Risk Factors For Atherosclerosis Research Articles

Chemical Composition and Therapeutic Potential of Syngonium podophyllum L. Leaves against Hypercholesterolemia in Rats: Liver, Kidney, and Heart Crosstalk

Background: One of the main risk factors for atherosclerosis is hypercholesterolemia Objective: This study aimed to assess hypercholesterolemia's effect on the liver, heart, and kidney and the impact of Syngonium podophyllum L. leaves methanolic extract as a treating agent in a rat model. Methods: Flavonoid components were isolated and identified from the methanolic extract of Syngonium podophyllum L. leaves. Total serum leptin, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), aspartate and alanine aminotransferases (AST and ALT), urea, and creatinine levels were all measured as part of the biochemical evaluation. The liver tissue was tested for levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and DNA fragmentation. Results: Thirty-nine compounds were identified by GC/MS profiling of the n-hexane fraction of Syngonium podophyllum L leaves. The major volatile constituents were decane, 4-methyl, decane, N-acetyl 3-pentenyl, 1-amine, 2-methyl, 1-hexene, and 3-hydroxy, propanenitrile, while the major phenolic compounds isolated from methanolic extract were luteolin-7- α-L rhamnoside-4'- O-β-glucopyranoside (1), apigenin 6, 8-di-C-β-glucopyranoside (vicenin 2) (2), quercetin-3-Oα-L-rhamnoside (3), quercetin-7-O-β-glucoside compound (4), luteolin-7-O-β-glucoside (5), 5- hydroxy-6,7,8,4'-tetramethoxy flavone (6), gallic acid (7) and quercetin (8). Hypercholesterolemic rats revealed significant alterations (p ≤ 0.05) in the lipid profile, liver and kidney function, DNA fragmentation pattern and antioxidant indices. With oral cholesterol administration of 30 mg/0.3 mL, 0.7% tween/rats fed a high-fat diet for nine weeks, treatment with leaves extract (250 mg/kg body weight) was able to restore all biochemical parameters as well as the architectures of the liver and heart. Conclusion: Due to its abundance in physiologically active phenolic and flavonoid components, the methanolic extract of Syngonium podophyllum L. leaves successfully served as a hypolipidemic, anti-atherosclerotic, and antioxidant therapeutic agent.

Early-Onset or Premature Coronary Artery Disease.

The aim of this review was to examine the literature regarding younger individuals without classical risk factors for atherosclerosis who develop coronary artery disease (CAD) prematurely at an early age. An extensive literature review was undertaken in Pubmed, Scopus, and Google Scholar regarding early-onset or premature atherosclerosis, CAD, its diagnosis, management, and prophylaxis. There are individuals of both genders, particularly in the younger age group of 20-40 years of age, who lack the traditional/ classical risk factors and still develop CAD and other manifestations of atherosclerosis. Even the 10-year age gap in manifesting CAD that is noted between women and men ascribable to a cardioprotective effect of sex hormones may not be noted under these circumstances. This indicates that the risk profile differs in young patients with non-- classical atherosclerotic risk factors, and factors such as genetics, inflammation, thrombosis, psychosocial, environmental, and other parameters play an important role in atherosclerosis and other mechanisms that lead to CAD in younger individuals. These patients are at risk of major adverse cardiac events, which determine their prognosis. Unfortunately, current major guidelines do not acknowledge that many patients who manifest premature CAD are at high risk, and as a consequence, many of these patients may not be receiving guideline-directed hypolipidemic and other therapies before they present with symptoms of CAD. Caretakers need to be more vigilant in offering efficacious screening and strategies of prevention for early-onset or premature CAD to younger individuals.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference.

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2024 Scientific Session of the American College of Cardiology (ACC) conference. The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk. The BE ACTIVE trial showed significant improvement in step counts in patients given behavioral and financial incentives. The DRIVE study showed a significant increase in the prescription of either sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus (T2DM) at elevated CV or renal risk with a remote team-based, non-licensed navigator and clinical pharmacist approach. The TACTiC trial showed increased and sustained use of statin therapy by patient-driven use of a web-based portal that calculated the ASCVD risk score and gave prompts. The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70mg/dL despite maximally tolerated statin therapy. The ARISE-HF trial showed no difference in change of peak oxygen consumptionwith the use of an oral aldose reductase inhibitor, AT-001, in patients with well-controlled T2DM and diabetic cardiomyopathy with high-risk features compared to placebo. The PREVENT trial showed a significant reduction in target vessel failure at 2years in patients with non-flow limiting vulnerable plaques with percutaneous coronary intervention and optimal medical therapy (OMT) compared to OMT alone. The late-breaking clinical science presented at the 2024 Scientific Session of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Knowledge, Attitude, and Practice Regarding Dyslipidemia among Adult Patients Visiting Medicine Outpatient Department of a Tertiary Care Teaching Hospital in Delhi

Abstract Background: Dyslipidemia, a key risk factor for atherosclerosis, affects 25%–30% of urban and 15%–20% of rural individuals in India, as per the Indian Heart Watch study. Despite its association with cardiovascular diseases, there is insufficient understanding among the public. Given the scarcity of studies on knowledge, attitudes, and practices of dyslipidemia among the Indian population, this study aims to fill that gap. Materials and Methods: A cross-sectional observational study was conducted from September 2022 to February 2024. A total of 288 adult patients visiting the medicine outpatient department were included in the study through convenience sampling. A structured questionnaire consisting of 42 questions was designed, pretested, and administered to the participants to assess their knowledge, attitude, and practices regarding dyslipidemia. Data regarding lipid profile tests (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein) were collected, and medication adherence was also asked from the patients. Results: The study revealed a lack of knowledge, negative attitudes, and poor practices regarding dyslipidemia among the participants. The study included 288 participants with an average age of 40 years, predominantly males (53.1%). The majority of participants lacked knowledge about dyslipidemia (81.9%), with a prevalent misconception identified, with many participants incorrectly associating dyslipidemia exclusively with obesity. Among dyslipidemic patients, medication adherence was suboptimal, with a significant proportion discontinuing medication over time (87.3%). Factors associated with better knowledge of dyslipidemia included younger age, male gender, higher education level, professional occupation, higher income, unmarried status (who tend to be younger), urban residence, absence of comorbidities, and lower body mass index. Conclusion: The findings reveal significant gaps in awareness, negative attitudes, and suboptimal practices related to dyslipidemia and its management among the study participants. The majority of participants lacked knowledge about dyslipidemia, with a prevalent misconception associating it primarily with obesity.

Evaluation of 13 Formulae for Calculated LDL-C Using Direct Homogenous Assay in a South Indian Population.

LDL cholesterol (LDL-C) is regarded as a significant therapeutic target and a known risk factor for atherosclerosis. It can be calculated using the results of the other lipid tests or tested directly. Despite its shortcomings, the Friedewald formula is most frequently utilized since it is simple and practical. Until now, several formulae have been proposed for calculating LDL-C; however, their accuracy has not been evaluated across different populations. We sought to evaluate the validity of calculated LDL-C by comparing the findings with values acquired by the direct homogeneous technique, utilizing 13 distinct formulae from the literature. This study was a retrospective observational study conducted for a year at SRIHER, Chennai, Tamil Nadu, India. From the total 25 043 patients who had their serum lipid profile tested, 16 314 participants had their fasting blood sugar and fasting lipid profile measured simultaneously, and they were chosen for the research. The de Cordova, Chen, Martin/Hopkins (initial), and Teerakanchana equations correlated well with the direct LDL-C assay. When the dataset was stratified according to triglycerides, the Chen and Martin/Hopkins initial equations had the better measurement of agreement compared to other equations. The Martin/Hopkins initial equation outperformed all the other equations when the whole dataset irrespective of the triglyceride population was considered. Our study suggests that the Martin/Hopkins initial equation outperformed all the other equations and can be used as an alternative to direct LDL-C measurement in a South Indian population.

Aging promotes mast cell activation and antigen presenting capacity in atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation Aging is an independent and dominant risk factor for atherosclerosis and is associated with a low-grade chronic inflammation termed inflammaging. This age-induced pro-inflammatory environment may have great impact on plaque-residing immune cells, including mast cells. Mast cells have been found to accumulate in the human atherosclerotic plaque upon disease progression and have been associated with plaque instability. However, it is currently unknown whether aging drives the pro-atherogenic effects of mast cells in atherosclerosis. To assess the effects of aging on mast cell phenotype, we examined mast cell populations in young and old male Ldlr-/- mice fed either a chow (CD) or Western-type (WD) diet. We observed a 6-fold increase in the number of mast cells in the aged atherosclerotic aorta compared to young (Y-CD: 4.5±0.7 vs. O-CD: 279.4±9 cells, p&amp;lt;0.01; Y-WD: 45.3±15.2 vs. O-CD: 279.4±9 cells, p&amp;lt;0.01). Furthermore, we detected a marked increase in activation status with age as shown by the significantly augmented number of CD63+ mast cells in the atherosclerotic aorta (Y-CD: 1.8±0.6 vs. O-CD: 259.7±85.4 cells, p&amp;lt;0.01; Y-WD: 41.3±13.6 vs. O-CD: 259.7±85.4 cells, p&amp;lt;0.01). In line, we identified that aged bone-marrow derived mast cells displayed elevated basal CD63 expression compared to young cells, indicative of intrinsic low-grade activation. Moreover, we demonstrated that aging increases the amount of MHCII+ mast cells in atherosclerosis, allowing them to act as antigen-presenting cells, which correspondingly led to increased CD4+ T cell proliferation in vitro (young: 35.2±1.2% vs. old: 45.8±1.2%, p&amp;lt;0.001). Finally, single-cell RNA sequencing of human atherosclerotic plaques confirmed mast cell-specific expression of MHC-II orthologs. To conclude, we established that aging induces phenotypic changes of mast cells in atherosclerosis, regarding both activation status and antigen presenting capacity, which can contribute to disease progression.

Identification of a functional missense variant in the matrix metallopeptidase 10 (MMP10) gene in two families with premature myocardial infarction

A positive family history is a major independent risk factor for atherosclerosis, and genetic variation is an important aspect of cardiovascular disease research. We identified a heterozygous missense variant p.L245P in the MMP10 gene in two families with premature myocardial infarction using whole-exome sequencing. The aim of this study was to investigate the consequences of this variant using in-silico and functional in-vitro assays. Molecular dynamics simulations were used to analyze protein interactions, calculate free binding energy, and measure the volume of the substrate-binding cleft of MMP10-TIMP1 models. The p.L245P variant showed an altered protein surface, different intra- and intermolecular interactions of MMP10-TIMP1, a lower total free binding energy between MMP10-TIMP1, and a volume-minimized substrate-binding cleft of MMP10 compared to the wild-type. For the functional assays, human THP-1 cells were transfected with plasmids containing MMP10 cDNA carrying the p.L245P and wild-type variant and differentiated into macrophages. Macrophage adhesion and migration assays were then conducted, and pro-inflammatory chemokine levels were evaluated. The p.L245P variant led to macrophages that were more adherent, less migratory, and secreted higher levels of the pro-inflammatory chemokines CXCL1 and CXCL8 than wild-type macrophages. Thus, the p.L245P variant in MMP10 may influence the pathogenesis of atherosclerosis in families with premature myocardial infarction by altering protein - protein interactions, macrophage adhesion and migration, and expression of pro-inflammatory chemokines, which may increase plaque rupture. These results could contribute to the development of selective MMP10 inhibitors and reduce the risk of atherosclerosis in families with a history of premature myocardial infarction.

Correlation and risk factors of peripheral and cervicocephalic arterial atherosclerosis in patients with ischemic cerebrovascular disease

Patients with ischemic cerebrovascular disease (ICVD) frequently develop concomitant peripheral artery disease (PAD) or renal artery stenosis (RAS), and multiterritorial atherosclerotic patients usually have a worse prognosis. We aimed to evaluate the status of peripheral atherosclerosis (AS) and cervicocephalic AS (CAS) in ICVD patients with AS, their correlation, and related risk factors contributing to coexisting cervicocephalic-peripheral AS (CPAS). Based on the severity and extent of AS evaluated by computed tomography angiography and ultrasound, the degree of AS was triple categorized to assess the correlation between CAS and PAD/RAS. CAS and PAD/RAS were defined as the most severe stenosis being ≥ 50% luminal diameter in cervicocephalic or lower limb arteries, and a peak systolic velocity at the turbulent site being ≥ 180 cm/s in the renal artery. Among 403 patients with symptom onset within 30 days, CAS, PAD, and RAS occurrence rates were 68.7%, 25.3%, and 9.9%, respectively. PAD was independently associated with the degree of extracranial and intracranial CAS (p = 0.042, OR = 1.428, 95% CI 1.014–2.012; p = 0.002, OR = 1.680, 95% CI 1.206–2.339), while RAS was independently associated with the degree of extracranial CAS (p = 0.001, OR = 2.880, 95% CI 1.556–5.329). Independent CPAS risk factors included an ischemic stroke history (p = 0.033), increased age (p < 0.01), as well as elevated fibrinogen (p = 0.021) and D-dimer levels (p = 0.019). In conclusion, the occurrence rates of RAS and PAD in ICVD patients with AS is relatively high, and with the severity of RAS or PAD increase, the severity of CAS also increase. Strengthening the evaluation of peripheral AS and controlling elevated fibrinogen might be crucial for preventing and delaying the progression of multiterritorial AS in ICVD patients with AS, thereby improving risk stratification and promoting more effective prevention and treatment strategies.

#2009 FGF23 in patients with diabetic kidney disease and atherosclerosis

Abstract Background and Aims Diabetes mellitus (DM) and chronic kidney disease (CKD) are risk factors for vascular atherosclerosis, a pathological process with an important inflammatory component. The coexistence of these conditions in patients with diabetic kidney disease (DKD) has additive effects with worst cardiovascular mortality and morbidity rates when compared to non-diabetic CKD patient on cardiovascular outcomes. Accumulating research has shown that increased levels of bone-derived fibroblast growth factor 23 (FGF23), the major phosphate-regulating hormone, constitute a novel predictor of cardiovascular and all-cause mortality in CKD patients, with potential effects on disorders of glucose metabolism as well. The objective of this comparative study is to determine the differences in FGF23 levels in two groups of patients with CKD, with and without DM, matched by age, sex and renal function, all of them with clinical atherosclerotic disease. We also evaluated the relationships of FGF23 with several inflammatory markers and parameters of glucose metabolism. Method Sixty-six patients with CKD stages 3-4 (33 of them with DM) and diagnosed with peripheral vascular disease were included in the study. Whole blood and serum samples were obtained from all participants. CRP values, neutrophil/lymphocyte (N/L) ratio, HbA1c (%), fasting glucose, and Triglycerides and glucose (TyG) index, among other parameters, were obtained using standardized routine methods. Circulating levels of the intact form of FGF23, tumor necrosis factor (TNF) α, interleukin (IL) 6, and IL10 were determined by ELISA immunoassays in both groups. We also performed gene expression analysis for these three cytokines in peripheral blood cells (PBCs) using qPCR. Results The mean values of eGFR, ACR and phosphate were 37.6 ± 11.2 ml/min/1.73 m2; 294.1 ± 271.2 mg/g; 3.8 ± 0.82 mg/dL; respectively without differences between patients with and without DM The median circulating FGF23 values were higher in the DM group (51.59 [37.73-89.68] vs. 38.1 [33-54.14] pg/mL; p&amp;lt;0.001). Likewise, patients with DM presented higher levels of TNFα both in serum concentration (1.78 [0.72-2.47] vs. 1.28 [1.01-1.88] pg/mL; p&amp;lt;0.01) as in the expression of mRNA in PBCs (2.1 ± 1.26 vs. 1.87 ± 1.16 a.u.; p&amp;lt;0.05). No differences were observed for IL6 and IL10 levels, nor for CRP concentration or N/L ratio. As expected, fasting glucose, HbA1c and TyG index were higher in the group of subjects with DM. FGF23 was inversely correlated with eGFR (r=−0.435, p&amp;lt;0.0001), while it showed a positive association with ACR (r=0.416, p&amp;lt;0.001) and, interestingly, with proinflammatory cytokines including circulating TNFα (r=0.44, p&amp;lt;0.001), circulating IL6 (r=0.27, p=0.04), and TNF mRNA expression in PBCs (r=0.245, p=0.047). Furthermore, circulating FGF23 was also direct and significantly correlated with HbA1c (r=0.34, p&amp;lt;0.01). Conclusion These results suggest that FGF23 levels are higher in DKD than in non-DM CKD patients with similar renal function. DKD patients also had higher levels of the proinflammatory cytokine TNFα. Our results also show positive correlations of FGF23 with the inflammatory cytokines TNFα and IL6, as well as with HbA1c. Previous studies, shown that elevated TNFα and glucose promote FGF23 production, which may help to explain the higher levels of FGF23 in patients with DM Future studies should clarify whether FGF23 is simply a marker of atherosclerosis disease severity or a contributing factor to this complication in CKD.

The impact of smoking on third-degree atrioventricular block outcomes: A propensity-matched analysis

BackgroundThird-degree atrioventricular (AV) blocks are rare but cause significant symptoms and require immediate intervention. Coronary artery disease (CAD) is felt to be the most common etiology. Although smoking is a prominent risk factor for CAD, there is a paucity of data assessing the direct effect of smoking on third-degree AV block. MethodsWe performed a retrospective cohort study on adult-weighted admissions in 2019–2020 with a primary diagnosis of third-degree AV block and a history of smoking using the National Inpatient Sample (NIS) database. In-hospital mortality, rates of pacemaker insertion, cardiogenic shock, cardiac arrest, acute kidney injury (AKI), stroke, tracheal intubation, mechanical ventilation, mechanical circulatory support, vasopressor use, length of stay (LOS), and total hospitalization costs were analyzed using regression analysis. We performed a secondary analysis using propensity score matching to confirm the results. ResultsA total of 77,650 admissions met inclusion criteria (33,625 females [43.3 %], 58,315. Caucasians [75 %], 7030 African American [9 %], 6155 Hispanic [7.9 %]; mean [SD] age 75.4.[10.2] years) before propensity matching. A total of 29,380 (37.8 %) patients with AV block were smokers.A total of 5560 patients with and without a history of smoking were matched for the analysis. Smokers had.decreased odds of mortality (aOR, 0.59; CI, 0.44–0.78; p < 0.001), cardiogenic shock, cardiac arrest, tracheal intubation, mechanical ventilation, shorter LOS, and lower total hospital costs in both the multivariable regression and propensity-matched analyses. ConclusionThird-degree AV block had lower in-hospital mortality, cardiogenic shock, cardiac arrest, LOS, and total hospitalization cost in patients with smoking history.

Study on risk factors of carotid atherosclerosis in type 2 diabetes mellitus and development of prediction model

Study on risk factors of carotid atherosclerosis in type 2 diabetes mellitus and development of prediction model

Elevated remnant cholesterol is a risk factor for acute ischemic stroke.

Remnant cholesterol (RC) is thought to be an important pathogenic risk factor for atherosclerosis, however, the relationship between RC and acute ischemic stroke (AIS) is still unclear. This study aimed to determine whether fasting blood RC level is an independent risk factor for AIS. A retrospective analysis was performed on 650 patients with AIS and 598 healthy controls during the same time period. The association between RC and AIS was investigated using binary logistic regression, and the relationship between RC and AIS risk was demonstrated using Restricted Cubic Splines (RCS). RC was significantly higher in the AIS group compared with control group, and was an independent risk factor for AIS when the covariates were not adjusted;After adjusting some covariates, RC was still an independent risk factor for AIS. The RCS analysis found the risk was non-linear: when RC concentration was less than 0.69 mol/L, the risk of AIS increased with the elevation of RC, and when RC concentration was more than or equal to 0.69 mol/L, the risk of AIS was insignificant with the elevation of RC. Correlation analysis revealed that RC was associated with diabetes and fasting glucose. Further analysis revealed that the incidence of AIS in diabetic patients increased significantly with the increase of RC, and RCS analysis revealed that the risk of AIS in diabetic patients increased with the increase of RC when RC was more than 1.15 mol/L. This study confirms RC as an independent risk factor for AIS, which highlights a distinct non-linear association between RC levels and AIS risk. These findings suggest the need for targeted AIS risk assessment strategies, especially in diabetic patients, and underscore the relevance of RC as a biomarker in AIS risk stratification.

Histological Changes in the Popliteal Artery Wall in Patients with Critical Limb Ischemia.

This prospective study aims to illustrate the histopathological arterial changes in the popliteal artery in peripheral arterial disease of the lower limbs. A total of 60 popliteal artery segments taken from patients who had undergone lower limb amputation were examined between April and June 2023. The degree of arterial stenosis, medial calcinosis, and the vasa vasorum changes in the arterial adventitia were quantified. The presence of risk factors for atherosclerosis was also observed. Atherosclerotic plaque was found in all of the examined segments. Medial calcinosis was observed in 40 (66.6%) of the arterial segments. A positive association between the degree of arterial stenosis and the vasa vasorum changes in the arterial adventitia was also found (p = 0.025). The level of blood sugar and cholesterol were predictive factors for the severity of atherosclerosis. Atherosclerosis and medial calcinosis are significant in patients who underwent lower limb amputation. Medial calcinosis causes damage to the arterial wall and leads to a reduction in responsiveness to dilator stimuli.

Causal role of circulating inflammatory cytokines in cardiac diseases, structure and function

BackgroundInflammation is implicated in cardiovascular disease (CVD) pathogenesis, but causal roles of specific circulating inflammatory cytokines remain unclear. Mendelian randomization (MR) studies are well-poised to provide etiological insights beyond constraints of conventional research. MethodsWe conducted a large-scale MR study to investigate potential causal relationships of 91 inflammatory proteins with CVD outcomes and cardiac remodeling using summary-level genetic data. Outcomes included coronary artery disease, myocardial infarction, stroke, atrial fibrillation, heart failure, abdominal aortic aneurysm, deep vein thrombosis of lower extremities, pulmonary embolism, cardiac structure and functional parameters. Inverse-variance weighted analysis was undertaken as the primary analysis, with several sensitivity analyses applied. ResultsHepatocyte growth factor (HGF) demonstrated a causal relationship with increased susceptibility to both any stroke (OR 1.111; 95 % CI 1.044 - 1.183; P = 9.50e-04) and ischemic stroke (OR 1.121; 95 % CI 1.047 - 1.200; P = 1.04e-03). Programmed cell death 1 ligand 1 (PD-L1) was negatively associated with atrial fibrillation risk (OR 0.936, 95 % CI 0.901 - 0.973; P = 7.69e-04). CCL20, CDCP1, Flt3L and IL-10RA were identified as causal coronary artery disease risk factors, while LIF and ST1A1 had protective effects. IL-4 and LIF-R demonstrated causal links with right heart functional changes. ConclusionsOur MR study nominates specific circulating inflammatory cytokines as potential targets for CVD treatment and prevention. Further research into mechanisms and clinical translation are warranted.

Autoimmune thyroid disease as a risk factor of atherosclerosis

Autoimmune thyroid disease as a risk factor of atherosclerosis

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BackgroundInsulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes.MethodsThe baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status.ResultsIn 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status.ConclusionsIn type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Association of Blood Copper With the Subclinical Carotid Atherosclerosis: An Observational Study.

Copper exposure is reported to be associated with increased risk of stroke. However, the association of copper exposure with subclinical carotid atherosclerosis remains unclear. This observational study included consecutive participants from Xinqiao Hospital between May 2020 and August 2021. Blood metals were measured using inductively coupled plasma mass spectrometry and carotid atherosclerosis was assessed using ultrasound. Modified Poisson regression was performed to evaluate the associations of copper and other metals with subclinical carotid plaque presence. Blood metals were analyzed as categorical according to the quartiles. Multivariable models were adjusted for age, sex, body mass index, education, smoking, drinking, hypertension, diabetes, dyslipidemia, estimated glomerular filtration rate, and coronary artery disease history. Bayesian Kernel Machine Regression was conducted to evaluate the overall association of metal mixture with subclinical carotid plaque presence. One thousand five hundred eighty-five participants were finally enrolled in our study, and carotid plaque was found in 1091 subjects. After adjusting for potential confounders, metal-progressively-adjusted models showed that blood copper was positively associated with subclinical carotid plaque (relative risk according to comparing quartile 4 to quartile 1 was 1.124 [1.021-1.238], relative risk according to per interquartile increment was 1.039 [1.008-1.071]). Blood cadmium and lead were also significantly associated with subclinical carotid plaque. Bayesian Kernel Machine Regression analyses suggested a synergistic effect of copper-cadmium-lead mixture on subclinical carotid plaque presence. Our findings identify copper as a novel risk factor of subclinical carotid atherosclerosis and show the potential synergistic proatherogenic effect of copper, cadmium, and lead mixture.

The Prevalence of Coronary Artery Disease in Bicuspid Aortic Valve Patients: An Overview of the Literature.

The prevalence of coronary artery disease (CAD) in bicuspid aortic valve (BAV) patients is a debatable topic. Several studies have indicated that BAV patients have a lower prevalence of CAD compared with patients with a tricuspid aortic valve (TAV), but the effects of age and gender have not always been considered. This systematic review provides an overview of articles which report on CAD in BAV and TAV patients. Searches were executed in April 2021 and January 2022 according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines in three online databases: Medline, Embase, and Scopus. Screening and data extraction was done by two investigators separately. Primary and secondary outcomes were compared between BAV and TAV patients; a fixed effects model was used for correcting on confounders. Literature search yielded 1,529 articles with 44 being eligible for inclusion. BAV patients were younger (56.4 ± 8.3 years) than TAV patients (64 ± 10.3 years, p < 0.001). All CAD risk factors and CAD were more prevalent in TAV patients. No significant difference remained after correcting for age and gender as confounders. BAV patients have a lower prevalence of CAD and CAD risk factors compared with TAV patients. However, when the age differences between both groups are considered in the analyses, a similar prevalence of both CAD and CAD risk factors is found.

Role of C1q/TNF-Related Protein 6 for the Evaluation of Coronary Heart Disease Associated with Type 2 Diabetes.

Coronary artery disease (CAD) and type 2 diabetes (T2DM) are closely associated with increased rate of death. C1q/TNF-related protein 6 (CTRP6) is a novel adipocytokine which plays an important role in glucose and lipid metabolism. Little is known about the function of CTRP6 in CAD and T2DM patients. Herein, we aimed to study the association of CTRP6 level with CAD and T2DM. This study included 51 CAD, 44 CAD+T2DM and 65 non-CAD+T2DM patients from Affiliated Aoyang Hospital of Jiangsu University. Serum CTRP6 concentrations were detected by ELISA. Multiple logistic regression was used to analyze the association of serum CTRP6 with CAD and T2DM. Serum CTRP6 concentrations were significantly lower in CAD patients than controls. However, there is no significant statistical difference between CAD+T2DM patients and non-CAD+T2DM patients. Serum CTRP6 was negatively correlated with low-density lipoprotein cholesterol (LDL-C) (ρ=-0.2769, p=0.028) in controls. Serum CTRP6 was positively correlated with age (ρ=0.4121, p=0.0027), systolic blood pressure (SBP) (ρ=0.4012, p=0.0035), Creatinine (ρ=0.3295, p=0.0194), uric acid (UA) (ρ=0.3386, p=0.0162), and left ventricular end diastolic diameter (LVD) (ρ=0.4277, p=0.0042) and negatively correlated with ejection fraction (EF) (ρ=-0.3237, p=0.0342) in CAD patients. Serum CTRP6 was negatively correlated with high-density lipoprotein cholesterol (HDL-C) (ρ=-0.3164, p=0.0387) in CAD+T2DM patients. Multiple logistic regression showed that the decrease of CTRP6 was significantly related to the increased prevalence of CAD. What is more, CTRP6 increased prevalence of T2DM in CAD patients. Lower serum CTRP6 could be a risk factor of CAD. However, higher circulating CTRP6 associated with the increased prevalence of T2DM in CAD patients.

Prevalence and risk factors associated with coronary artery disease in Iranian patients with peripheral artery disease

IntroductionIt is well known that peripheral artery disease (PAD) and coronary artery disease (CAD) coexist and therefore, patients diagnosed with PAD have an increased chance of developing concomitant CAD. CAD-related complications could be a leading cause of postoperative mortality in individuals with PAD undergoing vascular surgery. We present a case series of 48 patients who underwent coronary angiography before vascular surgery and an updated review of previous reports to determine the prevalence of concomitant CAD in a convenience sample of Iranian patients. MethodsThis cross-sectional study was performed on 48 patients with confirmed PAD admitted to Imam Ali Hospital, affiliated with the Kermanshah University of Medical Sciences (KUMS), Kermanshah Province, Iran. A vascular surgeon diagnosed PAD based on the patient's symptoms, Doppler ultrasound, and CT angiography (CTA). All patients underwent coronary angiography to determine if they also had CAD. We defined significant CAD as a ≥70% luminal diameter narrowing of a major epicardial artery or a ≥50% narrowing of the left main coronary artery. ResultsOf 48 patients, 35 (72.9%) were male, 13 (27.1%) were female, and the mean age was 64.18±12.11 years (range, 30 to 100 years). The incidence of CAD in patients with PVD was 85.42% (41/48). The patients with CAD were more likely to be hypertensive than those without CAD (80.5 vs. 14.3, p-value<0.001). Of 41 patients with CAD, 9 (22.0%) had one-vessel disease, 10 (24.3%) had two-vessel disease, and 22 (53.7%) had three-vessel disease. ConclusionHypertension was a significant risk factor for CAD. Patients with hypertension and multiple major coronary risk factors scheduled for PVD surgery should be carefully evaluated for concomitant CAD.