Coronary Artery Disease Subjects Research Articles

Circulating trimethylamine N-oxide is correlated with high coronary artery atherosclerotic burden in individuals with newly diagnosed coronary heart disease

BackgroundTrimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota and has been reported to be correlated with cardiovascular diseases. Although TMAO is associated with the severity of coronary artery disease in subjects with coronary heart disease (CHD) history. However, the correlation between TMAO and the atherosclerotic burden in newly diagnosed cases of CHD is unknown.MethodsIn this hospital-based study, we enrolled 429 individuals newly diagnosed with CHD undergoing coronary angiography. Plasma TMAO was assessed before coronary angiography. SYNTAX score was computed during coronary angiography to estimate the coronary artery atherosclerotic burden. Both linear and logistic regression analyses were conducted to explore the correlation between plasma TMAO levels and SYNTAX score in newly diagnosed CHD population.ResultsThe TMAO in patients with SYNTAX ≥ 33 and subjects with SYNTAX < 23 were 6.10 (interquartile range [IQR]: 3.53 to 9.15) µmol/L and 4.90 [IQR: 3.25 to 7.68] µmol/L, respectively. Linear regression adjusting for traditional risk factors showed TMAO level was positively correlated with SYNTAX score (β = 0.179; p = 0.006) in CHD population. When TMAO was added to models with traditional risk factors, the predictive value improved significantly, with the receiver operating characteristic curve (AUC) increased from 0.7312 to 0.7502 (p = 0.003). Stratified analysis showed that the correlations did not hold true for subjects who were non-smoker or with histories of diabetes. None of the stratifying factors significantly altered the correlation (all p for interaction < 0.05).ConclusionsWe found a positive linear correlation between plasma TMAO and SYNTAX score among newly diagnosed CHD individuals in Chinese population.

Upstroke time is a more useful marker of atherosclerosis than percentage of mean arterial pressure for detecting coronary artery disease in subjects with a normal ankle-brachial index.

Upstroke time (UT) and percentage of mean arterial pressure (%MAP) at the ankle have been shown to serve as atherosclerotic markers. The purpose of this study was to directly compare the diagnostic accuracy of UT with that of %MAP for clinical coronary artery disease (CAD) in subjects with a normal ankle-brachial index (ABI) in both legs. We measured UT and %MAP in 1953 subjects with a normal ABI. The optimal cutoff values of UT and %MAP derived from a receiver operating characteristic (ROC) curve to diagnose CAD were 148 ms and 40.4%, respectively. Multivariable analyses revealed that both UT ≥ 148 ms (odds ratio [OR], 2.72; p < 0.001) and %MAP ≥ 40.4% (OR, 1.28; p = 0.003) were significantly associated with CAD. When the subjects were divided into four groups according to the cutoff values of UT and %MAP, there was no significant difference in the risk of CAD between subjects with UT ≥ 148 ms and %MAP < 40.4% and those with UT ≥ 148 ms and %MAP ≥ 40.4% (OR, 1.45; p = 0.09). ROC curve analyses revealed that the area under the curve value of UT was significantly higher than that of %MAP (0.69 vs. 0.53, p < 0.001). The addition of UT to traditional risk factors significantly improved the diagnostic accuracy for CAD (0.82 to 0.84, p = 0.004), whereas the addition of %MAP to traditional risk factors did not improve the diagnostic accuracy for CAD (0.82 to 0.82, p = 0.84). UT is more useful than %MAP for identifying individuals with CAD among those with a normal ABI.

Enhancing Coronary Artery Diseases Screening: A Comprehensive Assessment of Machine Learning Approaches Using Routine Clinical and Laboratory Data.

Introduction: Coronary artery disease (CAD) stands among the leading global causes of mortality, underscoring the critical necessity for early detection to facilitate effective treatment. Although Coronary Angiography (CA) serves as the gold standard for diagnosis, its limitations for screening, including side effects and cost, necessitate alternative approaches. This study focuses on the development and comparison of machine learning techniques as substitutes for CA in CAD screening, leveraging routine clinical and laboratory data.Material and Methods: Various machine learning classification algorithms—decision tree, k-nearest neighbor, artificial neural network, support vector machine, logistic regression, and stacked ensemble learning—were employed to differentiate CAD and healthy subjects. Feature selection algorithms, namely LASSO and ReliefF, were utilized to prioritize relevant features. A range of evaluation metrics, including accuracy, precision, sensitivity, specificity, AUC, F1 score, ROC curve, and NPV, were applied. The SHAP technique was employed to elucidate and interpret the artificial neural network model.Results: The artificial neural network, support vector machine, and stacked ensemble learning models demonstrated excellent results in a 10-fold cross-validation evaluation using features selected by LASSO and ReliefF. With the LASSO feature selection algorithm, these models achieved accuracies of 90.38%, 90.07%, and 90.39%, sensitivities of 94.43%, 93.03%, and 93.96%, and specificities of 80.27%, 82.77%, and 81.52%, respectively. Using ReliefF, the accuracies were 88.79%, 88.77%, and 90.06%, sensitivities were 92.12%, 91.66%, and 93.98%, and specificities were 80.13%, 81.38%, and 80.13%, respectively. The SHAP technique revealed that typical and atypical chest pain, hypertension, diabetes mellitus, T inversion, and age were the most influential features in the neural network model.Conclusion: The machine learning models developed in this study exhibit high potential for non-invasive screening and diagnosis of CAD in the Z-Alizadeh Sani dataset. However, further studies are essential to validate and apply these models in real-world and clinical settings.

Prevalence and Burden of Carotid and Femoral Atherosclerosis in Subjects Without Known Cardiovascular Disease in a Large Community Hospital in South-America.

Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD). To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD. We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries. Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF. We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA.

Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Artery Disease.

Monocytes are associated with human cardiovascular disease progression. Monocytes are segregated into three major subsets: classical (cMo), intermediate (iMo), and nonclassical (nMo). Recent studies have identified heterogeneity within each of these main monocyte classes, yet the extent to which these subsets contribute to heart disease progression is not known. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects within the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using the Gensini Score (GS). We employed high-dimensional single-cell transcriptome and protein methods to define how human monocytes differ in subjects with low to severe coronary artery disease. We analyzed 487 immune-related genes and 49 surface proteins at the single-cell level using Antibody-Seq (Ab-Seq). We identified six subsets of myeloid cells (cMo, iMo, nMo, plasmacytoid DC, classical DC, and DC3) at the single-cell level based on surface proteins, and we associated these subsets with coronary artery disease (CAD) incidence based on Gensini score (GS) in each subject. Only frequencies of iMo were associated with high CAD (GS > 32), adj.p = 0.024. Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r = 0.314, p = 0.014) and further showed a robust sex-dependent positive correlation in female subjects (r = 0.663, p = 0.004). cMo frequencies did not correlate with CAD severity. Key gene pathways differed in iMo among low and high CAD subjects and between males and females. Further single-cell analysis of iMo revealed three iMo subsets in human PBMC, distinguished by the expression of HLA-DR, CXCR3, and CD206. We found that the frequency of immunoregulatory iMo_HLA-DR+CXCR3+CD206+ was associated with CAD severity (adj.p = 0.006). The immunoregulatory iMo subset positively correlated with GS in both females (r = 0.660, p = 0.004) and males (r = 0.315, p = 0.037). Cell interaction analyses identified strong interactions of iMo with CD4+ effector/memory T cells and Tregs from the same subjects. This study shows the importance of iMo in CAD progression and suggests that iMo may have important functional roles in modulating CAD risk, particularly among females.

Detection of Coronary Artery Disease Based on Clinical Phonocardiogram and Multiscale Attention Convolutional Compression Network.

Heart sound is an important physiological signal that contains rich pathological information related with coronary stenosis. Thus, some machine learning methods are developed to detect coronary artery disease (CAD) based on phonocardiogram (PCG). However, current methods lack sufficient clinical dataset and fail to achieve efficient feature utilization. Besides, the methods require complex processing steps including empirical feature extraction and classifier design. To achieve efficient CAD detection, we propose the multiscale attention convolutional compression network (MACCN) based on clinical PCG dataset. Firstly, PCG dataset including 102 CAD subjects and 82 non-CAD subjects was established. Then, a multiscale convolution structure was developed to catch comprehensive heart sound features and a channel attention module was developed to enhance key features in multiscale attention convolutional block (MACB). Finally, a separate downsampling block was proposed to reduce feature losses. MACCN combining the blocks can automatically extract features without empirical and manual feature selection. It obtains good classification results with accuracy 93.43%, sensitivity 93.44%, precision 93.48%, and F1 score 93.42%. The study implies that MACCN performs effective PCG feature mining aiming for CAD detection. Further, it integrates feature extraction and classification and provides a simplified PCG processing case.

Diagnostic potential of SORT1 gene in coronary artery disease

BackgroundGenome-wide association studies identify SORT1 gene associated with risk of coronary artery disease (CAD). Sortilin protein enhances LDL absorption, form cell development, and atherosclerosis in macrophages. AimWe therefore explored SORT1 expression in CAD patients and its gene expression’s predictive usefulness for the severity of the disease. MethodologyThis is a case control study and Quantitative real-time PCR; Sandwich ELISA and western blotting were used to determine the expression of SORT1 gene at the mRNA and protein level in two hundred healthy controls and two hundred patients with various CAD syndromes. ResultsCAD patients exhibit higher SORT1 gene expression in CAD patients, a higher concentration of sortilin in their plasma, and distinct expression patterns in various CAD syndromes. The study reveals a positive correlation between gene expression and the severity of coronary artery stenosis, the number of diseased vessels, and the presence of diabetes. ROC curve analysis of SORT1 gene expression both at mRNA and protein level showed strong discrimination between significant CAD and control subjects. ConclusionTherefore, elevated SORT1 gene expression in various CAD syndromes may be a potential biomarker for the disease.

Correlation of circulatory VEGF and miRNA 126 in angiographically proven coronary artery disease and its clinical importance

Background: Atherosclerotic ischemic coronary artery disease (CAD) is a major cause of morbidity and mortality in both developed and developing countries, indicating the need for the discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Vascular endothelial growth factor (VEGF) may have some role, in the progression of human coronary atherosclerosis. Circulating microRNAs (miR) have a potential as a diagnostic as well as a prognostic biomarker of cardiovascular disease and dysfunctions. Aims and Objectives: The aim of the study was to correlate the levels of miRNA-126 and VEGF in the serum of CAD patients. Materials and Methods: The study was conducted on 100 cases of freshly diagnosed CAD patients (angiographically proven) and 80 normal healthy patients. Various serum biomarkers were estimated. The level of serum VEGF and Mi-RNA was correlated for CAD patients. Results: Highly significantly difference was found in levels of hemoglobin A1C, low density lipoprotein, total cholesterol, and total homocysteine while high-density lipoproteins and triglycerides were less significantly different for controls and cases. VEGF levels of CAD cases were found to be very significantly higher as compared to controls. The miRNA-126 expression was found to be lower in the CAD subjects compared to non-CAD subjects. Conclusion: The study was suggested the role of VEGF in atherogenesis and plaque instability. No significant correlation was found among between miR-126 levels and VEGF levels among CAD cases. The study is limited by a smaller sample size and was single-centered; therefore, multicentric study with a larger patient cohort needs to be done and to validate our findings.

Plasma Lipid Profile and Apolipoproteins in Patients with Coronary Artery Diseases and Healthy Persons, in Sana'a City, Yemen

Background: Cardiovascular disease (CVD) is the primary cause of all disease loads and accounts for almost half of all fatalities. The early detection of coronary artery disease (CAD) has drawn a lot of attention because it is anticipated that the global burden of cardiovascular disease will rise by almost 75% by 2020. They are easily oxidized, which causes an increase in affinity for arterial proteoglycans and a decrease in affinity for LDL receptors. It demonstrates significant CAD importance.&#x0D; Objective: The measurement of plasma lipid profiles and apolipoproteins (ApoA-1, ApoB, and Apo B/A-1 ratio) in healthy individuals and patients suffering from coronary artery disease.&#x0D; Methods: In this cross-sectional comparative study, 90 Yemeni subjects aged 45 to 70 years were divided into three groups: Group I: 30 cases as CAD positive (CAD+). Group II: 30 cases CAD negative (CAD -). Group III: 30 healthy person was as control. A standardized questionnaire was administered to collect demographic and clinical data from participants. Venous blood (10 ml) was collected from each individual and divided into two portions. The first portion was 5 ml in plain tubes, ApoA-1 and Apo B vacuum tubes for freezing at -20°C until analysis. 5ml in a plain tube for measuring fasting blood glucose, and lipid profile.&#x0D; Results: ApoB and Apo B/A ratios were significantly higher in CAD+ and CAD− subjects compared to controls. In addition, ApoB and Apo B/A ratios were significantly higher in CAD+ subjects compared to CAD- subjects. (P. value =0.002). In contrast, Apo A-1 was significant in CAD+ compared to CAD- and controls, and not significantly different between CAD and controls P. value = (0.001, 0.032). Furthermore, FBS and LDL-c were significantly higher in CAD+ compared to CAD subjects (P value = 0.05). In contrast, HDL-c was significantly lower in CAD+ compared to CAD and controls, with no significant difference between CAD and controls (P value=0.038, 0.004, 0.70). However, TG was not substantially different between CAD- and controls, but it was significantly greater in CAD+ compared to controls (P. value =0.002, 0.09, 0.31). Nevertheless, there was no difference in TC between study groups (P. value = 0.08, 0.12, 0.98).&#x0D; Conclusions: The degree of CAD is significantly positively correlated with WHR. More important than overall obesity, abdominal obesity is a risk factor for coronary heart disease (CHD). A significant positive connection has been observed between the Apo B/Apo A ratio and CAD. One thing to think about as a CAD risk factor is Apo B.

CORRELATION OF POINCARE PLOT DERIVED STRESS SCORE AND HEART RATE VARIABILITY PARAMETERS IN THE ASSESSMENT OF CORONARY ARTERY DISEASE

Atherosclerosis-generated coronary artery disease (CAD) causes the anomaly of autonomic activity. The assessment of autonomic balance under disease conditions is of clinical interest. Thus, this work aimed to evaluate the CAD using Poincare-derived stress score (SS) and sympathetic/sympathetic-parasympathetic (S/PS). A total of 60 male (50–55 years) volunteers including CAD ([Formula: see text]=30) and control ([Formula: see text]=30) participated in this work. Digital lead-II electrocardiogram (ECG) was recorded for 10 min in a supine position and filtered to remove noises. A total of 10 tachogram samples were computed from each subject for a 5 min ECG signal duration with a shift of 30 s on the processed signal using Acqknowledge 4.0 (Biopac Systems Inc., USA). The heart rate variability (HRV) parameters were computed from the obtained tachogram. The computed Poincare plot parameters were used to derive the SS and S/PS ratios. The regression model was employed to observe the correlation of SS and S/PS to the HRV parameters. The obtained results revealed reduced HRV with higher sympathetic and reduced parasympathetic activity under CAD than the control subjects. The autonomic dysfunction was observed with significantly higher values of SS and S/PS in CAD than in the control subjects. The S/PS was observed to be positively associated with LF/HF and SD2/SD1 parameters. While SS was found to be positively correlated to the LF and LF/HF parameters in CAD and control subjects. The obtained linear strong correlation of SS and S/PS with control and CAD subjects suggested the use of SS and S/PS as excellent sympathetic activity and sympathovagal balance markers.

Prognostic value of CT-derived fractional flow reserve and fat attenuation index in patients with suspected coronary artery disease: a sex-disaggregated analyses

BackgroundThere are sex differences in many risk factors associated with coronary artery disease (CAD). CT-derived fractional flow reserve (CT-FFR) and fat attenuation index (FAI) have been shown to independently predict cardiovascular events. We aimed to examine the impact of sex on the prognostic value of CT-FFR and FAI in suspected CAD patients, and to examine the incremental prognostic value of FAI over CT-FFR in both sex.MethodsA total of 1334 consecutive suspected CAD subjects who underwent coronary computed tomographic angiography (CCTA) were retrospectively collected. We divided the patients into males and females and calculated CT-FFR and FAI data from CCTA images. Kaplan-Meier analysis was used to assess the risk of major adverse cardiovascular events (MACE) stratified by CT-FFR and FAI in both sex. Cox regression models were used to assess the incremental prognostic value of FAI by adding the variable to a model that included CT-FFR and clinical variables.ResultsDuring a median follow-up of 2.08 years, 212 patients had MACE. CT-FFR ≤ 0.80 was significantly associated with MACE in both sex. FAI value of left anterior descending artery (FAI[LAD]) and FAI value of left circumflex (FAI[LCX]) ≥ 70.1 were significantly associated with MACE in females. FAI[LCX] added incremental prognostic value over clinical and CT-FFR variables in females, with hazard ratio (HR) 3.230 (1.982–5.265, P = 0.000), Harrel’s C 0.669 (P < 0.001), net reclassification improvement (NRI) 0.161 (0.073–0.260, P < 0.001), and integrated discrimination index (IDI) 0.036 (0.008–0.090, P = 0.010). FAI[LAD] did not enhance risk prediction in females (Harrel’s C 0.643, P = 0.054; NRI 0.041, P = 0.189; IDI 0.005, P = 0.259). The decision curve analysis demonstrated that the model including FAI[LCX] resulted in the highest net benefit.ConclusionsIn suspected CAD patients, the prognostic value of CT-FFR is not significantly biased by sex. The prognostic value of FAI[LAD] and FAI[LCX] were significantly associated with MACE in females, but not males. FAI[LCX], not FAI[LAD], added incremental prognostic value over CT-FFR and might enhance CT-FFR risk stratification in females.

The effect of homocysteine-lowering therapy on the formation of carotid atherosclerosis: A follow-up study in the rural areas of northwest China

ObjectiveTo explore the risk factors for carotid atherosclerosis in the rural areas of Northwest China, and to assess whether reducing serum homocysteine can prevent carotid atherosclerosis in subjects with hyperhomocysteinemia. MethodThis observational study with 767 participants aged 40 years or older was conducted over 3 years. Color Doppler ultrasonography was performed to measure carotid atherosclerosis. We recorded biochemical indexes and carotid ultrasound results in the first and fourth years. ResultA total of 767 individuals (48.5 % men) were analyzed. Older age, hypertension, and higher levels of baseline low-density lipoprotein cholesterol (LDL-C) were risk factors for increased carotid intima-media thickness (CIMT), carotid plaque, and carotid stenosis (All P < 0.05). No association was found between decreased serum homocysteine (Hcy) levels and CIMT, carotid plaque, or carotid stenosis in individuals with hyperhomocysteinemia. ConclusionOlder age, hypertension, and higher baseline levels of LDL-C were independent risk factors for carotid atherosclerosis. Reducing serum Hcy levels may not prevent carotid atherosclerosis in the general population with hyperhomocysteinemia.

Peripheral blood mononuclear cells expression of miR-200c, miR-125b, miR-27b, miR-203, and miR-155 in patients with significant or insignificant coronary artery stenosis

Coronary artery disease (CAD) is one of the principal causes of death worldwide. Among several predisposing factors, inflammation and inflammatory genes play a significant role in disease pathogenesis. Inflammatory microRNAs, small noncoding RNAs involved in regulating inflammation, are promising candidates for understanding pathogenesis of CAD and developing diagnostic biomarkers. The aim of the study was to evaluate the alteration of miR-200c, miR-125b, miR-27b, miR-203 and, miR-155 in patients suffering from coronary artery stenosis and insignificant coronary artery stenosis compared to healthy subjects. In this study we compared expressions of five inflammatory miRNAs in peripheral blood mononuclear cells (PBMCs) of 72 patients suffering significant coronary artery stenosis (CAD), 74 individuals without coronary artery disease and 30 individuals with insignificant coronary artery stenosis (ICAD). After blood collection, PBMCs were isolated and RNA was extracted. Gene expression levels were assessed by SYBR green based real-time PCR. Statistical analysis was performed using R program. Expression levels of miR-200c, miR-203, and miR-155 were lower in subjects with ICAD than that in CAD patients and subjects of the control group. MiR-125b was downregulated in CAD and ICAD groups compared to the control group. PBMC miR-27b was upregulated in the CAD group as compared to the ICAD and control groups. Receiver operating characteristic curve analysis verified potential of three miRNAs in separating subjects with ICAD from CAD patients and healthy individuals. In conclusion, this original investigation suggested that altered expression of these five miRNAs may serve as a novel diagnostic biomarker discriminating clinical presentations of coronary artery diseases.

Borderline hyperlipidemia preventive management with Berberine PL in asymptomatic prevention of early atherosclerosis.

The aim of this pilot, efficacy supplement registry was to use a supplementary management with berberine to control hyperlipidemia. The supplement Berberine (Berbevis™ as Sophy® tablets) was used to control lipids and to evaluate (as a natural, preventive management) the early evolution of subclinical atherosclerosis in subjects (otherwise healthy, not using drugs) with borderline hyperlipidemia. The registry involved two groups of subjects not using drugs for a total of 50 subjects and three months of supplementation. The registry groups using standard management (SM) or SM and supplement were resulted comparable. No side effects were observed during the three months of berberine supplementation. No tolerability problems were reported. All subjects managed with berberine completed the three-month registry. Compliance was >97% (% of correctly used tablets). Total cholesterol was significantly decreased with berberine (P<0.05) and HDL was significantly improved (P<0.5) with supplementation. Triglycerides decreased in the berberine groups (P<0.05) and the levels of CoQ10 remained within normal values in supplemented subjects. Oxidative stress - measured in Carr units - was significantly decreased with berberine (P<0.05). Routine blood tests remained within normal values during the registry. Body weight was significantly more decreased (P<0.05) with berberine in comparison with standard management. The fat proportion also decreased (P<0.05) with berberine supplementation and the abdominal fat thickness (in the peri-umbilical area) was significantly decreased after berberine supplementation (P<0.05). This pilot registry indicates that berberine administration is effective in reducing lipids (decreasing weight, fat percentage and abdominal fat) in otherwise healthy subjects not using drugs. A longer study, with more advanced hyperlipidemic subjects is suggested. Predictive analytics according to Siegel suggests that a six-month study with 60 patients, in more advanced hyperlipidemic, also evaluating the intima-media thickness for the analysis of vascular benefits, may produce a stronger evaluation for this product.

High Atherogenic Risk in Ketosis-Prone Type 2 Diabetic Individuals with Ketosis Episodes: A Cross-Sectional Study.

Diabetes is an important contributor to the progression of atherosclerosis (AS). We aimed to investigate the correlation between ketosis episodes and lipid-related parameters in patients with new-onset ketosis-prone type 2 diabetes (KPT2D), further attempting to assess the impact of ketosis episodes on AS. A cross-sectional study of 147 subjects with new-onset diabetes was performed, including 65 KPT2D subjects (KPT2D group) and 82 non-ketotic type 2 diabetes (T2D) (T2D group) subjects. Anthropometric and biochemical parameters were measured in all subjects. Calculation of atherogenic index of plasma (AIP) by traditional lipid parameters. The AIP (P = 0.008) level and the percentage of AIP ≥ 0.24 (P = 0.026) in subjects with KPT2D were higher than in subjects with T2D. The apoA1 (P = 0.001) levels were significantly lower in patients with KPT2D than in patients with T2D. In the KPT2D group, plasma ketones were positively correlated with AIP (P = 0.023) and negatively correlated with apoA1 (P = 0.002). Univariate logistic regression suggested that plasma ketone (OR = 1.704, P = 0.040) was an important related factor for the AS in subjects with KPT2D. Multiple linear regression suggested plasma ketone was significantly positive with AIP (β = 0.437, P = 0.020). In multiple linear regression analysis suggests that apolipoprotein A1 (β = -0.335, P = 0.033) is strongly associated with ketotic episodes in newly diagnosed ketosis-prone type 2 diabetic patients. Ketosis episodes in patients with KPT2D were significantly and positively associated with elevated AIP levels and reduced apoA1 levels. Frequent ketosis episodes may accelerate the progression of AS.

Long-term efficacy and safety of early alogliptin initiation in subjects with type 2 diabetes: an extension of the SPEAD-A study

We previously reported in the study of preventive effects of alogliptin on diabetic atherosclerosis (SPEAD-A) that alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the progression of carotid atherosclerosis in subjects with type 2 diabetes and no history of cardiovascular disease. This extension study of the SPEAD-A trial investigated whether early alogliptin initiation improved long-term cardiovascular outcomes. The SPEAD-A trial randomized 341 subjects with type 2 diabetes to either alogliptin or conventional treatment to investigate the effects of alogliptin on atherosclerosis. All subjects who completed that trial were eligible for this prospective, observational cohort study. The primary endpoint was the first occurrence of a major cardiovascular event, defined as death due to any cause, acute myocardial infarction, or stroke. During the 520-week follow-up period, composite primary outcome events occurred in only a few subjects in each group [8 (5.4%) in the alogliptin group and 9 in the conventional treatment group (5.9%)]. There were no significant differences in the incidence rate of the primary outcome between the two groups. Post hoc Poisson regression analysis showed no significant difference between the two groups in the incidence rate of composite recurrence events for the same outcomes as the primary endpoint. On the other hand, this incidence rate was significantly lower in subjects who received DPP-4 inhibitors before an initial cardiovascular event than in those who did not (5.8 vs. 13.3 per 1000 person-years, respectively, p = 0.04). Early initiation of alogliptin was not associated with a reduced risk of composite cardiovascular disease, which could be attributed to fewer events and/or the addition of DPP-4 inhibitors during the follow-up period.

Association of Klotho with Coronary Artery Disease in Subjects with Type 2 Diabetes Mellitus and Preserved Kidney Function: A Case-Control Study.

Circulating Klotho levels are significantly reduced in subjects with type 2 diabetes mellitus (T2DM) and in kidney disease patients. In this work, the relationship between Klotho levels and the coronary artery disease (CAD) burden in subjects with T2DM and preserved kidney function was analyzed. For this, we performed a cross-sectional case-control study involving 133 subjects with T2DM and 200 age-, sex- and CAD-incidence-matched, non-diabetic patients undergoing non-emergency diagnostic coronary angiography. All of them were non-albuminuric and with normal glomerular filtration rates. The concentrations of serum Klotho, fibroblast growth factor 23, and inflammatory markers were also measured. As expected, the serum Klotho concentration was lower in the T2DM group (12.3% lower, p = 0.04). However, within the group of patients with T2DM, those subjects with CAD presented significantly higher Klotho levels than those without significant coronary stenosis (314.5 (6.15-562.81) vs. 458.97 (275.2-667.2) pg/mL; p = 0.02). Multiple regression analysis revealed that serum Klotho was positively related with stenosis values exclusively in subjects with T2DM (adjusted R2 = 0.153, p < 0.01). Moreover, logistic regression analysis showed that Klotho was positively associated with the presence of significant CAD in the group of T2DM patients (OR: 1.001; p = 0.041). Our data suggest that higher levels of circulating Klotho in subjects with T2DM and preserved kidney function are associated with the presence of significant CAD.

The microcirculatory endothelial function was a more sensitive method in evaluating the risk assessment of coronary artery disease in subjects with type2 diabetes

The microcirculatory endothelial function was a more sensitive method in evaluating the risk assessment of coronary artery disease in subjects with type2 diabetes

The incidence of subclinical atherosclerosis in subjects with low and moderate cardiovascular risk.

The cardiovascular risk models and subclinical atherosclerotic indicators are both recommended for cardiovascular risk stratification. The accordance between the incidence of subclinical atherosclerosis and subjects with low and moderate cardiovascular risk is unclear. Subjects with low and moderate cardiovascular risk have a lower incidence of subclinical atherosclerosis compared with subjects with high risk. Brachial-ankle pulse wave velocity (BaPWV) and brachial flow-mediated dilation (BFMD) were measured in 421 subjects without a history of atherosclerotic cardiovascular disease (ASCVD) from October 2016 to January 2020. All subjects were classified into low, moderate, and high risk based on Framingham and China-par risk models respectively. Mean age was 57.05 ± 9.35 years and 248 (58.9%) were male. In subjects with low, moderate, and high risk assessed by Framingham and China-par risk models, the percentage of abnormal BaPWV ( > 1400 cm/s) was 42.9%, 70.1%, 85.7%, and 40.4%, 71.4%, 89.7%, respectively. Meanwhile, the percentage of abnormal BFMD ( ≤ 7%) was 43.8%, 68.5%, 77.3%, and 44.9%,72.1%, and 76.6%. According to Framingham-based high-risk categories, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for BaPWV abnormality were 85.7%, 39.4%, 36.1%, and 87.5%, respectively. For BFMD abnormality, the values were 77.3%, 40.1%, 34.1%, and 81.8%, respectively. According to China-par high-risk categories, the values for BaPWV abnormality were 89.7%, 43.8%, 45.6%, and 89.0%, respectively. For BFMD abnormality, the values were 76.6%, 41.3%, 40.7%, and 77%, respectively. In multivariate analysis, age and blood pressure were the independent predictors for subclinical atherosclerosis in subjects with low-moderate risk. More than one-half of subjects with low and moderate risk already have detectable subclinical atherosclerosis, indicating higher cardiovascular risk beyond the traditional stratification.

Serum Urate Levels and Ultrasound Characteristics of Carotid Atherosclerosis across Obesity Phenotypes.

Existing evidence suggests a close link among high levels of serum urate (SU), obesity and carotid atherosclerosis. The aim of the present study was to evaluate the interrelations between SU levels and carotid atherosclerosis in subjects with different obesity phenotypes. In this study, a total of 2076 subjects (mean age 48.1 ± 13.1 years; 1307 women) were recruited: 59 with general obesity, 616 with central obesity, 715 with mixed (general-central) obesity and 686 non-obese. Anthropometric measurements, vascular risk factors, blood biochemistry analysis (including SU levels), and carotid ultrasound were performed. Ultrasound assessment included evaluation of intima-media thickness (IMT) and plaque characteristics, including number, total area and type (vulnerable vs. stable) of plaques. After adjustment for potential confounders, the highest levels of SU were observed in subjects with mixed obesity, followed by subjects with central obesity, general obesity and the non-obese (309.4 ± 82.2 vs. 301.2 ± 73.1 vs. 272.9 ± 61.8 vs. 234.2 ± 59.8 μmol/L, respectively; F = 149.2, post hoc p < 0.001). Similarly, subjects with mixed and central obesity presented higher values of IMT compared to subjects with general obesity and the non-obese (0.68 ± 0.16 vs. 0.67 ± 0.16 vs. 0.62 ± 0.14 vs. 0.57 ± 0.13 mm, respectively; F = 54.2, post hoc p < 0.001). No difference in number, total area and type of plaques among obesity groups were attested (all p > 0.05). Significantly higher IMT values were observed in subjects with increased SU levels compared to subjects with normal SU levels (0.70 ± 0.10 vs. 0.62 ± 0.14 mm, p = 0.02) only within the central obesity group. Increasing levels of SU were associated with a higher frequency of increased IMT only in subjects with central obesity (OR 1.033, 95% CI 1.025-1.041). Similarly, SU levels yielded a satisfactory performance in detecting subjects with increased IMT (AUC 0.65, 95% CI 0.50-0.73, subjects with carotid plaques (0.62, 95% CI 0.55-0.68) and subjects with vulnerable plaque types (0.68, 0.59-0.76) only within the central obesity group. Among the studied obesity types, the association between SU levels and markers of carotid atherosclerosis was of particular significance in subjects with central obesity.