Based on the data from the patients with acute stroke who were admitted to the Research Institute for Brain and Blood Vessels between 1969 and 1986, changes in stroke incidence were analyzed from the clinicoepidemiological point of view. 1. In all three types of stroke; cerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage, the mean age of onset became older by approximately 4 years in these 18 years. There was a tendency for male to develop stroke 3.5 years earlier on average as compared with female. 2. The incidence of cerebral infarction has been increasing whereas those of cerebral hemorrhage and subarachnoid hemorrhage have been declining. 3. In all three type of stroke, the mortality rate whithin a month of onset has been declining, and there was, in general, a trend that the severity of stroke has been lessened in recent years. In addition, the results from the Stroke Registration System which was conduced by the Group of Clinicoepidemiological Study in Akita was discussed in relation to the changes in stroke incidence.
Further study of the data from the EC/IC Bypass Trial has been pursued for three specific goals. Firstly, the issue of possible distortion of the conclusions by virtue of noncompliance in the centers with the obligation of randomization has been examined very closely. The thrice-yearly neurosurgical reports from the participating neurosurgeons in the 52 centers which entered 1191 patients (86.5% of the total study), reported that 1249 patients received bypass surgery outside the trial. Of these, 925 were medically ineligible by our protocol requirement, 258 refused to be placed in a trial which required randomization, and a mere 66 were deviated from the trial by a deliberate decision of the participating neurologists or neurosurgeons. The ratio of randomized and eligible to non-randomized and operated is 1191 : 1294, very close to 1 : 1. By contrast in the coronary artery study (CASS) this ratio, favoring non-randomization, was 25 : 1. Our participants in these key centers exhibited a disciplined approach to their commitments to the trial and they failed to randomize willing and eligible subjects on the average of 1.3 times per center every five years. Secondly, a number of prognostic studies were carried out in the medically-treated groups to clarify the impact of certain important variables on the outcome. The differential outcome of the radiological subgroups of TIA and minor stroke patients were examined. In the medically-treated patients, fatal and non-fatal strokes occurred within 18 months in 20% of those with ICA occlusion and continuing symptoms after the diagnostic arteriogram, and in 18% of the patients with intracranial carotid stenosis. By contrast patients with ICA occlusion without new symptoms and the patients with middle cerebral artery stenosis and occlusion had fatal and non-fatal 18 months stroke rates of 14%. At 5 years the patients with ICA occlusion and new symptoms after arteriographic confirmation, and those with ICA intracranial stenosis patients had 35% rates of fatal and non-fatal stroke; the rates for those with ICA occlusion without new symptoms and for MCA stenosis both stand at 30% and for MCA occlusion at 20%. Patients who entered the trial with minor stroke had a minimally worse prognosis than those who entered with TIA. The occurrence of recent events (less than 30 days prerandomization) portend greater risk of stroke than later events (30-91 days). Frequency of TIA in the 3 months prior to entry made a substantial difference, with the worst outlook for those having 3 or more compared with those having 2 or less ischemic events in this time-period. Except for those patients entering with recent stroke and having 2 or less TIA's in the 3 months pre-entry period, the highest rate of stroke and fatal stroke was in the 12 weeks period after entry. Thirdly, further intensive search has been made for possible subgroups which might benefit in strokeprevention from bypass surgery. None have surfaced including those with recent or frequent ischemic events, and in those without evidence of good collateral supply in the presence of occluded or stenosed MCA or similar occlusive or stenotic lesions of the ICA. It should be re-emphasized that this was not atrial to validate or deny benefit in ischemic recovery. Such a trial has never been conducted.
The prevalence, incidence and mortality of CVD in Chinese were lower than that in Japanese. In view of the relative ratio of occurrence within one year, it showed that ischemic stroke to hemorrhagic stroke was 46 : 51 in cities and 48.5 : 48.6 in rural areas. The results were thought to be poor control of hypertension. Hypertension are the high risk factor of either hemorrhagic or ischemic stroke. In view of geographical distribution, it tended to be higher prevalence of CVD in northern region than that in southern region in rural survey. In Chinese patietns with CVD, there was no difference between sexes. Incidence rate of CVD in cities was higher than that in rural areas. It showed higher incidence rate in young persons or in the prime of life. Alcohol drinking was regarded one of risk factors to CVD in rural areas. These are epidemiologic variations in patients with CVD between Chinese and Japanese. These variations might be largely explained with poor control of hypertension in Chinese and with differences in social environment and living condition. I would like to recognize that these are important problems to be studied in future. In overview of our data we can seen that there are similar fundamentally and nuance in CVD between Chinese and Japanese
An unique model, the stroke-prone spontaneously hypertensive rat (SHRSP) developing hemorrhagic or thrombotic stroke spontaneously without exception nowadays, was established by our hands and has been extensively studied not only on the pathogenesis but also prevention of stroke. Moreover, in search of “a model for lacular stroke” which is preponderant cause of cerebrovascular dementia in aged populations such as Japan, we recently succeeded in establishing the model by cross breeding between SHPSP and OM strain with accelerated platelet aggregavility. Studies on the pathogenesis showed the genetic factors (consisting of more than 5 major genes) and their interaction with environmental, especially nutritional factors such as salt, protein and lipid intakes were important : Cultured smooth muscle cells obtained from SHRSP are more vulnerable to hypoxia than those from normotensive control rats, offering the evidence suggestive of cellular desposition to cerebrovascular damages. Severe hypertension, through cerebral blood flow reduction in the brain region fed by recurrent arteries, induces initially medial necrosis of small intracerebral arteries which is the basic vascular lesions for either cerebral hemorrhage or infarction. Dietary conditions with Na/K ratio accelerate the development of such arterionecrothrombogenic strokes. Not only K but also dietary fibers, especially seaweed or alginic acid obtained from it, counteract the adverse effect of salt and the preventive mechanism of stroke by dietary fibers has been proven to be due to the reduction of gastro-intestinal Na absorption. In contrast, protein-rich diets decrease the incidence of stroke through the attenuation of hypertension, the acceleration of urinary Na excretion and the preservation of vascular wall distensibility. Further, taurine rich in fish protein has been proven to prevent stroke by the neurogenic attenuation of severe hypertension. Among several fatty acids chronically given to SHRSP palmitoleic acid (POA) was proven to be effective for stroke-prevention even in SHRSP on high salt diets. Some indices such as early development of hypertension, stress-sensitivity, salt-sensitivity tendency toward cardiovascular hypertrophy and biomembrance abnormalities resulting in intracelullar Na retention, are possibly related to predisposition to hypertension and stroke and, may be utilized for the scientific prediction of stroke. Our recent studies indicated vulnerability to hypoxia in SHRSP brain, detected by an abnormal increase in phosphate to phosphocreatine ratio under hypoxia or ischemia by using a 31P-NMR could be used as a clinically available index for predicting the development of stroke in advance. Thus, stroke is experimentally predictable, and evidently preventable by the control of blood pressure, nutritional conditions and also of thrombogenesis. The most important message obtained from our experimental models of stroke is that “stroke can be prevented by non-pharmacological dietary intervention even in animal models strongly predisposed to cerebrovascular diseases”. Accumulating evidence obtained by our epidemiological and clinical studies support that these experimental findings in animal models can be applied to humans.