Carotid Artery Wall Thickness Research Articles

Positive Echocardiographic Association between Carotid Artery and Coronary Artery Diameter and Z-Score in a Mouse Model of Kawasaki Disease.

LCWE was intraperitoneally injected into 5-week-old male C57BL/6 mice to induce CALs. We studied the longitudinal status of the carotid and coronary arteries and analyzed the Z-score of coronary artery diameter. Carotid artery wall thickness (day 7) and diameter (day 14) significantly increased in the LCWE group with a dose-dependent effect (p < 0.05). Aortic diameter and wall thickness demonstrated significant increases on day 28 and day 7, respectively (p < 0.05). Carotid artery outer diameter and wall thickness were positively associated with coronary artery diameter on day 28 (p < 0.01). Coronary artery diameter significantly increased in the LCWE group after day 7 (p < 0.05). The percentage of Z > 3.0 indicated was more than 80% in the high-dose LCWE group and 0% in the control group. This report is the first to use coronary artery Z-score in a mouse model of KD by echocardiography and to find a positive association between carotid artery and coronary artery diameter.

In Vivo Material Properties of Human Common Carotid Arteries: Trends and Sex Differences.

In vivo estimation of material properties of arterial tissue can provide essential insights into the development and progression of cardiovascular diseases. Furthermore, these properties can be used as an input to finite element simulations of potential medical treatments. This study uses non-invasively measured pressure, diameter and wall thickness of human common carotid arteries (CCAs) acquired in 103 healthy subjects. A non-linear optimization was performed to estimate material parameters of two different constitutive models: a phenomenological, isotropic model and a structural, anisotropic model. The effect of age, sex, body mass index and blood pressure on the parameters was investigated. Although both material models were able to model in vivo arterial behaviour, the structural model provided more realistic results in the supra-physiological domain. The phenomenological model predicted very high deformations for pressures above the systolic level. However, the phenomenological model has fewer parameters that were shown to be more robust. This is an advantage when only the physiological domain is of interest. The effect of stiffening with age, BMI and blood pressure was present for women, but not always for men. In general, sex had the biggest effect on the mechanical properties of CCAs. Stiffening trends with age, BMI and blood pressure were present but not very strong. The intersubject variability was high. Therefore, it can be concluded that finding a representative set of parameters for a certain age or BMI group would be very challenging. Instead, for purposes of patient-specific modelling of surgical procedures, we currently advise the use of patient-specific parameters.

Sex-specific associations of reservoir-excess pressure parameters with age and subclinical vascular remodeling.

Central artery reservoir pressure and excess pressure (XSP) are associated with cardiovascular disease (CVD) events and mortality. However, sex differences in the trajectory of central reservoir pressure and XSP with advancing age and their relations with vascular markers of subclinical CVD risk are incompletely understood. Therefore, we tested the hypothesis that central reservoir pressure and XSP would be positively associated with advancing age and vascular markers of subclinical CVD risk in men and women. Healthy adults ( n = 398; aged 18-80 years, 60% female individuals) had central (carotid) artery pressure waveforms acquired by applanation tonometry. Reservoir pressure and XSP peaks and integrals were derived retrospectively from carotid pressure waveforms using custom written software. Carotid artery intimal-medial thickness (IMT) was measured by ultrasonography, and aortic stiffness was determined from carotid-femoral pulse wave velocity (cfPWV). Reservoir pressure peak, reservoir pressure integral and XSP integral were higher with age in both men and women ( P < 0.05), whereas XSP peak was lower with age in men ( P < 0.05). In women, both reservoir pressure peak ( β = 0.231, P < 0.01) and reservoir pressure integral ( β = 0.254, P < 0.01) were associated with carotid artery IMT, and reservoir pressure peak was associated with cfPWV ( β = 0.120, P = 0.02) after adjusting for CVD risk factors. Central artery reservoir pressure and XSP were higher with advancing age in men and women, and reservoir pressure peak was associated with both carotid artery wall thickness and aortic stiffness in women but not men. Central reservoir pressure peak may provide some insight into sex differences in vascular remodeling and subclinical CVD risk with advancing age in healthy adults.

PS-C29-7: ASSOCIATION OF SERUM LEPTIN TO ADIPONECTIN RATIO AND CARDIOVASCULAR STRUCTURAL INDICES IN ESSENTIAL HYPERTENSIVE PATIENTS WITHOUT CHRONIC KIDNEY DISEASE

Objective: Dysregulated leptin and adiponectin profile is known to be associated with atherosclerotic disease. The evaluation of the leptin to adiponectin (L/A) ratio has been suggested as a powerful useful atherosclerotic index compared with adiponectin and leptin alone in patients with type 2 diabetes and obesity. In this study, we investigated the usefulness of L/A ratio for vascular structural abnormalities in essential hypertensive patients. Design and method: In 151 untreated essential hypertensive patients (86 males, average age 56 ± 12 years) without chronic kidney disease (urinary albumin excretion (UAE) less than 300 mg/g of creatinine and estimated glomerular filtration rate 60 mL/min/1.73m2 or more), blood sampling, 24-hour urine collection, and 24-hour blood pressure monitoring were performed. Intima-media thickness of carotid artery (IMT) and minimal forearm vascular resistance (MVR) (wall to lumen ratio in resistance vessel) were also measured by using ultrasonography and strain-gauge plethysmography, respectively. Results: L/A ratio was higher in men than in women (1.23 ± 1.56 vs 0.73 ± 0.87, p &lt; 0.05). There was no correlation between L/A ratio and systolic and diastolic blood pressure, and pulse rate. L/A ratio correlated positively with body mass index, triglyceride, hemoglobin A1c, HOMA-R and urinary C-peptide excretion (r = 0.57, 0.20, 0.20, 0.31, 0.27, p &lt; 0.05, respectively) and negatively with HDL-cholesterol (r = -0.24, p &lt; 0.05). In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively)In addition, UAE, IMT and MVR were increased accompanying incremental L/A ratio (r = 0.20, 0.17, 0.19, p &lt; 0.05, respectively), whereas these indices did not associated with leptin and adiponectin individually. In multiple regression analysis, L/A ratio was an independent determinant for UAE, IMT and MVR. Conclusions: In patients with essential hypertension, L/A ratio was associated with obesity, abnormal glucose and lipid metabolism, increase in microalbuminuria, and arterial and arteriolar sclerosis. L/A ratio was considered as a useful indicator of vascular structural abnormalities in patients with essential hypertension.

Reversible Improvement of Arterial Stenosis and Wall Thickness in Takayasu Arteritis Through Treatment With Tocilizumab

Early diagnosis and initiation of treatment in Takayasu arteritis (TA) is important to prevent irreversible arterial changes. A 39-year-old female was diagnosed with active TA. Subcutaneous administration of tocilizumab (162 mg/week) was initiated in combination with prednisolone (30 mg/d). After 21 months, the carotid arterial stenosis and wall thickness had normalized with only slight plaque on echocardiography. After 23 months, computed tomography showed normalization of the overall aortic stenosis and wall thickness. The prednisolone dosage could be reduced to 2 mg/d without relapse for >2 years. Early combination treatment of TA with tocilizumab prevented and normalized vascular stenosis and wall thickness.

Microembolic Signals in Arteries of the Base of the Brain after Ischemic Stroke.

Embolic strokes make up a significant proportion of acute cerebrovascular accidents. Doppler blood flow monitoring with microembolodetection allows suggesting the embolic nature of cerebral infarction. The aim of this study was to identify factors associated with the presence of microembolic signals in patients with ischemic stroke. The study included 515 patients, microembolic signals were detected in 48 (9.3%) of them. According to multispiral CT angiography, significant differences in patients with and without microembolic signals were found for wall thickness of both common carotid arteries and for left internal carotid artery (p<0.05). Factor analysis revealed a variable that reflects the severity of left carotid arteries atherosclerosis, which was a significant predictor of registration of the microembolic signals (p=0.016).

The predictive value of internal carotid artery wall thickness in computed tomography angiography to avoid complications of plaque removal failure in modified eversion carotid endarterectomy.

The benefits of computed tomography carotid angiography (CTA) in terms of evaluating the anatomical structure of the carotid arteries, surgical planning, and evaluating possible risks were reported in previous studies. This study aimed to calculate the predictive value of internal carotid wall thickness in CTA that can predict whether a modified carotid eversion endarterectomy (MCEE) will result in a successful or not. This study was designed in a retrospective cross-sectional format. Consecutive 83 symptomatic carotid surgery patients who were operated in our hospital and had CTA were included in this study. The wall thickness of the internal carotid artery (ICA) 20mm distal from the carotid bifurcation was calculated in axial sections using a three-dimensional imaging technique. In addition, all patients' characteristics and laboratory findings were recorded. Patients who failed MCEE and required classical carotid endarterectomy were compared with patients who had successful MCEE. MCEE technique was applied to 62 patients. In 21 patients, the MCEE technique failed and the classical endarterectomy technique was required. Preoperative clinical and laboratory characteristics were similar in both groups. The mean ICA wall thickness was 0.65mm 20mm distal to from the carotid bifurcation and it was lower in the group with successful MCEE (1.03 ± 0.21mm vs. 0.56 ± 0.08mm) (p < 0.001). The critical ICA wall thickness was calculated as 0.76mm in the group that MCEE failed and classical carotid endarterectomy was required. Cut-off analysis of ICA wall thickness was calculated as 0.755mm in ROC analysis (p < 0.001), (95% confidence interval, curve area; 0.985). Successful carotid endarterectomy with the MCEE method is associated with distal ICA wall thickness and distal extension of the atheroma plate. The use of ICA wall thickness 20mm distal to from the bifurcation as a predictive value for the success of the MCEE technique is beneficial to avoid serious complications.

Effect of menopausal hormone therapy on arterial wall echomorphology: Results from the Early versus Late Intervention Trial with Estradiol (ELITE)

ObjectiveTo evaluate the effect of hormone therapy (HT) on arterial wall composition by ultrasound. BackgroundThe effect of HT on the progression of subclinical atherosclerosis has been well-described using measurements of common carotid artery (CCA) wall thickness. However, it is unknown whether the change in arterial wall anatomic structure is accompanied by an effect of HT on arterial wall composition. MethodsA total of 643 healthy postmenopausal women divided into two strata according to the time since menopause (<6 years, the early-postmenopause group; or >10 years, the late-postmenopause group) were randomized to receive either active treatment or placebo. For hysterectomized women, the active treatment was oral micronized 17β-estradiol 1 mg/day; for women with a uterus, 4% vaginal micronized progesterone gel 45 mg/day for 10 days each month was added to the estradiol regimen. Gray-scale median of the CCA intima-media complex (IM-GSM), a (unitless) measurement of arterial wall composition based on echogenicity, was determined by high-resolution B-mode ultrasonography. Lower IM-GSM, or less echogenicity, indicates more atherosclerosis. IM-GSM and serum estradiol (E2) concentration were assessed every 6 months over a median 4.8-year trial period. Linear mixed effects regression models were used for all analyses. ResultsOverall, IM-GSM progression/year had a negative trajectory, reflecting reduction in echogenicity over time (worsening atherosclerosis). HT effects on IM-GSM progression/year differed by postmenopause strata (interaction p-value = 0.02). IM-GSM progression/year (95% CI) in the early postmenopause group randomized to HT was −0.50 (−0.82, −0.18)/year compared with −1.47 (−1.81, −1.13)/year among those randomized to placebo (p-value <0.0001). In the late postmenopause group, the annual IM-GSM progression rate did not significantly differ between HT and placebo (p = 0.28). Higher mean on-trial E2 (pg/ml) levels were associated with higher IM-GSM progression, indicating less atherosclerosis progression in all women (β (95% CI) = 0.006 (0.0003, 0.01), p = 0.04). For each pg/dl E2, IM-GSM progression/year was 0.007 ((−0.0002, 0.01), p = 0.056) in the early and 0.003 ((−0.006, 0.01), p = 0.50) in the late postmenopause group (interaction p-value = 0.51). CIMT progression rate (μm/year) was significantly inversely associated with the IM-GSM progression (β (95% CI) = −4.63 (−5.6, −3.7), p < 0.001). ConclusionsHT, primarily with oral estradiol, reduced atherogenic progression of arterial wall composition in healthy postmenopausal women who were within 6 years from menopause.Trial registration number: NCT01553084

Protective role of Dietary Choline and Docosahexaenoic acid or Environmental enrichment in attenuating high fat diet-induced arterial wall changes in obese rats

Childhood obesity increases body mass index and long term metabolic disturbances. The present study is designed to analyze postnatal obesity-induced changes in body mass index and common carotid artery wall thickness and the role of dietary choline and DHA or environmental enrichment in mitigating these changes. Four groups of male rat pups (n=8/group) were assigned as Normal control (NC), Obese (OB) fed high-fat diet, Obesity-induced supplemented choline and DHA (OB+CHO+DHA) with 5mmol/kg/day of choline and 150 mg/ day of DHA, Obesity-induced environmental enrichment (OB+EE) exposed to environmental enrichment for 90 days. Body mass index was calculated after 90 days. Subsequently, rats were euthanized to excise common carotid artery. 5µ thick sections were processed for haematoxylin and eosin and Verhoff –Vangeison stains. Mean body weight, body mass index, thickness of tunica intima, media and percentage of collagen fibers in artery were significantly higher in OB group (p&lt; 0.01, &lt;0.001,&lt; 0.01, &lt; 0.001, &lt; 0.05) as compared to the same in NC rats respectively. These changes were significantly (p&lt;0.01, &lt; 0.05) attenuated in OB+CHO+DHA and OB+EE groups compared to OB rats. Increased body mass index in early ages is an indicator for atherosclerosis. Supplementation of dietary choline and DHA or environmental enrichment exposure attenuates these changes from an early young age.

Carotid smooth muscle contractility changes after severe burn

Severe burns result in cardiovascular dysfunction, but responses in the peripheral vasculature are unclear. We hypothesize that severe burns disturb arterial contractility through acute changes in adrenergic and cholinergic receptor function. To address this, we investigated the changes in carotid artery contractility and relaxation following a severe burn. Thirty-four adult Sprague–Dawley male rats received a 40% total body surface area (TBSA) scald burn and fluid resuscitation using the Parkland formula. Control animals received sham burn procedure. Animals were serially euthanized between 6 h and 14 days after burn and endothelium-intact common carotid arteries were used for ex vivo force/relaxation measurements. At 6 h after burn, carotid arteries from burned animals demonstrated a > 50% decrease in cumulative dose-responses to norepinephrine (p < 0.05) and to 10−7 M angiotensin II (p < 0.05). Notably, pre-constricted carotid arteries also demonstrated reduced relaxation responses to acetylcholine (p < 0.05) 6 h after burn, but not to sodium nitroprusside. Histologic examination of cross-sectional planes revealed significant increases in carotid artery wall thickness in burned rats at 6 h versus 3 days, with increased collagen expression in tunica media at 3 days (p < 0.05). Carotid artery dysfunction occurs within 6 h after severe burn, demonstrating decreased sensitivity to adrenergic- and angiotensin II-induced vasoconstriction and acetylcholine-induced relaxation.

Abstract P154: Leisure-Time Physical Activity, Sedentary Behavior, And Carotid Atherosclerosis Morphology: The ARIC Carotid-MRI Study

Introduction: Studies suggest that greater physical activity (PA) may be associated with favorable carotid artery characteristics, while greater time spent in sedentary behavior (SB) may be a potential risk factor for atherosclerosis development and progression. We evaluated the association between leisure-time PA and SB in midlife and their temporal patterns with carotid atherosclerotic morphology measured by MRI. Methods: ARIC Carotid-MRI participants (n=1582, mean age: 53 years, 43% male, 18% Black) with self-reported assessments of PA and SB at visits 1 (1987-1989) and 3 (1993-1995), who participated in the Carotid MRI substudy in 2004-2006 were included. Self-reported leisure-time PA was categorized based on the American Heart Association’s Life Simple 7 categorization of ideal, intermediate, or poor PA. SB was ascertained based on participant report of how often they watched television during leisure-time, and categorized as low [“never”/ “seldom”], medium [“sometimes”], or high [“often”/“very often”]. To measure persistent PA and SB, we examined participants who reported the same level of PA (n=849) or SB (n=954) at both visits 1 and 3. Carotid MRI using a 1.5T scanner quantified internal carotid artery wall thickness, lipid core, and calcification measures. Weighted analyses accounted for the sampling design allowing for generalizability to the visit 1 ARIC population. Multivariable linear and logistic regression were used for continuous and categorical outcomes, respectively. All models were adjusted for demographic, behavioral, and lifestyle factors. Results: Though no clear trends were observed for PA, higher levels of SB were associated with a greater odds of lipid core presence and lower odds of calcification (Table). Similar trends were observed for the persistence analyses, though none were statistically significant. Conclusions: PA and SB may influence atherosclerotic plaque characteristics. SB and lack of PA may have different measurable effects on plaque morphology.

Ultrasound evaluation of cardiovascular function in male and female APOE3 and APOE4 mice

Introduction Alzheimer's disease (AD) is the most common form of dementia and is the 6th leading cause of death in the US. Growing evidence supports a link between AD and cardiovascular disease (CVD). Variant isoforms of apolipoprotein E (APOE) are risk factors for both AD and CVD. The most common APOE isoform, APOE3, has neutral risk for developing AD, whereas APOE4 increases AD risk. Pathogenic alterations in cardiac (C), aortic (TA) and carotid artery (CA) function are known to contribute to neurodegenerative diseases including AD. Previous studies in our lab have demonstrated cerebral arteries from APOE3 mice exhibit “normal” aging characteristics, whereas cerebral arteries from APOE4 mice exhibited a delay in age-related changes in vascular structure and function. Because of this observation, we investigated whether age-related changes in cardiac structure/function (in vivo) mirrored in vitro experiments of isolated cerebral arteries. Here, we evaluated age-related changes in cardiac structure/function, in mice expressing human-ApoE targeted replacement of APOE3 (B6.129P2-Apoetm2(APOE*3)Mae N8) or APOE4 (B6.129P2-Apoetm3(APOE*4)Mae N8)(Taconic Labs). We hypothesized that mice expressing APOE4 would have delayed age-related changes in cardiac structure/function compared to age matched APOE3 mice. Methods In vivo high-resolution ultrasound (U/S) imaging was performed to evaluate the structure and function of cardiac, thoracic aorta (TA), carotid artery (CA), and cerebral blood flow in young (3-4 months), adult (12-14 months) and aged (18-20 months), APOE3 and APOE4 mice. Male and female mice were used. Blood pressure (BP) was determined using the tail-cuff method. All U/S and BP values were collected under isoflurane anesthesia. Results were considered significant at p<0.05. Results Both hAPOE3 and hAPOE4 mice exhibited age-related increase in body weight. The peak velocity measurements of the posterior cerebral artery showed no statistical difference between the groups. CA structure and function was assessed by wall thickness (WT) and pulse wave velocity (PWV) respectively. Our data showed an age-related increase in CA PWV and WT in hAPOE3 and hAPOE4 mice. TA PWV also showed an age-related increase in both hAPOE3 and hAPOE4 mice (P<0.05). The indices of cardiac function, cardiac output (CO), ejection fraction (EF), stroke volume (SV) showed no significant difference between the groups. The left ventricle mass increased with age in both hAPOE3 and hAPOE4 mice. And finally, the systolic and diastolic BP values showed no significance difference between groups. Conclusion These data suggest that hAPOE3 and hAPOE4 mice show similar age-related cardiac and vascular changes. Future studies have been designed to assess whether psycho-social stress and/or diet are involved in APOE4 allele related development of CVD and AD/dementia.

ASSOCIATION OF PARITY AND GRAVIDITY WITH CAROTID INTIMA-MEDIA THICKNESS: THE OHASAMA STUDY

Abstract Objective: We aimed to investigate if any of parity, gravidity and menstrual factors are associated with carotid atherosclerosis diagnosed by ultrasound imaging. Design and method: We identified 543 women aged 60 years or older from the general population of Ohasama, a rural Japanese community, who answered a questionnaire on parity and gravidity and age at menarche, were free of previous cardiocerebrovascular disease. The carotid atherosclerosis was assessed based on the presence of focal carotid plaque and mean common carotid intima-media thickness (IMT) by using ultrasound imaging. Information on possible confounding factors including self-measured blood pressure at home (home BP) was simultaneously obtained. Results: Plaque lesion was observed in 138 (25%) and the median of IMT was 0.68 mm with interquartile range of 0.63–0.75. Means of home systolic and diastolic BP levels were 129.5 ± 14.2 mmHg and 74.0 ± 8.4 mmHg, respectively. Multivariate logistic regression models showed that compared with women who had two children, women who had three children (OR 1.82, 95%CI, 1.12–2.96) and women who had four or more children (OR 2.60, 95%CI, 1.47–4.58) were more likely to have an increased risk with the presence of focal carotid plaque adjusting for age (p &lt; 0.001), body mass index (p = 0.012), hypertensive drug use (p = 0.319), home systolic BP levels (p = 0.364), impaired glucose tolerance (p = 0.230) and hyperlipidemia (p = 0.808), and current smoker (p = 0.955) and drinker (p = 0.294). Adjusting for these covariates, the highest quartile of gravidity (4- vs. 2) was associated with an increased risk of the plaques lesion (OR 2.03; 95%CI: 1.14–3.62) and youngest age quartile of age at menarche (13- y/o vs. 14 years) was associated with a decreased risk of the presence of plaque (OR, 0.51, 95%CI: 0.28–0.92). Multivariate general linear regression model showed that the wall thickness of carotid artery appeared slightly thicker among women who had highest parity quartile (b = 0.036, p = 0.009) adjusting for same covariates. The wall thickness of carotid artery was not associated with both gravidity (p = 0.089) and age at menarche (p = 0.113). Conclusions: Higher parity and gravidity, and younger age at menarche were associated with carotid atherosclerosis, independent of major confounding factors including age and home BP levels.

Time in Range Does Not Associate With Carotid Artery Wall Thickness and Endothelial Function in Type 1 Diabetes.

Patients with Type 1 diabetes (T1D) have an increased risk of developing atherosclerosis and complications as myocardial infarction and peripheral artery disease. The thickening of the carotid wall and the brachial artery dysfunction are early and preclinical manifestations of atherosclerosis. The standard marker of care for assessment of glycemic control, glycated hemoglobin, does not associate with early atherosclerosis. We have hypothesized that the emerging metric of glycemic control, as the time spent in the target range (TIR), might be associated with carotid thickening and endothelial dysfunction. According to the hypothesis, we have designed the present research with the aim to evaluate the association between TIR collected in the short and long term and the measures of arterial morphology and function in patients with T1D. In our study, 70 patients and 35 healthy controls underwent ultrasound vascular study to measure carotid artery intima-media thickness (IMT) and brachial artery endothelial function by the flow-mediated dilation (FMD) technique. TIR was collected by a continuous glucose monitoring system for 2 weeks, 3 months, and 6 months before the vascular study. Patients with T1D showed a significantly higher carotid IMT (mean±SE, 644±19 vs. 568±29 µ; p= 0.04) and a significantly lower FMD (mean±SE, 7.6±0.4 vs. 9.8±0.6%; p=0.01) compared with control subjects. No significant relationship between IMT, FMD, and TIR collected in the short and long term emerged. Young patients with T1D have early vascular abnormalities. The percent of TIR does not correlate with preclinical atherosclerosis. This finding underlines the complexity of the interplay between diabetes and atherosclerosis.

Extent of optico-carotid recess is significantly associated with presence of bony dehiscences and bone thickness in the optico-carotid area

Background: The objectives of this study were to evaluate the frequency of bony dehiscences in the optico-carotid recess (OCR) area and to measure the thickness of the bony lamellas bordering the OCR, according to our previously proposed OCR classification taking into account the extent of the recess. Methodology: A total of 100 human cadaver heads (n= 200 sphenoid sinuses) were investigated. Samples were divided into groups according to the presence and extent of OCR (no OCR, sub-optical OCR, latero-optical OCR). Bony dehiscences were visually identified and bone thickness was measured by using a high-resolution micrometer. Results: A bony dehiscence in the OCR area was observed in 20%. A significant difference in bony dehiscence occurrence rate between OCR types was found. The wall thickness of the bony carotid artery- and optic nerve canals bordering the OCR were 0.25 ± 0.16 mm and 0.27 ± 0.15 mm, respectively. Significant differences between OCR groups in bony wall thickness of the carotid artery canal and optic nerve canal were found. Samples with a latero-optical OCR had a significant thinner wall of the carotid artery and optic nerve canal than samples with a sub-optical OCR and no OCR. Conclusions: The current results indicate that the presence of an extended OCR, e.g. latero-optical, is highly associated with a greater risk of bony dehiscences and thinner bony lamellas in the OCR region.

A cross-sectional, case-control study of intracranial arterial wall thickness and complete blood count measures in sickle cell disease.

In sickle cell disease (SCD), cerebral oxygen delivery is dependent on the cerebral vasculature's ability to increase blood flow and volume through relaxation of the smooth muscle that lines intracranial arteries. We hypothesised that anaemia extent and/or circulating markers of inflammation lead to concentric macrovascular arterial wall thickening, visible on intracranial vessel wall magnetic resonance imaging (VW-MRI). Adult and pediatric SCD (n = 69; age = 19.9 ± 8.6 years) participants and age- and sex-matched control participants (n = 38; age = 22.2 ± 8.9 years) underwent 3-Tesla VW-MRI; two raters measured basilar and bilateral supraclinoid internal carotid artery (ICA) wall thickness independently. Mean wall thickness was compared with demographic, cerebrovascular and haematological variables. Mean vessel wall thickness was elevated (P<0·001) in SCD (1·07±0·19mm) compared to controls (0·97±0·07mm) after controlling for age and sex. Vessel wall thickness was higher in participants on chronic transfusions (P=0·013). No significant relationship between vessel wall thickness and flow velocity, haematocrit, white blood cell count or platelet count was observed; however, trends (P<0·10) for wall thickness increasing with decreasing haematocrit and increasing white blood cell count were noted. Findings are discussed in the context of how anaemia and circulating inflammatory markers may impact arterial wall morphology.

The Effect of Exercise During Pregnancy on Maternal and Offspring Vascular Outcomes: a Pilot Study

The aim of this pilot study is to obtain estimates for the change in maternal cerebrovascular (primary) and offspring vascular structure (secondary) during healthy pregnancy that includes structured exercise. Eighteen pregnant women self-assigned to a moderate-intensity aerobic exercise intervention or a control group. Maternal cerebral blood flow (CBF) at the middle cerebral artery, cerebro- and peripheral-vascular function was assessed at the end of each trimester. Offspring carotid artery intima-media thickness (IMT) was measured within 12 weeks of birth. For exploratory purposes, we performed statistical analysis to provide estimates of the change for primary and secondary outcome variables. Maternal CBF reduced (− 8 cm s−1 [− 14 to − 2]) with evidence of change to cerebral autoregulation (normalised gain: 0.12 %cm s−1% mmHg−1mmHg/% [− 0.18 to 0.40]) during pregnancy. Offspring carotid IMT was smaller in the exercise group (− 0.04 mm [− 0.12–0.03]) compared with controls. Based upon this data, a sample size of 33 and 57 in each group is required for low-frequency normalised gain and offspring IMT, respectively. This would provide 90% power to detect statistically significant (P < 0.05) between group differences in a randomised controlled trial. CBF is reduced in pregnancy, possibly due to reduced vascular resistance and altered maternal cerebral autoregulation. Maternal exercise had negligible effects on cerebrovascular adaptation to pregnancy, but we observed lower offspring carotid artery wall thickness following maternal exercise. Our directional findings and sample size estimations should be explored in a fully powered randomised control trial.Clinical trial registration: The trial was registered on March 14th at https://register.clinicaltrials.gov (NCT03079258). Participant enrolment began on 3rd April 2016.

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events

It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden. To assess associations of CA MRI plaque characteristics with incident CVD events. The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020. Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed. Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics. Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated. The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

Longitudinal effects of smoking cessation on carotid artery atherosclerosis in contemporary smokers: The Wisconsin Smokers Health Study

Background and aimsWe quantified the effects of smoking and smoking cessation on carotid artery atherosclerosis and wall thickness in two unique cohorts of smokers making a quit attempt. MethodsOur primary analysis included 726 smokers making a quit attempt in a randomized clinical trial with long-term follow-up. Our secondary analysis included 889 smokers making a quit attempt in a subsequent trial. Participants underwent carotid artery ultrasonography at baseline and up to 3 subsequent visits. Primary outcomes were changes in carotid plaque score and intima media-thickness (IMT). We calculated a smoking burden score (SBS) that reflected the number of visits in which participants reported smoking after the quit attempt. Multivariable regression examined relations between SBS and carotid artery outcomes with adjustments for cardiovascular disease risk factors. ResultsIn the primary analysis, participants were mean (standard deviation) 46.1 (10.3) years old (57.9% female) and smoked 21.1 (8.9) cigarettes per day (CPD). After a median of 7 years, lower SBS predicted less increase in carotid plaque score (Chi-squared = 13.0, p = 0.012). SBS independently predicted change in carotid plaque score (p = 0.007; SBS 0 vs 4) as did baseline CPD (p = 0.024) and age (p<0.0001). SBS did not affect carotid IMT change. In the secondary analysis, increasing SBS was associated with increased likelihood of new plaques over 3 years among participants that smoked ≥15 CPD, (Chi-squared = 6.51, p = 0.011). ConclusionsSmoking cessation is associated with less progression of carotid plaque, but not IMT. Salutary associations of smoking cessation with carotid plaque progression are related to degree of abstinence.

Multidimensional Vascular Evaluation in Patients Treated with Tyrosine Kinase Inhibitors (TKIs): From Plaque Formation to Evolution and Follow up on 150 Patients

Background Among the unresolved issues concerning management of chronic myeloid leukemia (CML) patients, the most feared are long-term adverse events due to TKI treatment. Although TKIs have revolutionized CML outcomes, their use has also been associated with severe side effects including cardiovascular events, of which peripheral arterial occlusive disease (PAOD) is the most frequently reported. In 2010 we began a long-term collaboration with local angiologists and vascular surgeons to investigate, screen and follow patients on TKI therapy. Placque formation, evolution and follow up of 150 patients were studied and are presented here. Methods We analyzed 143 CML and 7 Ph+ Acute Lymphoid leukemia (ALL) patients, all of whom were treated with TKIs. Careful assessment of cardiovascular risk factors (i.e., age, smoking, obesity, diabetes, high blood pressure, high LDL or low HDL cholesterol levels, family history of heart disease or other cardiovascular disease) were done according to the European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) risk charts. A complete vascular screening, including physical examination, and a series of instrumental tests were performed for all patients. Tests included doppler echocardiography (US) of supra-aortic arteries with measurement of pre-bulbar IMT, abdominal arteries and inferior limbs arteries and veins (IL), ABI of the posterior tibial artery and digital photoplethysmography (FPG). Patients needing surgical intervention were referred to a surgeon. The team of hematologists, angiologists and surgeons met periodically to discuss results and intervention approaches. Results Patients included 76 males and 74 females with a median age of 53.7 yo (range 18-85). All patients were treated with a TKI at diagnosis, 87 (58%) with imatinib, 63 (42%) with other TKIs, including ponatinib (2 LLA), and all received TKI therapy for a minimum of 12 months since 2010. For analyses purposes, patients were divided in 7 different age groups at diagnosis (18-30, 31-40, 41-50, 51-60, 61-70, 71-80 and 81-85 years; patients incidence per group was 6%, 18%, 18.6%, 27.4%, 13.3%, 12.7% and 4%, respectively). Each patient in the study received yearly screening, and this increased to every 3-6 mo if abnormalities occurred. Of the 150 patients in the study, 10 (7%) developed severe PAOD (grade 3-4) requiring revascularization. Districts involved were: carotid (5), renal (2) and extremities (14 IL, 1 subclavian). Three patients were polyvascular requiring intervention in multiple regions. 18 patients with no malignancies requiring surgery were used as a control group and matched for sex, age, diabetes, smoking, district and intervention to compare patency rates, morbidity and mortality. At event, these 10 patients were taking imatinib (1), bosutinib (1), nilotinib (5) and ponatinib (3). None of them had a previous PAOD, but all had cardiovascular risk factors (100% were hypertensive). Median age was 66.8 yo (range 46-82) and the median number of PAOD risk factors (age &amp;gt;60, hypertension, diabetes, male gender, nicotine abuse and coronary heart disease) was 2 (range 1-5). Plaque was deemed significant when stenosis was &amp;gt;30%; at this point it developed very rapidly, with signs of arterial thrombosis within a year, requiring intervention. IMT scores (measuring thickness of carotid artery wall) and ABI followed by FPG and their variation over time proved predictive for plaque evolution. No patient died due to complications relating directly to surgical intervention or within 30 days post-surgery. One patient required a major limb amputation at 12 months. Patency rates were similar in the TKI and control group at 12 months (88.2% vs 80%), however the frequency of reintervention (endo or open) was 50% in TKI patients (n=5) and 11% in the control group (n=2; P&amp;lt;0.01). Discussion Multidisciplinary evaluation, comorbidity analysis and cardiovascular risk assessment in CML patients are highly recommended, at diagnosis if possible, to implement a tailored treatment strategy and to identify patients who require strict monitoring of risk factors during treatment. Extensive and detailed information on the 150 patients in this study will be presented with a focus on the onset and characteristics of thrombotic arterial events, medical/surgical interventions, analysis of instrumental parameters (ABI, IMT, FPG) and correlation with clinical data. Disclosures Abruzzese: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria.