Loss of consciousness, collapse and associated driving restrictions: a retrospective case note review - an important reminder regarding driving restrictions.

Background and aims National guidelines outlining medical standards for fitness to drive are provided by The Driver and Vehicle Licensing Agency. We aimed to establish whether patients presenting with collapse or loss of consciousness received documented advice regarding driving restrictions, if appropriate for their working diagnosis. Methods and results A retrospective case note review was undertaken over a four-month period for emergency patients clinically coded as seizure/convulsion (R568) and collapse/syncope (R55X); 163 patients had a primary or working diagnosis on discharge that suggested driving status and restrictions could have been reviewed. Six groupings of diagnoses were noted, and variation was seen amongst documentation for each. Current driving status was documented for 32 patients, and 34 had restriction advice documented; 73% (119 patients) had further investigations or clinic review planned. Conclusion Documentation of driving status and restrictions is poor. This audit serves to remind clinicians of the importance of considering driving status when discharging patients who have presented with collapse or loss of consciousness. Recent high-profile media coverage regarding medical driving restrictions, both locally and nationally, have emphasised the need for knowledge of The Driver and Vehicle Licensing Agency guidance.

Monotherapy With Major Antihypertensive Drug Classes and Risk of Hospital Admissions for Mood Disorders.

Major depressive and bipolar disorders predispose to atherosclerosis, and there is accruing data from animal model, epidemiological, and genomic studies that commonly used antihypertensive drugs may have a role in the pathogenesis or course of mood disorders. In this study, we propose to determine whether antihypertensive drugs have an impact on mood disorders through the analysis of patients on monotherapy with different classes of antihypertensive drugs from a large hospital database of 525 046 patients with follow-up for 5 years. There were 144 066 eligible patients fulfilling the inclusion criteria: age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days. The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641 685 person-years of follow-up). Patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had the lowest risk for mood disorder admissions, and compared with this group, those on ß-blockers (hazard ratio=2.11; [95% confidence interval, 1.12-3.98]; P=0.02) and calcium antagonists (2.28 [95% confidence interval, 1.13-4.58]; P=0.02) showed higher risk, whereas those on no antihypertensives (1.63 [95% confidence interval, 0.94-2.82]; P=0.08) and thiazide diuretics (1.56 [95% confidence interval, 0.65-3.73]; P=0.32) showed no significant difference. Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and ß-blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders.

Longitudinal Blood Pressure Control, Long-Term Mortality, and Predictive Utility of Serum Liver Enzymes and Bilirubin in Hypertensive Patients.

There is accruing evidence from general population studies that serum bilirubin and liver enzymes affect blood pressure (BP) and cardiovascular risk, but it is unclear whether these have an impact on hypertensive patients in terms of long-term survival or BP control. We analyzed 12 000 treated hypertensive individuals attending a tertiary care clinic followed up for 35 years for association between baseline liver function tests and cause-specific mortality after adjustment for conventional cardiovascular covariates. Generalized estimating equations were used to study the association of liver tests and follow-up BP. The total time at risk was 173 806 person years with median survival 32.3 years. Follow-up systolic BP over 5 years changed by -0.4 (alanine transaminase and bilirubin), +2.1(alkaline phosphatase), +0.9(γ-glutamyl transpeptidase) mm Hg for each standard deviation increase. Serum total bilirubin and alanine transaminase showed a significant negative association with all-cause and cardiovascular mortality, whereas alkaline phosphatase and γ-glutamyl transpeptidase showed a positive association and aspartate transaminase showed a U-shapedassociation. Serum bilirubin showed an incremental improvement of continuous net reclassification improvement by 8% to 26% for 25 year and 35 year cardiovascular mortality, whereas all liver markers together improved continuous net reclassification improvement by 19% to 47% compared with reference model. In hypertensive patients, serum liver enzymes and bilirubin within 4 standard deviations of the mean show independent effects on mortality and BP control. Our findings would support further studies to elucidate the mechanisms by which liver enzymes and bilirubin may exert an effect on BP and cardiovascular risk, but there is little support for using them in risk stratification.

Family history of premature cardiovascular disease: blood pressure control and long-term mortality outcomes in hypertensive patients.

AIMS: Current guidelines recommend early referral and initiation of intensive cardiovascular (CV) risk reduction in individuals with a positive family history of coronary heart disease (CHD). We hypothesized that a family history of premature CHD and stroke [CV disease (CVD)] would lead to earlier referral of hypertensive patients to secondary care clinic, leading to better control of risk factors, mitigating the excess risk seen in these individuals. METHODS AND RESULTS: We studied the association of a positive family history of CVD in 10 787 individuals with longitudinal changes in risk factors and long-term cause-specific mortality in the Glasgow Blood Pressure Clinic using generalized estimating equations and the Cox proportional hazard models, respectively. The total time at risk was 193 756 person-years with a median survival time of 29.2 years. A positive family history of CVD was associated with an earlier presentation to the clinic, a lower burden of traditional CV risk factors, and similar longitudinal blood pressure reduction and drug adherence compared with those without. But despite these positive features, all-cause [hazard ratio (HR) = 1.12, 95% confidence interval 1.01-1.25] and CV (HR = 1.20, 1.04-1.38) mortality independent of baseline risk factors were worse. Consistent results were observed in propensity score-matched analysis. Inclusion of family history of CVD did not improve mortality risk discrimination over and above traditional risk factors. CONCLUSION: Our study suggests that despite earlier referral and treatment of individuals with a positive family history of premature CVD, excess risk persists, indicating the need for continued and sustained efforts to reduce risk factors and drug adherence in these individuals.

Long-term and ultra long-term blood pressure variability during follow-up and mortality in 14,522 patients with hypertension.

Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be an independent cardiovascular risk predictor. The implication of this variability in hypertension clinical practice is unclear. BPV as average real variability (ARV) was calculated in 14,522 treated patients with hypertension in 4 time frames: year 1 (Y1), years 2 to 5 (Y2-5), years 5 to 10 (Y5-10), and years >10 (Y10+) from first clinic visit. Cox proportional hazards models for cause-specific mortality were used in each time frame separately for long-term BPV, across time frames based on ultra long-term BPV, and within each time frame stratified by mean BP. ARV in systolic blood pressure (SBP), termed ARV(SBP), was higher in Y1 (21.3±11.9 mm Hg) in contrast to Y2-5 (17.7±9.9 mm Hg), Y5-10 (17.4±9.6 mm Hg), and Y10+ (16.8±8.5 mm Hg). In all time frames, ARV(SBP) was higher in women (P<0.01) and in older age (P<0.001), chronic kidney disease (P<0.01), and prevalent cardiovascular disease (P<0.01). Higher long-term and ultra long-term BPV values were associated with increased mortality (all-cause, cardiovascular, and noncardiovascular mortality; P for trend, <0.001). This relationship was also evident in subgroups with mean SBP<140 mm Hg in all time frames. Monitoring BPV in clinical practice may facilitate risk reduction strategies by identifying treated hypertensive individuals at high risk, especially those with BP within the normal range.

Serum chloride is an independent predictor of mortality in hypertensive patients.

Chloride (Cl-) is the major extracellular anion in the body, accompanying sodium (Na+), and is primarily derived from dietary sources. Data suggest that increased dietary Cl- intake increases blood pressure, yet paradoxically, higher serum Cl- appears associated with lower mortality and cardiovascular risk. This implies that serum Cl- also reflects risk pathways independent of blood pressure, serum Na+, and bicarbonate (HCO3-). We analyzed 12,968 hypertensive individuals followed up for 35 years, using Cox proportional hazards model to test whether baseline serum Cl- was an independent predictor of mortality. To distinguish the effect of Cl- from Na+ and HCO3-, we adjusted for these electrolytes and also performed the analysis stratified by Na+ /HCO3- and Cl- levels. Generalized estimating equation was used to determine the effect of baseline Cl- on follow-up blood pressure. The total time at risk was 19,7101 person-years. The lowest quintile of serum Cl- (<100 mEq/L) was associated with a 20% higher mortality (all-cause, cardiovascular and noncardiovascular) compared with the remainder of the subjects. A 1 mEq/L increase in serum Cl- was associated with a 1.5% (hazard ratio, 0.985; 95% confidence interval, 0.98-0.99) reduction in all-cause mortality, after adjustment for baseline confounding variables and Na+, K+ , and HCO3- levels. The group with Na+ > 135 and Cl- > 100 had the best survival, and compared with this group, the Na+ >135 and Cl- <100 group had significantly higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11-1.31). Low, not high Serum Cl- (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl- and risk.

Blood pressure response to patterns of weather fluctuations and effect on mortality.

Very few studies have looked at longitudinal intraindividual blood pressure responses to weather conditions. There are no data to suggest that specific response to changes in weather will have an impact on survival. We analyzed >169 000 clinic visits of 16 010 Glasgow Blood Pressure Clinic patients with hypertension. Each clinic visit was mapped to the mean West of Scotland monthly weather (temperature, sunshine, rainfall) data. Percentage change in blood pressure was calculated between pairs of consecutive clinic visits, where the weather alternated between 2 extreme quartiles (Q(1)-Q(4) or Q(4)-Q(1)) or remained in the same quartile (Q(n)-Q(n)) of each weather parameter. Subjects were also categorized into 2 groups depending on whether their blood pressure response in Q(1)-Q(4) or Q(4)-Q(1) were concordant or discordant to Q(n)-Q(n). Generalized estimating equations and Cox proportional hazards model were used to model the effect on longitudinal blood pressure and mortality, respectively. Q(n)-Q(n) showed a mean 2% drop in blood pressure consistently, whereas Q(4)-Q(1) showed a mean 2.1% and 1.6% rise in systolic and diastolic blood pressure, respectively. However, Q(1)-Q(4) did not show significant changes in blood pressure. Temperature-sensitive subjects had significantly higher mortality (1.35 [95% confidence interval, 1.06-1.71]; P=0.01) and higher follow-up systolic blood pressure (1.85 [95% confidence interval, 0.24-3.46]; P=0.02) compared with temperature-nonsensitive subjects. Blood pressure response to temperature may be one of the underlying mechanisms that determine long-term blood pressure variability. Knowing a patient's blood pressure response to weather can help reduce unnecessary antihypertensive treatment modification, which may in turn increase blood pressure variability and, thus, risk.

Serum uric acid level, longitudinal blood pressure, renal function, and long-term mortality in treated hypertensive patients.

Uric acid may have a role in the development of hypertension and renal dysfunction. We explored the relationship among longitudinal blood pressure, renal function, and cardiovascular outcomes in a large cohort of patients with treated hypertension. We used data from the Glasgow Blood Pressure Clinic database. Patients with a baseline measure of serum uric acid and longitudinal measures of blood pressure and renal function were included. Mortality data were obtained from the General Register Office for Scotland. Generalized estimating equations were used to explore the relationship among quartiles of serum uric acid, blood pressure, and estimated glomerular filtration rate. Cox proportional hazard models were developed to assess mortality relationships. In total, 6984 patients were included. Serum uric acid level did not influence the longitudinal changes in systolic or diastolic blood pressure but was related to change in glomerular filtration rate. In comparison with patients in the first quartile of serum uric acid, the relative decrease in glomerular filtration rate in the fourth was 10.7 (95% confidence interval, 7.9-13.6 mL/min per 1.73 m(2)) in men and 12.2 (95% confidence interval, 9.2-15.2 mL/min per 1.73 m(2)) in women. All-cause and cardiovascular mortality differed across quartiles of serum uric acid in women only (P<0.001; hazard ratios for all-cause mortality 1.38 [95% confidence interval, 1.14-1.67] for the fourth quartile of serum uric acid compared with the first). Serum uric acid level was not associated with longitudinal blood pressure control in adults with treated hypertension but was related to decline in renal function and mortality in women.

Acetaminophen use and change in blood pressure in a hypertensive population.

OBJECTIVE: Recent data suggest that self-reported acetaminophen use is associated with increased risk of cardiovascular events and a rise in arterial blood pressure (BP). We investigated the association between acetaminophen use and BP in a large cohort of patients with hypertension using verified prescription data. METHODS: We extracted data from the UK General Practice Research Database for all hypertensive patients aged 65 years or older who were prescribed acetaminophen and had BP measured both before and during acetaminophen treatment. Patients were grouped according to whether their antihypertensive treatment remained unchanged or not during the study period. The change in SBP and DBP during acetaminophen use was determined and compared with the change in BP in a group of nonacetaminophen-exposed people identified using propensity matching. RESULTS: A total of 2754 acetaminophen-exposed individuals were included. BP rose slightly during the period of acetaminophen treatment wherein antihypertensive treatment was unchanged [change in SBP 1.6 [95% confidence interval (CI) 0.7-2.5) mmHg and change in DBP 0.5 (95% CI 0.1-1.0) mmHg)]. BP fell when new antihypertensive medications were prescribed. These BP changes were no different to those seen in matched nonacetaminophen-exposed individuals [between-group difference wherein antihypertensive treatment was unchanged was 0.6 (95% CI -0.6 to 1.9) mmHg and 0.5 (-0.1 to 1.1) mmHg for change in SBP and DBP, respectively]. CONCLUSION: We found no evidence of a sustained rise in blood pressure caused by acetaminophen treatment in a large population of patients with treated hypertension.

Hematocrit predicts long-term mortality in a nonlinear and sex-specific manner in hypertensive adults.

Hematocrit has been inconsistently reported to be a risk marker of cardiovascular morbidity and mortality. The Glasgow Blood Pressure Clinic Study cohort included 10951 hypertensive patients, who had hematocrit measured at their initial clinic visit and followed for ≤35 years. Cox proportional hazards models were used to estimate hazard ratios for all-cause, cardiovascular, ischemic heart disease, stroke, and noncardiovascular mortality. There were 3484 deaths over a follow-up period of 173245 person-years. Hematocrit was higher in men (median, 0.44; interquartile range, 0.42-0.47) than in women (median, 0.41; interquartile range, 0.38-0.43). The lowest risk for all-cause mortality was seen in quartile 2 for men (range, 0.421-0.440) and women (range, 0.381-0.400). Compared with quartile 2, the adjusted hazard ratios for quartiles 1, 3, and 4 were, respectively, 1.11 (range, 0.97-1.28), 1.19 (range, 1.04-1.37), and 1.22 (range, 1.06-1.39) in men and 1.17 (range, 1.01-1.36), 0.97 (range, 0.83-1.13), and 1.19 (range, 1.04-1.37) in women. Men showed a J-shaped pattern for cardiovascular mortality and a linear pattern for noncardiovascular mortality in cause-specific analysis, whereas in women a U-shaped pattern was observed for noncardiovascular mortality only. Higher baseline hematocrit was associated with higher on-treatment blood pressure during follow-up. Baseline hematocrit did not affect the time to reach target blood pressure. The increased risk of death attributed to higher hematocrit was seen in men and women irrespective of their achievement of target blood pressure, indicating that the risk is independent of the effect of hematocrit on blood pressure. Hypertensive patients with hematocrit levels outside of the sex-specific reference ranges identified in this study should be targeted for more aggressive blood pressure and cardiovascular risk reduction treatment.

Resting heart rate pattern during follow-up and mortality in hypertensive patients.

There is a linear relationship between resting heart rate (HR) and mortality in normotensive and untreated hypertensive individuals. However, it is not clear whether HR is a marker of increased risk in hypertensive patients on treatment. We investigated the relationship between HR and mortality in patients with hypertension. We analyzed baseline HR, final HR, and HR change during follow-up in patients attending the Glasgow Blood Pressure Clinic. Using a threshold of 80 bpm, we classified patients into those who had a consistently high (high-high) or low (low-low) HR or patients whose HR increased (low-high) or decreased (high-low) over time. Survival analysis was carried out using Cox proportional hazards models adjusted for age, sex, body mass index, smoking, rate-limiting therapy, systolic blood pressure, and serum cholesterol. For each beat of HR change there was a 1% change in mortality risk. The highest risk of an all-cause event was associated with patients who had increased their HR by >or=5 bpm at the end of follow-up (1.51 [95% CI: 1.03 to 2.20]; P=0.035). Compared with low-low patients, high-high patients had a 78% increase in the risk of all-cause mortality (HR: 1.78 [95% CI: 1.31 to 2.41]; P<0.001). Cardiovascular mortality showed a similar pattern of results. Rate-limiting therapy did not have an independent effect on outcomes in this analysis. Change in HR achieved during follow-up of hypertensive patients is a better predictor of risk than baseline or final HR. After correction for rate-limiting therapy, HR remained a significant independent risk factor.

Comparison of the effects of diuretics on blood pressure and arterial stiffness in patients with stroke.

OBJECTIVES: Indapamide (IND) and bendroflumethiazide (BDZ) are both widely used in patients with stroke. We compared their effects on arterial blood pressure (BP) and arterial stiffness in a group of patients with stroke. METHODS: In a prospective, randomized, double-blinded study we investigated the effect of 28-day treatment with BDZ (2.5 mg once daily) or IND (2.5 mg once daily) on BP and arterial stiffness in a group of patients with first-ever ischemic stroke. RESULTS: All data are expressed as mean (SD). In all, 23 patients completed the protocol (age 70.0 +/- 9.55 years). Group I (IND) and group B (BDZ) comprised 13 and 10 patients, respectively. Groups were well matched for demographics and baseline characteristics. Mean arterial pressure reduction from baseline was I = 14.3 +/- 10.3 mm Hg (P < .001) versus B = 9.1 +/- 11.2 mm Hg (P = .03). Augmentation index (AI) was reduced by: I = 4.94 +/- 7.22% (P = .037) versus B = 6.17 +/- 7.85% (P = .035). Time to reflection was increased by I = 3.22 +/- 9.57 milliseconds (P = .268) versus B = 4.71 +/- 5.30 milliseconds (P = .020). There was no significant difference between the two drugs with regard to change in BP or arterial stiffness. Pooled data showed a reduction in mean arterial pressure by 12.1 +/- 10.77 mm Hg (P < .0001) and in AI by 5.5 +/- 7.36% (P = .002), and a small increase in time to reflection by 3.9 +/- 7.79 milliseconds (P = .029). The change in BP explained up to 28% of the change in AI. CONCLUSION: Both diuretics altered hemodynamic parameters to a similar extent. The results are consistent with a direct effect of diuretic therapy on vascular function. The influence of both diuretics on arterial stiffness was similar.

Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke. The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models, reduces oxidative stress in the vasculature, and improves endothelial function. We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke. METHODS: We performed a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, and effect of 6 weeks' treatment with high- (300 mg once a day) or low- (100 mg once a day) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke. RESULTS: We enrolled 50 patients with acute ischemic stroke (17, 17, and 16 in the high, low, and placebo groups, respectively). Mean (+/-SD) age was 70 (+/-13) years. Groups had similar characteristics at baseline. There were no serious adverse events. Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group (by 0.14 mmol/L at 6 weeks, P=0.002). Intercellular adhesion molecule-1 concentration (ng/mL) rose by 51.2 in the placebo group, rose slightly (by 10.6) in the low-dose allopurinol group, but fell in the high-dose group (by 2.6; difference between groups P=0.012, Kruskal-Wallis test). CONCLUSIONS: Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke. Uric acid levels were lowered with high doses. These findings support further evaluation of allopurinol as a preventive measure after stroke.

Comparison of the effect of diuretics on carotid blood flow in stroke patients.

OBJECTIVES: Indapamide (IND) and bendroflumethiazide (BDZ) are both widely used in the management of blood pressure after stroke. There are theoretical reasons why these agents may differ with regard to their cardiovascular effects. We compared the effect of these agents on blood pressure and cerebral blood flow in a group of stroke patients. METHODS: In a prospective, randomized, double-blinded study we investigated the effect of 28 days' treatment with BDZ 2.5 mg od or IND 2.5 mg od on blood pressure and cerebral blood flow in a group patients with recent first-ever ischemic stroke. Using extracranial carotid and transcranial ultrasound we assessed carotid blood flow and intracranial hemodynamics. RESULTS: All data are expressed as mean (SD). Twenty-five patients completed the protocol (age 68.8 +/- 10.6 y). Groups I (IND) and B (BDZ) comprised 13 and 12 patients, respectively. Groups were well matched for demography and baseline characteristics. Percent change in mean arterial pressure reduction from baseline was (I = -14.7 +/- 12.5, P < 0.001 vs. B = -7.7 +/- 9.16 mm Hg, P = 0.02). There was a trend toward increased carotid blood flow in both groups (I = +10% +/- 47, P = 0.4 vs. B = +33% +/- 47, P = 0.12). No significant change in middle cerebral artery mean flow velocity or pulsatility index was observed. There was no significant difference between the 2 drugs with regard to change in blood pressure (95% confidence interval for difference -2.5 to 16.3 mm Hg, P = 0.14) or carotid blood flow (95% confidence interval for difference -58 to 27 mL/s, P = 0.45). CONCLUSIONS: Both diuretics reduced blood pressure to a similar and significant degree. There was no evidence of an adverse effect on cerebral blood flow or intracranial hemodynamics induced by either agent. No significant difference between the effect of IND and BDZ was observed.

Effect of perindopril on cerebral vasomotor reactivity in patients with lacunar infarction.

BACKGROUND AND PURPOSE: There is growing evidence that pharmacologic interference with the renin-angiotensin system may reduce risk of stroke, although the mechanism is unclear. Impaired reactivity of cerebral vessels has recently been recognized as a risk factor for stroke. We examined the effect of the angiotensin-converting enzyme (ACE) inhibitor perindopril on cerebral vasomotor reactivity to acetazolamide in patients with lacunar cerebral infarction. METHODS: We studied a cohort of male patients between 3 and 12 months after lacunar infarction confirmed on computed tomography. Each patient received perindopril 4 mg daily or matching placebo for 2 weeks in a randomized, double-blind, placebo-controlled crossover fashion. A 1-week washout period was observed between dosing periods. Cerebral vasomotor reactivity (increase in middle cerebral artery mean flow velocity in response to intravenous injection of 15 mg/kg acetazolamide) was measured before and after each dosing period using standard Doppler ultrasound techniques. RESULTS: Twelve patients (mean age 63.2+/-2.3 years) completed the protocol. There was no treatment order effect. Cerebral vasomotor reactivity was significantly greater after perindopril treatment (percent change from baseline +18.8+/-10.1% after perindopril, -4.6+/-4.1% after placebo; P=0.032). Dosing with perindopril did not affect resting cerebral blood flow velocity (percent change from baseline +3.1+/-9.5% after perindopril, -0.6+/-5.4% after placebo), nor was there a change in resting blood pressure (+1.8 mm Hg+/-3.1 after perindopril, +1.4 mm Hg+/-2.5 after placebo). CONCLUSIONS: This study provides evidence of a significant improvement in cerebral vasomotor reactivity induced by perindopril, beyond any effect on blood pressure. The results suggest a possible mechanism for the beneficial effect of ACE inhibition on stroke risk observed in recent clinical trials, and suggest a role for the renin-angiotensin axis in the pathophysiology of subcortical small vessel disease.

Serum urate as an independent predictor of poor outcome and future vascular events after acute stroke.

BACKGROUND AND PURPOSE: Serum urate concentration is associated with cardiovascular disease, and hyperuricemia predicts first-ever stroke. We explored the association of admission urate level with mortality, placement, and risk of further vascular events after acute stroke. METHODS: In patients with ischemic stroke or primary intracranial hemorrhage, we determined the association of urate level with 90-day placement (alive at home, good outcome; dead or living in care, poor outcome) and with the subsequent occurrence of ischemic stroke, myocardial infarction, or vascular death. In multivariate analysis (logistic regression for 90-day placement, proportional-hazards regression for time to further vascular event), we adjusted for stroke severity (modified National Institutes of Health stroke scale) and other clinical, biochemical, and radiological variables known to influence stroke outcome. RESULTS: We studied 3731 patients and measured serum urate in 2498. Elevated urate level predicted a lower chance of good 90-day outcome (odds ratio, 0.78 per additional 0.1 mmol/L; 95% confidence interval [CI], 0.67 to 0.91) independently of stroke severity and other prognostic factors. Vascular event risk increased with urate level (relative hazard, 1.27 per additional 0.1 mmol/L; 95% CI, 1.18 to 1.36). Higher urate levels have a greater effect on vascular event rates in the presence of diabetes (additional relative hazard, 1.22 per additional 0.1 mmol/L; 95% CI, 1.06 to 1.41). CONCLUSIONS: Independently of other prognostic factors, higher serum urate levels predicted poor outcome (dead or in care) and higher vascular event rates. The role of urate in stroke pathophysiology remains uncertain, but intervention to lower urate may be worth considering.