Incidence and characteristics of spontaneous platelet macro-aggregation in acute ischemic stroke.

Spontaneous platelet aggregation is a trigger for additional development of larger thrombi. Micro-aggregation is observed in 10% of diabetes approximately and blocked by P2Y12 inhibitors, whereas macro-aggregation is associated with overexpression of platelet α2-adrenoreceptors and is not blocked by conventional anti-platelet medicines. We examined the incidence of spontaneous platelet macro-aggregation (SPMA) in acute ischemic stroke and analyzed its clinical characteristics. Out of 665 consecutive acute ischemic strokes, SPMA was found in 10 patients (1.5%, one tenth of micro-aggregation) despite no detection in 588 control subjects. Types of ischemic stroke were 4 atherothrombotic, 4 cardioembolic, and 2 lacunar strokes. Stroke with SPMA exhibited higher (worse) values of modified Rankin Scales (mRS) at discharge (3.00 ± 0.53 vs 1.93 ± 0.07, p = 0.042 by Wilcoxon) compared with stroke without SPMA despite no difference at admission. The proportion of patients who were functionally independent (score 0-2 on the mRS) at discharge was lower in stroke with SPMA compared with stroke without SPMA (p < 0.05 by chi-square test; OR 3.60, 95% CI 1.08-12.03; RR 2.04, 95% CI 1.05-2.86). It was intriguing that severe (high magnitude) SPMA was observed in 4 atherothrombotic stroke. Although anti-platelet therapy underwent, the proportion of atherothrombotic patients who were functionally improved and independent at discharge was lower in the presence of SPMA compared with the absence of SPMA (p < 0.05 by chi-square test). The patients with SPMA were more likely to be older, having major disabilities, being less functionally improved during hospitalization, and being less functionally independent at discharge.

Serum Albumin, Body Mass Index, and Preceding Xa and P2Y12 Inhibitors Predict Prognosis of Recurrent Ischemic Stroke.

BACKGROUND: A third to half of recurrent stroke occur while on antiplatelet therapy, but no study has explored factors relating to prognosis of recurrent ischemic stroke. This study aimed to clarify the risk factors to determine the clinical outcome of recurrent ischemic stroke. METHODS: A total of 1,333 consecutive acute ischemic stroke patients (first n = 492, recurrent n = 841) were enrolled. We explored factors influencing the modified Rankin Scales (mRS) at discharge that included platelet aggregability, preceding medicines, and well-known risks of biochemical data using Chi-square test or Fisher's exact probability test. RESULTS: As to preceding medicines, the proportion of patients who were functionally independent (mRS 0-2) at discharge was higher in preceding P2Y12 inhibitor that suppressed ADP- and collagen-induced macro-aggregation of platelet and Xa inhibitor or warfarin in cardioembolic stroke, but lower in P2Y12 inhibitor and Xa inhibitor or warfarin in lacunar stroke compared with no medicine. Regardless of LDL-cholesterol and HA1c, the mRS at discharge ≤ 2 was increased in the third tertile of serum albumin and body mass index (BMI) in atherothrombotic stroke; serum albumin and high-density lipoprotein cholesterol (HDL-C) in lacunar stroke; and serum albumin, HDL-C and BMI in cardioembolic stroke. Logistic regression analysis identified the following independent predictors for clinical outcome: serum albumin, HDL-C, BMI, and preceding Xa inhibitor and P2Y12 inhibitor. CONCLUSION: Regardless of well-known risk factors such as diabetes and high LDL-C, preceding treatment for Xa inhibitor or P2Y12 inhibitor, serum albumin, HDL-C, and BMI were associated with prognosis in recurrent ischemic stroke.

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina.

Calcium antagonists are used for coronary spastic angina (CSA) treatment. We previously identified a phospholipase C (PLC) -δ1 gene variant that results in enhanced PLC activity in patients with CSA and developed a CSA animal model by generating vascular smooth muscle cell-specific human variant PLC-δ1 overexpression (PLC-TG) mice. In this study, we investigated the molecular mechanism of CSA using the PLC-TG mice and the inhibitory effect of a calcium antagonist, diltiazem hydrochloride (DL).We treated the PLC-TG and wild-type (WT) mice with oral DL or trichlormethiazide (TM) (control) for 2 weeks. Ergometrine injection-induced coronary spasm was observed on the electrocardiogram in all 5 PLC-TG mice treated with TM, but only in 1 of 5 PLC-TG mice treated with DL. Voltage-dependent calcium channel (Cav1.2) phosphorylation and protein kinase C (PKC) activity were enhanced in the aortas of PLC-TG mice treated with TM. DL treatment significantly inhibited Cav1.2 phosphorylation and PKC activity. Although total Cav1.2 expression was similar between WT and PLC-TG mice treated with TM, DL treatment significantly increased its expression in PLC-TG mice. Furthermore, its expression remained high after DL discontinuation. DL and PKC inhibitor suppressed intracellular calcium response to acetylcholine in cultured rat aortic smooth muscle cells transfected with variant PLC-δ1.These results indicate that enhanced PLC activity causes coronary spasm, presumably via enhanced Cav1.2 phosphorylation and PKC activity, both of which were inhibited by DL. Enhanced total Cav1.2 expression after DL discontinuation and high PKC activity may be an important mechanism underlying the calcium antagonist withdrawal syndrome.

Psychological and Antibacterial Effects of Footbath Using the Lindera umbellata Essential Oil.

Lindera umbellata (Lu) essential oil primarily contains linalool and has relaxation properties. We investigated the psychological and antibacterial effects of footbath with Lu essential oil. The participants included 20 women without medical history and received two intervention plans: footbath without any essential oil and footbath using Lu essential oil. Next, questionnaires regarding impressions and mood states were provided for them to answer. In addition, their autonomic nervous system activity was measured, and the aerobic viable of count on the feet was determined. The high-frequency value reflecting the parasympathetic nervous system activity significantly increased after footbath using Lu essential oil. In the questionnaire about the mood states, the subscale scores of tension-anxiety, depression, fatigue, and confusion after intervention were lower than those before intervention regardless of the use of the essential oil. Conversely, the anger-hostility score decreased only in the group using Lu essential oil. Furthermore, the decrease in aerobic viable count after intervention was not significantly different between the two groups. Footbath using Lu essential oil increased the parasympathetic nervous system activity and relieved anger. Taken together, we suggest that footbath using Lu essential oil has a relaxation effect.

Factors Influencing Quality of Life in Stroke Patients: Focus on Eating Habits.

BACKGROUND: Adherence to healthy lifestyle factors has been shown to improve outcomes after stroke. This study aimed to identify lifestyle factors about eating habits that may affect the quality of life (QOL) in elderly stroke patients. METHODS: Fifty elderly patients with a first-ever stroke were enrolled. QOL was assessed by the Stroke and Aphasia QOL Scale-39-J. Lifestyle factors about eating habits were collected using questionnaires (Questions 1-17) for the intake of salt, calcium, magnesium, potassium, taurine, fiber, and protein, and the frequency of breakfast. RESULTS: QOL of physical, communication, and psychosocial subdomains was better in the low (healthy) tertile of poststroke eating habits (Questions 1-17) compared with the high tertile of post-troke eating habits (Questions 1-17). This relationship appeared in eating habits except for salt intake but not in eating habits of salt intake and directly measured salt intake. Compared with prestroke eating habits score, poststroke eating habits score was decreased (improved) in 36 patients concerning eating habits of salt intake, but only in 12 patients concerning eating habits except for salt intake (P < .05 by chi-square test). Poststroke eating habits of calcium and magnesium were associated with better psychosocial QOL and better physical or energy QOL, respectively. CONCLUSIONS: Poststroke eating habits of calcium and magnesium were associated with QOL in elderly patients with a first-ever stroke. Since eating habits except for salt intake was poorly improved after stroke, intensive interventions regarding eating habits might be important.

Collagen-Induced Platelet Aggregates, Diabetes, and Aspirin Therapy Predict Clinical Outcomes in Acute Ischemic Stroke.

BACKGROUND: Aggregation of platelets is a trigger for additional development of larger thrombi. This study aimed to identify factors that may affect platelet aggregability and their role in clinical outcomes in acute ischemic stroke. METHODS: Consecutive acute ischemic stroke patients (n = 352) who were transferred within 24 hours after its onset were enrolled. Peripheral venous blood was sampled to measure platelet aggregability and other parameters. RESULTS: Mean values of spontaneous small-sized platelet aggregates and collagen- or adenosine diphosphate (ADP)-induced large-sized aggregates were elevated in acute ischemic stroke. In atherothrombotic stroke (n = 178), collagen and ADP-induced large-sized aggregates were positively correlated with HbA1c, respectively. High incidence of the modified Rankin Scales (mRS) 5-6 at discharge was associated with diabetes complication (odds ratio [OR] 8.77, 95% confidence interval [CI] 1.32-57.56). The proportion of patients who were functionally independent (the mRS 0-2) at discharge was lower in the middle tertile of collagen and ADP-induced large-sized aggregates than their low tertile (OR 2.46, 95% CI 1.09-5.58; OR 2.43, 95% CI 1.05-5.59, respectively). Prestroke administration of aspirin recovered the proportion of independence at discharge (OR 0.25, 95% CI 0.06-0.99), and ameliorated incidence of the mRS 5-6. On logistic regression analysis, diabetes, HbA1c, collagen-induced large-sized aggregates, and prestroke administration of aspirin remained independent predictors of clinical outcomes in atherothrombotic stroke. In cardioembolic and lacunar stroke, no relations with clinical outcomes were found. CONCLUSIONS: High plasma level of HbA1c is involved in enhanced platelet aggregability in acute atherothrombotic stroke patients, and prestroke administration of aspirin may be beneficial to clinical outcomes.

Effects of Blackcurrant Anthocyanin on Endothelial Function and Peripheral Temperature in Young Smokers.

BACKGROUND: Blackcurrant anthocyanin (BCA) is expected to repair endothelial dysfunction, but it remains unclear whether beneficial effects are present in young healthy persons. This study examines whether supplements containing blackcurrant anthocyanin improve endothelial function and peripheral temperature in young smokers. METHODS: Young, healthy male nonsmokers (N group: n = 11; mean age 22 ± 2 years) and smokers (S group: n = 13; mean age 21 ± 1 years) were enrolled. A randomized and double-blind trial was designed to compare the effects of no supplement, a supplement containing 50 mg of blackcurrant anthocyanin (supplement A), and a supplement containing 50 mg of blackcurrant anthocyanin plus vitamin E (supplement B) on flow-mediated dilatation (FMD) and skin temperature. RESULTS: Under no supplement, FMD was unchanged during the 2 h period after smoking in the N group, whereas it was decreased during the 2 h period after smoking in the S group. Under the A supplement, FMD was decreased 1 h after smoking and returned to the baseline level 2 h after smoking in the S group. The skin temperature in the area of the foot dorsum was decreased in the S group after smoking compared with that in the N group, who did not smoke, whereas under A and B supplements, it was higher in the S group compared with that in the N group. CONCLUSIONS: BCA could attenuate the smoking-induced acute endothelial dysfunction and improve peripheral temperature in young smokers.

Novel anti-aging gene NM_026333 contributes to proton-induced aging via NCX1-pathway.

Diet-induced metabolic acidosis is associated with the impairment of bone metabolism and an increased risk of a number of chronic noncommunicable diseases, such as type 2 diabetes mellitus and hypertension. Low serum bicarbonate is associated with high mortality in healthy older individuals. Recently, we demonstrated that both coupling factor 6 (CF6)-overexpressing transgenic (TG) and high salt-fed mice which had sustained intracellular acidosis, due to enhanced proton import through ecto-F1Fo complex and/or reduced proton export through Na+-K+ ATPase inhibition, displayed shortened lifespan and early senescence-associated phenotypes such as signs of hair greying and alopecia, weight loss, and/or reduced organ mass. In this study, we searched causative genes of proton-induced aging in CF6-overexpressing TG and high salt-fed mice. We discovered NM_026333 as a novel anti-aging gene which was downregulated in the heart and kidney in both types of mice. NM_026333 protein consists of 269 amino acids with transmembrane region (90-193aa). Induction of NM_026333 or recombinant protein rescued TG cells and CF6-treated human cells from aging hallmarks of impaired autophagy, genomic instability, and epigenetic alteration. NM_026333 protein directly bound plasma membrane Na+-Ca2+ exchanger 1 (NCX1) to suppress its reverse mode, and cancelled proton-induced epigenetic regression of Atg7 that was caused by H3K4 and H4K20 tri-methylation via suppression of demethylase and H4K5 acetylation via suppression of nuclear HDAC3-HDAC4-emerin system. NM_026333 also attenuated proton-induced impaired formation of autolysosome, an increase in nuclear acetylated LC3 II, and acetylation of Atg7. These effects reappeared by NCX1 inhibitor. Furthermore, NCX1 inhibitor extended lifespan compared with vehicle-treatment in TG mice. This study will shed light on novel aging mechanism and provide implications in a target for anti-aging therapy.

Mitochondrial inhibitory factor protein 1 attenuates coupling factor 6-induced aging signal.

Coupling factor 6 (CF6) forces a counter-clockwise rotation of plasma membrane F1 Fo complex, resulting in proton import and accelerated aging. Inhibitory factor peptide 1 (IF1) suppresses a unidirectional counter-clockwise rotation of F1 Fo complex without affecting ATP synthesis. We tested the hypothesis that IF1 may attenuate CF6-induced aging signaling in CF6-overexpressing transgenic (TG) cells. In IF1-GFP overexpressing wild type (WT) cells, the diffuse peripheral staining of tubular mitochondria was observed with a dense widely distributed network around the nucleus. In TG cells, however, the only peri-nuclear network of fragmented mitochondria was observed at 24 h, but it was developed to a widely distributed mitochondrial network of tubular mitochondria at 72 h. TG cells displayed aging hallmarks of telomere attrition, epigenetic alterations, defective proteostasis, and genomic instability with a decrease in emerin and lamin and loss of heterochromatin. IF1 induction rescued TG cells from telomere attrition, expression of genomic instability with the increase in emerin and lamin, and that of epigenetic alterations with recovery of heterochromatin. In defective proteostasis, IF1 induction restored a potent peri-nuclear staining of autolysosomes compared with the baseline weak staining. The decrease in Atg7 was restored, whereas the increase in P62 was abolished. We conclude that genetic disruption of proton signals by IF1 induction suppressed CF6-induced expression of aging hallmarks such as telomere attrition, epigenetic alterations, defective proteostasis, and genomic instability. Given the widespread biological actions of CF6, the physiological and pathological actions of IF1 may be complex.

Intracellular protons accelerate aging and switch on aging hallmarks in mice.

Diet-induced metabolic acidosis is associated with the impairment of bone metabolism and an increased risk of a number of chronic noncommunicable diseases, such as type 2 diabetes mellitus and hypertension. The serum bicarbonate level is an independent predictor of chronic kidney disease progression. We investigated whether proton accelerates aging by analyzing both coupling factor 6-overexpressing transgenic (TG) and high salt-fed mice which display sustained intracellular acidosis, due to enhanced proton import through ecto-F1 Fo complex and/or reduced proton export through Na+ -K+ ATPase inhibition. Both types of mice displayed shortened lifespan and early senescence-associated phenotypes such as signs of hair greying and alopecia, weight loss, and/or reduced organ mass. In chronic intracellular acidosis mice, autophagy was impaired by regression of Atg7, an increase in nuclear acetylated LC3 II, and acetylation of Atg7. The increase in histone 3 trimethylation at lysine 4 (H3K4me3) and H4K20me3 and the decrease in H3K9me3 and H3K27me3 were observed in the heart and kidney obtained from both TG and high salt-fed mice. The decrease in lamin A/C, emerin, and heterochromatin protein 1α without changes in barrier-to-autointegration factor and high-mobility group box 1 was confirmed in TG and high salt-fed mice. Suppression of nuclear histone deacetylase 3-emerin system is attributable to epigenetic regression of Atg7 and H4K5 acetylation. These findings will shed light on novel aging and impaired autophagy mechanism, and provide implications in a target for antiaging therapy.

Spontaneous Micro-Aggregation of Platelets Predicts Clinical Outcome in Acute Ischemic Stroke.

BACKGROUNDS: Spontaneous micro-aggregation of platelets (SMAP) is frequently observed in stroke patients and is a trigger for the additional development of larger thrombi. We tested the hypothesis that SMAP may predict clinical outcome in acute ischemic stroke patients. METHODS AND RESULTS: Consecutive acute ischemic stroke patients (n = 358) who were transferred to our hospital within 24 hours after its onset were enrolled. Peripheral venous blood was sampled to measure various parameters when they arrived. SMAP was correlated with plasma brain natriuretic peptide and diastolic blood pressure positively, and with serum albumin and body weight negatively. Multivariable Cox regression analysis showed that only serum albumin was an independent predictor of the SMAP (P = .0023). The proportion of patients who were functionally independent (score 0-2 on the modified Rankin Scales) at discharge was lower in the third tertile of SMAP (higher level) as compared with the first and the second tertiles in ischemic stroke (odds ratio [OR], 5.76; 95 % confidence interval [CI], 3.31-10.05; P < .0001) and atherothrombotic stroke (P = .02 by chi-square test). The lower proportion of patients achieving independence was found in the first tertile of serum albumin (lower level) as compared with the second and third tertiles in ischemic (OR, 4.60; 95% CI, 2.66-7.95; P < .0001), atherothrombotic, and cardioembolic stroke (P = .004 and P < .0001 by chi-square test). On logistic regression analysis, SMAP and serum albumin remained independent predictors of poor outcome in ischemic stroke. CONCLUSIONS: SMAP within 24 hours after stroke onset is a novel independent predictor of clinical outcome in acute ischemic stroke patients.

Blood Pressure-Independent Effect of Olmesartan on Albuminuria in Mice Overexpressing Renin.

Enhanced renin-angiotensin activity contributes to hypertension, albuminuria, and glomerular hypertrophy. The angiotensin (Ang)-converting enzyme (ACE) 2/Ang (1-7)/Mas axis pathway acts against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits albuminuria independently of blood pressure and elucidated the potential mechanisms.Three- to 4-month-old male mice overexpressing renin in the liver (Ren-TG) were given olmesartan (5 mg/kg/day) or hydralazine (Hyd) (3.5 mg/kg/day) orally for 2 months. Ren-TG mice had higher systolic blood pressure (SBP) than wild-type (WT) mice (158.2 ± 6.3 versus 112.8 ± 8.8 mmHg, n = 3-4, P < 0.01). Ren-TG mice treated with Olm or Hyd for 2 months had lower SBP than untreated Ren-TG mice. Urinary albumin excretion (UAE) was significantly increased in Ren-TG mice compared with WT mice (78.2 ± 31.2 versus 28.6 ± 13.8 µg/day, n = 5-6, P < 0.01). Olm treatment for 2 months reduced UAE, whereas Hyd treatment did not. Olm treatment reversed decreased gene and protein expressions of ACE2 and Mas receptor (Mas 1) in the kidney of Ren-TG mice and inhibited enhanced NADPH oxidase (Nox) 4 expression, whereas Hyd treatment had no influence. Furthermore, increased reactive oxygen species (ROS) in the kidney of Ren-TG mice were decreased by Olm treatment but not by Hyd treatment.Olm treatment inhibits albuminuria and glomerular hypertrophy independently of blood pressure not only through its original AT1R blockade but also partly through the enhancement of the ACE2/Ang (1-7)/Mas axis and suppression of ROS generation.

Mitochondrial Inhibitory Factor Protein 1 Functions as an Endogenous Inhibitor for Coupling Factor 6.

Coupling factor 6 (CF6) forces a counter-clockwise rotation of plasma membrane F1 Fo complex unlike a proton-mediated clockwise rotation in the mitochondria, resulting in ATP hydrolysis, proton import, and apoptosis. Inhibitory peptide 1 (IF1) inhibits a unidirectional counter-clockwise rotation of F1 Fo complex without affecting ATP synthesis by a clockwise rotation. We tested the hypothesis that IF1 may antagonize the biological action of CF6 in human embryonic kidney 293 cells. We generated mature and immature IF1 expression vectors and those labeled with GFP at the C-terminus. In the immature IF1-GFP overexpressing cells, the mitochondrial network of IF1-GFP was newly found at the plasma membrane after peripheral translocation, whereas in mature IF1-GFP transfected cells, a less punctuate rather homogenous pattern was found in the cytoplasm. IF1 protein was detected in the exosome fraction of culture media, and it was enhanced by mature or immature IF1 transfection. Extracellular ATP hydrolysis was enhanced by CF6, whereas immature or mature IF1 transfection suppressed ATP hydrolysis in response to CF6. Intracellular pH was decreased by CF6 but was unchanged after immature IF1 transfection. CF6-induced increase in apoptotic cells was blocked by immature or mature IF1, being accompanied by protein kinase B (PKB) phosphorylation. IF1 antagonizes the pro-apoptotic action of CF6 by relief of intracellular acidification and resultant phosphorylation of PKB. Given the widespread biological actions of CF6, the physiological and pathological functions of IF1 may be expected to be complex. J. Cell. Biochem. 117: 1680-1687, 2016. © 2015 Wiley Periodicals, Inc.

Modified sympathetic nerve regulation in AKAP5-null mice.

Genetic analyses have revealed an important association between A-kinase anchoring proteins (AKAPs) and the intracellular calcium modulating system. AKAP5, also known as AKAP79/150, is an anchoring protein between PKA and voltage-dependent calcium channels, ryanodine receptor-2, phospholamban and other molecules. The aim of the present study was to elucidate the physiological importance of AKAP5 in the creation of cardiac rhythm using AKAP5-null mice. ECG analysis showed a normal sinus rhythm and a decreased responsiveness to isoproterenol in AKAP5-null mice compared with wild-type mice. Analysis of heart rate variability revealed that the R-R interval was unstable in AKAP5-null mutants and that the low-frequency components had decreased, indicating that the tonus of the sympathetic nervous system was affected. Furthermore, the atrium of the AKAP5-null mice showed a decreased positive inotropic response to isoproterenol, indicating the involvement of AKAP5 in a PKA-dependent pathway. Thus, our present study revealed that AKAP5 plays a significant role in the regulation of sympathetic nerve activities.

Olmesartan Inhibits Cardiac Hypertrophy in Mice Overexpressing Renin Independently of Blood Pressure: Its Beneficial Effects on ACE2/Ang(1-7)/Mas Axis and NADPH Oxidase Expression.

Enhanced renin-angiotensin activity causes hypertension and cardiac hypertrophy. The angiotensin (Ang)-converting enzyme (ACE)2/Ang(1-7)/Mas axis pathway functions against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits cardiac hypertrophy independently of blood pressure, and evaluated the potential mechanisms. The 3- to 4-month-old male mice overexpressing renin in the liver (Ren-Tg) were given Olm (5 mg/kg/d) and hydralazine (Hyd) (3.5 mg/kg/d) orally for 2 months. Systolic blood pressure was higher in the Ren-Tg mice than in wild-type littermates. Olm and Hyd treatments lowered systolic blood pressure to the same degree. However, cardiac hypertrophy, evaluated by echocardiography, heart weight, cross-sectional area of cardiomyocytes, and gene expression, was inhibited by only Olm treatment, but not by Hyd. Olm treatment reversed decreased gene expressions of ACE2 and Mas receptor of Ren-Tg mice and inhibited enhanced NADPH oxidase (Nox)4 expression and reactive oxygen species, whereas Hyd treatment had no influence on them. These findings indicate that Olm treatment inhibits cardiac hypertrophy independently of blood pressure, not only through its original AT1R blockade but partly through enhancement of ACE2/Ang(1-7)/Mas axis and suppression of Nox4 expression.

Quality of Life in Physical and Psychological Health and Social Environment at Posthospitalization Period in Patients with Stroke.

BACKGROUND: Interaction of quality of life (QOL) in physical and psychological health and social environment has not been tested in stroke during a posthospitalization period, and a better understanding of the components of QOL would lead to a more integrated and person-centered approach to health management and outcome optimization. We investigated how QOL emerges from the sequelae of stroke and interacts with each other during the posthospitalization period. METHODS: We performed a cross-sectional study in 53 outpatients of stroke survivors (39 men and 14 women with a mean age of 66 years, 46 infarctions, and 7 hemorrhages). RESULTS: Eight QOL domains of psychological health were scored by interview, and 2 of them ("desire to distend what they can do" or "desire to do rehabilitation") were associated with the improvement of physical health during the posthospitalization period (P < .05 and P = .08, respectively). These patients were characterized by the items like "I need to succeed for health improvement, to go home, to go back to work, and to see grandchildren" as goals to achieve their desire (P < .05). In interaction of QOL in psychological health and social environment, another psychological domain "to gain satisfaction from the experience" was closely related to the presence of hobby or work before stroke attack (P < .05). CONCLUSION: During the posthospitalization period, QOL of psychological health may support that of physical health, being associated with the presence of hobby or work before stroke attack.

Plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 as a novel prognostic biomarker in patients with ST-segment elevation acute myocardial infarction.

BACKGROUND: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) level is a reliable prognostic biomarker in acute coronary syndrome. However, it is unclear whether its plasma level at acute phase is related to the long-term prognosis in patients with ST-segment elevation acute myocardial infarction (STEMI). METHODS AND RESULTS: We prospectively examined the relation between plasma sLOX-1 level on admission and prognosis in 153 consecutive STEMI patients admitted within 24 h of onset. Primary percutaneous coronary intervention was performed in 144 patients. The patients were divided into 2 groups by the median value (71 pg/ml) of plasma sLOX-1 level on admission [sLOX-1 level ≤71 pg/ml (n=77) and >71 pg/ml (n=76)], and were followed for median of 1,156 days. All-cause mortality and the combined endpoints of major adverse cardiovascular events (MACE) defined as cardiovascular mortality and recurrent MI were both significantly higher in patients with sLOX-1 values above median than in those below median (25.0% vs. 3.9%, P<0.001, and 19.4% vs. 6.5%, P=0.019 by log-rank test, respectively). Even after adjustment for confounders, a level of sLOX-1 above median was an independent predictor for all-cause mortality (hazard ratio (HR): 5.893; 95% confidence interval (CI): 1.665-20.854, P=0.006) and MACE (HR: 3.457; 95% CI: 1.164-10.270, P=0.030). CONCLUSIONS: Elevated plasma sLOX-1 level on admission independently predicts long-term all-cause mortality and MACE after STEMI.

Impact of Sex Difference on Severity and Functional Outcome in Patients with Cardioembolic Stroke.

INTRODUCTION: Female sex is a risk factor for thromboembolic events in Caucasian, but not in Japanese, patients with nonvalvular atrial fibrillation. However, it remains unclear whether the female sex is also a risk factor for severe stroke and unfavorable functional outcome in patients with cardioembolic (CE) stroke. METHODS: Three hundred fifty-five consecutive patients with CE stroke within 48 hours after onset and with a modified Rankin Scale (mRS) score of 1 or lower before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between female (n = 157) and male (n = 198) patients. RESULTS: The mean age was higher in female than in male patients (80 ± 8 versus 75 ± 9 years, P < .00001). The congestive heart failure, hypertension, age [≥ 75 years], diabetes, stroke/transient ischemic attack [TIA] (CHADS2) score before onset was similar between the two groups (median, 3 [2-4] in both groups). Stroke severity on admission, assessed by the National Institutes of Health Stroke Scale (NIHSS), was higher in female than in male patients (13 [5-20] versus 8 [3-16], P = .0009). Functional outcome at discharge, assessed by mRS, was unfavorable in female than in male patients (3 [1-5] versus 2 [1-4], P = .005). An mRS score of 3 or higher at discharge was found more in female than in male patients (59% versus 39%, P = .0001). Multivariate analyses confirmed that female sex was a significant determinant of severe stroke (NIHSS ≥ 8) on admission (odds ratio [OR] to male = 1.97; 95% confidence interval [CI]; 1.24-3.15, P = .004) and for the mRS score of 3 or higher at discharge (OR = 1.83; 95% CI, 1.16-2.89; P = .01). Similar results were obtained by propensity-score matching analysis. CONCLUSIONS: Female sex is a risk factor for severe stroke on admission and unfavorable functional outcome at discharge in Japanese patients with CE stroke.

Characteristics of intracerebral hemorrhage during rivaroxaban treatment: comparison with those during warfarin.

BACKGROUND AND PURPOSE: Neuroradiological characteristics and functional outcomes of patients with intracerebral hemorrhage (ICH) during novel oral anticoagulant treatment were not well defined. We examined these in comparison with those during warfarin treatment. METHODS: The consecutive 585 patients with ICH admitted from April 2011 through October 2013 were retrospectively studied. Of all, 5 patients (1%) had ICH during rivaroxaban treatment, 56 (10%) during warfarin, and the other 524 (89%) during no anticoagulants. We focused on ICH during rivaroxaban and warfarin treatments and compared the clinical characteristics, neuroradiological findings, and functional outcomes. RESULTS: Patients in the rivaroxaban group were all at high risk for major bleeding with hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS-BLED) score of 3 and higher rate of past history of ICH. Moreover, multiple cerebral microbleeds (≥4) were detected more frequently in rivaroxaban group than in warfarin (80% versus 29%; P=0.04). Hematoma volume in rivaroxaban group was markedly smaller than that in warfarin (median: 4 versus 11 mL; P=0.03). No patient in the rivaroxaban group had expansion of hematoma and surgical treatment. Rivaroxaban group showed lower modified Rankin Scale at discharge relative to warfarin, and the difference between modified Rankin Scale before admission and at discharge was smaller in rivaroxaban than in warfarin (median: 1 versus 3; P=0.047). No patient in the rivaroxaban group died during hospitalization, whereas 10 (18%) warfarin patients died. CONCLUSIONS: Rivaroxaban-associated ICH occurs in patients at high risk for major bleeding. However, they had a relatively small hematoma, no expansion of hematoma, and favorable functional and vital outcomes compared with warfarin-associated ICH.

Imidapril and enalapril similarly inhibit plasma matrix metalloproteinase activities and attenuate left ventricular remodeling in patients with acute myocardial infarction.

Matrix metalloproteinase (MMP) plays a critical role in the development of ventricular remodeling after acute myocardial infarction (AMI). Imidapril, an angiotensin-converting enzyme inhibitor, has been shown to inhibit MMP activity. We investigated whether imidapril inhibits plasma MMP activities and attenuates ventricular remodeling in patients with AMI in comparison with enalapril. We enrolled 70 patients with AMI. All patients underwent primary percutaneous coronary intervention and were randomly assigned either to imidapril (n = 35) or to enalapril (n = 35) treatment. Left ventriculography was performed in acute (day 14) and chronic (6 months) phases, and plasma MMP-2 and MMP-9 activities were measured by zymography. Any changes in left ventricular end-diastolic volume index and ejection fraction from acute to chronic phases did not differ between the 2 groups. The plasma MMP-2 and MMP-9 activities at day 14 were both significantly decreased compared with those at day 1 in both groups (all P < 0.05). At 6 months, MMP-9 activity still remained decreased in both groups (P < 0.05 vs. day 1). Overall, there were no differences between the 2 groups both in plasma MMP-2 and MMP-9 activities. These results demonstrate that imidapril exerts inhibitory effects on plasma MMP activities and attenuates left ventricular remodeling in patients with AMI similar to enalapril.