the ratio that would have been obtained if a standard reference thromboplastin preparation with an assigned international sensitivity index (ISI) of 1.0 had been used. 2,3When the PT is not done on fresh samples, a prolongation of the clotting time may occur from ex vivo factor V degradation (if plasma is stored at room temperature for more than 6 hours), whereas artifactual shortening may occur because of cold activation of FVII if plasma is stored at 4°C. 4 One way to circumvent these problems is to apply the prothrombin-proconvertin time (PP or P&P) on plasma kept at room temperature. The PP is a modified PT that is only sensitive to changes in FTJ, FVII, and FX because addition of adsorbed bovine plasma to the thromboplastin supplies the test mixture with optimal amounts of fibrinogen and FV for clot formation.5 When the PP is done on dilute patient plasma, it is also insensitive to direct anticoagulants, such as the lupus anticoagulant or heparin.6 ' 7 The PP results traditionally have been reported as the percentage of total coagulant activity of HI, FVII, and FX based on a dilution curve of normal plasma and not as clotting time ratios (or INR). This complicates the interpretation of anticoagulation intensity in relation to PT-based results and may be one reason for the decreasing use of the PP as a monitoring device. Also, although the PP is derived from the PT, clinical studies using the INR calculated directly from the PP are lacking. In clinical studies using the PP, conversions to INR have 672 Downloaded from https://academic.oup.
The efficacy and safety of oral anticoagulation (OA) with vitamin K antagonists depends on maintaining anticoagulation intensity, measured as international normalized ratio (INR), within defined target ranges. We assessed the quality of our current software-assisted warfarin dosing in the year 2006 in 941 unselected consecutive patients on stable OA with atrial fibrillation (AF), venous thromboembolism (VTE) and prosthetic heart valves (PHV) by comparing it to our previous cardiologist-based dosing practice in 1992 when a study was carried out on 241 comparable patients. Over 14 years, the time within target range increased in all three anticoagulated groups, i.e. in AF patients from 46% to 81%, in VTE patients from 62% to 84% and in patients with PHV from 40% to 64%. Only 1% of the treatment time is now spent at INR < 1.5 compared to 7% previously (P < 0.0001) and 0.4% of the treatment time at INR > 4.0 presently compared to 2.8% in the past (P < 0.0001). INR-targets are better achieved with the current software-assisted dosing practice and extreme low and high values are less common than previously. The results provide indirect evidence suggesting that both efficacy and safety has improved with the current practice.
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