Carotid Plaque Occurrence Research Articles

Impact of Classical Risk Factors on Subclinical Carotid Atherosclerosis Progression: Insights from a Non-Diabetic Cohort.

Several markers have been proposed for the detection and progression of subclinical atherosclerosis. We aimed to analyse the impact of classical risk factors on the presence and short-term progression of subclinical carotid atherosclerosis in a non-diabetic, primary prevention cohort. This analysis included participants with completed visits at baseline and at 5-year follow-up (N = 141; 56.7% females, 43.3% males; aged 49.6 4.7 years). Clinical and laboratory parameters, risk profiles, carotid artery intima-media thickness (CIMT) and plaque presence were analysed. There was a significant progression in mean CIMT (0.54 0.09 mm-0.62 0.10 mm; p 0.001), prevalence of carotid plaque (4.8%-17.9%; p 0.001) and age- and sex-adjusted abnormal CIMT (52.9%-78.8%; p 0.001) at the end of follow-up, compared to baseline. In multivariate regression analysis, among the classical risk factors, their number, metabolic syndrome and SCORE (Systematic Coronary Risk Estimation) risk only the number of risk factors showed an independent and significant impact on the occurrence of a carotid plaque (Exp(B) = 1.71; p = 0.017) and 5-year CIMT progression. During a short follow-up, the significant progression of subclinical atherosclerosis was confirmed. The number of risk factors predicted the occurrence of carotid plaques and CIMT progression. The high prevalence and short-term progression of subclinical carotid atherosclerosis underly the rationale for its screening in personalized cardiovascular risk stratification in asymptomatic middle-aged subjects over 50 years old, at low-to moderate cardiovascular risk, particularly with several risk factors.

Association of Lipoprotein-associated phospholipase A2 With Carotid Intima-Media Thickness in Acute Cerebral Infarction Patients.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory marker associated with atherosclerotic and cardiovascular diseases. This study aimed to explore the association of Lp-PLA2 with carotid intima-media thickness (cIMT) in patients with acute ischemic stroke (AIS) and explore a threshold level to predict the risk of vulnerable plaques. This retrospective observational study included patients with AIS in the Neurology Department of our Hospital between January 2018 and December 2019. The study included 293 patients aged 65.29 ± 12.11years, including 212 males, of whom 124 had carotid intima-media thickening (42.32%). Multivariable logistic regression showed that Lp-PLA2 level was an independent risk factor for cIMT (odds ratio [OR] = 1.004, 95% confidence interval [95% CI] 1.001-1.008, P = .008). Threshold effect analysis showed that the risk of vulnerable carotid plaque occurrence increased by 2% for every 1ng/mL increase in Lp-PLA2 level with serum Lp-PLA2 levels between 157 and 279ng/mL; this increase was statistically significant (OR = 1.02, 95% CI 1.01-1.03, P < .001). Serum Lp-PLA2 is an independent risk factor for increased cIMT in patients with AIS, and a threshold Lp-PLA2 level between 157 and 279ng/mL showed a higher risk of carotid plaque rupture.

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.

Utilizing machine learning algorithms for the prediction of carotid artery plaques in a Chinese population.

Background: Ischemic stroke is a significant global health issue, imposing substantial social and economic burdens. Carotid artery plaques (CAP) serve as an important risk factor for stroke, and early screening can effectively reduce stroke incidence. However, China lacks nationwide data on carotid artery plaques. Machine learning (ML) can offer an economically efficient screening method. This study aimed to develop ML models using routine health examinations and blood markers to predict the occurrence of carotid artery plaques. Methods: This study included data from 5,211 participants aged 18-70, encompassing health check-ups and biochemical indicators. Among them, 1,164 participants were diagnosed with carotid artery plaques through carotid ultrasound. We constructed six ML models by employing feature selection with elastic net regression, selecting 13 indicators. Model performance was evaluated using accuracy, sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), F1 score, kappa value, and Area Under the Curve (AUC) value. Feature importance was assessed by calculating the root mean square error (RMSE) loss after permutations for each variable in every model. Results: Among all six ML models, LightGBM achieved the highest accuracy at 91.8%. Feature importance analysis revealed that age, Low-Density Lipoprotein Cholesterol (LDL-c), and systolic blood pressure were important predictive factors in the models. Conclusion: LightGBM can effectively predict the occurrence of carotid artery plaques using demographic information, physical examination data and biochemistry data.

Relationship between the circulating N-terminal pro B-type natriuretic peptide and the risk of carotid artery plaque in different glucose metabolic states in patients with coronary heart disease: a CSCD-TCM plus study in China

ObjectiveCirculating N-terminal pro B-type natriuretic peptide (NT-proBNP) is a marker for heart failure in patients with coronary heart disease (CHD) and associated with glycemic abnormalities. Studies on the association and diagnostic value of NT-proBNP in carotid plaques (CAP) in patients with CHD are limited.MethodsThe relationships between NT-proBNP and the risk of CAP in different glucose metabolic states, sexes, and age categories were also examined using 5,093 patients diagnosed with CHD. The NT-proBNP tertiles were used to divide patients into three groups in which the NT-proBNP levels, blood glucose levels, the occurrence of CAP, and the number and nature of CAP were measured using normoglycemic (NG), prediabetes (Pre-DM), and diabetes mellitus (DM) glucose metabolic statuses. Logistic regression analyses were used to compare the relationship between NT-proBNP and the risk of CAP occurrence and the number and nature of CAP. The diagnostic value of NT-proBNP for CAP risk was measured using receiver operating characteristic (ROC) curves.ResultsWe found a 37% relative increase in the correlation between changes in NT-proBNP per standard deviation (SD) and the incidence of CAP. After adjusting for potential confounders, NT-proBNP at the T3 level was found to be associated with an increased CAP odds ratio (OR) when T1 was used as the reference. This relationship was also present in males, patients aged > 60 years, or both pre-DM and DM states. NT-proBNP was more likely to present as hypoechoic plaques at T1 and as mixed plaques at T3. We also measured the diagnostic accuracy of CAP for NT-proBNP in patients with CHD, with an AUC value of 0.627(95% CI 0.592–0.631), sensitivity of 50.7%, and specificity of 68.0%.ConclusionAn increase in NT-proBNP was significantly associated with the risk of CAP in patients with CHD, especially in males and patients aged > 60 years, and exhibited specific characteristics under different glucose metabolism states.Trial registration The study was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (Approval number TJUTCM-EC20210007) and certified by the Chinese Clinical Trials Registry on April 4, 2022 (Registration number ChiCTR2200058296) and March 25, 2022 by ClinicalTrials.gov (registration number NCT05309343).Graphical

Serum uric acid predicts the development of atherosclerosis in women but not in men: A ten-year cohort study in China

Background and aimAtherosclerosis is becoming a significant health burden. Serum uric acid (SUA) is the final enzymatic product of purine metabolism and can contribute to the development of atherosclerosis. The aim of this study was to explore the possible predictive value of SUA in the development of atherosclerosis in a healthy Chinese population. Methods and resultsIn this study, a total of 11,222 healthy subjects with no carotid plaque at baseline were enrolled and divided into sex-specific groups, and then the occurrence of carotid plaque during the follow-up time was documented. The association between carotid plaque and SUA levels was examined using Cox proportional-hazards regression models. The mean SUA level was 5.35 ± 1.41 mg/dL. A total of 2,911 individuals (25.94%) developed carotid plaque during the follow-up time, including 1,071 females and 1,840 males. After adjusting for potential confounding factors, the hazard ratio (HR) and 95% confidence interval (95% CI) in women for the occurrence of carotid plaque associated with SUA levels were 1.163 (1.017–1.330), but no significant correlation was found in men, as the HR was 1.050 (0.965–1.143). ConclusionOur results indicate that SUA levels predict the development of carotid plaque independent of traditional risk factors only in women.

The association between sodium intake and coronary and carotid atherosclerosis in the general Swedish population.

A high intake of salt raises blood pressure and the risk of cardiovascular disease. Previous studies have reported on the association between salt intake and carotid stenosis, but the association with coronary atherosclerosis has not been reported. Therefore, this project aimed at studying the association between salt intake and both carotid and coronary atherosclerosis in a contemporary community-based cohort. Estimated 24-h sodium excretion (est24hNa) was calculated by the Kawasaki formula for participants of two sites (Uppsala and Malmö) of the Swedish Cardiopulmonary bioImage Study, who underwent a coronary computed tomography (n = 9623) and measurement of coronary artery calcium score (CACS, n = 10 289). Carotid ultrasound was used to detect carotid plaques (n = 10 700). Ordered logistic regression was used to calculate odds ratios (OR) per 1000 mg increase in est24hNa. We also investigated potential J-formed associations using quintiles of est24hNa. Increased est24hNa was associated with increased occurrence of carotid plaques [OR: 1.09, P < 0.001, confidence interval (CI): 1.06-1.12], higher CACS (OR: 1.16, P < 0.001, CI: 1.12-1.19), and coronary artery stenosis (OR: 1.17, P < 0.001, CI: 1.13-1.20) in minimal adjusted models. Associations were abolished when adjusting for blood pressure. When adjusting for established cardiovascular risk factors (not including blood pressure), associations remained for carotid plaques but not for coronary atherosclerosis. There was no evidence of J-formed associations. Higher est24hNa was associated with both coronary and carotid atherosclerosis in minimal adjusted models. The association seemed mainly mediated by blood pressure but to some degree also influenced by other established cardiovascular risk factors.

Cadmium contributes to atherosclerosis by affecting macrophage polarization.

Chronic cadmium (Cd) exposure contributes to the progression of atherosclerosis, but the direct role of Cd and its mechanisms in atherosclerosis remains incompletely understood. Atherosclerosisis a chronic inflammatory disease promoting macrophage polarization to M1 phenotype and producing pro-inflammations that are vital in regulating the inflammatory response. Herein, through a case-control study, we found that Cd exposure may promote the occurrence of carotid plaque via inflammation, where interleukin-6 (IL-6) may play an important role. We also combined in vivo and in vitro experiments to explore the underlying mechanism of Cd promoted plaque formation and the production of IL-6. With or without cadmium chloride (CdCl2) fed ApoE-/- mouse and treated RAW264.7 cells, we found Cd accumulated in the aortas which significantly increased the plaque area in atherosclerotic mice, macrophage accumulation, and lipid accumulation, and Cd promoted M1 phenotype macrophage polarization reflected by the increased expression of CD86 which produced tumor necrosis factor-α (TNF-α) and IL-6. However, the influences on M2 phenotype and anti-inflammatory cytokines IL-4 and IFN-γ were non-significant. Moreover, we found that JAK2/STAT3 pathway was greatly activated in the plaques and CdCl2-treated macrophages. The inhibition of JAK2/STAT3 substantially reversed the Cd-stimulated macrophage M1 phenotype macrophage polarization and the expression of pro-inflammatory cytokines including TNF-α and IL-6. Altogether, Cd intensifies atherosclerosis by modulating macrophage polarization via JAK2/STAT3 to up-regulated the exression of IL-6.

The blood monocyte to high density lipoprotein cholesterol ratio (MHR) is a possible marker of carotid artery plaque

BackgroundMHR is the ratio of monocyte to high-density lipoprotein cholesterol (HDL-C). It has been reported that MHR changes are associated with cardiovascular and cerebrovascular disease. Carotid plaque is a common vascular lesion of the carotid artery and is a manifestation of atherogenesis. This study investigated the relationships between the MHR and the incidence of carotid plaques.MethodsThe data of 3848 physical examiners were analyzed for retrospective analysis, which included 1428 patients with noncarotid plaque, 1133 patients with single carotid plaque, and 1287 patients with bilateral or multiple carotid plaques. Statistical analysis was performed on SPSS 22.0 0 software and statistical software R and its GAM package.ResultsThe difference was statistically significant in the levels of MHR, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), blood lipids (HDL-C, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (Tg)), blood glucose (Glu), hemoglobin A1c (HbA1c), renal function (urea, creatinine (Crea)), estimated glomerular filtration rate (eGFR), and uric acid (Ua) in the carotid plaque groups (P < 0.001, respectively). There was no significant difference between the sex (P = 0.635) and age (P = 0.063) in the different groups. MHR levels were positively correlated with BMI (r = 0.364, P < 0.001), hs-CRP (r = 0.320, P < 0.001), Tg (r = 0.417, P < 0.001), Crea (r = 0.323, P < 0.001), eGFR (r = − 0.248, P < 0.001), Ua (r = 0.383, P < 0.001) and HbA1c (r = 0.197, P < 0.001). Levels of TC, Glu, and urea were slightly correlated with the MHR level (r = − 0.150, P < 0.001; r = 0.187, P < 0.001; r = 0.137, P < 0.001, respectively). The MHR level increased with elevated severity of carotid plaque in subjects without hypertension or diabetes (P < 0.001). In adjusted models, with the rise of MHR level, the probability of occurrence of carotid plaque had a 1.871-fold (95% CI: 1.015–3.450, P = 0.045) increase; the probability of multiple occurrences of carotid plaques had a 2.896-fold (95% CI: 1.415–5.928, P < 0.001) increase. The GAM curve showed a nonlinear correlation between the normalized MHR and the probability of carotid plaque occurrence.ConclusionsMHR could be used as a possible marker for plaque formation and severity.

Divergent Occurrence of Carotid Intima-Media Thickness and Carotid Arteries Plaques in Stable Kidney Transplant Recipients.

Carotid atherosclerosis is one of the main cerebrovascular complications in kidney transplant recipients (KTRs). We analyzed the relationships between carotid intima-media thickness (IMT) and the occurrence and characteristics of carotid plaques in a cohort of KTRs. In 500 KTRs (aged 49.9 12.0 years), IMT was measured and carotid plaques were semi-qualitatively assessed. Concomitantly, biochemical and hormonal inflammatory, vascular and calcium-phosphate metabolism parameters were also assessed. In 10.2% of patients, a side-to-side IMT difference 0.1 mm was observed, whereas 26.8% of patients with no plaques in one carotid artery had at least one contralateral calcified plaque. Multivariate logistic regression analysis revealed that age ( = 0.409; p 0.001), male sex ( = 0.199; p 0.001), and coronary artery disease ( = 0.139; p 0.01) independently increased IMT ( = 0.25). For the occurrence of calcified carotid plaques, age ( = 0.544; p 0.001), male gender ( = 0.127; p 0.05), and the duration of renal insufficiency prior to transplantation ( = 0.235; p 0.001) were confirmed as independent variables. Substantial side-to-side differences in IMT values and carotid plaques distribution are present in a large percentage of stable KTRs. In addition, there are different clinical risk factors profiles associated with IMT and the presence of calcified plaques. Vascular and calcium-phosphate metabolism biomarkers were not associated with any carotid atherosclerosis characteristics.

Serum LDL-C/HDL-C ratio and the risk of carotid plaques: a longitudinal study

BackgroundDyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population.MethodsWe followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association.ResultsAmong 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55–2.58) and over 60 years (HR: 3.36, 95% CI: 2.47–4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01–1.56), diabetes (HR: 1.46, 95% CI: 1.06–2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07–1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12–1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction < 0.05).ConclusionA high LDL-C/HDL-C ratio could accelerate the occurrence of carotid plaques. Older men with diabetes and dyslipidemia are the critical target population. Women may be more likely to benefit from lipid-lowering interventions and thus avoid carotid plaque formation.

Association between the triglyceride-glucose index and carotid plaque incidence: a longitudinal study

BackgroundCarotid plaque and triglyceride-glucose (TyG) index are associated with insulin resistance. However, a highly debated question is whether there is an association between the TyG index and carotid plaque incidence. Thus we performed an in-depth longitudinal study to investigate the relationship between carotid plaque occurrence and the TyG index among Chinese individuals.MethodsTwo thousand and three hundred seventy subjects (1381 males and 989 females) were enrolled and followed up for three years. The subjects were stratified into four groups based on the quartile of the TyG index at baseline. Univariate and multivariate Cox proportional hazard models were conducted to examine the role of TyG played in the carotid plaque. The strength of association was expressed as hazard ratio (HR) and 95% confidence interval (CI).ResultsAfter three years of follow-up, 444 subjects were detected with newly formed carotid plaque. The overall 3-year cumulative carotid plaque incidence was 18.7%, and the risk of carotid plaque increased with elevated TyG index (p < 0.001). The Cox regression analysis showed that males (HR: 1.33, 95% CI: 1.10–1.61), and people with higher systolic blood pressure (HR:1.01, 95% CI: 1.01–1.02), lower high-density lipoprotein cholesterol (HR: 0.68, 95% CI: 0.50–0.93), diabetes (HR: 2.21, 95% CI: 1.64–2.97), and hypertension (HR:1.49, 95% CI: 1.23–1.81) had a significantly increased risk for the carotid plaque formation. Similar results remained in the sensitivity analysis.ConclusionsThe TyG index can be used as a dose-responsive indicator of carotid plaque in the Chinese population. Elderly males with dyslipidemia, diabetes, or hypertension should be more vigilant about their TyG index since they are susceptible to developing carotid plaque. Physicians are encouraged to monitor the TyG index to help identify and treat patients with carotid plaque at an early stage.

Obesity is associated with coronary artery stenosis independently of metabolic risk factors: The population-based SCAPIS study

Background and aimsPrevious studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. MethodsIn the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. ResultsThe severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. ConclusionsIndividuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.

Association between circulating asprosin levels and carotid atherosclerotic plaque in patients with type 2 diabetes

BackgroundCarotid plaque is one of the typical manifestations and precursors of diabetic cardiovascular complications. As a new adipokine, asprosin participates in the development of diabetes and cardiovascular diseases, and is considered to be closely related to insulin resistance and glucolipid metabolism. This study aimed to analyze the relationship between serum asprosin level and carotid plaque in patients with type 2 diabetes mellitus (T2DM). MethodsA total of 180 patients with T2DM were selected. The basic parameters and biochemical indexes of the subjects were measured, and the serum asprosin concentration of the subjects was detected by ELISA. The carotid plaque was evaluated by color Doppler ultrasound. ResultsThe level of serum asprosin in the T2DM with carotid plaque group was significantly higher than that in T2DM without carotid plaque group [2.53(1.73–3.21) vs 1.72(1.23–2.34) ng/mL, P < 0.05]. The incidence of carotid plaque in the low, middle and high quartiles was 31.7 %, 48.3 % and 70 % respectively. Correlation analysis showed that serum asprosin was positively correlated with BMI, WHR, SBP, DBP, FIns, LDL-C, HOMA-IR, and HOMA-β (P < 0.05). Linear regression analysis showed that WHR, DBP, FIns, and LDL-C were independent influencing factors of asprosin. Logistic regression analysis showed that serum asprosin was still significantly correlated with carotid plaque in T2DM patients after adjusting for multiple confounding factors. The area under receiver-operating curve (ROC) of asprosin predicting carotid plaque was 0.701 (0.625–0.777) in T2DM. ConclusionThe level of serum asprosin in T2DM patients with carotid plaques is significantly higher, suggesting that asprosin may play a role in the occurrence and development of carotid plaques in T2DM. Detection of this index can provide new clinical evidence for the prevention and treatment of diabetic cardiovascular disease.

Serum sulfatide as a biomarker of carotid atherosclerosis in patients with rheumatoid arthritis

PurposeRheumatoid arthritis (RA) patients have accelerated atherosclerosis (AS) leading to excess cardiovascular morbidity and mortality, but traditional risk factors for cardiovascular disease (CVD) are invalid to explain the problem. Sulfatides, as major components of serum lipoproteins, are synthesized in the liver. These molecules are reported to play an important role in the development of AS, thrombogenesis, and inflammation. However, it is unclear whether sulfatides are responsible for such issue. To elucidate the possible association between serum sulfatide and the accelerated progress of AS, evaluated by carotid intima-media thickness (CIMT), and ascertain the related mechanism underlying the correlation in RA cases. MethodsWe performed an observational study of 144 patients with RA and 120 sex and age-matched controls. Meanwhile, 107 patients (of the 144 RA patients enrolled at baseline) were invited to undergo a second measurement after 12 months. Serum sulfatide levels of all the enrolled subjects were quantified by mass spectrometry after they were converted into lysosulfatides (LS), and then calculated as the sum of the levels of seven LS molecular species. Serum oxidative stress marker, malondialdehyde (MDA) was detected by ELISA. We subsequently statistically analyzed the causalities between carotid AS and clinical parameters, and the association of serum sulfatide with other variables. Multivariable logistic regression analysis was finally employed by taking all factors to identify independent determinant for carotid atherosclerotic plaque and serum sulfatide level. ResultsA gradual declined trend in serum sulfatide levels was observed in control subjects, non-plaque group, and the plaque group (8.56 ± 1.37 nmol/mL, 5.63 ± 1.57 nmol/mL, 3.18 ± 1.32 nmol/mL, respectively, p < 0.01), along with an increased value of CIMT (0.63 ± 0.07 mm, 0.92 ± 0.14 mm, 1.43 ± 0.22 mm, respectively, p < 0.01). Meanwhile, a negative linear correlation between CIMT and serum sulfatide was further confirmed by Spearman’s analysis (r = -0.622, p < 0.01). Eventually, multivariate logistic regression analysis identified serum MDA as the only independent factor for the abnormal level of serum sulfatide, and serum sulfatide was detected as a significant protective factor for the occurrence of carotid plaques in RA cases (p < 0.01), which was confirmed repeatedly by our cross-sectional and longitudinal studies. ConclusionExcessive abnormal levels of oxidative stress decreased serum sulfatide levels, followed by a high occurrence of AS in RA patients. Serum sulfatide level might be useful as a predictor (biomarker) for the progression of AS in RA cases.

An accurate and explainable ensemble learning method for carotid plaque prediction in an asymptomatic population

Background and objectiveThe identification of carotid plaque, one of the most crucial tasks in stroke screening, is of great significance in the assessment of subclinical atherosclerosis and preventing the onset of stroke. However, traditional ultrasound examination is not prevalent or cost-effective for asymptomatic people, particularly low-income individuals in rural areas. Thus, it is necessary to develop an accurate and explainable model for early identification of the risk of plaque prevalence that can help in the primary prevention of stroke. MethodsWe developed an ensemble learning method to predict the occurrence of carotid plaques. A dataset comprising 1440 subjects (50% with plaques and 50% without plaques) and ten-fold cross-validation were utilized to evaluate the model performance. Four machine learning methods (extreme gradient boosting (XGBoost), gradient boosting decision tree, random forest, and support vector machine) were evaluated. Subsequently, the interpretability of the XGBoost model, which provided the best performance, was analyzed from three aspects: feature importance, feature effect on prediction model, and feature effect on prediction decision for a specific subject. ResultsThe XGBoost algorithm provided the best performance (sensitivity: 0.8678, specificity: 0.8592, accuracy: 0.8632, F1 score: 0.8621, area under the curve: 0.8635) in carotid plaque prediction and also had excellent performance under missing data circumstances. Further, interpretability analysis showed that the decisions of the XGBoost model were highly congruent with clinical knowledge. ConclusionThe model results are superior to those of state-of-the-art methods. Thus, it is a promising carotid plaque prediction tool that could be used in the primary prevention of stroke.

Elevated serum uric acid was associated with pre-inflammatory state and impacted the role of HDL-C on carotid atherosclerosis

Background and aimsUric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with atherosclerosis, respectively. UA and HDL-C are involved in the balance of proinflammatory and anti-inflammatory processes in atherosclerosis. However, it is still unclear whether UA affects the effect of HDL-C on atherosclerosis. Methods and resultsIn this retrospective study, we enrolled 1437 patients with multiple risk factors for atherosclerosis. Patients were categorized into two groups according to their baseline UA level. Multivariate logistic regression analysis and restricted cubic spline curves were used to assess the relationship between HDL-C and carotid atherosclerosis (abnormal carotid intima–media thickness [cIMT] and carotid artery plaque) at different UA levels. Compared to patients with normouricemia, patients with hyperuricemia were older and had a more extensive history of disease and unhealthy behavior. In the normouricemia group, multivariate-adjusted odds ratios (95% CIs) for HDL-C were 0.55 (0.33–0.92) for abnormal mean cIMT, 0.59 (0.35–1.00) for abnormal maximum cIMT, and 0.53 (0.29–0.94) for the occurrence of carotid artery plaque, while the correlation between each of these three indicators with HDL-C were not significant in those with hyperuricemia. Spline regression models yielded similar results. The effect of UA on the association between HDL-C and carotid atherosclerosis remained in the subset of patients with optimal low-density lipoprotein cholesterol. ConclusionElevated UA marks a pre-inflammatory state and impacts the role of HDL-C on carotid atherosclerosis.

Skin autofluorescence, a measure of tissue accumulation of advanced glycation end products, is associated with subclinical atherosclerosis in coronary and carotid arteries

Background and aimsSkin autofluorescence (AF), a measure of tissue accumulation of advanced glycation end products (AGEs), has been associated with diabetes and cardiovascular disease. However, the association of skin AF with subclinical coronary atherosclerosis in the general population is largely unknown. Our study aimed to examine the associations between skin AF and subclinical atherosclerosis in coronary and carotid arteries in a middle-aged population. MethodsSkin AF and subclinical atherosclerosis were measured in 4416 subjects (aged 50–64 years) from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Skin AF was measured non-invasively using an autofluorescence reader. Subclinical atherosclerosis was assessed by ultrasonography of carotid arteries for evaluation of carotid plaques and computed tomography for the evaluation of the coronary artery calcium score (CACS). ResultsA total of 615 (13.9%) individuals had CACS >100 and 1340 (30.3%) subjects had bilateral carotid plaques (median total plaque area: 8 mm2). After controlling for confounding factors, there were significant associations between skin AF (per 1 standard deviation (SD) increase) and CACS >100: odds ratio (OR) = 1.17, 95% confidence interval (CI): 1.06–1.29, p = 0.001. Total carotid plaque area and occurrence of bilateral carotid plaques (OR per 1 SD increase: 1.10, 95%CI: 1.01–1.19, p = 0.02) were similarly associated with skin AF after multivariable adjustments. ConclusionsElevated skin AF was significantly associated with subclinical atherosclerosis in coronary and carotid arteries independently of conventional risk factors. Skin AF, a measure of accumulation of AGEs, could be a marker for the identification of middle-aged subjects with elevated atherosclerotic risk.

Prevalence of Microalbuminuria and Its Association with Subclinical Carotid Atherosclerosis in Middle Aged, Nondiabetic, Low to Moderate Cardiovascular Risk Individuals with or without Hypertension.

Microalbuminuria is closely associated with the risk of cardiovascular disease and all-cause mortality in the general population. Less is known about its relationship with subclinical atherosclerosis. We aimed to assess the prevalence of microalbuminuria and its relationship with subclinical atherosclerosis in middle-aged, nondiabetic, apparently healthy individuals (N = 187; 40.1% men, 59.9% women; aged 35–55 years) as well as to evaluate its potential associations with established risk modifiers, especially with the presence of carotid plaque. Clinical and laboratory parameters, the estimated 10-year fatal cardiovascular risk (SCORE), as well as circulating, functional (flow mediated vasodilation, ankle-brachial index, augmentation index, and pulse wave velocity), and morphological markers (mean carotid intima–media thickness, and carotid plaque) of subclinical atherosclerosis were analysed in group with vs. without microalbuminuria. Microalbuminuria was present in 3.8% of individuals with SCORE risk 0.43 ± 0.79%. Functional markers predominated in both groups. Carotid intima–media thickness (mean ± SD) in both groups was in range: 0.5–0.55 ± 0.09–0.14 mm. Carotid plaque was more frequent in group with (14.3%) vs. without (4.4%) microalbuminuria. Microalbuminuria had no statistically significant effect on most markers of subclinical atherosclerosis, but the increasing value of microalbuminuria was significantly associated with the occurrence of carotid plaque (p = 0.035; OR = 1.035; 95% CI = 1.002–1.07). Additional multiple logistic regression analysis, where variables belonged to microalbuminuria, number of risk factors, and family history, finally showed only two variables: microalbuminuria (p = 0.034; OR = 1.04; 95%CI = 1.003–1.09) and the number of risk factors (p = 0.006; OR = 2.15; 95% CI = 1.24–3.73) with independent and significant impact on the occurrence of carotid plaque. Our results may indicate an association of microalbuminuria with the presence of carotid atherosclerotic plaque; in addition, microalbuminuria and the number of risk factors appear to be possible predictors of the carotid plaque occurrence. Monitoring microalbuminuria may improve the personalized cardiovascular risk assessment in nondiabetic, low-to-moderate cardiovascular risk individuals with or without hypertension.

Relationship of Neutrophil-to-Lymphocyte Ratio with Carotid Plaque Vulnerability and Occurrence of Vulnerable Carotid Plaque in Patients with Acute Ischemic Stroke.

Background Carotid plaque is an undefined risk factor in ischemic stroke and is driven by inflammation. Mounting evidence suggests that neutrophil-to-lymphocyte ratio (NLR) is crucial not only for cerebrovascular events but also in atherosclerosis progression. Here, we aimed to explore the association between the admission NLR and carotid plaque vulnerability as well as the occurrence of vulnerable carotid plaque detected by carotid ultrasonography in patients with acute ischemic stroke (AIS) among Chinese. Methods We conducted a retrospective study composed of 588 patients with AIS and 309 healthy controls free of carotid plaque in the Department of Neurology in The Second Hospital of Lanzhou University from March 2014 to February 2015. All patients were classified as nonplaque, stable plaque, and vulnerable plaque groups on the basis of carotid ultrasonography results. The baseline information was collected and compared among the four different groups. The correlation between variables and carotid plaque vulnerability was tested by Spearman linear correlation analysis. To identify the independent predictors for vulnerable carotid plaque, univariate and multivariate logistic regression analysis was performed. Results The comparisons of age, sex proportion, history of hypertension, diabetes, and smoking, the levels of HDL-C, Lp(a), BMI, SBP, DBP, Fib, CRP, leukocyte, and NLR among the four groups showed a statistically significant difference (P < 0.05); in particular, the NLR was significantly higher in the vulnerable plaque group as compared to the control (P = 0.043), nonplaque (P = 0.022), and stable plaque groups (P = 0.015). The Spearman correlation analysis presented a positive correlation between carotid plaque vulnerability and age (r = 0.302; P < 0.001), SBP (r = 0.163; P < 0.001), and NLR (r = 0.087; P = 0.034), while the lymphocyte was negatively related to the carotid plaque vulnerability (r = −0.089; P = 0.030). The multivariate logistic regression analysis adjusted for confounding factors revealed that age (odds ratio [OR], 1.042; 95% confidence interval [CI], 1.025-1.060; P < 0.001), male gender (OR, 2.005; 95% CI, 1.394-2.884; P < 0.001), diabetes (OR, 1.481; 95% CI, 1.021-2.149; P = 0.039), SBP (OR, 1.012; 95% CI, 1.003-1.021; P = 0.010), and NLR (OR, 1.098; 95% CI, 1.018-1.184; P = 0.015) are independent predictors of vulnerable carotid plaque in patients with AIS. Conclusion The admission NLR is a novel and meaningful biomarker that can be used in predicting carotid plaque vulnerability and the presence of vulnerable carotid plaque assessed by carotid ultrasonography in patients with AIS among Chinese.