Femoral Atherosclerosis Research Articles

Characteristics of atheromatosis in the prediabetes stage: a cross-sectional investigation of the ILERVAS project

BackgroundPrediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage.MethodsAtheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines.ResultsPrediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects.ConclusionsThe prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner.Trial registration NCT03228459 (clinicaltrials.gov)

Role of femoral artery ultrasound imaging in cardiovascular event risk prediction in a primary prevention cohort at a medium-term follow-up

BackgroundCardiovascular (CV) disease prevention guidelines have addressed how imaging may influence CV risk determined by established risk score systems in primary prevention. Nevertheless, data are lacking regarding the use of femoral artery ultrasonography for CV risk modification. Herein, we hypothesized that femoral artery plaque and its characteristics, as well as femoral intima-media thickness (fIMT) measurements, may predict major adverse cardiovascular events (MACE). MethodsSubjects free from documented CV disease who were scheduled for coronary computed tomographic angiography at our institution from September 2016-June 2017 were included. IMT measurements and plaque assessment were performed at femoral and carotid arteries. Coronary artery calcium score (CACS) was recorded. Patients were followed-up for MACE. ResultsA total of 215 subjects (mean age: 54.85 years, 47.91% male) were eligible. Median number of CV risk factors was 3. Median 10-year atherosclerotic CV disease risk based on Pooled Cohort Equation (PCE) equation was 6.3%. At a median follow-up of 24 months, 9 subjects (4.19%) had MACE. Patients who experienced MACE at follow-up were older (p=0.047), more of male gender (p=0.015), had higher serum creatinine levels despite being within reference limits (p=0.031) and PCE equation risk score (p=0.011). In patients who experienced MACE at follow-up, distal (p=0.027), bifurcation (p=0.007), and proximal carotid IMT (p=0.030) and fIMT (p=0.015) were increased. Surface irregularities and ulceration in femoral artery plaques were more common (p=0.001) and CACS was higher (p<0.001). When adjusted for other subclinical atherosclerosis imaging markers, femoral artery plaque surface irregularities and ulceration and only coronary calcification (without concomitant carotid or femoral atherosclerosis) were found to be independent predictors of MACE at follow-up (both p=0.004). ConclusionsOur data emphasize that baseline ultrasonographic assessment of the femoral arteries to define plaque characteristics may provide prognostic information for predicting MACE in a primary prevention cohort.

Genetically elevated levels of metals and subclinical atherosclerosis in an adult population from Spain

TPS 636: Metals and health 2, Johan Friso Foyer, Floor 1, August 28, 2019, 3:00 PM - 4:30 PM Background/Aim: While the evidence supporting a causal association of metals with clinical cardiovascular disease is substantial, fewer studies have evaluated subclinical atherosclerosis. We tested the association of non-essential metals with subclinical atherosclerosis by using genetic polymorphisms in candidate genes as a proxy of unconfounded metal exposure. Methods: Urine Antimonium (Sb), Barium (Ba), Cadmium (Cd), Chromium (Cr), Titanium (Ti), Tungsten (W), Uranium (U) and Vanadium (V), and urine Arsenic (As) speciation, were measured by ICPMS and HPLC-ICPMS, respectively, in 1815 workers from a car assembly factory in Figueruelas (Spain) participating in the Aragon Workers’ Health Study. Atherosclerosis presence (yes/no) was measured in carotid and femoral arteries with ultrasounds, and in coronary arteries with NMR. For statistically significant metals in traditional logistic models, we evaluated the association of genetically controlled biomarker levels with atherosclerosis presence using 2-stage least squares Mendelian Randomization methods. Results: The geometric mean of Sb, sum of inorganic As (∑iAs), Ba, Cd, Cr, Ti, W, U and V was 0.22, 8.1, 1.88, 0.43, 1.06, 213.05, 0.23, 0.03, and 0.5 μg/g, respectively. In multi-adjusted models (including arsenobetaine adjustment for ∑iAs), the odds ratio (95% CI) for atherosclerosis presence in any of the evaluated vascular territories were, 1.21 (1.00-1.46) for ∑iAs, 1.60 (1.17-2.19) for Cd and 1.26 (1.05-1.52) for Ti. These associations were driven by ∑iAs and Cd in carotid, Cd and Ti in femoral and Ti in coronary territories. For ∑iAs the associations of genetically-elevated concentrations (3 ∑iAs-associated SNPs) were statistically significant and directionally consistent compared to the observational associations. For Cd the corresponding associations (2 Cd-associated SNPs) were only consistent in femoral atherosclerosis models. Conclusions: Replication of findings is needed. Our results, however, support a role of As and Cd as cardiovascular risk factors. Reinforced exposure reduction interventions may decrease cardiovascular disease.

Polyvascular subclinical atherosclerosis in familial hypercholesterolemia: The role of cholesterol burden and gender

Background and aimHeterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical atherosclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences. Methods and Results154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid profiles and HeHF history were obtained from patients' files in order to calculate total CB. Atherosclerotic burden was defined by the presence of CACs > 0 or by the presence of carotid or femoral plaque. Study population was stratified according to gender. The prevalence of CAC, carotid and femoral atherosclerosis was of 62%, 55% and 56%, respectively. Coronary district was the least involved in women, who had a higher prevalence in carotid atherosclerosis. When two vascular districts were affected, women had an increased prevalence of femoral and carotid atherosclerosis whereas men had a higher prevalence of coronary and femoral atherosclerosis. CB correlated to the presence of atherosclerosis in any of the three vascular districts with a significant increasing trend depending on the number of affected areas. ConclusionsA polyvascular atherosclerotic burden is found in asymptomatic HeFH patients. Gender differences in the territory distribution were observed. The early and lasting exposure to high cholesterol, as expressed by CB, is a major determinant of atherosclerotic burden.

Relationship Among Fatty Liver, Specific and Multiple‐Site Atherosclerosis, and 10‐Year Framingham Score

Despite a well-documented increase in the prevalence of subclinical atherosclerosis in patients with steatosis, the relationship among steatosis and atherosclerosis, specific atherosclerotic sites, multiple-site atherosclerosis, and cardiovascular risk prediction is incompletely understood. We studied the relationship among steatosis, atherosclerosis site, multiple-site atherosclerosis, coronary artery calcification (CAC), and 10-year Framingham Risk Score (FRS) in 2,554 patients with one or more cardiovascular risk factors (CVRF), free of cardiovascular events and other chronic liver diseases, and drinking less than 50 g alcohol/day. All patients underwent arterial ultrasound (carotid [CP] and femoral [FP] plaques defined as intima-media thickness (IMT) > 1.5 mm), coronary computed tomography scan (severe CAC if ≥ 100), 10-year FRS calculation, and steatosis detection by the fatty liver index (FLI, present if score ≥ 60). Patients with steatosis (36% of total) had higher prevalence of CP (50% versus 45%, P = 0.004) and higher CAC (181 ± 423 versus 114 ± 284, P < 0.001) but similar prevalence of FP (53% versus 50%, P = 0.099) than patients without steatosis. Steatosis was associated with carotid IMT and CAC, but not with FP, independent of age, diabetes, hypertension, and tobacco use (P < 0.001). Fifty-three percent of patients had at least 2-site atherosclerosis and steatosis was associated with at least 2-site atherosclerosis independent of age and CVRF (odds ratio = 1.21, 95% confidence interval 1.01-1.45, P = 0.035). Sixty-four percent of patients with steatosis had a FRS score of 10% or more. FLI was associated with FRS beyond the CVRF or the number of atherosclerosis sites (P < 0.001). Adding FLI to CVRF predicted an FRS greater than or equal to 10% better than CVRF alone (area under the receiver operating characteristic curve = 0.848 versus 0.768, P < 0.001). Conclusion: Steatosis is associated with carotid and coronary, but not femoral atherosclerosis, and with cardiovascular mortality risk. The multiple-site involvement and quantitative tonic relationship could reinforce the prediction of cardiovascular mortality or events over classical CVRF or imaging-based detection of atherosclerosis.

Evaluation of TurboHawk Plaque Rotation System in Treatment of Superficial Femoral Atherosclerosis.

BackgroundTo investigate the curative effect and utility of the TurboHawk plaque circumcision system in the treatment of patients with superficial femoral atherosclerosis (SFA).Material/MethodsWe retrospectively analyzed 60 cases of superficial femoral atherosclerotic stenosis and occlusion treated with the TurboHawk plaque circumcision system for endovascular ablation of the superficial femoral artery in the People’s Hospital of Xinjiang Uygur Autonomous Region between January 2016 and December 2017.ResultsThe sample comprised of 50 male and 10 female patients with an average age of 65±4.5 years (range 47 to 70 years). This group of patients had varying degrees of limb ischemia, with disease duration ranging from 1 week to 3 years. The main symptoms included markedly cooler lower-extremity skin temperature, pale and cyanotic, intermittent claudication (10 cases), resting pain (31 cases), distal limb mild ischemic ulcer (14 cases), and tissue ischemic necrosis and gangrene (5 cases). All cases were in stages 3–6 of the Rutherford classification. Almost half (28 patients, 47%) had a significant improvement in their affected limbs and more than half (32 cases, 53%) had a moderate improvement in clinical symptoms after the intervention. After surgery, lumen stenosis decreased and ankle brachial index (ABI) increased significantly (P<0.05).ConclusionsThe TurboHawk plaque circumcision system is a feasible and effective method for the treatment of SFA with the advantages of less trauma and better safety, and shows a significant curative effect in a short period.

Abstract 17357: Magnetic Resonance Imaging Detected Intraplaque Hemorrhage and Expansive Remodeling in Superficial Femoral Artery

Introduction: Compared to coronary and carotid arteries, there is much less knowledge on atherosclerotic plaque characteristics and their clinical relevance in lower-extremity arteries. Magnetic resonance (MR) vessel wall imaging allows for in vivo detection of intraplaque hemorrhage (IPH), which has been consistently associated with increased risks for clinical events in coronary and carotid artery disease. Objective: In a pilot study, we sought to estimate the prevalence of IPH in peripheral artery disease and examine plaque progression in the presence of IPH. Methods: Ten patients with ankle brachial index &lt;0.90 in one or both legs were recruited. A 3D MR imaging protocol with a large coverage (30 or 45 cm in the head-feet direction) and isotropic resolution (voxel size: 0.8x0.8x0.8 mm 3 ) was used to scan bilateral legs in the coronal plane from the common femoral artery bifurcation to the popliteal artery at baseline and 6 months later. Images were reformatted into axial slices for detailed visualization of vessel wall. Following previous publications on carotid MRI, IPH was detected as hyperintense signals on heavily T1-weighted images. Superficial femoral artery (SFA) segments (3 cm in length) with IPH were identified, of which lumen and outer wall were segmented on black-blood images (motion-sensitized flow suppression for improved vessel wall delineation) to measure plaque progression and remodeling. Image analysis was performed in a blinded fashion without knowing time relationship between serial images. Results: Twenty SFAs were analyzed. After excluding 4 arteries with total occlusion, 5 out of the 16 arteries (31%) or 50% of the subjects showed IPH in 1 or more SFA segments. After 6 months, there was significant progression in vessel wall area in SFA segments with IPH (mean ± standard deviation: 43.5 ± 13.9 mm 2 versus 47.3 ± 17.3 mm 2 , p=0.045), which resulted in outer wall expansion (mean [95% confidence intervals]: +3.9 mm 2 [+0.4, +7.4], p=0.035) rather than lumen reduction (-0.02 mm 2 [-2.6, +2.5], p=0.99). Conclusions: MR vessel wall imaging revealed that IPH is likely a common feature in femoral atherosclerosis. SFA segments with IPH showed expansive remodeling in 6 months, of which the clinical significance needs to be further studied.

BLTR1 and CD36 Expressing Microvesicles in Atherosclerotic Patients and Healthy Individuals.

Aims: Monocytes/macrophages play a crucial role in the development, progression, and complication of atherosclerosis. In particular, foam cell formation driven by CD36 mediated internalization of oxLDL leads to activation of monocytes and subsequent release of microvesicles (MVs) derived from monocytes (MMVs). Further, pro-inflammatory leukotriene B4 (LTB4) derived from arachidonic acid promotes atherosclerosis through the high-affinity receptor BLTR1. Thus, we aimed to investigate the correlation between different MMV phenotypes (CD14+ MVs) on the one hand, and arachidonic acid and eicosapentaenoic acid contents in different compartments including atherosclerotic plaques, plasma, and granulocytes on the other.Methods and Results: Samples from patients with femoral atherosclerosis and healthy controls were analyzed on an Apogee A60 Micro-PLUS flow cytometer. Platelet-poor plasma was labeled with lactadherin-FITC, anti-CD14-APC, anti-CD36-PE, and anti-BLTR1-AF700. Eicosapentaenoic acid and arachidonic acid content in different compartments in patients were analyzed using gas chromatography. Compared to controls, patients had lower levels of BLTR1+ MVs (p = 0.007), CD14+BLTR1+ MVs (p = 0.007), and CD14+BLTR1+CD36+ MVs (p = 0.001). Further, in patients CD14+ MVs and CD14+CD36+ MVs correlated inversely with arachidonic acid in granulocytes (r = −0.302, p = 0.039 and r = −0.322, p = 0.028, respectively). Moreover, CD14+CD36+ MVs correlated inversely with arachidonic acid in plasma phospholipids in patients (r = −0.315, p = 0.029), and positively with triglyceride in both patients (r = 0.33, p = 0.019) and controls (r = 0.46, p = 0.022).Conclusion: This is the first study of its kind and thus the results are explorative and only indicative. BLTR1+ MVs and CD14+CD36+ MVs has potential as markers of atherosclerosis pathophysiology, but this needs further investigation.

Endovascular Treatment of Common Femoral Artery Atherosclerotic Disease

Common femoral artery atherosclerosis is a common cause of claudication and critical limb ischaemia. Surgical endarterectomy with or without patch angioplasty has been considered the gold standard for the treatment of common femoral peripheral artery disease. Endovascular intervention to the common femoral artery has gained popularity in recent years as devices and technical skills have advanced. A systematic review of the literature from 1987 to 2018 for endovascular treatment of common femoral artery disease was conducted. This article summarises the data on acute and long-term outcomes for endovascular treatment of common femoral artery disease.

Carotid and femoral atherosclerosis in the middle-aged general population of the Russian federation: Its prevalence and association with coronary artery disease

Aim: The aim of this study was to assess the prevalence of carotid and femoral atherosclerosis in the middle-aged general population of Russia and analyze association of carotid and femoral atherosclerosis with coronary artery disease (CAD).

COMPARISON OF TWO FORMS OF LEFT VENTRICULAR MASS INDEXATION IN PATIENTS WITH BMI GREATER THAN 25

Objective: 1- Compare the prevalence of left ventricular hypertrophy (LVH) using traditional indexing versus height indexation to 2.7 in the entire sample 2- To compare the anthropometric and vascular characteristics among those with LVH detected with index 2.7 versus those detected with traditional indexing. Design and method: We evaluated 680 patients in the context of a cardiovascular primary prevention program (Cardiometabolic Unit, Hospital Universitario Austral), which includes measurement of anthropometric parameters, body mass index (BMI), laboratory, measurement of the PA (ESH), echocardiogram, oscillometric determination of the pulse wave velocity (PWV)(Mobil-o-Graph), measurement of the intima media thickness (IMT) in common carotid artery, and tracking of subclinical carotid and femoral atherosclerosis. The exclusion criteria were the following: BMI < 25, age < 18, > 80 years; Secondary hypertension, history of cardiovascular disease, missing studies. Four groups were defined: Without LVH (group1), with LVH by both methods (Group2), with LVH exclusively by LVMI (group3), and by LVMI2.7 (group4). Subsequently, Age, Body Mass Index (BMI), Systolic BP (SBP), IMT, PWV and subclinical atherosclerosis were evaluated through number of plaques (n-PLC) and plate area (A-PLC) between the 4 groups Results: A total of 422 patients were included: 52.34 ± 12.43 years, 129.63 ± 16.01/84.95 ± 10.81 mmHg, BMI: 29.54 ± 16, 26.5% female, 46.4% hypertensive, 5.7% diabetics.The prevalence of LVH with LVMI was 12.3%, while with LVMI2.7 the prevalence was 14.2% (p > 0,05). Group 1 turned out to be younger (p = 0.002), with a lower average IMT (p = 0.0104) compared to the other 3 groups. Group 2 resulted in the oldest group (p = 0.002), with the highest number of atherosclerotic plaques (p = 0.0025) and highest PWV (p = 0.00061), respecting the other 3 groups. Finally, group 4 was the group with the highest BMI (p = 0.001), highest mean of IMT (p = 0.0104) and largest A-PLC (p = 0.03). Conclusions: Those who present LVH exclusively according to Index 2.7 seem to be associated with a higher degree of obesity and an increased IMT. Given that these patients with these anthropometric and vascular risk characteristics were not detected with traditional indexation but with index 2.7, it makes us reflect on whether it would be necessary to use both in patients with BMI > 25.

Assessment of longitudinal distribution of subclinical atherosclerosis in femoral arteries by three-dimensional cardiovascular magnetic resonance vessel wall imaging

BackgroundLower extremity peripheral artery disease has become a significant health burden worldwide. Since the treatment strategies can be different if atherosclerotic disease involves different femoral artery segments, it is important to assess plaque distribution among different segments of femoral arteries. We sought to investigate the longitudinal distribution of subclinical femoral artery atherosclerosis in asymptomatic elderly adults using cardiovascular magnetic resonance (CMR) vessel wall imaging.MethodsAsymptomatic elderly subjects underwent three-dimensional (3D) CMR vessel wall imaging for femoral arteries. The 3D motion sensitized-driven equilibrium prepared rapid gradient-echo (3D-MERGE) sequence was acquired from the common femoral artery to the popliteal artery. The femoral artery was divided into 4 segments: common femoral artery (CFA), proximal superficial femoral artery (pSFA), adductor canal (AC) segment of femoral artery, and popliteal artery (PA). The morphological characteristics including lumen area, wall area, maximum and minimum wall thickness, normalized wall index (NWI = wall area / [lumen area + wall area] × 100%), and eccentricity index ([maximum wall thickness - minimum wall thickness] / maximum wall thickness), luminal stenosis, and presence of atherosclerotic plaque were evaluated and compared between bilateral sides and among different femoral artery segments in each side of femoral artery. The associations between ankle-brachial index (ABI) and cardiovascular risk factors and femoral artery plaque characteristics were also determined.ResultsOf 107 recruited subjects (71.9 ± 5.6 years; 48 males), 70 (65.4%) were found to have femoral artery plaques. The atherosclerotic plaques were most frequently found in PA (41.1%) and CFA (40.2%) segments, followed by pSFA (31.8%) and AC (23.4%) segments (p = 0.002). Similarly, PA and CFA segments showed significantly greater maximum wall thickness and eccentricity index compared with pSFA and AC segments (all p < 0.001). Significant differences can be found in NWI among four segments of femoral arteries (p < 0.001) and PA showed the highest NWI (54.8%), followed by AC (54.3%), pSFA (52.4%) and CFA (45.9%) segments. Compared with right femoral artery, left femoral artery had significant smaller lumen area and greater NWI in most of segments (p < 0.002). There were no significant differences in ABI between subjects with and without atherosclerotic plaques (p = 0.161). The presence of subclinical atherosclerotic plaque in femoral arteries was significantly associated with cardiovascular risk factors including age (odds ratio [OR], 1.133; 95% confidence interval [CI], 1.048–1.224, p = 0.002), male gender (OR, 3.914; 95% CI, 1.612–9.501, p = 0.003), and hypertension (OR, 4.000; 95% CI, 1.700–9.411, p = 0.001), respectively.ConclusionsSubclinical femoral artery atherosclerosis is prevalent in the elderly population, particularly in the left femoral artery and segments of CFA and PA, and is associated with age, male gender and hypertension. Our findings suggest that, for screening subclinical atherosclerosis, more attention needs to be paid to the specific side and segments of femoral arteries, particularly older individuals and those with these cardiovascular disease risk factors.

Relationship Between Total Serum Bilirubin Levels and Carotid and Femoral Atherosclerosis in Familial Dyslipidemia.

Bilirubin is a potent antioxidant that has been inversely related to cardiovascular disease. There is little information on serum total bilirubin (TB) in relation to atherosclerosis in familial dyslipidemia. We assessed the association between TB and carotid and femoral atherosclerosis in this high-risk group. We evaluated 464 individuals with familial dyslipidemia (56% men; median age, 48 years), 322 with familial hypercholesterolemia, and 142 with familial combined hyperlipidemia. Carotid and femoral arteries were imaged bilaterally with a standardized ultrasonographic protocol. Mean and maximum intima-media thickness and plaque presence (≥1.2 mm) and height were recorded. Cross-sectional associations between TB and atherosclerosis variables were investigated in multivariable-adjusted models, including lipid values and hypolipidemic drug use. Inflammatory markers (C-reactive protein, total leukocyte count, and lipoprotein[a]) were also determined. Increasing TB levels were associated with decreasing intima-media thickness of all carotid segments (P<0.05, all). TB also related to carotid plaque, present in 78% of individuals, and to plaque burden (≥3 plaques), with odds ratios (95% confidence interval) 0.59 (0.36-0.98) and 0.57 (0.34-0.96) for each increase of 0.5 mg in TB, respectively. Findings were confirmed in a validation cohort of 177 subjects with nonfamilial dyslipidemia. Only the familial combined hyperlipidemia group, with higher inflammation-related markers, showed an inverse association between TB and femoral plaque height (β=-0.183; P=0.030). TB was inversely and independently associated with carotid plaque burden in familial and nonfamilial dyslipidemia. These findings support the use of TB as a biomarker of atherosclerosis in this high-risk group.

Carotid and femoral atherosclerosis in antiphospholipid syndrome: Equivalent risk with diabetes mellitus in a case-control study.

Antiphospholipid syndrome (APS) may carry a worse prognosis for vascular complications when co-existing with subclinical atherosclerosis; however, the association between the two conditions remains ambiguous. We evaluated ultrasonographic markers of subclinical atherosclerosis in carotid and femoral arteries of 86 patients with thrombotic APS [43 primary APS (PAPS), 43 systemic lupus erythematosus-associated APS (SLE/APS)], 86 patients with diabetes mellitus (DM) and 86 healthy controls, individually matched for age and gender, and investigated their associations with traditional and disease-related factors in APS. Carotid plaques were found in 28% of PAPS, 23% of SLE/APS, and 30% of DM patients versus 9% of controls (p = 0.006). Femoral plaques were found in 33% of PAPS, 19% of SLE/APS, 20% of DM, and 9% of controls (p = 0.032). Multivariate regression-derived relative risk estimates for atherosclerotic plaques in any location were 2.72 for PAPS, 2.63 for SLE/APS, and 1.98 for DM (p = 0.004, 0.009, and 0.032 respectively), after adjusting for age, gender, hypertension, dyslipidemia, smoking, BMI, and family history of coronary disease. Among patients with APS, atherosclerotic plaques were associated with the number of traditional CVD risk factors in both PAPS (RR = 2.75, p < 0.001) and SLE/APS (RR = 1.84, p < 0.001), and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS. Patients with PAPS and SLE/APS have a nearly 2.5-fold risk of atherosclerotic plaques in carotid and femoral arteries compared to healthy controls, similar to DM patients. Atherosclerotic plaques are associated with the number of traditional risk factors in both APS and SLE/APS, and with IgG anti-beta2-glycoprotein I antibodies in SLE/APS.

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle‐brachial index (ABI) is inadequate to detect early‐stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and ResultsIn 2007–2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal‐range ABI (1.00–1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4‐m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4‐m walk performance in the normal‐range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal‐range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life.

Association of Mild-to-Moderate Reduction in Glomerular Filtration Rate with Subclinical Atherosclerosis in Postmenopausal Women.

Due to loss of hormonal protective effects, postmenopausal women have an increased cardiovascular (CV) risk. Chronic kidney disease (CKD) is a well-established risk factor for CV disease, but little is known whether mild-to-moderate kidney dysfunction is associated with atherosclerosis burden in the postmenopausal asymptomatic women. Subclinical atherosclerosis was evaluated in 125 postmenopausal women with no clinical form of atherosclerosis, by carotid and femoral ultrasonography, ankle-brachial index (ABI), and flow-mediated dilation (FMD). Carotid and femoral atherosclerosis were defined as increased intima-media thickness (IMT) and/or the presence of plaques. Endothelial function was assessed by endothelial dependent (flow-mediated dilation at 1 minute [FMD1]) and independent (flow-mediated dilation after nitroglycerin [FMDNTG]) vasodilation. Classical CV risk factors (age, smoking, obesity, diabetes, blood pressure, and lipids) were evaluated. Kidney function was evaluated in terms of estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Univariate linear regression and multivariate logistic regressions were used to evaluate the independent associations between kidney function and markers of subclinical atherosclerosis. In the unadjusted linear analysis, eGFR showed a significant negative association with markers of subclinical atherosclerosis: carotid IMT (R2 = 0.305; p < 0.001), femoral IMT (R2 = 0.19, p < 0.001), carotid plaques (R2 = 0.22; p < 0.001), femoral plaques (R2 = 0.09; p = 0.0005), ABI (R2 = 0.05; p = 0.01), FMD1 (R2 = 0.45; p < 0.001), and FMDNTG (R2 = 0.205, p < 0.001). After adjustment for classical CV risk factors the association remained significant. Mild-to-moderate reduced eGFR is related to subclinical atherosclerosis, independent of traditional CV risk factors. It is important to detect renal function decline, even if it is mild, to improve risk stratification of subclinical atherosclerosis in postmenopausal women.

1A.12

Abstract Femoral atherosclerosis, a major cause of peripheral artery disease, has been associated with higher cardiovascular risk in lower extremity peripheral arterial disease patients. The purpose of our study was to assess the effects of the heritable components of atherosclerotic plaque formation in the femoral artery. 161 Hungarian and Italian twin pairs (n = 322, 75 Hungarian and 86 Italian pairs from Padua, Perugia and Terni; 83 monozygotic /MZ/, 78 dizygotic /DZ/; mean age 50 ± 13 years) recruited from the Hungarian and Italian Twin Registries underwent B-mode sonography of bilateral common and superficial femoral arteries (CFA, SFA). Concordance rates between members of the MZ and DZ pairs were calculated, and compared by Chi-square test. Rough heritability was analysed by Falconer formula. Plaques were identified in 24% and 6% of patients in CFA and SFA, respectively. Significantly higher concordance rate was found in MZ twins compared to DZ pairs regarding the presence of plaques in CFA (rMZ = 0.869 vs. rDZ = 0.696) and SFA (rMZ = 0.622 vs. rDZ = 0.403) on left or right side, which indicated a 34% and 44% rough heritability, respectively. Femoral atherosclerotic plaque formation in CFA and SFA is moderately genetically determined. Further studies should elucidate whether offsprings of families at high risk for femoral atherosclerosis may benefit from early ultrasound screening.

Is hepatitis C associated with atherosclerotic burden? A systematic review and meta-analysis.

Background and AimsIncreasing evidence demonstrates that hepatitis C virus (HCV) infection is associated with atherosclerosis. However, there are contrasting findings in several studies that the atherosclerotic burden is not associated with HCV infections. Therefore, we performed a meta-analysis to clarify if HCV infection is associated with atherosclerosis compared to non-infected people.MethodsStandard guidelines for performance of meta-analysis were followed.ResultsA thorough database search performed by two independent investigators identified 14 eligible studies for analysis. The data from 11 studies were synthesized to report unadjusted odds ratios (ORs) for carotid atherosclerosis; the pooled unadjusted OR (95% confidence interval (CI)) was 1.65 (1.21, 2.09). By synthesizing the data from 8 studies to report adjusted ORs for carotid atherosclerosis the pooled multi-confounder adjusted OR (95% CI) was 1.76 (1.20, 2.32). However, the numbers of studies on coronary or femoral atherosclerosis were limited and not enough for analysis.ConclusionsOur meta-analysis indicats that HCV infection is associated with carotid atherosclerosis independent of classical risk factors. Therefore, we would recommend for HCV infected patients to be counseled on their risk for carotid atherosclerosis.

Signature of subclinical femoral artery atherosclerosis in peripheral blood mononuclear cells

Peripheral arterial disease is a relevant public health problem associated with increased risk of morbimortality. Most of the patients with this condition are asymptomatic. Therefore, the development of accessible biochemical markers seems to be necessary to anticipate diagnosis. Our hypothesis is that asymptomatic subjects with objectively confirmed femoral artery atherosclerosis could be distinguished from control subjects by gene expression analysis in peripheral blood mononuclear cells (PBMC). A total of 37 asymptomatic males over 50years old were recruited at the University Clinic of Navarra (Spain). Nineteen participants were free from atherosclerotic vascular disease and 18 participants presented subclinical femoral artery atherosclerosis defined by means of Doppler ultrasound. PBMC were isolated from blood and the RNA extracted. A panel of atherosclerotic-related genes were evaluated by Taqman low-density array. In univariate logistic regression models, we found a direct relationship between IL4, ITGAM and TLR2 expression levels in PBMC and femoral atherosclerosis, even when the models were adjusted for age and hypertension prevalence. Multivariate logistic regression models showed that elevated IL4 expression levels were intimately associated with subclinical femoral atherosclerosis after adjusting for the same potential confounders. Current data suggest that gene expression in PBMC, in particular IL4 expression, could be a useful tool in the diagnosis of femoral artery atherosclerosis in asymptomatic patients. Furthermore, in patients with no differences in cardiovascular risk factors except for hypertension, the results point to the immune and inflammatory deregulation as a feature of subclinical peripheral atherosclerosis.

Altered atherosclerotic-related gene expression signature in circulating mononuclear leukocytes from hypercholesterolemic patients with low HDL cholesterol levels

HDL exerts atheroprotective effects through modulation of theimmune system physiology [1,2]. An abnormal function of immunecells including mononuclear leukocytes has been associated with thepathogenesis of cardiovascular disease (CVD) and their complications[3,4]. Nevertheless, the impact of blood HDL-C levels on leukocytefunctionality in populations at high cardiovascular risk has not beenpreviouslyexplored.Anadditionalapproachseemstobenecessary.Thepurpose of the current investigation was to compare Peripheral BloodMononuclearCells(PBMCs)atherosclerotic-relatedgeneexpressioninhypercholesterolemic patients with optimal and low HDL-C levels.Atotalof75subjectsover30 yearsoldwererecruitedatthetimeofattending the outpatient clinic for vascular risk assessment at theUniversity Clinic of Navarra, Spain (Table 1S, Supplementary content).Attendingtocurrentcardiovascularguidelines,hypercholesterolemiawasdefined as: total cholesterol ≥ 200 mg/dL and/or LDL-C ≥ 130 mg/dL.LowHDL-Clevelswerede finedasHDL-C ≤ 40 mg/dLformalesandHDL-C≤ 50 mg/dLforfemales.Exclusioncriteriawerethepresenceofseverelyimpaired renal function, chronic in flammatory conditions, and adminis-tration of anti-inflammatory, antithrombotic or hormonal therapy in theprevious 2 weeks. Patients with signifi cant acute infection, according toclinical criteria applied by the attending physician, were also excluded.The institutional ethics committee approved this study, and writteninformed consent was obtained from all patients.PBMCs were isolated from the blood using the Ficoll separationmethod. Total RNA was extracted using the RNeasy mini kit (Qiagen,Hilden,Germany)asspecifiedbythemanufacturer'sinstructions.Geneexpression analyses were performed at mRNA level by TaqMan Low-Density Array(TLDA). Pre-designed TaqManprobeand primer sets fortargetgeneswerechosenfromanon-linecatalog(AppliedBiosystems,Foster City, CA, USA). Genes were chosen based on literature reviewand previous data from our group (Table 2S, Supplementary content).Multiplelogisticregressionanalyseswereperformedtoexploretheassociations between HDL-C levels and PBMC gene expression inhypercholesterolemic patients. Previous investigations have demon-stratedthatTG-andcholesterol-richlipoproteinsotherthanHDLhavearegulatoryeffectonimmunecellgeneexpression[5].Todeterminetheinfluenceof theselipidparametersonthe associationsbetweenHDL-Clevels and PBMC gene expression, we made an analysis in duplicateadjusting by non-HDL-C or TG levels. The logistic regression modelsshowed an inverse and close association between HDL-C levels andPBMC CD36, CD40 and IL4 gene expression in models adjusted byage,sexandnon-HDL-ClevelsandPBMCCD36andCD40geneexpressioninmodels adjusted by age, sex and TG levels (Table 3S, Supplementarycontent).Sincethemodeladjustedbyageandsexshowedasignificantassociation between IL4 expression and low HDL-C level in hyperch-olesterolemia, these data suggest that this relation depends, at least inpart,onTGlevels.PreviousstudiessuggestedalinkbetweenstatinsandHDL-C levels [6]. We thus included this covariable in the logisticregression models. For all non-HDL-C and TG models, the associationsbetween gene expression and HDL-C levels remained unchangedincluding statin treatment (Table 3S, Supplementary content).Importantly, many investigations have reported an altered geneexpression of circulating leukocytes in relationwith conditions linkedto CVD [7,8]. Therefore, we explored whether the association betweenlow HDL-C levels and PBMC gene expression in hypercholesterolemicpatients was influenced by subclinical femoral atherosclerosis,hypertension or type 2 diabetes. Our results show that the relationbetween HDL-C and CD36/CD40 mRNA levels remains statisticallysignificant even after adjusting by age, sex, non-HDL-C or TG levels,statin intake and prevalence of subclinical femoral atherosclerosis,hypertension or type 2 diabetes (Tables 1 and 2). In contrast, theassociation with IL4 expression, observed in models adjusted by non-HDL-C levels and hypertension or type 2 diabetes, was lost in a modeladjustedbysubclinical femoralatherosclerosis(Tables1 and2).Theseresultssupportpreviousunpublisheddatafromourgroupshowinganinverse association between PBMC IL4 mRNA levels and the presence