Major Risk Factor For Atherosclerosis Research Articles

ASSESSMENT OF CORONARY ARTERY DISEASES IN DIABETIC AND NON-DIABETIC PATIENTS WITH ANGIOGRAPHY IN DIFFERENT AGE GROUPS

Background: Coronary artery disease (CAD) is a leading cause of morbidity and mortality globally, particularly in Indo-Asians, where its prevalence is significantly higher. Diabetes mellitus (DM), a major risk factor for CAD, exacerbates disease progression through metabolic dysfunctions such as hyperglycemia and dyslipidemia. The increasing global prevalence of DM necessitates a deeper understanding of its impact on coronary artery stenosis and clinical symptoms to guide early interventions and risk management strategies. Objective: This study aimed to assess the prevalence and severity of coronary artery disease among diabetic and non-diabetic patients using angiography across different age groups. Methods: A cross-sectional comparative study was conducted at Punjab Cardiology Lahore with 170 participants recruited through convenience sampling. The study included diabetic and non-diabetic patients presenting with angina and categorized them into three age groups: 20–40 years, 40–60 years, and above 60 years. Exclusion criteria included individuals with prior cardiac surgeries, pre-stenting, hypertension, or age above 80 years. Data were collected over four months, analyzing demographic characteristics, clinical symptoms, and angiographic findings to determine patterns of stenosis. Results: Among 170 participants, 54.7% were female and 45.3% male. Age distribution included 26.5% in the 20–40 group, 44.1% in 40–60, and 29.4% above 60. Severe chest pain was reported by 37.6%, severe shortness of breath by 40%, and nausea/vomiting by 71.8%. Diabetic patients showed significantly higher stenosis rates: LCA (64.7% vs. 35.3%), LDA (52.9% vs. 47.1%), and Left Circumflex (58.8% vs. 41.2%) compared to non-diabetics. The 40–60 age group demonstrated the highest incidence of stenosis across all arteries, particularly among diabetics. Conclusion: Diabetic individuals, particularly those aged 40–60, exhibited higher rates and severity of coronary artery stenosis and more severe symptoms. These findings emphasize the importance of targeted screening, interventions, and lifestyle modifications to reduce CAD risk in middle-aged diabetic populations.

The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model.

Cigarette smoking is a major risk factor for atherosclerosis. Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Prevalence and Characteristics of Dyslipidemia in a Hospital in Madagascar.

Introduction Dyslipidemia is a major risk factor for atherosclerosis and is included in the metabolic syndrome. Data on dyslipidemia are still lacking in some parts of Africa. Our objectives were to report the prevalence of dyslipidemia and to describe the lipid profile of patients in a hospital in Madagascar. Materials and methods This was a descriptive cross-sectional study of patients admitted to the medical departments of Mahavoky Atsimo Hospital in Mahajanga,Madagascar, and followed for a period of 15 months. To be eligible, patients had to be over 18 years of age, have a lipid panel including total cholesterol, triglycerides, HDL, and LDL cholesterol, and agree to participate in the study. Results Of the 384 patients included in the study, 262 patients (68.23%) had dyslipidemia. The prevalence of dyslipidemia was 61.45% (n = 102) in men and 73.39% (n = 160) in women. In patients older than 65 years, the prevalence was 70.64% (n = 77). The different types of dyslipidemia were distributed as follows: hypercholesterolemia (24.22%, n = 93), hypo-HDL cholesterolemia (22.4%, n = 86), mixed hyperlipidemia (7.81%, n = 30), hyper-LDL cholesterolemia (7.29%, n = 28), and hypertriglyceridemia (6.51%, n = 25). Female gender (p = 0.013), diabetes mellitus (p = 0.007), and morbid obesity (p = 0.036) were associated with dyslipidemia. Conclusion The prevalence of dyslipidemia was high. Pure hypercholesterolemia and hypo-HDL-c were the most common types. Female gender, diabetes mellitus, and morbid obesity were associated with dyslipidemia. Prevention and treatment programs are essential to reduce the prevalence of dyslipidemia and the risk of cardiovascular events in low-income countries.

Plasma from type 1 diabetes patients promotes pro-atherogenic cholesterol transport in human macrophages.

Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits RCT by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HCs) and 20 patients with type 1 diabetes mellitus (T1DM), 10-19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, and 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, and CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of N-(carboxymethyl)-lysine-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells' uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized low-density lipoprotein. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.

Targeting vascular senescence in cardiovascular disease with aging.

Aging is a major risk factor for atherosclerosis and cardiovascular disease (CVD). Two major age-associated arterial phenotypes, endothelial dysfunction and large elastic arterial stiffness, are autonomous predictors of future CVD diagnosis and contribute to the progression of CVD in older adults. Senescent cells lose the capacity to proliferate but remain metabolically active and secrete inflammatory factors termed senescence-associated secretory phenotype (SASP), leading to an increase in inflammation and oxidative stress. Accumulation of senescent cells is linked with the progression of age-related diseases and has been known to play a role in cardiovascular disease. In this brief review, we describe the characteristics and mechanisms of senescent cell accumulation and how senescent cells promote endothelial dysfunction and arterial stiffness. We focus on a range of novel therapeutic strategies aimed at reducing the burden of endothelial dysfunction leading to atherosclerosis through targeting senescent cells. Studies have begun to investigate a specific class of drugs that are able to selectively eliminate senescent cells, termed senolytics, which have shown great promise in reversing the aging phenotype and ameliorating pathologies in age-related disorders, creating a new opportunity for aging research. Generating therapies targeting the elimination of senescent cells would improve health span and increase longevity, making senolytics a promising therapy for cardiovascular diseases.

Study of active components and mechanisms mediating the hypolipidemic effect of Inonotus obliquus polysaccharides.

Hyperlipidemia is a multifaceted metabolic disease, which is the major risk factor for atherosclerosis and cardiovascular diseases. Traditional Chinese medicine provides valuable therapeutic strategies in the treatment of hyperlipidemia. Inonotus obliquus has been used in traditional medicine to treat numerous diseases for a long time. To screen and isolate the fractions of I. obliquus polysaccharides (IOP) that can reduce blood lipid in the hyperlipemia animals and cell models, and investigate its mechanisms. The active component IOP-A2 was isolated, purified, and identified. Invivo, rats were randomly divided into blank control group (NG), the high-fat treatment group (MG), lovastatin group (PG), and IOP-A group. Compared with MG, the hyperlipidemic rats treated with IOP-A2 had decreased body weight and organ indexes, with the level of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) significantly decreased (p < .05), and level of serum high-density lipoprotein cholesterol (HDL-C) significantly increased (p < .05). Hepatocyte steatosis in hepatic lobules was significantly reduced. Invitro, the accumulation of lipid droplets in the model of fatty degeneration of HepG2 cells was significantly alleviated, and cellular TC and TG content was significantly decreased (p < .01). Moreover, the expression of recombinant cytochrome P450 7A1 (CYP7A1) and Liver X Receptor α (LXRα) were up-regulated (p < .05) both invivo and invitro. The results showed that IOP-A2 may exert its hypolipidemic activity by promoting cholesterol metabolism and regulating the expression of the cholesterol metabolism-related proteins CYP7A1, LXRα, SR-B1, and ABCA1.

Evaluation of the Influence of oral administration of Aqueous Leaf Extract of Sida acuta on Lipid Profile and Body Weight of Wistar Rats

Abnormalities in serum lipid profiles play a central role in endothelial functional abnormality which is a major risk factor for atherosclerosis including coronary artery disease, cerebrovascular disease and peripheral vascular diseases. Hepatic damage disturbs hepatic functions such as lipid metabolism which can translate to a distorted lipid profile. Therefore, the aim of this study was to evaluate the influence of oral administration of Sida acuta on the lipid profile and body weight of Wistar rats. Freshly harvested leaves of Sida acuta was dried under room temperature and afterwards ground to powder which was subsequently processed into extract. Thirty adults male Wistar rats were divided into five groups of five rats each. Group I (normal control) was administered with 2 ml of distilled water, groups II–VI were induced hepatic damage. While group II was left untreated, groups III-V were administered with 100, 200 and 300 mg/kg of aqueous extract of Sida acuta (AESD) respectively. Group VI was administered with silymarin (standard drug). Treatment lasted for 28 days after which animals were humanely sacrificed and blood sample collected for analysis. Treatment with extract significantly (P&lt;0.05) reduced the activities of the liver enzymes; aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP). While the serum levels of TC, TG, HDL and LDL reported for group II were significantly (P&lt;0.05) higher than those reported for the normal control. Oral administration of extract significantly (p&lt;0.05) reduced the levels of TC, TG, HDL and LDL reported for groups III-V. Oral administration of extract did not adversely affect the body weight of animals. In conclusion, it can be deduced from this study that oral administration of Sida acuta reversed a distorted lipid profile and did not result in weight loss.

Cells in Atherosclerosis: Focus on Cellular Senescence from Basic Science to Clinical Practice.

Aging is a major risk factor of atherosclerosis through different complex pathways including replicative cellular senescence and age-related clonal hematopoiesis. In addition to aging, extracellular stress factors, such as mechanical and oxidative stress, can induce cellular senescence, defined as premature cellular senescence. Senescent cells can accumulate within atherosclerotic plaques over time and contribute to plaque instability. This review summarizes the role of cellular senescence in the complex pathophysiology of atherosclerosis and highlights the most important senotherapeutics tested in cardiovascular studies targeting senescence. Continued bench-to-bedside research in cellular senescence might allow the future implementation of new effective anti-atherosclerotic preventive and treatment strategies in clinical practice.

Lipid Profile in Olympic Athletes: Proposal for a “Lipid Athlete Score” as a Clinical Tool to Identify High-Risk Athletes

Dyslipidemia is a major risk factor for atherosclerosis. Identification of dyslipidemia in athletes has raised interest in establishing preventive strategies and reducing cardiovascular (CV) events. Nowadays, targets or “scores” for athletes are undefined. The aim of our study was to create a “Lipid Athlete Score” based on lipid parameters and derive score indexes to identify high-risk athletes. We retrospectively enrolled 957 Olympic athletes practicing different sporting disciplines (power, skills, endurance, and mixed), analyzing their CV profiles and anthropometrics; 55.4% were male, the mean age was 27.1 ± 5 years, and the mean body mass index (BMI) was 23.1 ± 3.2 kg/m2. Three hundred and forty-three athletes (35.8%) were dyslipidemic (LDL ≥ 115 mg/dL or LDL/HDL ≥ 1.90). Multivariate analysis revealed the following: male p = 0.001, OR 1.88 [0.41–2.51], familiarity for dyslipidemia p = 0.001, OR 2.82 [1.72–4.59], BMI ≥ 30 kg/m2 p = 0.001, OR 2.53 [1.46–4.38], and fat mass p = 0.001, OR 2.29 [1.38–3.80] were significant. Endurance athletes presented the lowest CV risk. We proposed a lipid athlete score including major (LDL ≥ 115 mg/dL and LDL/HDL ≥ 1.90) and minor criteria (male, BMI &gt; 30 kg/m2 or fat mass &gt;22% for males and 32% for females, familiarity for dyslipidemia, and conventional CV risk factors). Twelve athletes (1.2%) were at high risk, 150 athletes (15.7%) at medium risk, 171 athletes (17.9%) at low risk, and 624 (65.2%) were at no risk. Dyslipidemia is very common in elite athletes. We have defined a specific lipid athlete score based on lipid parameters and derived score indexes for the stratification of risk. In accordance with this tool, a substantial proportion of athletes (16.9%) were at medium-to-high risk and need early preventive strategies to improve their lipid profiles and reduce the future development of atherosclerotic CV diseases.

Helicobacter pylori (H. pylori) Infection-Associated Dyslipidemia in the Asir Region of Saudi Arabia.

H. pylori-associated dyslipidemia has been reported to be a major risk factor for atherosclerosis and coronary heart diseases. We aimed to investigate the association of the H. pylori infection with dyslipidemia. A retrospective case-control study was undertaken to evaluate H. pylori-associated dyslipidemia, where H. pylori-positive individuals were treated as the case group (n = 260) while H. pylori-negative individuals were considered as the control group (n = 250). The mean ± SD of the age of the patients included (n = 510) was 44.01 ± 13.58 years. Study subjects with a total cholesterol level of >5.17 mmol/L and/or a triglyceride level of >1.69 mmol/L and/or an LDL-C level of >2.59 mmol/L and/or an HDL-C level of <1 mmol/L in males and/or an HDL-C level of <1.3 mmol/L in females were defined as dyslipidemia. Descriptive (mean, standard deviation, median, and IQR) and inferential (t-test, chi-square test, and logistic regression) statistical analyses were undertaken using the R-base/R-studio (v-4.0.2)/tidyverse package. Univariate and bivariate logistic regressions were executed to calculate the crude and adjusted odds ratio along with the p-value. A p-value of <0.05 was the cut-off for statistical significance. We used ggplot2 for data visualization. The differences in overall mean ± SD (H. pylori positive vs. negative) of the cholesterol (5.22 ± 1.0 vs. 5.49 ± 0.85, p < 0.01), triglyceride (1.66 ± 0.75 vs. 1.29 ± 0.71, p < 0.001), LDL-C (3.43 ± 0.74 vs. 3.26 ± 0.81, p < 0.05), and HDL-C (1.15 ± 0.30 vs. 1.30 ± 0.25, p < 0.001) levels were statistically significant. The cholesterol and LDL-C levels in ages >60, age = 30-60, in females, and LDL-C levels in males were not significantly different for the H. pylori-positive and -negative groups. The proportion (H. pylori positive vs. negative) of hypercholesterolemia (190/59.9% vs. 127/40% p < 0.01), hypertriglyceridemia (136/68% vs. 64/32% p < 0.001), high LDL-cholesterolemia levels (234/53% vs. 201/46% p < 0.01), and low HDL-cholesterolemia levels (149/71% vs. 60/28.7% p < 0.01) were statistically significant. The odds of having hypercholesterolemia (AOR: 2.64, 95%CI: 1.824-3.848, p < 0.001), hypertriglyceridemia (AOR: 3.24, 95%CI: 2.227-4.757, p < 0.001), an increased LDL-C level (AOR: 2.174, 95%CI: 1.309-3.684, p < 0.01), and a decreased HDL-C level (AOR: 4.2, 95%CI: 2.937-6.321, p < 0.001) were 2.64, 3.24, 2.17, and 4.2 times higher in the H. pylori-infected individuals as compared with the H. pylori-uninfected group. Our results demonstrate that an enhanced risk of dyslipidemia is associated with the H. pylori infection, which can aggrandize the atherosclerosis process. The evaluation of temporal variation in the lipid profile in H. pylori-infected individuals is recommended for the effective management of H. pylori-infected patients.

Signal Pathways and Intestinal Flora through Trimethylamine N-oxide in Alzheimer's Disease.

The current studies show signs of progress in treating Alzheimer's disease (AD) with the "brain-gut axis." Restoring intestinal flora balance can alleviate neurodegeneration in the central nervous system. However, due to the complex mechanisms involved in the brain-gut axis, the neuroprotective mechanism brought by intestinal flora has not been fully understood. Trimethylamine N-oxide (TMAO) is a microbiota-dependent metabolism production; TMAO has been proven to be a major risk factor for atherosclerosis, thrombosis, type II diabetes, and other diseases. Meanwhile, all the above diseases are associated with AD; thus, we speculate that TMAO and AD are also correlated. Microbiota, such as Firmicutes, Ruminococcaceae, Escherichia coli, Bifidobacterium, Akkermansia, etc., correlate with the production process of TMAO. High choline intake and insulin resistance have also been identified as contributors to TMAO synthesis. With the increasing TMAO in plasma, TMAO can enter the central nervous system, causing neuroinflammation and immune responses and damaging the blood-brain barrier. TMAO can increase the expression of Aβ and the hyperphosphorylation of tau protein, regulate the signal pathways of NLRP3/ASC/caspase1, SIRT1/p53/p21/Rb, PERK/eIF2α/ER-stress, SIRT3-SOD2-mtROS, TXNIP-NLPR3, and PERK/Akt/mTOR, and stimulate the inflammation, apoptosis, endoplasmic reticulum stress, and the ROS. In this mini-review, we have summarized the diseases induced by TMAO through clinical and signal pathways, and intestinal flora correlated with TMAO. Through the analysis of diseases and mechanisms involved in TMAO, we have concluded TMAO to be a potentially important pathological factor of AD.

Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review.

Hyperlipidemia is a metabolic disorder, which is a major risk factor for atherosclerosis, stroke, and coronary heart disease. Although lipid-lowering treatments have been extensively studied, safer treatments with fewer adverse effects are needed. Rhubarb is a traditional Chinese medicine that has lipid-lowering, anti-inflammatory, and antioxidant properties. Disturbance in lipid metabolism is the basis of tissue damage caused by hyperlipidemia and plays a key role in the development of hyperlipidemia; however, the molecular mechanisms by which rhubarb regulates lipid metabolism to lower lipid levels are yet to be elucidated. We conducted this study to summarize the phytochemical constituents of Rheum officinale and provide a comprehensive review of the molecular mechanisms underlying the regulation of lipid metabolism during hyperlipidemia treatment. It was found that rhubarb extracts, including emodin, rhubarb acid, and rhubarb phenol, regulate total cholesterol, triglyceride, TNF-α, and IL-1β levels through signaling pathways such as C/EBP α, 3T3-L1, PPAR α, and AMPK, thereby improving the hyperlipidemic state. This suggests that rhubarb is a natural drug with lipid-lowering potential, and an in-depth exploration of its lipid-lowering mechanism can provide new ideas for the prevention and treatment of hyperlipidemia.

Evaluation of Serum Cysteine-rich Angiogenic Inducer 61 for Peripheral Arterial Disease in Patients with Type 2 Diabetes Mellitus

Abstract Background: Peripheral artery disease (PAD) is a common manifestation of atherosclerotic disease, which is related to considerable disability and mortality. Currently, approximately 202 million people worldwide are suffering from lower extremity arterial disease, giving rise to a major public health problem and a heavy economic burden. Type 2 diabetes mellitus (T2DM) is one of the major risk factors for atherosclerosis, and the prevalence of PAD increases with the prevalence of T2DM. Materials and Methods: A cross-sectional case–control study comprising 100 cases and 40 age- and sex-matched healthy controls was done. The cases were divided into three groups: Group 1 (T2DM with PAD) – 40, Group 2 (T2DM without PAD) – 40, and Group 3 (PAD without T2DM) – 20. The serum cysteine-rich angiogenic inducer 61 (CYR61) levels were assessed using the sandwich enzyme-linked immunosorbent assay. Statistical analysis was done using MedCalc version 20.114. P &lt;0.005 is taken as statistically significant. Results: The mean concentrations of CYR61 in Group 1, Group 2, and Group 3 were 3680 pg/ml, 3059 pg/ml, and 2866 pg/ml, respectively, whereas, in controls, it was 2318 pg/ml. The serum CYR61 levels were significantly higher in cases compared to controls (P &lt; 0.0001). CYR61 concentrations are significantly higher in Group 1 compared to the other two groups – Group 2 and Group 3. CYR61 levels showed a statistically significant difference between Stage 2 and Stage 4 of PAD in Group 1. Receiver operating characteristic analysis has shown area under curve (0.946) for CYR61 higher than ankle-brachial index (0.750). Conclusions: CYR61 proved to be a better marker for diagnosing PAD in patients with T2DM.

Design, optimization, and in vivo evaluation of invasome-mediated candesartan for the control of diabetes-associated atherosclerosis

Atherosclerosis is an inflammatory disease characterized by the accumulation of arterial plaque. Diabetes mellitus stands out as a major risk factor for atherosclerosis. Candesartan is a potent angiotensin II receptor antagonist that enhances arterial blood flow and reduces insulin resistance. However, oral candesartan has limited activity because of its low bioavailability, water solubility, hepatic first-pass degradation, and efficacy. The current study aims to develop nasal candesartan-loaded invasome (CLI) drops to improve candesartan’s permeation, release, and bioavailability as a potential treatment for diabetes-associated atherosclerosis. Design expert software was used to prepare various CLI formulations to determine the impact of the concentrations of ethanol, cineole, and phospholipid. The desirability index was used to estimate the optimized formulation composition to maximize entrapment efficiency and minimize vesicle size. The optimized formulation had a 1% ethanol concentration, a 1.5% cineole concentration, and a 2.32% phospholipid concentration. The selected optimized formulation was then tested in a rat model of diabetes and atherosclerosis to evaluate its activity. The results showed that nasal CLI drops significantly raised serum HDL levels by a ratio of 1.42 and lowered serum glucose, cholesterol, triglycerides, LDL, and VLDL levels by 69.70%, 72.22%, 36.52%, 58.0%, and 65.31%, respectively, compared with diabetic atherosclerotic rats, throwing an insight on the potential for promising anti-diabetic and anti-atherosclerotic activities. Additionally, atherosclerotic lesions were improved in rats treated with CLI, as shown in histopathology. In conclusion, the results of this investigation showed that treatment with nasal CSN-loaded invasome formulation drops prevented the initiation and progression of diabetes-associated atherosclerosis.Graphical

Abstract P3033: Thrombospondin-1 Promotes Vascular Smooth Muscle Cell De-differentiation In Diabetes

Diabetes is a major risk factor for atherosclerosis. Diabetic patients are prone to increased vascular smooth muscle cell (VSMC) migration and proliferation, hallmarks of VSMC de-differentiation, critical for the evolution of atherosclerosis. Multiple studies, including our earlier work, support the role of thrombospondin-1 (TSP1), a proatherogenic matricellular protein, as a putative link between diabetes and vascular disease. However, molecular mechanism(s) by which TSP1 promotes diabetic vasculopathy are incompletely understood. The goal of this work was to explore whether smooth muscle TSP1 (smTSP1) regulates VSMC phenotypic switch in diabetes. We generated conditional SMC-specific TSP1 knockout (smTSP1 KO ) mice by crossing female TSP1 fl/fl mice with tamoxifen (tmx)-inducible Myh11-CreER T2 male mice. For Cre recombination, 5-wks-old male TSP1 fl/fl Cre tg and age-matched TSP1 +/+ Cre tg littermate mice were treated with 60 mg/Kg/day tmx i.p. once daily for 5 consecutive days. To induce type 2 diabetes, mice cohorts were placed on western diet at 7-wks-age followed by streptozotocin (50 mg/Kg/day, i.p. x 5 days) at 16-wks-age. Mice were harvested at 20-wks-age for plasma and tissue collection. Immunoblotting of aortic lysates revealed significant decrease in TSP1 expression in tmx-treated TSP1 fl/fl Cre tg , validating smTSP1 KO mice. Lack of smTSP1 increased ACTA2 (SM contractile marker) expression by 2-fold accompanied with 50% reduction in CDK4 (cell cycle regulator) expression in diabetic smTSP1 KO vs. smTSP1 WT aortic vessels. Consistently, in murine aortic SMC (MASMC) primary cultures derived from smTSP1 KO mice, loss of smTSP1 augmented (&gt;65%) LMOD1 (SM contractile marker) and SRF (transcriptional activator of SM contractile genes) expression coupled with diminished (45%) vimentin (SM synthetic marker) expression in 25mM glucose-treated smTSP1 KO vs. smTSP1 WT cells. Further, propidium iodide staining via flow cytometry revealed reduced S-phase cell counts concomitant to increased G 0 -G 1 cell distribution in glucose-treated smTSP1 KO vs. smTSP1 WT MASMC. Together, our data demonstrates a direct role of TSP1 in VSMC phenotypic transition and opens novel avenues for cell-specific TSP1-based therapies for treatment of diabetes.

Prognostic value of hematological parameters in older adult patients with acute coronary syndrome undergoing coronary intervention: a single centre prospective study.

Cardiovascular disease is a significant contributor to the disease burden in geriatric patients. Underlying systemic inflammation is thought to be the cause of age-related changes in the bone marrow and a major risk factor for atherosclerosis. The purpose of the study was to assess the accuracy of these hematological biomarkers in predicting 30-day mortality in older patients with acute coronary syndrome (ACS). This was a prospective observational study of 601 older adult patients (age > 60 years) with ACS who underwent percutaneous coronary intervention over two years (2017-2019). The relationship between baseline hematological parameters and mortality was assessed during the 30-day follow-up. Logistic regression analysis and receiver operating characteristic curve analysis were done to evaluate for diagnostic accuracy of various hematological parameters. The mean age of presentation was 77 ± 17 years. The mean neutrophil-lymphocyte ratio (NLR) value was 5.07 ± 4.90 and the mean platelet-lymphocyte ratio (PLR) value was 108.65 ± 85.82. On univariate analysis, total leucocyte count [odds ratio (OR) = 0.85, P = 0.021], hematocrit (OR = 0.91, P = 0.018), NLR (OR = 1.10, P = 0.001) and PLR (OR = 1.05, P = 0.001) were associated with mortality. On receiver operating characteristic curve analysis, NLR predicted mortality with 68.1% and PLR with 65.7% accuracy. On multivariate analysis, NLR (OR = 1.096, 95% CI: 1.006-1.15, P = 0.035) was an independent predictor of 30-day mortality. For the risk classification of all elderly ACS patients, we highly advise using NLR rather than the total white blood cell count.

The cardioprotective effects of secoisolariciresinol diglucoside (flaxseed lignan) against cafeteria diet-induced cardiac fibrosis and vascular injury in rats: an insight into apelin/AMPK/FOXO3a signaling pathways.

Introduction: Fast food is a major risk factor for atherosclerosis, a leading cause of morbidity and mortality in the Western world. Apelin, the endogenous adipokine, can protect against cardiovascular disease via activating its receptor, APJ. Concurrently, secoisolariciresinol diglucoside (SDG), a flaxseed lignan extract (FLE), showed a therapeutic impact on atherosclerosis. The current study aimed to examine the effect of SDG on cafeteria diet (CAFD)-induced vascular injury and cardiac fibrosis via tracking the involvement of the apelin/APJ pathway. Methods: Thirty male rats were allocated into control, FLE-, CAFD-, CAFD/FLE-, and CAFD/FLE/F13A-treated rats, where F13A is an APJ blocker. All treatments lasted for 12weeks. Results and discussion: The CAFD-induced cardiovascular injury was evidenced by histological distortions, dyslipidemia, elevated atherogenic indices, cardiac troponin I, collagen percentage, glycogen content, and apoptotic markers. CAFD increased both the gene and protein expression levels of cardiac APJ, apelin, and FOXO3a, in addition to increasing endothelin-1, VCAM1, and plasminogen activator inhibitor-1 serum levels and upregulating cardiac MMP-9 gene expression. Moreover, CAFD reduced serum paraoxonase 1 and nitric oxide levels, cardiac AMPK, and nuclear Nrf2 expression. FLE attenuated CAFD-induced cardiovascular injury. Such effect was reduced in rats receiving the APJ blocker, implicating the involvement of apelin/APJ in FLE protective mechanisms. Conclusion: FLE supplementation abrogated CAFD-induced cardiac injury and endothelial dysfunction in an apelin/APJ-dependent manner.

463-P: Risk Stratification of Coronary Artery Disease (CAD) according to LDL-C, HDL-C Levels, and Glucose Status

Whereas elevated LDL-C is a major risk factor for CAD, the inverse association between HDL-C levels and risk of CAD is well-known. Although insulin resistance, and glucose intolerance are associated with low HDL-C levels, it is not clear whether the association of LDL-C with CAD differs depending on glucose status and HDL-C values. We examined associations of LDL-C with the incidence of CAD according to HDL-C and glucose status using a nationwide claims database on 1,524,289 individuals during 2008-2019 with no history of CAD or familial hypercholesterolemia. Cox proportional hazards model identified risks of CAD events among combinations of 3 levels of HDL-C and 7 levels of LDL-C according to glucose status. During a mean follow-up period of 5.5 years, 8,301 CAD events occurred. CAD risk increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of glucose status (Table). Even in people with LDL-C &amp;lt;80mg/dl, HDL-C &amp;lt;40mg/dl conferred 2.5-fold increased risk of CAD all glucose status. HDL-C and LDL-C values had a synergistic effect on the incidence of CAD in people with normoglycemia, whereas an addictive effect in people with prediabetes and diabetes. Although more strict LDL-C target need to be achieved as worsening of glucose status, results demonstrated that the necessity of modulating the LDL-C target according to HDL-C levels is not affected by glucose status. Disclosure M.H.Yamada: None. M.Iwanaga: None. T.Yamada: None. S.Kodama: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. K.Fujihara: None. T.Osawa: None. M.Kitazawa: None. Y.Yaguchi: None. T.Sato: None. Y.Mitsuma: None. M.Yamamoto: None. Y.Matsubayashi: None.

Relation between aortic elasticity parameters and SYNTAX score in postmenopausal diabetic women

BackgroundPostmenopausal women are at increased risk of coronary artery disease (CAD). Diabetes Mellitus is a major risk factor for CAD. The stiffening of the aorta is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the relation of aortic elasticity parameters to CAD severity assessed by SYNTAX score (SS) in diabetic postmenopausal women. The study prospectively included 200 consecutive diabetic postmenopausal women with CAD who underwent elective coronary angiography. Patients were classified into 3 groups based on SS, low-SS ≤ 22, intermediate-SS ≥ 23– ≤ 32, and high-SS ≥ 33. Echocardiographic aortic elasticity parameters, including aortic stiffness index (ASI), aortic strain (AS) (%) and aortic distensibility (AD) were obtained in all patients.ResultsPatients in the high SS group were older age and had a higher aortic stiffness. After adjusting different co-variates AD, AS, and ASI could be used as independent predictors of high SS with the following P-values (0.019, 0.016 and 0.010) and cut-off values (2.5, 3.6 and 2.9), respectively.ConclusionsIn diabetic postmenopausal women, the simple echocardiography-derived aortic elasticity parameters might predict the severity and complexity of angiographic coronary lesions assessed by the SS.

Hyperhomocysteinemia, Hyperlipidemia and Retina

Hyperhomocysteinemia is a disease with an increase in the plasma level of homocysteine, an intermediate of methionine metabolism, and predisposes to thrombosis. It is a well-established risk factor for occlusive cardiovascular illnesses and has been linked to ocular pathologies such as retinal vascular disorders, age-related macular degeneration, and most notably ectopia lentis. Lipids compose approximately 20% of the dry weight of the retina. Apart from their structural significance, lipids also serve a critical function in providing the necessary energy for the metabolic needs of the retina. Hyperlipidemia is described as an abnormally high level of blood cholesterol and triglycerides and is a major risk factor for atherosclerosis. It may increase the risk of retinal vascular disorders secondary to atherosclerosis-like processes in the retina. Through the inflammatory process they generate, hyperhomocysteinemia and hyperlipidemia may also contribute to the progression of retinal vascular disorders such as diabetic and hypertensive retinopathy and retinopathy of prematurity.