Antiplatelet cilostazol is beneficial in diabetic and/or hypertensive ischemic stroke patients. Subgroup analysis of the cilostazol stroke prevention study.

BACKGROUND AND PURPOSE: Although antiplatelets are known to be effective for secondary prevention of cerebral infarction, the number needed to treat is rather large and the effects in stroke patients with complications such as hypertension or diabetes are inadequately defined. This study was conducted to examine the effect of such complications on recurrence of cerebral infarction, and to assess the effect of cilostazol, an antiplatelet agent, in these high-risk subjects. METHODS: A post hoc subgroup analysis of the already reported Cilostazol Stroke Prevention Study, which was a placebo-controlled double-blind trial, has been carried out to clarify the influence of various complications on recurrence in the placebo group and the effects of cilostazol in 1,095 patients with noncardioembolic ischemic cerebrovascular disease. Treatment continued for an average of 1.8 +/- 1.3 years (maximum 4.8 years). RESULTS: The recurrence rate of the diabetic stroke patients was significantly higher compared with the nondiabetics in the placebo group (9.4 vs. 4.7%/year, p = 0.01). Furthermore, our study showed that the relative risk reduction (RRR) for recurrence of infarction was 41.7% with cilostazol. This treatment provided a significant benefit in patients with lacunar infarction (RRR 43.4%, p = 0.04), with diabetes (RRR 64.4%, p = 0.008), or with hypertension (RRR 58.0%, p = 0.003). CONCLUSIONS: Diabetic patients are particularly at risk for recurrence of cerebral infarction. Cilostazol is useful for the prevention of the recurrence of vascular events in patients with lacunar infarction, and is probably effective in high-risk patients with diabetes and/or hypertension.

Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A randomized, double-blind, aspirin-controlled trial.

BACKGROUND AND PURPOSE: The antiplatelet agent sarpogrelate is a selective inhibitor of 5-hydroxytryptamine receptors. The purpose of this study was to compare the efficacy and safety of sarpogrelate with those of aspirin in Japanese ischemic stroke patients. METHODS: In total, 1510 patients with recent cerebral infarction (1 week to 6 months after onset) were randomly assigned to receive either sarpogrelate (100 mg TID) or aspirin (81 mg/d). Mean follow-up period was 1.59 years. The primary efficacy end point was recurrence of cerebral infarction. Clusters of serious vascular events (stroke, acute coronary syndrome, or vascular event-related death) were selected as secondary end points. The aim of the primary efficacy analysis was to demonstrate the noninferiority of sarpogrelate with respect to aspirin, with the criterion that the upper limit of the 95% CI of the hazard ratio (sarpogrelate vs aspirin) for recurrence of cerebral infarction should not exceed 1.33. RESULTS: Cerebral infarction recurred in 72 patients (6.09%/y) in the sarpogrelate group and in 58 (4.86%/y) in the aspirin group (hazard ratio=1.25; 95% CI, 0.89 to 1.77; P=0.19). A serious vascular event occurred in 90 (7.61%/y) and in 85 (7.12%/y) patients, respectively (hazard ratio=1.07; 95% CI, 0.80 to 1.44; P=0.65). The overall incidences of bleeding events were 89 (11.9%) and 131 (17.3%), respectively (P<0.01). CONCLUSIONS: Sarpogrelate was not noninferior to aspirin for prevention of recurrence of cerebral infarction. Bleeding events were significantly fewer with sarpogrelate than aspirin. The effect of aspirin in Japanese patients was similar to that in Western studies.

Frontotemporal lobar degeneration with ubiquitin pathology: an autopsy case presenting with semantic dementia and upper motor neuron signs with a clinical course of 19 years.

We report a case of a right-handed 74-year-old man who showed semantic dementia with a disease duration of 19 years. He initially presented with excessive use of pronouns and semantic paraphasia at the age of 55 years. Impairment of object recognition developed 5 years after the onset. Face recognition impairment and stereotypic behaviors developed 11 years after onset, and pyramidal signs 2 years before death. Pathological examination disclosed circumscribed severe atrophy in not only the bilateral temporal tips but also in the left precentral gyrus and pars opercularis in a motor speech field. Pyramidal tract involvement and loss of Betz cells were also evident. On the other hand, neurons in the anterior horns and hypoglossal nuclei were spared in number, although astrocytes were mildly proliferated. Ubiquitin-positive lesions were observed in the hippocampus, and frontal and temporal cortices. Neither Bunina bodies nor Pick bodies were present. These features clinically fit the international diagnostic criteria of semantic dementia and, histopathologically, frontotemporal lobar degeneration with motor neuron disease (FTLD-MND). This case suggests that (1) the distribution of cortical lesions associated with language disturbance is not uniform in FTLD-MND. It may be that only some cases of FTLD with ubiquitin pathology develop semantic dementia despite the high incidence of language disturbance, and (2) the precentral gyrus can be severely affected in FTLD-MND. After reviewing previous cases of FTLD-MND with a clinical course of more than 10 years, we also noticed that (3) FTLD-MND cases with a long disease duration often show upper motor neuron-predominant involvement.

Pulmonary artery systolic pressure is elevated in the elderly: relationships between echocardiographic and pathological findings.

OBJECTIVE: We investigated the relationship between the right cardiac system and increased pulmonary artery systolic pressure (PASP) in the elderly. PATIENTS AND METHODS: Echocardiography stable state data were available for 163 of 200 consecutive autopsied patients. Of these, PASP could be estimated by extrapolation from the maximum pressure gradient in tricuspid valve regurgitation from echocardiograms in 73 cases; however, 22 cases with secondary changes attributable to left cardiac insufficiency had to be excluded. We studied the remaining 51 patients in detail (16 men, 35 women, age 68-103 years; mean, 87.7 +/- 8.1). We investigated the following: echocardiographic and pathologic variables, age, sex, body mass index, the survival time (from echocardiography to autopsy), and the presence or absence of chronic pulmonary disease. RESULTS: The average PASP was 39.8 +/- 10.3 mmHg, elevated compared with young persons. Linear regression analysis showed a close correlation of PASP with age (r = 0.35, p = 0.011), thickness of the right ventricle (RV) outflow tract wall as an index of RV hypertrophy (r = 0.35, p = 0.013) and the survival time (r = -0.36, p = 0.0083). By multiple regression analysis, PASP was correlated with the thickness of RV outflow tract (p = 0.0037) even after adjustment for other factors including chronic pulmonary disease. CONCLUSIONS: PASP is elevated in the elderly and it is correlated with the thickness of the RV outflow tract wall as an index of RV hypertrophy.

Soluble Abeta homeostasis in AD and DS: impairment of anti-amyloidogenic protection by lipoproteins.

In order to assess whether lipoproteins are physiologically able to balance and modulate the sAbeta homeostasis in vivo, soluble Abeta levels in lipoprotein-depleted plasma were measured as a function of age in normal controls, Alzheimer's disease (AD) patients, and Down's syndrome (DS) cases. The reshaping of sAbeta homeostasis, in particular the sAbeta42-lipoprotein interaction, takes place over normal-60's, whereas mild AD patients appear to have impaired this anti-amyloidogenic mechanism resulting in a significant increase of lipoprotein-free sAbeta42. Similar loss of function takes place in Down's syndrome patients. Lipoprotein-free sAbeta remains significantly elevated from the pre-symptomatic through the symptomatic stages of the disease, and declines with the progression of the AD-like pathology. The dissociation of sAbeta from lipoprotein-particles also occurs in brain parenchyma and the presence of soluble dimeric lipoprotein-free Abeta prior to its parenchymal deposition in AD brains would support the hypothesis that functionally declined lipoproteins may be major determinants in the production of metabolic conditions leading to higher levels of sAbeta species and cerebral amyloidosis.

Prognostic value of high plasma brain natriuretic peptide concentrations in very elderly persons.

BACKGROUND: Many elderly persons without heart failure have high plasma concentrations of brain natriuretic peptide (BNP). We investigated the prognostic implications and potential causes of these increased levels. METHODS: We enrolled 111 persons aged 80 years or older who had no history of hospitalization for cardiac disease, a cardiothoracic ratio < or =55% on chest radiographs, and a serum creatinine level < or =2.0 mg/mL. All subjects had participated in a regular health screening program at our hospital, and were followed for up to 24 months. We studied the correlation of plasma BNP concentration with age, nutritional state, and activities of daily living. Cox proportional hazards models were used to determine the association between BNP levels and clinical outcomes (cardiac hospitalizations, mortality), adjusted for other risk factors. RESULTS: During follow-up, 8 subjects (7%) were hospitalized with cardiac disorders, and 21 (19%) died. Each 50-pg/mL increase in the plasma BNP concentration was associated with a 1.6-fold increase in the risk of cardiac events (95% confidence interval [CI]: 1.2 to 2.1) and a 1.4-fold increase in total mortality (95% CI: 1.2 to 1.6). Plasma BNP concentration correlated positively with age (r = 0.31, P = 0.001), serum creatinine level (r = 0.23, P = 0.02), and the activities of daily living (r = 0.36, P = 0.0001). CONCLUSION: In very elderly persons, the plasma BNP concentration may be a biochemical marker of an increased risk of cardiac morbidity and total mortality.