Prevalence of frailty in the TIA clinic and its associations with mortality.

Introduction Frailty is a clinical syndrome of increased vulnerability to stressors. Frailty is associated with adverse outcomes after stroke, but frailty and transient ischaemic attack (TIA) are less well described. Methods Retrospective analysis of patients referred by the emergency department (ED) to TIA clinic (01/01/2016-12/03/2022), linked to hospital records for electronic follow-up. Only those with Clinical Frailty Scale (CFS) recorded within two weeks of clinic were included. Prevalence of frailty was determined based on CFS score >4. Hazard ratios (HR) for mortality were determined through Cox proportional hazard regression, adjusted for prognostic factors. Where repeat CFS data were available, temporal change in frailty was recorded (~15 months). Results Of 1185 patients included, 53.5% (n=634) had frailty. Patients with frailty tended to be older (median age 81 vs 74 years, p<0.001) and female (53.9% vs 39.9% p<0.001). Of 335 diagnosed with TIA following review, 61.2% (n=205) were frail. Prevalence of frailty by clinic diagnosis was: TIA 61.2% (205/335); stroke 46.7% (128/274); other diagnoses 52.3% (301/575). In TIA patients and the whole cohort (WC), frailty (TIA:HR:2.69 [95%CI:1.23-5.87, p=0.013], WC:2.58 [95%CI:1.64-4.08, p<0.001]) and increasing age [HR:1.07 95%CI:1.04-1.12], were predictive of mortality. In stroke patients, only increasing age was predictive of death (HR:1.11 [95%CI:1.04-1.19, p=0.003]). Of 414 patients with repeat CFS, median interval 15 months, median change was +1 point (IQR:0-2). Conclusion Frailty is common in TIA and becomes more common following TIA. Strength of association of frailty with poor outcome was greater for TIA patients than for those with stroke. Routine assessment of frailty may be a useful addition to TIA services.

Mortality in a Multiethnic Population Attending a One-Stop TIA Clinic.

INTRODUCTION: Studies indicate a 13-27% mortality rate following a transient ischaemic attack (TIA). However, outcomes following TIA/minor stroke since the introduction of rapid-access TIA clinics and prompt vascular risk factor intervention are not known. Specifically, there is paucity of data comparing outcomes between people who are diagnosed with an "acute cerebrovascular" (CV) event or an alternative non-cardiovascular diagnosis (non-CV) in a rapid-access TIA clinic. We aimed to assess the mortality in such a setting. METHODS: A retrospective observational study was undertaken at the Leicester rapid-access secondary care TIA clinic. Data included information collected at the first clinic visit (including comorbidities, and primary diagnosis, categorized as CV and non-CV) and the date of death for people dying during follow-up. RESULTS: 11,524 subjects were included with 33,164 years of follow-up data; 4,746 (41.2%) received a CV diagnosis. The median follow-up time was 2.75 years (interquartile range 1.36-4.32). The crude mortality rate was 37.3 (95% CI: 35.3-39.5) per 1,000 person-years (PTPY). The mortality rate was higher following a CV diagnosis (50.8 [47.2-54.7] PTPY) compared to a non-CV diagnosis (27.9 [25.7-30.4] PTPY), and for males, older people, those of white ethnicity, and people with orthostatic hypotension (OH). DISCUSSION: This study identified possible risk factors associated with a higher mortality in TIA clinic attendees, who may benefit from specific intervention. Future research should explore the underlying causes and the effect of specific targeted management strategies.

High non-adherence rates to secondary prevention by chemical adherence testing in patients with TIA.

INTRODUCTION: Transient ischaemic attack (TIA) clinics are important for secondary prevention of fatal or disabling stroke. Non-adherence to prescribed medications is an important reason for treatment failure but difficult to diagnose. This study ascertained the utility of a novel biochemical tool in the objective biochemical diagnosis of non-adherence. METHODS: One-hundred consecutive urine samples collected from patients attending the TIA clinic, at a tertiary centre, were analysed for presence or absence of prescribed cardiovascular medications using liquid chromatography-mass spectrometry (LC-MS/MS). Patients were classified as adherent or non-adherent, respectively. Demographic and clinical characteristics were compared between the two cohorts. Univariate regression analyses were performed for individual variables and model fitting was undertaken for significant variables. RESULTS: The mean duration of follow-up from the index event was 31 days [standard deviation (SD): 18.9]. The overall rate of non-adherence for at least one medication was 24%. In univariate analysis, the number of comorbidities [3.4 (SD: 1.9) vs. 2.5 (1.9), P = 0.032] and total number of all prescribed medications [6.0 (3.3) vs 4.4 (2.1), P = 0.032] were higher in the non-adherent group. On multivariate analysis, the total number of medications prescribed correlated with increased non-adherence (odds ratio: 1.27, 95% Confidence Intervals: 1.1-1.5, P = 0.01). CONCLUSIONS: LC-MS/MS is a clinically useful tool for the diagnosis of non-adherence. Nearly a quarter of TIA patients were non-adherent to their cardiovascular medications Addressing non-adherence early may reduce the risk of future disabling cardiovascular events.

Antiplatelet treatment for acute secondary prevention of non-cardioembolic minor stroke / transient ischaemic attack: an update for the acute physician.

Acute stroke is the leading cause of disability in the UK and a leading cause of mortality worldwide. The majority of patients with ischaemic stroke present with minor deficits or transient ischaemic attack (TIA), and are often first seen by patient-facing clinicians. Urgent evaluation and treatment are important as many patients are at high risk of major vascular events and death within hours to days after the index event. This narrative review summarises the evidence on four antiplatelet treatments for non-cardioembolic stroke prevention: aspirin, clopidogrel, dipyridamole and ticagrelor. Each of these drugs has a unique mechanism and has been tested as a single agent or in combination. Aspirin, when given early is beneficial and short-term treatment with aspirin and clopidogrel has been shown to be more effective in high-risk TIA / minor stroke. This review concludes by highlighting gaps in evidence, including scope for future trials that could potentially change clinical practice.

What is the optimal blood pressure level for patients with atrial fibrillation treated with direct oral anticoagulants?

OBJECTIVE: Limited data exist to inform blood pressure (BP) thresholds for patients with atrial fibrillation prescribed direct oral anticoagulants (DOAC) therapy in the real world setting. METHODS: SBP was measured in 9051 primary care patients in England on DOACs for atrial fibrillation with postinitiation BP levels available within the Clinical Practice Research Datalink. The incidence rate for the primary outcome of the first recorded event (defined as a diagnosis of first stroke, recurrent stroke, myocardial infarction, symptomatic intracranial bleed, or significant gastrointestinal bleed) and of secondary outcomes all-cause mortality and cardiovascular mortality were calculated by postinitiation BP groups. RESULTS: The Cox proportional hazard ratio of an event [crude and adjusted hazard ratio 1.04 (95% confidence interval (CI) 1.00-1.08), P = 0.077 and 0.071, respectively] did not differ significantly with a 10 mmHg increase in SBP. The hazard of all-cause mortality [crude hazard ratio 0.83 (95% CI 0.80-0.86), P = 0.000; adjusted hazard ratio 0.84 (95% CI 0.81-0.87), P = 0.000] and cardiovascular mortality [crude hazard ratio 0.92 (95% CI 0.85-0.99), P = 0.021; adjusted hazard ratio 0.93 (95% CI 0.86-1.00), P = 0.041] demonstrated a significant inverse relationship with a 10 mmHg increase in SBP. Patients with a SBP within 161-210 mmHg had the lowest all-cause death rate, while patients with SBP within 121-140 mmHg had the lowest cardiovascular death rate. CONCLUSION: SBP values below 161 mmHg are associated higher all-cause mortality, but lower event risk in patients with atrial fibrillation on DOAC therapy. The nadir SBP for lowest event rate was 120 mmHg, for lowest cardiovascular mortality was 130 mmHg and for lowest all-cause mortality was 160 mmHg. This demonstrates a need for a prospective interventional study of BP control after initiation of anticoagulation.

Clinical Relevance of Orthostatic Hypotension in Patients with Atrial Fibrillation and Suspected Transient Ischemic Attack.

INTRODUCTION: Orthostatic hypotension (OH) and atrial fibrillation (AF) are both regarded as independent risk factors for transient ischemic attack (TIA). However, the clinical implication of OH in the presence of AF is unclear. This study investigates, for the first time, the association between blood pressure (BP), OH and mortality in a cohort of patients with AF and TIA symptoms. AIM: To investigate the incidence of the association between OH, AF and TIA. METHODS: This retrospective observational study utilised the Leicester one-stop transient TIA clinic patient database to consider the initial systolic and diastolic BP of 688 patients with a diagnosis of AF. The primary outcome was time until death. Covariant measures included status of AF diagnosis (known or new AF), cardiovascular risk factors, and primary clinic diagnosis [cerebrovascular (CV) versus non-cerebrovascular (non-CV)]. Statistical models adjusted for sex, age, previous AF diagnosis. RESULTS: Mortality rate was higher in the over 85 age group [191.5 deaths per 1000 person years (py) (95% CI 154.0-238.1)] and lower in the aged 75 and younger age group [40.0 deaths per 1000 py (95% CI 27.0-59.2)] compared to intermediate groups. A 10 mmHg increase in supine diastolic BP was associated with a significant reduction in the hazard of mortality for patients suspected of TIA with AF [adjusted HR 0.79 (95% CI 0.68-0.92), p < 0.001]. The mortality rate for patients with OH was 119.0 deaths per 1000 py compared with a rate of 98.0 for patients without OH (rate ratio 1.2, p = 0.275). CONCLUSION: Higher diastolic BP may be a marker for reduced mortality risk in patients with a previous AF diagnosis and non-CV diagnosis. Lower diastolic BP and the presence of AF pertain to a higher mortality risk. This study raises the importance of opportunistic screening for both OH and AF in patients presenting to TIA clinic.

Lisinopril for the treatment of hypertension within the first 24 hours of acute ischemic stroke and follow-up.

BACKGROUND: Hypertension immediately after acute ischemic stroke is associated with impaired morbidity and mortality, although there are few data on antihypertensive use immediately after ictus. This randomized, double-blinded, placebo-controlled, parallel-group study explored the hemodynamic effect and safety of oral lisinopril initiated within 24 h after an ictus. METHODS: Forty hypertensive (systolic blood pressure [BP] >/=140 or diastolic BP >/=90 mm Hg) acute ischemic stroke patients (14 lacunar, 13 partial anterior, 7 total anterior, 6 posterior circulation infarct) were randomized to 5 mg of oral lisinopril (n = 18) or matching placebo (n = 22). Dose was increased to 10 mg (or 2 x placebo) on day 7 if casual systolic BP was >/=140 mm Hg and continued to day 14. After the initial dose, automated BP levels were monitored for 16 h. The BP levels and stroke outcome measures were assessed at day 14, and all patients were followed to day 90. RESULTS: At h 4 after the first dose, systolic/diastolic BP change was -20 +/- 21/-6 +/- 10 mm Hg (mean +/- SE) in the lisinopril group and 1 +/- 11/0 +/- 8 mmHg in the placebo group (group differences: systolic BP, P < .05; diastolic BP, P = .07). With a daily dosing regime, systolic BP, mean arterial pressure (MAP), diastolic BP, and pulse pressure (PP) were significantly lower in the lisinopril group compared to the placebo group at day 14 (P < .01). Neurologic and functional measures were similar between groups at follow-up. CONCLUSIONS: Lisinopril, even at small dosages, is well tolerated and an effective hypotensive agent after acute ischemic stroke, gradually reducing BP by 4 h after oral first-dose administration. Oral lisinopril is now being studied in a larger outcome-based trial in acute hypertensive stroke patients.

Abnormalities in cardiac baroreceptor sensitivity in acute ischaemic stroke patients are related to aortic stiffness.

Cardiac BRS (baroreceptor reflex sensitivity) is impaired following ischaemic stroke and predicts the risk of subsequent long-term death and disability. Impaired cardiac BRS may be due to impaired central processing of baroreceptor information following stroke or reduced baroreceptor activity due to increased large artery stiffness. We evaluated the relationship between large (aortic) artery stiffness and cardiac BRS during the acute phase of ischaemic stroke and in comparison with a group of stroke-free control subjects. Thirty-one ischaemic stroke patients were studied within 48 h of onset and again on day 14, along with 26 control subjects free of cerebrovascular disease. Cardiac BRS (determined by spectral analyses) and arterial stiffness estimated by PWVcf (carotid-femoral pulse wave velocity) using applanation tonometry were obtained. At baseline, cardiac BRS was lower in the stroke compared with the control group (4.3+/-2.3 compared with 6.5+/-4.2 ms/mmHg; P < 0.05). Cardiac BRS values were correlated with PWVcf at < 48 h (r = -0.51, P < 0.01) and on day 14 (r = -0.54, P < 0.01), but not in the control group (r = -0.27, P = not significant). In quantile regression models, taking into account the effect of all cardiovascular variables, cardiac BRS was independently related to PWVcf at baseline and on day 14 in the stroke patients, but stroke was not related to cardiac BRS level when other cardiovascular variables were considered. Wall stiffness of the arterial vessels involved in the baroreflex arc may account for, at least in part, the reduced cardiac BRS observed in acute stroke patients.