Primary Sjögren's syndrome independently promotes premature subclinical atherosclerosis.

OBJECTIVES: Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage. METHODS: Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers. RESULTS: Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6-65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren's Syndrome Disease Activity Index (p<0.001) and anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed. CONCLUSIONS: Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus.

BACKGROUND: Compelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: This study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM. METHODS: Serum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models. RESULTS: This cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05). CONCLUSIONS: T2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

Deep phenotyping of dementia in a multi-ethnic cardiovascular cohort: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Our understanding of the specific aspects of vascular contributions to dementia remains unclear. OBJECTIVES: We aim to identify the correlates of incident dementia in a multi-ethnic cardiovascular cohort. METHODS: A total of 6806 participants with follow-up data for incident dementia were included. Probable dementia diagnoses were identified using hospitalization discharge diagnoses according to the International Classification of Diseases Codes (ICD). We used Random Forest analyses to identify the correlates of incident dementia and cognitive function from among 198 variables collected at the baseline MESA exam entailing demographic risk factors, medical history, anthropometry, lab biomarkers, electrocardiograms, cardiovascular magnetic resonance imaging, carotid ultrasonography, coronary artery calcium and liver fat content. Death and stroke were considered competing events. RESULTS: Over 14 years of follow-up, 326 dementia events were identified. Beyond age, the top correlates of dementia included coronary artery calcification, high sensitivity troponin, common carotid artery intima to media thickness, NT-proBNP, physical activity, pulse pressure, tumor necrosis factor-α, history of cancer, and liver to spleen attenuation ratio from computed tomography. Correlates of cognitive function included income and physical activity, body size, serum glucose, glomerular filtration rate, measures of carotid artery stiffness, alcohol use, and inflammation indexed as IL-2 and TNF soluble receptors and plasmin-antiplasmin complex. CONCLUSION: In a deeply phenotyped cardiovascular cohort we identified the key correlates of dementia beyond age as subclinical atherosclerosis and myocyte damage, vascular function, inflammation, physical activity, hepatic steatosis, and history of cancer.

Mobility-related brain regions linking carotid intima-media thickness to specific gait performances in old age.

BACKGROUND: Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations. METHODS: A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators. RESULTS: Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (ß = 0.129, p = 0.010) as well as gait performances related to pace (ß=-0.213, p < 0.001) and symmetry (ß = 0.096, p = 0.045). Besides, gait performances were correlated with mobility-related brain regions responsible for motor, visuospatial attention, executive control, memory, and balance (all FDR < 0.05). Notably, significant regions differed depending on the gait outcomes measured. The primary motor (41.9%), sensorimotor (29.3%), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules) (13.8%), entorhinal cortex (36.4%), and motor imagery (precuneus, parahippocampus, posterior cingulated cortex) (27.3%) mediated the association between increased carotid intima-media thickness and poorer Timed-Up-and-Go performance. For the pace domain, the primary motor (37.5%), sensorimotor (25.8%), visuospatial attention (12.3%), entorhinal cortex (20.7%), motor imagery (24.9%), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) (11.6%) acted as mediators. CONCLUSIONS: Carotid intima-media thickness is associated with gait performances, and mobility-related brain volume mediates these associations. Moreover, the distribution of brain regions regulating mobility varies in the different gait domains. Our study adds value in exploring the underlying mechanisms of gait disturbance in the aging population.

Association between atherosclerosis and height loss among older individuals.

Atherosclerosis and height loss are each reportedly associated with cardiovascular disease. However, no studies have found an association between atherosclerosis and height loss. A retrospective study of 2435 individuals aged 60-89 years who underwent annual health check-ups was conducted. Atherosclerosis was defined as carotid intima-media thickness (CIMT) ≥ 1.1 mm. Height loss was defined as being in the highest quintile of height decrease per year, as in our previous studies. Among study participants, 555 were diagnosed as having atherosclerosis. Independent of known cardiovascular risk factors, atherosclerosis was positively associated with height loss. The adjusted odds ratio (OR) was 1.46 (95% confidence interval, 1.15, 1.83). Essentially the same associations were observed for men and women. The adjusted OR (95% CI) was 1.43 (1.01, 2.04) for men and 1.46 (1.07, 1.99) for women. Among older individuals, atherosclerosis is associated with height loss. This result can help clarify the mechanism underlying the association between height loss and cardiovascular disease.

Long-term effects of abatacept on atherosclerosis and arthritis in older vs. younger patients with rheumatoid arthritis: 3-year results of a prospective, multicenter, observational study.

BACKGROUND: We aimed to reveal the effect of abatacept (ABT) on atherosclerosis in rheumatoid arthritis (RA) patients, 3-year efficacy for arthritis, and safety in a population of older vs. younger patients. METHODS: In this open-label, prospective, observational study, patients were stratified into four groups: younger (20-64 years old) and older (≥ 65 years) patients taking ABT (AY and AO) and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (CY and CO). Primary endpoints were change from baseline in mean intima-media thickness (IMT) of the common carotid artery, IMT max (bulbus, bifurcation, and internal and common carotid artery), and plaque score at Week 156. Disease activity, retention rate, and adverse effects were also evaluated. RESULTS: The ABT group (AY + AO) tended to have smaller increases in mean IMT, max IMT, and plaque score than the csDMARD group (CY + CO) at Week 156, although the differences between groups were not statistically significant. Multivariate analysis showed significantly lower increases in plaque score with ABT than with csDMARDs, only when considering disease activity at 156 weeks (p = 0.0303). Proportions of patients with good or good/moderate European League Against Rheumatism response were higher in the ABT group, without significant difference between older and younger patients. No significant differences were observed in ABT retention rates between older and younger patients. Serious adverse effects, especially infection, tended to be more frequent with ABT than with csDMARDs, although no significant differences were found. CONCLUSIONS: ABT may decelerate atherosclerosis progression and may be useful for patients with high risk of cardiovascular disease, such as older patients. TRIAL REGISTRATION NUMBER: UMIN000014913.

Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

Prediction of the left ventricular mass index in hypertensive patients using the product of red cell distribution width and mean corpuscular volume.

The product of red cell distribution width (RDW) and mean corpuscular volume (MCV) has been identified as an indicator of target organ damage in cases of hypertension. However, the role of the RDW-MCV product in assessing carotid alteration, renal damage, and left ventricular hypertrophy in patients with hypertension has not been elucidated. In this cross-sectional study, a total of 1115 participants with hypertension were included. The RDW and MCV at admission were measured using an automated hematology analyzer. Organ damage was determined by the left ventricular mass index (LVMI), carotid intima-media thickness, and estimated glomerular filtration rate. The prevalence rates of carotid alteration and left ventricular hypertrophy were 57.0% and 18.0%, respectively. A higher RDW-MCV product and RDW were observed in hypertensive patients who developed carotid alteration. After adjusting for potential confounding factors, the correlations of the RDW-MCV product (P = .285) and RDW (P = .346) with carotid alteration were not significant. Moreover, the analysis of variance showed no significant correlation between RDW and LVMI (P = .186). However, the RDW-MCV product was higher in individuals with a high LVMI compared to those with a normal LVMI. Multivariable linear regression analysis revealed that the RDW-MCV product was independently associated with the LVMI (ß = 2.519, 95% CI: 0.921-4.116; P = .002), but not the estimated glomerular filtration rate (ß = -0.260, 95% CI: -2.031-1.511; P = .773). An elevated RDW-MCV product may be a predictor for left ventricular hypertrophy in patients with hypertension.

Evaluation of measured and calculated small dense low-density lipoprotein in capillary blood and association with the metabolic syndrome.

BACKGROUND AND AIMS: Small-dense-low-density-lipoprotein cholesterol (sdLDL-C) is proatherogenic and not commonly measured. The aims were to evaluate capillary blood and its stability for sdLDL-C measurement and measure sdLDL-C in patients with metabolic syndrome (MS). METHODS: 182 patients were studied (49 with MS). sdLDL-C was measured by electrophoresis (LipoPrint®), direct measurement (Roche Diagnostics) and Sampson equation. Intima-media thickness (IMT) and presence of atheroma was evaluated. sdLDL-C was compared in paired venous and capillary blood according to CLSI-EP09c (n = 40). sdLDL-C stability was studied after 24 h at room temperature (RT). RESULTS: sdLDL-C in capillary blood and venous blood showed agreement with the direct measurement (bias: 4.17 mg/dL, LOA 95 %:-5.66; 13.99) and estimation (bias:8.12 mg/dL, LOA 95 %:-8.59; 24.82). sdLDL-C is stable in capillary blood for 24 h at RT. The electrophoretic method yielded lower (p < 0.05) sdLDL-C than the equation or direct measurement. Patients with MS had (p < 0.05) higher sdLDL-C (%) than patients without MS. Patients with atheroma plaques had higher sdLDL-C (p < 0.05). Estimated sdLDL-C correlated with IMT (r = 0.259, p < 0.001). CONCLUSIONS: Capillary blood is an alternative to venous blood for sdLDL-C measurement and is stable for 24 h after collection. Estimated and directly measured sdLDL-C associate with the MS being accessible tools for cardiovascular risk assessment.

TRIGLYCERIDE - GLUCOSE INDEX, REMNANT CHOLESTEROL AND COMMON CAROTID ARTERY INTIMA-MEDIA THICKNESS AS AN ATHEROSCLEROTIC MARKER IN ISCHEMIC STROKE PATIENTS.

Ischemic stroke (IS) is a major global health concern, often resulting from atherosclerosis and insulin resistance (IR). The triglyceride-glucose index (TyG index), remnant cholesterol (RC), and common artery intima-media thickness (CIMT) are potential markers for assessing atherosclerosis and cardiovascular risk in IS patients. A cross-sectional study was conducted to investigate the association between TyG index, RC, CIMT, and IS in adult patients recruited from a hospital. Demographic, clinical, and laboratory data were collected, and statistical analysis was performed. The study included 50 participants with a balanced gender distribution and a mean age of 57.64 years. Laboratory characteristics showed notable values, and CIMT > 0.6 mm was associated with higher NIH Stroke Scale scores. RC exhibited significant correlations with age, CIMT, lipid profile, and TyG index. The study highlights the potential of TyG index, RC, and CIMT as atherosclerotic markers in IS patients. Favorable prognostic outcomes were observed, emphasizing the importance of early diagnosis and management to improve patient outcomes.

Evaluation of the relationship between atherosclerosis and Helicobacter pylori infection with measurement of growth differentiation factor 15 and atherosclerosis indicators in adults with no comorbidity / Evaluación de la relación entre aterosclerosis e infección por Helicobacter pylori con medición del factor de diferenciación de crecimiento 15 e indicadores de aterosclerosis en adultos sin comorbilidad

Background The aim of this study was to investigate presence of subclinical atherosclerosis by measuring carotid intima-media thickness (CIMT) in patients with Helicobacter pylori (HP) and to assess effects of HP on atherosclerosis by evaluating markers of atherosclerosis and blood growth differentiation factor (GDF-15) levels. Materials and methods This cross-sectional study included 59 patients without comorbid disease who had HP and 30 healthy controls without HP in upper endoscopic biopsy. In order to assess atherosclerosis, the CIMT measurement was performed by sonography. Serum GDF-15 level was measured by ELISA method. In all patients, atherosclerosis markers were recorded. Atherogenic indices were calculated, including Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), plasma atherogenic index (PAI; log TG/HDL-c), non-HDL-c (TH-HDL-c) and atherogenic coefficient (AC; non-HDL-HDL-c). Results The GDF-15 level and CIMT were significantly higher in HP-positive group when compared to HP-negative group (p≤0.001). There was a significant correlation between serum GDF-15 level and CIMT (r=0.445; p≤0.001). There was no correlation between other atherosclerosis markers and serum GDF-15 level or CIMT. The bacterial intensity on endoscopic specimen was only correlated with CIMT (p<0.001). Vitamin B12 and D levels were comparable among groups. Conclusion This study suggested that there was a correlation between GDF-15 level and subclinical atherosclerosis development in patients with HP. However, GDF-15 level, which was found to be elevated while atherogenic indices were normal, can be an earlier marker for subclinical atherosclerosis. (AU)

Antecedentes El objetivo de este estudio fue investigar la presencia de aterosclerosis subclínica mediante la medición del grosor íntima-media de la carótida (GIMC) en pacientes con Helicobacter pylori y evaluar los efectos de H.pylori sobre la aterosclerosis mediante la evaluación de marcadores de aterosclerosis y de niveles de factor de diferenciación del crecimiento sanguíneo (growth differentiation factor 15 [GDF-15]). Materiales y métodos Este estudio transversal incluyó 59 pacientes sin enfermedad comórbida que tenían H.pylori y 30 controles sanos sin H.pylori en la biopsia endoscópica superior. Para evaluar la aterosclerosis, la medición de GIMC se realizó mediante ecografía. El nivel de GDF-15 en suero se midió mediante el método ELISA. En todos los pacientes se registraron marcadores de aterosclerosis. Se calcularon los índices aterogénicos, incluyendo el índice de riesgo de Castelli I y II (TG/cHDL y cLDL-cHDL, respectivamente), el índice aterogénico plasmático (PAI; log TG/HDL-c), no-cHDL (TH-cHDL) y el coeficiente aterogénico (no-HDL-cHDL). Resultados Los niveles de GDF-15 y de GIMC fueron significativamente más altos en el grupo H.pylori positivo en comparación con el grupo H.pylori negativo (p≤0,001). Hubo una fuerte correlación entre el nivel sérico de GDF-15 y el GIMC (r=0,445; p≤0,001). No hubo correlación entre otros marcadores de aterosclerosis y el nivel sérico de GDF-15 o GIMC. La intensidad bacteriana en la muestra endoscópica solo se correlacionó con GIMC (p≤0,001). Los niveles de vitaminaB12 y de vitaminaD fueron comparables entre los grupos. Conclusión Este estudio sugirió que había una correlación entre el nivel de GDF-15 y el desarrollo de aterosclerosis subclínica en pacientes con H.pylori. Sin embargo, el nivel de GDF-15, que se encontró elevado mientras que los índices aterogénicos eran normales, puede ser un marcador temprano de aterosclerosis subclínica. (AU)

Effect of fasting glucose levels on carotid intima-media thickness in premenopausal versus postmenopausal women.

Objective: To investigate the relationship between fasting blood glucose (FBG) and carotid intimamedia thickness (IMT) in premenopausal and postmenopausal women. Subjects and methods: The study enrolled 2,959 women seen at the Maanshan People's Hospital of Anhui Province from December 2013 to December 2018. Carotid IMT was measured using Doppler ultrasound. Linear regression and R smoothing curves were used to analyze the relationship between blood glucose level and carotid IMT in the premenopausal and postmenopausal groups. Results: Postmenopausal compared with premenopausal women had higher mean IMT (mIMT; 0.81 ± 0.23 mm versus 0.70 ± 0.14 mm, respectively, p < 0.001) and maximum IMT (maxIMT; 0.86 ± 0.35 mm versus 0.74 ± 0.16 mm, respectively, p < 0.001) values. On linear regression analysis, mIMT values increased with increasing FBG values when FBG level was ≤ 7 mmol/L, but no significance was found between FBG and maxIMT. After stratification by menopausal status, mIMT and maxIMT increased with increasing FBG when FBG was ≤ 7 mmol/L in the premenopausal group. In the postmenopausal group, mIMT and maxIMT increased with increasing FBG. After adjustment for covariate factors, the relationship between FBG and mIMT remained the same as before the adjustment, but when FBG was ≤ 11 mmol/L, the maxIMT increased with increasing FBG. In the stratification analysis, maxIMT increased with increasing FBG when FBG was ≤ 7 mmol/L in the premenopausal group, while both mIMT and maxIMT increased with increasing FBG when FBG was > 10 mmol/L in the postmenopausal group. Conclusion: Levels of FBG contributed more to increased IMT in postmenopausal than premenopausal women. The influence of FBG was greater on maxIMT than mIMT. Additionally, FBG was helpful in assessing focal thickening of the carotid intima.

Role of klotho and fibroblast growth factor 23 in arterial calcification, thickness, and stiffness: a meta-analysis of observational studies.

This meta-analysis was conducted to clarify the role of klotho and fibroblast growth factor 23 (FGF-23) in human arterial remodeling across recent studies, in terms of arterial calcification, thickness, and stiffness. A systematic literature search was conducted on five databases for articles up to December 2023. Arterial calcification, thickness, and stiffness were determined using the calcification score and artery affected, carotid intima-media thickness (CIMT), and pulse wave velocity (PWV), respectively. Sixty-two studies with a total of 27,459 individuals were included in this meta-analysis. Most studies involved chronic kidney disease patients. Study designs were mostly cross-sectional with only one case-control and nine cohorts. FGF-23 was positively correlated with arterial calcification (r = 0.446 [0.254-0.611], p < 0.0001 and aOR = 1.36 [1.09-1.69], p = 0.006), CIMT (r = 0.188 [0.02-0.354], p = 0.03), and PWV (r = 0.235 [0.159-0.310], p < 0.00001). By contrast, Klotho was inversely correlated with arterial calcification (r = - 0.388 [- 0.578 to - 0.159], p = 0.001) and CIMT (r = - 0.38 [- 0.53 to - 0.207], p < 0.00001). In conclusion, FGF-23 and Klotho were associated with arterial calcification, thickness, and stiffness, clarifying their role in arterial remodeling processes.

Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Intima-Media Thickness: Systematic Review and Meta-Analysis.

Background: Beyond glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been proposed to reduce the risk of cardiovascular events. The aim of the present systematic review and meta-analysis is to demonstrate the effects of GLP-1 RA and SGLT2is on intima-media thickness (IMT). Methods: PubMed, EMBASE, Web of Science, SCOPUS, and Google Scholar databases were searched from inception to September 9, 2023. All interventional and observational studies that provided data on the effects of GLP-1 RAs or SGLT2is on IMT were included. Critical appraisal was performed using the Joanna Briggs Institute checklists. IMT changes (preintervention and postintervention) were pooled and meta-analyzed using a random-effects model. Subgroup analyses were based on type of medication (GLP-1 RA: liraglutide and exenatide; SGLT2i: empagliflozin, ipragliflozin, tofogliflozin, and dapagliflozin), randomized clinical trials (RCTs), and diabetic patients. Results: The literature search yielded 708 related articles after duplicates were removed. Eighteen studies examined the effects of GLP-1 RA, and eleven examined the effects of SGLT2i. GLP-1 RA and SGLT2i significantly decreased IMT (MD = -0.123, 95% CI (-0.170, -0.076), P < 0.0001, I2 = 98% and MD = -0.048, 95% CI (-0.092, -0.004), P = 0.031, I2 = 95%, respectively). Metaregression showed that IMT change correlated with baseline IMT, whereas it did not correlate with gender, duration of diabetes, and duration of treatment. Conclusions: Treatment with GLP-1 RA and SGLT2i can lower IMT in diabetic patients, and GLP-1 RA may be more effective than SGLT2i.

The Relationship between Mitochondrial Genome Mutations in Monocytes and the Development of Obesity and Coronary Heart Disease.

BACKGROUND: Metabolic disorders, including obesity, are often accompanied by an increased risk of cardiovascular complications. Monocytes are the common link between obesity and cardiovascular diseases (CVDs). The bias of innate cellular immunity towards pro-inflammatory activation stimulates the development of diseases associated with chronic inflammation, in particular metabolic disorders, including obesity, as well as CVDs. Disorders in the functional state of monocytes and activation of inflammation may be associated with mitochondrial dysfunction. Mutations accumulating in mitochondrial DNA with age may lead to mitochondrial dysfunction and may be considered a potential marker for developing chronic inflammatory diseases. METHODS: The present study aimed to study the relationship between mitochondrial heteroplasmy in CD14+ monocytes and cardiovascular risk factors in 22 patients with obesity and coronary heart disease (CHD) by comparing them to 22 healthy subjects. RESULTS: It was found that single-nucleotide variations (SNV) A11467G have a negative correlation with total cholesterol (r = -0.82, p < 0.05), low density lipoproteins (LDL) (r = -0.82, p < 0.05), with age (r = -0.57, p < 0.05) and with mean carotid intima-media thickness (cIMT) (r = -0.43, p < 0.05) and a positive correlation with HDL level (r = 0.71, p < 0.05). SNV 576insC positively correlated with body mass index (BMI) (r = 0.60, p < 0.001) and LDL level (r = 0.43, p < 0.05). SNV A1811G positively correlated with mean cIMT (r = 0.60, p < 0.05). CONCLUSIONS: It was revealed that some variants of mitochondrial DNA (mtDNA) heteroplasmy are associated with CVD risk factors. The results demonstrate the potential for using these molecular genetic markers to develop personalized CVD and metabolic disorder treatments.

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.

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.

Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. METHODOLOGY: Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. RESULTS: No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. CONCLUSION: This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.

A Siamese ResNeXt network for predicting carotid intimal thickness of patients with T2DM from fundus images.

Objective: To develop and validate an artificial intelligence diagnostic model based on fundus images for predicting Carotid Intima-Media Thickness (CIMT) in individuals with Type 2 Diabetes Mellitus (T2DM). Methods: In total, 1236 patients with T2DM who had both retinal fundus images and CIMT ultrasound records within a single hospital stay were enrolled. Data were divided into normal and thickened groups and sent to eight deep learning models: convolutional neural networks of the eight models were all based on ResNet or ResNeXt. Their encoder and decoder modes are different, including the standard mode, the Parallel learning mode, and the Siamese mode. Except for the six unimodal networks, two multimodal networks based on ResNeXt under the Parallel learning mode or the Siamese mode were embedded with ages. Performance of eight models were compared via the confusion matrix, precision, recall, specificity, F1 value, and ROC curve, and recall was regarded as the main indicator. Besides, Grad-CAM was used to visualize the decisions made by Siamese ResNeXt network, which is the best performance. Results: Performance of various models demonstrated the following points: 1) the RexNeXt showed a notable improvement over the ResNet; 2) the structural Siamese networks, which extracted features parallelly and independently, exhibited slight performance enhancements compared to the traditional networks. Notably, the Siamese networks resulted in significant improvements; 3) the performance of classification declined if the age factor was embedded in the network. Taken together, the Siamese ResNeXt unimodal model performed best for its superior efficacy and robustness. This model achieved a recall rate of 88.0% and an AUC value of 90.88% in the validation subset. Additionally, heatmaps calculated by the Grad-CAM algorithm presented concentrated and orderly mappings around the optic disc vascular area in normal CIMT groups and dispersed, irregular patterns in thickened CIMT groups. Conclusion: We provided a Siamese ResNeXt neural network for predicting the carotid intimal thickness of patients with T2DM from fundus images and confirmed the correlation between fundus microvascular lesions and CIMT.