Reduced neurovascular coupling is associated with increased cardiovascular risk without established cerebrovascular disease: A cross-sectional analysis in UK biobank.

Mid-life vascular risk factors predict late-life cerebrovascular diseases and poor global brain health. Although endothelial dysfunction is hypothesized to contribute to this process, evidence of impaired neurovascular function in early stages remains limited. In this cross-sectional study of 31,934 middle-aged individuals from UK Biobank without established cerebrovascular disease, the overall 10-year risk of cardiovascular events was associated with reduced neurovascular coupling (p < 2 × 10) during a visual task with functional MRI, including in participants with no clinically apparent brain injury on MRI.

Early neurological deterioration in acute lacunar ischemic stroke: Systematic review of incidence, mechanisms, and prospects for treatment.

Background: Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischemic strokes. In acute lacunar ischemic stroke, despite often mild initial symptoms, early neurological deterioration (END) occurs in approximately 15-20% of patients and is associated with poor functional outcome, yet its mechanisms are not well understood.

Aims: In this review, we systematically evaluated data on: (1) definitions and incidence of END, (2) mechanisms of small vessel occlusion, (3) predictors and mechanisms of END, and (4) prospects for the prevention or treatment of patients with END.

Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies.

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects.

Circadian and Diurnal Regulation of Cerebral Blood Flow.

Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with cerebrovascular regulatory mechanisms, including cerebrovascular reactivity, autoregulation, and neurovascular coupling. We review the evidence for the circadian and diurnal variation in each of these mechanisms and their integration, from the detailed evidence for mechanisms underlying the nocturnal nadir and morning surge in blood pressure to identifying limited available evidence for circadian and diurnal variation in cerebrovascular compensatory mechanisms.

Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial.

Background: Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease.

Methods: We did a multicentre, open-label, randomised crossover trial with blinded endpoint assessment at five specialist centres in Europe.

Associations between neurovascular coupling and cerebral small vessel disease: A systematic review and meta-analysis.

Purpose: The pathogenesis of cerebral small vessel disease (cSVD) remains elusive despite evidence of an association between white matter hyperintensities (WMH) and endothelial cerebrovascular dysfunction. Neurovascular coupling (NVC) may be a practical alternative measure of endothelial function. We performed a systematic review of reported associations between NVC and cSVD.

Consensus Recommendations for Standardized Data Elements, Scales, and Time Segmentations in Studies of Human Circadian/Diurnal Biology and Stroke.

Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data elements, including what constitutes daytime versus nighttime. Contemporary methodologic advances in human neurovascular investigation have the potential to substantially increase understanding, including the use of large multicenter and national data registries, detailed clinical trial data sets, analysis guided by individual patient chronotype, and multimodal computed tomographic and magnetic resonance imaging.

The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial.

Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs.

Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs.

Prevalence of stroke, associated risk factors and stroke related physical, mental, and economic burden in the Republic of Georgia.

Introduction: We investigated the prevalence, risk factors and physical, mental, and economic consequences of ischemic Janelidze and hemorrhagic stroke in the population of the Republic of Georgia.

Materials And Methods: A population-based, cross-sectional study was conducted among 3036 adults residing in the Imereti Region of Georgia, selected using a multistage, probability proportionate-to-size, cluster sampling technique. Data were collected by medical students, using an interviewer-administered questionnaire.

European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack.

Recurrent stroke affects 9% to 15% of people within 1 year. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations on pharmacological management of blood pressure (BP), diabetes mellitus, lipid levels and antiplatelet therapy for the prevention of recurrent stroke and other important outcomes in people with ischaemic stroke or transient ischaemic attack (TIA). It does not cover interventions for specific causes of stroke, including anticoagulation for cardioembolic stroke, which are addressed in other guidelines.

Low Heart Rate Is Associated with Cerebral Pulsatility after TIA or Minor Stroke.

Objective: Beta-blockers are beneficial in coronary artery disease but less so in stroke prevention and dementia, potentially due to reduced heart rate (HR). Cerebral pulsatility is strongly associated with cerebral small vessel disease (SVD) and may be increased by lower diastolic pressures resulting from longer cardiac cycles.

Methods: Patients 4-6 weeks after TIA or non-disabling stroke (Oxford Vascular Study) underwent 5 minutes continuous monitoring of blood pressure (BP), electrocardiogram (ECG), and middle cerebral artery flow velocity (transcranial ultrasound).

Consistencies and Differences in Intermediate Physiological Phenotypes of Vascular Ageing between Ischaemic Stroke Aetiologies.

Objective: Arterial stiffness, cerebral pulsatility, and beat-to-beat blood pressure variability partly mediate the relationship between hypertension and stroke, but it is unknown if these intermediate phenotypes of vascular ageing differ between stroke aetiologies. We therefore aimed to characterize differences in these intermediate cardiovascular phenotypes between patients presenting with strokes of different aetiologies.

Methods: In consecutive patients on best medical management 1 month after TIA or nondisabling stroke (Oxford Vascular Study), arterial stiffness (PWV) was measured by applanation tonometry (Sphygmocor), middle cerebral blood flow velocity, and pulsatility index (MCA-PI) were measured by transcranial ultrasound (TCD, DWL Doppler Box), and beat-to-beat BP variability was measured with a Finometer.

New Insights Into Cerebrovascular Pathophysiology and Hypertension.

Despite advances in acute management and prevention of cerebrovascular disease, stroke and vascular cognitive impairment together remain the world's leading cause of death and neurological disability. Hypertension and its consequences are associated with over 50% of ischemic and 70% of hemorrhagic strokes but despite good control of blood pressure (BP), there remains a 10% risk of recurrent cerebrovascular events, and there is no proven strategy to prevent vascular cognitive impairment. Hypertension evolves over the lifespan, from predominant sympathetically driven hypertension with elevated mean BP in early and mid-life to a late-life phenotype of increasing systolic and falling diastolic pressures, associated with increased arterial stiffness and aortic pulsatility.

Blood Pressure Complexity Discriminates Pathological Beat-to-Beat Variability as a Marker of Vascular Aging.

Background Beat-to-beat blood pressure variability (BPV) is associated with an increased risk of stroke but can be driven by both healthy physiological processes and failure of compensatory mechanisms. Blood pressure (BP) complexity measures structured, organized variations in BP, as opposed to random fluctuations, and its reduction may therefore identify pathological beat-to-beat BPV. Methods and Results In the prospective, population-based OXVASC (Oxford Vascular Study) Phenotyped Cohort with transient ischemic attack or minor stroke, patients underwent at least 5 minutes of noninvasive beat-to-beat monitoring of BP (Finometer) and ECG to derive the following: BPV (coefficient of variation) and complexity (modified multiscale entropy) of systolic BP and diastolic BP, heart rate variability (SD of R-R intervals), and baroreflex sensitivity (BRS; Welch's method), in low- (0.

Aortic Stiffness, Pulse Pressure, and Cerebral Pulsatility Progress Despite Best Medical Management: The OXVASC Cohort.

Background: Increased cerebral arterial pulsatility is associated with cerebral small vessel disease, recurrent stroke, and dementia despite the best medical treatment. However, no study has identified the rates and determinants of progression of arterial stiffness and pulsatility.

Methods: In consecutive patients within 6 weeks of transient ischemic attack or nondisabling stroke (OXVASC [Oxford Vascular Study]), arterial stiffness (pulse wave velocity [PWV]) and aortic systolic, aortic diastolic, and aortic pulse pressures (aoPP) were measured by applanation tonometry (Sphygmocor), while middle cerebral artery (MCA) peak (MCA-PSV) and trough (MCA-EDV) flow velocity and Gosling pulsatility index (PI; MCA-PI) were measured by transcranial ultrasound (transcranial Doppler, DWL Doppler Box).

Design of a randomised, double-blind, crossover, placebo-controlled trial of effects of sildenafil on cerebrovascular function in small vessel disease: Oxford haemodynamic adaptation to reduce pulsatility trial (OxHARP).

Background: Cerebral small vessel disease (SVD) is associated with increased cerebrovascular pulsatility, endothelial dysfunction, and impaired vascular reactivity. Vasodilating phosphodiesterase inhibitors may improve cardiovascular pulsatility and reactivity, and potentially reduce progression of SVD.Hypothesis: Sildenafil, a PDE5 inhibitor, will reduce cerebrovascular pulsatility and increase cerebrovascular reactivity compared to placebo, and is non-inferior to cilostazol, a PDE3 inhibitor.

Consistency of associations of systolic and diastolic blood pressure with white matter hyperintensities: A meta-analysis.

Background: White matter hyperintensities are the commonest manifestation of cerebral small vessel disease, associated with stroke, functional impairment, and cognitive decline. They are commonly preceded by hypertension, but the magnitude and clinical importance of this association is unclear.

Aims: Quantify the relationship between blood pressure and white matter hyperintensities across studies.