Estimated glomerular filtration rate and risk of poor outcomes after stroke.

BACKGROUND AND PURPOSE: The relationship of the estimated glomerular filtration rate (eGFR) with complications after stroke has not been fully characterized for the entire clinical spectrum of eGFR and for the fluctuation in eGFR during hospital stay. METHODS: Data from the Norfolk and Norwich Stroke Registry recorded between January 2003 and April 2015 were analysed. eGFR was categorized into six clinically relevant categories as per the Kidney Disease Improving Global Outcomes guidelines. The change in eGFR during acute admission was categorized into the following: within 5% change (reference), 5%-20% decline, >20% decline, 5%-20% increase and >20% increase. All-cause mortality, recurrent stroke, incident myocardial infarction, prolonged hospital stay and stroke disability at discharge were outcomes of interest. RESULTS: In all, 10 329 stroke patients (mean age 77.8 years) were followed for a mean of 2.9 years (30 126 person-years). Multivariable adjusted hazard ratios (95% confidence interval) for all-cause mortality were 0.91 (0.80-1.04), 0.96 (0.83-1.11), 1.23 (1.06-1.43), 1.54 (1.31-1.82) and 2.38 (1.91-2.97) for eGFR levels 60-89, 45-59, 30-44, 15-29 and <15 respectively, compared to eGFR ≥ 90 ml/min/1.73 m2 . The hazard ratios (95% confidence interval) for eGFR change were 1.56 (1.36-1.79), 1.17 (1.05-1.30), 1.47 (1.32-1.62) and 1.71 (1.55-1.88) for >20% decline, 5%-20% decline, 5%-20% increase and >20% increase, respectively, compared to change within 5%. Results were similar for other outcomes except recurrent stroke. CONCLUSIONS: Stroke patients with eGFR < 45 ml/min/1.73 m2 at hospital admission and >5% decline or increase in eGFR during hospital stay were at substantially higher risk of poor outcomes, particularly all-cause mortality, myocardial infarction, prolonged hospital stay and disability at discharge.

Impact of stroke-associated pneumonia on mortality, length of hospitalization, and functional outcome.

OBJECTIVES: Stroke-associated pneumonia (SAP) is common and associated with adverse outcomes. Data on its impact beyond 1 year are scarce. MATERIALS AND METHODS: This observational study was conducted in a cohort of stroke patients admitted consecutively to a tertiary referral center in the east of England, UK (January 2003-April 2015). Logistic regression models examined inpatient mortality and length of stay (LOS). Cox regression models examined longer-term mortality at predefined time periods (0-90 days, 90 days-1 year, 1-3 years, and 3-10 years) for SAP. Effect of SAP on functional outcome at discharge was assessed using logistic regression. RESULTS: A total of 9238 patients (mean age [±SD] 77.61 ± 11.88 years) were included. SAP was diagnosed in 1083 (11.7%) patients. The majority of these cases (n = 658; 60.8%) were aspiration pneumonia. After controlling for age, sex, stroke type, Oxfordshire Community Stroke Project (OCSP) classification, prestroke modified Rankin scale, comorbidities, and acute illness markers, mortality estimates remained significant at 3 time periods: inpatient (OR 5.87, 95%CI [4.97-6.93]), 0-90 days (2.17 [1.97-2.40]), and 91-365 days (HR 1.31 [1.03-1.67]). SAP was also associated with higher odds of long LOS (OR 1.93 [1.67-2.22]) and worse functional outcome (OR 7.17 [5.44-9.45]). In this cohort, SAP did not increase mortality risk beyond 1 year post-stroke, but it was associated with reduced mortality beyond 3 years. CONCLUSIONS: Stroke-associated pneumonia is not associated with increased long-term mortality, but it is linked with increased mortality up to 1 year, prolonged LOS, and poor functional outcome on discharge. Targeted intervention strategies are required to improve outcomes of SAP patients who survive to hospital discharge.

Addition of sodium criterion to SOAR stroke score.

OBJECTIVES: To examine the usefulness of including sodium (Na) levels as a criterion to the SOAR stroke score in predicting inpatient and 7-day mortality in stroke. MATERIALS AND METHODS: Data from the Norfolk and Norwich University Hospital Stroke & TIA register (2003-2015) were analysed. Univariate and then multivariate models controlling for SOAR variables were used to assess the association between admission sodium levels and inpatient and 7-day mortality. The prognostic ability of the SOAR and SOAR Na scores for mortality outcomes at both time points were then compared using the Area Under the Curve (AUC) values from the Receiver Operating Characteristic curves. RESULTS: A total of 8493 cases were included (male=47.4%, mean (SD) 77.7 (11.6) years). Compared with normonatremia (135-145 mmol/L), hypernatraemia (>145 mmol/L) was associated with inpatient mortality and moderate (125-129 mmol/L) and severe hypontraemia (<125 mmol/L) with 7-day mortality after adjustment for stroke type, Oxfordshire Community Stroke Project classification, age, prestroke modified Rankin score and sex. The SOAR and SOAR-Na scores both performed well in predicting inpatient mortality with AUC values of .794 (.78-.81) and .796 (.78-.81), respectively. 7-day mortality showed similar results. Both scores were less predictive in those with chronic kidney disease (CKD) and more so in those with hypoglycaemia. CONCLUSION: The SOAR-Na did not perform considerably better than the SOAR stroke score. However, the performance of SOAR-Na in those with CKD and dysglycaemias requires further investigation.

Age but not ABCD(2) score predicts any level of carotid stenosis in either symptomatic or asymptomatic side in transient ischaemic attack.

BACKGROUND: The ABCD(2) score is routinely used in assessment of transient ischaemic attack (TIA) to assess the risk of developing stroke. There remains uncertainty regarding whether the ABCD(2) score could be used to help predict extent of carotid artery stenosis (CAS). OBJECTIVES: We aimed to (i) collate and analyse all available published literature on this topic and (ii) compare the data from our local population to the existing evidence base. MATERIALS AND METHODS: We conducted a retrospective-observational study over a 6-month period using our East of England hospital-based TIA clinic data with a catchment population of ~750,000. We also searched the literature on studies reporting the association between ABCD(2) score and CAS. RESULTS: We included 341 patients in our observational study. The mean age in our cohort was 72.86 years (SD 10.91) with 52% male participants. ABCD(2) score was not significantly associated with CAS (p = 0.78). Only age > 60 years was significantly associated with ipsilateral (> 50%) and contralateral CAS (> 50% and > 70%) (p < 0.01) after controlling for other confounders. The systematic review identified four studies for inclusion and no significant association between ABCD(2) score and CAS was reported, confirming our findings. CONCLUSION: Our systematic review and observational study confirm that the ABCD(2) score does not predict CAS. However, our observational study has examined a larger number of possible predictors and demonstrates that age appears to be the single best predictor of CAS in patients presenting with a TIA. Selection of urgent carotid ultrasound scan thus should be based on individual patient's age and potential benefit of carotid intervention rather than ABCD(2) score.

The SOAR stroke score predicts hospital length of stay in acute stroke: an external validation study.

AIMS: The objective of this study is to externally validate the SOAR stroke score (Stroke subtype, Oxfordshire Community Stroke Project Classification, Age and prestroke modified Rankin score) in predicting hospital length of stay (LOS) following an admission for acute stroke. METHODS: We conducted a multi-centre observational study in eight National Health Service hospital trusts in the Anglia Stroke & Heart Clinical Network between September 2008 and April 2011. The usefulness of the SOAR stroke score in predicting hospital LOS in the acute settings was examined for all stroke and then stratified by discharge status (discharged alive or died during the admission). RESULTS: A total of 3596 patients (mean age 77 years) with first-ever or recurrent stroke (92% ischaemic) were included. Increasing LOS was observed with increasing SOAR stroke score (p < 0.001 for both mean and median) and the SOAR stroke score of 0 had the shortest mean LOS (12 ± 20 days) while the SOAR stroke score of 6 had the longest mean LOS (26 ± 28 days). Among patients who were discharged alive, increasing SOAR stroke score had a significantly higher mean and median LOS (p < 0.001 for both mean and median) and the LOS peaked among patients with score value of 6 [mean (SD) 35 ± 31 days, median (IQR) 23 (14-48) days]. For patients who died as in-patient, there was no significant difference in mean or median LOS with increasing SOAR stroke score (p = 0.68 and p = 0.79, respectively). CONCLUSION: This external validation study confirms the usefulness of the SOAR stroke score in predicting LOS in patients with acute stroke especially in those who are likely to survive to discharge. This provides a simple prognostic score useful for clinicians, patients and service providers.

TIA, stroke and orthostatic hypotension: a disease spectrum related to ageing vasculature?

AIMS: We sought to identify the determinants of orthostatic hypotension (OH) among patients referred to the transient ischaemic attack (TIA) clinic. METHODS: We conducted a retrospective analysis of prospectively collected data on patients who attended the TIA clinic in a UK hospital between January 2006 and September 2009. Each patient had their supine and standing or sitting blood pressure measured. Logistic regression was used to estimate the univariate and multivariate odds of OH for the subgroups of patients based on their diagnosis. A 10% significance level for the univariate analysis was used to identify variables in the multivariate model. RESULTS: A total of 3222 patients were studied of whom 1131 had a TIA, 665 a stroke and 1426 had other diagnoses. The prevalence of either systolic or diastolic OH in the TIA, stroke and patients with other diagnoses was similar being 22% (n = 251), 24% (n = 162) and 20% (n = 292), respectively. Multivariate analyses showed age, prior history of TIA, and diabetes were independently significantly associated with systolic OH alone or diastolic OH alone or either systolic or diastolic OH [ORs 1.03 (1.02-1.05); 1.56 (1.05-2.31); 1.65 (1.10-2.47), respectively]. Among the patients with the diagnosis of stroke, peripheral vascular disease (PVD) was significantly associated with increased odds of OH (3.56, 1.53-8.31), whereas male gender had a significantly lower odds of OH (0.61, 0.42-0.88). In patients with other diagnoses, age (1.04, 1.02-1.05) and diabetes (1.47, 1.04-2.09) were associated with OH, whereas male gender was (0.76, 0.58-1.00) not associated with OH. CONCLUSION: Orthostatic hypotension is prevalent among patients presenting to TIA clinic. Previous history of vascular disease (prior TIA/stroke/PVD) appears to be a significant associate of OH in this patient population.

A systematic review of the pharmacological management of orthostatic hypotension.

OBJECTIVES: The 'short' and 'long-term' benefits of pharmacological interventions to treat orthostatic hypotension (OH) remain unclear. The aim was to systematically examine the published literature on the effectiveness of different drug regimens for the treatment of OH. DESIGN: Systematic review. SETTING: MEDLINE (1950-Week 7, 2011), EMBASE (1980-Week 7, 2011), CINAHL (1981-Week 7, 2011) databases and hand-searching of bibliographies were used to identify suitable papers. PARTICIPANTS: Studies selected were those, which investigated drug treatment of OH in a single- or double-blind randomised controlled trial (RCT) in humans over 18 years of age. MEASUREMENTS: Data were extracted from suitable full-text articles by three investigators independently. RESULTS: The 13 trials met the criteria for systematic review amongst which was considerable variation in the size of postural blood pressure (BP) change with active treatment. However, there was evidence that commonly used drugs midodrine or fludrocortisone therapy did increase standing or head-up-tilt (HUT) systolic blood pressure in certain patient groups. CONCLUSION: The evidence that pharmacological therapy is of benefit for the treatment of OH is limited by the lack of good quality clinical trial evidence. Further well-designed RCTs of pharmacological treatment of OH investigating the impact on postural symptoms as well as actual BP changes are needed.

Current practice of carotid endarterectomy in the UK.

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with internal carotid stenosis of 50-99 per cent. This study assessed national surgical practice through audit of CEA procedures and outcomes. METHODS: This was a prospective cohort study of UK surgeons performing CEA, using clinical audit data collected continuously and reported in two rounds, covering operations from December 2005 to December 2007, and January 2008 to September 2009. RESULTS: Some 352 (92·6 per cent) of 380 eligible surgeons contributed data. Of 19,935 CEAs recorded by Hospital Episode Statistics, 12,496 (62·7 per cent) were submitted to the audit. A total of 10,452 operations (83·6 per cent) were performed for symptomatic carotid stenosis; among these patients, the presenting symptoms were transient ischaemic attack in 4507 (43·1 per cent), stroke in 3572 (34·2 per cent) and amaurosis fugax in 1965 (18·8 per cent). The 30-day mortality rate was 1·0 per cent (48 of 4944) in round 1 and 0·8 per cent (50 of 6151) in round 2; the most common cause of death was stroke, followed by myocardial infarction. The rate of death or stroke within 30 days of surgery was 2·5 per cent (124 of 4918) in round 1 and 1·8 per cent (112 of 6135) in round 2. CONCLUSION: CEA is performed less commonly in the UK than in other European countries and probably remains underutilized in the prevention of stroke. Increasing the number of CEAs done in the UK, together with reducing surgical waiting times, could prevent more strokes.

Death-associated protein kinase (DAPK1) in cerebral cortex of late-onset Alzheimer's disease patients and aged controls.

AIMS: Here our objective was to detect the pro-apoptotic serine/threonine kinase death-associated protein kinase (DAPK1) in aged human cerebral cortex and to test the hypothesis that DAPK1 abundance is associated with late-onset Alzheimer's disease (AD). METHODS: Using Western analysis and immunohistochemistry we evaluated post mortem frontal cerebral cortex from patients with severe AD (mean age 76 years, range 66-91, n = 11, all male), and from control cases without serious central nervous system illness (mean age 77 years, range 61-95, n = 12, all male). We also examined brains of Tg2576 transgenic mice (males, aged 16-21 months), a model for chronic amyloid-induced brain injury. RESULTS: Immunohistochemical labelling showed DAPK1 expression in cortical neurones of human cortex and axonal tracts within subcortical white matter, both in AD and in control brains. Western analysis confirmed DAPK1 expression in all samples, although expression was very low in some control cases. DAPK1 abundance in the AD group was not significantly different from that in controls (P = 0.07, Mann-Whitney test). In brains of Tg2576 mice DAPK1 abundance was very similar to that in wild-type littermates (P = 0.96, Mann-Whitney test). CONCLUSION: We found that DAPK1 was expressed in neurones of aged human frontal cortex, both in AD and in control cases.

Continuous estimates of dynamic cerebral autoregulation: influence of non-invasive arterial blood pressure measurements.

Temporal variability of parameters which describe dynamic cerebral autoregulation (CA), usually quantified by the short-term relationship between arterial blood pressure (BP) and cerebral blood flow velocity (CBFV), could result from continuous adjustments in physiological regulatory mechanisms or could be the result of artefacts in methods of measurement, such as the use of non-invasive measurements of BP in the finger. In 27 subjects (61+/-11 years old) undergoing coronary artery angioplasty, BP was continuously recorded at rest with the Finapres device and in the ascending aorta (Millar catheter, BP(AO)), together with bilateral transcranial Doppler ultrasound in the middle cerebral artery, surface ECG and transcutaneous CO(2). Dynamic CA was expressed by the autoregulation index (ARI), ranging from 0 (absence of CA) to 9 (best CA). Time-varying, continuous estimates of ARI (ARI(t)) were obtained with an autoregressive moving-average (ARMA) model applied to a 60 s sliding data window. No significant differences were observed in the accuracy and precision of ARI(t) between estimates derived from the Finapres and BP(AO). Highly significant correlations were obtained between ARI(t) estimates from the right and left middle cerebral artery (MCA) (Finapres r=0.60+/-0.20; BP(AO) r=0.56+/-0.22) and also between the ARI(t) estimates from the Finapres and BP(AO) (right MCA r=0.70+/-0.22; left MCA r=0.74+/-0.22). Surrogate data showed that ARI(t) was highly sensitive to the presence of noise in the CBFV signal, with both the bias and dispersion of estimates increasing for lower values of ARI(t). This effect could explain the sudden drops of ARI(t) to zero as reported previously. Simulated sudden changes in ARI(t) can be detected by the Finapres, but the bias and variability of estimates also increase for lower values of ARI. In summary, the Finapres does not distort time-varying estimates of dynamic CA obtained with a sliding window combined with an ARMA model, but further research is needed to confirm these findings in healthy subjects and to assess the influence of different physiological manoeuvres.

Cerebral critical closing pressure estimation from Finapres and arterial blood pressure measurements in the aorta.

Estimates of cerebral critical closing pressure (CrCP) and resistance-area product (RAP) are often derived using noninvasive measurements of arterial blood pressure (ABP) in the finger, but the errors introduced by this approach, in relation to intra-vascular measurements of ABP, are not known. Continuous recordings of ABP (Finapres and solid-state catheter-tip transducer in the ascending aorta), cerebral blood flow velocity (CBFV, bilateral Doppler), ECG and transcutaneous CO(2) were performed following coronary catheterization. CrCP and RAP were calculated for each of 12,784 cardiac cycles from 27 subjects using the classical linear regression (LR) of the instantaneous CBFV-ABP relationship and also the first harmonic (H(1)) of the Fourier transform. There was a better agreement between LR and H(1) for the aortic measurements than for the Finapres (p < 0.000,01). For LR there were no significant differences for either CrCP or RAP due to the source of ABP measurement, but for H(1) the differences were highly significant (p < 0.000,03). The coherence functions between either CrCP or RAP values calculated with aortic pressure (input) or the Finapres (output) were significantly higher for H(1) than for LR for most harmonics below 0.2 Hz. When using the Finapres to estimate CrCP and RAP values, the LR method produces similar results to intra-arterial measurements of ABP for time-averaged values, but H(1) should be preferred in applications analysing beat-to-beat changes in these parameters.

Cerebral autoregulatory responses to head-up tilt in normal subjects and patients with recurrent vasovagal syncope.

BACKGROUND: The effect of orthostatic stress on dynamic cerebral autoregulation (CA) in normal subjects and patients with recurrent vasovagal syncope (VVS) is unclear. This study assessed the dynamic CA responses of both groups to head-up tilt. METHODS AND RESULTS: Seventeen patients with recurrent VVS and 17 pair-matched control subjects underwent 70 degrees head-up tilt for up to 30 minutes. Bilateral middle cerebral artery blood flow velocities (CBFV) were measured with transcranial Doppler ultrasound along with noninvasive beat-to-beat blood pressure (BP), heart rate, and transcutaneous and end-tidal CO(2) concentrations. Indices of dynamic CA were derived for periods before, during, and after tilt. Eight normal subjects who developed VVS in an identical protocol but who had no previous clinical history of syncope were also studied. CBFV and transcutaneous and end-tidal CO(2) levels declined significantly during head-up tilt in all groups (P<0.0001). Dynamic CA indices were unchanged throughout tilt in nonsyncopal control subjects and were initially unchanged in patients but deteriorated significantly in patients and syncopal control subjects in the minutes before (P=0.027 and P=0.012, respectively) and after (P=0.002 and P=0.007, respectively) syncope. CONCLUSIONS: Dynamic CA is preserved in patients and control subjects initially after head-up tilt. Autoregulatory function remains intact in nonsyncopal control subjects during prolonged orthostasis but deteriorates in patients and syncopal control subjects immediately before and after VVS.

A study of statin use in the prevention of cognitive impairment of vascular origin in the UK.

INTRODUCTION: There is increasing evidence suggesting that control of hypertension and antiplatelet therapy may prevent or reduce progression of vascular-related cognitive impairment (VCI), though a similar role of statins in this group of patients has yet to be established. METHODS: We conducted a postal survey of a group of 296 medical practitioners (comprising of physicians and psychiatrists specialising in the elderly, and general practitioners) inquiring into their management of (a) patients at high risk of developing VCI and (b) patients with established VCI. RESULTS: The overall response rate was 60% (177/296), with the highest response rate from psychiatrists. (a) For patients at high risk of developing VCI: 47% of clinicians believed that statins had an important role in preventing subsequent dementia: 4% would commence statins at a total cholesterol (TC) of 4-5 mmol/L; 38% with a TC of 5.1-6.5 mmol/L; and 32% with a TC of 6.6-8 mmol/L. Cardiovascular risk profile, age, cost and gender were other factors considered as important factors influencing statin prescription. (b) In those patients with established VCI: 32% of clinicians felt that statins had an important role in arresting progression, usually in people with a mild degree of cognitive impairment: 4% would commence statins at a TC of 4-5 mmol/L; 25% with a TC of 5.1-6.5 mmol/L; and 22% with a TC of 6.6-8 mmol/L. There were no major differences between clinicians in their prescribing habits. CONCLUSIONS: A substantial proportion of clinicians favour the use of statins in primary and secondary prevention of cognitive impairment of vascular origin, despite a lack of definite evidence to support their use at the present time.

Insights into the neurodegenerative process of Alzheimer's disease: a role for mononuclear phagocyte-associated inflammation and neurotoxicity.

Since the first description of Alzheimer's disease (AD) in 1907, significant progress was made into understanding disease pathophysiology. The enormous effort in AD research has translated into the discovery of genetic linkages for disease, into elucidating the structure and function of the etiologic beta-amyloid protein, and into unraveling the seemingly complex neuroimmunological cascade that affects neuronal dysfunction. Although effective therapies do not currently exist, many are being developed. We propose that the neuropathogenesis of AD, in measure, revolves around the immunological activation of glial cells, which in turn leads to alterations in inflammatory neurotoxin production, and ultimately to neuronal injury and death. Elucidating the mechanisms involved in such glial cell immune activation should provide valuable insights into understanding the disease process and in providing effective therapeutics to prevent and/or retard the devastating neurodegeneration that afflicts so many of our elderly.

Dynamic cerebral autoregulation is unaffected by aging.

BACKGROUND AND PURPOSE: Normal aging is associated with marked changes in the cardiovascular and cerebrovascular systems. Although cerebral autoregulation (CA) is impaired in certain disease states, the effect of age per se on dynamic CA in humans is unknown and the focus of this study. METHODS: Twenty-seven young subjects (/=55 years), matched for sex and systolic blood pressure (BP), underwent measurement of cerebral blood flow velocity by transcranial Doppler ultrasound and noninvasive beat-to-beat arterial BP measurement during induced and spontaneous dynamic BP stimuli. A standard dynamic autoregulatory index (ARI) was derived for each spontaneous and induced dynamic BP stimulus to include the step response, as well as cardiac baroreceptor sensitivity (BRS), for the 2 groups. RESULTS: The mean age of the young group was 29+/-5 years, and that of the older group was 68+/-5 years. Cardiac BRS was reduced in the older group (8. 6+/-4.5 versus 16.9+/-8.8 ms/mm Hg; P:<0.0001). However, no age-related differences were demonstrated in step response plots or in ARI values for any pressor or depressor dynamic BP stimulus (P:=0. 62), with mean ARI values for all stimuli combined being 4.9+/-1.8 for the young group and 5.0+/-2.3 for the older group. CONCLUSIONS: Although increasing age is associated with a decrease in cardiac BRS, dynamic CA, as assessed by step response analysis as well as cerebral blood flow responses to transient and induced BP stimuli, is unaffected by aging.

The pressor and metabolic effects of alcohol in normotensive subjects.

Changes in blood pressure, pulse rate, and plasma catecholamines, renin activity, cortisol, and calcium were studied in 16 normotensive subjects (eight with a family history of hypertension) for 5 hours following ingestion of alcohol-free and alcohol-loaded beer. Both systolic and diastolic blood pressure rose after alcohol consumption; maximum responses occurred at peak blood alcohol concentrations and were significantly higher than those seen after placebo. Pulse rate was also significantly higher after alcohol ingestion and continued to rise throughout the study. There was no difference in the pressor response to alcohol between the groups with and without a family history of hypertension. No difference was found in plasma norepinephrine or epinephrine levels between alcohol and placebo phases. However, subjects with no family history of hypertension had significantly higher plasma norepinephrine levels (p less than 0.01) than did those with a family history during both the alcohol and placebo phases, although baseline blood pressures were not significantly different. Plasma epinephrine level was similar in both groups. Plasma renin activity was unchanged throughout, but plasma cortisol fell during both phases. Plasma calcium showed a small but significant fall with alcohol consumption in both groups (p less than 0.001). These results indicate that in normotensive subjects alcohol ingestion causes a rise in systolic and diastolic blood pressure that is not influenced by a family history of hypertension. This effect does not appear to be sympathetically mediated but may be due to a direct vasoconstrictor effect of alcohol, possibly with an alcohol-induced shift in intracellular calcium.

Arterial baroreceptor-cardiac reflex sensitivity in the elderly.

Uncertainty still remains regarding the differing effects of blood pressure and age on baroreceptor-cardiac reflex sensitivity in elderly individuals; these differences are at least partly due to the differing methods and subject groups used in previous studies. We sought to resolve these issues by examining baroreflex sensitivity in 54 subjects aged 70 +/- 1 years (mean +/- SE; range, 60 to 81) divided into groups with combined systolic-diastolic hypertension (CH group, n = 16), isolated systolic hypertension (ISH group, n = 16), or normotension (NT group, n = 22). Baroreflex sensitivity was quantified from the pulse interval and blood pressure responses to the Valsalva maneuver and pressor (phenylephrine) and depressor (sodium nitroprusside) stimuli. Baroreflex sensitivity was significantly reduced in the two hypertensive groups but did not differ between them (Valsalva maneuver: CH group, 1.9 +/- 0.3 ms/mm Hg; ISH group, 2.8 +/- 0.5; NT group, 4.4 +/- 0.4; phenylephrine: CH group, 3.1 +/- 0.6; ISH group, 3.5 +/- 0.7; NT group, 7.7 +/- 1.0; sodium nitroprusside CH group, 2.1 +/- 0.3; ISH group, 3.6 +/- 0.8; NT group, 5.4 +/- 0.3; all P < .05 for comparison with the NT group). Thus, this study demonstrated reductions in baroreflex sensitivity with hypertension in elderly subjects consistent across all methods but with no difference between subjects with combined hypertension and isolated systolic hypertension matched for similar systolic pressure. Baroreflex sensitivity was related only to the level of systolic pressure independent of diastolic pressure or age. If elderly subjects with isolated systolic hypertension have a greater reduction in large-artery compliance than combined hypertensive subjects with similar systolic pressure, this does not appear to lead to further reductions in baroreflex sensitivity in these individuals.

Pulse pressure and resistance artery structure in the elderly.

There has been recent interest in the possibility that resistance vessel structural adaptation in hypertension may be more closely related to pulse pressure than to other blood pressure parameters. We investigated the relation between blood pressure and resistance vessel structure in a group of subjects from an age group (older than 60 years) in which a widening of pulse pressure is a typical finding and characterized blood pressure parameters using 24-hour ambulatory blood pressure monitoring. We studied resistance vessels retrieved from biopsies of skin and subcutaneous fat taken from the gluteal region of 32 subjects under local anesthesia (age, 70 +/- 1 years [mean +/- SEM], 21 of whom were hypertensive and 11 normotensive. Media-lumen ratio was higher in the hypertensive than the normotensive subjects (18.6 +/- 1.6% versus 12.8 +/- 1.2%, P < .01) and correlated with age (r = .44, P < .05), clinic systolic pressure (r = .35, P < .05), 24-hour systolic pressure (r = .40, P < .05), and 24-hour pulse pressure (r = .56, P < .001). Stepwise multivariate regression analysis identified clinic and 24-hour pulse pressure as the only significant predictors of media-lumen ratio independent of age, other parameters of clinic blood pressure, and blood pressure variability (R2 = 41%, P < .05). These findings confirm those from animal models of hypertension in demonstrating the importance of pulse pressure in relation to cardiovascular structural adaptation and have important implications for the goals of treatment of hypertension in the elderly.

Reproducibility of ambulatory and clinic blood pressure measurements in elderly hypertensive subjects.

OBJECTIVES: To compare the reproducibility of clinic and ambulatory blood pressure measurements in elderly hypertensive subjects. SUBJECTS: Twenty-two untreated elderly hypertensives, with a clinic systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood pressure (DBP) > 95 mmHg, and a mean age of 76 years (range 66-86). METHODS: Following three supine clinic blood pressure readings the subjects underwent 24-h non-invasive ambulatory blood pressure monitoring, measurements being taken at 20-min intervals from 0700 to 2200 h and at 30-min intervals from 2200 to 0700 h. Measurements were repeated during a further visit at a median interval of 10 weeks (range 1-10 months). RESULTS: Daytime ambulatory SBP levels were 20 mmHg (95% confidence interval 14-27 mmHg, P < 0.001) lower than clinic SBP, although DBP values were similar. The mean 24-h ambulatory SBP and DBP reproducibility [assessed by the standard deviation of differences (SDD) between visits] was significantly better than that for mean clinic blood pressure (SBP 6.3 versus 17.4 mmHg, P < 0.001; DBP 4.8 versus 7.0 mmHg, respectively, P < 0.05). With daytime defined as 1000-1959 h, the SDD between visits was 12.4 mmHg for SBP and 8.3 mmHg for DBP, but with daytime defined as 0700-2159 h, the SDD fell to 6.0 mmHg for SBP and 4.8 mmHg for DBP, values almost identical to those obtained with full 24-h blood pressure monitoring. There was no difference in night-time blood pressure reproducibility, whether night-time was defined as 2400-0559 h or 2200-0659 h. CONCLUSIONS: Both 24-h and daytime ambulatory blood pressure monitoring significantly improve the reproducibility of blood pressure measurements compared with clinic blood pressure readings in elderly hypertensive subjects. Increasing the number of daytime blood pressure readings by 50% (from 30 to 45) reduced the variability of blood pressure measurement by 50%. Twenty-four-hour ambulatory blood pressure monitoring is of value in obtaining reproducible blood pressure measurements in elderly hypertensive subjects. However, more than 30 readings are needed during a daytime recording to significantly reduce variability compared with repeated clinic measurements, although night-time variability is not significantly affected if the number of readings is reduced to 12 over a 6-h period.