Dose-Dependent Association of Inflammatory Cytokines with Carotid Atherosclerosis in Transient Ischaemic Attack: Implications for Clinical Trials.

INTRODUCTION: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. METHODS: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1ß, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. RESULTS: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1ß, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003). CONCLUSION: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

Maximal oxygen consumption and oxygen uptake efficiency in adolescent males.

BACKGROUND/OBJECTIVE: Measures of oxygen uptake efficiency (OUE) have been used to evaluate cardiorespiratory fitness (CRF) in adolescents unable to perform maximal exercise. The oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) have been proposed as surrogates for maximal oxygen consumption (V̇O2max). We assessed the validity of the OUES and OUEP as predictors of V̇O2max in healthy male adolescents. METHODS: Sixty-three healthy male adolescents aged 15.40 ± 0.34 years underwent an incremental treadmill test to determine V̇O2max, OUES and OUEP. OUE throughout the test was assessed by dividing each V̇O2 value by the corresponding minute ventilation (V̇E) value. OUEP was determined as the 90 s average highest consecutive values for OUE. OUES was determined using data up to the ventilatory threshold (VT) by calculating the slope of the linear relation between V̇O2 and the logarithm of V̇E. RESULTS: Limits of agreement for V̇O2max predicted by OUES (±13.3 mL kg-1.min-1) and OUEP (±16.7 mL kg-1.min-1) relative to V̇O2max were wide and a magnitude bias was found for OUES and OUEP as predictors of V̇O2max (p < 0.001). CONCLUSION: The OUES and OUEP do not accurately predict V̇O2max in male adolescents and should not replace V̇O2max when assessing CRF in this population.

The implications of different criteria for grading carotid artery stenosis by duplex ultrasound.

PURPOSE: Duplex ultrasound is the first-line mode of investigation for carotid stenosis, whose severity could be graded according to NASCET or St. Mary's ratio criteria. The aim of this study was to compare these two methods and review the literature. METHODS: All patients who had carotid duplex ultrasound in a 1-month period were included. The reports and images were retrospectively reviewed, and the grade of carotid artery stenosis was then recalculated using the St. Mary's Ratio. RESULTS: A total of 245 (160 men) patients with a mean age 70.4 years (±11.5) were assessed, and 469 extracranial carotid systems were analyzed. Pearson's Coefficient revealed strong correlation (r = 0.79, p = 0.05) between the two methods. In 114 (24.3%) internal carotid arteries, results were different. Of these, 26 (22.8%) would have gone for surgery had they been assessed using the St. Mary's Ratio and not the NASCET grading criteria. Conversely, two internal carotid arteries (1.75%) went for surgery using the NASCET grading criteria that would not have had to should the St. Mary's Ratio been used. CONCLUSIONS: Although there is a strong level of correlation between the two criteria, choosing one or the other would have a significant impact on the patient' selection for surgery.

Biomarkers in Unstable Carotid Plaque: Physiopathology and Prediction.

AIMS: To study the role of cytokines and vascular inflammatory biomarkers in unstable carotid plaque. BACKGROUND: Clinical studies showed that not only the degree of stenosis but also the type of carotid plaque can be responsible for ipsilateral ischemic stroke. OBJECTIVE: The objective of this study is to suggest a role for vulnerable carotid atherosclerotic disease in the occurrence of ischemic stroke. METHODS: PubMed, Embase, Cochrane library, and reference lists have been used to evaluate articles published until February 15, 2021. RESULTS: Several factors may be involved in unstable plaque. Clinical studies support the involvement of brain inflammatory biomarkers as well as cytokines in the unstable carotid plaque. CONCLUSIONS: Biomarkers could help to stratify patients with a vulnerable carotid plaque and to personalize the drug treatment. In this review, we briefly discuss the characteristics of vulnerable plaque and the role of biomarkers in the vulnerable carotid plaque.

Ultrasound Diagnostic Method in Vascular Dementia: Current Concepts.

BACKGROUND: Increasing interest in identifying cerebral hemodynamics alterations as a cause of possible onset or worsening of cognitive impairment in elderly patients with vascular risk factors. INTRODUCTION: Intracranial ultrasound is a non-invasive, repeatable inexpensive method for recording variation of the cerebral vascular tree in physiological and pathological conditions and the diagnosis of vascular dementia (VaD). METHODS: PubMed, Embase, Cochrane library and reference lists have been searched for articles published until March 30, 2020. RESULTS: Clinical studies reported different Transcranial Doppler (TCD) parameters and subsequently transcranial duplex with color code (TCCD) in patients affected by vascular dementia. The number of studies using TCCD remains limited and most of the available data are still based on TCD. However, the use of transcranial Doppler could better stratify elderly patients with initial signs of cognitive impairment. CONCLUSION: Intracranial ultrasound employment to detect cerebral hemodynamic changes in VaD patients has been briefly discussed in this review.

Endovascular Aneurysm Repair Increases Aortic Arterial Stiffness When Compared to Open Repair of Abdominal Aortic Aneurysms.

OBJECTIVES: The initial survival advantage seen with endovascular aneurysm repair (EVAR) over open repair does not persist in the long term. Pulse wave velocity (PWV) is a measure of arterial stiffness, and increased PWV is an independent risk factor for increased cardiovascular morbidity and mortality. This prospective comparative pilot study examined the effect of implantation of an aortic graft on PWV in patients undergoing open or endovascular aortic aneurysm repair. PATIENTS AND METHODS: Thirty-four patients (15 open and 19 EVAR) were recruited. Patient demographics were similar in both the groups. Pulse wave velocity was calculated for all patients preoperatively and postoperatively using a standardized technique on a Philips IU22 Vascular Ultrasound machine and the results compared. RESULTS: An increase in mean PWV following EVAR was demonstrated. The mean postprocedure PWV of 9.7 (± 4.5) cm/sec detected in the open group was significantly lower than the elevated 12.2 (± 4.5) cm/sec detected in the EVAR group. The surgical group also demonstrated a mean decrease of 0.2 (± 4.9) cm/sec in PWV following open repair compared to a mean increase of 3.3 (± 3.7) cm/sec in the EVAR group. CONCLUSION: EVAR patients have a significantly higher postoperative PWV measurement than those undergoing open abdominal aortic aneurysm repair. Patients who have undergone EVAR may be at a higher risk of cardiovascular morbidity in the long term. A larger scale study with a longer prospective follow-up is required.

Screening for Peripheral Arterial Disease and Carotid Artery Disease in Patients With Abdominal Aortic Aneurysm.

Screening for concomitant atherosclerotic disease is important in cardiovascular risk reduction. This study assessed the prevalence of carotid artery disease (CAD) and peripheral arterial disease (PAD) in patients with known abdominal aortic aneurysms (AAAs). All patients with AAA attending the vascular laboratory between the January 1, 2007, and December 31, 2009, were eligible for a carotid ultrasound and measurement of ankle brachial indices. A total of 389 (305 males) patients were identified on the AAA surveillance program with a mean (±standard deviation) age of 76 (±8) years. The mean age of the males was 75.4 (±7.8) years, and the mean age of the females was 77 (±11) years. A total of 332 patients were assessed for CAD, and 101 (30.4%) of those were found to have significant disease. A total of 289 patients were assessed for PAD of which 131 (45.3%) were found to have PAD at rest, and 289 patients were assessed for both and 59 (20.4%) patients had significant CAD + PAD. Patients with AAAs are at high risk of other atherosclerotic disorders, and, therefore, they should receive intensive medical optimization.

Statins promote residual aneurysm sac regression following endovascular aortic aneurysm repair.

BACKGROUND: Regression of the residual sac is indicative of successful endovascular aortic aneurysm (EVAR) repair. Using color duplex ultrasound (CDU), we monitored the residual aneurysm sac following EVAR and correlated sac behavior with perioperative risk factors. METHODS: Of 145 patients with EVAR, 106 (73.1%) patients between January 01, 2003, and July 01, 2010, had at least 2 consecutive postoperative scans and thus were eligible for inclusion. Mean (± standard deviation [SD]) CDU scans per person was 4.6 (± 1.4). All were conducted by the same technologist using a standard protocol on the same machine. Aneurysm sac change in centimeters and percentage terms was calculated. The presence or absence of an endoleak was also recorded. Change in aneurysm sac size was correlated with preoperative risk factors. FINDINGS: Mean sac size change at 1 month was a decrease of 0.24 cm, equating to a percentage change of 4.3%. At 7 months, the decrease was 0.59 cm (9.8%), at 12 months, 0.73 cm (12.4%), at 18 months 0.92 cm (15.8%), and at 36 months 1.0 cm (16.6%). Both univariate and multivariate analyses demonstrated that statin therapy (P = .002) was the only risk factor variable positively associated with aneurysm regression while the presence of an endoleak was inversely related to sac reduction (P = .01). INTERPRETATION: Maximum aneurysmal sac reduction seems to occur in the first year following endograft implantation. Statin therapy appears to be associated with an increased likelihood of sac regression following EVAR. Further investigation of the role of statins in the biology of abdominal aortic aneurysmal disease is warranted.