Yoshiko Iwamoto

Renal Nerve-Mediated Erythropoietin Release Confers Cardioprotection During Remote Ischemic Preconditioning

BACKGROUND Remote ischemic preconditioning (RIPC) induced by transient limb ischemia is a powerful innate mechanism of cardioprotection against ischemia. Several described mechanisms explain how RIPC may act through neural pathways or humoral factors; however, the mechanistic pathway linking the remote organ to the heart has not yet been fully elucidated. This study aimed to investigate the mechanisms underlying the RIPC-induced production of Janus kinase (JAK)-signal transducer and activator of the transcription (STAT)-activating cytokines and cardioprotection by using mouse and human models of RIPC. METHODS AND RESULTS Screened circulating cardioprotective JAK-STAT-activating cytokines in mice unexpectedly revealed increased serum erythropoietin (EPO) levels after RIP induced by transient ischemia. In mice, RIPC rapidly upregulated EPO mRNA and its main transcriptional factor, hypoxia-inducible factor-1α (HIF1α), in the kidney. Laser Doppler blood flowmetry revealed a prompt reduction of renal blood flow (RBF) after RIPC. RIPC activated cardioprotective signaling pathways and the anti-apoptotic Bcl-xL pathway in the heart, and reduced infarct size. In mice, these effects were abolished by administration of an EPO-neutralizing antibody. Renal nerve denervation also abolished RIPC-induced RBF reduction, EPO production, and cardioprotection. In humans, transient limb ischemia of the upper arm reduced RBF and increased serum EPO levels. CONCLUSIONS Based on the present data, we propose a novel RIPC mechanism in which inhibition of infarct size by RIPC is produced through the renal nerve-mediated reduction of RBF associated with activation of the HIF1α-EPO pathway.

High-sensitive troponin T is associated with atrial fibrillation in a general population

by the working status and the presence of CVD will be shown against the control group. The severity of CVD was not considered in their analysis, and expenditure for CVD medication was not considered while evaluating the association between CVD and income poverty. I would like to recommend further analysis with separation of their global definition of CVD into each disease component and also by considering the comorbidity of CVD with other diseases, which would yield precise information on the association between income poverty and chronic health conditions. I wish to express my appreciation to the members of Hygiene and Public Health, Nippon Medical School, for the preparation of this study. The author of this manuscript has certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (2010;144:1–2.).

Benefit of losartan/hydrochlorothiazide-fixed dose combination treatment for isolated morning hypertension: The MAPPY study

Abstract Morning hypertension is an established risk factor for cardiovascular events. In the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study, a 50-mg losartan/12.5-mg hydrochlorothiazide combination (Los/HCTZ) lowered morning blood pressure (BP) more effectively than 100-mg losartan (High-Los) in treated hypertensive patients with morning hypertension. The aim of this MAPPY study sub-analysis was to determine whether Los/HCTZ was effective for controlling isolated morning hypertension (morning BP ≥ 135/85 mmHg and evening BP < 135/85 mmHg), sustained hypertension (morning and evening BP ≥ 135/85 mmHg), or both. Of the 110 patients studied, 25 (22.7%) had isolated morning hypertension, and 85 (77.3%) had sustained hypertension at baseline. After 3-month treatment, isolated morning hypertension developed into controlled hypertension (morning and evening BP < 135/85 mmHg) in 9 of 11 Los/HCTZ patients (81.8%) and 3 of 14 High-Los patients (21.4 %) (p = 0.003, chi-square test). Sustained hypertension developed into controlled hypertension in 21 of 44 Los/HCTZ patients (47.7%) and 13 of 41 High-Los patients (31.7%)(NS). The rates of achievement of SBP < 135 mmHg both in the morning and evening were: 81.8% and 21.4% in Los/HCTZ- and High-Los-treated isolated morning hypertension (p = 0.003), respectively; and 61.4% and 36.6% in Los/HCTX- and High-Los-treated sustained hypertension (p = 0.022), respectively. In conclusion, Los/HCTZ was effective for controlling both types of morning hypertension, especially isolated morning hypertension. Los/HCTZ was superior to High-Los in treating both types of morning hypertension.

Losartan/hydrochlorothiazide combination is safe and effective for morning hypertension in Very-Elderly patients

ABSTRACT Morning hypertension is an independent risk for cerebrovascular and cardiovascular events. Although the prevalence of morning hypertension increases with age, treatment of morning hypertension has not been established, particularly in Very-Elderly patients. We compared the safety and efficacy of a losartan/hydrochlorothiazide (HCTZ) combination in controlling morning hypertension between Very-Elderly (≥75 years) and Young/Elderly patients (<75 years). This study was a subanalysis of the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy study, in which patients with morning hypertension (≥135/85 mmHg) received a 50-mg losartan/12.5-mg HCTZ combination tablet (combination therapy) or 100-mg losartan (high-dose therapy) for 3 months. High adherence rates and few adverse effects were observed in Very-Elderly patients receiving combination (n = 32) and high-dose (n = 34) therapies and in Young/Elderly patients receiving combination (n = 69) and high-dose (n = 66) therapies. Baseline morning systolic BP (SBP) was similar in both age groups receiving either therapy. Morning SBP was reduced by 20.2 and 18.1 mmHg with combination therapy and by 7.1 and 9.1 mmHg with high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Morning BP target (<135/85 mmHg) was achieved in 40.6% and 55.1% by combination therapy and in 14.7% and 24.2% by high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Neither therapy changed renal function and serum potassium in Very-Elderly patients. In conclusion, the losartan/HCTZ combination was safe and effective in controlling morning hypertension in Very-Elderly as well as Young/Elderly patients. In addition, combination therapy was also superior to high-dose therapy for lowering morning SBP in Very-Elderly patients.