Risk Of Atherosclerosis In Patients Research Articles

Abstract 13313: Risk of Atherosclerosis in Thoracic Aortic Disease: A Study of Multi-Modal Imaging Data From 40,479 UK Biobank Participants

Background: Despite some shared risk factors, aortic aneurysms and atherosclerosis manifest differently across the aorta. While atherosclerosis commonly co-exists with descending and abdominal aortic aneurysms, some observations suggested a decreased risk of atherosclerosis in patients with ascending aortic aneurysms. This has led to the suggestion that drivers of ascending aortic aneurysms may be anti-atherogenic. Aim: Using carotid intima-media thickness (cIMT) as a surrogate for atherosclerosis and deep learning-derived estimates of aortic diameter, this study examines whether ascending aortic aneurysms are protective against atherosclerosis in a longitudinal analysis of UK Biobank participants. Methods: Individuals who underwent both carotid ultrasound and cardiovascular MRI in the UK Biobank (N=40,479) were identified. We derived ascending and descending aortic measurements from a previously developed deep learning model that was trained to quantify dimensions in >4 million MRI images and extract diameter during ventricular systole. Measures of mean cIMT at 2 standardized angles for bilateral carotid arteries were utilized. The relationship between cIMT and aortic diameter was assessed using univariable and multivariable linear regression. β was calculated as μm change in cIMT per cm of aortic diameter. Results: In individuals with an aneurysmal ascending aorta ( > 4.5cm), there was no significant association between aortic diameter and cIMT after accounting for age, sex, height, and weight (adjusted β=-15.4, P=0.26). There was also no significant correlation between ascending aortic diameter at baseline and cIMT progression in follow-up (adjusted β=-2.5; P=0.48). In the entire cohort, larger ascending aortic size was nominally associated with greater cIMT (adjusted β=5.0; P=0.005). As expected, larger diameter in the descending thoracic aorta was associated with higher cIMT (adjusted β=23.9; P=1.9x10 -16 ). Conclusion: Based on multi-modal imaging data from over 40K individuals, we find no evidence of an inverse relationship between ascending aortic aneurysmal disease and atherosclerosis.

Effects of long term antiseizure medications on atherosclerosis

Long-term therapy with antiseizure medications (ASMs) has been associated with metabolic consequences that lead to an increase in the risk of atherosclerosis in patients with epilepsy. This study was conducted to assess the effects of ASMs on vascular risk factors namely, serum Lipid profile and C-reactive protein (CRP) in epileptic patients and to assess the correlation between the duration of the ASMs, and carotid intima media thickness (IMT). Forty three adult patient participants who were receiving ASM monotherapy for more than 2 years and 43 control patients were enrolled in this study. All participants received measurement of common carotid artery (CCA) and IMT by B-mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index (BMI), serum lipid profile and CRP. The correlation between duration of ASM and average carotid IMT was calculated by using the Pearson's correlation coefficient method. The majority of subjects on phenytoin 8 (66.7%) were positive for CRP. There was an equal proportion of patients on carbamazepine who were equally positive 5(50%) and negative 5(50%) for CRP. There was a statistically significant association between phenytoin consumption and CRP positivity. There was positive correlation between duration of phenytoin consumption and average IMT. There was a strong positive correlation between duration of phenobarbitone consumption and average IMT and was statistically significant. Our results also suggest that long-term use of ASMs with prominent effects on the enzyme system, including Carbamazepine, phenytoin, sodium valproate or phenobarbitone may contribute to the progression of atherosclerosis in patients with epilepsy. Keywords: epilepsy; ASMs; IMT; CRP; phenytoin; carbamazepine; sodium valproate; phenobarbitone

Associations Between Atherosclerosis and Elevated Serum Alkaline Phosphatase in Patients With Coronary Artery Disease in an Inflammatory State.

Serum alkaline phosphatase (ALP) has been shown to be associated with cardiovascular disease (CVD) risk. Inflammation is the initiator of atherosclerosis, throughout the life of atherosclerosis. This study investigated the relationship between serum ALP and atherosclerosis in patients with coronary artery disease (CAD) in an inflammatory state. This was a multicentre retrospective study including 22,989 patients with CAD. Serum alkaline phosphatase was converted into the quartiles. C-reactive protein (CRP) was assayed as a marker of systemic inflammation. The atherosclerosis index (AI) was used to assess the degree of atherosclerosis. Binary logistic regression was used to analyse the relationship between ALP and AI. Stratified analysis was performed according to sex and age. Elevated serum ALP was associated with the risk of atherosclerosis in patients with CAD, and after quartiling ALP, the OR for Q4 was 1.17 (95% CI 1.08-1.26; p<0.001) when using Q1 as reference. The odds ratio (OR) for ALP and risk of atherosclerosis was higher in patients aged ≤60 years (OR 1.33, 95% CI 1.15-1.53; p<0.001) than in patients aged >60 years (OR 1.11, 95% CI 1.01-1.23; p<0.05), and higher in males (OR 1.21, 95% CI 1.09-1.35; p<0.001) than in females (OR 1.16, 95% CI 1.03-1.31; p<0.05). Q4 (ALP >83.00 U/L) was significantly associated with increased risk of atherosclerosis in the inflammatory state (OR 1.48, 95% CI 1.18-1.86; p<0.001), and it remained after stratified analysis according to sex and age. The risk of atherosclerosis tended to increase with increasing ALP levels and the correlation between ALP and the degree of atherosclerosis was significantly stronger when ALP was >83.00 U/L. This relationship was more pronounced in inflammatory states, and there were sex and age differences. URL: https://www. gov; Unique identifier: NCT04026724.

Coronary Artery Disease Risk Prediction in Patients With Severe Aortic Stenosis: Development and Validation of the Aortic Stenosis-Coronary Artery Disease (AS-CAD) Score

Patients at a low risk of coronary artery disease (CAD) could be triaged to noninvasive coronary computed tomography angiogram instead of invasive coronary angiography, reducing health care costs and patient morbidity. Therefore, we aimed to develop a CAD risk prediction score to identify those who underwent transcatheter aortic valve implantation (TAVI) at a low risk of CAD. We enrolled 1,782 patients who underwent TAVI and randomized the patients to the derivation or validation cohort 2:1. The aortic stenosis-CAD (AS-CAD) score was developed using logistic regression, followed by separation into low- (score 0 to 5), intermediate- (6 to 10), or high-risk (>11) categories. The AS-CAD was validated initially through the k-fold cross-validation, followed by a separately held validation cohort. The average age of the cohort was 82 ± 7years, and 41% (730 of 1,782) were female; 35% (630) had CAD. The male sex, previous percutaneous coronary intervention, stroke, peripheral arterial disease, diabetes, smoking status, left ventricular ejection fraction <50%, and right ventricular systolic pressure >35mm Hg were all associated with an increased risk of CAD and were included in the final AS-CAD model (all p <0.03). Within the validation cohort, the AS-CAD score stratified those into low, intermediate, and high risk of CAD (p <0.001). Discrimination was good within the internal validation cohort, with a c-statistic of 0.79 (95% confidence interval 0.74 to 0.84), with similar power obtained using k-fold cross-validation (c-statistic 0.74 [95% confidence interval 0.70 to 0.77]). In conclusion, The AS-CAD score robustly identified those at a low risk of CAD in patients with severe AS. The use of AS-CAD in practice could avoid potential complications of invasive coronary angiogram by triaging low-risk patients to noninvasive coronary assessment using existing computed tomography data.

Lipoprotein(a) as a Higher Residual Risk for Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus than without.

Lipoprotein(a) (Lp[a]) is well-known as a residual risk factor for coronary artery disease (CAD). However, the different adverse effects of Lp(a) about CAD in patients with or without type 2 diabetes mellitus (T2DM) are unclear. This study aimed to investigate the Lp(a) thresholds for CAD diagnosis in T2DM and non-T2DM patients, and further compare the Lp(a) alarm values along with optimal low-density lipoprotein cholesterol (LDL-C) level. This retrospective study consecutively enrolled patients with suspected CAD who underwent coronary angiography in Guangdong Provincial People's Hospital between September 2014 and July 2015. A logistic regression model was established to explore the association of Lp(a) and CAD in patients. Restricted cubic splines were used to compare the threshold values of Lp(a) for CAD in patients with and without T2DM, and further in optimal LDL-C level situation. There were 1522 patients enrolled finally. After multivariable adjustment, Lp(a) was an independent risk factor for CAD in patients with T2DM (odds ratio [OR]: 1.98, 95% CI]: 1.12-3.49, p = 0.019) and without T2DM (OR: 3.42, 95% CI: 2.36-4.95, p < 0.001). In the whole population, the Lp(a) threshold of CAD was 155, while 145 mg/L for T2DM and 162 mg/L for non-T2DM ones, respectively. In patients with LDL-C<1.8 mmol/l, the alarm value of Lp(a) was even lower in T2DM than non-T2DM patients (155 vs 174 mg/L). Lp(a) was a significant residual risk for CAD in patients whether with T2DM or not. And Lp(a) had a lower alarm value in T2DM patients, especially in optimal LDL-C level.

28-LB: Role of Glycine N-methyltransferase in Electronegative Lipoproteins-Induced Vascular Dysfunction in a Diabetic Rodent Model

Several studies showed low-density lipoprotein (LDL) is associated with high risk of atherosclerosis in patients with diabetes. However, aggressively decreasing total LDL does not prevent all vascular complications. A novel culprit electronegative LDL (L5) was significantly increased in diabetic patients and could induce vascular damage according to our previous studies. However, the mechanism of L5 formation and how to reduce plasma L5 level are still unclear. In the present study, we found both aqueous and ethylacetate extracts of a traditional Chinese remedy Artemisia capillaris (AC) could decrease plasma L5 level in western diet-fed hamster (22.45 and 28.64 vs. 56.83%, respectively), while clinical remedies Simvastatin and Niacin could not. AC could also reverse western diet-induced vascular senescence (b-gal staining) and relaxation dysfunction in aortic rings (63.66±2.14 vs 40.13±1.48% of maximum contraction when compared to western diet hamsters; P&amp;lt;0.01). To further determine the underlying mechanism, we have found that AC reversed western diet-reduced Glycine N-methyltransferase (GNMT) protein abundance and altered several microRNA expression by analyzing the microarray heatmap in liver tissue. In conclusion, AC could significantly reverse western diet-induced vascular injury by lowering plasma L5 level through restore the liver enzyme GNMT activity. Disclosure A. Lee: None. Y. Chen: None. W. Chen: None.

Increased selenium and decreased iron levels in relation to risk of coronary artery disease in patients with diabetes.

Observational studies have reported inconsistent associations between micronutrient levels and the risk of coronary artery disease (CAD) in diabetic patients. We aim to explore the causal association between genetically predicted concentrations of micronutrients (phosphorus, magnesium, selenium, iron, zinc, and copper) and CAD in patients with diabetes. Single nucleotide polymorphisms (SNPs) connected to serum micronutrient levels were extracted from the corresponding published genome-wide association studies (GWASs). Summary-level statistics for CAD in diabetic patients were obtained from a GWAS of 15,666 patients with diabetes. The primary analysis was carried out with the inverse variance weighted approach, and sensitivity analyses using other statistical methods were further employed to assess the robustness of the results. Genetically predicted selenium level was causally associated with a higher risk of CAD in diabetic patients (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.10-1.42; p = 5.01 × 10-4). While, genetically predicted iron concentrations in patients with diabetes were inversely associated with the risk of CAD (OR: 0.82; 95% CI: 0.75-0.90; p = 2.16 × 10-5). The association pattern kept robust in most sensitivity analyses. Nominally significant associations were observed for magnesium and copper with the risk of CAD in patients with diabetes. No consistent evidence was found for the causal associations between phosphorus and zinc levels, and the risk of CAD in patients with diabetes. We provide consistent evidence for the causal effect of increased selenium and decreased iron levels on CAD in patients with diabetes, highlighting the necessity of micronutrient monitoring and application in these patients.

B-28 | Management of Clinical Stent-In-Stent Restenosis (SISR) in High Risk Coronary Artery Disease Patients With Percutaneous Coronary Intervention (PCI) Followed by Coronary Intravascular Brachytherapy (IVBT)

In-stent-restenosis (ISR) is seen in 10% of patients with DES and is often treated with a repeat DES placement. Recurrent ISR or SISR has a high repeat failure rates, requiring target vessel revascularization (TVR). A combination of the presence of multiple layers of stents, previous restenosis, and other additional comorbidities make this patient population complex and higher risk. Angioplasty followed by IVBT is one possible treatment option in the high-risk patients. This study reviewed the efficacy and safety of PCI followed by IVBT for coronary artery disease in high-risk patients experiencing SISR. A retrospective study was performed which reviewed 78 patients treated between 2016-2021 with SISR involving a total of 91 vessels. All patients underwent PCI with balloon angioplasty followed by IVBT. These patients received localized IVBT radiation using the Novoste Beta-Cath System using a strontium-90 isotope. Radiation dose was delivered based on the vessel diameter, with vessels ≥ 3.5mm in diameter receiving 23 Gy, while vessels of <3.5mm in diameter received 18.4 Gy. Major adverse cardiac events (MACE) were defined as all-cause death, myocardial infarction (MI), and stroke. All patients in the cohort had 2 previously placed DESs in the target lesion. Of total 91 treatments, 67% and 33% treatments were delivered to the LAD or the RCA and circumflex vessel or the marginal arteries, respectively. One patient had intraprocedural cardiac arrest due to suspected intracoronary thrombosis. All patients were symptomatic pre-IVBT and 44% experienced symptomatic reduction after treatment. MACE after IVBT includes MI in 18%, stroke in 5%, and all-cause death occurred in 16% of patients at a median time of 9.3 months post treatment with median follow-up being 22.8 months. Of total, 77% retained patency of the irradiated lesion, while 23% percent experienced restenosis requiring TVR. Coronary restenosis post-deployment of multiple layers of DES remains an ongoing challenge in current times. PCI followed by balloon angioplasty with IVBT is a safe and efficacious treatment option for high-risk coronary artery disease patients with SISR, who have very few treatment options otherwise.

SMAD4 Expression in Monocytes as a Potential Biomarker for Atherosclerosis Risk in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.

Smoking and coronary artery disease risk in patients with diabetes: A Mendelian randomization study.

Previous observational studies have shown an association between smoking and coronary artery disease (CAD) in patients with diabetes. Whether this association reflects causality remains unestablished. This study aimed to explore the causal effect of smoking on CAD in patients with diabetes. Genetic signatures for smoking were extracted from a large genome-wide association study (GWAS), consisted of up to 1.2 million participants. Four smoking phenotypes were included: smoking initiation, cigarettes per day, age at initiation of regular smoking, and smoking cessation. Genetic associations with CAD in patients with diabetes were extracted from another GWAS, which included 15,666 participants (3,968 CAD cases and 11,696 controls). The analyses were performed using the univariable and multivariable Mendelian randomization (MR) method. MR analysis revealed that smoking initiation was positively related to CAD risk in patients with diabetes (OR = 1.322, 95% CI = 1.114 - 1.568, P = 0.001), but this association was attenuated when adjusted for cardiovascular risk factors (OR = 1.212, 95% CI = 1.008 - 1.457, P = 0.041). Age at initiation of regular smoking was negatively related to CAD in patients with diabetes (OR = 0.214, 95% CI = 0.070 - 0.656, P = 0.007), but this association became insignificant when adjusted for cardiovascular risk factors. This study supported the effect of smoking initiation on the risk of CAD in patients with diabetes.

FIB-4 Index and Neutrophil-to-Lymphocyte-Ratio as Death Predictor in Coronary Artery Disease Patients.

Nonalcoholic fatty liver disease (NAFLD)-associated liver fibrosis is likely related to coronary artery disease (CAD) by the mediation of systemic inflammation. This study aimed at evaluating the predictive value of neutrophil-to-lymphocyte-ratio (NLR) and fibrosis-4 index (FIB-4), indices of inflammation and fibrosis, respectively, on CAD mortality. Data from 1460 CAD patients (1151 males, age: 68 ± 10 years, mean ± SD) were retrospectively analyzed. Over a median follow-up of 26 months (interquartile range (IQR) 12-45), 94 deaths were recorded. Kaplan-Meier survival analysis revealed worse outcomes in patients with elevation of one or both biomarkers (FIB-4 &gt; 3.25 or/and NLR &gt; 2.04, log-rank p-value &lt; 0.001). In multivariate Cox regression analysis, the elevation of one biomarker (NLR or FIB-4) still confers a significant independent risk for mortality (hazard ratio (HR) = 1.7, 95% confidence interval (95% CI): 1.1-2.7, p = 0.023), whereas an increase in both biomarkers confers a risk corresponding to HR = 3.5 (95% CI: 1.6-7.8, p = 0.002). Categorization of patients with elevated FIB-4/NLR could provide valuable information for risk stratification and reduction of residual risk in CAD patients.

Novel nomogram for predicting coronary vulnerable plaque risk in patients with coronary artery disease.

Objective: To develop and validate a nomogram for predicting coronary vulnerable plaques (VPs) in coronary artery disease (CAD) patients. Methods: One hundred seventy-seven CAD patients were enrolled in the training group. Another 60 patients were included for validation. Based on the identified independent risk factors, a nomogram model was developed and then validated. Results: Type 2 diabetes, hypertension, neutrophil-to-lymphocyte ratio, low-density lipoprotein cholesterol, MCP-1 and MMP-9 were found to be independent risk factors for coronary VPs. Both internal and external validation showed this nomogram had satisfactory discrimination via receiver operating characteristic curves, calibration via calibration plots and clinical application values via decision curve analysis. Conclusion: The authors established a nomogram model predicting coronary VP risk in CAD patients with promising clinical application value.

Decreased Epicardial CTRP3 mRNA Levels in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease Undergoing Elective Cardiac Surgery: A Possible Association with Coronary Atherosclerosis.

(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.

Biomarkers for Non-Invasive Stratification of Coronary Artery Disease and Prognostic Impact on Long-Term Survival in Patients with Stable Coronary Heart Disease.

Knowledge about cardiac and inflammatory biomarkers in patients with stable coronary artery disease (CAD) is limited. To address this, we analyzed 3072 patients (36% female) with a median follow-up of 10 years in the Leipzig LIFE Heart Study with suspected CAD with coronary angiography. Selected biomarkers included troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, C-reactive protein (hsCRP), and interleukin-6 (IL-6). Patients were stratified by CAD severity: CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis < 50%), and CAD2 (≥one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2; GC2: CAD0 vs. CAD1 + 2. CAD0, CAD1, and CAD2 were apparent in 1271, 631, and 1170 patients, respectively. Adjusted for classical risk factors, hs-cTnT, NT-proBNP, and IL-6 differed significantly in both GC and hsCRP only in GC2. After multivariate analysis, hs-cTnT, NT-proBNP, and IL-6 remained significant in GC1. In GC2, hs-cTnT (p < 0.001) and copeptin (p = 0.014) reached significance. Ten-year survival in groups CAD0, CAD1, and CAD2 was 88.3%, 77.3%, and 72.4%. Incorporation of hs-cTnT, NT-proBNP, copeptin, and IL-6 improved risk prediction (p < 0.001). The studied cardiac and inflammatory biomarkers enable fast and precise non-invasive identification of mortality risk in CAD patients, allowing the tailoring of primary and secondary CAD prevention.

Remnant Cholesterol and the Risk of Coronary Artery Disease in Patients With Type 2 Diabetes.

Among statin-treated patients with type 2 diabetes mellitus (T2DM), there is still a great residual cardiovascular risk. Previous studies found that the level of remnant cholesterol (RC) could predict the coronary artery disease (CAD) risk. In the present study, we enrolled 4145 patients with T2DM; 2784 (67.2%) were male and their median age was 62years. After multivariate logistic analyses, plasma RC level was significantly and independently associated with CAD [odds ratio (OR) 13.524, 95% confidence interval (CI) = 7.058-25.912, P < .001) after adjustment for conventional risk factors, such as age, gender, hypertension, and other lipid levels. Even in the presence of high high-density lipoprotein cholesterol (HDL-C) level, the elevated RC could still predict CAD in T2DM patients (OR 2.064, 95%CI 1.438-2.964, P < .001). Furthermore, RC had relationships with age, hypertension, and smoking status in promoting CAD progression in T2DM patients, with all p for interactive <.001. In conclusion, RC level was independently associated with CAD risk in patients with T2DM.

Association between Influenza and COVID-19 Viruses and the Risk of Atherosclerosis: Meta-Analysis Study and Systematic Review.

There is a lot of evidence to suggest that patients infected with the COVID-19 and influenza viruses are at risk of atherosclerosis. Additionally, there are heterogeneous studies on the risk of arthrosclerosis in patients infected with the influenza and COVID-19 viruses. We conducted a case-control and cross-sectional study and examined the association between the risk of atherosclerosis, and influenza virus (IV-A and IV-B) and&amp;nbsp;COVID-19 infections in this study. We searched for keywords such as influenza virus, COVID-19 and atherosclerosis in English and Persian in well-known databases such as PubMed, SID, Magiran and Google Scholar. In this study, we analyzed the information using a meta-analysis, the random effect model, the I2 index and STAT (version 11.2). The results from the analysis of ten studies on influenza virus and nine studies on COVID-19 reviewed individually (totaling 6428 samples for influenza virus infections and 10,785 samples for COVID-19 infections) demonstrated a risk of arthrosclerosis in patients with influenza and COVID-19 infections, with an OR (odds ratio) = 0.45 ((95% CI): 0.25 to 0.64) and an OR (odds ratio) = 1.04 ((95% CI): 0.82 to 1.26), respectively. The present study provides new insights into the risk of atherosclerosis in patients infected with the COVID-19 and influenza viruses. Therefore, it seems necessary to consider different strategies for managing and eradicating viral infections among individuals.

Kawasaki Disease: Pathology, Risks, and Management.

Kawasaki disease (KD), first reported as an acute febrile mucocutaneous lymph node syndrome, is a self-limiting vasculitis of unknown etiology. The most important aspect of KD is the prevention of coronary artery lesion (CAL) because myocardial ischemia or infarction due to CAL might be lethal. In addition to the CAL, patients with KD develop systemic vasculitis, which indicates the presence of vascular endothelial damage. Studies assessing pulse wave velocity or percentage change in flow-mediated dilatation have shown that aortic stiffness is increased in patients with KD history. In contrast, the cardio-ankle vascular index, a novel parameter not affected by blood pressure, has not demonstrated increased aortic stiffness in patients with KD. Although many studies using various parameters have suggested a risk of atherosclerosis in patients with a history of KD, a few others have reported no significant differences between KD patients and controls. Therefore, it will be necessary to thoroughly understand the characteristics of each parameter, before evaluating the results of those studies, to understand systemic vascular dysfunction in these populations, and to manage their vascular health. Although it is controversial whether the risk of atherosclerosis in patients with KD is higher, those with CAL are thought to be at a high risk of atherosclerosis. Therefore, appropriate treatment to prevent CAL in the acute phase and subsequent regular follow-up is important. Here, we review the pathology, risk, and management of vascular disorders, especially systemic vascular disorders, in patients with KD history.

Abstract #1184265: Endothelial Dysfunction and Increased Carotid Intima-Media Thickness in the cardiovascularly asymptomatic Growth hormone naive Patients of Sheehan’s Syndrome

Inflammation plays an important role in the atherosclerotic process of the arterial wall, and peripheral markers of inflammatory activity such as C - reactive protein, TNF-α and IL-6 have been shown to correlate with the risk of atherosclerosis in patients with Growth hormone deficiency(GHD). While severe GHD is a well-established feature of Sheehan's syndrome (SS) and is associated with clustering of adverse CV risk factors. There is evidence linking adverse CV events with elevated circulating levels of inflammatory markers in the general population undermining the importance of determination of such markers in patients with SS.We aim to determine the proinflammatory markers of endothelial dysfunction and carotid artery IMT in GH naive patients of SS.

OA28 Exploring the potential of polygenic risk scores for predicting coronary artery disease in patients with rheumatoid arthritis

Abstract Background/Aims Patients with rheumatoid arthritis (RA) have a higher prevalence of coronary artery disease (CAD) than the general population which contributes to early mortality. Current screening tools for CAD, which are developed in the general population, are less effective for estimating CAD risk in patients with RA. This reduced performance is mainly due to the differing contribution from traditional risk factors and the contribution from disease-specific factors. Our understanding of the genetic basis of CAD has improved over recent years and shows promise for improving risk prediction in the form of polygenic risk scores (PRS). We hypothesise that PRS can help us improve CAD risk prediction in patients with RA by providing more accurate models of risk. Methods Patients were recruited from the Norfolk Arthritis Register (NOAR), a detailed community-based longitudinal observational study focused on the cause and outcome of inflammatory polyarthritis, between 1990 and 2017. Analysis was restricted to patients who satisfied the 2010 ACR criteria cumulatively over five years and had detailed clinical history at baseline and follow-up. We developed a prediction model based on traditional risk factors and explored the inclusion of a PRS (49K SNPs) in a subset of patients with available genetic data. Cox proportional hazards models were used to derive risk equations for evaluation of 10-year risk of CAD. We applied multiple imputations with chained equations using the Random Forest algorithm to replace missing values. Measures of calibration and discrimination were determined in the validation cohort of 423 individuals. Results A total of 2123 patients were included in the analysis with 136 incident cases of self-reported CAD. The model using only traditional risk factors achieved an AUC of 0.72 (95% CI 0.71, 0.73), with a calibration slope of 1.03, and explained approximately 50% (95% CI 47, 52%) of the variance of the outcome. We found that being male reduces the risk by a factor of 0.82 (95% CI 0.68, 1.00). The hazard ratio for age was found to be 1.00 (95% CI 0.99, 1.01) indicating risk remains the same across all age groups. Inclusion of a CAD PRS increased the performance with an AUC of 0.76 (95% CI 0.75, 0.77), explained variance of 53% (95% CI 49, 56%) but with a slightly worse calibration slope of 0.91. Conclusion An integrated risk score, that combines traditional risk factors with a PRS, improves CAD prediction in patients with RA. Further research is required to better understand the role of heritable components contributing to CAD risk in RA patients. By refining the underlying PRS, we hope to further improve CAD risk prediction in RA patients, through this integrated approach. Disclosure M. Soomro: None. M. Stadler: None. S. Viatte: None. A. MacGregor: None. S. Verstappen: None. A. Barton: None. J. Bowes: None.

Elevated blood urea nitrogen-to-creatinine ratio increased the risk of Coronary Artery Disease in patients living with type 2 diabetes mellitus

BackgroundHigh Blood Urea Nitrogen (BUN) and high Serum Creatinine (SCr) levels are risk factors for Coronary Artery Disease (CAD). However, the relationship between the Blood Urea Nitrogen to Creatinine (BUN/SCr) ratio (UCR) and the risk of CAD in patients living with new-onset diabetes is unclear. This study aimed to examine the relationship between blood UCR and the risk of CAD in patients living with new-onset type 2 diabetes mellitus (T2DM).MethodsWe analyzed the data from the cohort of 12,299 patients living with type 2 diabetes mellitus. Primary endpoints were the events of CAD. The ANOVA test (continuous indicators) and χ2 test (categorical indicators) were used to assess the differences of baseline characteristics across the groups of UCR. In order to understand the correlation between variables, we performed correlation analysis on variables that have significant differences between CAD group and non-CAD group. Multivariate-adjusted Cox proportional hazard regression models were applied to estimate the association of the blood UCR with the risk of CAD in patients living with T2DM. The Kaplan–Meier survival function plotting and the log-rank test were used to evaluate the event-free survival according to the groups of UCR. The restricted cubic spline model was used to show the adjusted association between blood UCR and risk of CAD in patients living with T2DM.ResultsDuring a median follow-up of 2.66 years, 1173 CAD were recorded with an event rate of 28.49 events per 1000 person-years. In multivariate-adjusted Cox regression models, elevated blood urea nitrogen to creatinine ratio (UCR) was associated with higher risk of CAD in patients living with T2DM [hazard ratio (HR), 1.782; 95% confidence interval (CI), 1.237–2.567]. The Kaplan–Meier survival curves indicated that the high group of UCR tended to have a lower event-free survival than the low group and medium group. There was a nonlinear trend toward increasing risk of CAD across the groups of UCR. And cubic spline function graph suggested that the influence of UCR level on HR for CAD increased significantly at UCR levels above 6.67.ConclusionsAn elevated UCR was significantly associated with an increased risk for CAD in patients living with T2DM.