Lipoprotein(a) as a blood marker for large artery atherosclerosis stroke etiology: validation in a prospective cohort from a swiss stroke center.

BACKGROUND: Lipoprotein (a) [Lp(a)] serum levels are highly genetically determined and promote atherogenesis. High Lp(a) levels are associated with increased cardiovascular morbidity. Serum Lp(a) levels have recently been associated with large artery atherosclerosis (LAA) stroke. We aimed to externally validate this association in an independent cohort. METHODS: This study stems from the prospective multicentre CoRisk study (CoPeptin for Risk Stratification in Acute Stroke patients [NCT00878813]), conducted at the University Hospital Bern, Switzerland, between 2009 and 2011, in which Lp(a) plasma levels were measured within the first 24 hours after stroke onset. We assessed the association of Lp(a) with LAA stroke using multivariable logistic regression and performed interaction analyses to identify potential effect modifiers. RESULTS: Of 743 patients with ischaemic stroke, 105 (14%) had LAA stroke aetiology. Lp(a) levels were higher for LAA stroke than non-LAA stroke patients (23.0 nmol/l vs 16.3 nmol/l, p = 0.01). Multivariable regression revealed an independent association of log10and#xA0;Lp(a) with LAA stroke aetiology (aOR 1.47 [95% CI 1.03and#x2013;2.09], p = 0.03). The interaction analyses showed that Lp(a) was not associated with LAA stroke aetiology among patients with diabetes. CONCLUSIONS: In a well-characterised cohort of patients with ischaemic stroke, we validated the association of higher Lp(a) levels with LAA stroke aetiology, independent of traditional cardiovascular risk factors. These findings may inform randomised clinical trials investigating the effect of Lp(a) lowering agents on cardiovascular outcomes. The CoRisk (CoPeptin for Risk Stratification in Acute Patients) study is registered on ClinicalTrials.gov. REGISTRATION NUMBER: NCT00878813.

[How do I investigate... the vulnerability of a carotid artery plaque in 2024]. / Comment j'explore la vulnérablilité d'une plaque carotidienne en 2024.

Carotid artery atherosclerosis is one of the leading causes of stroke. Even though the association between the risk of stroke and the level of morphological stenosis of a carotid plaque has been known for a long time, growing evidence has since proven necessary to assess the composition of the plaque itself to identify vulnerability predictors. These vulnerable plaques, even more if non-stenosing, may be responsible for a significant - but hard to quantify - proportion of strokes so far classified cryptogenic. As a matter of fact, plaque composition may escape detection and characterisation with classical imaging. Several biomarkers associated with its vulnerability to destabilization and with the risk of stroke such as intraplaque hemorrhage and inflammation are now routinely assessable. After a few pathophysiological reminders and a critical reading of the historical literature concerning carotid artery atherosclerosis management, we will review in this article the imaging techniques that can be used in the routine work-up of a carotid atherosclerotic plaque, with a focus on vessel wall magnetic resonance imaging and contrast enhanced ultrasonography.

L'athérosclérose carotidienne est une des causes les plus fréquentes d'accident ischémique cérébral (AIC). Si la dangerosité d'une plaque d'athérome est historiquement vue uniquement à travers le prisme de la sténose qu'elle engendre, l'évolution des connaissances nous pousse à considérer sa composition à la recherche de facteurs de vulnérabilité. Ces plaques à risque, a fortiori «non sténosantes¼, sont responsables d'une proportion difficilement quantifiable, mais probablement non négligeable d'AIC jusqu'ici considérés cryptogéniques. En effet, ces critères échappent pour beaucoup aux méthodes d'imagerie traditionnelle. Plusieurs propriétés associées à la vulnérabilité de la plaque et au risque d'AIC, principalement l'hémorragie intra-plaque et l'inflammation, sont désormais accessibles en pratique courante. Après quelques rappels physiopathologiques et une lecture critique de la littérature historique de la prise en charge de l'athérome carotidien, nous passerons en revue les différentes techniques d'imagerie utilisables en routine dans la mise au point de la plaque d'athérosclérose, avec un focus pratique sur l'imagerie pariétale vasculaire par résonance magnétique et, dans une moindre mesure, par échographie de contraste.

Remnant cholesterol and the risk of carotid plaque in hypertension: results from a community-based screening among old adults in Hangzhou, China.

Elevated remnant cholesterol (RC) is considered a risk factor for atherosclerotic cardiovascular disease, but the evidence on this association applies to the Chinese population with hypertension is limited. We aimed to explore the association between RC levels and carotid plaque in old adults with hypertension. 8523 hypertensive patients aged ≥ 60 years with serum lipids and carotid ultrasonography data were included in this community-based screening. Fasting RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDLC). The associations of RC levels with carotid plaque risk were evaluated using Logistic regression and restricted cubic spline models. Carotid plaque was screened in 4821 (56.56%) subjects. After multivariable-adjusted, RC was significantly related to carotid plaque [Odd ratio (OR)] = 1.043 per 0.1 mmol/L increase, 95% confidence interval (CI): 1.030-1.056). The highest versus the lowest quartile of RC was 1.928 (1.673-2.223) for carotid plaque. A nonlinear association was found between serum RC levels and the risk of carotid plaque (P for nonlinearity < 0.001). Moreover, an RC > 0.78 mmol/L differentiated patients at a higher risk of carotid plaque compared to those at lower concentrations, regardless of whether LDLC was on target at 2.59 mmol/L. In old adults with hypertension, elevated RC was positively associated with carotid plaque, independent of LDLC and other conventional risk factors.

The Impact of Atherosclerotic Burden on Vascular Outcomes in Patients with Stroke and Atrial Fibrillation: The ATHENA study.

Introduction: Patients with ischemic stroke (IS) and atrial fibrillation (AF) face a higher risk of recurrent vascular events. This study evaluates the impact of atherosclerotic vascular disease burden across different vascular territories on the risk of vascular events in patients with recent ischemic stroke and AF within 90 days. Patients and Methods: We included patients with IS and AF from the International RAF network in a prospective 90-day follow-up. Atherosclerotic vascular disease was identified by at least one of the following: Symptomatic ischemic heart disease, symptomatic peripheral artery disease, internal carotid stenosis ≥50%, or the presence of plaques in the aorta. The primary outcome was a composite of stroke, transient ischemic attack, systemic embolism, cerebral bleeding, and major extracranial bleeding within 90 days postacute stroke. Patients were categorized into 5 groups based on the number of affected atherosclerotic vascular territories, with those with no atherosclerotic vascular disease as the reference. Kaplan-Meier curves were generated and compared using the log-rank test to determine the predictive value of the number of diseased territories for the risk of events. Data analysis was performed with SPSS/PC Win Package 25.0. Results: Of the 2148 patients (mean age 77.59; 53.86% female), 744 (34.60%) had atherosclerosis. Multivariable analysis revealed that involvement of 3 (hazard ratio [HR] 2.80, 95% confidence interval [CI]: 1.20-6.53) or 4 (HR 6.81, 95% CI: 1.02-36.24) vascular territories was significantly associated with the risk of combined events. Conclusions: In patients with recent ischemic stroke and AF, atherosclerosis across multiple territories correlates with a higher risk of future vascular events.

Prognostic impact of carotid plaque imaging using total plaque area added to SCORE2 in middle-aged subjects: the ARteris Cardiovascular Outcome (ARCO) cohort study.

AIMS: Many cardiovascular events occur in seemingly healthy individuals.We set out to assess the predictive value of atherosclerosis imaging in combination with cardiovascular risk calculators in subjects aged 40-65 years. METHODS: We compared PROCAM (PROspective CArdiovascular Münster study), SCORE (Systematic COronary Risk Evaluation) and SCORE2 with carotid ultrasound (total plaque area, TPA) in subjects without cardiovascular disease. In this prospective cohort study, follow-up was obtained by phone or mail from patients; or from clinical records, if needed. RESULTS: In 2842 subjects (mean age 50±8 years; 38% women), cardiovascular events occurred in 154 (5.4%) of them over an mean follow-up period of 5.9 (range 1-12) years, specifically: 41 cases of AMI (myocardial infarction), 16 strokes, 21 CABG (coronary artery bypass grafting), 41 PTCA (percutaneous transluminal coronary angioplasty) and 35 CAD (coronary artery disease). Mean PROCAM risk was 5±6%, mean SCORE risk was 1.3±1.6% and mean SCORE2 risk was 5±3%. Both for the primary outcome (major adverse cardiovascular events, MACEs, i.e. AMI + strokes) and the secondary outcome (atherosclerotic cardiovascular disease, ASCVD, i.e. MACEs + CABG + CAD + PTCA), hazards increased significantly for TPA tertiles and SCORE2 post-test risk between 6.7 to 12.8 after adjustment for risk factors (age, smoke, sex, systolic blood pressure, lipids, medication) and after adjustment for results from PROCAM, SCORE and SCORE2. Model performance was statistically improved regarding model fit in all models using TPA. Net reclassification improvement for SCORE2 with TPA post-test risk increased significantly by 24% for MACEs (p = 0.01) and 39% for ASCVD (p <0.0001). CONCLUSIONS: Integration of TPA post-test risk into SCORE2 adds prognostic information, supporting the use of carotid ultrasound when assessing ASCVD risk in subjects aged 40-65 years.

Atherosclerosis and depression: is carotid intima-media thicker in patients with depression compared to matched control individuals? A systematic review and meta-analysis.

OBJECTIVE: To investigate if there is an association between atherosclerosis and depression by using as imaging biomarker the carotid intima media thickness (cIMT), a surrogate marker for atherosclerosis. METHODS: PubMed/Medline, Embase and Cochrane databases were comprehensively searched to identify studies investigating the association between cIMT and depression. The results were pooled using a random-effects statistical model, appropriate for the expected high heterogeneity. Sensitivity and subgroup analyses were conducted where data was available. RESULTS: Overall, 22 and 13 studies met inclusion criteria for the qualitative and the quantitative synthesis, respectively, with a total of 4466 patients and 21,635 control participants. Results showed that cIMT is significantly higher in the depression, compared to the control groups with an overall mean difference of 0.07 mm (95% CI 0.04-0.10, p < 0.01). Subgroup analysis showed that diabetes could present as a confounding factor in patients with depression and an increased cIMT. CONCLUSIONS: This study confirms a significantly increased cIMT in patients with depression, compared with controls and suggests a possible bidirectional link between atherosclerosis and depression. An early screening of cardiovascular disease in individuals suffering with depression should be considered.

Impact of direct-acting antiviral on subclinical atherosclerosis in chronic hepatitis C infected patients.

INTRODUCTION: The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. AIM: To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). RESULTS: At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). CONCLUSIONS: SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.

Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non-HIV populations generalize to people with HIV is not well understood. METHODS AND RESULTS: PRSs for CAD (GPSMult) and lipid traits were calculated in a global cohort of people with HIV treated with antiretroviral therapy with low-to-moderate atherosclerotic cardiovascular disease risk enrolled in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV). The PRSs were associated with baseline lipid traits in 4495 genotyped participants, and with subclinical CAD in a subset of 662 who underwent coronary computed tomography angiography. Among participants who underwent coronary computed tomography angiography (mean age, 50.9 [SD, 5.8] years; 16.1% women; 41.8% African, 57.3% European, 1.1% Asian), GPSMult was associated with plaque presence with odds ratio (OR) per SD in GPSMult of 1.42 (95% CI, 1.20-1.68; P=3.8×10-5), stenosis >50% (OR, 2.39 [95% CI, 1.48-3.85]; P=3.4×10-4), and noncalcified/vulnerable plaque (OR, 1.45 [95% CI, 1.23-1.72]; P=9.6×10-6). Effects were consistent in subgroups of age, sex, 10-year atherosclerotic cardiovascular disease risk, ancestry, and CD4 count. Adding GPSMult to established risk factors increased the C-statistic for predicting plaque presence from 0.718 to 0.734 (P=0.02). Furthermore, a PRS for low-density lipoprotein cholesterol was associated with plaque presence with OR of 1.21 (95% CI, 1.01-1.44; P=0.04), and partially calcified plaque with OR of 1.21 (95% CI, 1.01-1.45; P=0.04) per SD. CONCLUSIONS: Among people with HIV treated with antiretroviral therapy without documented atherosclerotic cardiovascular disease and at low-to-moderate calculated risk in REPRIEVE, an externally developed CAD PRS was predictive of subclinical atherosclerosis. PRS for low-density lipoprotein cholesterol was also associated with subclinical atherosclerosis, supporting a role for low-density lipoprotein cholesterol in HIV-associated CAD. REGISTRATION: URL: https://www.reprievetrial.org; Unique identifier: NCT02344290.

Cardiovascular event in a cohort of rheumatoid arthritis patients in Castilla-La Mancha: Utility of carotid ultrasound.

Rheumatoid Arthritis (RA) has a mortality rate 1,3 to 3 times higher than the general population, with cardiovascular mortality accounting for 40-50% of cases. Currently, cardiovascular disease is considered an extraarticular manifestation of RA (OR: 1,5-4,0). Ultrasound measurement of the intima-media thickness (IMT) of the common carotid artery and the presence of atherosclerotic plaques (AP) is a non-invasive method and a surrogate marker of subclinical arteriosclerosis. OBJECTIVE: To determine if subclinical arteriosclerosis findings through carotid ultrasound can serve as a good predictor of cardiovascular events (CVE) development in a cohort of RA patients over a 10-year period. METHODOLOGY: A cohort of RA patients seen in the Rheumatology outpatient clinic of a hospital in Castilla La Mancha in 2013 was evaluated. A prospective evaluation for the development of CVE over the following 10 years was conducted, and its correlation with previous ultrasound findings of IMT and AP was analyzed. RESULTS: Eight (24%) patients experienced a CVE. Three (9%) had heart failure, three (9%) had a stroke, and two (6%) experienced acute myocardial infarction. RA patients who developed a CVE had a higher IMT (0,97 +/- 0.08 mm) compared to the RA patients without CV complications (0,74 +/- 0.15 mm) (p = 0,003). The presence of IMT ≥ 0.9 mm and AP had a relative risk of 12,25 (p = 0,012) and 18,66 (p = 0,003), respectively, for the development of a CVE. CONCLUSIONS: Carotid ultrasound in RA patients may allow for early detection of subclinical atherosclerosis before the development of CVE, with IMT ≥ 0.9 mm being the most closely associated finding with CVE, unaffected by age.

[GLP-1 receptor agonists in type 2 diabetes : paradoxical real-life underuse in patients with atherosclerotic cardiovascular disease]. / Agonistes des récepteurs du GLP-1 et diabète de type 2 : sous-utilisation paradoxale chez les patients avec maladie cardiovasculaire athéromateuse.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of cardiovascular (CV) complications in patients with type 2 diabetes (T2DM) and atherosclerotic cardiovascular disease (ASCVD) in placebo-controlled CV outcome trials. This article compares the proportion of T2DM patients treated with GLP-1RAs in retrospective observational studies that recruited T2DM patients with versus without established ASCVD. Nine cohorts from seven studies were collected in the international literature between 2019 and 2022. Overall, the percentages of patients treated with GLP-1RAs were low (< 10 %) in most studies. Surprisingly, the use of GLP-1RAs in patients with ASCVD was slightly lower in 7 out of 9 cohorts when compared to the use in patients without ASCVD (odds ratio 0.80, 95% CI 0.79-0.81). Despite a positive trend over the last decade, the real-world use of GLP-1RAs remains limited, especially in patients with established ASCVD. The reasons for this underuse are diverse. Bridging the gap between clinical evidence of cardioprotective effects of GLP-1RAs and their underuse in clinical practice in T2DM patients at high/very high CV risk, more particularly those with established ASCVD, should be considered as a key objective for health care providers, especially cardiologists.

Les agonistes des récepteurs du glucagon-like peptide-1 (ARGLP-1) réduisent le risque de complications cardiovasculaires (CV) chez les patients avec un diabète de type 2 (DT2) et une maladie cardiovasculaire athéromateuse (MCVA) dans des essais contrôlés versus placebo. Cet article compare l'utilisation des ARGLP-1 dans des études observationnelles rétrospectives en vie réelle chez des patients DT2 avec MCVA versus sans MCVA. Neuf cohortes provenant de 7 études ont été collectées dans la littérature internationale entre 2019 et 2022. Au total, les pourcentages de patients DT2 traités par un ARGLP-1 restent faibles (< 10 %) dans la plupart des études, même si une certaine progression a été notée ces dernières années. Curieusement, le recours à un ARGLP-1 chez des patients DT2 avec MCVA s'avère être légèrement inférieur chez les patients avec MCVA par rapport à ceux sans MCVA dans 7 cohortes sur 9 (odds ratio 0,80, intervalle de confiance à 95 % 0,79-0,81). Les raisons de cette sous-utilisation sont multiples. Combler le fossé entre l'évidence clinique d'une cardioprotection procurée par les ARGLP-1 et leur sous-utilisation en pratique clinique chez les patients DT2 à haut ou très haut risque CV, en particulier ceux avec une MCVA avérée, doit être considéré comme un objectif par les professionnels de la santé, en particulier les cardiologues.

The Association of Total Meat Intake with Cardio-Metabolic Disease Risk Factors and Measures of Sub-Clinical Atherosclerosis in an Urbanising Community of Southern India: A Cross-Sectional Analysis for the APCAPS Cohort.

AIM: Meat is commonly consumed in India; however, in comparison to Western settings, it is eaten in relatively lower quantities and with minimal processing. The association between meat intake and cardio-metabolic diseases (CMDs) and their risk factors in India is currently uncertain. We examined whether meat intake is associated with risk factors for CMDs and the measures of subclinical atherosclerosis in urbanising villages in southern India. METHODS: We conducted a cross-sectional analysis of 6012 adults (52.3% male) participating in the Andhra Pradesh Children and Parents' Study (APCAPS), which is a large prospective, intergenerational cohort study in Southern India that began with the long-term follow-up of the Hyderabad Nutrition Trial (1987-1990). We used cross-sectional data from the third wave of data collection conducted in 2010-2012, where total meat intake was assessed using 100-item, semi-quantitative validated food frequency questionnaires (FFQ). The FFQs were validated using multiple weighed 24 h dietary recalls. The main predictor, 'total meat intake', was calculated as the sum of chicken, red meat, and fish consumption. The risk factors for CMDs [systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist circumference (WC), fasting glucose, total cholesterol, homeostasis model assessment insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and C-reactive protein] and measures of subclinical atherosclerosis [Carotid Intima-Media Thickness, Pulse Wave Velocity, and Augmentation Index] were assessed using standardised clinical procedures. Stratified by gender, the association of meat intake with the risk factors of CMDs and measures of subclinical atherosclerosis was examined using linear multilevel models with random intercept at the household level. RESULTS: The mean (SD) age of the male (n = 3128) and female participants (n = 2828) was 34.09 years (15.55) and 34.27 years (12.73), respectively. The median (IQR) intake of meat was 17.79 g/day (8.90, 30.26) in males and 8.90 g/day (4.15, 18.82) in females. In males, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with DBP, BMI, WC, total cholesterol, LDL-C, and triglycerides, whereas in females, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with SBP, DBP, fasting glucose, HOMA-IR, total cholesterol, LDL-C, and triglycerides. There was no relationship between meat consumption and measures of subclinical atherosclerosis. CONCLUSIONS: Meat intake had a linear positive association with CMD risk factors among the relatively younger Indian population who were consuming meat at lower levels compared to their European counterparts.

[Multidistrict atherosclerotic disease: epidemiological and clinical framework]. / Malattia aterosclerotica polidistrettuale: inquadramento epidemiologico e clinico.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

3-D transesophageal echocardiography aids in assessment of embolic stroke due to aortic atherosclerotic plaque: A case series.

Atherosclerosis is the most common cause of heart disease and stroke. Plaque thickness ≥4 mm in the ascending aorta or aortic arch is strongly correlated with cerebral embolic events and ischemic stroke. However, despite imaging workup, the cause of embolic stroke remains unidentified in many patients. Transesophageal echocardiography (TEE) is the preferred echocardiographic method for the evaluation of cardiac source of emboli. 2D TEE imaging evaluates aortic root and aortic arch in a single plane or two planes with biplane imaging. However, 2D TEE often fails to detect mobile or complex components in the ascending aorta and aortic arch plaques. The routine availability of 3D TEE in current ultrasound systems may significantly improve the assessment of aortic plaques as a potential embolic source. In this case series, we present four consecutive patients with stroke who underwent TEE by a single cardiologist for possible cardioembolic source. Some of these patients may have been labelled as "cryptogenic stroke" or "embolic stroke of undetermined source" (ESUS) due to the presence of insignificant or nonmobile ascending aortic or aortic arch plaques on 2D TEE imaging. In our four consecutive patients with ESUS who underwent TEE by a single operator, 3D TEE showed complex aortic arch plaques with ulceration with mobile components and established these plaques as the likely source of embolic stroke.

Natural Autoantibodies in Biologic-Treated Rheumatoid Arthritis and Ankylosing Spondylitis Patients: Associations with Vascular Pathophysiology.

Cardiovascular (CV) morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Natural autoantibodies (nAAb) are involved in innate immunity, as well as autoimmunity, inflammation, and atherosclerosis. There have not been any studies assessing the effects of biologics on nAAbs in RA and AS, also in relation to vascular pathophysiology. Fifty-three anti-TNF-treated RA and AS patients were included in a 12-month follow-up study. Anti-citrate synthase (CS) and anti-topoisomerase I fragment 4 (TOPO-F4) IgM and IgG levels were determined by ELISA. Ultrasonography was performed to assess brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV). Other variables were also evaluated at baseline and 6 and 12 months after treatment initiation. Anti-TNF therapy improved FMD in RA and PWV in AS and stabilized ccIMT. TNF inhibition increased anti-CS IgM and IgG, and possibly also anti-TOPO-F4 IgG levels. Various correlation analyses revealed that nAAbs might be independently involved in autoimmunity as well as changes in inflammation and vascular pathology over time in biologic-treated patients (p < 0.05). We also found associations between anti-TOPO-F4 IgG and anti-Hsp60 IgG (p < 0.05). Baseline nAAb levels or nAAb level changes might determine changes in CRP, disease activity, FMD, PWV, and ccIMT over time (p < 0.05). The interplay between arthritis and inflammatory atherosclerosis, as well as the effects of anti-TNF biologics on these pathologies, might independently involve nAAbs.

Polyvascular atherosclerosis and renal dysfunction increase the odds of cognitive impairment in vascular disease: findings of the LipidCardio study.

INTRODUCTION: Growing evidence suggests a causal role for atherosclerotic vascular disease in cognitive impairment and dementia. Atherosclerosis may present as monovascular disease (monoVD) or as widespread polyvascular atherosclerotic disease (polyVD). Evidence on the relationship between monoVD or polyVD and cognitive impairment is limited. METHODS: We conducted a cross-sectional analysis of baseline data from the LipidCardio Study. The main outcome measure was the presence of cognitive impairment, defined as a Mini-Mental State Examination (MMSE) score < 26. RESULTS: The mean age was 71.5 years, 30.3% were female, 17.3% had no evidence of large-vessel atherosclerosis, 71.1% had monoVD, and 11.7% had polyVD, defined as the presence of atherosclerosis in ≥ 2 vascular territories (coronary, cerebral, aortic, or lower extremity). A total of 21.6% had cognitive impairment according to the prespecified cutoff (MMSE < 26). Overall, the odds of cognitive impairment increased for each additional vascular territory affected by atherosclerosis [adjusted odds ratio 1.76, 95% confidence interval (CI) 1.21-2.57, p = 0.003]. Furthermore, there was evidence for an interaction between vascular disease and chronic kidney disease (CKD). The odds of cognitive impairment were not greater in the monoVD subgroup compared to those without any atherosclerosis, if CKD was absent (OR 0.98, 95% CI 0.48-2.10; p = 0.095), while the odds ratio (OR) of cognitive impairment with polyVD compared to no atherosclerosis was 2.71 (95% CI 1.10-6.92; p = 0.031). In contrast, in patients with CKD, both monoVD and polyVD were associated with significantly higher odds of cognitive impairment than no atherosclerosis. CONCLUSIONS: PolyVD is associated with increased odds of cognitive impairment. MonoVD is associated with cognitive impairment only in the presence of CKD.

Age and Aspirin Dosing in Secondary Prevention of Atherosclerotic Cardiovascular Disease.

BACKGROUND: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. METHODS AND RESULTS: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant (P=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (P>0.05 for all). CONCLUSIONS: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Systemic immune-inflammation index as a predictor of early stroke progression/recurrence in acute atherosclerotic ischemic stroke.

OBJECTIVES: Although the systemic immune-inflammatory index (SII) has recently been correlated with stroke severity and functional outcome, the underlying pathogenesis remains largely unknown. The objective of this study was to explore whether SII could predict early neurologic deterioration (END) in different etiologies of acute ischemic stroke. MATERIALS AND METHODS: From January 2019 to December 2021, a total of 697 consecutive patients with acute ischemic stroke, admitted within 72 hours from stroke onset, were prospectively enrolled. The patients were categorized into 4 groups based on quartiles of SII, calculated as platelets multiplied by neutrophils divided by lymphocytes. END and stroke progression/recurrence were assessed during the first 7 days after stroke onset using predetermined definitions. Logistic regression analysis was conducted to evaluate the association between SII and END, while considering the variation in association across stroke etiologies. RESULTS: END occurred in 135 patients: 24 (3.4%) for Group I, 25 (3.6%) for Group II, 33 (4.7%) for Group III, and 53 (7.6%) for Group IV. Among the END subtypes, stroke progression/recurrence stroke was the most prevalent. In the logistic regression model, the adjusted odds ratios (ORs) of END and stroke progression/recurrence for group IV were 2.51 (95% CI, 1.27-4.95) and 1.98 (95% CI, 1.03-3.89), respectively. Among the stroke etiologies, group IV showed a significant increase in END (OR 4.24; 95% CI, 1.42-12.64) and stroke progression/recurrence (OR 4.13; 95% CI, 1.39-12.27) specifically in case of large artery atherosclerosis. CONCLUSIONS: SII independently predicts early stroke progression/recurrence in patients with acute atherosclerotic ischemic stroke.

High glucose levels accelerate atherosclerosis via NLRP3-IL/ MAPK/NF-κB-related inflammation pathways.

BACKGROUND: As a chronic inflammatory disease, diabetes mellitus (DM) contributes to the development of atherosclerosis (AS). However, how the NLRP3 inflammasome participates in diabetes-related AS remains unclear. Therefore, this study aimed to elucidate the mechanism through which NLRP3 uses high glucose (HG) levels to promote AS. METHODS: Serum and coronary artery tissues were collected from coronary artery disease (CAD) patients with and without DM, respectively. The expression of NLRP3 was detected, and the effects of this inflammasome on diabetes-associated AS were evaluated using streptozotocin (STZ)-induced diabetic apoE-/- mice injected with Adenovirus-mediated NLRP3 interference (Ad-NLRP3i). To elucidate the potential mechanism involved, ox-LDL-irritated human aortic smooth muscle cells were divided into the control, high-glucose, Si-NC, and Si-NLRP3 groups to observe the changes induced by downregulating NLRP3 expression. For up-regulating NLRP3, control and plasmid contained NLRP3 were used. TNF-α, IL-1ß, IL-6, IL-18, phosphorylated and total p38, JNK, p65, and IκBα expression levels were detected following the downregulation or upregulation of NLRP3 expression. RESULTS: Patients with comorbid CAD and DM showed higher serum levels and expression of NLRP3 in the coronary artery than those with only CAD. Moreover, mice in the Ad-NLRP3i group showed markedly smaller and more stable atherosclerotic lesions compared to those in other DM groups. These mice had decreased inflammatory cytokine production and improved glucose tolerance, which demonstrated the substantial effects of NLRP3 in the progression of diabetes-associated AS. Furthermore, using the siRNA or plasmid to downregulate or upregulate NLRP3 expression in vitro altered cytokines and the MAPK/NF-κB pathway. CONCLUSIONS: NLRP3 expression was significantly increased under hyperglycemia. Additionally, it accelerated AS by promoting inflammation via the IL/MAPK/NF-κB pathway.

Potential Protein Signatures for Recurrence Prediction of Ischemic Stroke.

BACKGROUND: Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months. This study aimed to identify potential biomarkers for predicting stroke recurrence. METHODS AND RESULTS: We conducted a nested case-control study using a hospital-based cohort from the Third China National Stroke Registry selecting 214 age- and sex-matched patients with ischemic stroke with hypertension and no history of diabetes or heart disease. Using data-independent acquisition for discovery and multiple reaction monitoring for quantitative validation, we identified 26 differentially expressed proteins in large-artery atherosclerosis (Causative Classification of Ischemic Stroke [CCS]1), 16 in small-artery occlusion (CCS3), and 25 in undetermined causes (CCS5) among patients with recurrent stroke. In the CCS1 and CCS3 subgroups, differentially expressed proteins were associated with platelet aggregation, neuronal death/cerebroprotection, and immune response, whereas differentially expressed proteins in the CCS5 subgroup were linked to altered metabolic functions. Validated recurrence predictors included proteins associated with neutrophil activity and vascular inflammation (TAGLN2 [transgelin 2], ITGAM [integrin subunit α M]/TAGLN2 ratio, ITGAM/MYL9 [myosin light chain 9] ratio, TAGLN2/RSU1 [Ras suppressor protein 1] ratio) in the CCS3 subgroup and proteins associated with endothelial plasticity and blood-brain barrier integrity (ITGAM/MYL9 ratio and COL1A2 [collagen type I α 2 chain]/MYL9 ratio) in the CCS3 and CCS5 subgroups, respectively. CONCLUSIONS: These findings provide a foundation for developing a blood-based biomarker panel, using causative classifications, which may be used in routine clinical practice to predict stroke recurrence.

Cardiovascular complications of rheumatoid arthritis.

PURPOSE OF REVIEW: Rheumatoid arthritis (RA) patients remain at higher cardiovascular (CV) risk compared to non-RA patients, driven by accelerated atherosclerosis, leading to plaque rupture and acute CV events (CVE), including heart failure (HF). It has been hypothesized that chronic inflammation is the main driving force behind such outcomes. We summarize the current evidence supporting this hypothesis, focusing on arterial disease and myocardial disease. RECENT FINDINGS: RA patients demonstrate higher prevalence of subclinical atherosclerosis (high risk plaque and arterial inflammation) compared to non-RA patients, with RA disease activity correlating independently with CVE and death. Nonischemic HF with preserved ejection fraction (HFpEF) is more common in RA compared to non-RA, with subclinical myocardial structural and functional alterations also more prevalent in RA. HFpEF and myocardial remodeling and dysfunction bear a strong and independent association with inflammatory correlates. SUMMARY: All of this suggests that inflammation contributes to enhanced risk of CVE in RA. A more accurate and specific CV risk stratification tool for RA, incorporating biomarkers or imaging, is needed. Likewise, more prospective studies outlining the trajectory from preclinical to clinical HF, incorporating biomarkers and imaging, are also needed.