Background— Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. Methods and Results— We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. Conclusions— Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

There is a relationship between perceived chewing ability (number of foods considered chewable) and physical fitness in this 80-year-old population. Chewing ability may be an independent predictor of physical fitness, thus preventative dental care aimed at preserving chewing ability may be able to enhance activities of daily life and quality of life in very elderly individuals.

Abstract-Ghrelin is an orexigenic peptide originally isolated from the stomach. Intracerebroventricular administration of ghrelin has been shown to elicit decreases in arterial pressure and renal sympathetic nerve activity in conscious rabbits. The aim of the present study was to determine the role of ghrelin in the brain stem in cardiovascular responses in rats. Unilateral microinjection of ghrelin into the nucleus of the solitary tract significantly decreased the mean arterial pressure and heart rate (Ϫ17.3Ϯ0.8 mm Hg and Ϫ13.6Ϯ3.5 bpm by 20 pmol). The microinjection of ghrelin into the nucleus of the solitary tract also suppressed the renal sympathetic nerve activity (Ϫ29.5Ϯ3.4%; PϽ0.0001). Pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion-blocking agent, eliminated these cardiovascular responses induced by the microinjection of ghrelin (20 pmol) into the nucleus of the solitary tract; however, pretreatment with intravenous injection of atropine sulfate (0.1 mg/kg), an antagonist of muscarinic acetylcholine receptors, failed to prevent them. In contrast, unilateral microinjection of ghrelin into the area postrema, rostral, and caudal ventrolateral medulla caused no significant changes in the mean arterial pressure and heart rate. On the other hand, immunohistochemical study revealed that the receptor for ghrelin, the growth hormone secretagogue receptor, was expressed in the neuronal cells of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus, but not in the cells of the area postrema. These results suggest that ghrelin acts at the nucleus of the solitary tract to suppress sympathetic activity and to decrease arterial pressure in rats. Key Words: blood pressure Ⅲ immunohistochemistry Ⅲ rats G hrelin, an acylated 28-residue peptide originally isolated from rat stomach, is an endogenous ligand for the growth hormone secretagogue (GHS) receptor. 1,2 Although ghrelin is likely to regulate pituitary growth hormone (GH) secretion, along with GH-releasing hormone and somatostatin, 2,3 intracerebroventricular (ICV) administration of ghrelin has been shown to generate a dose-dependent increase in food intake and body weight, 4,5 suggesting that ghrelin participates in the regulation of both food intake and GH secretion.It has been suggested that ghrelin may participate not only in feeding behavior but also in cardiovascular and sympathetic regulation. 6 -10 Ghrelin has a vasodilatory effect in humans, 6 and intravenous injection of human ghrelin has been shown to elicit a decrease in blood pressure without an increase in heart rate (HR) in healthy men. 7 We have recently reported that ICV administration of ghrelin suppresses the renal sympathetic nerve activity (RSNA) and decreases arterial pressure in conscious rabbits, suggesting that intravenous injection of ghrelin acts, at least in part, on the central nervous system to decrease arterial pressure and RSNA. 8 Moreover, ICV administration of ghrelin augments baroreflex control of RSNA and HR. 8 Our previous finding...

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BackgroundVascular endothelial growth factor (VEGF) is a well-known molecule mediating neuronal survival and angiogenesis. However, its clinical significance in ischemic stroke is still controversial. The goal of this study was to examine the temporal profile of plasma VEGF value and its clinical significance in ischemic stroke with taking its subtypes into consideration.MethodsWe prospectively enrolled 171 patients with ischemic stroke and age- and gender-matched healthy subjects. The stroke patients were divided into 4 subtypes: atherothrombotic infarction (ATBI, n = 34), lacunar infarction (LAC, n = 45), cardioembolic infarction (CE, n = 49) and other types (OT, n = 43). Plasma VEGF values were measured as a part of multiplex immunoassay (Human MAP v1.6) and we obtained clinical information at 5 time points (days 0, 3, 7, 14 and 90) after the stroke onset.ResultsPlasma VEGF values were significantly higher in all stroke subtypes but OT than those in the controls throughout 90 days after stroke onset. There was no significant difference in the average VEGF values among ATBI, LAC, and CE. VEGF values were positively associated with neurological severity in CE patients, while a negative association was found in ATBI patients. After adjustment for possible confounding factors, plasma VEGF value was an independent predictor of poor functional outcome in CE patients.ConclusionsAlthough plasma VEGF value increases immediately after the stroke onset equally in all stroke subtypes, its significance in functional outcome may be different among the stroke subtypes.

Background and Purpose-Few studies have shown the association between glucose tolerance status defined by a 75-g oral glucose tolerance test and the development of different types of cardiovascular disease. Methods-A total of 2421 community-dwelling Japanese subjects aged 40 to 79 years who underwent the oral glucose tolerance test were followed up for 14 years. Results-In multivariable analysis, the risks of ischemic stroke in both sexes and coronary heart disease (CHD) in women were significantly higher in subjects with diabetes determined by the World Health Organization criteria than in those with normal glucose tolerance even after adjustment for other confounding factors, but such association was not seen for CHD in men (ischemic stroke: adjusted hazard ratio