Randomized Controlled Trial of Cardiac Rehabilitation Using the Balance Exercise Assist Robot in Older Adults with Cardiovascular Disease.

BACKGROUND: Recent studies have investigated the effects of exercise on the functional capacity of older adults; training with a balance exercise assist robot (BEAR) effectively improves posture. This study compared the clinical safety and efficacy of training using BEAR video games to conventional resistance training in older adults with cardiovascular disease (CVD). METHODS: Ninety patients (mean age: 78 years) hospitalized due to worsening CVD were randomized to cardiac rehabilitation (CR) Group R (conventional resistance training) or Group B (training using BEAR). After appropriate therapy, patients underwent laboratory testing and functional evaluation using the timed up-and-go test (TUG), short physical performance battery (SPPB), and functional independence measure (FIM) just before discharge and 4 months after CR. The rates of CVD readmission, cardiac death, and fall-related fractures were monitored. RESULTS: BEAR had no adverse effects during exercise. At 4 months, TUG and SPPB improved significantly in both groups, with no significant difference between them. FIM motor and the Geriatric Nutritional Risk Index were significantly improved in Group B versus Group R. There was no significant difference in cardiac events and fall-related fractures between the two groups. CONCLUSION: CR with BEAR is safe and comparable to conventional resistance training for improving balance in older adults with CVD.

Evolution of a Large Language Model for Preoperative Assessment Based on the Japanese Circulation Society 2022 Guideline on Perioperative Cardiovascular Assessment and Management for Non-Cardiac Surgery.

Background: The Japanese Circulation Society 2022 Guideline on Perioperative Cardiovascular Assessment and Management for Non-Cardiac Surgery standardizes preoperative cardiovascular assessments. The present study investigated the efficacy of a large language model (LLM) in providing accurate responses meeting the JCS 2022 Guideline. Methods and Results: Data on consultation requests, physicians' cardiovascular records, and patients' response content were analyzed. Virtual scenarios were created using real-world clinical data, and a LLM was then consulted for such scenarios. Conclusions: Google BARD could accurately provide responses in accordance with the JCS 2022 Guideline in low-risk cases. Google Gemini has significantly improved its accuracy in intermediate- and high-risk cases.

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are associated with AF, but many senior individuals do not develop AF despite having multiple risk factors. This finding suggests that other factors may be involved in AF onset. This study aimed to identify upregulated genes in the peripheral blood and left atrium of patients with AF. These genes may serve as potential biomarkers to predict AF onset risk and its complications. METHODS: Gene expression data was analyzed from blood (n = 3) and left atrial samples (n = 15) of patients with AF and sinus rhythm. We evaluated the significant genes identified using p-value analysis of weighted average difference to confirm their rankings. We created figures for the genes using GeneMANIA and performed a functional analysis using Cytoscape3.10.1. Hub and bottleneck genes were identified based on degree and betweenness centrality. We used RefEx to confirm the organs in which the extracted genes were expressed. Heatmaps and Gene ontology term evaluation were performed to further elucidate the biological functions of the genes. RESULTS: We identified 12 upregulated genes (CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1, BNIP3L, PABPC1, YBX3, and S100A6) in both the blood and left atrium of patients with AF. We analyzed the gene functions using GeneMANIA and Cytoscape. The identified genes were involved in a variety of pathways, including lysosomal function and lipid and sphingolipid catabolism. Next, we investigated whether the 12 identified genes identified were systemically expressed or had high organ specificity. Finally, Reference expression (RefEx) was used to analyze the gene expression levels in various tissues. Four genes; FTL, ASAH1, S100A6, and PABPC1, were highly expressed in the normal heart tissue. Finally, we evaluated the expression levels of the 12 genes in the blood of patients with AF using a heatmap. Our findings suggest that the 12 genes identified in this study, especially the lysosome-related genes (FTL and ASAH1), may be involved in AF pathogenesis. CONCLUSION: Lysosome-related genes may be important to understand the AF pathophysiology and to develop AF-related future studies.

Transcriptome Discovery of Genes in the Three Phases of Autophagy That Are Upregulated During Atrial Fibrillation.

Background: Autophagy may contribute to the maintenance of atrial fibrillation (AF), but no previous study has concurrently surveyed all 3 phases of autophagy, namely autophagosome formation, lysosome formation, and autophagosome-lysosome fusion. Here we aimed to identify disorders involving various phases of autophagy during AF. Methods and Results: We used bioinformatic techniques to analyze publicly available DNA microarray datasets from the left atrium (LA) and right atrium (RA) of 7 patients with AF and 6 patients with normal sinus rhythm who underwent valvular surgeries. We compared gene expression levels in the LA (AF-LA) and RA of patients with AF with those in the LA and RA of patients with normal sinus rhythm. Several differentially expressed genes in the AF-LA sample were significantly associated with the Gene Ontogeny term 'Autophagy', indicating that the expression of autophagic genes was specifically altered in this dataset. In particular, the expression of genes known or suspected to be involved in autophagosome formation (autophagy related 5 [ATG5], autophagy related 10 [ATG10], autophagy related 12 [ATG12], and light chain 3B [LC3B]), lysosome formation (lysosomal associated membrane protein 1 [LAMP1] and lysosomal associated membrane protein 2 [LAMP2]), and autophagosome-lysosome fusion (synaptosome associated protein 29 [SNAP29], SNAP associated protein [SNAPIN], and syntaxin 17 [STX17]) was significantly upregulated in the LA-AF dataset. Conclusions: Autophagy is activated excessively in, and may perpetuate, AF.

Septal E/e' Ratio Is Associated With Cerebral White Matter Hyperintensity Progression in Young-Old Hypertensive Patients.

Background: The incidence of hypertension increases with age, as does that of brain abnormalities associated with cerebral pathologic and functional degeneration. Little is known about the relationship between hypertension-related cardiac changes and cerebral pathologic degeneration. We examined the relationship between left ventricular (LV) diastolic dysfunction and cerebral white matter hyperintensity (WMH) progression in young-old hypertensive patients. Methods and Results: This single-center prospective longitudinal observational study included 156 individuals aged 65-75 years with well-controlled hypertension, normal LV contraction, and no history of symptomatic heart failure. WMH was quantified on brain magnetic resonance imaging (MRI). The primary outcome was the rate of WMH volume progression between the baseline and follow-up MRI (∆WMH). Participants were classified into tertiles on the basis of ∆WMH (small, medium, and large ∆WMH). The mean (±SD) age at recruitment was 69.6±2.8 years, and the mean follow-up period was 4.6 years. The ratio of early diastolic mitral inflow velocity to early diastolic septal mitral annulus velocity (septal E/e') was significantly higher in the large ∆WMH group than in the small and medium ∆WMH groups. On multiple regression analysis, septal E/e' was significantly positively associated with square-root-transformed ∆WMH (ß=0.457, P<0.001). Conclusions: Septal E/e' was significantly positively associated with the rate of progression of WMH volume, suggesting that LV diastolic dysfunction is associated with the progression of abnormal brain aging.

Life-Space Activities Are Associated with the Prognosis of Older Adults with Cardiovascular Disease.

Life-space activities are a measure of daily activity level. Here, we examined the association between life-space activities and prognosis in 129 cardiovascular diseases (CVD) patients 65 years of age or older (average age, 79.2 ± 7.6 years; mean left ventricular ejection fraction, 56.7 ± 13.2%) who had been admitted to our hospital for worsening CVD. Subjects were followed, and the primary endpoints were cardiovascular hospitalization and cardiovascular death. Receiver operating characteristic analysis produced a cutoff value for life-space assessment (LSA) score for increased risk of cardiovascular hospitalization for two years of 53.0 points (sensitivity, 55.9%; specificity, 82.1%). Kaplan−Meier analysis using this cutoff value revealed that the rates of cardiovascular hospitalization and cardiovascular death were significantly higher in subjects with an LSA score below the cutoff than in those with a score above the cutoff (both p < 0.001). Cox proportional analysis revealed that low LSA score was independently associated with cardiovascular hospitalization (HR, 2.540; 95% CI, 1.135−5.680; p = 0.023) and cardiovascular death (HR, 15.223; 95% CI, 1.689−137.180; p = 0.015), even after adjusting for age, sex, left ventricular ejection fraction, and log-transformed brain natriuretic peptide level. Thus, life-space activities are associated with prognosis in older adults with CVD.

Benefits of a Balance Exercise Assist Robot in the Cardiac Rehabilitation of Older Adults with Cardiovascular Disease: A Preliminary Study.

We examined whether adding robot-supported balance exercises to cardiac rehabilitation improves the ability to balance in older adults with cardiovascular disease (CVD). We conducted a prospective study in 52 older adults who had been hospitalized for worsening CVD. Once weekly for four months, for a total of sixteen sessions as outpatients, the subjects used a Balance Exercise Assist Robot (BEAR) to perform balance exercises and an ergometer for aerobic exercises. Participants' mean age was 76.9 ± 6.8 years (range, 65−95 years), and their mean brain natriuretic protein level was 164.0 ± 190.0 pg/mL. After the intervention, participants showed significant improvements in gait speed (before, 1.06 ± 0.33 m/s; after, 1.23 ± 0.30 m/s; p < 0.001), Short Physical Performance Battery score (before, 10.02 ± 2.25; after, 10.88 ± 1.79; p ˂ 0.001), timed up-and-go (before, 11.11 ± 5.07 s; after, 9.45 ± 3.45 s; p ˂ 0.001), and knee extension (before, 26.97 ± 11.78 kgf; after, 30.13 ± 13.04 kgf; p = 0.001). Cardiac rehabilitation including exercises using BEAR improved physical functioning and the ability to balance in older adults with CVD. Frail and prefrail patients improved, whereas robust ones did not change.

Systematic Review of the Effectiveness of Community Intervention and Health Promotion Programs for the Prevention of Non-Communicable Diseases in Japan and Other East and Southeast Asian Countries.

Background: Non-communicable diseases (NCDs) are the leading cause of death worldwide. However, current evidence regarding the efficacy and cost-effectiveness of community intervention and health promotion programs for NCDs, specifically hypertension, obesity, diabetes, and dyslipidemia, in East and Southeast Asia has not yet been systematically reviewed. We systematically reviewed the literature from East and Southeast Asian countries to answer 2 clinical questions: (1) do health promotion programs for hypertension, obesity, diabetes, and dyslipidemia reduce cardiovascular events and mortality; and (2) are these programs cost-effective? Methods and Results: Electronic literature searches were performed across Medline, Cochrane Library, and Ichushi using key words and relevant subject headings related to randomized controlled trials, comparative studies, quasi-experimental studies, or propensity score matching that met eligibility criteria that were defined for each question. In all, 3,389 records were identified, of which 12 full-text articles were reviewed. Three papers were from Japan, 7 were from China/Hong Kong Special Administrative Region, and 2 were from South Korea. None were from Southeast Asia. Four papers examined the effect of community intervention or health promotion on the incidence of cardiovascular events or mortality. Eight studies examined the cost-effectiveness of interventions. Conclusions: The literature review revealed that community intervention and health promotion programs for the control of NCDs are a cost-effective means of reducing cardiovascular events and mortality in East Asian countries.

Composite Biomarkers for Assessing Frailty Status in Stable Older Adults With Cardiovascular Disease.

Background: The relationship between frailty status and laboratory measurements in cardiovascular disease (CVD) remains unclear. We investigated which laboratory measurements indicated frailty in stable older CVD patients. Methods and Results: One-hundred thirty-eight stable older CVD patients were evaluated by laboratory measurements, with frailty assessed using the Kihon Checklist (KCL). Laboratory measurements were compared between frail and non-frail groups. Across the entire cohort, mean age was 81.7 years, mean left ventricular ejection fraction was 57.8%, and mean plasma B-type natriuretic peptide was 182 pg/mL. KCL scores were used to divide patients into non-frail (n=43; KCL <8) and frail (n=95; KCL ≥8) groups. Serum iron was significantly lower in the frail than non-frail group (mean [±SD] 61.2±30.3 vs. 89.5±26.1 µg/dL, respectively; P<0.001). Blood urea nitrogen (BUN; 27.3±16.5 vs. 19.7±8.2 mg/dL; P=0.013) and C-reactive protein (CRP; 1.05±1.99 vs. 0.15±0.21 mg/dL; P=0.004) were significantly higher in the frail than non-frail group. Multivariate analysis revealed that serum iron, CRP, and BUN were significant independent predictors of frailty (ß=-0.069, 0.917, and 0.086, respectively). Conclusions: Frailty status was significantly associated with iron, CRP, and BUN in stable older CVD patients. Composite biomarkers (inflammation, iron deficiency, and renal perfusion) may be useful for assessing frailty in these patients.

Exercise Capacity and Frailty Are Associated with Cerebral White Matter Hyperintensity in Older Adults with Cardiovascular Disease.

Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO2 was 15.2 ± 3.7 mL kg-1 minute-1 (mild group), 12.9 ± 3.5 mL kg-1 min-1 (moderate), and 11.4 ± 2.3 mL kg-1 minute-1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO2. WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

Short physical performance battery score and driving a car are independent factors associated with life-space activities in older adults with cardiovascular disease.

AIM: Decreased use of life spaces, as reflected in decreased Life-Space Assessment (LSA) scores, is associated with poor prognosis in older adults. The purpose of this study was to examine factors affecting the extent of life-space activities in older adults with cardiovascular disease. METHODS: We carried out a prospective observational study in 98 older adults (minimum age 65 years; mean age 79.5 ± 7.4 years) who were admitted to our hospital due to cardiovascular disease. Once their medical condition was stable, they underwent cardiopulmonary exercise testing, echocardiography and physical evaluation, and completed questionnaires. RESULTS: The LSA score was significantly associated with the ability to drive a car (driving 95.1 ± 21.1 points, not driving 60.4 ± 30.3 points, P < 0.001). In addition, LSA was significantly correlated with age; peak VO2 ; brain natriuretic peptide; and Short Physical Performance Battery, Geriatric Depression Scale and Mini-Mental State Examination scores. In a multiple regression analysis, Short Physical Performance Battery and driving a car were significantly associated with LSA (ß = 0.28, ß = 0.37, respectively). CONCLUSION: Assessment of motor function and social factors in addition to clinical cardiac function might be important to understand the complete context of life-space activity in older adults with cardiovascular disease. Geriatr Gerontol Int 2021; 21: 900-906.

Peak Work Rate during Exercise Could Detect Frailty Status in Elderly Patients with Stable Heart Failure.

The Kihon Checklist (KCL) is a reliable tool for determining frailty status in the elderly. However, there is no information in the literature about the relationship between frailty status and exercise capacity. Here, we examined the associations between cardiopulmonary exercise testing parameters and frailty status in elderly patients with stable heart failure (HF).Ninety-two elderly patients with stable HF were evaluated using cardiopulmonary exercise testing and the KCL. A KCL score of 0-3 was classified as robust, 4-7 as pre-frail, and ≥ 8 as frail.Mean age, peak VO2, and KCL score were 81.7 years, 13.2 mL/kg/minute, and 10.7, respectively. KCL score was significantly correlated with peak VO2 (r = -0.527, P < 0.001) and peak work rate (r = -0.632, P < 0.001). In patients with frailty (n = 63), the peak work rate (WR) was significantly lower than it was in patients without frailty (n = 29; 39.9 versus 69.5 W, respectively; P < 0.001). Multivariate analysis revealed that peak WR and peak systolic blood pressure were significant, independent predictors of frailty (ß = -0.108 and -0.045, respectively). In a diagnostic performance plot analysis, a cutoff value for peak WR of 51.9 W was the best predictor of frailty.Frailty status was significantly associated with peak WR and peak systolic blood pressure in elderly patients with stable HF. Therefore, cardiopulmonary exercise testing may be useful for assessing frailty status in this patient population.

Association of Glucose Fluctuations with Sarcopenia in Older Adults with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus accelerates loss of muscle mass and strength. Patients with Alzheimer's disease (AD) also show these conditions, even in the early stages of AD. The mechanism linking glucose management with these muscle changes has not been elucidated but has implications for clarifying these associations and developing preventive strategies to maintain functional capacity. This study included 69 type 2 diabetes patients with a diagnosis of cognitive impairment (n = 32) and patients with normal cognition (n = 37). We investigated the prevalence of sarcopenia in diabetes patients with and without cognitive impairment and examined the association of glucose alterations with sarcopenia. Daily glucose levels were evaluated using self-monitoring of blood glucose, and we focused on the effects of glucose fluctuations, postprandial hyperglycemia, and the frequency of hypoglycemia on sarcopenia. Diabetes patients with cognitive impairment displayed a high prevalence of sarcopenia, and glucose fluctuations were independently associated with sarcopenia, even after adjusting for glycated hemoglobin A1c (HbA1c) levels and associated factors. In particular, glucose fluctuations were significantly associated with a low muscle mass, low grip strength, and slow walking speed. Our observation suggests the importance of glucose management by considering glucose fluctuations to prevent the development of disability.

Postprandial Hyperglycemia Is Associated With White Matter Hyperintensity and Brain Atrophy in Older Patients With Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus is associated with neurodegeneration and cerebrovascular disease. However, the precise mechanism underlying the effects of glucose management on brain abnormalities is not fully understood. The differential impacts of glucose alteration on brain changes in patients with and without cognitive impairment are also unclear. This cross-sectional study included 57 older type 2 diabetes patients with a diagnosis of Alzheimer's disease (AD) or normal cognition (NC). We examined the effects of hypoglycemia, postprandial hyperglycemia and glucose fluctuations on regional white matter hyperintensity (WMH) and brain atrophy among these patients. In a multiple regression analysis, postprandial hyperglycemia was independently associated with frontal WMH in the AD patients. In addition, postprandial hyperglycemia was significantly associated with brain atrophy, regardless of the presence of cognitive decline. Altogether, our findings indicate that postprandial hyperglycemia is associated with WMH in AD patients but not NC patients, which suggests that AD patients are more susceptible to postprandial hyperglycemia associated with WMH.

Impact of night-time blood pressure on cerebral white matter hyperintensity in elderly hypertensive patients.

AIM: Cerebral white matter hyperintensity (WMH) is highly prevalent in the elderly population, and increases the risk of dementia and stroke. We investigated the relationship between ambulatory blood pressure monitoring levels and quantitatively measured WMH volumes among elderly hypertensive patients with well-controlled blood pressure (BP) to re-evaluated effective hypertension management methods to prevent the progression of WMH. METHODS: Participants comprised 84 hypertensive patients aged between 65 and 75 years without symptomatic heart failure, ischemic heart disease, atrial fibrillation, stroke or cognitive dysfunction. RESULTS: Linear regression analysis showed that office BP was not associated with WMH volume increases. Raised night-time systolic BP (P = 0.013) were associated with greater WMH volumes during ambulatory blood pressure monitoring. To clarify the effect of asleep systolic BP on WML volume, we then classified patients into two systolic BP groups as follows: <125 mmHg (n = 47) and ≥125 mmHg (n = 37). Baseline characteristics were almost similar in both groups, except the dipper type of circadian BP variation was significantly common in the group with night-time systolic BP <125 mmHg. However, WMH volume was greater in the group with night-time systolic BP ≥125 mmHg than that in the <125 mmHg group (9.0 ± 8.4 mL vs 4.1 ± 4.3 mL, P = 0.015). CONCLUSION: Higher night-time systolic BP levels were observed to contribute greater WMH volumes in elderly hypertensive patients. To prevent the progression of WMH, controlling BP on the basis of ambulatory blood pressure monitoring is important.

Left ventricular diastolic dysfunction is associated with cerebral white matter lesions (leukoaraiosis) in elderly patients without ischemic heart disease and stroke.

AIM: Cerebral white matter lesions (WML) are known to increase with age, as is left ventricular (LV) diastolic dysfunction with normal contraction. Although aging is a common risk factor, the link between these diseases is not fully understood. The aim was to clarify this relationship, using the ratio between early diastolic mitral inflow and early diastolic mitral annular tissue velocity (E/E'). E/E' measured by tissue Doppler echocardiography offers an indicator of the severity of LV diastolic dysfunction, reflecting both diastolic LV stiffness and diastolic LV filling pressure. METHODS: Participants comprised 75 patients aged between 65 and 75 years with normal LV contraction and no signs or history of symptomatic heart failure, ischemic heart diseases, atrial fibrillation, stroke, or cognitive dysfunction. The volume of WML was quantified on brain magnetic resonance imaging. RESULTS: The participants were classified into three groups: Low E/E', E/E' ≤ 8; Middle E/E', 8 < E/E' < 15; and High E/E', E/E' ≥ 15. WML volume was 3.6 ± 3.0 mL in Low E/E', 5.4 ± 6.5 mL in Middle E/E' and 12.0 ± 11.0 mL in High E/E', increasing significantly with increased diastolic LV stiffness (Low vs High, P = 0.034; Middle vs High, P = 0.016). Linear regression analysis showed the positive association between the volume of WML and E/E' ratio (r = 0.377, P = 0.0009). CONCLUSIONS: This investigation identified an association between LV diastolic dysfunction and WML. Further investigations are required to clarify whether there is a direct association between the two diseases.

BDNF-mediated cerebellar granule cell development is impaired in mice null for CaMKK2 or CaMKIV.

The Ca(2+)/calmodulin-activated kinases CaMKK2 and CaMKIV are highly expressed in the brain where they play important roles in activating intracellular responses to elevated Ca(2+). To address the biological functions of Ca(2+) signaling via these kinases during brain development, we have examined cerebellar development in mice null for CaMKK2 or CaMKIV. Here, we demonstrate that CaMKK2/CaMKIV-dependent phosphorylation of cAMP response element-binding protein (CREB) correlates with Bdnf transcription, which is required for normal development of cerebellar granule cell neurons. We show in vivo and in vitro that the absence of either CaMKK2 or CaMKIV disrupts the ability of developing cerebellar granule cells in the external granule cell layer to cease proliferation and begin migration to the internal granule cell layer. Furthermore, loss of CaMKK2 or CaMKIV results in decreased CREB phosphorylation (pCREB), Bdnf exon I and IV-containing mRNAs, and brain-derived neurotrophic factor (BDNF) protein in cerebellar granule cell neurons. Reexpression of CaMKK2 or CaMKIV in granule cells that lack CaMKK2 or CaMKIV, respectively, restores pCREB and BDNF to wild-type levels and addition of BDNF rescues granule cell migration in vitro. These results reveal a previously undefined role for a CaMKK2/CaMKIV cascade involved in cerebellar granule cell development and show specifically that Ca(2+)-dependent regulation of BDNF through CaMKK2/CaMKIV is required for this process.

Noninvasive evaluation of the time course of change in cardiac function in spontaneously hypertensive rats by echocardiography.

The spontaneously hypertensive rat (SHR) has been well established as a suitable model for studies of hypertension, but little is known about the processes of left ventricular (LV) hypertrophy and the changes in cardiac function in this model. The present study was designed to provide a noninvasive evaluation of the time-dependent alteration of cardiac function in male SHR at 4 to 24 weeks of age and age-matched Wistar-Kyoto rats (WKY). Echocardiographic studies were performed after blood pressure (BP) and heart rate (HR) were measured by a tail-cuff method. The body weight (BW) of SHR was lighter than that of WKY at all ages, and HR was consistently lower, with significantly elevated systolic BP from 4 weeks of age. In the echocardiographic study, LV mass at 4 weeks of age was similar between WKY and SHR, although the ratio of LV mass to BW was higher in SHR than WKY. The ejection fraction, fractional shortening (FS) and midwall FS did not differ between the two groups at 4 weeks, but after 8 weeks, these parameters were decreased in the SHR. The deceleration time was prolonged in SHR after 16 weeks and the E/A ratio was lowered at 12 weeks. We also analyzed the expression levels of calcineurin, which were found to be increased in both groups with age. These results suggest that calcineurin does not play a major role in the development of LV hypertrophy. Thus, in SHR, cardiac hypertrophy develops by 4 weeks of age, and systolic and diastolic dysfunction is evident at 2 to 3 months.