Carotid Atherosclerosis In Patients Research Articles

The Relationship between the complement system and subclinical carotid atherosclerosis in patients with rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) events and CV mortality. Subclinical carotid atherosclerosis is independently associated with rates of incident CV events among patients with RA. The complement system has been related to both the etiopathogenesis of RA and CV disease. In this study, we aimed to evaluate the association between a comprehensive assessment of the complement system and carotid intima media thickness and carotid plaque in patients with RA.Methods430 patients with RA were recruited. Functional assays of the three pathways of the complement system, utilizing new-generation techniques, were assessed. Additionally, serum levels of individual components of the complement system belonging to the three pathways were measured: C1q (classical), lectin (lectin), C2, C4, and C4b (classical and lectin), factor D and properdin (alternative), C3 and C3a (common), C5, C5a, and C9 (terminal), as well as regulators factor I and C1-inhibitor. Subclinical carotid atherosclerosis was evaluated by ultrasonography. Multivariable linear regression analysis was conducted to investigate the association between the complement system and carotid intima media thickness and carotid plaque.ResultsAfter multivariable adjustment, which included traditional CV risk factors and disease-related data, C3a and C5a exhibited significant positive correlations with carotid intima media thickness. Additionally, higher values of C1-inhibitor, properdin, C3, C5, and C5a were independently associated with the presence of carotid plaque.ConclusionThe complement system and subclinical carotid atherosclerosis are linked in patients with RA.

The predictive value of plasma uridine for type 2 diabetes and its atherosclerotic complications.

Uridine might be a common link between pathological pathways in diabetes and cardiovascular diseases. This study aimed to investigate the predictive value of plasma uridine for type 2 diabetes and type 2 diabetes with atherosclerosis. Individuals with type 2 diabetes (T2D) and healthy controls (n=218) were randomly enrolled in a cross-sectional study. Patients with T2D were divided into two groups based on carotid ultrasound: patients with carotid atherosclerosis (CA) (group DCA), and patients without CA (group D). Plasma uridine was determined using high-performance liquid chromatography-tandem mass spectrometry. Correlation and logistic regression analyses were used to analyze the results. Fasting and postprandial uridine were significantly increased in patients with T2D compared with healthy individuals. Logistic regression suggested that fasting and postprandial uridine were independent risk factors for T2D. The receiver operating characteristic (ROC) curve showed that fasting uridine had a predictive value on T2D (95% CI,0.686-0.863, sensitivity 74.3%, specificity 71.8%). Fasting uridine was positively correlated with LDL-c, FBG, and PBG, and negatively correlated with CP-0h and HOMA-IS. The change in postprandial uridine from fasting baseline (Δ uridine) was smaller in T2D patients with CA compared with those without (0.80(0.04-2.46) vs. 2.01(0.49-3.15), P=0.010). Δuridine was also associated with T2D with CA and negatively correlated with BMI, CP-0h, and HOMA-IR. Fasting uridine has potential as a predictor of diabetes. Δuridine is closely associated with carotid atherosclerosis in patients with T2D.

Circulating miR-423-5p levels are associated with carotid atherosclerosis in patients with chronic kidney disease

Background and aimsCarotid atherosclerosis is associated with an elevated risk of stroke in patients with chronic kidney disease. However, the molecular basis for the incidence of carotid atherosclerosis in patients with CKD is poorly understood. Here, we investigated whether circulating miR-423-5p is a crucial link between CKD and carotid atherosclerosis. Methods and resultsWe recruited 375 participants for a cross-sectional study to examine the occurrence of carotid plaque and plaque thicknesses. Levels of miR-423-5p were determined by qPCR analysis. We found that non-dialysis CKD patients had higher circulating exosomal and plasma miR-423-5p levels, and dialysis-dependent patients had lower miR-423-5p levels than non-dialysis CKD patients. After excluding for the influence of dialysis patients, linear regression analysis indicated that levels of circulating miR-423-5p are negatively correlated with eGFR (P < 0.001). Higher plasma miR-423-5p levels were associated with the incidence and severity of carotid plaques. In parallel, we constructed a murine model of CKD with a 5/6 nephrectomy protocol and performed RNA sequencing studies of aortic tissues. Consistent with these findings in CKD patients, circulating exosomal miR-423-5p levels in CKD mice were elevated. Furthermore, our RNA-seq studies indicated that the putative target genes of miR-423-5p were related to oxidative stress functions for aorta of CKD mice. ConclusionLevels of miR-423-5p are associated with the presence and severity of carotid plaque in CKD. Data from our mouse model suggests that miR-423-5p likely influences gene expression programs related to oxidative stress in aorta of CKD mice.

Albumin-Globulin Ratio and Common Carotid Artery Intima-Media Thickness in Patients with Ischemic Stroke

Background: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in acute ischemic stroke (AIS) remain uncertain. We investigated the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with AIS. background: The relationships between serum albumin, albumin-globulin (A/G) ratio, globulin and atherosclerosis in the setting of ischemic stroke are unclear. Methods: A total of 1,339 AIS patients were enrolled. Admission A/G ratio was divided into quartiles, and serum albumin and globulin levels were also categorized. Carotid atherosclerosis was detected through the assessment of common carotid artery intima-media thickness (cIMT), and abnormal cIMT was characterized by mean and maximum cIMT values of ≥1 mm. We evaluated the relationships between A/G ratio, albumin, globulin and abnormal cIMT, using multivariable logistic regression models. objective: We aimed to evaluate the associations between serum albumin, A/G ratio, globulin levels and carotid atherosclerosis in patients with ischemic stroke. Results: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was linked to a 59% decreased risk of abnormal mean cIMT (OR 0.41; 95% CI 0.29-0.60) and a 58% decreased risk of abnormal maximum cIMT (OR 0.42; 95% CI 0.30-0.60) when compared to the lowest quartile (Q1), respectively. Moreover, decreased albumin and elevated globulin levels were also associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided supplementary predictive capability beyond the already established risk factors, and the C-statistic of the A/G ratio for abnormal cIMT is larger than globulin (P &lt;0.01). Conclusion: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in AIS patients. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT. result: In the multivariable-adjusted analysis, the highest A/G ratio quartile (Q4) was associated with a 59% (OR 0.41; 95% CI 0.29-0.60) decreased risk of having abnormal mean cIMT and 58% (OR 0.42; 95% CI 0.30-0.60) decreased risk of having abnormal maximum cIMT in comparison to Q1, respectively. Moreover, decreased albumin and increased globulin levels were associated with abnormal mean cIMT and maximum cIMT. In addition, the A/G ratio provided incremental predictive capacity beyond established risk factors, and the C-statistic of A/G ratio for abnormal cIMT is larger than globulin (P&lt;0.01). conclusion: Decreased serum A/G ratio, albumin and elevated serum globulin were independently associated with abnormal cIMT in patients with ischemic stroke. Moreover, the A/G ratio appeared to be a better predictor of abnormal cIMT. other: No

Qualitative and quantitative ultrasound parameters of carotid atherosclerotic plaques in patients with moderate cardiovascular risk according to the SCORE scale: 7-year prospective follow-up study

Aim. To assess asymptomatic carotid atherosclerosis in patients with moderate cardiovascular risk over a 7-year prospective follow-up using non-invasive ultrasound markers.Material and methods. Eighty patients (47 men and 33 women) aged 53,1±5,9 years with moderate Systematic Coronary Risk Evaluation (SCORE) level, low-density lipoprotein cholesterol (LDL-C) of 2,7-4,8 mmol/l and asymptomatic hemodynamically insignificant (stenosis &lt;50%) carotid atherosclerosis (CA). Patients underwent CA ultrasound (PHILIPS IU22) at baseline and after 7 years. Plaque number, maximum plaque height, total plaque height, total CA stenosis, visual plaque morphology, gray-scale median (GSM), and intima- media thickness of the right and left common CAs were assessed. All patients were prescribed atorvastatin therapy at a dose of 10-40 mg until a target LDL-С level &lt;2,6 mmol/l was achieved.Results. During the follow-up period, a significant increase was noted in the number of plaques, the maximum and total plaque height, total CA stenosis, and intima- media thickness of the right and left common CAs. An increase in GSM was detected in 79% of plaques on statin therapy. Plaque echoicity increased by 4,90 [0,51; 17,41] (p &lt;0,001) or 7,2% [0,7%; 29%] (p&lt;0,001) over seven years. Regression analysis adjusted for sex and age showed the dependence of GSM changes (ΔGSM) on changes in the LDL-C level (ΔLDL-C) (p=0,049). With a decrease in LDL-C by 1 mmol/l, an increase in average GSM was noted by 5,9 (0,03-11,78). The maximum plaque height increased significantly after 7-year follow-up from 1,80 [1,50; 2,20] to 2,00 [1,63; 2,68] mm (p=0,044). In patients who reached a LDL-C level of 1,8 mmol/l, the maximum plaque height decreased more than in patients who did not reach this level (-0,07 [-0,45; 0,14] mm and 0,20 [-0,05; 0,40] mm, respectively (p=0,028)). Regression analysis adjusted for sex and age did not reveal a relationship between the change of maximum plaque height with ΔLDL-C and Δhigh-density lipoprotein cholesterol, but with LDL-C level after 7 years.Conclusion. Statin therapy in patients with CA stenosis &lt;50% stabilizes the plaques due to echogenicity increase. LDL-C &lt;1,8 mmol/l can lead to a decrease in maximum plaque height.

The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia

BackgroundDiabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia.MethodsThis study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients.ResultsIn symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P < 0.05). Furthermore, when compared to the fasting blood glucose (FBG) or triglyceride (TG) level, the TyG index had a greater area under the ROC curve for predicting coronary lesions and carotid plaques. The subgroup analysis demonstrated the TyG index to be an equally effective predictor of coronary and carotid artery disease, regardless of diabetes and hyperlipidaemia.ConclusionThe TyG index is a useful marker for predicting coronary and carotid atherosclerosis in patients with symptomatic CAD, regardless of diabetes mellitus and hyperlipidaemia. The TyG index is of higher value for the identification of both coronary and carotid atherosclerotic plaques than the FBG or TG level alone.

Long-term observation of estimated fluid volume reduction after the initiation of ipragliflozin in patients with type 2 diabetes mellitus: a sub-analysis from a randomized controlled trial (PROTECT)

Backgrounds/AimRecent studies have shown that the addition of sodium-glucose co-transporter 2 (SGLT2) inhibitors gradually reduces the estimated fluid volume parameters in a broad range of patient populations, suggesting that this mediates the clinical benefits of SGLT2 inhibitors in preventing heart failure. Here, we sought to examine the long-term (24 months) effect of the SGLT2 inhibitor ipragliflozin on the estimated fluid volume parameters in patients with type 2 diabetes mellitus (T2DM).MethodsIn this prespecified sub-analysis of the PROTECT (Prevention of Atherosclerosis by SGLT2 Inhibitor: Multicenter, Randomized Controlled Study) trial, which was an investigator-initiated, multicenter, prospective, randomized, open-label, clinical trial primarily designed to evaluate the effect of ipragliflozin treatment administered for 24 months on carotid atherosclerosis in patients with T2DM, we evaluated serial changes in estimated plasma volume (ePV, %) calculated using the Straus formula and estimated extracellular volume (eEV, mL) calculated by the body surface area by 24 months following the initiation of 50-mg ipragliflozin once daily and compared them with those following standard care for T2DM (non-SGLT2 inhibitor use).ResultsThis sub-analysis included 464 patients (ipragliflozin, n = 232; control, n = 232), a full analysis set of the PROTECT trial. In an analysis using mixed-effects models for repeated measures, relative to the control group, ipragliflozin significantly reduced ePV by − 10.29% (95% confidence interval [CI] − 12.47% to − 8.11%; P < 0.001) at 12 months and − 10.76% (95% CI − 12.86% to − 8.67%; P < 0.001) at 24 months. Additionally, ipragliflozin significantly reduced eEV by − 190.44 mL (95% CI − 249.09 to − 131.79 mL; P < 0.001) at 12 months and − 176.90 mL (95% CI − 233.36 to − 120.44 mL; P < 0.001) at 24 months. The effects of ipragliflozin on these parameters over 24 months were mostly consistent across various patient clinical characteristics.ConclusionsThis prespecified sub-analysis from the PROTECT trial demonstrated that ipragliflozin treatment, compared with the standard care for T2DM, reduced two types of estimated fluid volume parameters in patients with T2DM, and the effect was maintained for 24 months. Our findings suggest that SGLT2 inhibitor treatment regulates clinical parameters incorporated into the calculating formulas analyzed and consequently fluid volume status for the long-term, and this may be at least partly associated with clinical benefits from chronic use of SGLT2 inhibitors.Trial registration Japan Registry of Clinical Trials, ID jRCT1071220089

Association between remnant cholesterol and subclinical carotid atherosclerosis among Chinese general population in health examination

ObjectiveRemnant cholesterol (RC) was associated with carotid atherosclerosis in patients with clinical settings. But the value of RC as a risk management indicator for subclinical carotid atherosclerosis in health examination has not been fully determined. MethodsThis was a real-world, cross-sectional study including 12317 Chinese general population. Carotid intima-media thickness (CIMT) and carotid atherosclerotic plaque (CAP) were assessed by ultrasound. RC was calculated by total cholesterol minus low density lipoprotein-cholesterol (LDL-C) minus high density lipoprotein-cholesterol (HDL-C).Carotid atherosclerosis (CAS) was defined as a composite of increased CIMT and CAP. Multivariable logistic regression models were used to investigate the association of RC and CAS, increased CIMT and CAP. ResultsAmong 12317 participants (mean age: 51.21±13.76 years; 8303 men and 4014 women), the prevalence of CAS and increased CIMT was higher in participants with higher RC levels (P for trend<0.01). After multivariable adjustment, the highest quartile of RC was significantly associated with higher risk of CAS (OR: 1.45 95%CI: 1.26-1.67) and increased CIMT (OR: 1.48 95%CI: 1.29-1.71) with the lowest quartile of RC as reference. And the relationships remained significant even after adjustment of LDL-C and HDL-C. Every 1-SD increase of RC level was positively associated with 17% risk increment for CAS (6-30%) and 20% risk increment for increased CIMT (8-34%). ConclusionElevated serum RC levels were significantly associated with CAS and increased CIMT among Chinese general population, independent of LDL-C and HDL-C. RC evaluation could be applied for the risk management of early stage of subclinical carotid atherosclerosis in health examination.

473-P: Differences in Carotid Arteriosclerosis according to Waist Circumference and Thigh Circumference Appear Differently in Diabetic Patients and Prediabetic Patients

This study investigated the relationships of thigh and waist circumference with the glycemic variability and carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) and prediabetes. This observational study included 3,453 Korean patients with T2DM and prediabetes, in whom anthropometric measurements and carotid ultrasonography were conducted. Carotid plaque was defined as focal structures encroaching the arterial lumen by ≥ 0.5 mm or 50% of the surrounding IMT value or a thickness ≥1.5 mm. In men with T2DM, it was found that the larger the thigh circumference, the lower the risk of carotid plaque after adjustment for potential confounding variables. In women with T2DM, a similar tendency was observed before adjustment, but no statistically significant relationship was seen after adjustment. In women with T2DM, the presence of carotid plaque was higher in the thickest waist group compared to the reference group, but there is no statistical significance after adjustment. However, no difference in carotid arteriosclerosis according to waist and thigh circumference was found in both men and women in prediabetic patients. It suggests that the risk of cardiovascular disease according to the difference in body type such as waist circumference and thigh thickness may appear differently depending on the glucose status. However, further longitudinal studies are warranted. Disclosure C.Kim: None. S.A.Jang: None. K.Kim: None. S.Park: None.

Transforming growth factor beta 1 is associated with subclinical carotid atherosclerosis in patients with systemic lupus erythematosus

BackgroundTransforming growth factor beta (TGF-β1) is a multifunctional cytokine that has anti-inflammatory and immunosuppressive effects. TGF-β1 has been linked to cardiovascular disease in the general population. The immunosuppressive effect of TGF-β1 is believed to be dysregulated in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to study the relationship of serum levels of TGF-β1 with subclinical carotid atherosclerosis in patients with SLE.MethodsThe study included 284 patients with SLE. Serum levels of TGF-β1 and subclinical carotid atherosclerosis (by carotid ultrasonography) were evaluated. In addition, the complete lipid profile and insulin resistance were analyzed. Multivariable linear and logistic regression analysis was performed to establish the relationship of TGF-β1 with carotid subclinical atherosclerosis adjusting for traditional cardiovascular risk factors that included lipid profile and insulin resistance.ResultsCirculating TGF-β1 was positively and significantly associated with higher levels of LDL:HDL cholesterol ratio and atherogenic index. TGF-β1 was also associated with significantly lower levels of HDL cholesterol and apolipoprotein A1. Remarkably, TGF-β1 was associated with the presence of carotid plaque not only after adjustment for demographics (age, sex, body mass index, diabetes, hypertension, and aspirin use) but also after adjustment for relationships of TGF-β1 with lipid profile molecules, insulin resistance, and SLEDAI disease score (odds ratio 1.14 [95% confidence interval 1.003–1.30], p = 0.045).ConclusionTGF-β1 serum levels are positively and independently associated with the presence of subclinical atherosclerosis disease in patients with SLE.

Subclinical Carotid Atherosclerosis in Patients with Rheumatoid Arthritis at Low Cardiovascular Risk.

To evaluate the rate of subclinical carotid atherosclerosis and clinical significance of immunoinflammatory markers in patients with rheumatoid arthritis (RA) at low cardiovascular risk. The study included 275 RA patients and a control group of 100 participants without autoimmune diseases. All study participants were at low cardiovascular risk, calculated by the QRISK3 scale (<20%), and free of cardiovascular disease. Ultrasound examination of carotid arteries was performed to measure cIMT and to detect atherosclerotic plaques (ASP) in carotid arteries. sIСАМ-1, sVСАМ, and sCD40L levels were determined by enzyme immunoassay. Carotid ASP was observed more frequently in RA patients (27%) than in the control group (17%), p = 0.03. The frequency of ASP in RA patients did not depend on the disease's stage or activity. There was a significant correlation between cIMT and age, cardiovascular risk determined by QRISK3, level of total cholesterol, LDL, and blood pressure in RA patients, p < 0.05 in all cases. No correlation between cIMT and blood levels of sCD40L, sVCAM, and sICAM was found. In RA patients, a higher concentration of sVCAM was detected in the carotid ASP group compared to the non-atherosclerotic group. sCD40L was associated with cIMT and total cholesterol in the ASP group and with total cholesterol and blood pressure in non-atherosclerotic patients. Subclinical atherosclerotic lesions of the carotid arteries were observed significantly more frequently in RA patients with low cardiovascular risk than in the control group. The results of the study demonstrate the association between cIMT, traditional cardiovascular risk factors, and immunoinflammatory markers in RA patients.

Association between triglyceride‑glucose index and carotid atherosclerosis in patients with psoriatic arthritis.

To investigate the association of triglyceride-glucose (TyG) index with atherosclerotic risk among patients with psoriatic arthritis (PsA). This cross-sectional study included 165 consecutive PsA patients receiving carotid ultrasonography with integrated TyG index, calculated as ln [fasting triglycerides (mg/dl)×fasting glucose (mg/dl)/2]. Logistic regression models were applied to analyze the association of TyG index as continuous variables and tertiles with carotid atherosclerosis and carotid artery plaque. Fully adjusted model included sex, age, smoking, body mass index, comorbidities, and psoriatic related variables. Overall, PsA patients with carotid atherosclerosis had substantially higher TyG index than those without (8.82 ± 0.50 vs 8.54 ± 0.55, p= 0.002). The frequency of carotid atherosclerosis was increased with increases in TyG index tertiles, showing 14.8%, 34.5%, 44.6% for tertile 1, 2 and 3, respectively (p= 0.003). Multivariate logistic analyses showed that each 1-unit increase in TyG index was significantly associated with prevalent carotid atherosclerosis (unadjusted OR 2.65 [1.39-5.05]; fully-adjusted OR 2.69 [1.02-7.11]). Compared with patients with tertile 1 of TyG index, the unadjusted and fully-adjusted OR for occurrence of carotid atherosclerosis were 4.64 (1.85-11.60) and 5.10 (1.54-16.93) in patients with tertile 3. Similarly, higher prevalent carotid artery plaque was observed with increasing TyG index (unadjusted OR 3.11 [1.54-6.26]; fully-adjusted OR 3.61 [1.15-11.38]) or with tertile 3 vs. tertile 1 (unadjusted OR 10.20 [2.83-36.82]; fully-adjusted OR 17.89 [2.88-111.11]). Additionally, TyG index provided incremental predictive capacity beyond established risk factors, shown by an increase in discrimination ability (all P < 0.001). TyG index was positively correlated with the burden of atherosclerosis in PsA patients, independent of traditional cardiovascular risk factors and psoriatic-related factors. These findings suggest that TyG index may be a promising atherosclerotic marker for PsA population.

Development and validation of a nomogram for evaluating the incident risk of carotid atherosclerosis in patients with type 2 diabetes.

The purpose of this study was to evaluate the clinical characteristics of carotid atherosclerotic disease in patients with type 2 diabetes mellitus, investigate its risk factors, and develop and validate an easy-to-use nomogram. 1049 patients diagnosed with type 2 diabetes were enrolled and randomly assigned to the training and validation cohorts. Multivariate logistic regression analysis identified independent risk factors. A method combining least absolute shrinkage and selection operator with 10-fold cross-validation was used to screen for characteristic variables associated with carotid atherosclerosis. A nomogram was used to visually display the risk prediction model. Nomogram performance was evaluated using the C index, the area under the receiver operating characteristic curve, and calibration curves. Clinical utility was assessed by decision curve analysis. Age, nonalcoholic fatty liver disease, and OGTT3H were independent risk factors associated with carotid atherosclerosis in patients with diabetes. Age, nonalcoholic fatty liver disease, smoke, HDL-C, and LDL-C were characteristic variables used to develop the nomogram. The area under the curve for the discriminative power of the nomogram was 0.763 for the training cohort and 0.717 for the validation cohort. The calibration curves showed that the predicted probability matched the actual likelihood. The results of the decision curve analysis indicated that the nomograms were clinically useful. A new nomogram was developed and validated for assessing the incident risk of carotid atherosclerotic in patients with diabetes; this nomogram may act as a clinical tool to assist clinicians in making treatment recommendations.

Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus.

We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis. Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients. NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.

The Correlation between Increased Expressions of NLRP3 Inflammasome Components in Peripheral Blood Mono-Nuclear Cells and Plaque Vulnerability in Human Carotid Atherosclerosis.

We aimed to determine whether NLRP3 inflammasomes in peripheral blood mononuclear cells (PBMC) were associated with carotid plaque instability in carotid atherosclerosis patients. Consecutive 38 carotid atherosclerosis with vulnerable plaques, 22 carotid atherosclerosis with stable plaques, and 40 healthy subjects with no carotid or coronary artery stenosis were enrolled. They were referred to the Second Hospital of Dalian Medical University from 2013-2019. Carotid plaques were evaluated by modified plaque vulnerability risk score (MPVRS) and pathological assessment. The mRNA and protein expression of NLRP3 inflammasome components in PBMC were determined by quantitative real time PCR and Western blot analysis or ELISA. When consecutive study subjects undergoing carotid endarterectomy were divided into stable (≤4) and unstable (>4) plaque groups according to the MPVRS, the unstable plaque group had significantly raised mRNA and protein expression of NLRP3 inflammasome components in PBMC as compared with the stable plaque group and healthy subject group. Furthermore, subjects with higher NLRP3 protein expression in PBMC had greater incidence of cerebrovascular events. Increased NLRP3 inflammasome components in PBMC is associated with instability of human carotid atherosclerotic plaques, suggesting NLRP3 inflammasome as a potential biomarker for monitoring carotid plaque instability.

JS-HR-11: HOT TOPICS IN URIC ACID RESEARCH

The mechanism between hyperuricemia, arteriosclerosis, hypertension, chronic kidney disease, and cardiovascular disease is becoming clearer (Figure cited from the article ‘Update on Hypertension Research in 2021’, Hypertension Research. 2022;45(8):1276 to 1297). However, it remains unclear whether treatment of hyperuricemia improves these diseases. In this session, we will introduce some recent topics of uric acid research. The PERL (Preventing Early Renal Loss in Diabetes) trial and the CKD-FIX (Controlled Trial of Slowing of Kidney Disease Progression from the Inhibition of Xanthine Oxidase) showed that urate-lowering treatment with allopurinol, one of xanthine oxidase (XO) inhibitors, did not slow the decline in eGFR as compared with placebo. These results were similar with the results of FEATHER (Febuxostat Versus Placebo Randomized Controlled Trial Regarding Reduced Renal Function in Patients with Hyperuricemia Complicated by Chronic Kidney Disease Stage 3) from Japan. Furthermore, the PRIZE (Program of Vascular Evaluation Under Uric Acid Control by the Xanthine Oxidase Inhibitor Febuxostat: Multicenter, Randomized, Controlled) study showed that febuxostat did not delay progression of carotid atherosclerosis in patients with asymptomatic hyperuricemia. These results suggest that treatment of hyperuricemia could not directly prevent chronic kidney disease (CKD) and/or arteriosclerosis. In contrast, there are many studies that showed the positive relationship between uric acid and hypertension. Lowering serum uric acid levels could reduce blood pressure, but it is unclear that lowering serum uric aclid levels might be directly causing the results in preventing CKD progression, arteriosclerosis, and cardiovascular events. These results suggest that we should carefully choose the treatable patients with hyperuricemia and hypertension.

Correlation Study of Serum Dickkopf 4 Level with Metabolic Syndrome and Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

To investigate the characteristics of Dickkopf 4 changes in patients with type 2 diabetes mellitus and its correlation with carotid atherosclerosis, is the objective of the study. A cross-sectional survey was performed and eligible patients with type 2 diabetes mellitus were taken as the subjects. Lifestyle, physical measurements, blood biochemical parameters and relevant imaging examinations were collected from all participating subjects. 237 type 2 diabetes mellitus patients were included in present study and divided into four groups according to the quartiles of serum Dickkopf 4. The incidence of body mass index, fasting plasma glucose, fasting C-peptide, glycated haemoglobin, insulin resistance index, total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, high-density lipoprotein, and non-alcoholic fatty liver disease, carotid atherosclerosis were compared between groups, p<0.05. Dickkopf 4 was positively correlated with body mass index, C-reactive protein, fasting plasma glucose, fasting C-peptide, glycated haemoglobin, total cholesterol, triglycerides, low-density lipoprotein, insulin resistance index and creatinine, and negatively correlated with high-density lipoprotein and estimated glomerular filtration rate, p<0.05. Non-metabolic syndrome group and metabolic syndrome group were compared and non-carotid atherosclerosis group and carotid atherosclerosis group were compared for all the parameters (p<0.05). High Dickkopf 4 was an independent risk factor for metabolic syndrome (odds ratio=2.023, 95 % confidence interval: 1.042-3.926, p=0.037). Binary logistic regression analysis, high Dickkopf 4 was an independent risk factor for carotid atherosclerosis (odds ratio=2.513, 95 % confidence interval: 1.379-2.513, p=0.003). High Dickkopf 4 is a risk factor for hypertension and non-alcoholic fatty liver disease in type 2 diabetic patients and an independent risk factor for metabolic syndrome and carotid atherosclerosis in type 2 diabetic mellitus patients.

Salivary metabolic signatures of carotid atherosclerosis in patients with type 2 diabetes hospitalized for treatment.

Atherosclerosis is a life-threatening disease associated with morbidity and mortality in patients with type 2 diabetes (T2D). This study aimed to characterize a salivary signature of atherosclerosis based on evaluation of carotid intima-media thickness (IMT) to develop a non-invasive predictive tool for diagnosis and disease follow-up. Metabolites in saliva and plasma samples collected at admission and after treatment from 25 T2D patients hospitalized for 2weeks to undergo medical treatment for diabetes were comprehensively profiled using metabolomic profiling with gas chromatography-mass spectrometry. Orthogonal partial least squares analysis, used to explore the relationships of IMT with clinical markers and plasma and salivary metabolites, showed that the top predictors for IMT included salivary allantoin and 1,5-anhydroglucitol (1,5-AG) at both the baseline examination at admission and after treatment. Furthermore, though treatment induced alterations in salivary levels of allantoin and 1,5-AG, it did not modify the association between IMT and these metabolites (p interaction > 0.05), and models with these metabolites combined yielded satisfactory diagnostic accuracy for the high IMT group even after treatment (area under curve = 0.819). Collectively, this salivary metabolite combination may be useful for non-invasive identification of T2D patients with a higher atherosclerotic burden in clinical settings.

The Relationship between Atherosclerosis and Gut Microbiome in Patients with Obstructive Sleep Apnoea

Background: Obstructive sleep apnoea (OSA) and gut dysbiosis are known risk factors for atherosclerosis. However, only very few studies have been focused on the relationship between OSA, atherosclerosis, and the intestinal microbiome, all in animal models. Methods: Twenty-two patients with OSA, 16 with and 6 without carotid atherosclerosis were involved in the study. After a diagnostic sleep examination, the intima media thickness (IMT) was measured and plaques were found using carotid ultrasound. Blood was also drawn for metabolic profile, and a stool sample was provided for 16S ribosomal RNA microbiome investigation. Results: An increased maximal common carotid artery (CCA) IMT was significantly associated with decreased phylum-level diversity. The level of Peptostreptococcaceae was significantly lower in atherosclerotic subjects. Some other candidate microbes appeared in the two groups at the genus level as well: Bilophila, Romboutsia, Slackia, and Veillonella in the non-atherosclerotic group; and Escherichia-Shigella, Prevotella, and Ruminococcaceae in the atherosclerotic group. Conclusions: This is the first pilot research to analyze the association between the gut microbiome and atherosclerosis in adult patients with OSA with and without carotid atherosclerosis. Dysbiosis and individual bacteria may contribute to the development of carotid atherosclerosis in patients with OSA. Further investigations are necessary to reveal a more precise background in a larger sample.

Circulating microparticles are associated with plaque burden and cause eNOS uncoupling in patients with carotid atherosclerosis.

Aims: The study aimed to evaluate the correlation of different microparticle (MP) phenotypes with plaque burden and their diagnostic value and preliminarily explore the role of MPs in atherosclerosis (AS). Methods: Carotid intima-media thickness (CIMT) and maximal plaque area in 23 patients with carotid atherosclerosis (CAS) and 22 healthy subjects were measured by ultrasound. Transmission electron microscopy, nanoparticle tracking analysis and western blot were used to identify MPs. Flow cytometry assay measured absolute number of MPs, and receiver operating characteristic (ROC) analysis was used to assess the relationship between plaque burden and MPs. To study the preliminary mechanism of MPs in AS, MPs were administered to 32 male Kunming mice, which were randomly divided into control, CAS, healthy, and tetrahydrobiopterin (BH4) groups. Hematoxylin-eosin staining, immunohistochemistry staining, and Western blot were adopted to detect relevant indexes 24h after the injection. Results: The plasma levels of CD45+ leukocyte-derived microparticle (LMP), CD11a+ LMP, CD11a+/CD45+ LMP, and CD31+/CD42b+ platelet-derived microparticle (PMP) in CAS patients were significantly higher than those in healthy subjects, and were positively correlated with the maximal plaque area. Moreover, the levels of CD11a+ LMP, CD11a+/CD45+ LMP were also positively correlated with CIMT. The area under the ROC curve of the four MPs was 0.689, 0.747, 0.741, and 0.701, respectively. Compared with healthy subjects, MPs from CAS patients resulted in a significantly lower expression of endothelial nitric oxide synthase (eNOS) dimer/monomer, and BH4 could improve eNOS uncoupling. Moreover, the level of VCAM-1 in intima in the CAS group was significantly higher than in the other three groups. Conclusion: CD11a+ LMP and CD11a+/CD45+ LMP might be potential biomarkers for CAS prediction. BH4-related eNOS uncoupling occurs in CAS patients, and circulating MPs from them lead to endothelial dysfunction through eNOS uncoupling.