Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions.

Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in mice, which is reiterated by chemogenetically induced microglial dysfunction associated with impaired ATP sensitivity. Hypercapnia induces rapid microglial calcium changes, P2Y12R-mediated formation of perivascular phylopodia, and microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Microglial actions modulate vascular cyclic GMP levels but are partially independent of nitric oxide. Finally, microglial dysfunction markedly impairs P2Y12R-mediated cerebrovascular adaptation to common carotid artery occlusion resulting in hypoperfusion. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation, with broad implications for common neurological diseases.

Superiority of 24-Hour Aortic Over 24-Hour Brachial Pressure to Associate With Carotid Arterial Damage on the Basis of Pressure Amplification Variability: the SAFAR Study.

BACKGROUND: Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP (bSBP) regarding the association with organ damage and prognosis of cardiovascular disease (CVD). The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-hour bSBP. We aimed at comparing the association of 24-hour aSBP and 24-hour bSBP with indices of arterial damage and examining the role of 24-hour SBP amplification variability (within-subjects' SD) in this association. METHODS: Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ambulatory BP monitoring using a validated oscillometric device (Mobil-O-Graph). Arterial damage was assessed by carotid intima-media thickness (IMT) and detection of carotid and femoral atheromatosis (plaque presence). RESULTS: Cross-sectionally 501 individuals (aged 54±13 years, 57% men, 80% hypertensives) were examined. Multivariable analysis revealed superiority of 24-hour aSBP regarding the association with IMT, carotid hypertrophy and carotid-but not femoral-atheromatosis. In receiver operator characteristics analysis, 24-hour aSBP displayed a higher discriminatory ability-compared to 24-hour bSBP-for the detection of both carotid hypertrophy (area under the curve, 0.662 versus 0.624, P<0.05) and carotid atheromatosis (area under the curve, 0.573 versus 0.547, P<0.05). This effect was more prominent in individuals with above-median 24-hour SD of SBP amplification. CONCLUSIONS: Our results suggest that 24-hour aSBP assessment may be of significant value in clinical practice to detect site-specific arterial damage on the basis of pressure amplification variability and should be prospectively examined in clinical trials.

Association of Lower Extremity Vascular Disease, Coronary Artery, and Carotid Artery Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

The motive of this article is to present the case study of patients to investigate the association between the ultrasonographic findings of lower extremity vascular disease (LEAD) and plaque formation. Secondly, to examine the association between the formation of coronary artery and carotid artery atherosclerosis in patients with type 2 diabetes mellitus. 124 patients with type 2 diabetes (64 males and 60 females with the age group 25-78 years) are considered for the research studies who have registered themselves in the Department of Endocrinology and Metabolism from April 2017 to February 2019. All participants have reported their clinical information regarding diabetes, alcohol consumption, smoking status, and medication. The blood samples from subjects are collected for measurement of HbA1c, total cholesterol, triglycerides, HDL-c, and LDL-c levels. Two-dimensional ultrasound has been used to measure the inner diameter, peak flow velocity, blood flow, and spectral width of the femoral artery, pop artery, anterior iliac artery, posterior tibial artery, and dorsal artery and to calculate the artery stenosis degree. Independent factors of atherosclerosis are determined by multivariate logistic regression analysis. The results are evaluated within the control group and it is found that there is no significant impact of gender, age, and body mass index (P > 0.05) on the lower extremity vascular diseases. Those with smoking, alcohol consumption, hypertension, and dyslipidemia have higher positive rate (P < 0.05). The type 2 diabetes mellitus group has higher diastolic blood pressure and lower triglyceride (P < 0.05). Diastolic blood pressure, HbA1C, total cholesterol, HDL-c, and LDL-C are not remarkably dissimilar between the type 2 diabetes mellitus group and the control group (P > 0.05). Compared with the control group, the type 2 diabetes mellitus group has higher frequency of lower extremity vascular diseases in the dorsal artery than in the pop artery (P < 0.05). The blood flow of type 2 diabetes mellitus group is found to be lower than that of the control group, especially in the dorsal artery (P < 0.05). The blood flow velocity of the dorsal artery is accelerated (P < 0.01). Among 117 patients of type 2 diabetes mellitus (94.35%) with a certain degree of injury, there are 72 cases of type I carotid stenosis (58.06%), 30 cases of type II carotid stenosis (24.19%), and 15 cases of type III carotid stenosis (12.10%). Out of 108 subjects in the control group, there are 84 cases of type 0 carotid stenosis (77.78%), 19 cases of type I carotid stenosis (17.59%), 5 cases of type II carotid stenosis (4.63%), and 0 case of type III carotid stenosis (0.00%). Compared with the control group, carotid stenosis is more common in patients with type 2 diabetes mellitus (P < 0.05). Age, smoking, duration of diseases, systolic blood pressure, and degree of carotid stenosis are found to be associated with atherosclerosis. The findings suggest that the color Doppler ultrasonography can give early warning when applied in patients with carotid and lower extremity vascular diseases to delay the incidence of diabetic macroangiopathy and to control the development of cerebral infarction, thus providing an important basis for clinical diagnosis and treatment.

Endothelial Progenitor Cells Count after Acute Ischemic Stroke Predicts Functional Outcome in Patients with Carotid Atherosclerosis.

OBJECTIVES: Circulating Endothelial Progenitor Cells (EPCs) predict cardiovascular outcomes in patients with coronary disease. However, the predictive value of EPCs after ischemic stroke is not well established. We aimed to study the prognostic role of EPCs in patients with acute ischemic stroke and carotid atherosclerosis, focusing on post-stroke functional outcome and stroke recurrences. MATERIALS AND METHODS: We studied consecutive adult patients with an acute (<7 days) anterior circulation ischemic stroke and carotid atherosclerosis. Cardioembolic strokes were excluded. We measured circulating EPCs by flow cytometry (CD34+/CD133+/KDR+) at inclusion (7±1 days after stroke) and at one year of follow-up. At three months and at one year we registered the modified Rankin Scale score, stroke recurrences and coronary syndromes during the follow-up. RESULTS: We studied 80 patients with a mean age of 74.3±10.4 years. We divided the population in tertiles according to the EPCs count. At three months we observed a favorable outcome in 25/36 (69.4%) patients in the lowest, 19/22 (86.4%) in the medium and 21/22 (95.5%) in the highest tercile (p=0.037). In the multivariable analysis a higher EPCs count was associated with favorable functional outcome after adjusting for age and baseline NIHSS score (OR=3.61, 95%CI 1.34-9.76; p=0.011). This association persisted at one year of follow-up. We did not find association between counts of EPCs and stroke recurrence. CONCLUSIONS: In patients with acute ischemic stroke and carotid atherosclerosis, a higher count of EPCs was associated with favorable functional outcome in the mid and long-term follow-up. Counts of EPCs did not predict stroke recurrences.

Association between Periodontitis and Carotid Artery Calcification: A Systematic Review and Meta-Analysis.

Recent studies have supported the relationship between periodontitis and carotid artery calcification (CAC), but still uncertain. This systematic review is aimed at evaluating the association between periodontitis and CAC. The search was conducted in four electronic databases: PubMed, EMBASE, Web of Science, and The Cochrane Library, supplemented by checking references of included articles and related review articles. Eligibility assessment and data extraction were conducted independently. The quality assessment and publication bias analysis were performed. The association between periodontitis and CAC was presented in odd ratio (OR) with 95% confidence interval (CI). Additional outcomes included the percentage of alveolar bone loss in CAC versus non-CAC. Twelve studies were included, and 10 were performed quantity analysis. Periodontitis with secure definition (OR = 2.02, 95%CI = 1.18 - 3.45) and insecure definition (OR = 10.78, 95%CI = 4.41 - 26.34) was associated with CAC. And a higher average percentage of alveolar bone loss (weighted mean difference = 10.84%; 95%CI = 6.40 - 15.48) was also observed in CAC patients compared to non-CAC patients. No significant publication bias was found. The results of this systematic review and meta-analysis revealed a significant relationship between periodontitis and CAC.

Transition from metabolically healthy to unhealth status associated with risk of carotid artery plaque in Chinese adults.

OBJECTIVE: We aimed to evaluate the association between the shift of metabolic status and future risk of carotid artery plaque (CAP) in community-based Chinese adults. METHODS: The current study included 9836 Chinese adults (4085 males and 5751 females, mean age 35.8 years) with metabolically healthy status at baseline (2013). Metabolically healthy status was defined as no self-reported history of metabolic diseases and cancer, and normal blood pressure, fasting blood glucose, glycated hemoglobin A1c level, and lipid profiles. Metabolically unhealthy status was defined if any of the following metabolic abnormalities were confirmed twice during follow up: high blood pressure, impaired glucose regulation, high triglycerides, high total cholesterol, high low-density lipoprotein cholesterols, or low high-density lipoprotein cholesterols. The transition was confirmed if participants' metabolic status shifted from baseline healthy to unhealthy status during follow up (2014-2018). RESULTS: We have identified 133 incident cases of CAP during follow up. Compared to those who remained metabolically healthy, the transition to high blood pressure, high total cholesterol, and high low-density lipoprotein cholesterols, were associated with high risk of developing carotid artery plaque (Hazards ratios (HRs) ranged from 1.69 to 2.34; p < 0.05 for all). The transition to impaired glucose regulation, high total triglycerides, and low high-density lipoprotein cholesterols, were associated with high risk of carotid artery plaque only in participants with metabolically healthy overweight at baseline (HR ranged from 1.95 to 4.62; p < 0.05 for all). CONCLUSION: The transition from baseline metabolically healthy status to unhealth status was associated with high risk of incident CAP.

Efficacy of Carotid Artery Stenting Performed under General Anesthesia with Somatosensory Evoked Potential Monitoring.

OBJECTIVES: During carotid artery stenting (CAS), hemodynamics may be affected by the carotid sinus reflex in some cases. Although general anesthesia has been reported to stabilize intraoperative hemodynamics, the patient's neurological condition must be assessed indirectly. Therefore, we investigated the changes in intraoperative hemodynamics and perioperative complications of CAS under general anesthesia and evaluated the efficacy of somatosensory evoked potential (SEP) monitoring in detecting a reduction in perfusion during CAS. MATERIALS AND METHODS: From April 2011 to August 2016,57 consecutive patients who underwent CAS under general anesthesia were evaluated. The follow-up period ranged from 3 to 8 years. During CAS, anesthesiologists monitored and managed the hemodynamics. SEP monitoring was performed during the CAS procedure in all patients. RESULTS: Intraoperative hypotension (systolic blood pressure ≤ 100 mmHg) was evident in 16 patients (28.1%), and 13 patients (22.8%) experienced intraoperative bradycardia; however, all of these cases were promptly managed under general anesthesia. None of the patients showed systolic blood pressure < 50 mmHg from baseline. Regarding perioperative complications, none of the patients exhibited myocardial infarction or postoperative hyperperfusion symptoms, and there was no mortality. Among 21 patients (36.8%) with a decrease in the intraoperative SEP, 3 (5.3%) exhibited transient ischemic symptoms and 1 (1.8%) had postoperative infarction. CONCLUSIONS: CAS under general anesthesia is a safe and effective management option in terms of intraoperative hemodynamic stability. In addition, our findings indicate that SEP monitoring could be helpful in evaluating transient postoperative cerebral ischemia or cerebral infarction after CAS.

Variation in perioperative cerebral and hemodynamic monitoring during carotid endarterectomy.

BACKGROUND: Hemodynamic disturbances cause half of the perioperative strokes following carotid endarterectomy (CEA). Guidelines strongly recommend strict pre- and postoperative blood pressure (BP) monitoring in CEA patients, but do not provide firm practical recommendations. Although in the Netherlands 50 centres perform CEA, no national protocol on perioperative hemodynamic, and cerebral monitoring exists. To assess current monitoring policies of all Dutch CEA-centres, a national survey was conducted. METHODS: Between May and July 2017 all 50 Dutch CEA-centres were invited to complete a 42-question survey addressing perioperative hemodynamic and cerebral monitoring during CEA. Nonresponders received a reminder after 1 and 2 months. By November 2017 the survey was completed by all centres. RESULTS: Preoperative baseline BP was based on a single bilateral BP-measurement at the outpatient-clinic in the majority of centres (n = 28). In 43 centres (86%) pre-operative monitoring (transcranial Doppler (TCD, n = 6), electroencephalography (EEG, n = 11), or TCD + EEG (n = 26)) was performed as a baseline reference. Intraoperatively, large diversity for type of anaesthesia (general: 45 vs. local [LA]:5) and target systolic BP (>100 mm hg - 160 mm hg [n = 12], based on preoperative outpatient-clinic or admission BP [n = 18], other [n = 20]) was reported. Intraoperative cerebral monitoring included EEG + TCD (n = 28), EEG alone (n = 13), clinical neurological examination with LA (n = 5), near-infrared spectroscopy with stump pressure (n = 1), and none due to standard shunting (n = 3). Postoperatively, significant variation was reported in standard duration of admission at a recovery or high-care unit (range 3-48 hr, mean:12 hr), maximum accepted systolic BP (range >100 mm hg - 180 mm Hg [n = 32]), postoperative cerebral monitoring (standard TCD [n = 16], TCD on indication [n = 5] or none [n = 24]) and in timing of postoperative cerebral monitoring (range directly postoperative - 24 hr postoperative; median 3 hr). CONCLUSIONS: In Dutch centres performing CEA the perioperative hemodynamic and cerebral monitoring policies are widely diverse. Diverse policies may theoretically lead to over- or under treatment. The results of this national audit may serve as the baseline dataset for development of a standardized and detailed (inter)national protocol on perioperative hemodynamic and cerebral monitoring during CEA.

Hypertriglyceridemia impact on arterial parameters in patients with metabolic syndrome.

BACKGROUND: The development of metabolic syndrome (MS) augments risk for atherosclerotic cardiovascular disease (CVD), but pathophysiological mechanisms of this relation are still under discussion. Overlapping CVD risk factors make it difficult to assess the importance of individual elements. This study aimed to analyze subclinical atherosclerosis based on arterial structure and function parameters in patients with MS and different triglycerides levels. METHODS: Patients (aged 40-65 years) were divided into two groups: patients with MS and with or without hypertriglyceridemia (hTG). Noninvasive assessment of vascular parameters-aortic augmentation index adjusted for heart rate 75 bpm (AIxHR75), pulse wave velocity (PWV), and common carotid artery intima-media thickness (cIMT) were performed. RESULTS: Carotid-femoral PWV (cfPWV) and carotid-radial PWV (crPWV) were significantly higher in patients with hTG. After adjusting for age, gender, waist circumference, fasting glucose, smoking status, cardiovascular family history and mean arterial pressure, crPWV (OR 1.150; CI 95% 1.04-1.28), cfPWV (OR 1.283; CI 95% 1.14-1.42) and cIMT (OR 1.13; CI 95% 1.02-1.25) were significantly associated with hTG (p < 0.05), while AIxHR75 did not show significant association. CONCLUSION: Increased triglycerides are independently associated with a cfPWV, crPWV, and cIMT and may modify CVD risk in patients with MS.

Resistive index of ophthalmic artery as an imaging biomarker of hypertension-related vascular and kidney damage.

Aim: Resistive index of ophthalmic artery (RI-OA) is associated with atherosclerotic diseases. The aim of this study was to evaluate the association of RI-OA and hypertension-related vascular and kidney damage. Materials and methods: Two-hundred and eighty hypertensive patients underwent evaluation of RI-OA, carotid atherosclerosis and level of 24 h albuminuria. Results: Albuminuria and carotid atherosclerosis were positively associated with RI-OA independently of other cardiovascular risk factors. Receiver-operating characteristic curve analysis allowed us to calculate a cut-off value of RI-OA >0.625, which would be suspicious about the existence of atherosclerotic disease. Conclusion: The ophthalmic vascular circulation allows to study connections between macro- and microcirculation in vivo. RI-OA could be a useful marker for a better stratification of the risk of developing kidney and cardiovascular disease.

HOXA5 induces M2 macrophage polarization to attenuate carotid atherosclerosis by activating MED1.

Macrophage polarization is of great importance in the formation of atherosclerotic plaque. Homeobox A5 (HOXA5), one of the homeobox transcription factors, has been revealed to be closely associated with macrophage phenotype switching. This study aims to investigate the role of HOXA5 in carotid atherosclerosis (CAS). Herein, the role of HOXA5 was explored in polarized RAW264.7 macrophages in vitro and ApoE-/- mice in vivo. Interestingly, compared with that in M0 macrophages, both the mRNA and protein expression levels of HOXA5 were decreased in lipopolysaccharide (LPS)/interferon (IFN)-γ-induced M1 macrophages, while increased in IL-4-induced M2 macrophages. In addition, in the presence of IL-4, HOXA5-overexpressing RAW264.7 cells preferred to polarizing toward M2 phenotypes. Furthermore, we found that HOXA5 bound to the promoter region and activated the expression of mediator subunit 1 (MED1), a gene known to regulate macrophage differentiation. Knocking MED1 down inhibited HOXA5-enhanced M2 macrophage polarization. In vivo, the CAS model was induced in ApoE-/- mouse fed with a Western-type diet and placed a perivascular carotid collar. Decreased mRNA and protein expressions of HOXA5 were observed in carotid arteries of CAS mice. Forced overexpression of HOXA5 reduced intimal hyperplasia and lipid accumulation in carotid vessels, and it also promoted the polarization of macrophages to M2 subtypes. The expression of MED1 was decreased in atherosclerotic carotid vessels, while HOXA5 overexpression restored its change. Collectively, HOXA5 in carotid arteries is involved in the macrophage M1/M2 switching in atherosclerotic plaque, which may be associated with its transcriptional regulation of MED1.

Assessment of Carotid Artery Distensibility and Elasticity in Patients with Asthma.

As asthma and atherosclerosis have similar pathophysiological mechanisms and risk factors, asthmatic patients may have an increased risk of atherosclerosis. This study aimed to determine the possibility of a higher risk of atherosclerosis in asthma patients compared with healthy controls by measuring carotid elasticity and distensibility. This was a cross-sectional study on 326 participants including 221 patients (129 [58.37%] females) with persistent asthma, aged 46.47±11.58 years, body mass index (BMI) of 29.74±3.99, and 105 healthy control subjects (60 [57.14%] females) aged 46.08±11.35 years, and BMI of 29.42±3.76. Of the 221 patients with asthma, 75 (33.93%) had mild, 74 (33.48%) had moderate and 72 (32.57%) had severe asthma. The carotid distensibility and elasticity were recorded and compared in both patients and control groups. There was no statistically significant difference between the patients and healthy control groups in terms of age, BMI and gender (p=0.775, p=0.482, and p=0.834, respectively). A statistically significant difference was determined between the patient and control groups in respect of both distensibility and elasticity (10.93±1.64 vs. 11.5±1.31, p=0.002 and 0.21±0.03 vs. 0.22±0.04, p=0.001, respectively). Statistically significant differences were determined between the control group and the asthma subgroups in respect of distensibility and elasticity (p<0.001, for both comparisons). The results showed that the difference was mainly due to the patients with severe asthma. Carotid distensibility and elasticity were decreased in asthmatic patients, and the main reason for this decrease was the patients in the severe asthma group. These results may suggest that the risk of subclinical carotid atherosclerosis is increased in patients with asthma, especially those with severe asthma.

Ipsilateral carotid bypass outcomes in hostile neck anatomy.

OBJECTIVE: To determine differences in outcomes among patients undergoing ipsilateral carotid bypass with hostile or normal neck anatomy. METHODS: Single-center retrospective review of all ipsilateral extracranial carotid bypasses performed between 1998 and 2018. RESULTS: Forty-eight patients underwent ipsilateral carotid bypass from the common carotid artery to either the internal carotid artery or carotid bifurcation during the study period. Seven patients were excluded owing to either a lack of follow-up or missing data. The indications for intervention included infected patches, aneurysmal degeneration, symptomatic and asymptomatic stenosis or restenosis, carotid body tumors, neck malignancy, and trauma. In 25 procedures (61%), there was a hostile neck anatomy defined as a prior history of external beam neck irradiation or neck surgery. Among this group, 12 pectoralis muscle flaps were performed for reconstructive coverage. Conduits included polytetrafluorethylene (n = 21), great saphenous vein (n = 9), superficial femoral artery (n = 7) and arterial homograft (n = 4). All superficial femoral artery conduits were used in the hostile neck group (P = .03). The overall mean time of follow-up was 22 months, with all bypasses remaining patent with no significant clinical stenosis. The 30-day ipsilateral stroke and myocardial infarction rates were 4.88% each, all within the hostile neck group, with no 30-day mortalities for the entire cohort. One-third of the muscle flaps were performed in the setting of infected patches (P = .02) with no significant differences in perioperative outcomes with use. The overall median hospital length of stay was significantly increased in patients receiving muscle flap coverage (3.0 vs 7.0 days; P = .04). CONCLUSIONS: In patients with a complex carotid pathology, ipsilateral carotid bypass is an effective solution for carotid reconstruction. Different conduits should be used depending on the indication. Muscle flap coverage should be considered in hostile settings when primary wound closure is not feasible.

Evaluation of Staged TCAR and Cardiac Surgery or Structural Heart Intervention.

INTRODUCTION: The optimal treatment strategy for patients with concomitant carotid and cardiac disease remains controversial. Transcarotid artery revascularization stenting with reversed flow protection (TCAR) has achieved results equivalent to carotid endarterectomy (CEA) in high risk patients. METHODS: A retrospective review of all patients at a single center who received staged TCAR prior to cardiac intervention was performed. RESULTS: 37 patients underwent 42 TCAR procedures prior to cardiac intervention (25 requiring open cardiac surgery and 12 requiring percutaneous intervention). There were no myocardial or neurological complications following TCAR prior to cardiac intervention. Three patients (8%) developed a neck hematoma which required evacuation. CONCLUSION: A staged approach to combined carotid and cardiac pathology with TCAR prior to cardiac intervention appears to be a safe and effective strategy.

Cerebral cortical microinfarcts in patients with internal carotid artery occlusion.

Cerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and probably have multiple etiologies. Cerebral hypoperfusion has been proposed as a causal factor. We studied CMI in patients with internal carotid artery (ICA) occlusion, as a model for cerebral hemodynamic compromise. We included 95 patients with a complete ICA occlusion (age 66.2 ± 8.3, 22% female) and 125 reference participants (age 65.5 ± 7.4, 47% female). Participants underwent clinical, neuropsychological, and 3 T brain MRI assessment. CMI were more common in patients with an ICA occlusion (54%, median 2, range 1-33) than in the reference group (6%, median 0; range 1-7; OR 14.3; 95% CI 6.2-33.1; p<.001). CMI were more common ipsilateral to the occlusion than in the contralateral hemisphere (median 2 and 0 respectively; p<.001). In patients with CMI compared to patients without CMI, the number of additional occluded or stenosed cervical arteries was higher (p=.038), and cerebral blood flow was lower (B -6.2 ml/min/100 ml; 95% CI -12.0:-0.41; p=.036). In conclusion, CMI are common in patients with an ICA occlusion, particularly in the hemisphere of the occluded ICA. CMI burden was related to the severity of cervical arterial compromise, supporting a role of hemodynamics in CMI etiology.

Extent and progression of atherosclerosis in carotid and subclavian arteries: the Carotid Artery Subclavian Artery study.

AIMS: To define the prevalence, progression, and the relationship between carotid and subclavian artery atherosclerosis and to identify factors associated with disease progression in a population of asymptomatic patients. METHODS: Among all consecutive patients without a history of cardiovascular disease admitted to our hospital for duplex ultrasound examinations of the supra-aortic arteries, from January to December 2012, we retrospectively identified 530 patients with two evaluations at least 3 years apart. Each artery was graded according to stenosis degree, as absent or less than 20%, 20-49%, 50-69%, 70-99% and total occlusion. Disease progression was defined for any class increase at any time interval. Patients were grouped according to the presence of a more than 20% stenosis of the supra-aortic district at baseline, as controls, without atherosclerosis: n = 111, 21%; isolated carotid artery disease: n = 390, 74%; concomitant subclavian artery-carotid artery disease: n = 29, 5%. There were no cases with isolated subclavian artery atherosclerosis. RESULTS: The mean time-lapse between the two evaluations was 3.1 ±â€Š0.3 years; we documented disease progression in 32 patients (6%), all limited to the carotid artery (P = 0.009 vs. controls, with no differences between isolated carotid artery disease and concomitant carotid and subclavian artery disease). Hypertension was significantly (P < 0.001) associated with disease progression, regardless of the single or double district involvement. CONCLUSION: The subclavian artery is far less prone to atherosclerosis than the carotid artery, and features lesser disease progression. Understanding factors for the different susceptibility to atherosclerosis in these two close arterial districts provides insight into local factors prompting vascular disease.

Association of Carotid Intima-Media Thickness and Other Carotid Ultrasound Features With Incident Dementia in the ARIC-NCS.

Background Increased carotid intima-media thickness, interadventitial diameter, presence of carotid plaque, and lower distensibility are predictors for cardiovascular disease. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer disease-related dementia. Therefore, we assessed the relationship of carotid measurements and arterial stiffness with incident dementia in the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results A total of 12 459 ARIC participants with carotid arterial ultrasounds in 1990 to 1992 were followed through 2017 for dementia. Dementia cases were identified using in-person and phone cognitive status assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for incident dementia. Participants were aged 57±6 at baseline, 57% were women, and 23% were Black individuals. Over a median follow-up time of 24 years, 2224 dementia events were ascertained. After multivariable adjustments, the highest quintile of carotid intima-media thickness and interadventitial diameter in midlife was associated with increased risk of dementia (HR [95% CIs], 1.25 [1.08-1.45]; and 1.22 [1.04-1.43], respectively) compared with its respective lowest quintile. Presence of carotid plaque did not have a significant association with dementia (HR [95% CI], 1.06 [0.97-1.15]). Higher distensibility was associated with lower risk of dementia (HR [95% CI] highest versus lowest quintile, 0.76 [0.63-0.91]). Conclusions Greater carotid intima-media thickness, interadventitial diameter, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.

Detection of Early Vascular Atherosclerosis in Type 2 Diabetes Mellitus Using Ultrasound Radiofrequency-Data Technique.

OBJECTIVES: To quantitatively evaluate changes in vascular elasticity and intima-media thickness (IMT) of the common carotid artery (CCA) with Ultrasound radiofrequency (RF)-data technology in asymptomatic patients with type-2 diabetes mellitus (T2DM) and controls. MATERIALS AND METHODS: Thirty-seven T2DM patients and 39 controls were enrolled. Arterial elasticity and CCA-IMT were quantitatively assessed by RF-data technology. The CCA diameters in the diastolic and systolic phases, carotid distensibility (CD), IMT, values of stiffness (ß) and local pulse wave velocity (PWVß) were measured and compared between the two groups. RESULTS: The T2DM group had significantly larger CCA diastolic and systolic diameter, lower CD values, higher IMT measurements (all p < 0.001), and higher values of ß and PWVß (all P < 0.05) than the controls. Significant differences were not revealed in the mean values of IMT, ß, PWVß and CD across both sides of the CCA (all P > 0.05). CONCLUSIONS: Higher IMT measurement and lower arterial elasticity of the CCA are significantly pronounced in asymptomatic T2DM patients and may suggest atherosclerotic changes, and the ultrasound RF-data technique may be used as a potential approach for detection of early-stage atherosclerosis.

Dapagliflozin effect on endothelial dysfunction in diabetic patients with atherosclerotic disease: a randomized active-controlled trial.

BACKGROUND: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.

Efficacy and safety of traditional Chinese patent medicine on carotid artery atherosclerosis in adults: A network meta-analysis protocol.

BACKGROUND: Atherosclerosis (AS), the predominant pathological basis of ischemic cardiovascular and cerebrovascular diseases, remains a common and severe clinical problem. The experiments in vitro and in vivo indicate that Traditional Chinese patent medicine (TCPM) shows beneficial efficacy against AS through a variety of mechanisms. However, the existing therapeutic TCPM for the treatment of AS are diverse, and it is still significant to evaluate the pros and cons of a certain TCPM. Therefore, the study aims to compare the efficacy and outcomes of different anti-atherosclerotic TCPM in adults with the hope of providing references for clinical decision making. METHODS: Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure Database, Wanfang Database, Chinese BioMedical Literature Database, and China Science and Technology Journal Database will be searched. Randomized controlled trials (RCTs) of TCPM for aortic AS in adults will be included in this study if they meet the Population/Intervention/Comparison/Outcomes/Study Design (PICOS) criteria. Two reviewers will independently perform citations screening, data extraction and risk of bias assessment. STATA 15.0 and WinBUGS 1.4.3 will be employed to conduct statistical analyses under the Bayesian framework. RESULTS: The efficacy and safety of various TCPM strategies on aortic AS in adults will be compared. CONCLUSION: The study will expand the range of options for anti-atherosclerotic therapeutic strategies and encourages further clinical research in traditional Chinese medicine. INPLASY REGISTRATION NUMBER: INPLASY2020120036.