Salim Elyas

Blood Oxygen Saturation After Ischemia is Altered With Abnormal Microvascular Reperfusion.

We have previously described a distinct abnormality in the cutaneous microcirculation that is characterized by an abnormal reperfusion response following an ischemic stimulus. We investigated the physiological significance of this abnormality; by measuring microvascular perfusion and blood oxygen saturation in groups stratified by three distinct reperfusion responses.

Reactivity to low‐flow as a potential determinant for brachial artery flow‐mediated vasodilatation

Previous studies have reported a vasoconstrictor response in the radial artery during a cuff‐induced low‐flow condition, but a similar low‐flow condition in the brachial artery results in nonuniform reactivity. This variable reactivity to low‐flow influences the subsequent flow‐mediated dilatation (FMD) response following cuff‐release. However, it is uncertain whether reactivity to low‐flow is important in data interpretation in clinical populations and older adults. This study aimed to determine the influence of reactivity to low‐flow on the magnitude of brachial artery FMD response in middle‐aged and older individuals with diverse cardiovascular risk profiles. Data were analyzed from 165 individuals, divided into increased cardiovascular risk (CVR: n = 115, 85M, 67.0 ± 8.8 years) and healthy control (CTRL: n = 50, 30M, 63.2 ± 7.2 years) groups. Brachial artery diameter and blood velocity data obtained from Doppler ultrasound were used to calculate FMD, reactivity to low‐flow and estimated shear rate (SR) using semiautomated edge‐detection software. There was a significant association between reactivity to low‐flow and FMD in overall (r = 0.261), CTRL (r = 0.410) and CVR (r = 0.189, all P < 0.05) groups. Multivariate regression analysis found that reactivity to low‐flow, peak SR, and baseline diameter independently contributed to FMD along with sex, the presence of diabetes, and smoking (total R2 = 0.450). There was a significant association between reactivity to low‐flow and the subsequent FMD response in the overall dataset, and reactivity to low‐flow independently contributed to FMD. These findings suggest that reactivity to low‐flow plays a key role in the subsequent brachial artery FMD response and is important in the interpretation of FMD data.

Age-related change in endothelial and microvessel function and therapeutic consequences

As the absolute numbers and proportion of older adults increases across most of the developed world, a greater understanding of the aetiopathogenic mechanisms of the increased vascular risk and their therapeutic implications becomes essential to all clinicians assessing and managing the geriatric patient. The role of endothelial function and the microcirculation is increasingly recognized in the maintenance of adequate perfusion, and their dysfunction is thought to be an early and potentially reversible mechanism by which age acts to increase cardiovascular risk. Here we review evidence that altered microvascular function appears before other recognized predictors of vascular disease, and progresses from childhood to late adult life, preceding fulminant atherosclerotic or arteriosclerotic disease. Low birth-weight babies have reduced endothelial function in skin microvessels at 3 months, and by age ten brachial artery endothelial function is reduced in comparison with normal birth-weight babies. In overweight/obese adolescent children with clustering of traditional cardiovascular disease risk factors, endothelial function is lower compared with normal weight children and this appears to persist into early adulthood. Adult ageing is associated with impaired microvessel endothelial function and an increase in capillary blood pressure, independent of brachial artery blood pressure. Biological and lifestyle factors that influence microvessel function include body fat and visceral adiposity, sex hormone status, diet and physical activity. Exploration of the therapeutic implications for management of endothelial dysfunction remains in embryonic state. The use of ACE-inhibitors, angiotensin receptor blockers and direct renin inhibitors in patients with evidence of microvascular damage such as retinopathy and microalbuminuria has been established; however, in the general older population the benefit has yet to be established. Therefore current recommendations are to screen for microvascular damage and if present target treatments after control of other vascular risk factors such as hypertension.

Measurement of Wall Shear Stress Exerted by Flowing Blood in the Human Carotid Artery: Ultrasound Doppler Velocimetry and Echo Particle Image Velocimetry

Vascular endothelial cells lining the arteries are sensitive to wall shear stress (WSS) exerted by flowing blood. An important component of the pathophysiology of vascular diseases, WSS is commonly estimated by centerline ultrasound Doppler velocimetry (UDV). However, the accuracy of this method is uncertain. We have previously validated the use of a novel, ultrasound-based, particle image velocimetry technique (echo PIV) to compute 2-D velocity vector fields, which can easily be converted into WSS data. We compared WSS data derived from UDV and echo PIV in the common carotid artery of 27 healthy participants. Compared with echo PIV, time-averaged WSS was lower using UDV (28 ± 35%). Echo PIV revealed that this was due to considerable spatiotemporal variation in the flow velocity profile, contrary to the assumption that flow is steady and the velocity profile is parabolic throughout the cardiac cycle. The largest WSS underestimation by UDV was found during peak systole (118 ± 16%) and the smallest during mid-diastole (4.3± 46%). The UDV method underestimated WSS for the accelerating and decelerating systolic measurements (68 ± 30% and 24 ± 51%), whereas WSS was overestimated for end-diastolic measurements (-44 ± 55%). Our data indicate that UDV estimates of WSS provided limited and largely inaccurate information about WSS and that the complex spatiotemporal flow patterns do not fit well with traditional assumptions about blood flow in arteries. Echo PIV-derived WSS provides detailed information about this important but poorly understood stimulus that influences vascular endothelial pathophysiology.

Microalbuminuria could improve risk stratification in patients with TIA and minor stroke

Transient ischemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes. Current stroke risk prediction scores such as ABCD2, although widely used, lack optimal sensitivity and specificity. Elevated urinary albumin excretion predicts cardiovascular disease, stroke, and mortality. We explored the role of microalbuminuria (using albumin creatinine ratio (ACR)) in predicting recurrence risk in patients with TIA and minor stroke.

ECHOGENICITY OF THE COMMON CAROTID ARTERY INTIMA-MEDIA COMPLEX IN STROKE

The grey-scale median of the common carotid artery intima-media complex (IM-GSM) characterizes arterial wall composition, and a low IM-GSM is associated with increased cardiovascular mortality in the elderly. We aimed to determine differences in the IM-GSM between a cohort with cerebrovascular disease and a healthy cohort. Eighty-two healthy individuals (control group: 63.2 ± 8.7 y) and 96 patients with either stroke or transient ischemic attacks (CRVD group: 68.6 ± 9.8 y) were studied. Common carotid artery intima-media thickness and IM-GSM obtained by ultrasound were analyzed using semi-automated edge-detection software. The IM-GSM was significantly lower in the CRVD group than in the control group (106 ± 24 vs. 124 ± 27 au, p < 0.001). The IM-GSM was similar for the infarct and non-infarct sides in CRVD. In the pooled cohort of all participants, the lower the quartile of IM-GSM, the greater were the carotid artery intima-media thickness and carotid artery remodeling. These results suggest the presence of an altered atherosclerotic phenotype in the intima-media complex of CRVD patients that can be detected by ultrasound.

Microalbuminuria could improve risk prediction of stroke in patients with transient ischaemic attacks and minor strokes

Abstract Background Transient ischaemic attacks (TIA) and minor strokes are important risk factors for recurrent strokes; they precede 23% of strokes within 90 days. Identification of patients at high risk of developing further strokes is essential to allow early intervention and avoid the catastrophic outcome of strokes. Elevated urinary albumin excretion rate (AER) is a risk factor and predicts cardiovascular disease, stroke, and mortality. Elevated AER can be detected with a point-of-care bedside test. Methods Patient demographics and the ABCD2 score were obtained for 150 consecutive patients with TIA who presented to the daily stroke clinic and the stroke unit. The ABCD2 score composite for age, blood pressure, clinical features, duration, and diabetes is the risk score presently used for stratifying patients with TIA. All patients had their albumin:creatinine ratio (ACR) measured from a urine sample obtained during their visit to the clinic or the stroke unit at Royal Devon & Exeter Hospital. Patients were followed up for any events, cardiovascular events, stroke, or death at day 7, 30, and 90. Findings Nine patients had recurrent strokes or TIAs by day 7 and 13 by day 9. Patients who had a recurrent stroke or TIA at day 7 and day 90 had a significantly higher ACR than those who did not have an event (4·00 mg/mmol [95% CI 1·89–8·40] vs 1·89 [95% CI 1·58–2·25]; p=0·03 and 3·73 [95% CI 2·12–6·56] vs 1·85 [95% CI 1·55–2·22]; p=0·02, respectively). After adjustment for sex and ABCD2 score, the 90-day predictive role of ACR persisted for those with versus those without subsequent events (adjusted ACR 3·48 mg/mmol [95% CI 1·96–6·19] vs 1·87 [95% CI 1·56–2·24], p=0·04). Stratification of the population at an ACR of 3.0 mg/mmol identified 39 patients at higher risk. Cox proportional hazards of progressing to stroke by day 90 if ACR was more than 3·0 mg/mmol was 3·2 (95% CI 1·07–9·45, p Interpretation Increased urinary albumin excretion, as detected by urinary ACR, is significantly elevated in patients who present with TIA or minor strokes and go on to have further strokes. The use of clinic urinary ACR test could improve the risk prediction of currently available stroke risk scores such as the ABCD2 score. Funding National Institute for Health Research and Stroke Research Network.