Morning Home Blood Pressure and Cardiovascular Events in Japanese Hypertensive Patients.

SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated the benefit of achieving strict blood pressure control with a lower target blood pressure level in high-risk patients with hypertension. The aim of this post hoc analysis was to investigate the relationship between the 2-year average on-treatment home blood pressure and cardiovascular disease risk in subgroups stratified by risk status using data from the HONEST study (Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure). Participants in the HONEST study (n=21 591) were stratified according to risk level as follows: SPRINT population (n=5823)-patients (≥50 years of age) without diabetes mellitus or prior stroke, with SPRINT-defined cardiovascular risk and systolic blood pressure (SBP) of ≥130 mm Hg; SPRINT-excluded high-risk population (n=5481)-patients with diabetes mellitus or prior stroke; and non-SPRINT low-risk population-all other patients in the HONEST study (n=10 287). Cardiovascular disease event risk was 6.32 events per 1000 person-years in the SPRINT population, which was higher than in the non-SPRINT low-risk (3.39; P<0.001) and lower than the SPRINT-excluded high-risk (12.41; P<0.001) populations. In the SPRINT and the SPRINT-excluded high-risk populations, a lower home SBP achieved was associated with lower cardiovascular disease risk, with the lowest risk in patients with a home SBP <125 mm Hg. The non-SPRINT low-risk population showed a J-curve association between on-treatment home SBP and cardiovascular disease risk with the lowest risk at a home SBP of 135 to <145 mm Hg. Intensive therapy targeting home SBP of <125 mm Hg would be beneficial for high-risk hypertensive patients. Clinical Trial Registration- URL: http://www.umin.ac.jp/ctr/index.htm . UMIN Clinical Trials Registry, trial no.: UMIN000002567.

Recurrent Stroke and Bleeding Events after Acute Cardioembolic Stroke-Analysis Using Japanese Healthcare Database from Acute-Care Institutions.

BACKGROUND: To understand the reality of patients who experienced a cardioembolic stroke (CES) is important because of the high incidence of recurrent stroke and the need to account for bleeding risk in relation to the need for anticoagulation treatment. We elucidated the current real-world medical care in patients who had a CES and identified the risk factors for recurrent stroke. METHODS AND RESULTS: The study comprised 9804 patients who were diagnosed with CES between April 2008 and September 2013 as identified in a healthcare database used by acute-care institutions in Japan. We analyzed the incidence and risk factors of stroke and bleeding events in CES patients. The incidence of stroke was 10.3% during the median observation period of 68 days, mainly consisting of recurrent CES (8.5%). The incidence of bleeding events and intracranial bleeding was 10.3% and 7.0%, respectively. The recurrence of ischemic stroke was significantly lower, and brain hemorrhage was significantly higher in the anticoagulation treatment group. The factors related to an increased risk of stroke were a history of cerebral infarction or transient ischemic attack, diabetes, and increase of CHA2DS2-VASc and CHADS2 scores. The risk factors for bleeding events were hypertension, renal dysfunction, and use of proton pump inhibitors (PPIs). CONCLUSIONS: The patients who experienced CES had a high rate of recurrent stroke or CES, mainly consisting of recurrent CES. Although anticoagulation may be beneficial for reducing recurrence of ischemic stroke, careful management is required given consideration of increased risk of brain hemorrhage during anticoagulation treatment, especially for patients with hypertension, renal dysfunction, and use of PPIs.

Incidence of venous thromboembolism and bleeding events in patients with lower extremity orthopedic surgery: a retrospective analysis of a Japanese healthcare database.

BACKGROUND: Orthopedic surgeries of lower extremities such as total knee arthroplasty (TKA), total hip arthroplasty (THA), and hip fracture surgery (HFS) are widely considered to carry a high risk of developing deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE). Growing attention to epidemiological studies using a healthcare database led us to quantify the risks using a Japanese database to reveal recent medical care for such events. METHODS: The study comprised 36,947 patients who had undergone orthopedic surgeries of the lower extremities and whose medical information from April 2008 to September 2013 was available. The source population of the database was derived from 100 acute-care hospitals with Diagnosis Procedure Combination. The events were defined by diagnosis, medication, imaging, and laboratory tests. RESULTS: A breakdown of patients who underwent orthopedic surgeries by type of surgery showed 13.6% for TKA, 10.4% for THA, 56.8% for HFS, 1.5% for rupture of Achilles tendon, and 18.0% for simple fracture of lower extremities. The incidence for DVT, PTE, and bleeding events by type of surgery was 1.3, 0.2, and 1.0% for TKA; 0.9, 0.2, and 1.1% for THA; and 0.4, 0.1, and 1.8% for HFS, respectively. The population for risk factor analysis consisted of patients with similar background factors who underwent TKA, THA, or HFS. The statistically significant risk factors for PTE analyzed by the backward elimination procedure in a multivariate model were female sex, history of venous thromboembolism (VTE), thrombophilia, and varicose veins of lower extremity. CONCLUSIONS: The incidence of DVT, PTE, and bleeding events and the risk factors for DVT and PTE in patients by type of orthopedic surgeries of lower extremities found in our study are considered to be rational as they reflect evidence from real-world cases. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000012667.

Predictors of venous thromboembolism recurrence and the bleeding events identified using a Japanese healthcare database.

BACKGROUND: Treatment to prevent the recurrence of venous thromboembolism (VTE) and prevent bleeding events should be given to patients with VTE in an appropriate balance in relation to relevant predictors. We elucidated the current medical care in a real world setting and quantified predictors using a Japanese healthcare database. METHODS: The study included 3578 patients who were diagnosed with VTE between April 2008 and September 2013 at a Japanese acute-care hospital and included in the hospital database. Twenty-four patients who had a VTE event during the 180-day period after enrollment were excluded. We analyzed the incidence of recurrent VTE, incidence of bleeding events, and predictors in VTE patients. Events were defined by disease, medication, imaging, and laboratory testing, among other factors. RESULTS: The rate of recurrence of VTE events was 7.2 per 100 patient-years. The incidence rate of bleeding events was 8.3 per 100 patient-years. The presence of malignant disease, antipsychotic drugs, and nonsteroidal anti-inflammatory drugs increased the risk for recurrent VTE. The predictors for bleeding events were malignant disease, central venous catheterization, cancer chemotherapy, stroke, and diabetes. CONCLUSIONS: These findings obtained from healthcare database suggest predictors either for recurrent VTE and bleeding that should be considered when selecting treatment to reduce the risk of recurrent VTE and mitigate bleeding.

Usefulness of a healthcare database for epidemiological research in atrial fibrillation.

BACKGROUND: Big data are gaining attention as a valuable resource for providing insights into a range of issues and questions in healthcare. We evaluated the capacity of a Japanese healthcare database to conduct epidemiological research in non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: We examined data collected between April 2008 and September 2013 in a Japanese healthcare database. Prior to the risk factor analysis, we validated the criteria for defining the occurrence of a stroke, systemic embolic event (SEE), and intracranial bleeding event during the study period. The validity was considered appropriate based on the resulting high positive predictive values. The data of 18,998 NVAF patients demonstrated that the incidence rates of stroke, SEE, and any bleeding events were 2.2, 0.08, and 2.4 per 100 patient-years, respectively. In patients who had not been treated with an anticoagulant, incidence of stroke significantly increased in higher CHADS2 or CHA2DS2-VASc score, 1.7 and 1.5 fold by 1 point increase, respectively. The use of a proton pump inhibitor (PPI) was also identified as an independent risk factor for stroke. In patients who had been treated with an anticoagulant, the independent risk factors for any bleeding events were hypertension, renal dysfunction, hepatic failure, medical history of stroke, older age (≥65 years), use of nonsteroidal anti-inflammatory drug, and PPIs. CONCLUSION: The data obtained in this study were comparable with results obtained in prospective cohort studies conducted in Japan.

Pravastatin use and cancer risk: a meta-analysis of individual patient data from long-term prospective controlled trials in Japan.

PURPOSE: To assess the influence of pravastatin therapy on cancer morbidity and mortality by a meta-analysis of individual patient data (IPD) from three independent Japanese large-scale clinical trials. METHODS: We conducted a meta-analysis of IPD collected from three large-scale prospective studies, the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study, Kyushu Lipid Intervention Study (KLIS), and Hokuriku Lipid Coronary Heart Disease Study-Pravastatin Atherosclerosis Trial (Holicos-PAT), which compared cardiovascular outcomes with pravastatin therapy and non-statin therapy in Japanese patients with hypercholesterolemia over a follow-up period of >or=4 years. The incidence of cancer or cancer death in the pravastatin and non-statin therapy groups was compared by multivariate Cox proportional hazard models stratified by trial. Subgroup analyses by sex and age were also conducted using the same methods. RESULTS: In a total of 13 724 patients (mean age, 58 years; women, 48%) included in the analyses, pravastatin was not associated with an increased risk of developing cancer (hazard ratio [HR], 0.99; 95% confidence interval [95%CI], 0.81-1.19). Similarly, pravastatin therapy did not statistically affect cancer death (HR, 0.86; 95%CI, 0.61-1.21). Moreover, in subgroups analyses, no influence was observed on cancer incidence or death in relation to sex and age. CONCLUSION: Pravastatin did not increase the rate of cancer incidence or cancer death in a large population of Japanese patients followed for >70,000 patient-years.

Statins: beneficial or adverse for glucose metabolism.

Large-scale clinical trials have established that statin use for lowering blood cholesterol is beneficial in reducing atherosclerotic cardiovascular diseases in different populations. However, the general reputation of statins seems to be clouded by a potential adverse effect of a class of statins on glucose metabolism. This paper reviewed clinical data of statins regarding the effects on diabetes mellitus and glucose metabolism. At least five randomized controlled studies, primarily investigating the protective effect of statins on the risk of cardiovascular diseases, have addressed the effect of statins on glucose metabolism in Western countries. One study showed that pravastatin (40 mg/day) was protective against the development of diabetes mellitus. Two studies of atorvastatin (10 mg/day) and one study of simvastatin (40 mg/day) showed no measurable effect of these regimens on the risk of diabetes mellitus or the clinical course of diabetes mellitus. One study of atorvastatin (80 mg/day) versus pravastatin (40 mg/day) suggested a deterioration of glucose metabolism associated with a high dose of atorvastatin. In Japan, a few case reports have noted a potential adverse effect of atorvastatin on glycemic control in patients with diabetes mellitus; however, seven clinical trials have showed no such effect of atorvastatin although these studies were relatively small in size and short in follow-up. Only one of the two observational studies suggested a possible adverse effect of atorvastatin on glycemic control. Evidence is extremely limited regarding atorvastatin use and deterioration in glycemic control, and further studies are needed to draw a conclusion on this issue.

Relation of serum total cholesterol and other factors to risk of cerebral infarction in Japanese men with hypercholesterolemia.

BACKGROUND: Risk factors for cerebral infarction have not been well clarified, except for hypertension (HT), and few studies have examined the risk factors in the elderly. METHODS AND RESULTS: Clinical and behavioral risk factors for cerebral infarction were examined in 4,349 Japanese men aged 45-74 years with a serum total cholesterol (TC) concentration of 220 mg/dl or greater who participated in the Kyushu Lipid Intervention Study. A total of 81 men developed definite cerebral infarction in a 5-year follow-up period. The Cox proportional hazards model was used with serum TC at baseline and during the follow-up, serum high-density lipoprotein-cholesterol (HDL-C), HT, diabetes mellitus (DM), and other factors as covariates. Serum TC during the follow-up, not at baseline, was positively associated with cerebral infarction, showing a stronger association in the elderly (>or=65 years old) than in the middle-aged (<65 years old). Statin use was related to a moderate decrease in the risk of cerebral infarction when follow-up TC was not considered, but the decrease was almost nullified after adjustment for follow-up TC. A low concentration of serum HDL-C, diabetes mellitus, hypertension, and angina pectoris were each related to an increased risk. No clear association was observed for body mass index, smoking or alcohol use. CONCLUSIONS: Lowering cholesterol is important in the prevention of cerebral infarction in men with moderate hypercholesterolemia. A low concentration of HDL-C, DM, and HT are independent predictors of cerebral infarction.

Relation of serum total cholesterol and other risk factors to risk of coronary events in middle-aged and elderly Japanese men with hypercholesterolemia: the Kyushu Lipid Intervention Study.

BACKGROUND: The role of serum total cholesterol (TC) in the development of coronary heart disease (CHD) may differ in different age groups. METHODS AND RESULTS: The relation of serum TC and other risk factors to CHD events was examined in middle-aged (<65 years) and elderly (> or =65 years) men separately in the Kyushu Lipid Intervention Study (KLIS). Subjects were 4,349 men aged 45-74 years with serum TC of 220 mg/dl or greater who had no history of myocardial infarction, coronary angioplasty, or stroke. There were 123 CHD events (ie, myocardial infarction, coronary bypass surgery, coronary angioplasty, cardiac death, and sudden death) in a 5-year follow-up period. The Cox proportional hazards model was used with baseline and follow-up serum TC, baseline high-density lipoprotein (HDL) cholesterol, hypertension, diabetes mellitus, and other factors as covariates. Serum TC concentration during the follow-up, not at baseline, was associated with an increased risk of CHD events, especially in elderly men. High concentrations of serum HDL cholesterol were associated with a modest, statistically nonsignificant decrease in the risk among middle-aged men. An increased risk of CHD events associated with diabetes mellitus was greater in middle-aged men. Hypertension and smoking were not measurably related to the risk in either middle-aged or elderly men. CONCLUSIONS: Both the serum TC concentration during follow-up and diabetes mellitus are important predictors of CHD events in Japanese men with moderately elevated serum TC.

Reduction in serum total cholesterol and risks of coronary events and cerebral infarction in Japanese men: the Kyushu Lipid Intervention Study.

Lowering serum total cholesterol is shown to decrease the risk of coronary heart disease (CHD) in Western countries,but evidence is limited regarding cerebral infarction (CI). The present study used the Kyushu Lipid Intervention Study to examine the risks of CHD events and CI in relation to reduction in serum total cholesterol. Subjects were 4,615 men aged 45-74 years with serum total cholesterol of 220 mg/dl (5.68 mmol/L) or greater who had no history of CHD events or stroke. CHD events and CI numbered 125 and 92, respectively, in a 5-year follow-up. After adjustment for potential confounding factors, the relative risks of CHD events and CI for 15% or greater reduction in total cholesterol, compared with less than 5% reduction, were 0.78 (95% confidence limit [CL]0.46-1.32) and 0.39 (95% CL 0.22-0.69), respectively. As compared with on-treatment cholesterol levels of 240 mg/dl (6.20 mmol/L)or higher, the risk of CHD events was approximately 50% lower across 3 categories below 240 mg/dl (6.20 mmol/L), and that of CI was 70%lower at 2 categories below 220 mg/dl (5.68 mmol/L). Lowering serum total cholesterol below 220 mg/dl (5.68 mmol/L) seems desirable with regard to the prevention of CI.