pressure , cognition and cerebral blood flow in the cohort of " Men born 1914 "

”Men born 1914” is a population-based cohort study of the epidemiology of cardiovascular disease. Five hundred men born in 1914 were examined at the age of 68, 185 of them being re-examined at 81 years of age. Examination included medical and psychological investigation, ultrasonographic measurement of the carotid arteries, 24-hour ambulatory blood pressure monitoring, measurement of regional cerebral blood flow, and assessment of cardiovascular risk factors. Although risk factors for stroke and dementia have been identified, little is known about their influence on cerebral perfusion in the non-demented elderly. Ischemic cerebrovascular disease is usually a consequence of atherosclerosis and is the commonest cause of stroke. It is well known that hypertension plays a major etiological role in the development of cerebrovascular disease, ischemic heart disease, and cardiac failure. Active treatment of hypertension substantially reduces the risk of these complications. Little is known of how diurnal variations in blood pressure level influence cerebral perfusion in the very elderly. High blood pressure has often been discussed as a risk factor for cerebrovascular disorders and vacular dementia. Although much research has been done on elevated blood pressure, including its treatment and prevention, very little attention has been paid to low blood pressure, diurnal variation in blood pressure and orthostatic hypotension. A high prevalence of orthostatic hypotension in the elderly has been reported. It is well known that a fall in blood pressure can lead to cerebral hypoperfusion. It may also play a decisive role in the development of cerebrovascular insufficiency, i.e. of cerebral blood flow being inadequate in relation to the metabolic needs of the brain tissue. Haemodynamically, vascular insufficiency can develop through a drop in tissue perfusion in relation to vascular resistance. The resultant decrease in cerebral blood flow can give rise to ischemic hypoxia. The decrease in cerebral blood flow is usually caused by a reduction in systemic circulation. Cardiac arrest, cardiac arrhythmia, heart failure, occlusion or stenosis of the carotid arteries, and antihypertensive treatment are conditions in which the systemic circulation may fall off, jeopardizing the cerebral circulation as a whole and causing ischemic-hypoxic lesions in vulnerable areas. Four studies within the framework of this overall investigation were carried out within the thesis as a whole. Study I showed hypertension to be a potential risk factor for the development of carotid artery stenosis (CAS). In the ”Men born in 1914” cohort, the proportion of men with CAS changed noticeably during the period up to the 13 year followup. Of the 148 men with normal carotid blood flow at 68 years of age, there were only 12 who at the re-examination at 81 years of age in 1995-96 showed no signs of CAS, whereas 136 men, or 93% of the surviving study cohort, had developed it. A significantly higher proportion of the men with hypertension than those without were found to have developed carotid stenosis. A higher proportion of occurrence of hypertension was noted in the men with bilateral CAS than in the others. The proportion of those having hypertension was smaller for the men with unilateral CAS than in those with bilateral carotid artery stenosis. At follow-up there were 14 of 136 men (10%) with CAS who had experienced an incident stroke or transient ischemic attack (TIA) and that all of them were found among men with CAS. No significant differences for other major cardiovascular risk factors (diabetes, hyperlipidemia, obesity, alcohol consumption and lack of physical activity) were noted. Study II showed hypertension in late midlife and high diastolic blood pressure (DBP), in particular, to be associated with a decline in cognitive functioning in the men when they became elderly. DBP but not hypertension (HT) examined by tertiles at 68 years of age, was found to be inversely related to verbal (Paired Associates and Synonyms) and spatial functioning (Block Design and Benton Visual Retention Test), and speed (Digit Symbol Substitution) at 81 years of age, but only spatial functioning to be related to SBP at 68 years. High blood pressure at baseline examination, especially with regard to DBP with an accompanying decrease in DBP, was found to be inversely related to both speed performance and spatial functioning in psychometric tests taken 13 years later. Study III showed significant associations between blood pressure (BP) levels and cerebral blood flow (CBF), especially at night. DBP at night was found to be correlated with CBF in the temporal right medial (p=0.012) and the left medial (p=0.039) regions. DBP during the days was also found to be correlated with CBF in the right medial temporal region (p=0.025). Stratified analyses indicated subjects with a high DBP (>70 mmHg) during the day to show a stronger association between CBF and mean DBP at night in the right medial temporal region than subjects with a lower daytime DBP (r=0.323, p=0.009). No such association for any of the CBF areas was found for subjects with a low DBP during the day (<70 mmHg). Analyses of the correlations between CBF in the different regions and the mean DBP and SBP, respectively, showed there to be a significant negative correlation for the frontal regions between CBF and DBP at night and for the left frontal region between CBF and SBP at night. The associations found between CBF and low BP could indicate an increase in the nocturnal risk of cerebral ischemia. Study IV showed an extreme fall in nocturnal DBP in this cohort of elderly men to be correlated with focal changes in CBF and an associated increase in BP. The relative fall in DBP at night was negatively correlated with CBF in the temporal medial, temporal lateral, and parietal inferior areas in both hemispheres. Analyses of the office SBP at follow-up showed that subjects showing an increase in SBP to have a higher frequency of an extreme dip in nocturnal DBP than subjects did who showed a decrease in longitudinal SBP (Chi-Square 3.652; p=0.056), irrespective of the blood pressure level or the prevalence of hypertension, before and after the last follow-up. In conclusion, an extreme fall in blood pressure at night in a cohort of elderly men was found to be associated with focal changes in cerebral perfusion, which in turn was correlated with an increase in blood pressure over an extended period of time and resulting damage to vascular autoregulation.