Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial.

A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65-74 years and ≥ 75 years. Patients were randomized into febuxostat and non-febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non-fatal cerebral and cardiovascular events and all-cause death. Patients aged ≥ 75 years exhibited more pre-existing factors associated with cerebral and cardiorenovascular events than those aged 65-74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65-74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.

Role of Small Dense Low-density Lipoprotein Cholesterol in Cardiovascular Events in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Receiving Statin Treatment.

AIM: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. METHODS: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. RESULTS: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. CONCLUSIONS: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL.

Arterial Stiffness Is Associated With Small Vessel Disease Irrespective of Blood Pressure in Stroke-Free Individuals.

BACKGROUND: Arterial stiffness and hypertension are important risk factors for cerebral small vessel disease (CSVD). Clinically, there are hypertensive patients with low pulse wave velocity (PWV) and nonhypertensive individuals with high PWV. We aimed to determine the effects of arterial stiffness on CSVD in normotensive individuals. METHODS: An observational cross-sectional study was conducted in 1894 stroke-free participants who underwent brain magnetic resonance imaging and brachial-ankle pulse wave velocity (baPWV) measurements at a health checkup between 2013 and 2020. CSVD was defined as any of following: white matter hyperintensities, cerebral microbleeds, silent lacunar infarcts, and enlarged perivascular spaces. baPWV was measured using an automatic oscillometric device. Participants were divided into 4 groups according to the following cutoff points: low blood pressure (BP, <120/80 mm Hg) with low baPWV (<14.63 m/s, a cutoff value that predicted CSVD); high BP (≥120/80 mm Hg) with low baPWV; low BP with high baPWV (≥14.63 m/s); and high BP with high baPWV. RESULTS: The mean age of the participants was 57±13 years (41% women). The prevalence of CSVD was 718 (38%), which was higher in the low BP with high baPWV (56%) and high BP with high baPWV (55%) groups than in the high BP with low baPWV (24%) and low BP with low baPWV (22%) groups. Compared with the low BP with low baPWV group, the low BP with high baPWV group (odds ratio, 1.63 [95% CI, 1.09-2.43]) and the high BP with high baPWV group (odds ratio, 1.86 [95% CI, 1.39-2.49]) had a significantly higher multivariable-adjusted risk for CSVD. CONCLUSIONS: Individuals with a high baPWV had a higher prevalence of CSVD, independent of BP status. Higher arterial stiffness is likely to be a more important risk factor for CSVD than BP status in stroke-free individuals.

Reduced reactive hyperemia of the brachial artery in diabetic patients assessed by repeated measurements: The FMD-J B study.

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia.

The Association of Smoking and Hyperuricemia with Renal Arteriolosclerosis in IgA Nephropathy.

The combination effects of smoking (SMK) and hyperuricemia (HU) on renal arteriolosclerosis in patients with IgA nephropathy remain unknown. We examined the cross-sectional association between smoking (current or former) and renal arteriolar hyalinosis and wall thickening with or without HU [uric acid (UA) level ≥ 7 and ≥5 mg/dL in men and women] in 87 patients with IgA nephropathy who underwent renal biopsy. Arteriolar hyalinosis and wall thickening were assessed by the semiquantitative grading of arterioles. The SMK/HU subgroup showed the highest indices for hyalinosis and wall thickening, followed by the non-SMK/HU, SMK/non-HU, and non-SMK/non-HU subgroups. Multiple logistic analysis showed that SMK/HU, but not SMK/non-HU, was significantly associated with an increased risk of higher-grade renal arteriolar wall thickening. However, this did not occur with hyalinosis compared to non-SMK/non-HU. The adjusted odds ratio (95% confidence interval, p value) for SMK/HU was 12.8 (1.36-119, p < 0.05) for wall thickening. An association between SMK and renal arteriolar wall thickening might be prevalent only among patients with HU and in patients with IgA nephropathy. Further prospective studies are needed to determine whether patients with HU and SMK history exhibit rapid eGFR deterioration.

Factors associated with carotid intima-media thickness progression in patients with asymptomatic hyperuricemia: insights from the PRIZE study.

Hyperuricemia is reportedly associated with the progression of carotid intima-media thickness (IMT), a surrogate of cardiovascular risks and events. However, factors associated with carotid IMT progression in patients with asymptomatic hyperuricemia are largely unknown. In this post-hoc analysis of the multicenter, randomized PRIZE study, we analyzed data from a total of 326 patients who underwent carotid ultrasonography in a blind manner at baseline and 24 months to evaluate carotid IMT. Mean and maximum IMT at the common carotid artery (CCA) were measured at a central core laboratory. Factors related to the absolute change in mean and maximum IMT from baseline to 24 months were explored. Overall, the adjusted mean [0.0032 (- 0.0214 to 0.0278) mm] and maximum [0.0011 (- 0.0327 to 0.0351) mm] CCA-IMT increased numerically from baseline to 24 months. Multivariable analysis identified higher body mass index, history of atherosclerotic cardiovascular disease (ASCVD), and lower mean CCA-IMT at baseline as significant factors associated with the increase in mean CCA-IMT. In addition, older age and lower mean CCA-IMT at baseline were significant factors for an increased absolute change in the maximum CCA-IMT at 24 months. The present sub-analysis of the PRIZE study showed higher body mass index, history of ASCVD, and older age as significant factors associated with CCA-IMT progression in patients with asymptomatic hyperuricemia. These factors may be considered when identifying the possible risk of atherosclerotic progression in this specific patient population of hyperuricemia.Trial registration: UMIN000012911 and UMIN000041322.

Achievement rate of target blood pressure in patients with hypertension treated by hypertension specialists and non-specialists in a real-world setting.

Hypertension remains a major global healthcare issue. Considering that most Japanese patients with hypertension are managed by general practitioners, hypertension specialists should be involved in actual clinical practice. We investigated the blood pressure (BP), guidelines recommended for achievement rate of the target BP, and clinical variables of patients with hypertension treated by hypertension specialists and those treated by non-specialists in a real-world setting. Factors associated with the target BP achievement in this population were also investigated. Outpatients with hypertension from 12 medical facilities in Okinawa Prefecture were enrolled (n = 1469 [specialist group, 794; non-specialist group, 675]; mean age, 64.2 years; females, 45.8%). For all patients, BP and rate of the target BP achievement were 129.0 ± 15.5/74.6 ± 10.6 mmHg, and 51.8%, respectively. BP and the rate of target of BP achievement were 128.0 ± 15.1/73.4 ± 10.4 mmHg and 56.7% in the specialist group, and they were 130.1 ± 15.9/76.0 ± 10.8 mmHg and 46.1% in the non-specialist group. The urinary salt excretion and obesity rates were comparable between the specialist and non-specialist groups. Multivariable logistic analyses indicated that hypertension specialists and good medication adherence were positive factors, whereas obesity, chronic kidney disease, diabetes mellitus, and urinary salt excretion were inverse factors associated with target BP achievement in this population. Initiatives for salt reduction, medication adherence, and proper obesity management are crucial to improving BP management in patients with hypertension. Hypertension specialists are expected to play an essential role in them. For all patients, the target blood pressure (BP) achievement rate were 51.8%. Hypertension specialists and good medication adherence were positive factors in achieving target BP; conversely, obesity, diabetes mellitus, chronic kidney disease, and high urinary salt excretion were inverse factors in achieving target BP among patients with hypertension.

Urate-lowering drugs for chronic kidney disease with asymptomatic hyperuricemia and hypertension: a randomized trial.

INTRODUCTION: Xanthine oxidase (XO) inhibitors may slow down chronic kidney disease (CKD) progression. The comparative effectiveness of the different urate-lowering drugs is unknown. The aim of this study was to determine whether urate-lowering therapy with an XO inhibitor (febuxostat) and that with a uricosuric drug (benzbromarone) are comparable in slowing renal function decline in patients with CKD complicated with hypertension and hyperuricemia. METHODS: This study was an open-label randomized parallel-group clinical trial of 95 patients with stage G3 CKD in Japan. The patients had hypertension and hyperuricemia without a history of gout. They were randomized to receive febuxostat ( n  = 47; febuxostat group) or benzbromarone ( n  = 48; benzbromarone group) and titrated to reduce their serum urate level to <6.0 mg/dl. The primary end-point was change in estimated glomerular filtration rate (eGFR) from baseline to 52 weeks. The secondary end-points included changes in uric acid level, blood pressure, urinary albumin-to-creatinine ratio, and XO activity. RESULTS: Of the 95 patients, 88 (92.6%) completed the trial. There were no significant differences in change in eGFR (in ml/min/1.73 m 2 ) between the febuxostat [-0.23, 95% confidence interval (CI), -2.00 to 1.55] and benzbromarone (-2.18, 95% CI, -3.84 to -0.52) groups (difference, 1.95; 95% CI, -0.48 to 4.38; P  = 0.115) nor in the secondary end-points, except for XO activity. Febuxostat significantly reduced XO activity ( P  = 0.010). There were no significant differences in primary and secondary outcomes between the groups. A decrease in eGFR was significantly less in the febuxostat group than that of the benzbromarone group in the CKDG3a, but not in CKDG3b, in the subgroup analysis. There were no adverse effects specific to either drug. CONCLUSIONS: No significant differences were found in the effects of febuxostat and benzbromarone in renal function decline in stage G3 CKD complicated with hyperuricemia and hypertension.

Association between visceral fat mass and arterial stiffness among community-based screening participants.

Obesity and arterial stiffness are important risk factors for disease development. However, the relationship between obesity and arterial stiffness remains unclear. We examined the relationship of visceral fat area (VFA) and anthropometric obesity indices with arterial stiffness. This cross-sectional study was conducted among 2 789 participants (50% women) who underwent both VFA and brachial-ankle pulse wave velocity (baPWV) measurements during health checkups. Body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), a body shape index (ABSI), and body roundness index (BRI) were assessed. Visceral fat area was quantified using abdominal computed tomography. In women, VFA and all anthropometric indices positively correlated with age. In men, VFA, WHtR, ABSI, and BRI positively correlated with age; BMI inversely correlated with age; and WC did not correlate with age. Visceral fat area significantly correlated with anthropometric indices, but its correlation with ABSI was modest. In women, baPWV showed modest correlations with VFA and anthropometric indices and little correlations with BMI. In men, baPWV modestly correlated with VFA, WHtR, ABSI, and BRI, but inversely correlated with BMI and did not significantly correlate with WC. The multivariable-adjusted model showed that VFA and anthropometric indices, except ABSI, were inversely associated with baPWV; however, they were positively associated with metabolic syndrome components, including hypertension, dyslipidemia, and hyperglycemia. A body-shaped index weakly associated positively with baPWV, but misclassified individuals at risk for metabolic syndrome components. Visceral fat area and most anthropometric obesity indices were positively associated with hypertension, dyslipidemia, and hyperglycemia, but inversely associated with baPWV. Visceral fat area and anthropometric indices, except a body-shaped index, were inversely associated with brachial-ankle pulse wave velocity but positively associated with metabolic syndrome components, including hypertension, dyslipidemia, and hyperglycemia.

Association of blood pressure and hyperuricemia with proteinuria and reduced renal function in the general population.

This study aimed to investigate the effect of hyperuricemia (HU) on the association of systolic blood pressure (SBP) with the prevalence of proteinuria and low estimated glomerular filtration rate (eGFR) in the general population. This cross-sectional study enrolled 24,728 Japanese individuals (11,137 men and 13,591 women) who underwent health checkups in 2010. The prevalence of proteinuria and low eGFR (< 60 mL/min/1.73 m2) among participants classified according to serum uric acid levels and SBP was compared. HU was defined as serum uric acid levels higher than the 75th percentile in male and female participants (> 7.2 and > 5.4 mg/dL, respectively). The odds ratio (OR) for proteinuria increased with elevated SBP. This trend was significantly evident in participants with HU. Moreover, there was an interactive effect of SBP and HU on the prevalence of proteinuria in the male (Pfor interaction = 0.04) and female (Pfor interaction = 0.04) participants. Next, we evaluated the OR for low eGFR (< 60 mL/min/1.73 m2) with and without proteinuria based on the presence of HU. The multivariate analysis revealed that the OR for low eGFR with proteinuria increased with elevated SBP, but that for low eGFR without proteinuria decreased. These trends of OR tended to be prevalent among those with HU. The association between SBP and the prevalence of proteinuria was more pronounced in participants with HU. However, the association between SBP and decreased renal function with and without proteinuria might be different regardless of HU.

Febuxostat and renal outcomes: post-hoc analysis of a randomized trial.

Effect of urate-lowering on renal outcomes in patients at high-risk for cardiovascular disease with hyperuricemia without gout is not known. We conducted a post hoc analysis of a randomized trial (Febuxostat for Cerebral and　CaRdiorenovascular Events PrEvEntion StuDy [FREED]). The FREED trial enrolled 1070 asymptomatic, hyperuricemic elderly patients with at least one risk factor for cardiovascular disease, divided into febuxostat (n = 537) and non-febuxostat (n = 533) groups. We compared the effect of these treatments on renal outcomes including 40% decline in estimated glomerular filtration rate, new onset of microalbuminuria and development or worsening macroalbuminuria. The relative risk of developing or worsening macroalbuminuria was 56% lower in the febuxostat group (hazard ratio, 0.44; 95% CI, 0.24-0.82; P = 0.0098). However, the risks for other outcomes were comparable. In patients with asymptomatic hyperuricemia without gout, febuxostat reduces the risk of development or worsening of macroalbuminuria.

Study Protocol of Cardiac Rehabilitation for Acute Myocardial Infarction From the JROAD/JROAD-DPC Database　- JROAD-CR.

Background: Although cardiac rehabilitation (CR) has been reported to be effective for improving the prognosis of acute myocardial infarction (AMI), more patients must participate in CR during admission and as outpatients. Factors contributing to, and countermeasures against, the low CR participation rate need to be identified. Here we describe the protocol for a study designed to evaluate the effectiveness and problems of CR for AMI from the Japanese Registry of All Cardiac and Vascular Diseases (JROAD) and the JROAD-Japanese Diagnosis Procedure Combination system (JROAD-DPC) database. Methods and Results: This is a multicenter retrospective cohort study that will use the JROAD/JROAD-DPC database to evaluate the effectiveness of CR for AMI (JROAD-CR). Five thousand patients with AMI who were admitted to hospitals registered in the JROAD database in 2014 will be investigated with regard to their baseline characteristics, AMI severity and treatment, examination results, history of CR, and prognosis up to 5 years. We will also investigate the presence, quantity, and quality of CR, and evaluate the effectiveness of CR with respect to cost, exercise tolerance, and prognosis during admission and follow-up. Conclusions: The JROAD-CR study will seek to reveal the effectiveness of CR for AMI in the era of early reperfusion therapy and shortened hospitalization.

Anti-LGI4 Antibody Is a Novel Juxtaparanodal Autoantibody for Chronic Inflammatory Demyelinating Polyneuropathy.

BACKGROUND AND OBJECTIVES: The objective of this study was to discover novel nodal autoantibodies in chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We screened for autoantibodies that bind to mouse sciatic nerves and dorsal root ganglia (DRG) using indirect immunofluorescence (IFA) assays with sera from 113 patients with CIDP seronegative for anti-neurofascin 155 and anticontactin-1 antibodies and 127 controls. Western blotting, IFA assays using HEK293T cells transfected with relevant antigen expression plasmids, and cell-based RNA interference assays were used to identify target antigens. Krox20 and Periaxin expression, both of which independently control peripheral nerve myelination, was assessed by quantitative real-time PCR after application of patient and control sera to Schwann cells. RESULTS: Sera from 4 patients with CIDP, but not control sera, selectively bound to the nodal regions of sciatic nerves and DRG satellite glia (p = 0.048). The main immunoglobulin G (IgG) subtype was IgG4. IgG from these 4 patients stained a 60-kDa band on Western blots of mouse DRG and sciatic nerve lysates. These features indicated leucine-rich repeat LGI family member 4 (LGI4) as a candidate antigen. A commercial anti-LGI4 antibody and IgG from all 4 seropositive patients with CIDP showed the same immunostaining patterns of DRG and cultured rat Schwann cells and bound to the 60-kDa protein in Western blots of LGI4 overexpression lysates. IgG from 3 seropositive patients, but none from controls, bound to cells cotransfected with plasmids containing LGI4 and a disintegrin and metalloprotease domain-containing protein 22 (ADAM22), an LGI4 receptor. In cultured rat Schwann and human melanoma cells constitutively expressing LGI4, LGI4 siRNA effectively downregulated LGI4 and reduced patients' IgG binding compared with scrambled siRNA. Application of serum from a positive patient to Schwann cells expressing ADAM22 significantly reduced the expression of Krox20, but not Periaxin. Anti-LGI4 antibody-positive patients had a relatively old age at onset (mean age 58 years), motor weakness, deep and superficial sensory impairment with Romberg sign, and extremely high levels of CSF protein. Three patients showed subacute CIDP onset resembling Guillain-Barré syndrome. DISCUSSION: IgG4 anti-LGI4 antibodies are found in some elderly patients with CIDP who present subacute sensory impairment and motor weakness and are worth measuring, particularly in patients with symptoms resembling Guillain-Barré syndrome.

C-reactive Protein Levels and Cardiovascular Outcomes After Febuxostat Treatment in Patients with Asymptomatic Hyperuricemia: Post-hoc Analysis of a Randomized Controlled Study.

PURPOSE: Inflammation plays an important role in the initiation and progression of atherosclerosis, leading to poor clinical outcomes. Hyperuricemia is associated with the activation of the Nod-like receptor protein 3 inflammasome. Here, we investigated whether inhibition of inflammation using febuxostat lowered the risk of cardiovascular events. METHODS: This is a post-hoc analysis of the randomized trial, Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED). In total, 1067 patients (736 men and 331 women) were included in the analysis. We compared the serial changes in high-sensitivity C-reactive protein (hs-CRP) levels between febuxostat and non-febuxostat groups and assessed the correlation between the changes in uric acid (UA) and hs-CRP levels after febuxostat treatment. We also determined whether febuxostat could reduce a hard endpoint, defined as a composite of cardiovascular events and all-cause mortality. RESULTS: Serum UA levels in the febuxostat group were significantly lower than those in the non-febuxostat group after randomization (p < 0.05). However, hs-CRP levels were comparable between the two groups during the study. No significant correlation was observed between the changes in UA and hs-CRP levels after febuxostat treatment. The hard endpoints did not differ significantly between the two groups. In patients with baseline hs-CRP levels > 0.2 mg/dL or those administered 40 mg of febuxostat, the drug did not reduce hs-CRP levels or decrease the hard endpoint. CONCLUSION: Febuxostat reduced the UA levels but did not affect the CRP levels, and therefore may fail to improve cardiovascular outcomes after treatment. TRIAL REGISTRATION: ClinicalTrial.gov (NCT01984749). https://clinicaltrials.gov/ct2/show/NCT01984749.

Acquired factor V inhibitor with erythema and eosinophilia in a patient with end-stage renal disease.

Autoimmune factor V deficiency (AiFVD) is a rare bleeding disorder caused by factor V inhibitors. In this report, we present the case of an 89-year-old man who developed bleeding tendency during surgery to create arteriovenous fistula for hemodialysis. The bleeding tendency developed with prolongation of activated partial thromboplastin and prothrombin time, following drug-induced eruption and eosinophilia. Significant reduction in coagulation factor activity and inhibitory pattern in cross-mixing tests suggested the presence of inhibitors to coagulation factors. Subsequently, we detected a factor V inhibitor and anti-factor V autoantibodies was confirmed using enzyme-linked immunosorbent assay with purified human plasma factor V. Thus, the patient was 'definitely diagnosed' with AiFVD in accordance with the diagnostic criteria enacted by the Japanese Ministry of Health, Labor, and Welfare. The bleeding tendency improved after initiating oral prednisolone 50 mg (1 mg/kg) followed by normalization of activated partial thromboplastin time and prothrombin time at the 34th day. After improving the coagulation system prolongation, the inhibitor and autoantibodies has been eradicated. Since it is suggested that drug-induced immune response can cause AiFVD, AiFVD should be considered in patients who undergo hemodialysis and develop failure of hemostasis and drug-induced eruption.

Study Design of the Japanese Association of Cardiac Rehabilitation Registry (J-CARRY)　- Protocol for a Prospective, Multicenter, Open Registry.

Background: Guidelines for the prevention and management of cardiovascular disease (CVD) highly recommend cardiac rehabilitation (CR) on the basis of abundant evidence of its effectiveness. However, the current understanding and dissemination of CR in Japan are far from sufficient. Methods and Results: The Japanese Association of Cardiac Rehabilitation Registry (J-CARRY) is an academic society-led prospective multicenter observational registry conducted by the Registration and Facility Accreditation System Committee of the Japanese Association of Cardiac Rehabilitation. Data are collected prospectively using an electronic data capture system. Items related to patients' clinical background and CR, as well as mortality and major adverse cardiac and cerebrovascular events, will be collected in all cases. This Registry started in May 2014, and the number of participating medical institutions is expected to increase to >30; the targeted number of cases exceeded 3,000 per year as of April 30, 2022. Focusing on late Phase II data collection is a novel and significantly different approach compared with previous studies. The results of this study are currently under investigation. Conclusions: J-CARRY will provide real-world data regarding the current status and prognosis of CVD in patients who undergo Phase II CR in Japan.

Power spectral analysis of heart rate variability is useful as a screening tool for detecting sympathetic and parasympathetic nervous dysfunctions in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder that causes motor symptoms and autonomic dysfunction. However, autonomic function tests commonly performed in PD can only evaluate either the sympathetic or parasympathetic nervous system. Therefore, the purpose of this pilot study is to investigate whether power spectral analysis of heart rate variability could detect both sympathetic and parasympathetic nervous dysfunctions in patients with PD. METHODS: Seventeen patients with PD and 11 healthy control subjects underwent electrocardiogram recording for the spectral analysis of heart rate variability to obtain values of low-frequency (LF) (0.04-0.15 Hz) and high-frequency (HF) (0.15-0.4 Hz) powers. Moreover, we examined the coefficient of variation of R-R intervals (CVRR) as a parameter of parasympathetic function in all participants and performed 123I-metaiodobenzylguanidine scintigraphy to measure the heart-to-mediastinum ratio as a parameter of cardiac sympathetic innervation in patients with PD. RESULTS: The median age of control subjects and PD patients was 63 and 66 years old, respectively. The median Hoehn and Yahr scale of PD patients was stage 2. The values of resting LF and HF powers widely varied. The median values of resting LF powers of control subjects and PD patients and those of HF powers were 169 and 70 ms2, 279 and 65 ms2, respectively, the difference was statistically insignificant. Approximately 41% of patients with PD had values below the first quartile of resting LF powers (< 58 ms2) or HF powers (< 50 ms2); however, no control subject had such low values. Positive correlations were found between resting LF powers and heart-to-mediastinum ratios of 123I-metaiodobenzylguanidine uptake (r = 0.6) and between resting HF powers and CVRRs (r = 0.7). The resting LF power was also associated with CVRRs and constipation. Furthermore, a positive correlation was observed between resting LF powers and resting HF powers in patients with PD (r = 0.8). CONCLUSIONS: The power spectral analysis of heart rate variability may be useful as a screening tool for detecting autonomic dysfunctions by detecting low resting LF and HF powers in patients with PD. Sympathetic and parasympathetic nerves may be concurrently damaged in patients with PD.