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Resistant hypertension is defined as the official values of blood pressure (BP) >140/90 mmHg despite lifestyle changes and treatment with optimal or best tolerated doses of three or more antihypertensives (one of which is thiazide/diuretic like thiazide) and after the exclusion of pseudoresistance, secondary hypertension and hypertension caused by drugs. The inadequate BP control should be confirmed by out-of-office BP measurement showing an uncontrolled 24-hours BP (≥ 130 mmHg systolic or ≥ 80 mmHg diastolic) values. If confirmation of true resistant hypertension by ambulatory blood pressure monitoring is not feasible, home blood pressure monitoring may be used.1 The prevalence of true resistant hypertension is about 5%. But in patients with comorbidities the prevalence increases to 22.9% with chronic kidney disease, 56.0% with renal transplant and 12.3% with aging.2 These patients are at higher risk of complications including cardiovascular disease, stroke, kidney failure, and death. Effective treatment should combine lifestyle changes such as reduction of sodium and alcohol intake, implementation of regular physical activity and weight loss in overweight or obese patients, discontinuation of interfering substances, rationalization of current treatment and the sequential addition of antihypertensive drugs to the existing triple therapy. Considering the pathophysiological mechanism, an interplay between multiple neurohumoral factors such as increased levels of aldosterone, endothelin-1, vasopressin and increased sympathetic activity which contribute to volume and sodium overload, increase in peripheral vascular resistance, arterial stiffness the fourth lines of treatment are antagonists of mineralocorticoid receptors.1The PATHWAY-2 trial demonstrated that spironolactone was superior in reducing BP compared with bisoprolol (a beta-blocker), doxazosin (an alpha-blocker), or placebo as add-on therapy in patients with resistant hypertension on three blood pressure medications.3 This drug should be used with caution in chronic kidney disease because of hyperkalemia. The use of newer potassium binders such as patiromer or sodium zirconium cyclosilicate can reduce the risk of hyperkalemia. If gynecomastia becomes intolerable, spironolactone can be switched to eplerenone, a selective aldosterone receptor antagonist that has minimal interaction with sex hormone steroid receptors. The type of diuretic needs to be adapted to renal function. In patients with preserved glomerular filtration rate, the preferred first-line diuretic is either chlorthalidone or indapamide because of their longer half-life and more potent antihypertensive effect compared with hydrochlorothiazide. Chlortalidone (12.5 mg or 25 mg once daily) may be used with or without loop diuretic if eGFR <30mL/ min/1.73m2. Loop diuretics are preferred in patients with an estimated glomerular filtration rate less than 30 mL/min/1.73 m2. Torsemide can be used once a day, but shorter-acting loop diuretics such as furosemide or bumetanide must be dosed at least twice a day. Finally, new more selective nonsteroidal MRAs such as finerenone (approved for the treatment in diabetic kidney disease), esaxerenone (approved for the treatment of hypertension in Japan), and ocedurenone (KBP-5074, in development for resistant hypertension in CKD) might provide future alternatives to spironolactone. Renal denervation, a promising new treatment method, should be considered as an additional therapeutic option if the appropriate criteria are met in patients with eGFR >40 ml/min.1 [ABSTRACT FROM AUTHOR]

Aim: To determine the real‐world use of fixed‐dose combinations (FDC) of antihypertensive agents using data collected from a nationwide medical database of acute hospitals in Japan. Methods: We carried out a retrospective analysis of data from the Medical Data Vision database for patients with hypertension who received an antihypertensive drug prescription between April 2014 and March 2015. The prescription rate of antihypertensive FDC were assessed by class, age and according to combinations. Results: In total, data from 59 867 patients aged 70.0 ± 11.9 years (mean ± SD) were analyzed. Patients were prescribed 1.9 ± 1.0 oral antihypertensive agents (mean ± SD). Overall, 58.6% of patients were prescribed two or more antihypertensive agents, and the most frequently prescribed classes were calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB). As the number of concomitant antihypertensive agents prescribed increased, the prescription rate of a CCB + an ARB FDC decreased, whereas the prescription rate of an ARB + a diuretic FDC increased. This trend was the same regardless of age. Of the 12 222 patients who were prescribed a CCB + an ARB, 26.0% received a FDC. In contrast, of the 922 patients prescribed an ARB + a thiazide diuretic, 80.6% received a FDC. Medium doses of both CCB and ARB agents, and low doses of diuretics were the most frequently prescribed for each class. Conclusions: Our analyses show that the real‐world use of FDC varies depending on the combination of agent class and the number of prescriptions; the latter was similar regardless of age. Geriatr Gerontol Int 2019; 19: 1077–1083. [ABSTRACT FROM AUTHOR]

Aim: To analyze the current use of antihypertensive drug classes in Japanese hypertensive patients stratified by age, highlighting differences between older and younger patients. Methods: A nationwide medical database was used to evaluate antihypertensive use in patients (aged ≥20 years) who had received a prescription for one or more antihypertensive drug as an outpatient from April 2014 to March 2015. Patients (n = 59 867) were age‐stratified into three groups: <65 years (28.7%), 65–74 years (33.1%) and ≥75 years (38.2%). Results: The mean number of antihypertensive drugs prescribed for patients in the overall population was 1.9 ± 1.0, with no appreciable differences between age groups. The most commonly prescribed drug classes for all ages were calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB). CCB were prescribed more often than ARB in the 65–74 years (66.9% vs 60.5%) and ≥75 years (70.4% vs 56.8%) years age groups, and ARB were prescribed more often than CCB in patients aged <65 years (63.1% vs 61.9%). There were minimal differences by age in prescription rates for β‐blockers, angiotensin‐converting enzyme inhibitors and thiazide diuretics. ARB prescription rates were lower in patients aged ≥75 years with diabetes mellitus or renal disease than in younger age groups. Prescription rates for loop diuretics were higher in patients aged ≥75 years than in younger age groups, especially among those with renal disease. Conclusions: Antihypertensive drugs selected for patients aged ≥75 years differed from those selected for younger patients, in particular CCB and loop diuretics (prescribed more often), and ARB (prescribed less often). Geriatr Gerontol Int 2018; 18: 899–906. [ABSTRACT FROM AUTHOR]

Background: While body mass index (BMI) is the most widely used anthropometric measure, its association with all-cause mortality is generally J-shaped or U-shaped. A body shape index (ABSI) is a recently formulated anthropometric measure that shows linear relationship to all-cause mortality, especially in Caucasian cohorts. We aimed to address the relationship between ABSI and all-cause mortality in Asians and to assess the influence of sex difference and of chronic kidney disease (CKD) on this relationship. Methods: This was a longitudinal cohort study assessing the association of ABSI, BMI, waist circumference (WC), and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese nationwide Specific Health Checkup database. The study enrolled 160,625 participants followed-up between 2008 and 2012. We calculated the all-cause mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI, BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD. Results: During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD) significantly increased the risk for all-cause mortality after adjusting for other known risk factors including CKD; hazard ratio (HR) and 95% confidence intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p<0.01; HR and 95%CI of CKD cohort, 1.16 (1.01 to 1.34), p = 0.04. In women, ABSI (+1SD) did not show significant association with all-cause mortality, especially in the CKD cohort; HR and 95% CI of non-CKD cohort, 1.07 (0.99 to 1.17), p = 0.09; HR and 95%CI of CKD cohort, 0.98 (0.84 to 1.14), p = 0.78. Conversely, BMI (+1SD) was associated with significantly lower risk in men, although minimal association was found in women. WC and WHtR showed little association with all-cause mortality. On stratification per ABSI quartiles, mortality risk increased linearly and significantly with ABSI in men, but not in women with CKD. Both BMI and WC showed significant but U-shaped association with mortality in the non-CKD cohort and in men with CKD. WHtR also showed significant U-shaped association with mortality in men. Conclusions: In the Japanese population, ABSI showed significant and linear correlation with mortality risk in men but not in women, especially in the presence of CKD. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) usually peaks in the morning. The circadian variation of the onset of cardiovascular disease mimics this circadian BP variation. To examine the determinants of the BP difference between the self-recorded BP in the morning (home BP) and daytime average ambulatory BP a cross sectional study was done in the general population of Ohasama, Japan. 1207 subjects ≥20 years measured both home (more than 14 times) and ambulatory BPs (326 treated for hypertension and 881 untreated subjects). The prevalence of subjects with the systolic BP difference (home BP in the morning — daytime ambulatory BP) of ≥ 10 mmHg (high morning BP) was 5.6% in untreated normotensives, 2.9% in untreated hypertensives, and 25.8% in treated hypertensives. This trend was also observed for diastolic pressure. Multiple regression analysis demonstrated that age, male sex, and use of antihypertensive drugs were positively associated and day-night difference of BP was negatively associated with the high morning BP, respectively. These results suggest an insufficient duration of antihypertensive action of widely used antihypertensive drugs in Japan from the 1980s to 1990s. The amplitude of the day-night difference of ambulatory BP in subjects with a high morning BP was lower (non-dipping) than that without high morning BP. The high morning BP is not necessarily accompanied by hypertension but might be mediated, at least in part, by an insufficient duration of action of antihypertensive drugs. The high morning BP accompanies so-called non-dipper pattern of circadian BP variation. An insufficient duration of action of drugs may partly mediate non-dipping in subjects with antihypertensive medication. [ABSTRACT FROM AUTHOR]

In 2014, the Japanese Society of Hypertension (JSH) issued revised guidelines for hypertension management. To assess adherence to the guidelines, this retrospective study evaluated the real-world status of antihypertensive drug prescribing for Japanese patients with hypertension, classified by comorbidity: diabetes mellitus, dyslipidemia, gout/hyperuricemia and renal diseases. Data on 59,867 hypertensive patients who received their first prescription for antihypertensive therapy between April 2014 and March 2015, were obtained from a medical insurance claims database for hospitals participating in the Diagnosis Procedure Combination/Per-Diem payment system. The most common drugs prescribed for each comorbidity subgroup were calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs), with prescription rates of around 60-70%. Contrary to JSH recommendations, diuretics and angiotensin-converting enzyme inhibitors were prescribed less often than β-blockers. Whereas diabetes mellitus is a compelling indication for use of renin-angiotensin system inhibitors, CCBs were commonly prescribed in this subgroup. The treatment pattern for patients with comorbid dyslipidemia closely resembled that for the overall patient population. Loop diuretics were prescribed more frequently for patients with renal diseases or gout/hyperuricemia than for those with diabetes mellitus or dyslipidemia. Although antihypertensive drug prescribing varied by comorbidity, JSH 2014 guidelines appeared not to be incorporated adequately into actual clinical practice.