Age-specific incidence rates of atrial fibrillation and risk factors for the future development of atrial fibrillation in the Japanese general population.

BACKGROUND: Age-specific incidence rates of atrial fibrillation (AF) and risk factors for the development of AF have not been sufficiently determined in Japan. METHODS: A total of 130,396 community dwellers in Iwate Prefecture who did not have AF as assessed by an electrocardiogram at the 2010 annual health check-up were enrolled. We checked cases of newly developed AF in the following 3-year check-ups (in 2011, 2012, and 2013). Age-specific incidence rates (in subjects aged 45-54, 55-64, 65-74, 75-84, and 85 years or older) of AF were determined in both sexes, and multivariate-adjusted logistic regression analysis was performed using incident AF as an independent variable and already known risk factors at the 2010 survey as explanatory variables. RESULTS: Age-specific incidence rates (per 1000 person-years) of AF in subjects aged 45-54, 55-64, 65-74, 75-84, and 85 years or older were 1.42, 3.84, 6.73, 8.53, and 14.13, respectively, in males and 0.12, 0.53, 2.15, 3.40, and 10.48, respectively, in females. Odds ratios for incident AF and their 95% confidence intervals were 1.20 (1.01-1.43) in subjects with hypertension, 1.55 (1.30-1.85) in overweight subjects, 1.79 (1.23-2.61) in subjects with coronary artery disease, and 1.29 (1.08-1.53) in subjects who drank every day among male subjects and they were 1.70 (1.19-2.45) in subjects with hypertension and 1.64 (1.17-2.30) in overweight subjects among female subjects. CONCLUSIONS: Age-specific incidence rates of AF in Iwate were determined. The results showed age, hypertension, obesity, coronary artery disease, and regular drinking habit significantly increased the risk of future development of AF.

Impaired glucose tolerance and albuminuria in patients with chronic heart failure: a subanalysis of the SUPPORT trial.

AIMS: The study aims to evaluate the prognostic significance of impaired glucose tolerance (IGT) with reference to albuminuria in patients with chronic heart failure (CHF). METHODS AND RESULTS: We examined 535 CHF patients (mean 66 years, women 25%) in the control arm of our SUPPORT trial, in which we examined additive impact of olmesartan in hypertensive patients with symptomatic CHF treated with ß-blockers and/or angiotensin-converting enzyme inhibitors. We examined the association between glycaemic abnormality (assessed by 75 g of oral glucose tolerance test) and albuminuria for a composite outcome of all-cause death, myocardial infarction, stroke, and HF hospitalization. IGT patients (N = 113, mean 67.2 years) were older and more frequently treated with ß-blockers compared with those with normal glucose regulation (N = 142, mean 64.0 years) and those with diabetes mellitus (N = 280, mean 65.7 years). Multivariable Cox proportional hazard models revealed that, as compared with normal glucose regulation (NGR), IGT was associated with increased risk of the outcome when complicated by albuminuria [hazard ratio (HR) 2.25; 95% confidence interval (CI) 1.14-4.42; P = 0.019] but not when uncomplicated by albuminuria (HR 0.76; 95% CI 0.35-1.60, P = 0.47) (P for interaction = 0.041). This was also the case for diabetes mellitus and albuminuria (HR 2.06; 95% CI 1.17-3.61; P = 0.012). Among IGT patients without albuminuria, 21 (29%) developed albuminuria at 1-year visit, which was again associated with poor prognosis (HR 7.36; 95% CI 1.39-38.98, P = 0.019). CONCLUSIONS: These results indicate that IGT is associated with poor prognosis when complicated by albuminuria in CHF patients, demonstrating the importance of combined early stages of glucose intolerance and renal dysfunction in the management of CHF.

Trend in the Prevalence of Atrial Fibrillation During the Past 15 Years in Iwate (Northeastern Area of Japan).

BACKGROUND: The trend in age-specific prevalence of atrial fibrillation (AF) in Japan has not been reported.Methods and Results:Age-specific prevalence (40-49, 50-59, 60-69, 70-79 and 80-89 years old) of AF in Iwate Prefecture was determined in 1997, 2002, 2007 and 2012 (n=818,577). A positive linear trend in the prevalence of AF across calender years was observed only in males in their 60 s and 70 s. The direct age-standardized rate in males increased from 1.55% to 1.85%, while the rate in females remained around 0.5%. CONCLUSIONS: The age-specific prevalence of AF has increased only in elderly males.

Influence of Left Ventricular Ejection Fraction on the Effects of Supplemental Use of Angiotensin Receptor Blocker Olmesartan in Hypertensive Patients With Heart Failure.

BACKGROUND: There is no robust evidence of pharmacological interventions to improve mortality in heart failure (HF) patients with preserved left ventricular ejection fraction (LVEF) (HFpEF). In this subanalysis study of the SUPPORT Trial, we addressed the influence of LVEF on the effects of olmesartan in HF. METHODS AND RESULTS: Among 1,147 patients enrolled in the SUPPORT Trial, we examined 429 patients with reduced LVEF (HFrEF, LVEF <50%) and 709 with HFpEF (LVEF ≥50%). During a median follow-up of 4.4 years, 21.9% and 12.5% patients died in the HFrEF and HFpEF groups, respectively. In HFrEF patients, the addition of olmesartan to the combination of angiotensin-converting enzyme inhibitor (ACEI) and ß-blocker (BB) was associated with increased incidence of death (hazard ratio (HR) 2.26, P=0.002) and worsening renal function (HR 2.01, P=0.01), whereas its addition to ACEI or BB alone was not. In contrast, in HFpEF patients, the addition of olmesartan to BB alone was significantly associated with reduced mortality (HR 0.32, P=0.03), whereas with ACEIs alone or in combination with BB and ACEI was not. The linear mixed-effect model showed that in HFpEF, the urinary albumin/creatinine ratio was unaltered when BB were combined with olmesartan, but significantly increased when not combined with olmesartan (P=0.01). CONCLUSIONS: LVEF substantially influences the effects of additive use of olmesartan, with beneficial effects noted when combined with BB in hypertensive HFpEF patients. (Circ J 2016; 80: 2155-2164).

Clinical impacts of additive use of olmesartan in hypertensive patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial.

We examined whether an additive treatment with an angiotensin receptor blocker, olmesartan, reduces the mortality and morbidity in hypertensive patients with chronic heart failure (CHF) treated with angiotensin-converting enzyme (ACE) inhibitors, ß-blockers, or both. In this prospective, randomized, open-label, blinded endpoint study, a total of 1147 hypertensive patients with symptomatic CHF (mean age 66 years, 75% male) were randomized to the addition of olmesartan (n = 578) to baseline therapy vs. control (n = 569). The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke, and hospitalization for worsening heart failure. During a median follow-up of 4.4 years, the primary endpoint occurred in 192 patients (33.2%) in the olmesartan group and in 166 patients (29.2%) in the control group [hazard ratio (HR) 1.18; 95% confidence interval (CI), 0.96-1.46, P = 0.112], while renal dysfunction developed more frequently in the olmesartan group (16.8 vs. 10.7%, HR 1.64; 95% CI 1.19-2.26, P = 0.003). Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and ß-blockers was associated with increased incidence of the primary endpoint (38.1 vs. 28.2%, HR 1.47; 95% CI 1.11-1.95, P = 0.006), all-cause death (19.4 vs. 13.5%, HR 1.50; 95% CI 1.01-2.23, P = 0.046), and renal dysfunction (21.1 vs. 12.5%, HR 1.85; 95% CI 1.24-2.76, P = 0.003). Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence-based medications. Particularly, the triple combination therapy with olmesartan, ACE inhibitors and ß-blockers was associated with increased adverse cardiac events. This study is registered at clinicaltrials.gov-NCT00417222.

Increased risk of acute myocardial infarction after the Great East Japan Earthquake.

Strong psychosocial stress is considered to be a precipitating factor in acute coronary events. To assess the hypothesis that the incidence of acute myocardial infarction (AMI) and its severity was remarkably heightened after the great earthquake, we retrospectively analyzed the clinical data of patients with AMI admitted to our hospital during a 3-week period between March 11 and March 31, 2011 (disaster group) as compared with AMI patients during the corresponding time period of 2010 (non-disaster group). The number of patients with AMI in the disaster group increased by about threefold (22 in the disaster group vs. seven in the non-disaster group). Compared with the previous years 2010 or 2009, the odds ratios [OR] for AMI during a 3-week period in 2011 were 4.40 (95 % confidence interval [CI]: 1.05-18.35), 5.66 (95 % CI: 1.42-22.59), respectively. Although the number of patients who underwent coronary revascularization was higher in the disaster group than in the non-disaster group (68.2 vs. 42.9 %, p = 0.0397), peak serum creatine kinase (CK)-MB level was significantly higher in the disaster group than in the non-disaster group (208.0 ± 159.0 vs. 149.3 ± 102.7 IU/l, p = 0.0431). In the disaster group, four patients died of cardiac causes, whereas no patient died in the non-disaster group (in-hospital mortality rate in the disaster vs. non-disaster group: 18.2 vs. 0 %, p = 0.0281). These results suggest that patients with AMI after the earthquake might be subject to strong psychosocial stress, and that psychological stress brought on by such disaster could trigger cardiac events and cardiac death.

Occurrence of cardiovascular events after the 2011 Great East Japan Earthquake and tsunami disaster.

There are conflicting reports regarding the occurrence of cardiovascular events after a major earthquake. To understand the impact of the Great East Japan Earthquake on cardiovascular events, we retrospectively examined the clinical records prepared by emergency room physicians between 2009 and 2011 (n = 66,244), and compared the occurrence of these events between 2011 and 2009, and 2011 and 2010. There was a significant increase in the number of patients with cardiovascular events during the 3 week period after the earthquake in 2011 (n = 106) compared with that during the same period in 2009 (n = 72) or 2010 (n = 65) (P = 0.002). The number of patients with acute coronary syndrome or congestive heart failure in March 2011 was significantly increased compared with 2009 or 2010, however, there were no significant increases in 2011 in other cardiovascular events including stroke, aortic dissection, pulmonary thromboembolism, or out-of-hospital cardiac arrest compared with 2009 or 2010. These findings suggest that the incidence of cardiovascular events may have been heterogeneous after the disaster.

Characteristics of heart failure associated with the Great East Japan Earthquake.

BACKGROUND: On March 11, 2011, the Tohoku district was struck by the most powerful known earthquake to hit Japan. Although stress-induced heart diseases rise after strong psychosocial stress, little is known about the characteristics of heart failure (HF) caused by psychosocial stress related to earthquakes. METHODS: We examined patients admitted to our hospital for HF during a three-week period between March 11 and March 31, 2011 (Disaster group) and compared them to patients during the corresponding period of 2010 (Non-Disaster group). RESULTS: The number of patients was larger in the Disaster group (n=30, 18 men, 12 women; mean age 77.3±9.8 years) than in the Non-Disaster group (n=16, 8 men, 8 women; mean age 77.3±11.6 years). A total of 14 of 30 patients (46.7%) in the Disaster group did not have past history of admission for HF, compared to 2 patients (12.5%) in the Non-Disaster group (p=0.02). The number of patients with hypertension was larger in the Disaster group than in the Non-Disaster group (53.3% vs. 37.5%, p=0.04). The number of patients with atrial fibrillation was also larger in the Disaster group than in the Non-Disaster group (56.7% vs. 25.0%, p=0.03). Left ventricular systolic ejection fraction (EF) did not differ between the Disaster and Non-Disaster groups (45.2±17.8% vs. 45.6±14.0%, p=0.46), however, the proportion of patients whose EF was more than 45% were significantly higher in the Disaster group more than in the Non-Disaster group (56.7% vs. 43.8%, p=0.04). The in-hospital mortality rate for patients in the Disaster group was higher than in the Non-Disaster group (20.0% vs. 6.3%, p=0.04). CONCLUSION: The incidence and in-hospital mortality rate of HF increased after the Great East Japan Earthquake, suggesting that psychosocial stress brought on by such a disaster could lead to the development of HF with preserved EF more than that with reduced EF.

Prognostic impact of blood urea nitrogen changes during hospitalization in patients with acute heart failure syndrome.

BACKGROUND: Elevated blood urea nitrogen (BUN) observed in patients hospitalized for acute heart failure syndrome (AHFS) may represent increased neurohumoral activation. The purpose of this study was to examine the prognostic impact of BUN changes during hospitalization on the long-term prognosis of AHFS patients. METHODS AND RESULTS: The Tohoku Acute Heart Failure Registry (n=497) is a multicenter retrospective cohort study enrolling AHFS patients who were admitted in 2007. The 337 survivors (mean age, 76 years; 52% male) were divided into 3 groups according to tertiles of BUN change during hospitalization: Decreased (D-BUN, ΔBUN (BUN level at discharge-BUN level at hospitalization)≤-1.63 mg/dl, n=112); Unchanged (U-BUN, ΔBUN-1.64 to 5.73 mg/dl, n=113); Increased (I-BUN, ΔBUN>5.73 mg/dl, n=112). The D-BUN group had higher prevalence of lowest glomerular filtration rate during hospitalization, whereas the I-BUN group had higher systolic blood pressure. During a median follow-up period of 2.3 years after discharge, the Kaplan-Meier curve showed that D-BUN and I-BUN had worse prognosis compared with U-BUN. Multivariable logistic model showed that all-cause death was more frequent in I-BUN (hazard ratio, 2.94; 95% confidence interval, 1.51-5.73; P<0.001). Subgroup analysis revealed that BUN increase during hospitalization was associated with all-cause death, regardless of renal function. CONCLUSIONS: AHFS patients with a BUN increase during hospitalization have worse long-term prognosis, independent of renal function.

Rationale, design, and organization of the Diastolic Heart Failure Assessment Study in Tohoku District (DIAST).

BACKGROUND: High mortality and a high readmission rate characterize diastolic heart failure (DHF), but evidence-based therapeutic strategies have not been established for DHF. METHODS: The aim of a multicenter, randomized open trial (the Diastolic Heart Failure Assessment Study in Tohoku District, DIAST) is to evaluate the safety and prognostic efficacy of the multiple action non-selective beta-blocker carvedilol in 160 patients with DHF (left-ventricular ejection fraction > or =50%). The target dose of carvedilol is 10 mg twice a day and the mean follow-up is estimated to be 2 years. The primary endpoints are to evaluate (1) all-cause mortality or hospitalization, (2) cardiovascular mortality or hospitalization and (3) worsening heart failure. The secondary endpoints are to assess (1) cardiovascular events, (2) the individual components of the above combined endpoints, (3) the duration of hospitalization, (4) the functional class and exercise capacity and (5) the safety and tolerability. All patients' data are processed using an original registration system on an internet homepage. Several substudies to assess neurohumoral factors, heart rate variability, oxidative stress and sleep apnea will clarify the pathophysiology of DHF. CONCLUSIONS: The DIAST will contribute to establish therapeutic guidelines for DHF.

Greater impairment of right ventricular systolic function in patients with anterior myocardial infarction because of the extent of proximal lesions.

The present study examined the influence of the extent of the ischemic area on right ventricular (RV) systolic function and the relation between the RV global and regional systolic function in patients with anteroseptal myocardial infarction (MI). Biplane right ventriculography was performed in 15 subjects as the control group, and 46 patients with anteroseptal MI as the MI group. Three dimensions of the RV (the long axis dimension [LA], the anterior-posterior dimension [AP] and the septum-free wall dimension [SF]) were examined to assess regional function The MI group had a larger right ventricular end-systolic volume index and lower right ventricular ejection fraction than the control group. The more proximal the coronary lesion, the lower was the ejection fraction of the RV in the MI group. The MI group had lower percent shortening (% shortening) of the SF than the control group, but there were no significant change in the % shortening of AP and LA between the groups. The results suggest that the degree of impairment of RV systolic function depends on the extent of the infarcted area, and that the impairment is mainly from a reduction in the %shortening of the SF.