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Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Maintaining ideal body weight and muscle strength through lifestyle modification is essential for improving activities of daily living (ADL) and life expectancy in hypertensive patients. The effect of weight reduction in older patients with hypertension, however, is controversial. We evaluated the prognostic significance of body mass index (BMI) and handgrip strength (HG) in older patients with hypertension. Patients were stratified by the combination of BMI and HG. COX regression analysis was used to assess the mortality risk. A total of 563 patients (age 77 [71-84] years, 50% male, 40% frailty) were followed for a median duration of 41 (34-43) months. In total, 59 deaths occurred during the follow-up period. Validation of mortality by BMI level revealed that patients with BMI < 22 kg/m 2 were likely to have higher mortality risk. Low HG, however, was associated with a 3.7-fold increased mortality risk. The risk of all-cause mortality using BMI combined with HG (adjusted hazard ratio [95% confidence interval]) was as follows: (1) Normal HG + 22 kg/m 2  ≤ BMI, reference; (2) Normal HG + BMI < 22 kg/m 2 , 2.39 (0.12-16.46); (3) Low HG + 22 kg/m 2  ≤ BMI, 4.01 (1.42-14.38); and (4) Low HG + BMI < 22 kg/m 2 , 4.55 (1.33-18.13). These findings demonstrate that weight reduction may deteriorate the mortality risk in older patients with hypertension, and new lifestyle modification strategies for improving ADL, quality of life, and prognosis are warranted for older patients with hypertension. We assessed the association between BMI, handgrip strength, and risk of all-cause mortality to evaluate the validity of weight reduction in older patients with hypertension., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated., Methods: Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m 2 ) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses., Results: In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men., Conclusions: We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF., (© 2024. The Author(s).)

A 72-year-old man developed fever and chest pain, accompanied by an increase in C-reactive protein, four days after successful emergency catheter intervention for an acute wide anterior myocardial infarction (MI). A twelve-lead electrocardiogram (ECG) showed marked ST elevation in leads V1-6, I, and aVL, with reciprocal ST depression in leads II, III, and aVF. Although these ECG changes improved by day three, he developed fever and chest pain on day four, and an ECG at this timepoint showed ST elevation in leads II, III, aVF, and mild worsening of the ST elevation in the anterolateral leads, indicating diffuse ST-segment elevation consistent with acute pericarditis. Despite the presence of a typical friction rub, there was no pericardial effusion on an echocardiogram. No elevation of cardiac enzymes was noted. A diagnosis of early post-infarction pericarditis was made, and the patient was successfully treated with acetaminophen and colchicine. Early post-infarction pericarditis (EPIP), albeit rare in the era of emergency catheter treatment, is important because it may indicate a large transmural infarction and must be differentiated from re-infarction. Fever, chest pain, friction rub, ST elevation in the leads distant from the infarct area, recurrence of ST-segment elevation in the infarct area, and increase in inflammatory markers but not cardiac enzymes were crucial for establishing a diagnosis of EPIP., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hirata et al.)

Purpose: The effects of two types of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function remain unclear. Thus, we investigated the effect of anagliptin (ANA) and sitagliptin (SITA) on renal function in patients with type 2 diabetes who participated in the randomized evaluation of ANA versus SITA on low-density lipoprotein-cholesterol (LDL-C) in diabetes (REASON) trial., Patients and Methods: We measured the estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) before and after the REASON trial. ANA 200 mg/day was administered to 177 patients for 52 weeks, while SITA 50 mg/day was given to 176 patients. We investigated the relationship between differences in renal function and differences in hemoglobin A1c (HbA1c) levels, LDL-C levels, and blood pressure (BP)., Results: No significant differences were found in baseline eGFR and UACR between the two groups. The eGFR levels were significantly decreased in both groups; however, the UACR level was unchanged in the ANA group but elevated in the SITA group, although the difference did not reach significance between the two groups. The difference in eGFR was affected by the differences in HbA1c level and BP, and the difference in the UACR was affected by the differences in LDL-C level and BP, which were reduced only in the ANA group., Conclusion: These findings imply that the effects of DPP-4 inhibitors on renal function, especially on UACR, may be different between the types of DPP-4 inhibitors., Competing Interests: Dr H.T. reports lecturer fees from Daichi Sankyo, Mitsubish Tanabe, Bayer, Kowa, and Nihon Medi-Physics. Dr. T.M. has lecturer fees from AbbVie, AstraZeneca, Daiichi Sankyo, Japan Lifeline, Kowa, Toray, Tsumura, Kyorin, Mitsubishi Tanabe, Pfizer, and Bayer, as well as manuscript payments from Pfizer and advisory board roles with Asahi Kasei, Boston Scientific, Bristol-Myers Squibb, and Novartis. Dr. Y.F. and T.U. declare that they have no competing interests. Dr. M.S. is a member of Enomoto Pharmaceutical’s advisory board. Dr. M.S. has received research grants from AstraZeneca, Ono, and Sanwa Kagaku Kenkyusho, as well as nonpurpose research grants from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono, Taisho Toyama, and Takeda; lecturer fees from Astella. Dr O.A. reports lecturer fees from Abbott, Astellas, Boehringer Ingelheim, Medtronic, and St. Jude Medical. Dr. K.N. reports research grants from Abbott, Actelion, Air Water, Asahi Kasei, Astellas, Bayer, Terumo, Boehringer Ingelheim Japan, Mochida Pharmaceutical, Fuji Yakuhin, Medtronic, Daiichi Sankyo, Eli Lilly Japan, Takeda Pharmaceutical, GlaxoSmithKline, Mebix, Mitsubishi Tanabe, MSD, Novartis, Novo Nordia, Ono Pharmaceutical, and Teijin; nonpurpose research grants from Abbott, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb. Dr. T.N. has received research grants from Eli Lilly, Mitsubishi Tanabe, MSD, Novartis, Novo Nordisk, Ono, Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon, Taisho Toyama, Takeda, and Terumo, as well as lecturer fees from Arkray, Astellas, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Johnson & Johnson Dr. S.U. has received research funding from Bristol-Myers Squibb and Kowa, as well as non-purpose research grants from Bristol-Myers Squibb, Chugai, MSD, Pfizer, and Takeda. He also has lecturer fees from Boehringer Ingelheim and MSD. The authors report no other conflicts of interest in this work., (© 2022 Teragawa et al.)

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. We investigated PCSK9 concentration in type 2 diabetes mellitus (T2DM) and the impact of treatment with anagliptin or sitagliptin on PCSK9 level as a sub-analysis of the REASON trial., Methods: PCSK9 concentration was measured at baseline and after 52 weeks of treatment with anagliptin (n=122) or sitagliptin (n=128) in patients with T2DM who were receiving statin therapy. All of the included patients had been treated with a DPP-4 inhibitor prior to randomization., Results: Baseline PCSK9 level was positively, but not significantly, correlated with LDL-C and was independently associated with platelet count and level of triglycerides. Concomitant with reduction of LDL-C, but not hemoglobin A1c (HbA1c), by anagliptin, PCSK9 level was significantly increased by treatment with sitagliptin (218±98 vs. 242±115 ng/mL, P=0.01), but not anagliptin (233±97 vs. 250±106 ng/mL, P=0.07)., Conclusions: PCSK9 level is independently associated with platelet count and level of triglycerides, but not LDL-C, in patients with T2DM. Anagliptin reduces LDL-C level independent of HbA1c control in patients with T2DM who are on statin therapy possibly by suppressing excess statin-mediated PCSK9 induction and subsequent degradation of the LDL receptor.

Antihypertensive therapy is pivotal for reducing cardiovascular events. The 2019 Guidelines for the Management of Hypertension set a target blood pressure (BP) of <140/90 mmHg for persons older than 75 years of age. Optimal BP levels for older persons with frailty, however, are controversial because evidence for the relationship between BP level and prognosis by frailty status is limited. Here, we evaluated the relationship between systolic BP and frailty status with all-cause mortality in ambulatory older hypertensive patients using data from the Nambu Cohort study. A total of 535 patients (age 78 [70-84] years, 51% men, 37% with frailty) were prospectively followed for a mean duration of 41 (34-43) months. During the follow-up period, 49 patients died. Mortality rates stratified by systolic BP and frailty status were lowest in patients with systolic BP < 140 mmHg and non-frailty, followed by those with systolic BP ≥ 140 mmHg and non-frailty. Patients with frailty had the highest mortality regardless of the BP level. The adjusted hazard ratios (95% confidence intervals) of each category for all-cause mortality were as follows: ≥140 mmHg/Non-frailty 3.19 (1.12-11.40), <140 mmHg/Frailty 4.72 (1.67-16.90), and ≥140 mmHg/Frailty 3.56 (1.16-13.40) compared with <140 mmHg/Non-frailty as a reference. These results indicated that frail patients have a poor prognosis regardless of their BP levels. Non-frail patients, however, with systolic BP levels <140 mmHg had a better prognosis. Frailty may be a marker to differentiate patients who are likely to gain benefit from antihypertensive medication among older hypertensives., (© 2021. The Author(s).)

Background: Both frailty and chronic kidney disease (CKD) increase with age and share many similarities. Many studies have demonstrated an association between frailty and chronic kidney disease (CKD), but an association with dipstick proteinuria is limited., Methods: This is the cross-sectional analysis of the Nambu Cohort Study at the beginning of observation. Frailty was diagnosed using Kihon Checklist. Logistic analysis was used to evaluate the association between frailty and CKD or dipstick proteinuria., Results: Among a total of 630 outpatients [age, 78 (70-84) years, men, 50%], the prevalence of patients with pre-frailty and frailty was 32% and 40%, respectively. The proportion of patients with pre-frailty and frailty increased with decreasing estimated glomerular filtration rate (eGFR) and increasing dipstick proteinuria levels. The odds ratios (95% confidence intervals) for CKD stage of 60 < eGFR ≤ 45 ml/min/1.73 m 2 , and 45 ml/min/1.73 m 2  < eGFR for frailty was 0.87 (0.56-1.35) and 2.54 (1.46-4.53), respectively, compared with non-CKD as a reference. Furthermore, the odds ratios for the frailty of dipstick proteinuria with ± and + or over were 1.36 (0.88-2.09) and 1.78 (1.00-3.17), respectively, when dipstick proteinuria-was used as a reference. Moreover, the combination of eGFR and dipstick proteinuria levels increased the odds ratio for pre-frailty and frailty., Conclusion: Elderly patients with CKD had a higher prevalence of pre-frailty and frailty. By adding urinary protein information to eGFR, the link between CKD and frailty becomes even more robust., (© 2021. Japanese Society of Nephrology.)

Purpose: Experimental evidence has suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors have an anti-inflammatory effect as well as a glucose-lowering effect, but this has yet to be confirmed in diabetic patients. Therefore, we examined the anti-inflammatory effects of two kinds of DPP-4 inhibitors in patients who participated in the randomized evaluation of anagliptin (ANA) vs sitagliptin (SITA) on low-density lipoprotein cholesterol in diabetes (REASON) Trial, which compared low-density lipoprotein-cholesterol lowering effects between (ANA) and SITA in patients with type 2 diabetes, dyslipidemia, and atherosclerotic vascular lesions., Patients and Methods: The studied patients consisted of 177 patients who received ANA 200 mg per day and 176 patients who received SITA 50 mg per day for 52 weeks. We measured high-sensitivity C-reactive protein (hs-CRP), white blood cells (WBC), and interleukin-6 (IL-6) before and after treatment for 52 weeks, and the changes in inflammatory markers were measured as the differences between baseline and 52 weeks. Furthermore, we checked the relationship between the change in hs-CRP and several clinical factors such as the baseline hs-CRP level, use of a moderate-intensity statin, presence of coronary artery disease (CAD) and taking a previous DDP-4 inhibitor., Results: The levels of the inflammatory markers hs-CRP, WBC, and IL-6 were determined to have not significantly changed from baseline to the final follow-up in each arm; furthermore, the changes in these markers were not significantly different between the two groups. The change in hs-CRP level was not affected by the baseline hs-CRP level, use of a moderate-intensity statin, presence of coronary artery disease, and absence of prior DPP-4 inhibitor use., Conclusion: In this sub-analysis from the REASON Trial, taking a DPP-4 inhibitor, either ANA or SITA, for 52 weeks did not affect the levels of inflammatory markers., Competing Interests: Dr. Hiroki Teragawa reports lecturer fees from Daichi Sankyo, Mitsubishi Tanabe, Bayer, Kowa and Nihon Medi-Physics. Dr. Takeshi Morimoto reports lecturer fees from AbbVie, AstraZeneca, Daiichi Sankyo, Kyorin, Mitsubishi Tanabe, Pfizer, and Bayer; manuscript fees from Pfizer; advisory boards for Asahi Kasei, Boston Scientific, Bristol-Myers Squibb, and Sanofi. Dr. Yuichi Fujii declares no conflict of interest. Dr. Tomohiro Ueda declares no conflict of interest. Dr. Mio Sakuma reports advisory board for Enomoto Pharmaceutical. Dr. Michio Shimabukuro reports research grants from AstraZeneca, Ono, and Sanwa Kagaku Kenkyusho; non-purpose research grants from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Ono, Taisho Toyama, and Takeda; lecturer fees from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Eli Lilly, Kowa, Mitsubishi Tanabe, Mochida, MSD, Novo Nordisk, Ono, Taisho Toyama, and Takeda; advisory board for Novo Nordisk; and in sponsored office from Boehringer Ingelheim. Dr. Osamu Arasaki reports lecturer fees from Abbott, Astellas, Boehringer Ingelheim, Medtronic, and St. Jude Medical. Dr. Koichi Node reports research grants from Abbott, Actelion, Air Water, Asahi Kasei, Astellas, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Mebix, Mitsubishi Tanabe, and Teijin; non-purpose research grants from Abbott, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, Japan Lifeline, Kissei, Medtronic, Mitsubishi Tanabe, MSD, Novartis, Novo Nordisk, Ono, Otsuka, Pfizer, Sanofi, Sumitomo Dainippon, Takeda, and Teijin; lecturer fees from Abbott, Actelion, AnGes, Astellas, Astellas Amgen Bio Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Edwards Lifesciences, Eisai, Eli Lilly, Fukuda Denshi, Kowa, Kyowa Hakko Kirin, Medtronic, Mitsubishi Tanabe, Mochida, MSD, Nippon Shinyaku, Novartis, Ono, Otsuka, Pfizer, Roche Diagnostics, Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon, Taisho Toyama, Takeda, Teijin, and Toa Eiyo; manuscript fee from Takeda; advisory boards for Astellas, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Mitsubishi Tanabe, MSD, Novo Nordisk, Pfizer, and Takeda. Dr. Takashi Nomiyama reports research grants from Eli Lilly, Mitsubishi Tanabe, MSD, and Novartis; lecturer’s fees from Arkray, Astellas, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Mitsubishi Tanabe, MSD, Novartis, Novo Nordisk, Ono, Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon, Taisho Toyama, Takeda, and Terumo. Dr. Shinichiro Ueda reports research grants from Bristol-Myers Squibb, and Kowa; non-purpose research grants from Bristol-Myers Squibb, Chugai, MSD, Pfizer, and Takeda; lecturer fees from Boehringer Ingelheim, and MSD. The authors report no other conflicts of interest in this work., (© 2020 Teragawa et al.)

Objective: Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus. Methods: As a sub-analysis study of the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial, 256 patients (male/female: 146/110, age: 68 ± 10 years) with type 2 diabetes mellitus and dyslipidemia who were receiving statin therapy were recruited. Patients who had been treated with a thiazolidinedione were excluded. Results: Several drugs which may modulate FABP4 levels including statins, dipeptidyl peptidase-4 inhibitors and angiotensin II receptor blockers had been administered in 100, 81, and 51% of the recruited patients, respectively. The level of FABP4, but not that of FABP5, was significantly higher in females than in males. Multivariable linear regression analysis demonstrated that waist circumference (β = 0.21), estimated glomerular filtration rate (β = -0.31), triglycerides (β = 0.16), and FABP5 (β = 0.39) were independent predictors of FABP4 level after adjusting age and sex. On the other hand, FABP5 level was independently associated with levels of FABP4 (β = 0.57) and high-density lipoprotein (HDL) cholesterol (β = -0.12). Conclusions: Concentrations of FABP4 and FABP5 are independent predictors of each other in patients with type 2 diabetes mellitus. There are distinct independent associations of FABP4 with renal dysfunction, adiposity and hypertriglyceridemia and there is a distinct independent association of FABP5 with a low HDL cholesterol level in type 2 diabetic patients with dyslipidemia at high risks for cardiovascular disease who are receiving statin therapy., (Copyright © 2020 Furuhashi, Sakuma, Morimoto, Higashiura, Sakai, Matsumoto, Sakuma, Shimabukuro, Nomiyama, Arasaki, Node and Ueda.)

Background: Enzyme biomarkers-such as creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase-are associated with acute decompensated heart failure (ADHF) severity and, therefore, have a prognostic value in ADHF. However, the prognostic value of lactate dehydrogenase (LDH) is unclear. This study aimed to investigate the prognostic value of LDH in ADHF., Methods: This single-centre observational retrospective study enrolled 396 patients with ADHF between June 2014 and July 2016. The patients were categorised into groups based on the tertile values of serum LDH (LDH-low [<196 U/L], LDH-intermediate [196≤ LDH <239 U/L] and LDH-high [LDH ≥239 U/L]). Survival analysis for all-cause mortality was performed. This study also examined the ability of adding log-transformed LDH (LogLDH) on Get With The Guideline score, which is an established risk score to predict 90-day, 180-day and 365-day mortality using time-dependent receiver operating characteristic curves., Results: During the follow-up (median, 204 days), 100 (25%) patients died. The LDH-intermediate and LDH-high groups had worse survival (LDH-low vs LDH-intermediate, log-rank p=0.019; LDH-low vs LDH-high, log-rank p<0.001). Log LDH improved the ability to predict 90-day, 180-day and 365-day all-cause mortality, which was statistically significant (90 days, area under curve [AUC] = 0.79, p=0.012; 180 days, AUC = 0.79, p=0.017; and 365 days, AUC = 0.79, p=0.025)., Conclusions: Lactate dehydrogenase may be an important predictor of 90-day, 180-day and 365-day all-cause mortality in ADHF patients; however, further studies are needed to confirm these findings., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Oral anticoagulant (OAC) therapy reduces the risk of stroke in patients with atrial fibrillation (AF). This study elucidated the causes of death and related factors in elderly Japanese AF patients. Methods and Results: Over a median (interquartile range [IQR]) follow-up period of 46 (20-76) months, there were 171 all-cause deaths (28% cardiovascular, 46% non-cardiovascular, and 26% unknown causes) among 389 AF patients (median [IQR] age 80 [74-85] years; CHAD 2 DS 2 -VASc score 5 [4-6]). Cox regression analysis indicated that diabetes was associated with an increase in all-cause death (hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.02-2.13), whereas hypercholesterolemia (HR 0.53; 95% CI 0.35-0.79), pre-existing heart failure (HR 0.67; 95% CI 0.48-0.95), and OAC use (HR 0.62; 95% CI 0.44-0.88) were associated with reductions in all-cause death. Pre-existing heart failure was associated with both cardiovascular (HR 3.03; 95% CI 1.33-8.20) and non-cardiovascular (HR 0.44; 95% CI 0.30-0.65) deaths, in opposite directions. OAC use was associated with a reduction in cardiovascular death (HR 0.34, 95% CI 0.17-0.69). The predominance of non-cardiovascular death and death-related factors were equivalent regardless of when observations started (before 2009 or in 2009 and later). Conclusions: The predominant cause of death in elderly Japanese AF patients was non-cardiovascular. Distinct clinical factors were associated with cardiovascular and non-cardiovascular death., Competing Interests: The authors declare no potential conflicts of interest for the research, authorship, and/or publication of this article., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Epidemiologic findings indicate that unfavorable cardiovascular (CV) risk profiles, such as elevated systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and overweight, decelerate with aging. Few studies, however, have evaluated the association between the CV risk profile and frailty. We performed a cross-sectional analysis using the baseline data of a prospective cohort study. A total of 599 subjects (age, 78 [range: 70-83] years; men, 50%) were analyzed in an outpatient setting. Frailty was diagnosed in 37% of the patients according to the Kihon Checklist score. An unfavorable CV risk profile was associated with a lower risk of frailty. The adjusted odds ratios (ORs; 95% confidence interval [CI]) of each CV risk factor for frailty were as follows: SBP (each 10 mmHg increase) 0.83 (0.72-0.95), LDL-C (each 10 mg/dl increase) 0.96 (0.86-1.05), and body mass index (each 1 kg/m 2 increase) 1.03 (0.97-1.10). Moreover, the total number of CV risk factors within the optimal range was significantly associated with the risk of frailty with the following ORs (95% CI): 1, 2.30 (0.75-8.69); 2, 3.22 (1.07-11.97); and 3, 4.79 (1.56-18.05) compared with patients having no risk factors within optimal levels (p for trend 0.008). Abnormal homeostasis might lead to lower levels of CV risk factors, which together result in "reverse metabolic syndrome." Our findings indicate that a favorable CV risk profile is associated with frailty.

Background: Serum electrolyte concentrations on admission and after the administration of loop diuretics may be associated with prognosis in patients hospitalized due to acute heart failure (AHF). This study investigated the prognostic impact of early changes in chloride (Cl) concentrations after diuretic administration, according to stratified Cl concentrations on admission, in AHF. Methods and Results: In all, 355 consecutive patients hospitalized due to AHF were included in this single-center retrospective cohort study. Patients were divided into 2 groups based on whether Cl decreased (n=196) or not (n=159) during the first 5 days in hospital. These 2 groups were further stratified according to Cl on admission into 4 groups: Group 1, decrease in Cl and no hypochloremia (n=127); Group 2, decrease in Cl and hypochloremia (n=69); Group 3, no decrease in Cl and no hypochloremia (n=50); and Group 4, no decrease in Cl and hypochloremia (n=109). The risk of death was significantly higher in the group without than with a decrease in Cl (all-cause death hazard ratio [HR] 1.79; 95% confidence interval [CI] 1.15-2.78; P=0.009). Group 4 had the worst prognosis and a significantly higher risk of death (all-cause death [vs. Group 1 as a reference], HR 2.51; 95% CI 1.45-4.32; P=0.001). Conclusions: The absence of an early decline in Cl was associated with poor prognosis in AHF, especially in patients with hypochloremia on admission., Competing Interests: S.U. is a member of Circulation Journal ’ Editorial Team. The other authors have no conflicts of interest to declare., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Background: Fatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect. Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naïve and sulfonylurea-treated patients with type 2 diabetes mellitus. Anagliptin, another DPP-4 inhibitor, was shown to decrease low-density lipoprotein cholesterol (LDL-C) level to a greater extent than that by sitagliptin in the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial., Aim and Methods: As a sub-analysis study using data obtained from the REASON trial, we investigated the effects of treatment with anagliptin (n = 148, male/female: 89/59) and treatment with sitagliptin (n = 159, male/female: 93/66) for 52 weeks on FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular events who were receiving statin therapy., Results: The DPP-4 inhibitor had been administered in 82% of the patients in the anagliptin group and 81% of the patients in sitagliptin group prior to randomization. Serum FABP4 level was significantly decreased by 7.9% by treatment with anagliptin (P = 0.049) and was not significantly decreased by treatment with sitagliptin (P = 0.660). Change in FABP4 level was independently associated with basal FABP4 level and changes in waist circumference and creatinine after adjustment of age, sex and the treatment group., Conclusion: Anagliptin decreases serum FABP4 concentration independent of change in hemoglobin A1c or LDL-C in patients with type 2 diabetes mellitus and dyslipidemia who are on statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. Registered January 5, 2015, https://clinicaltrials.gov/ct2/show/NCT02330406.

Ezetimibe reduces cardiovascular risk by lowering the levels of low-density lipoprotein cholesterol (LDL-C). However, there is limited information regarding the factors associated with ezetimibe-mediated LDL-C reduction. We investigated the factors associated with LDL-C reduction after ezetimibe administration in Japanese patients with or without type 2 diabetes mellitus (T2DM). This single-center retrospective observational study enrolled a total of 266 consecutive ezetimibe-naïve patients, of which 154 were excluded because of either switching from statin or fenofibrate to ezetimibe (n = 52) or ezetimibe discontinuation (n = 102). Finally, 112 patients were eligible for analysis. To identify the factors influencing LDL-C levels, univariate and multivariate linear regression analyses were performed after 52 weeks of ezetimibe treatment. Overall, advanced age, T2DM, and high baseline LDL-C were significantly associated with a greater decrease in LDL-C levels. In the non-T2DM group, advanced age and high baseline LDL-C were associated with greater decrease in LDL-C levels. In the T2DM group, baseline LDL-C was the only factor that influenced the change in LDL-C levels. Advanced age was significantly associated with higher LDL-C reduction in non-T2DM patients, but not in T2DM patients. Ezetimibe use might be beneficial in older patients without T2DM. The lack of association between age and the LDL-C lowering effect by ezetimibe in patients with T2DM may be due to yet unknown mechanism except low statistical power.

The effects of antidiabetic agents on lipoprotein subclasses are assumed to be pivotal, but this assumption has not been studied. We evaluated lipoprotein subclasses in patients, randomly selected from REASON (Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes) Trial participants, with type-2 diabetes treated with either anagliptin or sitagliptin. We measured total cholesterol (TC) and triglycerides (TG) in 4 (chylomicron (CM), very low-density lipoprotein (VLDL), low density lipoprotein (LDL), and high-density lipoprotein (HDL)) lipoprotein classes and 20 (2 CM, 5 VLDL, 6 LDL, and 7 HDL) lipoprotein subclasses. Between 0 and 52 weeks, TC and TG in lipoprotein and the lipoprotein subclass were distributed differently in patients treated with anagliptin and sitagliptin. The preferable changes in TC and TG levels were observed dominantly in the anagliptin-treated group under standard statin therapy, but the benefits were observed in both the anagliptin- and sitagliptin-treated groups, at least partially under strong statin therapy. In future studies, the atherogenic properties of lipoprotein subclasses might be considered when employing antidiabetic dipeptidyl peptidase-4 (DPP-4) inhibitors, especially in patients with type-2 diabetes who are at risk of atherosclerotic cardiovascular disease (ASCVD) or are undergoing statin treatment.

Purpose: Left ventricular (LV) wall thickness can be measured at the posterior wall (PW) and the intraventricular septum (IVS) in a parasternal long axis view by transthoracic echocardiography. Thus, there are three methods to calculate relative wall thickness as follows: RWT PW  = 2 × PWth/LVDd; RWT IVS + PW  = (IVSth + PWth) /LVDd; and RWT IVS  = 2 × IVSth/LVDd (IVSth = interventricular septum thickness; LVDd = LV internal dimension at end--diastole; PWth = posterior wall thickness). The aim was to compare the prognostic values of these RWTs in patients with acute decompensated heart failure (ADHF)., Method: This was a single-center, retrospective, observational study at a Japanese community hospital. A total of 389 hospitalized ADHF patients were divided into two groups based on the three median RWT values. The primary outcome was all-cause death. Survival analysis was performed, and Cox proportional hazard models unadjusted and adjusted by Get With The Guideline score were used., Results: High-RWT PW had poor survival (log-rank, P = 0.009) and was a significant risk (unadjusted HR (95%CI), 1.72 (1.14-2.61), P = 0.01; adjusted HR, 1.95 (1.28-2.98), P = 0.02). High-RWT IVS + PW was not associated with poor survival on survival analysis or the unadjusted Cox model. Only the adjusted Cox model showed that High-RWT IVS + PW was associated with a significant risk of the primary outcome (unadjusted HR (95%CI), 1.45 (0.96-2.17), P = 0.07; adjusted HR, 1.53 (1.01-2.32), P = 0.045). High-RWT IVS did not have significant prognostic value., Conclusions: When calculating RWT, RWT PW should be recommended for evaluating the mortality risk in ADHF.

Background: Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain., Aim and Methods: We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353)., Results: There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06)., Conclusion: These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.

Background: Left ventricular (LV) wall thickening relative to the LV radius, known as a concentric LV structure, is a mechanism that compensates for pressure overload and is related to the risk of cardiovascular events and heart failure. The prognostic value of a concentric LV structure, however, has not been examined in acute decompensated heart failure (ADHF)., Methods: This single-center, observational, retrospective, cohort study analyzed 385 consecutive patients hospitalized due to ADHF. On hospital admission, relative wall thickness (RWT) and the ratio of LV mass to LV end-diastolic volume (LVM/LVEDV) were measured by transthoracic echocardiography as markers of a concentric LV structure. The association of either RWT or LVM/LVEDV with all-cause death as the primary outcome was analyzed., Results: During the follow-up period (median, 235 days), 95 (25%) patients died. The high-RWT group had a poorer prognosis than the low-RWT group (log-rank test, P = 0.009). High RWT was a significant risk (HR: 1.95, 95% CI: 1.28-2.97, P = 0.002) in the Cox proportional hazard model analysis adjusted by the Get With The Guideline score, which is an established risk score. In contrast, there was no significant difference in survival between the low and high-LVM/LVEDV groups (P = 0.42). In the non-severe valvular disease subgroup, patients with high RWT consistently showed worse survival than the low-RWT group (P = 0.028 by log-rank test, HR: 1.96, 95% CI: 1.24-3.11, P = 0.004). There was no significant difference in survival between the low and high-LVM/LVEDV groups (P = 0.42)., Conclusions: A concentric LV structure represented by a high RWT was associated with a poor prognosis in ADHF. The lack of association between LVM/LVEDV and mortality may result from methodological issues., (Copyright © 2018. Published by Elsevier B.V.)

Additional reductions in low-density lipoprotein-cholesterol (LDL-C) via antidiabetic therapies should be considered in statin-using patients with sub-optimal LDL-C levels. We compared the efficacy of anagliptin and sitagliptin, two antidiabetic therapies, in reducing LDL-C in type 2 diabetic patients. A randomized, open-label, parallel-group trial was conducted at 17 centres in Japan between April 2015 and January 2018. Adults (age ≥20 years) with type 2 diabetes, any atherosclerotic vascular lesions, and statin prescriptions were included. Anagliptin or sitagliptin were administered for 52 weeks. Primary and secondary endpoints were changes in LDL-C and haemoglobin A1C (HbA1c) levels, respectively. We assessed the superiority (primary endpoint) and non-inferiority (secondary endpoint) of anagliptin over sitagliptin. This study was registered at Clinicaltrials.gov (NCT02330406). Of 380 participants, 353 were eligible and randomized. Mean participant age was 68 years, and 61% were males. Baseline median LDL-C and HbA1c were 108 mg/dL and 6.9%, respectively. Changes in LDL-C were -3.7 mg/dL with anagliptin and +2.1 mg/dL with sitagliptin at 52 weeks, and the estimated treatment difference was a significant -4.5 mg/dL (P = 0.01 for superiority). Changes in HbA1c were +0.02% with anagliptin and +0.12% with sitagliptin (P < 0.0001 for non-inferiority). Overall, anagliptin was superior to sitagliptin in lowering LDL-C without deteriorating HbA1c.

Background: Acute heart failure (AHF) triggers platelet aggregation and platelet markers are associated with the severity of AHF. The present study aimed to investigate the prognostic value of platelet count (PLT) in patients with AHF., Methods and results: This single-center retrospective observational study analyzed 425 consecutive patients with AHF. The patients were divided into groups based on tertiles of PLT: low (PLT1 <170,000/μL), intermediate (170,000/μL≤PLT<230,000/μL), and high (PLT3 ≥230,000/μL). The endpoint was all-cause death with a composite endpoint of all-cause death and HF rehospitalization. Survival analysis was performed, and Cox proportional hazard models adjusted by an established risk score (Get With The Guidelines score) were generated. The PLT1 group had the worst survival for all-cause death (log-rank, P=0.003) and the composite endpoint (P=0.009). A significant trend of increasing survival was observed for all-cause death (log-rank trend, P<0.001) and the composite endpoint (P=0.002) in the following order: PLT1, PLT2, and PLT3. Adjusted Cox proportional hazard models demonstrated that low PLT was a risk factor of all-cause death and the composite endpoint., Conclusions: Low PLT was associated with risk for all-cause death and HF rehospitalization in patients with AHF.

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with post-ablation atrial fibrillation (AF), ranges of EATV predictive of post-ablation recurrence of AF remain unclear. In this study, we evaluated: (1) relationships between EATV and characteristics of AF, (2) impact of EATV on recurrent AF after radiofrequency ablation; , and (3) cut-off point for recurrent AF using a receiver operating characteristic curve. In 218 consecutive symptomatic patients undergoing who underwent ablation for AF (143 paroxysmal AF; 78 persistent AF), the EATV index (EATVI: EATV/body surface area, mL/m 2 ) was measured using 320-row multidetector computed tomography. The high EATV group showed specific cardiometabolic derangements as well as left atrial dilatation and left ventricular dysfunction. Multivariate regression analysis showed that the EATVI was an independent predictor of recurrent AF after catheter ablation. High EATV (EATVI ≥ 85 mL/m 2 ) or EATVI cutoff ≥116 mL/m 2 can predict recurrent AF after catheter ablation, independent of other risk factors. In conclusion, EATVI was an independent predictor of recurrent AF after catheter ablation; a high EATV tertile or EATVI cutoff may be useful for prediction of recurrent AF after catheter ablation. Future studies should determine the utility of the EATVI in the clinical setting of AF ablation., (Copyright © 2018. Published by Elsevier Inc.)

Background: Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling., Methods and results: Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m 2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m 2 , P<0.01)., Conclusions: The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Background: Reduction of low-density lipoprotein cholesterol (LDL-C) is important for patients with a high risk for atherosclerotic events, such as patients with diabetes and other risk factors. Anagliptin was reported to reduce LDL-C for 12 weeks in phase III trials regardless of the use of statins, but it is uncertain whether this effect is common to other dipeptidylpeptidase-4 (DPP-4) inhibitors., Methods: A multicenter, randomized, open-label, parallel-group trial was conducted to confirm the superiority of anagliptin to sitagliptin in terms of the primary endpoint of reduction of LDL-C for 52 weeks in patients with type 2 diabetes and atherosclerotic vascular lesions, as well as the non-inferiority of anagliptin to sitagliptin in terms of change in hemoglobin A1c (HbA1c). Patients are randomly assigned to receive anagliptin or sitagliptin at a ratio of 1:1, with those in the anagliptin group receiving anagliptin 100 mg orally twice per day and those in the sitagliptin group receiving sitagliptin 50 mg orally once per day. During the trial period, hypoglycemic agents and anti-dyslipidemia drugs should not be added and neither should their dosages be changed. A total sample size of 300 was estimated to provide a power of 0.8 with a two-sided alpha of 0.05 for LDL-C, considering a 30% dropout rate. Pre-specified factors for subgroup analyses are HbA1c, use of DPP-4 inhibitors, sex, body mass index, LDL-C, age, and the presence of treatment for existing ischemic heart disease., Discussion: If anagliptin were to be shown to reduce LDL-C in patients with type 2 diabetes and atherosclerotic vascular lesions despite pre-existing statin treatment, more intensive cholesterol management would be appropriate., Trial Registration: Clinicaltrials.gov NCT02330406.

Background: Little is known about clinical associations between glucose fluctuations including hypoglycemia, heart rate variability (HRV), and the activity of the sympathetic nervous system (SNS) in patients with acute phase of acute coronary syndrome (ACS). This pilot study aimed to evaluate the short-term effects of glucose fluctuations on HRV and SNS activity in type 2 diabetes mellitus (T2DM) patients with recent ACS. We also examined the effect of suppressing glucose fluctuations with miglitol on these variables., Methods: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group comparative study included 39 T2DM patients with recent ACS, who were randomly assigned to either a miglitol group (n = 19) or a control group (n = 20). After initial 24-h Holter electrocardiogram (ECG) (Day 1), miglitol was commenced and another 24-h Holter ECG (Day 2) was recorded. In addition, continuous glucose monitoring (CGM) was performed throughout the Holter ECG., Results: Although frequent episodes of subclinical hypoglycemia (≤4.44 mmo/L) during CGM were observed on Day 1 in the both groups (35% of patients in the control group and 31% in the miglitol group), glucose fluctuations were decreased and the minimum glucose level was increased with substantial reduction in the episodes of subclinical hypoglycemia to 7.7% in the miglitol group on Day 2. Holter ECG showed that the mean and maximum heart rate and mean LF/HF were increased on Day 2 in the control group, and these increases were attenuated by miglitol. When divided 24-h time periods into day-time (0700-1800 h), night-time (1800-0000 h), and bed-time (0000-0700 h), we found increased SNS activity during day-time, increased maximum heart rate during night-time, and glucose fluctuations during bed-time, which were attenuated by miglitol treatment., Conclusions: In T2DM patients with recent ACS, glucose fluctuations with subclinical hypoglycemia were associated with alterations of HRV and SNS activity, which were mitigated by miglitol, suggesting that these pathological relationships may be a residual therapeutic target in such patients. Trial registration Unique Trial Number, UMIN000005874 ( https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000006929 ).

Objectives: A purpose is to compare the in-hospital rehabilitation progress after minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) with that after off pump coronary artery bypass grafting( OPCAB)., Methods: We analyzed 60 patients who underwent coronary artery bypass grafting surgery from January 2015 to December 2016. Fourteen patients underwent MICS CABG (MICS CABG group) and 46 patients underwent OPCAB (OPCAB group). The post-operative days to start standing position and independent walking, and hospitalization duration were analyzed between the 2 groups., Results: There were no significant differences between the groups:standing position(1.2 vs 1.2 days) and independent walking(4.8 vs 4.9 days). Hospitalization duration was shorter in MICS CABG group(14.3 vs 17.5 days)., Conclusion: MICS CABG may shorten hospitalization length compared with OPCAB, however, further research will be needed.

Refractory coronary vasospasm subsequent to reperfusion, such as cardiopulmonary resuscitation or revascularization, for myocardial infarction may respond to fasudil in the superacute phase. Continuous low-dose fasudil administration should be an option for refractory coronary vasospastic angina (VSA).

We investigated the effects of purified eicosapentaenoic acid (EPA) on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol ≥220 mg/dL and/or triglycerides ≥150 mg/dL), lipid profile and forearm blood flow (FBF) during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP) cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition.