Do abnormalities in dynamic cerebral auto-regulation underlie the pathophysiological processes behind syncope in older people?

Do abnormalities in dynamic cerebral auto-regulation underlie the pathophysiological processes behind syncope in older people? Introduction: The aim of this thesis was to investigate whether abnormalities in dynamic cerebral auto-regulation (dCA) explain the symptoms associated with orthostatic (OH) and post-prandial hypotension (PPH). Methods: Based on clinical symptoms and signs for the OH study: 4 Groups: Asymptomatic No OH (control), Symptomatic No OH, Asymptomatic OH, and Symptomatic OH. PPH study: double-blind placebo controlled cross-over study of glucose (50g) drink. 2 Groups: No PPH (control) and PPH. Baseline and head-up-tilt (HUT, for OH maximum 30 minutes study or to symptoms; PPH study maximum 60 minutes per visit). All had Transcranial Doppler ultrasound, beat-to-beat BP, ECG and CO2 monitoring. Baseline autonomic function, arterial stiffness, cardiac baroreceptor sensitivity (BRS) were calculated and dynamic cerebral auto-regulation (as the autoregulatory index ARI) assessed before and during tilt. Results: OH: n=85, mean age 73.9±7.1 years; PPH: n= 40, mean age 73.4±7.3 years Baseline: No significant differences were found between groups for cardiac BRS, arterial stiffness, cerebral blood flow velocity (CBFV) or dCA in either study. HUT both studies: falls in BP, CO2 and CBFV, increases in HR, and fall in ARI amongst symptomatic subjects prior to the end of HUT (maximum duration or symptom onset) compared to pre-HUT values. PPH study: fall in ARI with HUT irrespective of whether glucose or placebo phase. Conclusions: The development of symptoms during tilt in both studies was related to a fall in CBFV and impaired cerebral auto-regulation. Abnormalities in cerebral autoregulation may explain the symptoms of OH and PPH although these changes can only be detected during head-up-tilt

Hemodynamic responses following dynamic resistance exercise in young and older adult women

This investigation examined the effects of age, exercise and test condition on hemodynamic variables, autonomic and vascular function in relation to resistance exercise (RE). The associations among these variables were also examined. METHODS: Sixteen young (21.4+1.4 yrs) and 16 older (69.7+3.9 yrs) women performed 5- and 15- repetition maximal (RM) of knee extension RE. Continuous blood pressure (BP) and electrocardiography (ECG) data were recorded. The dependent variables are reported at pre-exercise, peak exercise and recovery period. Heart rate variability data were derived from 5- and 10-min segments before and after exercise. Resting and after arterial occlusion forearm vascular function indices and pre- and post-exercise resting forearm blood flow and forearm vascular resistance (FVR) were measured using plethysmography technique. ANOVA with repeated measures was used for statistical analysis. LSD was used where post hoc comparison required. Pearson correlation and linear regression were used to examine associations between autonomic and vascular function indices and hemodynamic parameters; alpha=0.05. RESULTS: Resistance exercise resulted in increased BP (SBP=36.6+2.2; DBP=27.4+1.6 mmHg) and HR (37.8+1.6 beat/min). This was followed by a drop in BP below pre-exercise level throughout the recovery period up to 60 minutes. The 15-RM condition resulted in higher SBP at peak exercise (15-RM: 155.7+3.7 vs. 5-RM: 142.3+3.7 mmHg) and in the early phase of recovery (local min: 15-RM=127.0+2.7 vs. 5-RM=120.4+2.6 mmHg); however, the 5-RM condition resulted in greater 1-min and 3-min post-exercise SBP recovery ratios (15-RM: 1-min=0.78+0.01; 3-min=0.76+0.01 vs. 5-RM: 1-min=0.84+0.01; 3-min=0.82+0.01). Older women had higher SBP throughout the testing period, and higher 1-min and 3-min recovery ratios (Young: 1-min=0.80+0.01; 3-min=0.78+0.01 vs. Old: 1-min=0.83+0.01; 3-min=0.80+0.01). However, the older women experienced greater drops in BP (SBP: young=-0.02+2.6 vs. old=-9.4+2.3; DBP: young=-3.5+1.8 vs. old=-9.8+1.9 mmHg) during the recovery period. FVR after RE increased above pre-exercise only in the young (p\u3c0.03). Low-frequency variations in HR were related to recovery of mean arterial pressure (young: r=0.66, p\u3c0.001; older: r=0.79; p\u3c0.001) and FVR (young: r=0.93, p=0.001; old: r=0.95; p\u3c0.001). CONCUSION: Age-group differences in post-exercise BP drop, characterized by a greater decline in BP in older adults, might be attributed to smaller increases in vascular resistance in older women

Can frailty inform the management of hypertension in older people?

Background Hypertension increases the risk of cardiovascular disease. Whilst blood pressure (BP) lowering can reduce this risk, it can also cause adverse effects. This PhD study uses mixed methods to explore the utility of frailty to identify older people for whom the association of BP and outcomes is different. Methods Meta-analysis summarised observational studies to date. A retrospective cohort study used linked electronic health records from the Welsh Secure Anonymised Information Linkage (SAIL) databank. Frailty was measured using the electronic frailty index. Time to event analysis measured first ever major adverse cardiovascular event (MACE), all-cause mortality and injurious falls. Narrative interviews explored the perspectives of ten older people on the utility of frailty in managing hypertension on their terms. Results Meta-analysis identified that all-cause mortality was lower for older people who were not frail with systolic BP 140 mm Hg, but there was no association in the context of frailty. In a population of 145,598 people with hypertension over the age of 65, compared to participants who were fit, people with frailty were associated with significantly higher MACE events despite adjustment for known cardiovascular risk factors (increased risk of 38% in mild frailty, 84% in moderate frailty, 117% in severe frailty). Frailty did not modify the association of BP and outcomes, but frailty did modify the association of BP-lowering medication and outcomes. Narrative interviews explored ways in which frailty could guide hypertension management towards what matters most to the individual. Discussion Findings provide evidence that frailty can usefully identify older people with increased risk of cardiovascular and non-cardiovascular outcomes in the context of hypertension management and suggest that the modifying effect of frailty in this context is in the degree to which someone sustains benefit or suffers adverse effects of BP-lowering treatment

Heart rate and blood pressure variability : association with white matter lesions and cognitive function following stroke

Dementia presents a significant health care burden. Older post-stroke patients suffer high rates of dementia. Subcortical ischaemia may be an important mechanism of cognitive decline, particularly in older patients with cerebrovascular disease. It is hypothesised that abnormal heart rate and blood pressure variability will increase white matter lesion volume through hypoperfusion. This may lead to a subcortical pattern of cognitive decline characterised for example by deficits in attention and concentration. Stroke patients aged > 75 years and free of dementia had a series of cardiovascular autonomic, brain imaging and neuropsychometric investigations performed more than three months following incident stroke. Annual neuropsychometric assessment included CAMCOG score and measures of reaction time and concentration using a series of visual and numerical tasks presented on computer (Cognitive Drug Research Assessment System). Autonomic function is impaired in older stroke patients in the long term after stroke. These deficits are weakly associated with cross-sectional measures of sub-cortical performance but do not predict subsequent decline in cognitive function. Twenty-four hour blood pressure variability is associated with white matter disease and excessive nocturnal dipping is associated with impaired cognitive function. Again blood pressure variability does not help predict subsequent change in white matter lesion burden or cognitive function. This study provides limited support for the hypoperfusion theory of post-stroke cognitive impairment. However it does not indicate a role for heart rate and blood pressure variability in the mechanism of increasing white matter disease or decline in cognition in the two years following stroke.EThOS - Electronic Theses Online ServiceGBUnited Kingdo