Publications by authors named "Akihiro Tokushige"

36 Publications

Women with type 2 diabetes and coronary artery disease have a higher risk of heart failure than men, with a significant gender interaction between heart failure risk and risk factor management: a retrospective registry study.

BMJ Open Diabetes Res Care 2022 Apr;10(2)

Department of Clinical Research and Management, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan

Introduction: Women are generally perceived to have a lower risk of cardiovascular events than men, despite a lack of data, particularly among patients with diabetes. Here, we investigated gender differences in the risk of heart failure (HF) events in patients with type 2 diabetes and coronary artery disease (CAD). We also assessed the association between cardiovascular risk factor management and HF events.

Research Design And Methods: This retrospective registry study enrolled consecutive patients with both type 2 diabetes and CAD, based on angiography records and medical charts at 70 teaching hospitals in Japan, from January 2005 to December 2015.

Results: The registry included 7785 patients with a mean follow-up period of 1328 days. The mean age of the patients was 67.6 years. The risk of hospitalization for HF in patients with both type 2 diabetes and CAD was significantly higher among women than among men (HR, 1.26, 95% CI 1.06 to 1.50). The relationship between HF risk and achieved low-density lipoprotein cholesterol (LDL-c) and systolic blood pressure, but not hemoglobin A, differed between women and men, with statistically significant interactions (p=0.009 and p=0.043, respectively).

Conclusions: Women with type 2 diabetes and CAD have a higher risk of HF than men. A significant gender interaction was observed in the association between HF risk and risk factor management, particularly regarding LDL-c and systolic blood pressure. The effectiveness of risk factor management may differ between men and women regarding HF prevention among patients with type 2 diabetes and CAD.
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http://dx.doi.org/10.1136/bmjdrc-2021-002707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045107PMC
April 2022

Impact of Malnutrition on Prognosis and Coronary Artery Calcification in Patients with Stable Coronary Artery Disease.

Curr Probl Cardiol 2022 Mar 26:101185. Epub 2022 Mar 26.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Nutritional status is an important factor affecting prognosis of cardiovascular diseases. We compared major cardiovascular and cerebrovascular events (MACCE) between the malnutrition (geriatric nutritional risk index <92) and non-malnutrition (geriatric nutritional risk index ≥92) groups in 500 stable coronary artery disease patients undergoing percutaneous coronary intervention and evaluated coronary calcification by intravascular ultrasound. Incidences of all-cause death and MACCE differed between the malnutrition and non-malnutrition groups (22% vs 5%, P < 0.001 and 24% vs 6%, P < 0.001). In multivariate Cox proportional hazards regression, malnutrition significantly correlated with all-cause death (P = 0.006) and MACCE (P = 0.010). The proportion of moderate/severe calcification differed between the malnutrition (64%) and non-malnutrition groups (33%, P < 0.001). Multivariate logistic analysis identified age (P < 0.001), malnutrition (P = 0.048), and hemodialysis (P < 0.001) as significantly related to moderate/severe calcification. Malnutrition was an independent risk factor for all-cause death and MACCE in coronary artery disease patients after percutaneous coronary intervention and was associated with moderately/severely calcified lesions.
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http://dx.doi.org/10.1016/j.cpcardiol.2022.101185DOI Listing
March 2022

Association of wound, ischemia, and foot infection clinical stage with frailty and malnutrition in chronic limb-threatening ischemia patients undergoing endovascular intervention.

Vascular 2022 Feb 28:17085381221076943. Epub 2022 Feb 28.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, 12851Kagoshima University, Kagoshima, Japan.

Objective: The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in Chronic limb-threatening ischemia (CLTI) patients, and frailty and nutritional status appear to represent pivotal factor affecting prognosis among CLTI patients. The purpose of this study was to examine clinical factors (including frailty and nutritional status) relevant to WIfI clinical stage.

Methods: This retrospective study investigated 200 consecutive CLTI patients. We individually assessed WIfI clinical stage, frailty according to the Clinical Frailty Scale (CFS) score, and malnutrition according to Geriatric Nutritional Risk Index (GNRI). We then compared mortality after endovascular intervention between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated associations between baseline characteristics (including CFS and GNRI) and WIfI clinical stage.

Results: Among 200 patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. CFS score was significantly higher in the WIfI stage 3, 4 group [median 6.0, interquartile range (IQR) 5.5-7.0] compared with the WIfI stage 1, 2 group (median 5.0, IQR 4.0-6.0, < 0.001), and GNRI was significantly lower in the WIfI stage 3, 4 group (median 88, IQR 80-97) than in the WIfI stage 1, 2 (median 103, IQR 94-111, < 0.001). Forty patients (20%) died after endovascular intervention. Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, = 0.047 and 12% vs. 3%, = 0.040, respectively). Kaplan-Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group ( = 0.002 by log-rank test). Multivariate logistic regression analysis using relevant factors from univariate analysis showed CFS score [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.41-3.13, < 0.001), diabetes mellitus (OR 3.17, 95%CI 1.17-8.61, = 0.023) and GNRI (OR 0.93, 95%CI 0.89-0.97, = 0.002) significantly associated with WIfI stage 3 or 4. In addition, multivariate ordinal logistic regression analysis for WIfI clinical stage showed CFS score (OR 1.43, 95%CI 1.09-1.89, = 0.011), diabetes mellitus (OR 1.77, 95%CI 1.26-2.54, < 0.001), and high-sensitivity C-reactive protein (OR 1.14, 95%CI 1.02-1.28, = 0.041) were positively associated with WIfI clinical stage, and GNRI correlated negatively with WIfI clinical stage (OR 0.95, 95%CI 0.91-0.97, < 0.001).

Conclusions: These results indicate that CLTI patients with high WIfI clinical stage may be more frail and malnourished, and be associated with poor prognosis after endovascular intervention.
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http://dx.doi.org/10.1177/17085381221076943DOI Listing
February 2022

Clinical Outcomes in Biopsy-Proven Nonalcoholic Fatty Liver Disease Patients: A Multicenter Registry-based Cohort Study.

Clin Gastroenterol Hepatol 2022 Jan 17. Epub 2022 Jan 17.

Department of Clinical Pharmacology and Therapeutics, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Background & Aims: There are no detailed reports of clinical outcomes in Asian patients with nonalcoholic fatty liver disease (NAFLD) who undergo liver biopsy. We aimed to investigate the clinical outcomes of a large cohort of Asian patients with biopsy-proven NAFLD and evaluate the specific effects of nonalcoholic steatohepatitis and fibrosis stage.

Methods: This multicenter registry-based retrospective cohort study, called the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) in Asia, included 1398 patients.

Results: The median follow-up period was 4.6 years (range, 0.3-21.6 years), representing a total of 8874 person-years of follow-up. During that time, 47 patients died, and 1 patient underwent orthotopic liver transplantation. The leading cause of death was nonhepatic cancer (n = 10). The leading causes of liver-related death were liver failure (n = 9), hepatocellular carcinoma (HCC) (n = 8), and cholangiocellular carcinoma (n = 4). During follow-up, 37 patients developed HCC, 31 developed cardiovascular disease, and 68 developed nonhepatic cancer (mainly breast, stomach, and colon/rectum). Among our cohort of patients with NAFLD, liver-specific mortality was 2.34/1000 person-years (95% confidence interval [CI], 1.52-3.58), overall mortality was 5.34/1000 person-years (95% CI, 4.02-7.08), and HCC incidence was 4.17/1000 person-years (95% CI, 3.02-5.75). Liver fibrosis was independently associated with liver-related events but not overall mortality.

Conclusions: Liver-related mortality was the leading cause of mortality in Asian patients with biopsy-confirmed NAFLD. Although fibrosis stage was independently associated with liver-related events, it was not associated with overall mortality after adjusting for confounders, such as histologic features of steatohepatitis.
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http://dx.doi.org/10.1016/j.cgh.2022.01.002DOI Listing
January 2022

Impact of nutritional status on prognosis in acute myocardial infarction patients undergoing percutaneous coronary intervention.

BMC Cardiovasc Disord 2022 01 7;22(1). Epub 2022 Jan 7.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8520, Japan.

Background: Malnutrition affects the prognosis of cardiovascular disease. Acute myocardial infarction (AMI) has been a major cause of death around the world. Thus, we investigated the impact of malnutrition as defined by Geriatric Nutritional Risk Index (GNRI) on mortality in AMI patients.

Methods: In 268 consecutive AMI patients who underwent percutaneous coronary intervention (PCI), associations between all-cause death and baseline characteristics including malnutrition (GNRI < 92.0) and Global Registry of Acute Coronary Events (GRACE) risk score were assessed.

Results: Thirty-three patients died after PCI. Mortality was higher in the 51 malnourished patients than in the 217 non-malnourished patients, both within 1 month after PCI (p < 0.001) and beyond 1 month after PCI (p = 0.017). Multivariate Cox proportional hazards regression modelling using age, left ventricular ejection fraction and GRACE risk score showed malnutrition correlated significantly with all-cause death within 1 month after PCI (hazard ratio [HR] 7.04; 95% confidence interval [CI] 2.30-21.51; p < 0.001) and beyond 1 month after PCI (HR 3.10; 95% CI 1.70-8.96; p = 0.037). There were no significant differences in area under the receiver-operating characteristic (ROC) curve between GRACE risk score and GNRI for predicting all-cause death within 1 month after PCI (0.90 vs. 0.81; p = 0.074) or beyond 1 month after PCI (0.69 vs. 0.71; p = 0.87). Calibration plots comparing actual and predicted mortality confirmed that GNRI (p = 0.006) was more predictive of outcome than GRACE risk score (p = 0.85) beyond 1 month after PCI. Furthermore, comparison of p-value for interaction of malnutrition and GRACE risk score for all-cause death within 1 month after PCI, beyond 1 month after PCI, and the full follow-up period after PCI were p = 0.62, p = 0.64 and p = 0.38, respectively.

Conclusions: GNRI may have a potential for predicting the mortality in AMI patients especially in beyond 1 month after PCI, separate from GRACE risk score. Assessment of nutritional status may help stratify the risk of AMI mortality.
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http://dx.doi.org/10.1186/s12872-021-02448-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742435PMC
January 2022

A new pre-test probability score for diagnosis of deep vein thrombosis in patients before surgery.

J Cardiol 2022 May 23;79(5):664-670. Epub 2021 Dec 23.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Background: Venous thromboembolism is a serious perioperative complication. We developed a new pre-test probability score for predicting deep vein thrombosis (DVT) before surgery.

Methods: Whole leg ultrasonography was performed on 973 inpatients and outpatients with suspected DVT based on a preoperative D-dimer cut-off value of ≥ 1 μg/ml. We allocated two-thirds (n = 651) of the study participants to a derivation cohort and one-third (n = 322) to a validation cohort. The pre-test probability model was developed from the derivation cohort data.

Results: The pre-test probability model for DVT assigned 2 points to D-dimer ≥ 1.5 μg/mL and 1 point each to age ≥ 60 years, female sex, ongoing glucocorticoid therapy, prolonged immobility, and cancer with high risk of DVT. The area under the curve of the pre-test probability score was 0.72 and 0.70 in the derivation and validation cohorts, respectively. The rates of DVT according to pre-test probability scores in the derivation and validation cohorts were 7% and 6% in the low (score = 0-2), 23% and 22% in the intermediate (score = 3-4), and 47% and 50% in the high probability group (score ≥ 5), respectively (p < 0.0001).

Conclusions: The pre-test probability score (Kagoshima-DVT score) was helpful in detecting preoperative DVT in both inpatients and outpatients. We identified low probability group to reduce whole-leg ultrasonography and high probability group to detect more DVT before surgery.
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http://dx.doi.org/10.1016/j.jjcc.2021.11.025DOI Listing
May 2022

Evaluating the Khorana risk score of gastrointestinal cancer patients during initial chemotherapy as a predictor of patient mortality: A retrospective study.

J Cardiol 2022 May 17;79(5):655-663. Epub 2021 Dec 17.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, Japan; Department of Prevention and Analysis of Cardiovascular Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima City, Kagoshima, Japan.

Background: The Khorana risk score (KRS) has been recommended for predicting the incidence of cancer-associated thrombosis (CAT). However, it has been reported KRS was not useful in predicting CAT, but rather in predicting death by setting high scores for the primary tumor site or a low prevalence of severe obesity.

Methods: A total of 260 consecutive patients with no history of thrombosis and who started initial chemotherapy for gastrointestinal cancer from January 2017 to December 2018 at our hospital were divided into three groups according to KRS; they were observed until December 2019 [122 patients (46.9%) in the low-risk group, 114 patients (43.8%) in the intermediate-risk group, and 24 patients (9.2%) in the high-risk group]. The incidence of CAT and all-cause death were compared among the three groups.

Results: The median age of the patients was 67 years; 63.5% were men. CAT was observed in 61 patients (26.1%); 84 patients (37.9%) died during the observation period. The incidence rate of CAT was similar among the three groups (log-rank p = 0.4); but all-cause death showed a significant difference among the three groups (high-risk group: 58.2%, intermediate-risk group: 44.6%, low-risk group: 27.5%, log-rank p = 0.002). In the multivariate analysis, the high-risk KRS group remained at increased risk for all-cause death (HR, 2.83; 95% CI, 1.37-5.83; p = 0.005), but not with CAT.

Conclusions: The KRS at the start of chemotherapy for gastrointestinal cancer is not effective in predicting CAT, but it is effective in predicting prognosis in patients with gastrointestinal cancer.
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http://dx.doi.org/10.1016/j.jjcc.2021.11.024DOI Listing
May 2022

Prognostic impact of malnutrition on cardiovascular events in coronary artery disease patients with myocardial damage.

BMC Cardiovasc Disord 2021 10 6;21(1):479. Epub 2021 Oct 6.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, 890-8520, Japan.

Background: Stable coronary artery disease (CAD) patients with myocardial damage have a poor prognosis compared to those without myocardial damage. Recently, malnutrition has been reported to affect the prognosis of cardiovascular diseases. However, the effects of malnutrition on prognosis of CAD patients with myocardial damage remains uncertain. We investigated the effects of malnutrition on prognosis of CAD patients with myocardial damage who received percutaneous coronary intervention (PCI).

Methods: Subjects comprised 241 stable CAD patients with myocardial damage due to myocardial ischemia or infraction. Patients underwent successful revascularization for the culprit lesion by PCI using second-generation drug-eluting stents and intravascular ultrasound. The geriatric nutritional risk index (GNRI), which is widely used as a simple method for screening nutritional status using body mass index and serum albumin, was used to assess nutritional status. Associations between major cardiovascular and cerebrovascular events (MACCE) and patient characteristics were assessed.

Results: Mean GNRI was 100 ± 13, and there were 55 malnourished patients (23%; GNRI < 92) and 186 non-malnourished patients (77%). MACCE occurred within 3 years after PCI in 42 cases (17%), including 34 deaths (14%), and the malnourished group showed a higher rate of MACCE (38%) compared with the non-malnourished group (11%, p < 0.001). Univariate Cox proportional hazards analyses showed that MACCE was associated with age [hazard ratio (HR), 1.04; 95% confidence interval (CI), 1.04-1.07; p = 0.004], prior heart failure (HR 2.35; 95% CI 1.10-5.01; p = 0.027), high-sensitivity C-reactive protein (HR 1.08; 95% CI 1.03-1.11; p < 0.001), hemodialysis (HR 2.63; 95% CI 1.51-4.58; p < 0.001) and malnutrition (HR 3.69; 95% CI 2.11-6.42; p < 0.001). Multivariate Cox proportional hazards analysis revealed hemodialysis (HR 2.17; 95% CI 1.19-3.93; p = 0.011) and malnutrition (HR 2.30; 95% CI 1.13-4.67; p = 0.020) as significantly associated with MACCE. Furthermore, Cox proportional hazards models using malnutrition and hemodialysis revealed that patients with malnutrition and hemodialysis were at greater risk of MACCE after PCI than patients with neither malnutrition nor hemodialysis (HR 6.91; 95% CI 3.29-14.54; p < 0.001).

Conclusions: In CAD patients with myocardial damage, malnutrition (GNRI < 92) represents an independent risk factor for MACCE. Assessment of nutritional status may help stratify the risk of cardiovascular events and encourage improvements in nutritional status.
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http://dx.doi.org/10.1186/s12872-021-02296-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493704PMC
October 2021

WBC count predicts heart failure in diabetes and coronary artery disease patients: a retrospective cohort study.

ESC Heart Fail 2021 10 15;8(5):3748-3759. Epub 2021 Jul 15.

The CHD Collaborative Investigators are mentioned in the appendix.

Aims: White blood cell (WBC) count in healthy people is associated with the risk of coronary artery disease (CAD) and mortality. This study aimed to determine whether WBC count predicts heart failure (HF) requiring hospitalization as well as all-cause death, acute myocardial infarction (AMI) and stroke in patients with Type 2 diabetes mellitus and established CAD.

Methods: We conducted this retrospective registry study that enrolled consecutive patients with Type 2 diabetes mellitus and CAD based on coronary arteriography records and medical charts at 70 teaching hospitals in Japan from 2005 to 2015. A total of 7608 participants (28.2% women, mean age 68 ± 10 years) were eligible. In the cohort, the median (interquartile range) and mean follow-up durations were 39 (16.5-66.1 months) and 44.3 ± 32.7 months, respectively. The primary outcome was HF requiring hospitalization. The secondary outcomes were AMI, stroke, all-cause death, 3-point major adverse cardiovascular events (MACE) (AMI/stroke/death) and 4-point MACE (AMI/stroke/death/HF requiring hospitalization). Outcomes were reported as cumulative incidences (proportion of patients experiencing an event) and incidence rates (events/100 person-years). The primary and secondary outcomes were assessed using the Kaplan-Meier method and were compared using the log-rank test stratified by the baseline WBC count. The association between the WBC count at baseline and each MACE was assessed using the Cox proportional hazard model and expressed as the hazard ratio (HR) and 95% confidence interval (CI) after adjusting for other well-known risk factors for MACE.

Results: During the follow-up, 880 patients were hospitalized owing to HF. The WBC Quartile 4 (≥7700 cells/μL) had significantly lower HF event-free survival rate (log-rank test, P < 0.001). The HRs for HF events requiring hospitalization with each WBC quartile compared with the lowest in the first WBC quartile were 1 for Quartile 1 (WBC < 5300 cells/μL), 1.20 (95% CI, 0.96-1.5; P = 0.1) for Quartile 2 (5300 ≤ WBC < 6400), 1.34 (95% CI, 1.08-1.67; P = 0.009) for Quartile 3 (6400 ≤ WBC < 7700) and 1.62 (95% CI, 1.31-2.00; P < 0.001) for Quartile 4 after adjusting for covariates. Similar findings were observed for the risk of AMI and death; however, no significant difference was found for stroke. WBC Quartile 4 patients had a significantly lower 3- or 4-point MACE-free survival rate (log-rank test, P < 0.0001).

Conclusions: A higher WBC count is a predictor of hospitalization for HF, all-cause death and AMI but not for stroke in patients with concurrent Type 2 diabetes mellitus and established CAD.
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http://dx.doi.org/10.1002/ehf2.13513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497382PMC
October 2021

Sex-specific relationship between abdominal obesity and new-onset atrial fibrillation in the general Japanese population.

Heart Vessels 2021 Dec 27;36(12):1879-1884. Epub 2021 May 27.

Department of Cardiovascular Medicine and Hypertension, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.

The incidence of atrial fibrillation (AF) is expected to increase with increasing obesity and number of geriatric patients in Japan. Although higher body mass index and abdominal obesity are associated with an increased risk of AF, the sex-specific relationship between abdominal obesity and new-onset AF is unclear. This study aimed to investigate the sex-specific relationship between abdominal obesity and new-onset AF. This retrospective study evaluated the annual health checkup data of 67,379 adults (33,562 males; age, 54 ± 10 years) without baseline AF from April 2008 to March 2016. Participants were grouped according to waist circumference (WC): large-WC group (males, ≥ 85 cm; females, ≥ 90 cm) and normal-WC group. Logistic regression analyses were performed to determine the strength of the association between abdominal obesity and new-onset AF, overall and separately for males and females. During a median follow-up of 5 years, 280 (0.4%) new cases of AF were recorded. Univariate analysis revealed a significant increase in new-onset AF in males (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.49-2.60; p < 0.001) but not in females (OR, 1.69; 95% CI, 0.96-2.97; p = 0.068) in the large-WC group. After adjusting for clinical variables, multivariate analysis revealed that a large WC was significantly associated with new-onset AF in males (OR, 1.76; 95% CI, 1.31-2.36; p < 0.001) but not in females (OR, 1.22; 95% CI, 0.68-2.18; p = 0.514). Abdominal obesity is associated with an increased risk of new-onset AF in men.
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http://dx.doi.org/10.1007/s00380-021-01880-5DOI Listing
December 2021

The Priority of Non-HDL-C Assessment to Predict New Lesions among Stable Angina Patients with Strong Statins.

J Atheroscler Thromb 2021 May 25. Epub 2021 May 25.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University.

Aim: In this study, we aim to examine the clinical meaning of low-density lipoprotein cholesterol (LDL-C) <70 mg/dL as assessed by Friedewald equation [LDL-C (F)] and Martin method [LDL-C (M)] and non-high-density lipoprotein cholesterol (HDL-C) <100 mg/dL on the occurrence of new lesions among Japanese patients with stable angina who underwent percutaneous coronary intervention (PCI) and were prescribed with strong statins.

Methods: Among the 537 consecutive stable angina patients who had underwent PCI and had been prescribed with strong statins, the association between the occurrence of new lesions with myocardial ischemia at the 9-month follow-up coronary angiography and ≤ 2 years after PCI and baseline characteristics were assessed.

Results: New lesions appeared 9 months and ≤ 2 years after PCI in 31 and 90 patients, respectively. Multivariate logistic regression analysis revealed diabetes mellitus (DM) was significantly associated with the occurrence of new lesions ≤ 2 years after PCI [odds ratio (OR) 1.71, 95 % confidence interval (CI) 1.06-2.83, p=0.031], and only non-HDL-C ≥ 100 mg/dL was associated with the occurrence of new lesions both at 9 months and ≤ 2 years after PCI [OR 1.80, 95 % CI 1.10-3.00, p=0.021 and OR 1.85, 95 % CI 1.13-3.07, p=0.016].

Conclusions: Non-HDL-C ≥ 100 mg/dL was determined to be the independent risk factor for the occurrence of new lesions 9 months and ≤ 2 years after PCI among stable angina patients with strong statins. Residual risk after PCI should be considered by assessing not only DM but also non-HDL-C beyond the scope of LDL-C-lowering therapy with strong statins.
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http://dx.doi.org/10.5551/jat.62908DOI Listing
May 2021

Different characteristics of mitochondrial dynamics-related miRNAs on the hemodynamics of pulmonary artery hypertension and chronic thromboembolic pulmonary hypertension.

J Cardiol 2021 07 6;78(1):24-30. Epub 2021 Apr 6.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. Electronic address:

Background: Mitochondria are dynamic organelles that undergo fission or fusion. These mitochondrial dynamics are reported to be associated with pulmonary hypertension (PH). PH is divided into 5 groups, including pulmonary artery hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), based on its pathogenesis. However, it is still unknown whether and how miRNAs related to mitochondrial dynamics (MD) affect PAH and CTEPH.

Methods: We investigated patients who underwent right heart catheterization between October 2016 and January 2019. Out of 34 PH patients, 12 were diagnosed with PAH, and 22 were diagnosed with CTEPH. In addition, there were 30 patients diagnosed with left heart disease. We enrolled the 34 PH patients as the PH group and 30 left heart disease patients as the control group.

Results: Among MD-related miRNAs, the circulating levels of miR-140-3p were higher, and those of miR-485-5p were lower in the PH group than in the control group (p < 0.01), suggesting that miRNAs inducing mitochondrial fission are related to PH. The miR-140-3p levels in the PAH and CTEPH groups were higher than those in the control group (p < 0.01). The levels of miR-140-3p and miR-485-5p in the PAH group correlated with pulmonary vascular resistance (r = 0.582, p = 0.046) and cardiac index (r = -0.36, p = 0.04), respectively. The miR-485-5p levels in the CTEPH group correlated with right atrium pressure (r = -0.456, p = 0.049).

Conclusion: MD-related miRNAs levels change to induce fission and are closely related to the hemodynamics of PAH and CTEPH.
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http://dx.doi.org/10.1016/j.jjcc.2021.03.008DOI Listing
July 2021

Geriatric Nutritional Risk Index Is Associated With Prognosis in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

Circ Rep 2020 Jun 12;2(7):372-377. Epub 2020 Jun 12.

Departments of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima Japan.

The Geriatric Nutritional Risk Index (GNRI) is a simple tool for assessing nutritional risk that predicts prognosis in patients with heart failure. This study evaluated associations between the GNRI at first hospitalization and prognosis in patients with pulmonary artery hypertension (PAH) and those with chronic thromboembolic pulmonary hypertension (CTEPH). This retrospective investigation included 104 patients with either PAH or CTEPH who were treated at Kagoshima University Hospital in Japan. Patients were divided into a high (≥92) and low (<92) GNRI groups. Body mass index and serum albumin levels were significantly lower in the low GNRI group (P<0.001). Over a median follow-up period of 24 months, the incidence of pulmonary hypertension rehospitalization was higher in the low GNRI group (P=0.04). Kaplan-Meier analysis revealed that the cumulative event-free rate was significantly lower in the low GNRI group (P=0.002). Low GNRI was significantly associated with a poorer outcome after adjusting for different sets of confounding factors, including: age and sex (P=0.004); age, sex, and PAH (P=0.043); and age, sex, and mean pulmonary artery pressure (P=0.003). The GNRI at first hospitalization is useful for predicting prognosis in PAH and CTEPH patients.
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http://dx.doi.org/10.1253/circrep.CR-20-0046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932812PMC
June 2020

Endosonographic finding of the simultaneous depiction of bile and pancreatic ducts can predict difficult biliary cannulation on endoscopic retrograde cholangiopancreatography.

PLoS One 2020 9;15(7):e0235757. Epub 2020 Jul 9.

Department of Prevention and Analysis of Cardiovascular Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, Japan.

Thus far, no curved linear array endoscopic ultrasound (CLAEUS) findings were established as predictors of difficult selective bile duct cannulation (SBDC). This study aimed to identify CLAEUS findings to predict endoscopic retrograde cholangiopancreatography (ERCP) cases with difficult SBDC. This single-center, retrospective cohort study was conducted between July 2014 and June 2017. This study included all consecutive patients who underwent CLAEUS prior to naïve ERCP. A CLAEUS finding of the simultaneous depiction of bile and pancreatic ducts at the second portion of the duodenum (D2) (simultaneous depiction) was selected as a possible predictor of difficult SBDC, and the κ values in the evaluation of inter- and intra-observer variabilities for "simultaneous depiction" were 0.65 and 0.77, respectively, with substantial correlation. Among the 986 patients who underwent ERCP, 80 patients were relevant for evaluation. Logistic regression analysis revealed strong association between "simultaneous depiction" and difficult SBDC (odds ratio 15.4, 95% confidence interval 4.2-56.0; p<0.001). Among patients who underwent CLAEUS prior to naïve ERCP, a strong correlation was observed between "simultaneous depiction" and the risk of difficult SBDC. An endoscopist can prepare for difficult SBDC by "simultaneous depiction." The finding enables pertinent planning when performing ERCP, such as setting time limits and selecting alternative devices, techniques, and skilled endoscopists, for difficult SBDC with minimal complications including post-ERCP pancreatitis. However, a future prospective study is necessary to establish the procedure algorithm for suspected difficult SBDC cases based on CLAEUS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235757PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347092PMC
September 2020

How Should Rehabilitation Be Performed After Transcatheter Aortic Valve Replacement?

Circ J 2020 06 5;84(7):1055-1056. Epub 2020 Jun 5.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University.

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http://dx.doi.org/10.1253/circj.CJ-20-0504DOI Listing
June 2020

Association between contrast-induced nephrotoxicity and contrast enhanced computed tomography followed by endoscopic retrograde cholangiopancreatography.

Eur J Radiol 2020 Aug 19;129:109074. Epub 2020 May 19.

Department of Clinical Research and Quality Management, Center of Clinical Research and Quality Management, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan. Electronic address:

Purpose: To determine if endoscopic retrograde cholangiopancreatography (ERCP) performed within 72 h after contrast enhanced computed tomography (CECT) increases contrast-induced nephrotoxicity (CIN) risk in patients with abdominal complaints.

Method: This single-center retrospective cohort study included consecutive adult patients with abdominal complaints who underwent CECT between October 1, 2016, and June 30, 2019 at an emergency department (ED). CIN was diagnosed based on serum creatinine (SCr) level >0.5 mg/dL within 72 h after CECT or that increased >25 % compared to pre-CECT level. Logistic regression analysis was performed to determine independent risk factors for CIN, including age, sex, body mass index, comorbidities, medication, pre-CECT SCr level >1.5 mg/dL, and ERCP performed within 72 h after CECT. For persistent CIN, SCr level was obtained after 3 months at the earliest and compared to data obtained within 72 h after ERCP and CECT.

Results: Of 1457 patients with CECT, 90 (6.2 %) underwent ERCP within 72 h after CECT and 93 (6.4 %) developed CIN. Multivariate analysis revealed that ERCP performed within 72 h after CECT (odds ratio, 3.31; 95 % confidence interval, 1.74, 6.29; p < 0.001) and pre-CECT SCr level >1.5 mg/dL (odds ratio, 9.86; 95 % confidence interval, 5.08, 19.2; p < 0.001) were independent risk factors for CIN. Of 93 patients with CIN, 10 (11 %) had persistent CIN. No specific factors were correlated with persistent CIN in the 3-month time frame.

Conclusion: ERCP performed within 72 h after CECT and pre-CECT SCr level >1.5 mg/dL are associated with CIN development.
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http://dx.doi.org/10.1016/j.ejrad.2020.109074DOI Listing
August 2020

Risk factors for progressive sarcopenia 6 months after complete resection of lung cancer: what can thoracic surgeons do against sarcopenia?

J Thorac Dis 2020 Mar;12(3):307-318

Department of Thoracic Surgery, Kanagawa Cancer Center, Asahi-ku, Yokohama, Japan.

Background: Our previous report described how postoperative progression of sarcopenia predicted long-term prognosis after complete resection of non-small cell lung cancer (NSCLC) in heavy smokers. However, there are currently no effective means to treat progressive sarcopenia. In this study, we aimed to confirm our previous findings in a larger population and to identify factors associated with postoperative progression of sarcopenia to propose possible preventative measures.

Methods: This retrospective study analyzed the data of 1,095 patients who underwent curative lobar resection for NSCLC at Kanagawa Cancer Center. We divided patients into four groups according to sex and Brinkman index (BI) above or below 600. Six-month postoperative changes in the skeletal muscle index (SMI) were calculated and associations between clinicopathological factors including changes in SMI and mortality from postoperative 6 months were examined. Only in groups in which postoperative depletion of SMI was shown to be associated with the prognosis, we identified clinicopathological factors associated with depletive SMI.

Results: The overall survival rates of 1,095 patients were 89.8% and 82.5% at 3 and 5 years, respectively. The median 6-month change in SMI was -3.4% (range, -22.3% to +17.9%). Multivariate analysis revealed that poor prognosis was independently predicted by a large reduction in the SMI (cut-off value: -10%) in males with a BI ≥600. In 391 heavy-smoking males, factors associated with a postoperative change in SMI ≤-10% were history of other cancers (including gastric cancer) low forced expiratory volume in one second (FEV 1.0, cut-off value: 1,870 mL), and prolonged operation time (cut-off value: 200 minutes).

Conclusions: Perioperative measures to prevent postoperative sarcopenia are appropriate for heavy smokers. We obtained some clues regarding countermeasures, one of which may be avoiding long-time operation. Further studies including clinical trials to assess perioperative anti-sarcopenia treatments, are needed.
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http://dx.doi.org/10.21037/jtd.2020.01.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138994PMC
March 2020

Author Correction: Randomized Evaluation of Anagliptin vs Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) Trial: A 52-week, open-label, randomized clinical trial.

Sci Rep 2020 Feb 21;10(1):3548. Epub 2020 Feb 21.

Department of Pharmacology and Therapeutics, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-60644-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033276PMC
February 2020

Malnutrition and Clopidogrel Non-Use Worsen Prognosis of Critical Limb Ischemia Patients After Revascularization.

Circ Rep 2019 Dec 28;2(2):121-127. Epub 2019 Dec 28.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University Kagoshima Japan.

Critical limb ischemia (CLI) patients have high risk for major adverse cerebrovascular and cardiovascular events. This study investigated the risk factors of cerebrovascular or cardiovascular death in CLI patients with concomitant coronary artery disease (CAD). The association between baseline characteristics and cerebrovascular or cardiovascular death ≤2 years after revascularization for CLI was investigated in 137 CLI patients who previously underwent successful revascularization for CAD before treatment for CLI. Twenty-three patients (17%) died. Geriatric nutritional risk index (GNRI) in the deceased group (DG) was significantly lower than in the surviving group (SG). On Cox proportional hazard multivariate analysis, hemodialysis (HD) and malnutrition (defined as GNRI <92) were significantly associated with cerebrovascular or cardiovascular death. Also, on Kaplan-Meier analysis, survival rate was significantly lower in CLI patients with either malnutrition or HD compared with patients without either malnutrition or HD, respectively. Furthermore, clopidogrel was less used in the DG than in the SG. The use of clopidogrel was associated with cerebrovascular or cardiovascular death. Especially, non-use of clopidogrel in the malnutrition group further increased the correlation with cerebrovascular or cardiovascular death. Malnutrition is a crucial risk factor for cerebrovascular and cardiovascular death in CLI patients with CAD. Nutritional status intervention and use of clopidogrel may be an important strategy for CLI.
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http://dx.doi.org/10.1253/circrep.CR-19-0105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929756PMC
December 2019

Use of proton pump inhibitors is associated with an increase in adverse cardiovascular events in patients with hemodialysis: Insight from the kids registry.

Eur J Intern Med 2020 02 14;72:79-87. Epub 2019 Nov 14.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; Department of Prevention and Analysis of Cardiovascular Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Background: Proton pump inhibitors (PPIs) are known to increase the risk of mortality and cardiovascular events in the general population. However, in patients with maintenance hemodialysis, PPI effects are under investigated.

Methods: We analyzed the risk of PPIs for cardiovascular events using the Kagoshima Dialysis (KIDS) registry, a prospective, multicenter, observational study in patients with maintenance hemodialysis in Japan.

Results: In all, 531 patients were enrolled from June 2015 to December 2018. One-year follow-up data were available for 376 patients (Use of PPIs at baseline (PPI group): 217 patients and without PPIs (No PPI group): 159 patients). The incidence of a composite outcome (all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke) was higher in patients in the PPI group than the No PPI group (15.2% vs. 4.4%; hazard ratio (HR): 3.65, 95% confidence interval (CI): 1.61-8.23, P = 0.002). In the multivariate analysis, even after adjustment for covariates, the use of PPIs was an independent risk factor for a composite outcome (HR: 2.38, 95% CI: 1.02-5.54, P = 0.045). We performed propensity score matching analysis as a sensitivity analysis, showing a consistent result. The incidence of bleeding showed no difference between the two groups (15.7% vs. 11.3%; HR: 1.46, 95% CI: 0.83-2.59, P = 0.19).

Conclusions: These results indicate that the use of PPIs in patients with maintenance hemodialysis might increase mortality and cardiovascular events without decreasing the risk of bleeding. Therefore, it should always be analyzed if a patient truly needs PPIs.
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http://dx.doi.org/10.1016/j.ejim.2019.11.002DOI Listing
February 2020

Isolated Distal Deep Vein Thrombus Detected before Orthopedic Surgery: Is Preoperative Anticoagulation Preferable?

Ann Vasc Dis 2019 Sep;12(3):354-361

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, Japan.

: We evaluate the efficacy of anticoagulant administration for isolated distal deep vein thrombus (IDDVT), detected before orthopedic surgery. : The study included 32 patients diagnosed with IDDVT before orthopedic surgery in our hospital between October 2011 and October 2017. They were divided into two groups: the 'pre- and post-operative therapy group,' who were administered anticoagulants both pre- and post-operatively, and the 'post-operative therapy group,' who were administered anticoagulants only after surgery due to risk of bleeding judged by an orthopedic surgeon. We compared the primary efficacy (change in IDDVT size) between the two groups. : The proportion of patients with increased post-operative IDDVT sizes was significantly larger in the post-operatively treated group than in the pre- and post-operatively treated group (44.4% vs. 8.7%, p=0.026). No case demonstrated an IDDVT extension proximal to the popliteal vein or presented with symptomatic pulmonary thromboembolism in this study. : Based on our findings, we recommend that, in patients with IDDVT detected prior to orthopedic surgery and administered anticoagulant therapy only after the procedure because of a bleeding risk, a lower limb ultrasonography to re-evaluate the existing deep vein thrombus should be conducted before beginning rehabilitation.
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http://dx.doi.org/10.3400/avd.oa.19-00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766777PMC
September 2019

Effect of progressive sarcopenia during postoperative 6 months on long-term prognosis of completely resected lung cancer.

J Thorac Dis 2019 Aug;11(8):3411-3420

Department of Thoracic Surgery, Kanagawa Cancer Center, Asahi-ku, Yokohama, Japan.

Background: Preoperative sarcopenia has been indicated to be a potential prognostic factor for patients after complete resection of lung cancer. This study evaluated whether changes in the skeletal muscle mass index (SMI) over postoperative 6 months could predict long-term prognosis from 6 months after complete resection of non-small cell lung cancer (NSCLC).

Methods: This retrospective study analyzed data of 468 patients who underwent curative lobar resection for non-small cell lung cancer at our hospital. The 6-month postoperative change in SMI was calculated, and associations between clinicopathological factors (including the change in SMI) and postoperative mortality were examined.

Results: Rates of overall survival were 90.6% after 3 years and 80.7% after 5 years. The median 6-month change in SMI was -3.4% (range, -22.3% to 14.7%). Multivariate analysis revealed that poor outcomes were independently predicted by a large change in SMI, age, pathological stage, lymphovascular invasion, and a Brinkman index of ≥600. Through the analysis in training and validation sets, we determined a cut-off value of -9.9% for the 6-month postoperative change in SMI. Subgroup analysis showed that depletion of SMI during postoperative 6 months was a risk factor for poorer prognosis only in heavy smokers with a Brinkman index of ≥600.

Conclusions: A reduction in SMI during the 6 months after complete resection of non-small cell lung cancer significantly predicted prognosis, especially in heavy smokers. These results suggest that attention should be given to prevent the perioperative progression of sarcopenia after curative resection of lung cancer. Thoracic surgeons should take how to manage perioperatively against sarcopenia into consideration.
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http://dx.doi.org/10.21037/jtd.2019.08.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753447PMC
August 2019

Effects of Perioperative Administration of Acetaminophen on Postoperative Shivering: A Randomized, Triple-Blind, Placebo-Controlled Trial.

Anesth Analg 2020 04;130(4):983-990

Department of Anesthesiology, Faculty of Medicine, University of the Ryukyus, Nishihara-cho, Japan.

Background: In this randomized, triple-blind, placebo-controlled trial, we tested the hypothesis that perioperative acetaminophen administration has a prophylactic effect on postoperative shivering.

Methods: Forty-five women scheduled for gynecological laparotomy were randomized to either the acetaminophen or the placebo groups. After induction of general anesthesia, the test drug (acetaminophen 15 mg/kg) or placebo (0.9% saline) was intravenously administered over 15 minutes. The primary outcome measure was the incidence of severe postoperative shivering (ie, shivering score >2) in the postanesthesia care unit, where patients stayed for 30 minutes after their emergence from anesthesia. For the secondary outcomes, core body temperature (BT) was recorded at the forehead just before anesthesia induction (time 0 [T0]), at the start of surgery (time 1 [T1]), at the end of surgery (time 2 [T2]), at the initiation of postoperative observation in the postanesthesia care unit (time 3 [T3]), and 30 minutes after T3 (time 4 [T4]). At 1 hour after T4 (ie, time 5 [T5]), the BT was recorded from the axilla (BTA). Primary outcome was analyzed using a χ test. BT recorded at the forehead (BTF) and BTA were analyzed using a 2-way repeated-measures analysis of variance (ANOVA) and a 2-sample t test, respectively. For all comparisons, a P value <.05 was considered statistically significant.

Results: The study duration was 2 years. Of the 45 patients initially enrolled, 8 patients were excluded. The acetaminophen and placebo groups included 18 and 19 patients, respectively. The incidence of severe postoperative shivering in the postanesthesia care unit was significantly lower in the acetaminophen group (22.2%) than in the placebo group (73.7%) (relative risk, 0.302; 95% confidence interval, 0.122-0.746; P = .005). Two-way repeated-measures ANOVA showed a significant effect of time (F4,140 = 54.8; P < .001) and a significant time by treatment interaction (F4,140 = 9.61; P < .001) but did not show a main effect of the treatment (F1,35 = 1.83; P = .185) in BTF. Moreover, BTA at T5 was significantly lower in the acetaminophen group (mean [standard deviation {SD}], 37.2°C [0.48°C]) than in the placebo group (37.9°C [0.63°C]; P < .001).

Conclusions: Our findings in patients undergoing gynecological laparotomy suggest that perioperative acetaminophen administration can prevent postoperative severe shivering. This prophylactic effect might be due to suppressing the postoperative increase in the BT set point, rather than lowering the threshold for shivering, as observed with clonidine.
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http://dx.doi.org/10.1213/ANE.0000000000004306DOI Listing
April 2020

Randomized Evaluation of Anagliptin vs Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) Trial: A 52-week, open-label, randomized clinical trial.

Sci Rep 2019 06 12;9(1):8537. Epub 2019 Jun 12.

Department of Pharmacology and Therapeutics, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.

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.
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http://dx.doi.org/10.1038/s41598-019-44885-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561974PMC
June 2019

Reintroducing testosterone in the db/db mouse partially restores normal glucose metabolism and insulin resistance in a leptin-independent manner.

BMC Endocr Disord 2018 Jun 13;18(1):38. Epub 2018 Jun 13.

Clinical Pharmacology and Therapeutics University of the Ryukyus School of Medicine, Okinawa, Japan.

Background: Testosterone signals through the androgen receptor (AR) and AR knockout mice develop obesity, suggesting a functional association between AR and leptin signaling. Furthermore, physiological blood concentrations of testosterone have been found to inhibit the development of arteriosclerosis, obesity and diabetes. However, these findings have not been verified by testosterone replacement in animal models and whether or not testosterone acts directly by activating AR to enhance leptin signaling, or indirectly by its conversion into estrogen remains unclear. Therefore, we investigated the effect of exogenously supplemented testosterone on glucose and lipid metabolism.

Methods: Four-week-old male leptin receptor-knockout db/db mice were used as controls for a model of obesity retaining low testosterone. Mice were divided into sham-operated, castrated, or castrated and testosterone-supplemented groups and fed a high-fat diet (HFD) for 2 weeks from 5 weeks of age. Testosterone concentrations, blood glucose, plasma insulin levels, and intraperitoneal glucose tolerance and insulin tolerance were measured. At 7 weeks, triglyceride and glycogen content were measured in the liver and muscle. Lipid accumulation in the liver and soleus muscle was determined by immunohistochemistry with Oil Red O. Statistical analyses were performed using the Student's t-test or ANOVA where applicable.

Results: Lower testosterone levels in db/db mice compared with wild type (WT) db/+ mice were associated with glucose intolerance and fatty liver. Furthermore, castrated male db/db mice at 4 weeks of age progressively developed glucose intolerance accompanying a 15% increase in liver fat. Male mice fed a HFD had lower levels of testosterone compared with those fed a normal diet. We found that exogenous testosterone replacement injected subcutaneously into castrated male db/db mice alleviated the exacerbation of fatty liver and glucose intolerance, suggesting a leptin-independent mechanism. This mechanism is most likely mediated through gonadal axis suppression in this mouse model.

Conclusions: In summary, testosterone may use a novel pathway to complement leptin signaling to regulate glucose and lipid metabolism, and thus offers a new therapeutic target to treat metabolic disorders.
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http://dx.doi.org/10.1186/s12902-018-0266-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998571PMC
June 2018

Prospective Study on the Incidence of Cerebrovascular Disease After Coronary Angiography.

J Atheroscler Thromb 2018 Mar 30;25(3):224-232. Epub 2017 Aug 30.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University.

Aim: Previous studies have reported a 10.2%-22% rate of silent cerebral infarction and a 0.1%-1% rate of symptomatic cerebral infarction after coronary angiography (CAG). However, the risk factors of cerebral infarction after CAG have not been fully elucidated. For this reason, we investigated the incidence and risk factors of CVD complications within 48 h after CAG using magnetic resonance imaging (MRI) (Diffusion-weighted MRI) at Kagoshima University Hospital.

Methods: From September 2013 to April 2015, we examined the incidence and risk factors, including procedural data and patients characteristics, of cerebrovascular disease after CAG in consecutive 61 patients who underwent CAG and MRI in our hospital.

Results: Silent cerebral infarction after CAG was observed in 6 cases (9.8%), and they should not show any neurological symptoms of cerebral infarction. Only prior coronary artery bypass grafting (CABG) was more frequently found in the stroke group (n=6) than that in the non-stroke group (n=55); however, no significant difference was observed (P=0.07). After adjusting for confounders, prior CABG was a significant independent risk factor for the incidence of stroke after CAG (odds ratio: 11.7, 95% confidence interval: 1.14-129.8, P=0.04).

Conclusions: We suggested that the incidence of cerebral infarction after CAG was not related to the catheterization procedure per se but may be caused by atherosclerosis with CABG.
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http://dx.doi.org/10.5551/jat.41012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868508PMC
March 2018

Association Between Waist-to-Height Ratio and Endothelial Dysfunction in Patients With Morbidity - A Report From the FMD-J Study.

Circ J 2017 Nov 7;81(12):1911-1918. Epub 2017 Jul 7.

Department of Cardiology, Tokyo Medical University.

Background: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI) are known as easy anthropometric markers of abnormal obesity and screening tools for predicting cardiovascular outcomes, but which indices are best is unclear. We therefore investigated the superiority and association between each index and low flow-mediated dilatation (FMD) as a surrogate marker for cardiovascular outcomes in patients with morbidity in a large Japanese prospective cohort.Methods and Results:A total of 1,645 Japanese patients who had coronary artery disease and hypertension or diabetes mellitus were enrolled, and 1,087 of them were analyzed. The high-WHtR group (≥0.5) showed greater morbidity and increased inflammation in association with atherosclerosis compared with the low-WHtR group. High WHtR and advanced age were identified as predictors of low FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR 1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female: OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54).

Conclusions: WHtR offers a superior predictor of decreased FMD than other anthropometric indices, and progression of arteriosclerosis might be detected more sensitively. Further study is needed to investigate the relationship between cardiovascular mortality and WHtR.
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http://dx.doi.org/10.1253/circj.CJ-17-0211DOI Listing
November 2017

Coronary bifurcation model created using a novel directional heat injury catheter.

Cardiovasc Revasc Med 2018 Jan - Feb;19(1 Pt B):102-105. Epub 2017 Jun 7.

Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address:

Objectives: The present study aimed to develop a swine coronary bifurcation model.

Background: In human coronary bifurcation lesion, atherosclerotic plaques are usually observed in the lateral wall, whereas the flow divider regions are spared. There is currently no suitable coronary bifurcation animal model, on which a new stent can be tested.

Methods: We developed a novel directional heat injury catheter, which comprised of a non-compliant balloon catheter (diameter: 3.0mm, length: 15mm), and two electrode cables, that were attached to either side of the balloon catheter. The technique was performed on 4 healthy pigs, and assessed in 7 lesions. We inflated the balloon at the main bifurcation branch, following which a high frequency generator was used to transmit heat to the opposite side of the electrode, towards the bifurcation carina (duration: 5min, frequency: 2 times). We performed a post-angiography 28days after the pre-angiography, to observe the distribution of neointima. The neointimal area was divided into the carina side and the opposite side of carina, and the 2 sides were compared.

Results: The neointimal area at the opposite side of the carina was significantly larger than the carina side (1.51±0.40mm vs. 0.95±0.27mm, p<0.0001). The percentage of area of stenosis on the opposite side of carina was also higher than that on the carina side (55.4±7.0% vs. 34.9±4.2%, p<0.0001).

Conclusions: We successfully developed a novel swine coronary bifurcation model using directional heat injury catheter.
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http://dx.doi.org/10.1016/j.carrev.2017.06.004DOI Listing
March 2019

Angiotensin-Converting Enzyme Inhibitor Prevents the Worsening of Renal Function in the Late Phase after Percutaneous Coronary Intervention.

J Atheroscler Thromb 2016 19;23(2):233-40. Epub 2015 Dec 19.

Department of Cardiovascular Medicine and Hypertension, Graduate School of Medicine and Dental Sciences, Kagoshima University.

Aim: The amount of contrast media and renal atheroemboli are risk factors for acute kidney injury after percutaneous coronary intervention (PCI). However, the chronic kidney injury after PCI has not been fully characterized. The purpose of this study was to investigate factors affecting renal function in the late phase after PCI by measuring serum Cystatin C (CysC).

Methods: In 143 consecutive patients who underwent elective PCI, CysC was evaluated at baseline and at 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association between %CysC and baseline characteristics, including medication use, was assessed.

Results: Of 143 patients, 86 had worsening renal function (WRF; %CysC ≥0), and 57 did not (non-WRF; %CysC <0). Only the use of angiotensin-converting enzyme inhibitor (ACEI) and baseline CysC were significantly different between WRF and non-WRF patients (15 vs. 40%, p=0.001 and 1.02±0.26 vs. 1.13±0.26 mg/L, p=0.015). In univariate analysis, the use of ACEI and CysC were negatively associated with WRF [Odds ratio (OR)=0.26, 95% confidence interval (CI)=0.12-0.57, p<0.001 and OR=0.20, 95% CI=0.05-0.73, p=0.015]. Furthermore, multivariate analysis revealed that the use of ACEI and CysC significantly correlated with WRF (OR=0.26, 95% CI=0.11-0.57, p<0.001 and OR=0.20, 95% CI=0.05-0.74, p=0.016). The %CysC in 36 patients with ACEI was significantly lower than that in 107 patients without ACEI [median: -3.8%; interquartile range (IQR), -11.0 to 4.2%; vs. median: 3.3%; IQR -2.9 to 11.0%, p=0.001].

Conclusion: The use of ACEI was associated with lower CysC after PCI, suggesting that ACEI prevents worsening of renal function in late phase after PCI.
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http://dx.doi.org/10.5551/jat.33266DOI Listing
November 2016

Clinical efficacy of thrombus aspiration on 5-year clinical outcomes in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention.

J Am Heart Assoc 2015 Jun 15;4(6):e001962. Epub 2015 Jun 15.

Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan (H.W., H.S., K.N., T.T., T.K.) Department of Clinical Epidemiology, Hyogo College of Medicine, Hyogo, Japan (T.M.) Division of Cardiology, Kobe City Medical Center General Hospital, Kobe, Japan (Y.F.) Division of Cardiology, Tenri Hospital, Nara, Japan (Y.N.) Departments of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Otsu, Japan (M.H.).

Background: Adjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) was reported to promote better coronary and myocardial reperfusion. However, long-term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.

Methods And Results: The CREDO-Kyoto AMI Registry is a large-scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005-2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI. Clinical outcomes were compared between the 2 patient groups with or without TA. During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA (TA group). The cumulative 5-year incidence of all-cause death was significantly lower in the TA group than in the non-TA group (18.5% versus 23.9%, log-rank P<0.001). After adjusting for confounders, however, the risk for all-cause death in the TA group was not significantly lower than that in the non-TA group (hazard ratio: 0.90, 95% CI: 0.76 to 1.06, P=0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target-lesion revascularization were also not significantly different between the 2 groups.

Conclusions: Adjunctive TA during primary PCI was not associated with better 5-year mortality in STEMI patients.
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http://dx.doi.org/10.1161/JAHA.115.001962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599536PMC
June 2015
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