Twenty-four hour systolic blood pressure predicts long-term mortality following acute stroke.

OBJECTIVE: To assess the effects of acute blood pressure (BP) on long-term mortality following stroke. DESIGN: Prospective observational study. SETTING: Leicester Teaching Hospitals. PATIENTS: Two hundred and nineteen consecutive patients were recruited within 24 h of acute stroke. INTERVENTIONS: Clinic and 24 h BP levels were measured. Other risk factors previously associated with stroke mortality were recorded within 24 h of admission. No specific pharmacological interventions;were made. MAIN OUTCOME MEASURES: The primary outcome measure was death over a median follow-up period of over 2.5 years. The hazards ratios associated with predefined variables were assessed using Cox's proportional hazards modelling, and Kaplan-Meier survival plots were also calculated. RESULTS: On multiple variable analysis, 24 h systolic BP (> or = 160 mmHg) was associated with an increased hazards ratio of 2.41 (95% confidence intervals: 1.24-4.67) for death, compared to the reference group (140-159 mmHg). The addition of 24 h heart rate was significant, with increasing heart rate (> 83 bpm) associated with an increased mortality (P = 0.006), although this effect was not constant over time. Increasing age (> 80 years) at presentation was also associated with an increased hazards ratio of 2.53 (1.14-5.62) compared to age < or = 66 years. CONCLUSIONS: This study provides evidence that elevated 24 h systolic BP in the acute stroke period is associated with increased long-term mortality. This may have implications in the therapeutic management of BP following stroke, though further research is required to determine the timing, nature and effect of such an intervention.

Responses to the prolonged head-up tilt followed by sublingual nitrate provocation in asymptomatic older adults.

BACKGROUND: prolonged head-up tilt testing and sublingual nitrate provocation are increasingly used in the diagnosis of neurocardiogenic syncope. However there are few data regarding the results of these tests in asymptomatic older subjects. OBJECTIVE: to assess the responses to the prolonged head-up tilt test followed by sublingual glyceryl trinitrate provocation in asymptomatic subjects over the age of 60 years. DESIGN: observational study. METHODS: we recruited 64 asymptomatic subjects over the age of 60 (39 men, 25 women) from two general practice lists in Nottingham and Leicester. Exclusion criteria were: history of syncope, ischaemic heart disease, cerebrovascular disease, marked aortic stenosis, carotid artery disease and being unable to stand for the duration of the test. All subjects underwent a full clinical examination, a 12-lead electrocardiogram and a 30-40-min head-up tilt test, during which we monitored the heart rate and blood pressure continuously. We ended the test prematurely if the subjects developed syncope or symptoms of presyncope associated with hypotension with or without bradycardia. If they remained asymptomatic at the end of this period, they received 400 microg of sublingual glyceryl trinitrate and monitoring continued for another 15 min. SETTINGS: two teaching hospitals in Nottingham and Leicester. RESULTS: six (9%) of the subjects had a positive response (syncope or presyncope) to the prolonged head-up tilt test prior to glyceryl trinitrate provocation. After provocation, 30 (52%) of the remaining 58 subjects had a positive response. CONCLUSION: the role of sublingual glyceryl trinitrate provocation following prolonged head-up tilt testing in the diagnosis of neurocardiogenic (vasovagal) syncope in older people is questionable, as many asymptomatic older subjects demonstrate syncopal or presyncopal symptoms.

Mononuclear cell adhesion to collagen ex vivo is related to pulse pressure in elderly subjects.

Mononuclear cells and platelets are intimately involved in the pathogenesis and complications of cardiovascular disease. Platelet activation has been reported in hypertension, though the activation-state of monocytes has received less attention. In this study the adhesiveness of monocytes and platelets was assessed and any relationship between the adhesive properties of these cellular elements and plasma levels of soluble adhesion molecules and blood pressure parameters determined. Fifty six elderly volunteers, of whom 32 were classified hypertensive (daytime SBP > or = 135 mmHg), underwent 24 h blood pressure monitoring, assessment of monocyte and platelet adhesion and measurement of the plasma soluble adhesion molecules ICAM-1, L-selectin, E-selectin and vWF. In the elderly hypertensive subjects, monocyte adhesion to collagen coated (P < 0.05) and tissue culture plastic microwells (P < 0.05) was significantly elevated and circulating levels of soluble ICAM-1 (P < 0.01) and soluble E-selectin (P < 0.05) were significantly raised compared to their normotensive counterparts. A significant correlation was found to exist between monocyte adhesion to collagen and daytime pulse pressure (r = 0.39, P < 0.01) and also between plasma levels of soluble E-selectin and clinic DBP (r = 0.40, P < 0.001). The increased monocyte adhesion witnessed in hypertensive subjects and with increasing pulse pressure may contribute to the increased risk of cardiovascular disease in hypertension. Whether this increased adhesiveness is a property of the monocytes. or reflects endothelial cell activation, remains to be determined.

Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons.

OBJECTIVES: To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids. DESIGN: A 6-month double-blind randomized placebo-controlled cross-over study with a 1 -week washout between cross-over periods. METHODS: Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion. Clinic and 24-h ambulatory blood pressure, plasma ascorbate and lipids were measured at baseline and at the end of each cross-over phase. RESULTS: Clinic blood pressure did not change between placebo and vitamin C phases. Daytime ambulatory blood pressure showed a small but significant fall in systolic blood pressure (2.0 +/- 5.2 mmHg; 95% confidence interval 0-3.9 mmHg) but not in diastolic blood pressure. Regression analysis showed that with increasing baseline daytime blood pressure the fall in blood pressure with vitamin C supplementation increased. Regression analysis of the change in high-density lipoprotein (HDL) cholesterol showed a significant effect of sex on the change in HDL cholesterol. In women, but not men, HDL cholesterol increased significantly by 0.08 +/- 0.11 mmol/l, P=0.007. There was no change in low-density lipoprotein cholesterol between treatment periods. CONCLUSION: In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure, which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke.

Antihypertensive therapy in the prevention of stroke: what, when and for whom?

It is clear that antihypertensive regimens based on a low dose thiazide diuretic are effective for the primary prevention of stroke, particularly in older patients. In patients with diabetes mellitus who are at a higher risk of stroke, low dose thiazide diuretics and ACE inhibitors are of benefit. In those with isolated systolic hypertension, long-acting dihydropyridine calcium antagonists, in addition tolow dose thiazide diuretics, have also been shown to significantly reduce stroke risk. However, to attain sufficient lowering of blood pressure (BP) to most effectively reduce the risk of stroke (i.e. to levels of 140-150/80-85 mm Hg or lower and perhaps to <140/<80 mm Hg in patients with diabetes mellitus) combination therapy will be required. Immediately following stroke BP tends to fall spontaneously and therapy is probably not required in the great majority of patients during the first few days poststroke. If treatment is required shortly after this period, agents with a slow and gentle onset of action appear to be preferable; some preliminary data suggest that ACE inhibitors, despite lowering systemic BP, have no significant effect on cerebral blood flow. However, there is little clinical outcome data to clearly define the role of antihypertensive treatment in the early poststroke period. Whether existing antihypertensive therapy should be continued following stroke is also unclear, but such decisions may be influenced by factors such as the actual BP level, other indications for treatment (e.g. angina pectoris or cardiac failure) or the presence of dysphagia. There is more evidence to suggest that, some weeks to months following stroke (particularly a minor stroke), lower rather than higher BP is favourable, and better control of high BP with therapy reduces stroke recurrence.

Diurnal blood pressure change varies with stroke subtype in the acute phase.

BACKGROUND AND PURPOSE: It is unclear whether acute stroke is associated with a loss of the normal diurnal blood pressure (BP) change and whether stroke type influences this. Some of this confusion results from the use of fixed time definitions of day and night, which can be overcome by the use of cumulative sums analysis (cusums). METHODS: Ninety-eight stroke patients had 24-hour BP monitoring (Spacelabs 90207) performed within 48 hours of ictus. Three subgroups were identified: cortical infarct, n=50; subcortical infarct, n=29; and primary intracerebral hemorrhage [PICH], n= 19. An age-matched control group of 74 subjects was also studied. Diurnal change was assessed by both day-night differences (absolute and percentage) and cusums (cusums plot height [CPH] and circadian alteration magnitude [CDCAM]); ANCOVA was used to compare groups. RESULTS: Compared with control subjects, cortical infarct and PICH subgroups had significantly reduced mean diurnal systolic changes using day-night differences (absolute, -12 and -17 mm Hg; percentage, -10 and -12, respectively; P < 0.0001) and cusums (CDCAM, -6.96 and -8.6 mm Hg; CPH, -32.05 and -46.04 mm Hg, respectively; P < 0.005), only the subcortical infarct subgroup demonstrated reduced percentage differences (-4.4%, P < 0.02). Mean diastolic differences were significantly reduced in all stroke subgroups(CPH, -24.84, -17.31, and -36.92 mm Hg; absolute, -8.26, -4.04, and -11.44 mm Hg; percentage, -10.65, -5.81, and -15.23%, for cortical infarct, subcortical infarct, and PICH subgroups, respectively; P < 0.05), except for CDCAM, which was not reduced in subcortical infarcts (-4.78 and -7.70 mm Hg for cortical infarct and PICH subgroups, respectively; P < 0.001). CONCLUSIONS: Diurnal BP change was reduced in the 3 stroke subgroups studied, especially in patients with cortical infarcts and PICH. This may reflect damage to the central modulation of autonomic BP control. The implications in terms of prognosis and therapy in the acute period require further study.

Blood pressure measurement and antihypertensive therapy in acute stroke.

Inappropriate management of high blood pressure in acute stroke can adversely affect outcome. We examined blood pressure evaluation and antihypertensive therapy during the first week post-stroke in 40 patients at a district general hospital with no stroke unit. In the first 24 hours, median frequency of blood pressure recording was 3 (range 1-12). After day 1, 11 (28%) had no blood pressure readings for one or two consecutive days. The side of measurement was not recorded in any patient. None of the 22 hypertensives (55%) had a bilateral measurement to exclude interarm inequality, and only 3 (7%) of all patients had postural readings to exclude orthostatic hypotension. Fourteen (35%) received antihypertensive therapy without meeting recommended indications; some even had low blood pressure. As most stroke patients are managed in general medical wards rather than stroke units, a greater awareness of these important aspects of blood pressure evaluation and therapy are needed among medical and nursing staff.

Hypokalemia and potassium excretion in stroke patients.

OBJECTIVES: To determine (1) the prevalence of hypokalemia (plasma potassium < or = 3.4 mmol/L) in a group of stroke patients in comparison with age- and sex-matched groups of patients having sustained a myocardial infarction or having mild hypertension and (2) the association between plasma potassium concentration and stroke outcome. DESIGN: Observational study. PARTICIPANTS: A total of 421 consecutive stroke patients admitted to a teaching hospital, 150 consecutive patients 50 years or older with myocardial infarction admitted to the hospitals Coronary Care Unit, and 161 out-patients 60 years or older with borderline and established hypertension. MEASUREMENTS: All stroke and cardiac patients had plasma urea and electrolytes estimated within 2 hours of hospital admission; in the hypertensive group blood samples were taken in clinic. Stroke patients had blood pressure, stroke severity (Barthel score) and smoking status recorded. A sub-group of 61 stroke patients and all 79 hypertensive patients not taking antihypertensive medication had 24-hour urine electrolyte excretion measured. Outcome (independent, dependent, or dead) at 3 months post-stroke was established in 349 patients. RESULTS: Hypokalemia occurred more frequently in stroke patients than in patients with myocardial infarction (84 (20%) vs 15 (10%), P = .008) or patients with hypertension (84 (20%) vs 13 (8%), P < .001), even when patients taking diuretics were excluded from analysis (56 (19%) vs 12 (9%) of cardiac group, P = .014 and 56 (19%) vs 4 (5%) of hypertensive group, P = .005, respectively). 24-hour urine excretion of potassium and the potassium:creatinine ratio was lower in stroke patients than in hypertensive patients (41 +/- 21 vs 62 +/- 25 mmol/24 hour, P = .001, 5.5 +/- 2.2 vs 7.4 +/- 2.6 mmol/24 hour, P = .001, respectively). On survival analysis, a lower plasma potassium on admission to hospital was associated with an increased chance of death, independent of age, stroke severity, history of hypertension, blood pressure level, or smoking history (hazard ratio 1.73 (95% CI: 1.03-2.9) for a 1 mmol/L lower plasma potassium concentration). CONCLUSIONS: Hypokalemia post stroke is common and may be associated with a poor outcome.

Metabolic and orthostatic blood pressure responses to a low-sodium diet in elderly hypertensives.

In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.

Long-term potassium supplementation lowers blood pressure in elderly hypertensive subjects.

Following a randomised cross-over trial of the effect of a four-week 60 mmol/day potassium supplement versus placebo on blood pressure (BP), eight of the original 18 hypertensive subjects continued with a 48 mmol daily potassium supplement for four months. For these eight subjects 24-h potassium excretion during placebo, one month of 60 mmol and four months of 48 mmol daily potassium supplementation phases was 56 +/- 23, 102 +/- 28 and 90 +/- 35 mmol/24 hours, respectively, and mean 24-h BP following each phase was 160 +/- 16/89 +/- 11, 147 +/- 13/83 +/- 12 and 145 +/- 14/81+/- 9 mmHg respectively, a significant fall in mean 24-h SBP between four months of potassium supplement and placebo period of 15 +/- 13 mmHg (95% CI: 4, 26 mmHg, p = 0.02), although the fall in 24-h DBP was not significant (8 +/- 11 mmHg, 95% CI: 0, 17 mmHg, p = 0.08). Modest increases in dietary potassium intake could have significant effects on lowering BP in the large proportion of elderly subjects with hypertension.

Antihypertensive therapy and orthostatic responses in elderly hospital in-patients.

The study aim was to determine the association between use of antihypertensive drugs and orthostatic hypotension on prolonged standing in an elderly in-patient population. Hospital in-patients aged > 60 years had manually and automatically determined blood pressure (BP) measurements recorded in the supine position. On standing a total of nine measurements were taken over 10 min, six measurements were taken using a mercury sphygmomanometer and three by an automatic monitor. Seventy-four patients of mean age 73 +/- 7 years were studied; 52 (70%) were taking > or = 1 antihypertensive drug and 22 (30%) none. On standing, manually determined systolic BP (SBP) fell to a similar extent in the group of patients taking antihypertensive therapy compared to those not taking such treatment (at 9 min standing: -6 +/- 16 vs -10 +/- 15 mm Hg, respectively) and the frequency of orthostatic hypotension (SBP fall > or = 20 mm Hg) was similar in both groups [at 9 min: 9 (17%) vs 5 (23%)]. Automatically determined measurements also revealed similar orthostatic SBP responses in both treated and non-treated groups (at 8 min: -3 +/- 18 vs -6 +/- 13 mm Hg, respectively) and a similar frequency of orthostatic hypotension. No significant change in standing compared to supine diastolic BP (DBP) measured manually or automatically was seen in either group. Even in the subgroup of patients taking > or = 2 antihypertensive drugs the orthostatichypotension. BP response and the frequency of orthostatic hypotension was similar to that in the non-treated group. In conclusion no association was found between use of antihypertensive therapy and orthostatic hypotension in an elderly in-patient population.

The knowledge of hospital patients about vascular diseases and their risk factors.

The knowledge of 28 stroke patients on the nature, consequences, treatment and risk factors of stroke and ischaemic heart disease was examined using a questionnaire and compared with that of 26 patients with ischaemic heart disease and 41 controls without evidence of vascular disease. Information was also collected on the patients' willingness to change their life-style, the information and advice they had received and their desire for more information. It was found that about half of the elderly stroke and heart disease patients had a reasonable knowledge of the condition and its related risk factors. Only eight (14%) patients remembered receiving information and advice in relation to their condition during their hospital stay compared with one (2%) control. There was a significant difference between the number of stroke and heart disease patients who wanted to know more about their condition compared with the control group (32 vs 14; p = 0.03). A quarter of the patients and half of the controls knew that fruit and vegetables were good for you and excessive fat and alcohol were less inducive to good health. Most patients with a risk factor were willing to exercise more, stop smoking, cut down on their drinking, or lose weight. These results suggest that elderly hospital patients have a reasonable basic knowledge about vascular diseases, but that a significant number want to know more and would be willing to change their life-style.

Junior hospital doctors' views on their training in the UK.

To ascertain the views of senior house officers and registrars on the educational and training component of their posts, a questionnaire was sent to all full-time doctors working in training posts in general and/or geriatric medicine at three district general and three teaching hospitals. Completed questionnaires were received from 64 (61%) of 105 doctors who were contacted. Most had a careers counsellor or tutor, although less than two-thirds thought they had benefited from this arrangement. The majority of doctors attended at least two medical tutorials or meetings per week; most wanted to attend more but were unable to because of other work commitments. Supervision by more senior staff on the ward was deemed by most to be satisfactory, but less so in out-patient clinics. Overall, one-third of doctors thought that training was inadequate and three-quarters wanted a greater amount of formal education. The majority of junior doctors' time was spent on routine work and most considered :training' constituted less than 10% of their working time. Doctors in training require more sessions designated as educational, with protected time to attend these.

Differences in orthostatic blood pressure changes measured with an oscillometric blood pressure monitor and a mercury sphygmomanometer.

AIMS: To compare orthostatic blood pressure (BP) changes recorded with the SpaceLabs 90207 BP monitor (SL) and the standard mercury sphygmomanometer (HgS). METHODS: 85 hospital in-patients aged 60-90 years had nine BP measurements recorded by both instruments using the same arm sequential measurement technique in supine and standing position by two observers. Supine BP was taken as the final set of three supine measurements, ie, one made with the SL, and the mean of the two HgS readings immediately before and after the monitor reading. From the SL supine reading was subtracted the three standing SL monitor readings and from the mean of the 2 supine HgS readings was subtracted the six standing measurements taken by the HgS. The orthostatic BP changes recorded by the HgS immediately before and after each SL monitor reading were averaged and compared with the corresponding orthostatic change recorded by the monitor. RESULTS: The monitor underestimated orthostatic SBP changes at all 3 comparisons compared to the HgS; i) -0.9 +/- 14.9 vs 2.7 +/- 10.3 mmHg, p < 0.05; ii) 0.3 +/- 15.4 vs 4.5 +/- 12.1 mmHg, p < 0.05; iii) 3.5 +/- 16.9 vs 7.5 +/- 14.9 mmHg, p < 0.05, respectively. These differences were more pronounced in males than females. Orthostatic hypotension (defined as SBP fall on standing of > or = 20 mmHg) was recorded in males by the monitor in four (8%) and by the HgS in 12 (25%), p < 0.05. Mean orthostatic DBP changes were similarly recorded by the monitor and HgS. On average only 60% and 77% of orthostatic SBP measurements taken by both instruments agreed within 10 and 15 mmHg respectively while 75% and 88% respectively of orthostatic DBP changes agreed within these limits. CONCLUSION: Orthostatic BP falls measured by an automatic oscillometric BP monitor may not be equivalent to those taken with a HgS and their use adds a further variable to the comparison of orthostatic BP changes between studies.

Twenty-four-hour ambulatory blood pressure in old and very old subjects.

OBJECTIVE: To compare clinic and 24-h blood pressure levels and profiles in young elderly (aged 65-79 years) and old elderly (aged > or = 80 years) subjects. SUBJECTS AND METHODS: A cross-sectional observational study was conducted on 108 ambulant subjects (51 males) aged 65-95 years with no known history of hypertension, recruited from the community (55%) and hospital outpatients (35%) and inpatients (10%). Three clinic blood pressure measurements were taken, followed by 24-h ambulatory blood pressure monitoring and then a further three clinic measurements, the mean of these being defined as the clinic blood pressure. RESULTS: Clinic systolic blood pressure was significantly higher in females than males (148 +/- 20 versus 136 +/- 23 mmHg, P = 0.02), but 24-h systolic blood pressure was similar. Mean 24-h and daytime blood pressure levels were significantly lower than clinic blood pressure in females but in males only 24-h systolic blood pressure was lower than the clinic level. In young elderly compared to old elderly females the clinic-daytime ambulatory systolic blood pressure difference was significantly reduced (14 +/- 22 versus 1 +/- 17 mmHg, respectively; P = 0.04). A significant nocturnal systolic/diastolic blood pressure fall was seen in young elderly and old elderly males (9 +/- 12/7 +/- 7 versus 6 +/- 11/7 +/- 8 mmHg) but in females the nocturnal systolic blood pressure fall was inversely related to age (r = -0.32, P = 0.02). CONCLUSIONS: The white-coat effect is common in young elderly females, but uncommon in very elderly females and males aged > or = 65 years; a decline in casual blood pressure in the very elderly may partly arise from a reduction in the white-coat effect. Nocturnal blood pressure falls also decline in the very elderly, especially in females.

Pharmacological therapy for acute stroke: the future.

Stroke is a major cause of mortality, morbidity, and resource consumption. To reduce this burden, enormous efforts have focused on the development of drugs to limit brain damage. However, a breakthrough has not yet materialised, and data suggest that even if future drug trials do demonstrate a benefit, the overall impact of such drugs will be relatively limited. The pathophysiology of stroke is too complex to be markedly influenced by interruption of one or two components of the ischaemic cascade; intervention needs to be very soon post-stroke; and multiple pre-existing diseases and disabilities in elderly patients diminish their scope for recovery. In contrast, wider application of primary prevention, secondary prevention, and better organisation of services (eg setting up stroke units), could have a far greater effect on public health. Despite considerable enthusiasm for drug therapy in acute stroke, it is likely that the overall potential of such therapy will be disappointing.

Reproducibility of the circadian systolic blood pressure variation in the elderly.

OBJECTIVES: To establish the reproducibility of the nocturnal systolic blood pressure (SBP) change in elderly subjects and to examine the use of cumulative sums (cusums) analysis in the assessment of circadian SBP variation. SUBJECTS: Forty-two untreated elderly subjects (35 hypertensive, 7 normotensive) of mean age 75.5 years from the hypertension clinic at a large teaching hospital participated in a reproducibility study. METHODS: Twenty-four-hour ambulatory blood pressure monitoring was performed and repeated at a median interval of 2 months (range 2 weeks to 9 months). OUTCOME MEASURES: Reproducibility of circadian SBP variation from fixed time analysis of day-night SBP difference and from cusums-based parameters. RESULTS: Twenty-four-hour SBP values were highly reproducible with a coefficient of variation of 5.8%. However, the day-night SBP difference for fixed time periods was poorly reproducible, with a coefficient of variation > 130%. A substantial proportion of subjects (36-43%) altered their 'dipping status' between visits. The use of cusums analysis improved the reproducibility of measures of circadian SBP change (cusums plot height and maximum circadian variation) with coefficients of variation falling to 40 and 38%, respectively. CONCLUSIONS: The use of fixed time definitions results in poor reproducibility of the circadian SBP change in the elderly, which will lead to regression dilution bias when studying the relationship of circadian SBP variation to outcome measures in hypertension. The notion of dipping and non-dipping circadian blood pressure patterns should be abandoned in favour of more reproducible cusums-based measures of circadian blood pressure variation.