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Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P¼0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (Po0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R 2 ¼0.3499; Po0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients.

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Background and ObjectivesThe early morning blood pressure surge (EMBPS) has been reported to be associated with cardiovascular events. The aim of this study was to investigate the relationship between 24-hour ambulatory BP monitoring (ABPM) parameters and conventional cardiovascular risk factors.Subjects and MethodsPatients (n=346) never-treated for essential hypertension with no other cardiovascular risk factors, such as diabetes, dyslipidemia, and nephropathy were enrolled. The EMBPS was defined as the early morning systolic BP minus the lowest night systolic BP. We compared the 24-hour ABPM parameters in two groups divided by age (<60 and ≥60 years) and examined the association between the 24-hour ABPM parameters and cardiovascular risk factor.ResultsThe EMBPS (18±14 vs. 24±14 mmHg, p=0.002), 24-hour mean blood pressure {MBP; 102±9 vs. 105±11 mmHg, p=0.044}, and 24-hour mean pulse pressure (PP; 52±10 vs. 58±11 mmHg, p<0.001) were significantly increased in the elderly subjects compared to the younger subjects. The degree of decrease was less in the elderly subjects (10±8 vs. 7±10%, p=0.002). Based on multivariate analysis, age was an independent risk factor for the highest quartile of EMBPS (>28 mmHg) after adjusting for gender differences, body mass index, and various 24-hour ABPM parameters (odds ratio, 1.051; 95% confidence interval, 1.028-1.075; p<0.001).ConclusionAge is an independent risk factor for EMBPS in patients with never-treated hypertension. BP control in the early morning period is more important in elderly patients so as to prevent cardiovascular events.

Background and ObjectivesIt is known that angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor blockers (ACEIs and ARBs, respectively) are effective in preventing atrial fibrillation (AF) in high-risk patients. However, it is not known whether ACEIs and ARBs are effective in preventing the recurrence of AF after catheter ablation.Subjects and MethodsOne hundred fifty-two patients (mean age, 57±10 years; M : F=94 : 58) who underwent catheter ablation due to drug-refractory paroxysmal (mean age, 57±10 years; M : F=58 : 43) or persistent AF (mean age, 56±10 years; M : F=36 : 15) were enrolled. We compared the recurrence rates between the groups with and without ACEIs or ARBs use in paroxysmal and persistent AF. The mean duration of follow-up was 18±14 months.ResultsThe overall recurrence rate after ablation therapy was 26% (n=39). The recurrence rate was significantly decreased in the patients with persistent AF with the use of ACEIs or ARBs (12.1% vs. 61.1%, p<0.01), but this difference was not observed in the patients with paroxysmal AF (24.2% vs. 22.9%, p=0.87). In patients with persistent AF with and without recurrence, the size of the left atrium (44.2±8.4 mm vs. 44.3±5.8 mm, respectively, p=0.45) and the ejection fraction (62±6.5% vs. 61.5±6.2%, respectively, p=0.28) were not significantly different. In multivariate analysis, the use of ACEIs or ARBs was independently associated with recurrence after adjusting for the size of the left atrium and the ejection fraction {odds ratio (OR)=0.078, 95% confidence interval (CI)=0.02-0.35, p<0.01}.ConclusionACEIs and ARBs were shown to be effective in preventing AF recurrence after catheter ablation in patients with persistent AF.

SummarySmoking is associated with increased plasma homocysteine levels, and both are associated with an increased risk of cardiovascular disease. However, little information is available on the effects of passive smoking on the level of homocysteine in nonsmokers. We analyzed the data of self-reported never-smokers (aged ≥ 20 years, n = 3,232), who were from the Third National Health and Nutrition Examination Survey. We quantified the passive nicotine exposure by dividing the never-smokers into quartiles as based on the serum cotinine values. Multiple linear and logistic regression models were used to determine any independent relationships between serum cotinine concentration and levels of homocysteine, vitamin B12, and folate. An elevated homocysteine level was defined as a concentration greater than the 80th percentile. A reduced folate or vitamin B12 level was defined as a concentration less than the 20th percentile.After adjusting for age, gender, body mass index, race, folate and vitamin B12 levels, increased cotinine levels (quartile III and IV) were found to be associated with hyperhomocysteinemia. There was a strong nonlinear increase in the serum homocysteine levels across the quartiles of cotinine. Multivariate analysis showed that age, male gender, non-Caucasian, low levels of folate and vitamin B12, and increased serum cotinine (quartile II-IV) were independently associated with elevated homocysteine levels. In conclusion, these findings indicate that passive smoke exposure in never-smokers is positively and independently associated with plasma homocysteine levels in a dose-dependent manner. These findings may help further determine the link between passive smoking and cardiovascular events. (Int Heart J 2010; 51: 183-187)

We report the fabrication of p+∕n junctions using Ge+, C+, and B+ co-implantation and a spike anneal. The best junction exhibits a depth of 26nm, vertical abruptness of 3nm∕decade, and sheet resistance of 520Ohm∕square. The junction location is defined by where the boron concentration drops to 1018cm−3. These junctions are close to the International Technology Roadmap specifications for the 65nm technology node and are achieved by careful engineering of amorphization, stresses, and point defects. Advanced simulation of boron diffusion is used to understand and optimize the process window. The simulations show that the optimum process completely suppresses the transient-enhanced diffusion of boron and the formation of boron-interstitial clusters. This increases the boron solubility to 20% above the equilibrium solid-state solubility.