Aim: The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of ...this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. Methods: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. Results: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio=0.83, p=0.049, in all participants and hazard ratio=0.71, p=0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 µg/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 µg/mL) group. Conclusion: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events.
Abstract Obesity is a risk factor for atrial fibrillation (AF); however, obesity is associated with lower mortality in patients with established AF, a phenomenon known as the obesity paradox. ...Previous studies reported inconsistent results regarding effects of body weight on risk of cardiogenic embolism in AF patients. To determine relation between body mass index (BMI) and prognosis among Japanese patients with non-valvular AF (NVAF), a post-hoc analysis was conducted using observational data in the J-RHYTHM Registry. Subjects were categorized as underweight (BMI: <18.5), normal (18.5 to 24.9), overweight (25.0 to 29.9), or obese (≥30 kg/m2 ). Endpoints included thromboembolism, major hemorrhaging, all-cause mortality, and cardiovascular mortality. Of 7406 patients with NVAF, 6379 patients (70 ± 10 years old; BMI, 23.6 ± 3.9 kg/m2 ) having baseline BMI data constituted the study group. During the 2-year follow-up period, 111 patients suffered thromboembolism, 124 experienced major hemorrhage, and 159 died. Multivariate analysis with the Cox proportional hazards model showed none of BMI categories were independent predictors of thromboembolism. However, being underweight was an independent predictor of all-cause mortality (hazard ratio, 2.45; 95% confidence interval, 1.62–3.69; p<0.001) and cardiovascular mortality (3.00, 1.52–5.91, p=0.001) when normal weight was used as the reference. Additionally, being overweight was a predictor of lower all-cause mortality (0.60, 0.37–0.95, p=0.029). In conclusion, being underweight is associated with higher risks of all-cause and cardiovascular mortality compared with having a normal weight. Being overweight or obese is not associated with increased mortality among Japanese NVAF patients.
Aim: Posterior circulation stroke (PCS) has different clinical features and prognosis compared with anterior circulation stroke (ACS), and whether the effect of statin therapy on stroke prevention ...differs according to infarction location remains unclear. This post hoc analysis of the J-STARS study aimed to compare the usefulness of statin at different infarction locations (i.e., ACS and PCS). Methods: In the J-STARS study, 1578 patients were randomly assigned to the pravastatin or control group. The subjects were divided into two subgroups (ACS and PCS groups) based on the arteries responsible for the infarction. Cox proportional hazards models were used to investigate whether the all stroke recurrence rate was different between the ACS and PCS groups. Results: The PCS group (n=499) had a significantly higher prevalence of diabetes than the ACS group (n=1022) (30.7% vs. 19.8%, P＜0.001). During the follow-up (4.9±1.4 years), the incidence of all stroke was significantly lower in the pravastatin group than in the control group among patients with PCS (adjusted hazard ratio HR 0.46, 95% confidence interval CI 0.25–0.83, P=0.009); however, the stroke recurrence rates were not significantly different between both groups among patients with ACS (adjusted HR 1.32, 95% CI 0.93–1.88,P=0.123). A significant interaction between the ACS and PCS groups in terms of pravastatin effects was noted (P=0.003 for interaction). Conclusions: Pravastatin significantly reduced the recurrence rate of all stroke among patients with PCS. Thus, the effect of statin on the recurrence of stroke may differ according to infarction location.
Background: Underuse and an inadequate range for the international normalized ratio (INR) for warfarin use are still problems in the management of the patients with atrial fibrillation (AF) in Japan. ...Methods and Results: From January to July 2009, a total of 7,937 AF patients 5,468 men (68.6±10.0 years) and 2,469 women (72.2±9.0 years) were registered from 158 institutions for the J-RHYTHM Registry. Overall, 34.2% of the patients were over the age of 75. The associated cardiovascular diagnoses were hypertension in 59.1%, coronary artery disease in 10.1%, cardiomyopathy in 8.3%, valvular heart disease in 13.7% and artificial cardiac valves in 3.1% of the patients. The type of AF was paroxysmal in 37.1%, persistent in 14.4%, and permanent in 48.5%. Overall, 87.3% of patients were taking warfarin (2.9±1.2mg/day), of whom 66.0% had an INR between 1.6 and 2.6, and 35.4% were in the INR range from 2.0 to 3.0 at the time of registration. Aspirin was prescribed in 22.3% of cases. The CHADS2 score was 0 in 15.7% of patients, 1 in 34.0%, and ≥2 in 50.3%. Conclusions: At present, warfarin is used extensively in patients with AF whose stroke risk is relatively low (ie, in Japan) and half of them had CHADS2 scores of 0 to 1 (UMIN Clinical Trials Registry UMIN000001569). (Circ J 2011; 75: 1328-1333)
Background: Target anticoagulation levels for warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF) are unclear. Methods and Results: Of 7,527 patients with NVAF, 1,002 did not ...receive warfarin (non-warfarin group), and the remaining patients receiving warfarin were divided into 5 groups based on their baseline international normalized ratio (INR) of prothrombin time (≤1.59, 1.6–1.99, 2.0–2.59, 2.6–2.99, and ≥3.0). Patients were followed-up prospectively for 2 years. Primary endpoints were thromboembolic events (cerebral infarction, transient ischemic attack, and systemic embolism), and major hemorrhage requiring hospital admission. During the follow-up period, thromboembolic events occurred in 3.0% of non-warfarin group, but at lower frequencies in the warfarin groups (2.0, 1.3, 1.5, 0.6, and 1.8%/2 years for INR values of ≤1.59, 1.6–1.99, 2.0–2.59, 2.6–2.99, and ≥3.0, respectively; P=0.0059). Major hemorrhage occurred more frequently in warfarin groups (1.5, 1.8, 2.4, 3.3, and 4.1% for INR values ≤1.59, 1.6–1.99, 2.0–2.59, 2.6–2.99, and ≥3.0, respectively; P=0.0041) than in non-warfarin group (0.8%/2 years). These trends were maintained when the analyses were confined to patients aged ≥70 years. Conclusions: An INR of 1.6–2.6 is safe and effective at preventing thromboembolic events in patients with NVAF, particularly patients aged ≥70 years. An INR of 2.6–2.99 is also effective, but associated with a slightly increased risk in major hemorrhage. (UMIN Clinical Trials Registry UMIN000001569) (Circ J 2013; 77: 2264–2270)
Background:Guidelines for peripheral arterial disease (PAD) recommend long-term antiplatelet therapy in symptomatic patients to reduce cardiovascular morbidity and mortality risk. Although diabetes ...is a known risk factor for PAD, PAD has been undertreated in these patients. This study aimed to evaluate risk factors for major amputation in patients with diabetes undergoing antiplatelet therapy for PAD.Methods and Results:This retrospective analysis of a 2-year observational cohort study (1,745 clinics in Japan, September 2009–2013) evaluated predictors of amputation in patients with diabetes undergoing antiplatelet therapy for PAD. Among 4,016 eligible patients, 52 had an amputation during follow-up. Amputation risk (Cox regression analysis) was predicted at baseline by history of lower extremity revascularization/amputation (hazard ratio HR: 2.92; 95% confidence interval CI: 1.39, 6.14), chronic kidney disease (HR: 4.19; 95% CI: 1.95, 8.97), and comorbid cerebrovascular and heart disease (HR: 3.32; 95% CI: 1.19, 9.30), and was unaffected by choice of oral antiplatelet therapy. In patients with PAD and diabetes, amputation event rate was highest for those with ankle-brachial pressure index (ABI) <0.40 and progressively decreased at higher ABI cut-offs.Conclusions:These findings inform real-world understanding of PAD in diabetic patients receiving antiplatelet therapy in Japan, and showed that ABI <0.4 was the strongest risk factor for amputation.
Background: Epidemiology and clinical management of acute venous thromboembolism (VTE) are not readily available in Japan. Methods and Results: The Japan VTE Treatment Registry (JAVA) is a ...multicenter cohort study of consecutive patients with an objectively confirmed, symptomatic acute pulmonary embolism (PE), symptomatic acute deep vein thrombosis (DVT), or asymptomatic acute proximal DVT. Of the 1,076 patients enrolled with acute VTE, 68.7% presented with an isolated DVT; 17.0% had PE alone; and 14.4% had both. VTE management was characterized by a high rate of inferior vena cava filter insertion (40.6%), frequent thrombolysis (21.1%), and sub-therapeutic unfractionated heparin-based anticoagulation, followed by warfarin prescription, mostly targeting an international normalized ratio of 2.0 (range, 1.5–2.5). During a mean observation period of 252.5 days, 29 recurrent cases of VTE were documented, yielding an incidence rate of 3.9 per 100 patient-years. A total of 123 patients died during the study period, corresponding to a rate of 16.6 deaths per 100 patient-years. The incidence of major bleeding was 3.2% per patient-year, including 2 fatal hemorrhages and 7 intracranial hemorrhages. Conclusions: VTE management in Japan is characterized by a highly aggressive strategy in the acute phase, in contrast to protocols that use low-level anticoagulation. The VTE recurrence rates in Japan and Western countries are similar, but mortality is higher in Japan, with significant variability depending on patient and management characteristics. (Circ J 2014; 78: 708–717)
The EXPAND Study demonstrated the effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) in routine clinical practice in Japan. This sub-analysis was ...conducted to reveal the effectiveness and safety of rivaroxaban in Japanese NVAF patients according to baseline creatinine clearance (CrCl) levels and rivaroxaban doses in the EXPAND Study. We examined 6806 patients whose baseline CrCl data were available and classified them into 2 groups: normal renal function group with CrCl ≥ 50 mL/min (
n
= 5326, 78%) and renal dysfunction group with CrCl < 50 mL/min (
n
= 1480, 22%). In the normal renal function group, 1609 (30%) received 10 mg/day (under-dose), while in the renal dysfunction group, 108 (7%) received 15 mg/day (over-dose). In the normal renal function group, under-dose of rivaroxaban was associated with higher all-cause mortality, while in the renal dysfunction group, over-dose was associated with higher incidence of major bleeding. In contrast, the incidence of stroke or systemic embolism was not different between the 2 groups regardless of the dose of rivaroxaban. In the propensity score matched analysis to adjust the difference in characteristics according to doses of rivaroxaban, the incidences of clinical outcomes were comparable between the 2 dose groups in both renal function groups. These results indicate that the dose of rivaroxaban should be reduced depending on the renal function, considering the balance between risks of bleeding and ischemia.
Aims
We aimed to estimate the causes of death and their incidence rates and risk factors for all-cause mortality in Japanese people with type 2 diabetes using baseline data from the Japan Diabetes ...Complication and its Prevention (JDCP) prospective study.
Methods
We analyzed a multicenter prospective cohort of 5944 Japanese people with diabetes aged 40–74 years. Causes of death were categorized as cardiac or cerebrovascular disease, malignancy, infectious disease, accident or suicide, sudden death of unknown cause, and other unknown causes. The Cox proportional hazards model was used to estimate the hazard ratio of all-cause mortality risk factors.
Results
The mean age was 61.4 years, and 39.9% of the population was female. Overall, the mortality ratio per 100,000 person-years (95% confidence interval CI) was 515.3 (95% CI 445.1–596.9). Malignancies are the most common cause of death among people with type 2 diabetes, accounting for 46.9% of all deaths, followed by cardiac and cerebrovascular diseases at 11.7% and infectious diseases at 3.9%. Higher mortality risk was significantly associated with older age, lower body-mass index, alcohol intake, history of hypertension, and acute myocardial infarction (AMI).
Conclusions
The frequency of causes of death in people with type 2 diabetes identified in this study was similar to that from a recent survey on causes of death conducted by the Japan Diabetes Society. A lower body-mass index, alcohol intake, history of hypertension, and AMI were found to be associated with an increased total risk of type 2 diabetes.
Background
Low-dose aspirin is widely used for the prevention of cardiovascular events. The prevalence of gastroduodenal injuries and the risk factor profile including gastroprotective drug therapy ...needs to be clarified in Japanese patients taking daily aspirin for cardioprotection.
Methods
This Management of Aspirin-induced Gastro-Intestinal Complications (MAGIC) study was conducted with a prospective nationwide, multicenter, real-world registry of Japanese patients at high-risk of cardiovascular diseases who were taking regular aspirin (75–325 mg) for 1 month or more. All patients underwent endoscopic examination for detection of gastroduodenal ulcer and mucosal erosion. The risk factor profiles including the concurrent drug therapy were compared for those patients with gastroduodenal problems and those without.
Results
Gastroduodenal ulcer and erosion were detected in 6.5, and 29.2 % of the 1,454 patients receiving aspirin, respectively.
H. pylori
infection was associated with an increased risk for ulcer: OR 1.83 (1.18–2.88
p
= 0.0082). Risk of erosion was lower with enteric-coated aspirin than with buffered aspirin: odds ratio (OR) 0.47 (0.32–0.70,
p
= 0.0002). Patients receiving proton pump inhibitors had lower risks for both gastroduodenal ulcer and erosion: OR 0.34 (0.15–0.68,
p
= 0.0050) and 0.32 (0.22–0.46,
p
< 0.0001), respectively. However, those receiving histamine 2-receptor antagonists had reduced risks for erosion but not for ulcer: OR 0.49 (0.36–0.68,
p
< 0.0001).
Conclusion
Gastroduodenal ulcer and erosion are common in Japanese patients taking low dose aspirin for cardioprotection. Proton pump inhibitors reduce the risk of gastroduodenal mucosal injury.
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