Cognitive decline assessed using a brief screening test and cardiovascular and non-cardiovascular events in older patients with heart failure.

BACKGROUND: Although cognitive decline is recognized as a prognostic factor of heart failure (HF), the association of cognitive decline with specific clinical outcomes in patients with HF remains unclear. AIM: This study examines the relationship between cognitive decline using a brief test and cardiovascular and non-cardiovascular events in older patients with HF. METHODS: This study included 146 hospitalised patients with HF (median age, 77 years; male, 56.8%). Cognitive decline was defined as a score of ≤ 9 points on the Rapid Dementia Screening Test at the time of discharge. RESULTS: Cumulative incidence of cardiovascular events after discharge was twofold higher in patients with cognitive decline (Model 1 adjusted for basic characteristics, hazard ratio (HR) = 2.01, 95% confidence interval (CI): 0.94-4.31; Model 2 adjusted for potential confounders, HR = 2.30, 95% CI: 1.07-4.97). The association between cognitive decline and non-cardiovascular events decreased after adjusting for potential confounders. CONCLUSION: The results of this study emphasize the clinical utility of cognitive assessment for risk stratification of worsening cardiovascular conditions, including HF.

Association between the Big Five personality traits and medication adherence in patients with cardiovascular disease: A cross-sectional study.

The correlation between personality traits and health outcomes of primary prevention has been examined. However, there is a lack of evidence on the association between the assessment of personality traits and medication adherence for secondary prevention of cardiovascular disease. Thus, this study aimed to explore the association between personality traits and medication adherence, including compliance to prescribed medications and attitudes toward taking medications among patients with cardiovascular disease. This cross-sectional study included patients hospitalized for cardiovascular disease. We assessed the Big Five personality traits (conscientiousness, neuroticism, openness, extraversion, and agreeableness) of each patient at discharge using the Ten-Item Personality Inventory. In addition, we evaluated four aspects of medication adherence using a 12-item version of the medication adherence scale: medication compliance, collaboration with health care providers, willingness to access and use information on medication, and acceptance to take medication. Logistic regression analysis was performed to assess the correlation between the level of each medication adherence domain and each personality trait. The data of 128 patients with cardiovascular disease were analyzed. Higher conscientiousness score was significantly associated with a high compliance score (odds ratio per 1 point increase, 1.90; 95% confidence interval, 1.30-2.79; p = 0.001), high collaboration score (1.90; 1.31-2.76; p = 0.001), and high willingness score (1.74; 1.19-2.54; p = 0.004) after adjustment for potential confounders. Other combinations of personality traits and medication adherence showed no statistically significant correlations in multivariate analyses. The findings of this study suggest that assessment of personality traits, especially conscientiousness, may facilitate patient-medical staff communication for the improvement of medication adherence in patients with cardiovascular disease.

Association between Rapid Dementia Screening Test score and clinical events in elderly patients with cardiovascular disease: a retrospective cohort study.

AIMS: Cognitive decline is prevalent among patients with cardiovascular disease (CVD). Cognitive measurement has been considered as a standard assessment for secondary prevention; however, standard cognitive tests are sometimes infeasible due to time constraints. This study aimed to examine the association between the Rapid Dementia Screening Test (RDST), a brief screening tool for cognitive function, and clinical events in elderly patients with CVD. METHODS AND RESULTS: This retrospective cohort study included 140 hospitalized patients with CVD who participated in inpatient cardiac rehabilitation (median age, 75 years; male, 67%). Cognitive function for each patient was assessed using the RDST and Montreal Cognitive Assessment (MoCA), a standard test of mild cognitive impairment. The clinical events assessed as outcomes included all-cause mortality and unplanned rehospitalization. Receiver-operating characteristic (ROC) curve analysis showed similar predictive accuracy for the study outcome (P = 0.337) between the RDST [area under the curve, 0.651; 95% confidence interval (CI), 0.559-0.743] and MoCA (0.625; 0.530-0.720). The ROC analysis identified a cut-off value of 9 points for the RDST (sensitivity, 77.8%; specificity, 50.5%). Patients with RDST ≤9 showed a poor survival rate compared with those with ≥10 points (log-rank test, P = 0.002; hazard ratio, 2.94, 95% CI, 1.46-5.94). This result was consistent even after adjusting for potential confounders. CONCLUSION: The RDST was associated with clinical events in elderly patients with CVD and its predictive capability was comparable with that of MoCA, a standard cognitive test. The RDST may be useful in CVD as an alternative screening tool for cognitive decline.

Association among mild cognitive impairment, social frailty, and clinical events in elderly patients with cardiovascular disease.

BACKGROUND: Social support is considered a key factor for secondary prevention in patients with cardiovascular disease (CVD) and mild cognitive impairment (MCI). Recent studies have suggested the clinical importance of social frailty in CVD. OBJECTIVE: This study aimed to examine the association among coexistent MCI, social frailty, and clinical events in patients with CVD. METHODS: This study included 184 hospitalized elderly patients with CVD who participated in inpatient cardiac rehabilitation (median age, 75 years; male, 66.3%). MCI was defined as a Montreal Cognitive Assessment score of ≤25 points at discharge. Social frailty was defined using the Makizako criteria. Lack of caregiver support was also assessed as an indicator of poor social support. The Kaplan-Meier survival curve analysis and Cox regression analysis were conducted to evaluate the combined impact of MCI and social frailty or the lack of caregiver support on the composite endpoint of all-cause mortality or unplanned rehospitalization. RESULTS: The prevalence of MCI, social frailty, and lack of caregiver support were 65.2%, 70.7%, and 19.0%, respectively. There was a significant difference among subgroups by MCI and a lack of caregiver support (log-rank test, p = 0.018), and the MCI/non-caregiver group showed the worst prognosis (adjusted hazard ratio 3.96; 95% confidence interval 1.57-9.98). Likewise, MCI/social frailty group showed a significantly high event risk (3.94; 1.20-12.9) among the subgroups by MCI and social frailty. CONCLUSION: Our results highlight the clinical importance of assessing the presence of caregiver support along with conventional social frailty for patients with CVD and MCI.

Association between Big Five Personality Traits and Participation in Cardiac Rehabilitation in Japanese Patients with Cardiovascular Disease: A Retrospective Cohort Study.

Cardiac rehabilitation (CR) remains underutilised, despite its established clinical benefit. A personality traits assessment may help promote CR implementation, as they are determinants of health-related behaviour. This study aimed to examine the association between the Big Five personality traits and outpatient CR participation in patients with cardiovascular disease (CVD) after discharge. This retrospective cohort study included 163 patients aged <80 years, who underwent inpatient CR when hospitalised for CVD. The Big Five personality traits (conscientiousness, neuroticism, openness, extraversion, and agreeableness) of each patient were evaluated at discharge, using the Japanese version of the Ten-Item Personality Inventory. We examined the relationship of each personality trait with non-participation in outpatient CR and dropout within three months, using logistic regression analysis. Out of 61 patients who initiated the outpatient CR, 29 patients dropped out, leaving us with 32 subjects. The logistic regression analysis results showed that high conscientiousness was associated with non-participation in CR. The primary reason for this was a lack of motivation. Conversely, low conscientiousness and high openness were predictors of dropout. This study suggests that the assessment of the Big Five personality traits, especially conscientiousness and openness, can help improve health communication with patients to promote outpatient CR participation after discharge.

Usefulness of the Japanese version of Rapid Dementia Screening Test for mild cognitive impairment in older patients with cardiovascular disease: a cross-sectional study.

BACKGROUND: Cognitive decline is common among older patients with cardiovascular disease (CVD) and can decrease their self-management abilities. However, the instruments for identifying mild cognitive impairment (MCI) are not always feasible in clinical practice. Therefore, this study evaluated whether MCI could be detected using the Japanese version of the Rapid Dementia Screening Test (RDST-J), which is a simple screening tool for identifying cognitive decline. METHODS: This retrospective single-center study included patients who were ≥ 65 years old and hospitalized because of CVD. Patients with a pre-hospitalization diagnosis of dementia were excluded. Each patient's cognitive function had been measured at discharge using the RDST-J and the Japanese version of the Montreal Cognitive Assessment (MoCA-J), which is a standard tool for MCI screening. The correlation between the two scores was evaluated using Spearman's rank correlation coefficient. Receiver operating characteristic (ROC) analysis was also to evaluate whether the RDST-J could identify MCI, which was defined as a MoCA-J score of ≤ 25 points. RESULTS: The study included 78 patients (mean age: 77.2 ± 8.9 years). The RDST-J and MoCA-J scores were strongly correlated (r = 0.835, P < 0.001). The ROC analysis revealed that an RDST-J score of ≤ 9 points provided 75.4% sensitivity and 95.2% specificity for identifying MCI, with an area under the curve of 0.899 (95% CI: 0.835-0.964). The same cut-off value was identified when excluding patients with a high probability of dementia (RDST-J score of ≤ 4 points). CONCLUSIONS: The RDST-J may be a simple and effective tool for identifying MCI in older patients with CVD.

Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure.

Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer's ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer's ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93-365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P < 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan-Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7, n = 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7, n = 85) (log-rank, P < 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer's ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,; P < 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.

Prognostic Value of Delirium in Patients With Acute Heart Failure in the Intensive Care Unit.

BACKGROUND: Delirium is a common adverse event observed in patients admitted to the intensive care unit (ICU). However, the prognostic value of delirium and its determinants have not been thoroughly investigated in patients with acute heart failure (AHF). METHODS: We investigated 408 consecutive patients with AHF admitted to the ICU. Delirium was diagnosed by means of the Confusion Assessment Method for ICU tool and evaluated every 8 hours during the patients' ICU stays. RESULTS: Delirium occurred in 109 patients (26.7%), and the in-hospital mortality rate was significantly higher in patients with delirium (13.8% vs 2.3%; P < 0.001). Multivariate logistic regression analysis showed that delirium independently predicted in-hospital mortality (odds ratio [OR] 4.33, confidence interval [CI] 1.62-11.52; P = 0.003). Kaplan-Meier analysis showed that the 12-month mortality rate was significantly higher in patients with delirium compared with those without (log-rank test: P < 0.001), and Cox proportional hazards analysis showed that delirium remained an independent predictor of 12-month mortality (hazard ratio 2.19, 95% CI 1.49-3.25; P < 0.001). The incidence of delirium correlated with severity of heart failure as assessed by means of the Get With The Guidelines-Heart Failure risk score (chi-square test: P = 0.003). Age (OR 1.05, 95% CI 1.02-1.09; P = 0.003), nursing home residential status (OR 3.32, 95% CI 1.59-6.94; P = 0.001), and dementia (OR 5.32, 95% CI 2.83-10.00; P < 0.001) were independently associated with the development of delirium. CONCLUSIONS: Development of delirium during ICU stay is associated with short- and long-term mortality and is predicted by the severity of heart failure, nursing home residential, and dementia status.

Usefulness of the plasma branched-chain amino acid/aromatic amino acid ratio for predicting future cardiac events in patients with heart failure.

BACKGROUND: Heart failure (HF) is a hypercatabolic state that promotes branched-chain amino acid (BCAA) catabolic activity in the heart and skeletal muscle and reduces protein synthesis in the liver. Consequently, plasma free aromatic amino acids (AAAs) are increased. We investigated the prognostic value of the BCAA/AAA ratio (Fischer's ratio, FR) in patients with HF. METHODS: We enrolled 157 consecutive patients hospitalized for worsening HF (81 men, 76 women; mean ± SD age 75 ± 14 years). Plasma BCAA levels (i.e. total leucine, isoleucine, valine) and AAA levels (i.e. total tyrosine, phenylalanine) were measured at a time when the patients were stabilized (at discharge). FR was calculated as the combined plasma BCAA levels divided by the AAA level. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. RESULTS: The patients were divided into two groups based on the median FR (high-FR group: FR ≥ 3.1, n = 78; low-FR group: FR < 3.1, n = 79). Compared with the high-FR group, low-FR patients were older, had more prior hospitalizations for HF, lower albumin and cholinesterase levels, and lower geriatric nutritional risk index (GNRI). Altogether, 46 cardiac events occurred during the follow-up period (221 ± 135 days), including 14 cardiac deaths and 32 hospitalizations for worsening HF. In a Kaplan-Meier survival analysis, the low-FR group had more cardiac events than the high-FR group (log-rank, p < 0.001). The best cut-off value of FR was determined as 2.9 in the receiver operating characteristic curve for cardiac events. A multivariate Cox proportional hazards regression analysis showed that being in the low-FR group was an independent determinant of cardiac events from parameters of liver function tests and GNRI. CONCLUSIONS: FR might be useful for predicting future cardiac events in patients with HF, reflecting nutritional status which cannot be assessed by liver function tests and GNRI.

Neuromuscular electrical stimulation is feasible in patients with acute heart failure.

AIMS: In acute heart failure (AHF), immobilization is caused because of unstable haemodynamics and dyspnoea, leading to protein wasting. Neuromuscular electrical stimulation (NMES) has been reported to preserve muscle mass and improve functional outcomes in chronic disease. NMES may be effective against protein wasting frequently manifested in patients with AHF; however, whether NMES can be implemented safely without any adverse effect on haemodynamics has remained unknown. This study aimed to examine the feasibility of NMES in patients with AHF. METHODS AND RESULTS: Patients with AHF were randomly assigned to the NMES or control group. The intensity of the NMES group was set at 10-20% maximal voluntary contraction level, whereas the control group was limited at a visible or palpable level of muscle contraction. The sessions were performed 5 days per week since the day after admission. Before the study implementation, we set the feasibility criteria with following items: (i) change in systolic blood pressure (BP) > ±20 mmHg during the first session; (ii) increase in heart rate (HR) > +20 b.p.m. during the first session; (iii) development of sustained ventricular arrhythmia, atrial fibrillation (AF), and paroxysmal supraventricular tachycardia during all sessions; (iv) incidence of new-onset AF during the hospitalization period < 40%; and (v) completion of the planned sessions by >70% of patients. The criteria of feasibility were set as follows; the percentage to fill one of (i)-(iii) was <20% of the total subjects, and both (iv) and (v) were satisfied. A total of 73 patients (median age 72 years, 51 men) who completed the first session were analysed (NMES group, n = 34; control group, n = 39). Systolic BP and HR variations were not significantly different between two groups (systolic BP, P = 0.958; HR, P = 0.665). Changes in BP > ±20 mmHg or HR > +20 b.p.m. were observed in three cases in the NMES group (8.8%) and five in the control group (12.8%). New-onset arrhythmia was not observed during all sessions in both groups. During hospitalization, one patient newly developed AF in the NMES group (2.9%), and one developed AF (2.6%) and two lethal ventricular arrhythmia in the control group. Thirty-one patients in the NMES group (91%) and 33 patients in the control group (84%) completed the planned sessions during hospitalization. This study fulfilled the preset feasibility criteria. CONCLUSIONS: NMES is feasible in patients with AHF from immediately after admission.

Skeletal Muscle Pump Function Is Associated With Exercise Capacity in Patients With Heart Failure.

BACKGROUND: Skeletal muscle pump function may play a key role in maintaining cardiac output (CO), because of the lack of cardiac contractility reserve during incremental exercise in heart failure (HF) patients. We aimed to investigate the relationship between lower leg pump function and surrogate measures of CO during cardiopulmonary exercise testing (CPX) in HF patients.Methods and Results:Consecutive cardiac patients referred for CPX had their lower leg ejection fraction (LgEF) measured using strain gauge plethysmography as a marker of skeletal muscle pump function. We analyzed 88 patients, including 65 HF patients and 23 control subjects. Unlike the control subjects, LgEF correlated with peak oxygen consumption (V̇O2) and peak oxygen (O2) pulse (peak V̇O2: r=0.280, P=0.024; peak O2 pulse: r=0.540, P<0.001) in HF patients. Significant relationships among LgEF, peak V̇O2, and peak O2 pulse were observed in HF patients with reduced EF (peak V̇O2: r=0.367, P=0.026; peak O2 pulse: r=0.658, P<0.001), whereas LgEF in HF patients with preserved EF showed a weak correlation only with peak O2 pulse (r=0.407, P=0.032). LgEF was selected as an independent determinant of peak V̇O2 (ß=0.187, P=0.036) and peak O2 pulse (ß=0.520, P<0.001) in HF patients. CONCLUSIONS: Lower leg skeletal muscle function may contribute to exercise capacity through an indirect mechanism on cardiac function in HF.

Combinational risk factors of metabolic syndrome identified by fuzzy neural network analysis of health-check data.

BACKGROUND: Lifestyle-related diseases represented by metabolic syndrome develop as results of complex interaction. By using health check-up data from two large studies collected during a long-term follow-up, we searched for risk factors associated with the development of metabolic syndrome. METHODS: In our original study, we selected 77 case subjects who developed metabolic syndrome during the follow-up and 152 healthy control subjects who were free of lifestyle-related risk components from among 1803 Japanese male employees. In a replication study, we selected 2196 case subjects and 2196 healthy control subjects from among 31343 other Japanese male employees. By means of a bioinformatics approach using a fuzzy neural network (FNN), we searched any significant combinations that are associated with MetS. To ensure that the risk combination selected by FNN analysis was statistically reliable, we performed logistic regression analysis including adjustment. RESULTS: We selected a combination of an elevated level of γ-glutamyltranspeptidase (γ-GTP) and an elevated white blood cell (WBC) count as the most significant combination of risk factors for the development of metabolic syndrome. The FNN also identified the same tendency in a replication study. The clinical characteristics of γ-GTP level and WBC count were statistically significant even after adjustment, confirming that the results obtained from the fuzzy neural network are reasonable. Correlation ratio showed that an elevated level of γ-GTP is associated with habitual drinking of alcohol and a high WBC count is associated with habitual smoking. CONCLUSIONS: This result obtained by fuzzy neural network analysis of health check-up data from large long-term studies can be useful in providing a personalized novel diagnostic and therapeutic method involving the γ-GTP level and the WBC count.

The ratio of adiponectin to homeostasis model assessment of insulin resistance is a powerful index of each component of metabolic syndrome in an aged Japanese population: results from the KING Study.

We evaluated the ratio of adiponectin level to homeostasis model assessment of insulin resistance (A/H ratio) as a risk marker for metabolic syndrome (MetS) and each of its components. The A/H ratio may prove to be a powerful index for evaluation of risk for MetS and each of its components.

Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population.

Adiponectin is an adipocyte-derived protein that is down-regulated in obesity-linked disorders. Variants of the adiponectin gene (ADIPOQ) have been shown to affect adiponectin level. We have now examined the relation of polymorphisms of ADIPOQ to adiponectin concentration and to metabolic disorders in the Kita-Nagoya Genomic Epidemiology study, a population-based study of elderly Japanese. The genomic region including ADIPOQ was genotyped for 30 single nucleotide polymorphisms in 500 subjects of a screening population with the use of a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Four polymorphisms were then selected for genotyping in an additional 2797 subjects. Serum adiponectin level was negatively associated with metabolic abnormalities after adjustment for age and sex. The minor alleles of the rs1656930, Ile164Thr, and rs9882205 polymorphisms were associated with a low serum adiponectin level. Whereas the minor alleles of rs1656930 and rs9882205 were common (minor allele frequency of 6.2 and 38.5%, respectively), that of Ile164Thr was rare (0.9%). The minor allele of rs1656930 was positively associated with systolic blood pressure and the prevalence of hypertension. The association of rs1656930 with adiponectin level was replicated in an independent population. A subject with the 164Thr/Thr genotype had an extremely low serum adiponectin level (0.6 µg/ml) and the phenotype of metabolic syndrome. Our results suggest that a common variant of ADIPOQ, the minor allele of rs1656930, is associated with hypoadiponectinemia and hypertension. Screening for a common genetic background underlying low adiponectin levels might provide important information for assessment and management of metabolic disorders.