Impact of Blood Pressure Control on Thromboembolism and Major Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Subanalysis of the J‐RHYTHM Registry
Eitaro KodaniHirotsugu AtarashiHiroshi InoueKen OkumuraTakeshi YamashitaToshiaki OtsukaHirofumi TomitaHideki OrigasaM SakuraiYoshiaki KawamuraI. KubotaYoshiaki KanekoKazuo MatsumotoSatoshi OgawaYoshiyasu AizawaI. KodamaEiichi WatanabeYukihiro KoretsuneYuka OkuyamaAkihiko ShimizuOsamu IgawaShigenobu BandoM. FukataniTetsunori SaikawaAkiko ChishakiN KatoKatsuya KandaJ. KatoHiroaki ObataMasashi AokiHiroto HondaY. KontaToru HatayamaYukihiko AbeKen TerataTakahide YagiAkihiko IshidaT KomatsuHideaki TachibanaHidenori SuzukiYoshiyuki KamiyamaTomonori WatanabeMasaki OgumaM. ItohOsamu HironoYuichi TsunodaKenichi IkedaTohru KanayaKenzo SakuraiHiroyasu SukekawaSeigo NakadaTaihei ItohShoichi TangeMamoru ManitaMutsuko OhtaHiromi EgumaRitsushi KatoYoshiko EndoTadayoshi OginoMasahiro YamazakiHideaki KankiM UchidaSatoru MiyanagaKentaro ShibayamaNotitaka TorataniToshiaki KojimaMari IchikawaMakoto SaitoYuji UmedaTakao SawanoboriHiroshi SoharaS. OkuboTomoyuki ŌkuboT TokunagaOsamu KuboyamaHiroshi ItoYounosuke KitaharaKoichi SagaraToshihiko SatohKaoru SugiYuya KobayashiYukihito HigashiTomoe KatohYudai HirayamaNaoya MatsumotoMakoto TakanoTakanori IkedaSatoru YusuShinichi NiwanoYuji NakazatoYuhei KawanoMasataka SumiyoshiN HagiwaraKagari MurasakiHideo MitamuraShunki NakagawaKaoru OkishigeKouji AzegamiHideki AoyagiKazutoshi SugiyamaMitsuhiro NishizakiNoriyoshi YamawakeIsao WatanabeKimie OhkuboHarumizu SakuradaSeiji FukamizuMakoto SuzukiWataru NagahoriTsukasa NakamuraYuji MurakawaNoriyuki HayamiKazuhiro YoshiokaMari AminoKeizo HiraoAtsuhiko YagishitaKohsuke AjikiKatsuhito FujiuYutaka ImaiAkira YamashinaTaizou IshiyamaMasao SakabeKunihiro NishidaHidetsugu AsanoiHiroshi UenoJ. D. LeeYasuhiko MitsukeHiroshi FurushimaKatsuya EbeMinoru TagawaMiho SatoMasato MorikawaKazuo YamashiroKaoru TakamiTadashi OzawaMasato WataraiMoriyasu YamauchiH. KamiyaHiroyoshi HirayamaYoshitaro YoshidaToyoaki MuroharaYasuya IndenHiroyuki OsanaiNobuyuki OhteTeruaki GotoItsuro MorishimaTakashi YamamotoEitaro FujiiMichiharu SengaHidemori HayashiTsuyoshi UrushidaYoshiaki TakadaNobuo TsuboiTakashi NodaTakuo HiroseTomoya OnoderaShinji KageyamaTakafumi OsakaTakeshi TomitaKazuyuki ShimadaMiki NomuraHideo IzawaAtsushi SugiuraTomoharu ArakawaKenjiro KimuraTakanao MineToshinori MakitaHiroyuki MizunoAtsushi KoboriTetsuya HarunaMasahito TakagiNoriko TanakaHiroaki ShimizuTakashi KuritaKoichiro MotokiNorifumi TakedaYasufumi KijimaMasahiro ItoAtsuyuki NakataY. UedaA HirataShiro KamakuraKazuhiro SatomiYoko YamadaYasuhiro YoshigaHisashi OgawaM. KimuraTakashi HayanoTakeshi KinbaraH TatsunoMasako HaradaKuninori KusanoMasaki AdachiAkemi YanoMakoto SawaguchiJunichi YamasakiTomomi MatsuuraYoshihiro TanakaHisato MoritaniTakeshi MakiSadanori OkadaMineki TakechiTakashi HamadaAkiyoshi NishikadoYuichiro TakagiIchiro MatsumotoTakeshi SoekiYoshinori DoiMakoto OkawaHye Mi SeoS KitamuraKoujirou YAMAMOTOM AkizawaNoriyoshi KanameShin‐ichi AndoSumito NaritaT InouYutaka FukuizumiK. SakuMasaya OgawaYoji UrabeMayumi IkeuchiShoko HaradaHiroshige YamabeYusuke ImamuraYoshinori YamanouchiKenji SadamatsuKōji YoshidaTomoki KubotaNaohiko TakahashiNobuhiko MakinoYou HiguchiTatsuhiko OoieTetsu IwaoK KitamuraTeruhiko ImamuraKoji MaemuraN. KomiyaMotonobu HayanoHisako YoshidaKoji Kumagai
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To clarify the influence of hypertension and blood pressure (BP) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J-RHYTHM Registry was performed.A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05-2.21, P=0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73-1.52, P=0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow-up (Q1, <114; Q2, 114-125; Q3, 126-135; and Q4, ≥136 mm Hg), odds ratios for both events were significantly higher in Q4 than in Q1 (thromboembolism, odds ratio 2.88, 95% CI 1.75-4.74, P<0.001; major hemorrhage, odds ratio 1.61, 95% CI 1.02-2.53, P=0.041) after adjustment for components of CHA2DS2-VASc score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage.BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation.URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000001569.Keywords:
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Factor V Leiden and factor II G20210A mutations are two frequent genetic risk factors involved in venous thromboembolism (VTE). The goal of this pooled analysis of 8 case-control studies, comprising a total of 2310 cases and 3204 controls, was to precisely estimate the risk of VTE in patients bearing both mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9) for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation. Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1). Twelve percent of patients heterozygous for factor V Leiden were also heterozygous for factor II G20210A and conversely 23% of patients heterozygous for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in this large population we analyzed the effect of oral contraceptive (OC) in women carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29 (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was 10.25 (5.69-1 8.45). The odds ratio of the association of factor II mutation and OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of factor V Leiden was lower in patients with pulmonary embolism than in patients with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II G20210A mutation was equally balanced in both patient groups.
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Objective To explore the relationship between biomarkers of infammation and angiotensin Ⅱ(AngⅡ) and plasma renin activity(PRA) among Mongolians.Methods The data on demographics etc.were collected,blood pressures were measured and C-reactive protein(CRP),soluble E-selectin(sE-selectin),soluble intercellular adhesion molecule 1(sICAM-1),AngⅡ and PRA were examined for 2 589 Mongolian.Logistic regression was used to analyze the association between the biomarkers and abnormal AngⅡ and PRA among Mongolian.Results The average levels of sE-selectin was signifcantly higher in the participants with abnormal PRA than those with normal PRA(18.9 vs 17.5 ng/ml,P0.001).Compared with the lowest quartile of sE-selectin,the multivariable-adjusted odds ratio(95% confident interval) of abnormal PRA for the highest quartile was 1.42(1.08~1.87).The average levels of both CRP(6.3 vs 5.5 mg/L) and sICAM-1(335.3 vs 314.4 ng/ml) were signifcantly higher in the participants with abnormal AngⅡ than those with normal AngⅡ.Compared with the lowest quartile of CRP,the multivariable-adjusted odds ratio(95% confident interval) of abnormal Ang Ⅱ for the highest quartile was 1.94(1.44~2.60);compared with the lowest quartile of sICAM-1,the multivariable-adjusted odds ratio(95% confident interval) of abnormal AngⅡ for the highest quartile was 1.44(1.11~1.87).Conclusion The levels of sE-selectin is associated with abnormal PRA,and the levels of CRP and sICAM-1 are associated with abnormal AngⅡ.
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There is increasing interest in identifying children at risk for later development of cardiovascular disease. The authors studied 1,457 children who were first examined as part of the Bogalusa Heart Study in 1973 and again 15 years later as young adults. Age-, race-, and sex-specific quartiles were defined for each of three risk factor variables—ponderal index (weight/height3), systolic blood pressure, and cholesterol—for both the child and adult measures. Adults were classified as clustered if they were in the top quartile for each of the variables. Clustered adults had higher levels of several risk factor variables, in addition to the criteria variables, than did nonclustered individuals. Of children who placed in the top quartile on three factors, 21.8% were clustered as adults. Only 1.1% of those with no risk factor levels in the top quartile were clustered as adults (P < 0.0001). Logistic regression was used to predict adult cluster status from childhood variable levels. All three factors were significant predictors, with blood pressure being the most powerful. This well-fitting model is easily interpretable in terms of standard deviations and can be a useful model for identifying at-risk children.
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To evaluate the predictive value of white blood cell count (WBC) for short and long term mortality in patients with non-ST elevation acute coronary syndromes (NSTACS) treated with a very early invasive strategy.Prospective cohort study in 1391 consecutive patients with NSTACS undergoing very early revascularisation. Patients were stratified according to quartiles of WBC determined on admission.Kaplan-Meier survival analysis showed a cumulative three year survival of 93.8% in the first quartile of WBC (< 6800/mm(3)), 94.4% in the second quartile (6800-8000/mm(3)), 95.1% in the third quartile (8000-10000/mm(3)), and 82.4% in the fourth quartile (> 10000/mm(3)) at 36 months (p < 0.001 by log rank). Relative to patients in the three lower WBC quartiles, patients in the highest quartile were three times more likely to die during the hospitalisation (hazard ratio 3.2, 95% confidence interval (CI) 1.5 to 7.1; p = 0.003) and during long term follow up (hazard ratio 3.4, 95% CI 2.2 to 5.3; p < 0.001). By multivariate Cox regression analysis including baseline demographic, clinical, and angiographic covariables, WBC in the highest quartile remained a strong independent predictor of mortality (hazard ratio 3.3, 95% CI 1.9 to 5.6; p < 0.001).WBC is a strong independent predictor of short and long term mortality after NSTACS treated with very early revascularisation.
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Background: The National Kidney Foundation–Kidney Disease Outcomes Quality Initiative recommends that the serum aluminum level (SAL) should be below 20 µg/L for patients with maintenance hemodialysis (MHD). However, serum aluminum may have toxic effects on MHD patients even when it is in the apparently acceptable range (below 20 µg/L). Methods: The Medical Ethics Committee approved this study. Initially, 954 MHD patients in dialysis centers were recruited. A total of 901 patients met the inclusion criteria and were followed-up for 1 year. Patients were stratified by SAL into four equal-sized groups: first quartile (<6 µg/L), second quartile (6–9 µg/L), third quartile (9–13 µg/L), and fourth quartile (>13 µg/L). Demographic, biochemical, and dialysis-related data were obtained for analyses. A linear regression model was applied to identify factors associated with SAL. Cox proportional hazard model was used to determine the significance of variables in prediction of mortality. Results: Only 9.3% of MHD patients had SALs of 20 µg/L or more. At the end of the follow-up, 54 patients (6%) died, and the main cause of death was cardiovascular disease. Kaplan–Meier survival analysis showed that patients in the fourth SAL quartile had higher mortality than those in the first SAL quartile (log rank test, χ 2 =13.47, P =0.004). Using the first quartile as reference, Cox multivariate analysis indicated that patients in the third quartile (hazard ratio =1.31, 95% confidence interval =1.12–1.53, P =0.038) and the fourth quartile (hazard ratio =3.19, 95% confidence interval =1.08–8.62, P =0.048) had increased risk of all-cause mortality. Conclusion: This study demonstrates that SAL, even when in an apparently acceptable range (below 20 µg/L), is associated with increased mortality in MHD patients. The findings suggest that avoiding exposure of aluminum as much as possible is warranted for MHD patients. Keywords: aluminum, mortality, hemodialysis
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The purpose of this paper is to propose setting guidance levels on entrance surface dose for radiographic examinations on children in Japan. This proposal is based on the results of surveys conducted broadly on Japanese institutes. Each value of the entrance doses (the 1st quartile, median, the 3rd quartile, and mean) was calculated with the Numerical Dose Determination method (NDD). The difference between the values of the 1st quartile and the 3rd quartile for each part of all 7 subject parts of examination ranges from 2.7 times to 3.7 times among institutions. In some institutions, the values of the 3rd quartile appeared over ten times as many as the 1st quartile. We propose the guidance levels on entrance surface doses for the children's radiographic examinations to be the value of the 3rd quartile, which was calculated from the result of the surveys.
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Aims The aim of this study was to examine the bidirectional association between atrial fibrillation and congestive heart failure (CHF) in older adults. Methods We studied the association of atrial fibrillation at entry with incident CHF (N = 5281; 85% white, 42% male) and the association of CHF at entry with incident atrial fibrillation (N = 5233; 85% white, 42% male) in the Cardiovascular Health Study (CHS). Baseline atrial fibrillation was identified during the study electrocardiogram and by self-reported history, and incident cases were identified during subsequent study electrocardiograms and hospitalization data. Baseline CHF was identified by self-reported history and adjudication of medical records, and incident cases were identified using hospitalization data. Cox regression was used to compute hazard ratios and 95% confidence intervals (CIs) for the association between atrial fibrillation and incident CHF, and CHF and incident atrial fibrillation, separately. Results Over a median follow-up of 12.6 years, 534 (10%) participants developed atrial fibrillation. CHF was associated with an increased risk of atrial fibrillation (hazard ratio 2.0, 95% CI 1.4, 3.0). A total of 1692 (32%) participants developed CHF over a median follow-up of 11.7 years and atrial fibrillation was associated with an increased risk of CHF (hazard ratio 1.9, 95% CI 1.5, 2.2). Conclusion Our results suggest that a bidirectional relationship exists between atrial fibrillation and CHF, with each condition influencing the development of the other.
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Objective: It is uncertain whether high baseline uric acid (UA) or change in UA concentration over time is related to development of incident hypertension. To investigate relationships between: a) baseline serum uric acid concentration and b) change in UA concentration and incident hypertension. Design and Method: 96,606 Korean individuals (with follow up UA data available for 56,085 people) participating in a health check program was undertaken. Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CI) for incident hypertension comparing baseline UA quartiles to the lowest UA quartile, and comparing individuals with an increase in UA to those with a decrease in UA concentration over time. Results: 96606 individuals were followed for up to 8 years (median follow-up 3.3 years; IQR, 1.9 to 5.1). 10,405 cases of incident hypertension occurred. In the fully adjusted regression model, there was a significant increase in aHR across increasing UA quartiles at baseline (p value for trend < 0.001 and 0.001 in men and women, respectively), with aHRs comparing the highest to the lowest UA quartiles of 1.29 (95% CI 1.20, 1.39) in men and 1.24 (95% CI 1.09, 1.42) in women. Additionally, stable or increasing UA concentration over time was associated with increased risk of incident hypertension, particularly in participants with baseline UA concentration ≥median (aHRs 1.14 [95% 1.03–1.26] and 1.17 [95% 0.98–1.40] in men and women, respectively). Conclusions: High initial UA concentration and increases in UA concentration over time should be considered independent risk factors for hypertension.
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