Takuya Oikawa

Isolated uncontrolled hypertension at home and in the office among treated hypertensive patients from the J-HOME study.

Objectives To evaluate the current status of blood pressure (BP) control as measured at home and in the office, as well as to clarify and compare the prevalence and characteristics of isolated uncontrolled hypertension as measured at home (home hypertension) and in the office (office hypertension). Design A cross-sectional study. Setting Primary care offices in Japan. Participants A sample of 3400 patients with essential hypertension (mean age, 66 years; males, 45%) receiving antihypertensive treatment. Results Overall, the mean home systolic BP (SBP)/diastolic BP (DBP) was 140/82 mmHg, and the mean office SBP/DBP was 143/81 mmHg. Of the 3400 subjects, 19% had controlled hypertension (home SBP/DBP < 135/85 mmHg and office SBP/DBP < 140/90 mmHg), 23% had isolated uncontrolled home hypertension (home SBP/DBP ≥ 135/85 mmHg and office SBP/DBP < 140/90 mmHg), 15% had isolated uncontrolled office hypertension (home SBP/DBP < 135/85 mmHg and office SBP/DBP < 140/90 mmHg), and 43% had uncontrolled hypertension (home SBP/DBP ≥ 135/85 mmHg and office SBP/DBP ≥ 140/90 mmHg). Compared to controlled hypertension, factors associated with isolated uncontrolled home hypertension included obesity, relatively higher office SBP, habitual drinking, and the use of two or more prescribed antihypertensive drugs. Compared to uncontrolled hypertension, factors associated with isolated uncontrolled office hypertension included female gender, lower body mass index, and relatively lower office SBP. Conclusions The use of all four, three of four, or all three predictive factors might be useful for the clinician to suspect isolated uncontrolled home or office hypertension.

Characteristics of resistant hypertension determined by self-measured blood pressure at home and office blood pressure measurements: the J-HOME study.

Objectives To diagnose resistant hypertension using self-measured blood pressure (BP) at home and office BP, and to evaluate the characteristics of resistant hypertensive patients. Methods The subjects were 528 hypertensive patients taking at least three or more different antihypertensive drugs. Subjects were classified into four groups (controlled hypertension, isolated office resistant hypertension, isolated home resistant hypertension and sustained resistant hypertension) on the basis of the cut-off values of home BP (135/85 mmHg) and office BP (140/90 mmHg). The relationship between each resistant hypertension group and various factors was analysed using univariate and multivariate analyses. Results Of the 528 patients, 17.8% were classified with controlled hypertension, 16.1% with isolated office resistant hypertension, 23.5% with isolated home resistant hypertension and 42.6% with sustained resistant hypertension. The presence of hypercholesterolemia was found to have a significant and independent association with isolated office resistant hypertension. Higher office systolic blood pressure (SBP), a past history of ischaemic heart disease, and a lower prescription rate of potassium-sparing diuretics were found to have a significant and independent association with isolated home resistant hypertension. Patients with sustained resistant hypertension had a significantly lower prescription rate of potassium-sparing diuretics than those with controlled hypertension. Conclusions The present study demonstrated that resistant hypertension is mediated at least partly by the white-coat effect. Home BP measurements and other relevant factors associated with resistant hypertension, such as relatively higher office SBP, type of drugs prescribed, and cardiovascular complications, should be taken into account for the diagnosis and treatment of resistant hypertension.

Prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure value: from the Japan Home versus Office Measurement Evaluation Study.

ObjectiveTo evaluate the prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure values. MethodsThe study population consisted of 3303 essential hypertensive outpatients receiving antihypertensive treatment in Japan. Information on the characteristics of the patients was collected by a physicians self-administrated questionnaire. The office blood pressure value was calculated as the average of the four readings in two visits. All patients were asked to measure their blood pressure once every morning and once every evening. In the study, we included patients with at least three measurements in the morning and in the evening, respectively. The average of all home blood pressure values was taken as the home blood pressure value. ResultsThe mean value of home systolic/diastolic blood pressure was 136.8/79.3 mmHg, and the mean value of office systolic/diastolic blood pressure was 142.8/80.6 mmHg. Of the 3303 patients, 758 (23.0%) had controlled hypertension (home <135/85 mmHg and office <140/90 mmHg), 628 (19.0%) had masked uncontrolled hypertension (home ≥135/85 mmHg and office <140/90 mmHg), 640 (19.4%) had treated white-coat hypertension (home <135/85 mmHg and office ≥140/90 mmHg), and 1277 (38.7%) had uncontrolled hypertension (home ≥135/85 mmHg and office ≥140/90 mmHg). ConclusionsTreated white-coat hypertension and masked uncontrolled hypertension were often observed in clinical settings. Physicians need to understand the prevalence of such patients to prevent inadequate diagnosis and treatment in them.

Temporal Trends in Clinical Characteristics, Management and Prognosis of Patients With Symptomatic Heart Failure in Japan – Report From the CHART Studies –

BACKGROUND Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure (HF) remain to be elucidated in Japan. METHODSANDRESULTS From the Chronic Heart Failure Analysis and Registry in the Tohoku District-1 (CHART-1; 2000-2005, n=1,278) and CHART-2 (2006-present, n=10,219) Studies, we enrolled 1,006 and 3,676 consecutive symptomatic stage C/D HF patients, respectively. As compared with the patients in the CHART-1 Study, those in the CHART-2 Study had similar age and sex prevalence, and were characterized by lower brain natriuretic peptide, higher prevalence of preserved left ventricular ejection fraction (LVEF) and higher prevalence of hypertension, diabetes mellitus and ischemic heart disease (IHD), particularly IHD with LVEF ≥50%. From CHART-1 to CHART-2, use of renin-angiotensin system inhibitors, β-blockers and aldosterone antagonists was significantly increased, while that of loop diuretics and digitalis was decreased. Three-year incidences of all-cause death (24 vs. 15%; adjusted hazard ratio [adjHR], 0.73; P<0.001), cardiovascular death (17 vs. 7%; adjHR, 0.38; P<0.001) and hospitalization for HF (30 vs. 17%; adjHR, 0.51; P<0.001) were all significantly decreased from CHART-1 to CHART-2. In the CHART-2 Study, use of β-blockers was associated with improved prognosis in patients with LVEF <50%, while that of statins was associated with improved prognosis in those with LVEF ≥50%. CONCLUSIONS Along with implementation of evidence-based medications, the prognosis of HF patients has been improved in Japan. ( TRIAL REGISTRATION clinicaltrials.gov identifier: NCT00418041)

Characterization of heart failure patients with mid-range left ventricular ejection fraction—a report from the CHART-2 Study

The new category of heart failure (HF), HF with mid‐range left ventricular ejection fraction (LVEF) (HFmrEF), has recently been proposed. However, the clinical features of HFmrEF, with reference to HF with preserved LVEF (HFpEF) and HF with reduced LVEF (HFrEF) in the same HF cohort, remain to be fully examined.

Current Usage of Diuretics among Hypertensive Patients in Japan: The Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) Study

In the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study, we examined the current situation with respect to the prescription of diuretics, including the prevalence of diuretic treatment and the dosages used for patients with essential hypertension in primary care settings. Of the 3,400 hypertensive patients included in the study, 315 (9.3%) patients (mean age: 66.9±10.4 years; males: 43.5%) were prescribed diuretics. Compared with patients who were not using diuretics, those who were using diuretics were more obese and had more complications. The most commonly prescribed diuretic among the 331 prescriptions in the 315 diuretic users was trichlormethiazide (44%), followed by indapamide (15%) and spironolactone (14%). Among patients being treated with diuretics, monotherapy was used in only 5% of patients; in the majority of patients combination therapy including diuretics (95%) was used. Relatively low dosages of diuretics were generally used. There was a difference between the actual dosages prescribed and those recommended by the Japanese Society of Hypertension (JSH) guidelines or the product information approved in Japan. Compared with previous estimates of the prevalence of diuretic use in hypertensives in Japan (4.0–5.4%), the rate in the J-HOME study (9.3%) was higher. This may be attributable at least in part to the results of the many published, large-scale intervention trials confirming the clinical significance of diuretics. Although a relatively high dosage is recommended in the diuretic product information and in the JSH guidelines, dosages of diuretics should be reconsidered in Japan.

Prognostic Impact of New-Onset Atrial Fibrillation in Patients With Chronic Heart Failure – A Report From the CHART-2 Study –

BACKGROUND The prognostic impact of new-onset atrial fibrillation (AF) is not fully elucidated. METHODS AND RESULTS We examined 4,818 consecutive stage C/D chronic heart failure (CHF) patients in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (n=10,219). At enrollment, 1,859 (38.6%) of them had AF. Compared with the 2,953 patients without AF, AF patients were characterized by higher age (71 vs. 68 years), lower estimated glomerular filtration rate (58.9 vs. 61.9 ml/min/1.73 m(2)), higher brain natriuretic peptide (152 vs. 74.5 pg/ml), similar left ventricular ejection fraction (56.8 vs. 56.5%), and a similar prescription rate of β-blockers (48.1 vs. 50.6%) and renin-angiotensin system (RAS) inhibitors (72.9 vs. 71.6%). Among the patients without AF at enrollment, 106 (3.6%) developed new AF during the median 3.2-year follow-up, which was associated with increased mortality (adjusted hazard ratio, 1.72; P=0.013). In contrast, neither paroxysmal nor chronic AF at enrollment was associated with increased mortality. The mortality rate was significantly high in the first year after the onset of new AF. On inverse probability of treatment weighting analysis using propensity score, RAS inhibitors and statins were associated with reduced incidence of new AF, and diuretics were associated with increase of new AF. CONCLUSIONS Onset of new AF, but not a history of AF, is associated with increased mortality in CHF patients, especially in the first year.

Prognostic Impact of Loop Diuretics in Patients With Chronic Heart Failure – Effects of Addition of Renin-Angiotensin-Aldosterone System Inhibitors and β-Blockers –

BACKGROUND It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. METHODSANDRESULTS From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P<0001). Furthermore, on IPTW multivariate Cox modeling for multiple treatments, both low-dose (<40 mg/day) and high-dose (≥40 mg/day) loop diuretics were associated with worse prognosis with HR 1.32 and 1.56, respectively (both P<0.001). Triple blockade with RAS inhibitor(s), mineral corticoid (aldosterone) receptor antagonist(s) (MRA), and β-blocker(s) was significantly associated with better prognosis in those on low-dose but not on high-dose loop diuretics. CONCLUSIONS Chronic use of loop diuretics is significantly associated with worse prognosis in CHF patients in a dose-dependent manner, whereas the triple combination of RAAS inhibitor(s), MRA, and β-blocker(s) is associated with better prognosis when combined with low-dose loop diuretics. (Circ J 2016; 80: 1396-1403).

Prognostic Impact of Atrial Fibrillation and New Risk Score of Its Onset in Patients at High Risk of Heart Failure ― A Report From the CHART-2 Study ―

BACKGROUND The prognostic impact of atrial fibrillation (AF) among patients at high risk for heart failure (HF) remains unclear. In addition, there is no risk estimation model for AF development in these patients.Methods and Results:The present study included 5,382 consecutive patients at high risk of HF enrolled in the CHART-2 Study (n=10,219). At enrollment, 1,217 (22.6%) had AF, and were characterized, as compared with non-AF patients, by higher age, lower estimated glomerular filtration rate, higher B-type natriuretic peptide (BNP) level and lower left ventricular ejection fraction. A total of 116 non-AF patients (2.8%) newly developed AF (new AF) during the median 3.1-year follow-up. AF at enrollment was associated with worse prognosis for both all-cause death and HF hospitalization (adjusted hazard ratio (aHR) 1.31, P=0.027 and aHR 1.74, P=0.001, for all-cause death and HF hospitalization, respectively) and new AF was associated with HF hospitalization (aHR 4.54, P<0.001). We developed a risk score with higher age, smoking, pulse pressure, lower eGFR, higher BNP, aortic valvular regurgitation, LV hypertrophy, and left atrial and ventricular dilatation on echocardiography, which effectively stratified the risk of AF development with excellent accuracy (AUC 0.76). CONCLUSIONS These results indicated that AF is associated with worse prognosis in patients at high risk of HF, and our new risk score may be useful to identify patients at high risk for AF onset.

Long-term prognostic impact of the Great East Japan Earthquake in patients with cardiovascular disease – Report from the CHART-2 Study

BACKGROUND We and others have previously reported that the Great East Japan Earthquake (GEJE) caused a significant but transient increase in cardiovascular diseases and deaths in the disaster area. However, it remains to be examined whether the GEJE had a long-term prognostic influence in large-scale cohort studies. This point is important when analyzing the data before and after the GEJE in the cohort studies in the disaster area. METHODS We examined 8676 patients registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219) between 2006 and 2010 and were alive after March 10, 2011. RESULTS There were 48 GEJE-related deaths, causing a sharp and transient increase in all-cause death within a month after the GEJE. However, after excluding the GEJE-related deaths, the cubic polynomial spline smoothing showed no significant increase in all-cause death, heart failure admission, non-fetal acute myocardial infarction, or non-fetal stroke during the median 3-year follow-up after the GEJE. The extrapolation curves beyond the GEJE, which were obtained by the parametric survival models based on the survival data censored on the GEJE, were not significantly different from the Kaplan-Meier curves estimating the survival functions of deaths and cardiac events during the total follow-up period without considering the impacts of the GEJE. Furthermore, the multivariate Cox proportional hazard model applied to the matched cohort of the baseline data and the data after the GEJE showed no significant differences in the impacts of prognostic factors on all-cause mortality before and after the GEJE. CONCLUSIONS These results indicate that the GEJE had no significant long-term prognostic impact after the earthquake in cardiovascular patients in the disaster area.