Intima media thickness of the carotid artery in primary antiphospholipid syndrome: A systematic review and meta-analysis.

BACKGROUND: Primary antiphospholipid syndrome (PAPS) has been associated with an increase in clinical events associated with atherosclerotic vascular disease. Intima media thickness (IMT) of carotid arteries is a surrogate marker of atherosclerotic vascular disease. OBJECTIVES: To conduct a systematic review and meta-analysis of studies evaluating IMT and their clinical correlates in PAPS. METHODS: Systematic search of EMBASE and PubMed databases from January 2000 to December 2023; we employed random effect meta-analyses for continuous outcomes and Peto's odds ratio for rare events. RESULTS: The meta-analysis included 21 studies (20 case control and 1 cohort) showing that PAPS patients (n = 1103) had thicker IM than controls (n = 832) (p < 0.0001) with wide heterogeneity (I2 = 86.9 %); PAPS patients (n = 782) also had a greater pooled prevalence of carotid plaques than controls (n = 537) (13.1 % vs 2.97 %, p < 0.0001). A sensitivity analysis by meta-regression indicated that mean age, gender, disease duration, lipid profile, blood pressures, smoking and statin use all explained the heterogeneity variance; a sensitivity analysis by subgroups confirmed smoking status and statin use as explanatory variables with the addition of ethnicity. CONCLUSION: Atherosclerosis of the carotid artery represents a clinical feature of PAPS in relation to the traditional risk factors and to statin use. Minimising the atherogenic risk with statins could reduce the late arterial atherothrombotic risks of PAPS.

A case-control study investigating cardiovascular health in maintenance hemodialysis patients through oxidative stress biomarkers and carotid artery intima-media thickness.

INTRODUCTION: Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD).

Prevalence of Lipoprotein(a) Measurement and its Association with Arteriosclerosis in Asymptomatic Individuals in China.

AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), and its level is genetically determined. Although guidelines and consensuses in various cardiovascular fields have emphasized the importance of Lp(a), screening for Lp(a) in China has not been well studied. METHODS: A cross-sectional study was conducted using a random sample of 30,000 medical examiners from each of the five health check-up centres. The distribution of Lp(a) was described for those who completed Lp(a) testing, and logistic regression modelling was used to evaluate the relationship between Lp(a) levels and vascular structure and function in the population who underwent carotid ultrasound and brachial‒ankle pulse wave velocity (baPWV) measurements. RESULTS: Lp(a) was measured in only 4400 (3.02%) of the 150,000 participants. Among those tested for Lp(a), the median concentration was 15.85 mg/dL. The proportion of participants with Lp(a) levels ≥ 30 mg/dL was 15.00%. Multiple logistic regression analysis revealed a significant correlation between Lp(a) and cIMT ≥ 1.0 mm (OR: 1.008, 95% CI: 1.001-1.014, P=0.020) and carotid artery plaques (OR: 1.010, 95% CI: 1.004-1.016, P=0.001) but no correlation with baPWV ≥ 1400 (OR: 0.999, 95% CI: 0.993-1.005, P=0.788) or baPWV ≥ 1800 (OR: 1.002, 95% CI: 0.993-1.011, P=0.634). CONCLUSIONS: The detection rate of Lp(a) at health checkups is low, and Lp(a) is positively associated with cervical vascular sclerosis and plaque but not with baPWV. Therefore, the testing rate of Lp(a) and the awareness of the risk of vascular structural changes due to Lp(a) should be further improved.

Cardiometabolic risk assessment in transgender individuals - differential impact of sex hormones and sex chromosomes.

BACKGROUND: While transgender individuals represent a significant group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood. Therefore, the current study aimed to characterize the impact of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements. METHODS: 17 transmen and 17 transwomen were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12). We analyzed carotid intima-media thickness (cIMT) and arterial stiffness, lipoproteins and other metabolites comprehensively by nuclear magnetic resonance spectroscopy and HDL-mediated cholesterol efflux capacity (CEC) from macrophages. T0 to T12 comparisons informed the impact of sex hormones, comparisons of genetic XX and XY individuals at T1 the impact of sex chromosomes. RESULTS: Vascular function was comparable at T12 and T0; systolic blood pressure increased in transmen (p=0.002). Transmen developed a pro-atherogenic lipoprotein profile, estrogen treatment in transwomen tended to result in improvements. Several metabolites indicating increased diabetes risk including plasma glucose were changed in transmen (p=0.025), with opposite changes in transwomen (p=0.002). Interestingly, at T1 apparent diabetes risk was lower in XX compared with XY individuals (p=0.002). CEC decreased in transwomen (p<0.01), while remaining unchanged in transmen. However, in both groups the strong positive association of apoA-I with cholesterol efflux observed at T0 was lost at T12. CONCLUSIONS: The results are consistent with increased cardiometabolic risk in transmen, while transwomen show beneficial changes early during gender-affirming hormone therapy. Sex chromosomes have less intrinsic effects. XY individuals and transmen display an increased apparent diabetes risk. Further research of cardiometabolic risk is needed for transgender individuals.

Successful non-invasive imaging of the coronary artery IMT in pediatric patients with Kawasaki disease using high-resolution echocardiography.

Kawasaki Disease (KD) is a multisystemic vasculitis of medium- and small-sized arteries. Abnormal intimal thickening may develop in the involved arterial area after regression of coronary artery aneurysm (CAA). Intimal dysfunction may induce local stenosis or arteriosclerosis in the future. In this case-control study, we investigated 29 consecutive KD patients [20 male, median current age, 7.9 years; median follow-up duration, 5.7 years] and a group of 29 healthy matched controls (CON) [19 male, median current age, 10.8 years]. They were assesed and compared for CAA, LVFS, GCS, GLS, coronary artery (CA) Z scores, carotid intima-media thickness (IMT) and coronary artery IMT by high-resolution transthoracic echocardiography (hrTTE). Coronary artery IMT (caIMT) was significantly higher in patients with a maximal CA Z score > 2.5 in acute KD than in CON: KD caIMT: 0.62 mm [IQR, 0.57-0.72 mm] vs. 0.53 mm [0.51-0.60 mm], p = 0.043. CAAs were found in 15 (51.7%) patients with acute KD. The maximal median LCA Z score in acute KD was 2.57z [IQR, 1.93-3.2z] and in follow-up -0.39z [IQR, -1.25 to -0.36z]. There was no significant difference in carotid IMT between KD patients and CON. Signs of CA intima-media thickening were detected by hrTTE in patients with a maximal CA Z score > 2.5 in acute KD. These data indicate that these patients may be at risk for cardiovascular sequale even in the absence of permanent CA luminal abnormalities. Therefore long-term follow-up of this group of KD patients may be required.

Comparative analysis of retinal microvascular parameters in healthy individuals with or without carotid artery stenosis or plaque.

PURPOSE: To evaluate the correlations between retinal microvascular changes and carotid artery stenosis (CAS) with and without plaques using fundus photography. METHODS: Patients who had undergone bilateral carotid ultrasonography and bilateral fundus photography were divided into the following groups based on the carotid intima-media thickness (IMT) determined via ultrasonography in this retrospective, observational study: the control and CAS (comprising CAS with and without plaque subgroups) groups. The following retinal indicators were determined via fundus photography based on a deep learning algorithm: the arteriole-to-venule ratio (AVR), whole retinal fractal dimension (FD), arteriolar fractal dimension (AFD), venular fractal dimension (VFD), vascular density (VD), and VD within 3 mm (VD3mm) and 5 mm (VD5mm) from the macular fovea. The correlations between these indicators and IMT were also assessed. RESULTS: In total, 715 participants, comprising 313 participants with CAS (CAS group; 91 with plaque and 222 without plaque) and 402 participants without CAS (control group), participated in this study. AFD, VFD, and FD in the CAS group were significantly lower than those in the control group (all p < 0.001). VD, VD3mm, and VD5mm showed significant differences between the groups (all p < 0.05). VFD in the CAS with plaque group was lower than that in the group without plaque (p = 0.014). VD3mm, and VD5mm showed significantly negative correlations with IMTmin in the CAS subgroup. CONCLUSIONS: AFD, VFD, FD, VD, VD3 mm, and VD5 mm decreased, and fundus photography based on deep learning algorithm may provide new approaches for screening of CAS.

Plasma proteomics and carotid intima-media thickness in the UK biobank cohort.

Background and aims: Ultrasound derived carotid intima-media thickness (cIMT) is valuable for cardiovascular risk stratification. We assessed the relative importance of traditional atherosclerosis risk factors and plasma proteins in predicting cIMT measured nearly a decade later. Method: We examined 6,136 UK Biobank participants with 1,461 proteins profiled using the proximity extension assay applied to their baseline blood draw who subsequently underwent a cIMT measurement. We implemented linear regression, stepwise Akaike Information Criterion-based, and the least absolute shrinkage and selection operator (LASSO) models to identify potential proteomic as well as non-proteomic predictors. We evaluated our model performance using the proportion variance explained (R 2). Result: The mean time from baseline assessment to cIMT measurement was 9.2 years. Age, blood pressure, and anthropometric related variables were the strongest predictors of cIMT with fat-free mass index of the truncal region being the strongest predictor among adiposity measurements. A LASSO model incorporating variables including age, assessment center, genetic risk factors, smoking, blood pressure, trunk fat-free mass index, apolipoprotein B, and Townsend deprivation index combined with 97 proteins achieved the highest R 2 (0.308, 95% C.I. 0.274, 0.341). In contrast, models built with proteins alone or non-proteomic variables alone explained a notably lower R 2 (0.261, 0.228-0.294 and 0.260, 0.226-0.293, respectively). Chromogranin b (CHGB), Cystatin-M/E (CST6), leptin (LEP), and prolargin (PRELP) were the proteins consistently selected across all models. Conclusion: Plasma proteins add to the clinical and genetic risk factors in predicting a cIMT measurement. Our findings implicate blood pressure and extracellular matrix-related proteins in cIMT pathophysiology.

Carotid Intima-Media Thickness in Indian Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and a Meta-Analysis.

There is a significant association of non-alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD). Most CVDs begin with atherosclerosis in the arteries, which can be reliably measured as the carotid intima-media thickness (CIMT) by ultrasound. Given that ethnic and regional differences have an impact on NAFLD, we aimed to evaluate the association of NAFLD patients from India with subclinical atherosclerosis, measured as CIMT. A thorough literature search was performed on four electronic databases using combinations of several keywords. The relevant data were pooled in a random or fixed-effect model, based on heterogeneity, to calculate the pooled standardised mean difference (SMD), or odds ratio (OR) with 95% confidence interval (CI). The final analysis included a total of 15 studies with 1196 NAFLD and 1482 control subjects. NAFLD patients had a 21.3% higher mean CIMT than the controls. The pooled SMD was 1.001 (95% CI: 0.627-1.375, p < 0.001). Three studies that balanced cardiometabolic risk factors found a similar association (p = 0.037). Furthermore, NAFLD was significantly associated with the presence of high (>0.8 mm) CIMT (pooled OR = 5.4, 95% CI: 2.0-14 .9) and carotid plaques (pooled OR = 10.24, 95% CI: 5.74-18.26). The mean CIMT was also higher in diabetic NAFLD than in the diabetic control (pooled SMD = 1.07, 95% CI = 0.818-1.324, p < 0.001). There is a significant positive association between the marker of subclinical atherosclerosis and NAFLD in India. This might give more light on screening and follow-up plans for such patients.

Abdominal aorta intima-media thickness in children with hypothyroidism.

Hypothyroidism is associated with atherosclerosis, which is attributed mainly to an atherogenic lipid profile. Increased intima-media thickness (IMT) is the first structural change detected in atherosclerosis. This prospective cohort study investigated lipid profile and abdominal aorta IMT in patients newly-diagnosed with hypothyroidism and their change one year post-treatment. It included fifty patients divided into three groups according to their diagnosis: congenital hypothyroidism (CH), Acquired and CH stopped treatment/uncontrolled group. They were subjected to history, auxological, blood pressure, non-fasting lipid profile, and abdominal aorta IMT measurement by abdominal ultrasound. These demonstrated high basal cholesterol, triglycerides, and LDL (259.64 ± 82.06, 193.94 ± 71.54, and 144.70 ± 48.46 mg/dl, respectively) and significant reduction after treatment (216.66 ± 44.60, 165.70 ± 53.58 and 123.26 ± 29.79 mg/dl, respectively). Low basal HDL (47.92 ± 10.08 mg/dl) increased significantly (57.56 ± 7.94 mg/dl) after treatment. Abdominal aorta IMT decreased significantly after treatment and achievement of euthyroidism (1.47 ± 0.49 and 1.33 ± 0.41 mm, respectively). In conclusion, upon treatment of hypothyroidism and achievement of euthyroidism, abdominal aorta IMT, cholesterol, triglycerides, and LDL decreased significantly, and HDL increased. Abdominal aorta IMT measurement is an easy and feasible way for the early detection of atherosclerosis.

Vascular-endothelial adaptations following low and high volumes of high-intensity interval training in patients after myocardial infarction.

BACKGROUND: Determinants of coronary artery disease, such as endothelial dysfunction and oxidative stress, could be attenuated by high-intensity aerobic interval exercise training (HIIT). However, the volume of this type of training is not well established. OBJECTIVE: To assess the impact of two volumes of HIIT, low (LV-HIIT, <10 min at high intensity) and high (HV-HIIT, >10 min at high intensity), on vascular-endothelial function in individuals after an acute myocardial infarction (AMI). MATERIALS AND METHODS: Clinical trial in 80 AMI patients (58.4 ± 8.3 years, 82.5% men) with three study groups: LV-HIIT (n = 28) and HV-HIIT (n = 28) with two sessions per week for 16 weeks and control group (CG, n = 24) with unsupervised physical activity recommendations. Endothelial function (brachial flow-mediated dilation, FMD), atherosclerosis (carotid intima-media thickness ultrasound, cIMT), and levels of oxidized low-density lipoprotein (ox-LDL) as a marker of oxidative stress were determined before and after the intervention period. RESULTS: After the intervention, in the exercise groups, there was an increase in FMD (LV-HIIT, ↑58.8%; HV-HIIT, ↑94.1%; p < 0.001) concurrently with a decrease in cIMT (LV-HIIT, ↓3.0%; HV-HIIT, ↓3.2%; p = 0.019) and LDLox (LV-HIIT, ↓5.2%; HV-HIIT, ↓8.9%; p < 0.001), with no significant changes in the CG. Furthermore, a significant inverse correlation was observed between ox-LDL and endothelial function related to the volume of HIIT training performed (LV-HIIT: r = -0.376, p = 0.031; HV-HIIT: r = -0.490, p < 0.004), with no significance in the CG (r = 0.021, p = 0.924). CONCLUSION: In post-AMI patients, HIIT may lead to a volume-dependent enhancement in endothelial function, attributed to a decrease in oxidative stress, with added beneficial effects in reducing vascular wall thickness. An LV-HIIT program, with less than 10 min at high intensity per session, has proven enough efficiency to initiate favorable vascular-endothelial adaptations, potentially reducing cardiovascular risk among patients with coronary artery disease. TRIAL REGISTRATION: INTERFARCT, ClinicalTrials.gov: NCT02876952.

Assessing the Influence of Long-Term Gender-Affirming Hormone Therapy on Cardiovascular Risk in Transgender Men through Carotid Intima-Media Thickness.

Background: Transgender men use exogenous androgen for male pattern virilization. Hysterectomy and bilateral salpingo-oophorectomy (HBSO) is performed to stop the endogenous estrogen secretion. Cardiovascular disease (CVD) risk has been shown to increase with long-term use of androgens and the removal of estrogen. We aimed to investigate the CVD risk in these individuals by measuring internal and common carotid artery intima-media thicknesses (CIMT). Methods: In this cohort study, data were collected from transgender men who had undergone HBSO and used androgens for at least two years (median treatment duration was 5 years in our research). Cisgender women in the same age range were selected as the control group. Demographics, vital signs, and hematological values of transgender patients and cisgender women subjects in the control group were noted. CVD markers were compared with sonographically measured CIMT values. Results: The mean age and body mass index (BMI) of the study group were 32.6 and 25.3, respectively. Weight, systolic-diastolic blood pressure, hemoglobin, hematocrit, low-density lipoprotein (LDL), serum triglyceride (TG), HbA1c levels, internal CIMT, and common CIMT values of the study group were higher, while the high-density lipoprotein (HDL) level was significantly lower compared the control group (p1 = 0.025, p2 = 0.010, p3 = 0.002, p4 = 0.001, p5 = 0.001, p6 = 0.012, p7 = 0.008, p8 = 0.007, p9 = 0.013, and p10 = 0.001). There was also an increase in the body weight, BMI, LDL, and TG levels of the study group after the testosterone treatment (p1 = 0.025, p2 = 0.019, p3 = 0.001, p4 = 0.001, and p5 = 0.001). Conclusions: We demonstrated that the use of testosterone therapy in transgender men is associated with higher CIMT values. While further investigation is needed to assess morbidity and mortality rates, we recommend that regular clinical and radiological examinations be performed in these individuals to accurately evaluate the risk of CVD.

The impact of vildagliptin as an add-on therapy on matrix metalloproteinase-14 levels, liver stiffness and subclinical atherosclerosis in adolescents with type 1 diabetes and non-alcoholic steatohepatitis: A randomized controlled trial.

AIM: Many patients with type 1 diabetes mellitus (T1DM) met the histological criteria for non-alcoholic steatohepatitis (NASH), which leads to cardiovascular disease morbidity and mortality. Matrix metalloproteinase-14 (MMP-14) is involved in cardiovascular disease and atherosclerosis. OBJECTIVES: To assess the impact of oral dipeptidyl peptidase-4 inhibitor, vildagliptin, as adjunctive therapy on NASH in adolescents with T1DM and its effect on glycaemic control, MMP-14 levels and carotid intima media thickness (CIMT). METHODS: Sixty adolescents with T1DM and NASH were randomly assigned to receive oral vildagliptin (50 mg once daily) for 6 months or not. Glycated haemoglobin, lipid profile, hepatic steatosis index, triglyceride glucose (TyG) index and MMP-14 levels were assessed. Transient elastography with controlled attenuation parameter (CAP) was performed together with measuring CIMT. RESULTS: By transient elastography, 12 (20%) patients with T1DM with NASH had elevated liver stiffness ≥7 kPa (F2 stage or higher). Baseline MMP-14 was positively correlated to insulin dose (p = 0.016), triglycerides and TyG index, CIMT, liver stiffness and CAP levels among the studied patients (p < 0.001 for all). After 6 months, patients with T1DM on vildagliptin therapy had significantly lower glycated haemoglobin, lipid profile, hepatic steatosis index and TyG index, as well as MMP-14 (p < 0.001). CIMT, liver stiffness and CAP were significantly decreased post-therapy compared with baseline levels and compared with the control group (p < 0.001). Vildagliptin was safe and well-tolerated. CONCLUSIONS: Administration of vildagliptin for adolescents with T1DM and NASH improved glycaemic control, dyslipidaemia and MMP-14 levels and decreased liver stiffness and CIMT; hence, reducing subclinical atherosclerosis and disease progression.

Cardiovascular Risk in People Living with Human Immunodeficiency (HIV) Viremia Suppression in a Young, Mid-Eastern European Population - Preliminary Study.

Purpose: People living with HIV are twice as likely to develop cardiovascular diseases (CVDs) and myocardial infarction related to atherosclerosis than the uninfected population. This study aimed to evaluate the prevalence of subclinical atherosclerosis in a young, mid-eastern European population of PLWH receiving ART for undetectable viremia. Patients and Methods: This was a single-centre study. We included 34 patients below 50 years old, treated in Szczecin, Poland, with confirmed HIV-1 infection, treated with antiretroviral therapy (ART), and undetectable viremia. All patients underwent coronary artery computed tomography (CACT), carotid artery intima-media thickness (IMT) evaluation, and echocardiography. Results: In the primary assessment, only two (5.8%) patients had an increased CVD risk calculated using the Framingham Risk Score (FRS), but we identified coronary or carotid plaques in 26.5% of the patients. Neither traditional risk factors nor those associated with HIV significantly influenced the presence of the plaque. IMT was significantly positively correlated with age and the FRS (R=0.38, p=0.04). Relative wall thickness assessed in echocardiography was higher in those with plaque (0.49 vs 0.44, p=0.04) and significantly correlated with IMT (R=0.38, p=0.04). Conclusion: In our population, more than a quarter of PLWH with undetectable viremia had subclinical atherosclerosis in either the coronary or carotid arteries. The FRS underpredicted atherosclerosis in this population. The role of RWT as a possible early marker of atherosclerosis needs further studies.

Subclinical Atherosclerosis Progression in Low-Risk, Middle-Aged Adults: Carotid Leads Femoral in IMT Increase but Not in Plaque Formation.

This study investigated subclinical atherosclerosis progression in low-risk, middle-aged adults (N = 141; a mean age of 49.6 ± 4.7 years) using a 5-year ultrasound follow-up. We compared the involvement of the carotid and femoral arteries. METHODS: Clinical data, risk factors, carotid/femoral intima-media thickness (IMT), and plaque presence were analyzed. RESULTS: Cardiovascular risk factors and scores increased significantly at follow-up. Both carotid and femoral mean IMT increased (p < 0.001). While plaque prevalence rose and was similar in both arteries (carotid: 4.8% to 17.9%, femoral: 3.6% to 17.7%, p < 0.001 for both), the progression of plaque burden was greater in femorals. Notably, the carotid mean IMT demonstrated a faster yearly progression rate compared to the mean femoral IMT. The prevalence of pathological nomogram-based mean IMT right or left was higher in the carotids (52.9% to 78.8%, p < 0.001) compared to femorals (23.2% to 44.7%, p < 0.001), with a significant increase at the end of follow-up in both territories. CONCLUSIONS: This study demonstrates significant subclinical atherosclerosis progression in low-risk, middle-aged adults over 5 years. Carotid arteries showed a faster progression rate of mean IMT and a higher prevalence of pathological nomogram-based mean IMT compared to the femoral arteries. However, plaque burden was similar in both territories, with greater progression in femorals. Identifying carotid and femoral atherosclerosis burden may be a valuable tool for risk stratification in this population.

The Effect of Statins on Carotid Intima-Media Thickness and C-Reactive Protein in Type 2 Diabetes Mellitus: A Meta-Analysis.

BACKGROUND: The effect of statins on CIMT progression and C-reactive protein (CRP) in T2DM patients is widely reported. However, some studies demonstrated no effect of statins on CIMT and CRP in T2DM patients, while others reported otherwise. Thus, the current study comprehensively and quantitatively analyzes data from previous studies to evaluate the overall effect of statins on CIMT and CRP in T2DM to rule out any inconsistencies observed in previous clinical evidence. Therefore, the aim of this meta-oanalysis was to evaluate the effect of statins on CIMT progression and CRP in T2DM. METHODS: A comprehensive search for studies was performed using PubMed, Scopus, Web of Sciences, and the Cochrane Library, for publications from their inception to 16 July 2024. The meta-analysis was conducted using Jamovi (version 4.2.8) and Review Manager (version 5.4), with the overall effect sizes reported as standardized mean differences (SMD) and 95% confidence intervals (CI). RESULTS: Evidence from eleven studies (fifteen statin dosages) that met the inclusion criteria with a sample size of 983 T2DM patients on statin treatment was analyzed. The overall effect size from the random effect model meta-analysis showed a reduction in the CIMT status amongst T2DM patients post-statin treatment compared to at baseline [SMD = -0.47, 95%CI (-0.76, -0.18), p = 0.001]. Furthermore, there was a reduction in the level of CRP in T2DM patients post-treatment [SMD = -1.80, 95% CI (-2.76, -0.84), p < 0.001]. CONCLUSIONS: Evidence gathered in this study suggests that statin therapy effectively reduces CIMT and CRP levels among patients living with T2DM. Interestingly, this evidence suggests that 20 mg of atorvastatin is more effective in reducing CIMT and CRP. Therefore, we recommend conducting further trials with larger sample sizes and proper methodology for T2DM.

Relationship of proteins and subclinical cardiovascular traits in the population-based LIFE-Adult study.

BACKGROUND AND AIMS: Understanding molecular processes of the early phase of atherosclerotic cardiovascular disease conditions is of utmost importance for early prediction and intervention measures. METHODS: We measured 92 cardiovascular-disease-related proteins (Olink, Cardiovascular III) in 2024 elderly participants of the population-based LIFE-Adult study. We analysed the impact of 27 covariables on these proteins including blood counts, cardiovascular risk factors and life-style-related parameters. We also analysed protein associations with 13 subclinical cardiovascular traits comprising carotid intima media thickness, plaque burden, three modes of Vicorder-based pulse-wave velocities, ankle-brachial index and ECLIA-based N-terminal prohormone of brain natriuretic peptide (NT-proBNP). RESULTS: Estimated glomerular filtration rate, triglycerides and sex where the most relevant covariables explaining more than 1 % variance of 49, 22 and 20 proteins, respectively. A total of 43 proteins were significantly associated with at least one of the analysed subclinical cardiovascular traits. NT-pro-BNP, brachial-ankle pulse-wave velocity (baPWV) and parameters of carotid plaque burden accounted for the largest number of associations. Association overlaps were relatively sparse. Only growth/differentiation factor 15, low density lipoprotein receptor and interleukin-1 receptor type 2 are associated with these three different cardiovascular traits. We confirmed several literature findings and found yet unreported associations for carotid plaque presence (von-Willebrand factor, galectin 4), carotid intima-media thickness (carboxypeptidase A1 andB1), baPWV (cathepsin D) and NT-proBNP (cathepsin Z, low density lipoprotein receptor, neurogenic locus homolog protein 3, trem-like transcript 2). Sex-interaction effects were observed, e.g. for spondin-1 and growth/differentiation factor 15 likely regulated by androgen response elements. CONCLUSIONS: We extend the catalogue of proteome biomarkers possibly involved in early stages of cardiovascular disease pathologies providing targets for early risk prediction or intervention strategies.

Heritability of carotid intima-media thickness and inflammatory factors of atherosclerosis in a Chinese population.

Carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis, has been found to be associated with incident stroke. High-sensitivity C-reactive protein (CRP) and fibrinogen have been demonstrated to be associated with atherosclerosis. Previous studies on heritability estimates of IMT, CRP, and fibrinogen among Chinese populations are limited. This study aims to estimate the heritability of these risk factors in residents who participated in the Taichung Community Health Study (TCHS) and their family members. A total of 2671 study subjects from 805 families were enrolled in the study, selected from a random sample of TCHS participants and their family members. CRP, and fibrinogen were obtained from each participant, and a questionnaire interview was conducted. cIMT was measured by high-resolution B-mode ultrasound and expressed as the mean of the maximum. Heritability estimates and the familial correlation of cIMT, CRP, and fibrinogen among family pairs were determined with SAGE software. With multivariate adjustments, significant heritability was found for cIMT (h2 = 0.26, P < 0.001), CRP (h2 = 0.34, P < 0.001), and fibrinogen (h2 = 0.48, P < 0.001). The intrafamilial correlation coefficients for the three indexes in the parent-offspring pairs were significant (P < 0.001) and ranged from 0.17 to 0.41. The full sibship correlations were also significant (P < 0.001) for the three indexes and ranged from 0.19 to 0.47. This study indicates that a moderate proportion of the variability in CRP, fibrinogen, and cIMT can be attributed to genetic factors in Chinese populations. The findings suggest that CRP is associated with cIMT, whereas no significant association exists between fibrinogen and cIMT.

Association between metabolically healthy obesity and carotid intima-media thickness in Korean adolescents with overweight and obesity.

PURPOSE: Data regarding the association between metabolically healthy obesity (MHO) and preclinical atherosclerosis in childhood are lacking. Carotid intima-media thickness (cIMT) is a noninvasive method used to assess cardiovascular risk. This study examined the relationships among cIMT, metabolic phenotypes, and cardiometabolic risk factors (CMRFs) in overweight and obese adolescents. METHODS: Anthropometric, biochemical, and cIMT data were collected. The study participants were categorized as MHO or metabolically unhealthy obesity (MUO) based on insulin resistance. CMRFs were assessed using blood pressure (BP); levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), and fasting plasma glucose; or a diagnosis of diabetes mellitus. Differences in cIMT values were evaluated according to the metabolic phenotype and factors associated with cIMT. RESULTS: Among the 111 participants (80 boys, 72.1%), 23 (20.7%) were classified as MHO and 88 (79.3%) as MUO. The MHO group exhibited lower glycated hemoglobin and triglyceride levels and higher HDL-C levels compared to those exhibited by the MUO group (all P<0.01). The cIMT values did not differ significantly between the MHO and MUO groups. The high cIMT tertile group revealed higher systolic BP compared to that exhibited by the low cIMT tertile group (123.7±2.1 mmHg vs. 116.9±1.6 mmHg, P=0.028). Mean cIMT was positively correlated with age (ß=0.009) and body mass index (BMI) (ß=0.033) after adjusting for covariates (both P<0.05). CONCLUSION: In overweight and obese Korean adolescents, cIMT was associated with age and BMI but not with metabolic phenotype or CMRFs. Further research is warranted to determine the relationship between cIMT during adolescence and cardiovascular outcomes during adulthood.