Severity Of Carotid Atherosclerosis Research Articles

DETERMINANTS AND ASSOCIATIONS OF COMMON CAROTID INTIMA-MEDIA ROUGHNESS IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES

Objective: Carotid atherosclerosis, including increased intima-media thickness (IMT) and plaque, is associated with increased cardiovascular (CV) risk. The role of the irregularity of the carotid intima-media surface in terms of total CV risk has been insufficiently investigated. This study investigated determinants and associations of common carotid intima-media roughness in patients with type 2 diabetes and hypertension. Design and method: Adults with type-2 diabetes and hypertension were evaluated with (i) 24h ambulatory blood pressure (ABP) monitoring (20 min intervals, Microlife WatchBPO3), (ii) carotid ultrasonography for the calculation of the common carotid IMT (use of automated software that allows the calculation of the average value of multiple measurements), carotid plaque score (CPS), and standard deviation (SD) of the common carotid intima-media (derived for the multiple measurements performed for the calculation of the IMT), and (iii) ultrasound estimation of left ventricular mass index (LVMI). Results: Ninety-five individuals were analyzed [age 66.3±8.9 years, 61 men, body mass index (BMI) 30.8±4.8 kg/m2, HbA1c 6.6±0.8%, 24-hour ABP (systolic/diastolic) 123±13/69.4±7.3 mmHg, IMT 0.83±0.16 mm, SD IMT 0.07±0.03 mm, CPS 5.5±4.8 mm]. SD IMT was correlated with IMT (r=0.49, p<0.001), nighttime systolic ABP (r=0.21, p<0.05), 24h weighted SD of systolic ABP (r=0.26, p<0.05), CPS (r=0.30, p<0.01) and LVMI (r=0.39, p<0.001). In stepwise multivariable regression analysis with age, nighttime systolic ABP, 24h weighted SD of systolic ABP, total number of IMT measurements and IMT as independent variables, the SD IMT was determined by IMT (β=0.08, p<0.001) and 24h weighted SD of systolic ABP (β=0.003, p<0.05). Conclusions: These preliminary data suggest that in patients with type-2 diabetes and hypertension, carotid intima-media roughness is determined by IMT and the variability of 24h systolic ABP, and is associated with the severity of carotid atherosclerosis and left ventricular hypertrophy.

Association of breast arterial calcification and carotid atherosclerosis as a marker of cardiovascular risk

Aim. To study the relationship between breast arterial calcification (BAC) and the presence and severity of carotid atherosclerosis.Material and methods. We analyzed 4274 digital mammograms of women who underwent diagnostic mammography. In addition to the standard diagnosis of breast diseases, BAC was assessed in all mammograms. The study included 198 women aged 40-74 years, who made up 2 groups with and without BAC, each consisting of 99 people, formed on a case-control basis. The severity of BAC was assessed by a 12-point score. Duplex ultrasound of extracranial arteries determined plaque presence, the severity of CA stenosis (in percent) and intima-media thickness (IMT). All women underwent physical and laboratory examinations, electrocardiography, and were interviewed using a questionnaire assessing socio-demographic data, menopausal status, risk factors, and diseases.Results. The groups did not differ in lipid levels, blood glucose, body mass index, incidence of hypertension, diabetes, or smoking. Women with BAC had a higher incidence of menopause (94,9% vs 84,8%, p=0,033), coronary artery disease (13,1% vs 4,2%, p=0,039) and osteoporosis (18,2% vs 6,1%, p=0,016) in history. In women with BAC, at least one carotid plaque was observed significantly more often than in those without BAC — in 79,8% and 60,6% of cases, respectively (p=0,005). Women with BAC compared with women without BAC had a greater plaque number (1,0 [1,0; 3,0] vs, 1,0 [1,0; 2,0], p<0,001) and a more severe carotid stenosis, assessed by maximum (25,0 [17,5; 35,0] vs 20,0 [0,0; 27,5], p=0,001), total (30,0 [20,0; 92,5] vs 25,0 [0,0; 50,0], p<0,001) and mean arterial stenosis (25,0 [17,5; 30,0] vs 20,0 [0,0; 25,0], p=0,001). For the first time, a positive relationship was revealed between the severity of carotid atherosclerosis and BAC as follows: women with greater severity of maximum and total carotid stenosis had more severe BAC (p=0,018 and p=0,003, respectively). There was no association between BAC and IMT (p=0,115).Conclusion. BAC is associated with a higher incidence and severity of carotid atheromatosis. A positive relationship was found between the severity of BAC and carotid stenosis. The data obtained confirm the prospects of mammography as a screening technique for identifying individuals with an increased cardiovascular risk.

High Contrast Detection of Carotid Neothrombus with Strong Near-Infrared Absorption Selenium Nanosphere Enhanced Photoacoustic Imaging.

Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases. We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information. In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis. The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.

Long Noncoding RNA AC078850.1 Induces NLRP3 Inflammasome-Mediated Pyroptosis in Atherosclerosis by Upregulating ITGB2 Transcription via Transcription Factor HIF-1α.

As a chronic progressive inflammatory disease, atherosclerosis constitutes a leading cause of cardiovascular disease, with high mortality and morbidity worldwide. The effect of lncRNA AC078850.1 in atherosclerosis is unknown; this study aims to explore the regulatory mechanism of the lncRNA AC078850.1/HIF-1α complex in atherosclerosis. Initially, we identified the lncRNA AC078850.1 associated with atherosclerosis using multiple bioinformatic methods, finding that the level of lncRNA AC078850.1 in peripheral blood mononuclear cells was positively related to the severity of carotid atherosclerosis. LncRNA AC078850.1 was upregulated, and found to be predominately localized in the nucleus of THP-1 macrophage-derived foam cells. Both the knockdown of lncRNA AC078850.1 and the transcription factor HIF-1α can each markedly suppress ITGB2 gene transcription, ROS production, NLRP3 inflammasome, IL-1β/18 release, lipid accumulation, and pyroptotic cell death in ox-LDL-stimulated THP-1-derived macrophages. Additionally, the downregulation of HIF-1α attenuated the positive effects of lncRNA AC078850.1 on pyroptosis and foam cell formation. In addition, the knockdown of lncRNA AC078850.1 suppressed HIF-1α-aggravated macrophages pyroptosis and foam cell formation. Meanwhile, inhibition of ITGB2 gene expression ameliorated HIF-1α-aggravated ROS generation in THP-1-derived macrophages. Taken together, our study demonstrated that lncRNA AC078850.1 was involved in the regulation of ITGB2 gene transcription by binding to the HIF-1α and lncRNA AC078850.1/HIF-1α complex, promoting both NLRP3 inflammasome-mediated pyroptosis and foam cell formation through the ROS-dependent pathway in cases of atherosclerosis.

#3103 OMENTIN-1 AND SUBCLINICAL ATHEROSCLEROSIS IN ESKD PATIENTS UNDERGOING HEMODIALYSIS AND IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims In end-stage kidney disease (ESKD) patients, atherosclerosis is a key-player for cardiovascular risk, being influenced by endothelial dysfunction, inflammation and mineral dysmetabolism. Omentin-1 is an adipokine involved in various pathological conditions (diabetes, metabolic syndrome, obesity), and has recently been studied as a prognostic factor for atherosclerosis progression and mortality in the general population. In this study, we evaluated the possible relationships between Omentin-1 and incipient carotid atherosclerosis in the clinical setting of ESKD. Method Circulating blood Omentin-1 levels were measured in a cohort of 77 asymptomatic ESKD patients (40 kidney transplant recipients, Ktx and 37 chronic hemodialysis patients, HD) and in 30 healthy controls. Carotid intima-media thickness (cIMT) was measured before a single HD session or before a Ktx outpatient visit. Pathological cIMT was defined for mean values > 0.9 mm and/or an unilateral cIMT above the 75th percentile. Results Omentin-1 levels were higher in the entire ESKD cohort than in healthy controls (324 [90.3-770] vs. 110 [35.4-240.9] pg/ml; p = 0.03). Ktx patients had lower levels than HD patients (p = 0.01) while higher Omentin-1 levels were found in HD patients (474.9 [197.2-1432.1] ng/ml) compared to both healthy subjects (p = 0.009) and Ktx (p = 0.01). Mean cIMT in all ESKD was 0.78 ± 0.32 mm. 36 patients (46.7%) with pathological cIMT values displayed lower Omentin-1 levels as compared with others (168.7 [51.1-457.8] vs 474.9 [197.2-1432.1] and p = 0.004). Multivariate correlations analyses indicated Omentin-1 as the stronger independent predictor of carotid atherosclerosis (β-0.687; p = 0.03) in the whole cohort, even more than age, total cholesterol and diastolic BP. Conclusion In ESKD patients, Omentin-1 reflects the severity of carotid atherosclerosis independently from traditional confounders and may serve as an additive biomarker for risk prediction and risk stratification. Future studies are awaited to confirm these preliminary findings in larger cohorts.

Combined effects of hypertension, hyperlipidemia, and diabetes mellitus on the presence and severity of carotid atherosclerosis in community-dwelling elders: A community-based study.

Hypertension, hyperlipidemia, and diabetes mellitus (DM) are common cardiovascular disease (CVD) comorbidities and well-known major determinants of atherosclerosis. However, their combined effects and relative contributions have not been well explored. This study aimed to characterize the characteristics of carotid atherosclerosis and dissect the relative effects of these common CVD comorbidities on the presence and severity of carotid atherosclerosis in community-dwelling elderly individuals. We enrolled 817 elders from communities in northern Taiwan. We evaluated their cardiovascular risk profiles and scanned their extracranial carotid arteries using high-resolution ultrasonography systems. The prevalence rates for hypertension, hyperlipidemia, and DM were 45.4%, 37.1%, and 16.8%, respectively. Sixty-two (7.6%) and 188 (23.0%) elderly had all three and two of these common CVD comorbidities, respectively. The prevalent rates of carotid plaque and moderate-to-severe atherosclerosis were 62.9% and 35.5%, respectively. The percentages of one or more common CVD comorbidities in elders with carotid plaque and moderate-to-severe atherosclerosis were 78.2% and 83.1%, respectively. Multivariate analyses showed that the number of common CVD comorbidities was the most predictive determinant. Multivariable-adjusted odds ratios (ORs) per comorbidity for the presence of carotid plaque and advanced carotid atherosclerosis were 1.52 (95% CI, 1.28-1.81) and 1.57 (95% CI, 1.28-1.93), respectively. Models containing hypertension and DM were the second most predictive. Combinatory analyses showed distinct relationship patterns between carotid atherosclerosis and hypertension, hyperlipidemia, and DM. Hypertension was significantly correlated with higher ORs for the presence of carotid plaque and advanced carotid atherosclerosis but not for hyperlipidemia. Carotid plaques are highly prevalent in community-dwelling elders. The number of common CVD comorbidities was the most predictive determinant of carotid plaques and advanced carotid atherosclerosis. Our results indicate that to reduce the impact of atherosclerotic diseases, blood pressure controls precede the control of blood lipids and glucose in the community-dwelling elders.

Assessment of the predictive value of carotid color Doppler ultrasound Crouse score combined with high‐sensitivity C‐reactive protein in elderly diabetics with cerebral infarction

Both the carotid Crouse score and high-sensitivity C-reactive protein (hs-CRP) levels are commonly used to evaluate atherosclerosis and vascular inflammatory response. This study was to investigate the correlation between the Crouse score and hs-CRP and cerebral infarction (CI) in elderly diabetics. We compared the carotid Crouse scores and hs-CRP levels between two groups of diabetic patients with and without CIs (n = 100 each) and the relationship between changes in these indices and CI. Between the four groups (control, diabetic with a large CI, diabetic with a small CI, and diabetic with a lacunar CI) there was a significant difference in the age, sex, Crouse scores and hs-CRP levels, as well as fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) (all p < 0.05). Logistic regression analysis with CI as the dependent variable showed that the age (odds ratio [OR] = 1.114, 95% confidence interval [CFI]: 1.063-1.167, p = 0.000), FBG (OR = 1.260, 95% CFI: 1.102-1.570, p = 0.039), HbA1c (OR = 2.036, 95% CFI: 1.348-3.703, p = 0.001), Crouse score (OR = 2.721, 95% CFI: 1.800-4.114, p = 0.000) and hs-CRP level (OR = 3.364, 95% CFI: 2.185-5.180, p = 0.000) were risk factors for a CI in combination with diabetes mellitus. Significant differences were found in age, diastolic blood pressure, Crouse scores and hs-CRP levels between the male diabetic-non-CI subgroup, female diabetic-non-CI subgroup, male diabetic-CI subgroup and female diabetic-CI subgroup (All p < 0.05). The carotid Crouse score method has high reliability and reflects the severity of carotid atherosclerosis. The age, sex, fasting blood glucose, HbA1c, Crouse score, an elevated hs-CRP level, and the occurrence of CI in elderly with diabetes mellitus are closely related.

Lipoprotein(a) Modulates Carotid Atherosclerosis in Metabolic Syndrome

Background and Aim: High lipoprotein(a) [Lp(a)] is a well-established cardiovascular (CV) risk factor, but the effect of mildly elevated Lp(a) on CV health is largely unknown. Our aim was to evaluate if Lp(a) is associated with the severity of carotid atherosclerosis (CA) in the specific subset of metabolic syndrome (MetS). Patients and Methods: Subjects with diagnosed MetS and ultrasound-assessed CA were enrolled. Those patients were categorized according to the severity of CA (moderate vs. severe), and the circulating levels of Lp(a) alongside with clinical, anthropometric, and biochemical data were collected. Results: Sixty-five patients were finally included: twenty-five with moderate and forty with severe CA (all with asymptomatic disease). Intergroup comparison showed Lp(a) as the only significantly different variable [6 (2–12) mg/dl vs. 11.5 (6–29.5) mg/dl; p = 0.018]. Circulating levels of Lp(a) were also confirmed as the only variable independently associated with severity of CA at logistic regression analysis [OR 2.9 (95% CI 1.1–7.8); p = 0.040]. ROC curve analysis for Lp(a) confirmed a serum level of 10 mg/dl as the best cut-off value [AUC 0.675 (95% CI 0.548–0.786)]. Although sensitivity and specificity were suboptimal (69.0 and 70.4%, respectively)—likely due to the small sample size—this result is in line with those previously reported in the literature. Conclusion: Lp(a) is independently associated with severity of CA in the subgroup of MetS patients.

Is serum Osteopontin a predictor of carotid atherosclerosis severity among prevalent hemodialysis patients?

Background and aimChronic hemodialysis (HD) patients are among the highest population risk for accelerated atherosclerosis. Osteopontin (OPN) is a multifunctional protein that is increased in chronic kidney disease that may play a role in vascular remodelling and intimal proliferation. AimTo assess the relation between OPN levels and severity of carotid atherosclerosis among prevalent HD patients. MethodsEighty chronic HD patients underwent serum OPN levels assessment and were further classified into 3 subgroups according to the OPN tertiles’ levels; sub-group 1 (lower tertile) subgroup 2 (middle tertile) and sub-group 3 (upper tertile), together with the carotid duplex and Transthoracic Doppler Echocardiography examination. ResultsThe mean carotid intima-media thickness (CIMT) was 0.89±0.14mm. Out of the studied group, 50 (62.5%) patients had atheromatous plaques and 15 patients (18.8%). had significant stenosis. The 3rd group with the upper OPN tertile (78–270ng/dl) had the highest incidence of atherosclerosis. A significant correlation between the OPN levels and the CIMT (r=0.533, p=0.001). OPN values detect atherosclerosis with diagnostic sensitivity of 70%, specificity of 69%, positive predictive value (PPV) 73%, negative predictive value (NPV) 65% with area under the curve (AUC) 0.804 (95% CI: 0.711–0.897). Serum OPN detect carotid stenosis with sensitivity of 66%, specificity of 81%, PPV 45%, NPV 91% with AUC=0.769 and detect the presence of carotid atheroma with sensitivity 70%, specificity 66.67%, PPV 77.8%, NPV 57.1% and AUC=0.767 (p-value<0.001). Moreover, serum levels of OPN were significantly positively correlated with grade of diastolic dysfunction (r=0.312, p=0.005), E/A ratio (r=0.293, p=0.008) and inversely correlated with left ventricular ejection fraction (r=−0.304, p=0.006). ConclusionsSerum Osteopontin is of clinical value as a predictor biomarker of the severity of carotid atherosclerosis, presence of atheroma and carotid stenosis with high diagnostic sensitivity and specificity in chronic hemodialysis patients. Increased Osteopontin level is associated with left ventricular diastolic and systolic dysfunction in those patients.

Is serum Osteopontin a predictor of carotid atherosclerosis severity among prevalent hemodialysis patients?

Background and aimChronic hemodialysis (HD) patients are among the highest population risk for accelerated atherosclerosis. Osteopontin (OPN) is a multifunctional protein that is increased in chronic kidney disease that may play a role in vascular remodelling and intimal proliferation. AimTo assess the relation between OPN levels and severity of carotid atherosclerosis among prevalent HD patients. MethodsEighty chronic HD patients underwent serum OPN levels assessment and were further classified into 3 subgroups according to the OPN tertiles’ levels; sub-group 1 (lower tertile) subgroup 2 (middle tertile) and sub-group 3 (upper tertile), together with the carotid duplex and Transthoracic Doppler Echocardiography examination. ResultsThe mean carotid intima-media thickness (CIMT) was 0.89±0.14mm. Out of the studied group, 50 (62.5%) patients had atheromatous plaques and 15 patients (18.8%). had significant stenosis. The 3rd group with the upper OPN tertile (78–270ng/dl) had the highest incidence of atherosclerosis. A significant correlation between the OPN levels and the CIMT (r=0.533, p=0.001). OPN values detect atherosclerosis with diagnostic sensitivity of 70%, specificity of 69%, positive predictive value (PPV) 73%, negative predictive value (NPV) 65% with area under the curve (AUC) 0.804 (95% CI: 0.711–0.897). Serum OPN detect carotid stenosis with sensitivity of 66%, specificity of 81%, PPV 45%, NPV 91% with AUC=0.769 and detect the presence of carotid atheroma with sensitivity 70%, specificity 66.67%, PPV 77.8%, NPV 57.1% and AUC=0.767 (p-value<0.001). Moreover, serum levels of OPN were significantly positively correlated with grade of diastolic dysfunction (r=0.312, p=0.005), E/A ratio (r=0.293, p=0.008) and inversely correlated with left ventricular ejection fraction (r=−0.304, p=0.006). ConclusionsSerum Osteopontin is of clinical value as a predictor biomarker of the severity of carotid atherosclerosis, presence of atheroma and carotid stenosis with high diagnostic sensitivity and specificity in chronic hemodialysis patients. Increased Osteopontin level is associated with left ventricular diastolic and systolic dysfunction in those patients.

Ассоциация саркопении и атеросклероза сонных артерий у больных мужского пола пожилого возраста с остеоартритом коленного сустава

Aim: to evaluate the association of sarcopenia and carotid atherosclerosis in elderly male patients with knee osteoarthritis (OA). Materials and Methods: the study included 36 patients (mean age — 68.9 (66; 71) years) with an established diagnosis of grade II–III knee OA according to the Kellgren-Lawrence scale. Diagnosis of sarcopenia was conducted on the basis of the European Working Group on Sarcopenia in Older People (EWGSOP, 2010) recommendations with the determination of three parameters: muscle strength, muscle mass and muscle function. The severity of carotid atherosclerotic lesions was assessed by duplex color scanning with examination of the intima-media thickness (IMT), the presence of atherosclerotic plaques and the degree of aortic stenosis. Comparative analysis was performed in 3 groups: group 1 — 10 patients without sarcopenia, group 2— 12 patients with presarcopenia, and group 3 — 14 patients with sarcopenia. Results: IMT in group 3 with sarcopenia was statistically significantly (p=0.005) higher versus the same indicator in men without sarcopenia. The majority (23 (63.9%)) of the patients included in the study had carotid atherosclerotic lesions. The most severe carotid lesion with multiple atherosclerotic plaques and stenosis not less than 50% was significantly more commonly detected in patients with sarcopenia: 35.7% versus group 2 with presarcopenia (8.3%, p=0.015) and without sarcopenia (10.0%, p=0.013). According to the correlation analysis, a significant negative association was established between the severity of carotid atherosclerosis and the musculoskeletal index (r=-0.227, p=0.047). Conclusion: the association between carotid atherosclerosis and body composition disorders in men with knee OA allows discussing atherosclerosis and sarcopenia as two conditions with common pathogenetic mechanisms that potentially increase the risk of adverse outcomes. KEYWORDS: sarcopenia, presarcopenia, carotid atherosclerosis, osteoarthritis, elderly, male. FOR CITATION: Alekseeva L.I., Taskina E.A., Raskina T.A. et al. Association of sarcopenia and carotid atherosclerosis in elderly male patients with knee osteoarthritis. Russian Medical Inquiry. 2022;6(3):120–125 (in Russ.). DOI: 10.32364/2587-6821-2022-6-3-120-125.

Co-existence and interrelationship between intracranial artery stenosis and extracranial carotid atherosclerosis in an asymptomatic rural population of 13 villages in northern China

ObjectiveWe investigated the characteristics and relationship of co-existing intracranial artery stenosis (ICAS) and extracranial carotid atherosclerosis in an asymptomatic rural population in northern China. MethodsAsymptomatic residents ≥ 30 years old in 13 villages underwent simultaneous cervical vascular and transcranial Doppler ultrasound. ICAS was defined as ≥ 50% stenosis. Extracranial carotid atherosclerosis severity was classified as increased intimal medial thickness (IMT), plaques, and a plaque with ≥ 50% extracranial artery stenosis (ECAS). Demographic details, medical history, and blood biochemistry results were collected. The relationship between ICAS and extracranial carotid atherosclerosis severity was determined using the chi-square trend test and binary logistic regression analysis. ResultsA total of 2598 asymptomatic participants were included; 122 (4.7%) had ICAS, 1071 (41.2%) had extracranial carotid atherosclerosis, and 84 (3.2%) had co-existing extracranial carotid atherosclerosis and ICAS. Those with co-existing ICAS and extracranial carotid atherosclerosis were older (P = 0.006) and had a higher hypertension (HTN) and diabetes mellitus (DM) prevalence (P < 0.001). HTN (95% confidence interval [CI]=1.31–3.55, odds ratio [OR]=2.15) and DM (95% CI=1.17–4.30, OR=2.24) were found to be independent risk factors for asymptomatic ICAS with extracranial carotid atherosclerosis. Among those with ICAS, 38/122 had no extracranial carotid atherosclerosis, 8/122 had increased IMT, 64/122 had a plaque, and 12/122 had ECAS. As extracranial carotid atherosclerosis severity increases, ICAS prevalence increases. ConclusionCo-existing ICAS and extracranial carotid atherosclerosis occurred in 3.2% of asymptomatic populations in rural areas of northern China. As extracranial carotid atherosclerosis severity increased, ICAS prevalence also increased. HTN and DM might be independent indicators of co-existing ICAS and extracranial carotid atherosclerosis.

Soluble CD40 Levels in Plasma Are Associated with Cardiovascular Disease and in Carotid Plaques with a Vulnerable Phenotype.

Background and PurposeCD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 and CD40L as markers for cardiovascular disease (CVD) in humans and their association with plaque stability. MethodsSoluble CD40 and CD40L (sCD40L) were measured in plasma in 1,437 subjects from The SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) cohort. Intra-plaque levels of sCD40 and sCD40L were measured in atherosclerotic plaque homogenates from 199 subjects of the Carotid Plaque Imaging Project (CPIP) cohort. ResultsBoth plasma sCD40 and sCD40L levels were elevated in individuals with prevalent stroke, while sCD40 levels also were higher in individuals with a prior acute myocardial infarction. Plasma levels of sCD40 correlated with carotid intima-media thickness and total carotid plaque area and were associated with risk of cardiovascular events over a 3-year follow-up period. Intra-plaque levels of sCD40 and sCD40L were associated with plaque components characteristic for plaque vulnerability and extracellular matrix remodelling. ConclusionsHigher plasma sCD40 and sCD40L levels are associated with prevalent CVD. Plasma sCD40 levels also correlate with the severity of carotid atherosclerosis and predict future cardiovascular events, while intra-plaque levels correlate with a vulnerable plaque phenotype. Our findings thus demonstrate that elevated levels of sCD40 and sCD40L are markers of CVD.

Factors Associated with Carotid Atherosclerosis and Achilles Tendon Thickness in Japanese Patients with Familial Hypercholesterolemia: A Subanalysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study.

Aims: Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol levels, xanthomas including Achilles tendon thickening, and premature coronary artery disease (CAD). Carotid intima-media thickness (IMT) is a well-established surrogate marker for CAD in FH and Achilles tendon thickening is a specific physical finding in patients with FH. The objective of the present study was to identify factors associated with carotid IMT and Achilles tendon thickness in FH heterozygotes on lipid-lowering therapy. This study also aimed to examine the follow-up changes in carotid IMT and Achilles tendon thickness among them in the current real-world FH practice. Methods: The current study is a subanalysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study. The severity of carotid atherosclerosis was assessed with the maximal and mean IMT using ultrasonography, and Achilles tendon thickness was measured using X-rays. The present study used 571 patients under medical treatment for heterozygous FH who had baseline measurements for maximal IMT (n=511), mean IMT (n=459), or Achilles tendon thickness (n=486). The IMT was measured annually, and Achilles tendon thickness was evaluated every two years. Results: Higher LDL cholesterol (LDL-C) level and lower HDL cholesterol (HDL-C) level were associated with greater maximal and mean IMT as well as greater Achilles tendon thickness. Achilles tendon thickness tended to be greater in patients who had a smoking history than in never-smokers. Maximal IMT and Achilles tendon thickness were significantly greater in patients with CAD than in those without. Additionally, lower HDL-C level and hypertension were associated with higher values of maximal and mean IMT, suggesting the importance of comprehensive risk management including reduced HDL-C and blood pressure control in FH care. In longitudinal observations, percentage changes in maximal IMT and mean IMT gradually increased during the observation period. In contrast, percentage changes in Achilles tendon thickness became progressively thinner throughout the observation period. Conclusions: We found a positive association between LDL-C levels and severity of carotid atherosclerosis in heterozygous FH patients on treatment. This observation suggests the insufficiency of lipid-lowering therapy and the presence of therapeutic inertia among clinicians in the real-world FH practice.

Triglyceride/High-Density Lipoprotein Cholesterol Ratio: A Clue to Metabolic Syndrome, Insulin Resistance, and Severe Atherosclerosis.

High serum levels of triglycerides (Tg) and low levels of high-density lipoprotein cholesterol (HDL-C) are characteristic of the Metabolic Syndrome (MetS). We assessed the ratio of Tg to HDL-C as a way to identify MetS and insulin resistance. We also evaluated its association with severity of carotid atherosclerosis. Data were analyzed from three cohorts totaling 13,908 participants. MetS was defined according to the International Diabetes Federation criteria. Optimal cut-off for Tg/HDL-C ratio was obtained using Youden's index in receiver-operating characteristic (ROC) curve analyses. The risk of MetS and IR in those with a Tg/HDL-C ratio above the optimum cutoff was evaluated by logistic regression analysis. A Tg/HDL-C ratio above the optimal cutoff level significantly increased the odds ratio for MetS in the three cohorts (OR 6.00, 4.04, and 3.50, least in the healthy population), identified insulin resistance defined by the homeostatic model of insulin resistance (HOMA-IR) (p< 0.0001), and was strongly associated with atherosclerosis severity (p= 0.0001). Tg/HDL-C ratio identifies persons with MetS, insulin resistance, and severe atherosclerosis. It should be used more widely to identify patients at high risk. This is clinically important because insulin resistance is treatable.

CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable plaque phenotype and remodelling

Abstract Background and purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules and members of the TNF receptor superfamily well known for their involvement in inflammatory and autoimmune diseases. This study uses two large human cohorts – the SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) and the Carotid Plaque Imaging Project (CPIP) – to explore the potential of plasma or intra-plaque expression of CD40 and CD40L as biomarkers and to locally affect plaque stability. Methods Proximity Extension Assay (PEA) technique was used to measure soluble CD40 and CD40L (sCD40 and sCD40L) in plasma from 1437 subjects from the SUMMIT cohort, the majority of which (80%) with pre-existing cardiovascular disease, and in atherosclerotic plaque homogenates from 199 subjects of the CPIP cohort undergoing carotid endarterectomy. The Mann-Whitney U test was used to compare groups and Spearman's rank correlation/the Chi-square test was used to assess correlations. Multiple comparisons were corrected for using the Holm-Šídák test. A logistic regression model was used to test for associations with future cardiovascular events and mortality. Results In the SUMMIT cohort both plasma CD40 and CD40L levels were elevated in individuals with a history of stroke (p=0.000030 and p=0.020, respectively), while sCD40 levels also were higher in individuals with a prior acute myocardial infarction (p=0.016). Plasma levels of sCD40 correlated with carotid plaque burden (as measured by ultrasound imaging, r=0.355, p&amp;lt;1x10–16) and were associated with future cardiovascular events over a three year-follow up period (p=0.02, hazard ratio 1.3, 95% C.I: 1.042–1.625). sCD40 and sCD40L were associated with a plaque phenotype characterized by the strong presence of features both of vulnerability such as high content oxidized low-density lipoprotein (LDL; r=0.236, p=0.004 and r=0.259, p=0.0037, respectively) and pro-inflammatory cytokines (e.g. tumour necrosis factor-α: p=3.1x10–7 and p=0.0006, respectively) and low calcium content (r=−0.208, p=0.012 and r=0.268, p=0.00034, respectively). Conclusion High plasma CD40 and CD40L levels are associated with symptomatic cardiovascular disease. Plasma CD40 levels correlate with the severity of carotid atherosclerosis and are associated with an increased risk for future cardiovascular events. Additionally, intra-plaque levels are associated with a vulnerable plaque phenotype. Our findings thus support the value of sCD40 and sCD40L both as biomarkers and therapeutic targets for cardiovascular disease. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Swedish Heart and Lung Foundation (1) and the Swedish Research Council (2)

The differences of carotid atherosclerosis among non-OSAHS and OSAHS patients of different severities: a cross-sectional study.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a widely prevalent problem with many complications, such as hypertension and cerebral vascular diseases. Atherosclerosis, whose most severe outcome is ischemic stroke, is reported being affected by OSAHS. The objective of this article is to investigate the differences of carotid atherosclerosis patients with or without OSAHS by a cross-sectional research. Patients diagnosed with carotid atherosclerosis by ultrasonography were recruited. They were requested to fill the primary screening OSAHS questionnaire. Patients with high tendency ofOSAHS underwent polysomnography (PSG) tests into OSAHS group, and patients without OSAHS were into non-OSAHS group. Blood tests and medical history were collected. Carotid atherosclerosis severity was analyzed by carotid artery intima-media thickness (IMT), carotid plaque, blood flow velocity, etc. Differences between the two groups and subgroups were analyzed. A total of 242 carotid atherosclerosis patients were enrolled including 118 non-OSAHS patients (38 males and 80 females) and 124 OSAHS patients (40 mild, 32 moderate, and 52 severe). Significant differences were found in PSV-ICA and EDV-ICA on both sides (p < 0.05) but no significant differences on IMT and velocity of CCV. CA patients with OSAHS were younger than ones without OSAHS. With the severity of OSAHS increasing, the age of CA patients decreased. The more severity of OSAHS, the younger the patients were. There were no significant differences in comparing cholesterol, triglyceride, HDL, LDL, and glucose. As far as CIMT, carotid plaque, blood flow velocity, and blood lipid are concerned, the severity of CA is not affected by the severity of OSAHS accordantly. The relationship between OSAHS and CA may not be dose dependent. This study has been registered on clinical trials (No. NCT03665818).

Interrelation of the dynamics of serum concentrations of interleukin-1β, interleukin-6 and interleukin-10 with clinical data in acute ischemic stroke and the strategy of reperfusion therapy

Aim. To study the relationship between the dynamics of serum concentrations of interleukin-1β, interleukin-6 and interleukin-10 with clinical data in the acute period of ischemic stroke, and the strategy of reperfusion therapy.Materials and methods. In 28 patients with acute ischemic stroke, half of whom underwent intravenous thrombolysis, the concentration of interleukin-1β, interleukin-6 and interleukin-10 was assessed at admission, on the 3rd and 10th day of the disease.Results. The concentration of interleukin-1β and interleukin-6 decreases during the acute period of stroke. The concentration of interleukin-10 remains unchanged for the first 10 days since the development of stroke. When thrombolysis is performed, there is a more significant decrease in interleukin-1β concentration in the hyperacute period of stroke, whereas in patients without reperfusion there is a decrease in interleukin-6 concentration from 1 to 10 days. The concentration of cytokines is associated with age, lipid spectrum, severity of carotid atherosclerosis, myocardial hypertrophy and injection fraction of the heart. Only in the subgroup of thrombolysis, correlations of cytokine concentrations with systolic blood pressure at admission, hemoglobin concentration, total cholesterol and high-density lipoproteins, hematocrit, degree of stenosis of the contralateral carotid artery, injection fraction and the number of antihypertensive drugs prescribed in the hospital were recorded. The concentration of interleukin-6 at day 10 is associated with the severity of stroke at admission, and the level of IL-10 on day 3 of the disease, with the mobility of patients at discharge.Conclusions. In the hyperacute period of stroke, there is a decrease in the pro-inflammatory activity of blood serum, more pronounced in patients undergoing systemic thrombolysis. Concentrations of interleukin1β, interleukin-6 and interleukin-10 are associated with a wide range of parameters characterizing the cardiovascular and functional status, and the pattern of these associations differs depending on the reperfusion therapy strategy.

Prevalence of abdominal aortic aneurysms and iliac aneurysms in the UK population of 50,000 women

BACKGROUND AND AIMS: Screening men aged 65–80 years for abdominal aortic aneurysm (AAA) is considered economically viable when the prevalence of AAA is 1.0% or higher. Currently, women are not included in AAA screening programs because the prevalence of AAA is 1.0%. MATERIALS AND METHODS: Risk factors were collected from 50,000 females who attended for cardiovascular screening. Ultrasound was used to detect the presence of AAA or IIA, the severity of carotid atherosclerosis, and the measurement of ankle/brachial index (ABI). Electrocardiogram (ECG) was used to detect the presence of atrial fibrillation (AF). RESULTS: Aneurysms were detected in 116 women. Of these aneurysms, 34 (29%) were IIA and 82 were AAA. The presence of AAA or IA below the age of 66 years was rare (10 of 24,499). In the age group of 66–85, there were 102 (0.41%) in 27,170 women, of which 72 were AAA and 30 IIA. By including IIA in the screening protocol for AAA, it became easy to identify subgroups with an aneurysm prevalence >1%. Univariate analysis demonstrated that the presence of any one of the following risk factors, history of myocardial infarction or coronary artery disease, history of stroke/transient ischemic attack (TIA), pack-years ≥10, AF, ABI 1.0% (range 1.18–2.06). In a multivariable linear logistic regression, age ≥76, hypertension, pack-years, family history of AAA, and history of stroke/TIA were independent predictors for the presence of AAA or IIA. This model had an area under the receiver operator characteristic curve (AUC) of 0.725 (95% confidence interval [CI] 0.673–0.777) and could identify 2947 women who had 41 AAA or IIA present (prevalence 1.39%). By adding ABI and AF, which require a clinical examination and ECG, the receiver operator characteristic (ROC), AUC increased to 0.745 (95% CI 0.693–0.797). This model could identify 3693 women who had 51 AAA or IIA present (prevalence 1.40%). The presence of ≥50% diameter internal carotid stenosis found in 498 women was associated with a prevalence of AAA or IIA of 3.61%, and when added to the model the ROC AUC increased to 0.775 (95% CI 0.724–0.826). This model could identify 3701 women who had 58 AAA or IIA present (prevalence 1.6%). CONCLUSION: The findings of this study have important implications for developing a screening selection plan for women over 65. By including IIA in the screening protocol for AAA, it became easy to identify subgroups with an aneurysm prevalence >1%. The presence of any one or more of the risk factors listed above can be used to develop targeted screening because of increased risk (>1%). However, whether such screening will be associated with benefits can only be determined by randomized controlled trials and cost-benefit studies.

Carotid Atherosclerosis Severity in Unorganized Adult Population

Aim.To study sex and age distribution of ultrasound parameters characterizing carotid atherosclerotic (CAS) severity in the unorganized urban population.Material and methods. The data obtained in Tomsk as a fragment of the ESSE-RF study are presented (n=1600; 25-64 years age; 59% – women). All participants signed informed consent. We studied CAS plaque count, both total and maximum plaque thickness and stenosis degree in the carotid arteries.Results. The general population quantitative indicators of CAS increased with age, most actively in 40-54 years in men and 45-59 years in women. At the age of 40-44 years in men, the growth of the general population indicators was due to a noticeable increase in both plaque prevalence and of CAS severity. In 45-49 years, the prevalence increased intensively, whereas in 50-54 years growth of plaque count/size indicators were more attributive. In women 45-59 years old formation of the general population indicators concerned was mostly due to steady increase in the plaque prevalence, while out of all quantitative CAS parameters the total stenosis degree only increased significantly in 50-54 years. The general population indicators of CAS severity were higher in men than in women starting up with the age of 40 and until 55 the gender effect was merely explained by the difference in the plaque prevalence.Conclusion. Features of the gender and age distribution of the quantitative parameters of CAS among the adult urban population are determined; the age periods of their most active growth are established. The presented data on the CAS severity percentile distribution can be useful as an additional tool for risk stratification and the choice of therapy/lifestyle modification tactics in people of working age. Further studies are needed to help to explain the trends and to clarify the predictive role of the indicators studied.