Atherosclerotic Cardiovascular Risk Factors Research Articles

C-X-C motif chemokine receptor 4-directed PET signal in the arterial tree is not consistently linked to calcified plaque burden and cardiovascular risk.

Purpose: To establish the extent, distribution and frequency of in-vivo vessel wall [68Ga]Ga-PentixaFor uptake and to determine its relationship with calcified atherosclerotic plaque burden (CAP) and cardiovascular risk factors (CVRF). Methods: 65 oncological patients undergoing [68Ga]Ga-PentixaFor PET/CT were assessed. Radiotracer uptake (target-to-background ratio [TBR]) and CAP burden (including number of CAP sites, calcification circumference and thickness) in seven major vessel segments per patient were determined. We then investigated associations of vessel wall uptake with CAP burden, cardiovascular risk (CVRF and European Society of Cardiology [ESC] SCORE2/SCORE2-OP risk chart) and image noise (determined by coefficient of variation [CoV] from unaffected liver parenchyma). Results: We identified 1292 sites of high focal [68Ga]Ga-PentixaFor uptake (PentixaFor+ sites) in the vessel wall in 65/65 (100%) patients, with concomitant calcification in 385/1292 (29.8%) sites. There were no significant associations between vessel wall uptake and CAP burden (number of PentixaFor+ sites: r ≤ 0.18, P ≥ 0.14; PentixaFor+ TBR: r ≤ 0.08, P ≥ 0.54). The number of PentixaFor+ sites showed a moderate correlation with cardiovascular risk (ESC SCORE2/SCORE2-OP, r = 0.30; number of CVRF, r = 0.26; P = 0.04, respectively), but failed to reach significance for PentixaFor+ TBR (r ≤ 0.18, P ≥ 0.22). In univariable regression analysis, body mass index (odds ratio [OR] 1.08, 95%-confidence interval [CI] 1.02-1.14) and CoV (OR, 1.07; CI, 1.05-1.10) were linked to TBR and the number of PentixaFor+ sites (P < 0.01, respectively), while injected activity was only associated with the latter imaging parameter (OR, 0.99; CI, 0.98-1.00; P = 0.04). In multivariable regression, injected activity (OR, 1.00; CI, 0.99-1.00) and CoV (OR, 1.06; CI, 1.06-1.07) remained significantly associated with the number of PentixaFor+ sites (P < 0.01, respectively). CoV, however, was the only parameter significantly linked to PentixaFor+ TBR on multivariable analysis (OR, 1.02; CI, 1.01-1.03; P < 0.01). Conclusion: On a visual and quantitative level, high focal [68Ga]Ga-PentixaFor uptake in the arterial tree was not consistently linked to vessel wall calcification or cardiovascular risk. Image noise, however, may account for a substantial portion of apparent vessel wall uptake.

Antidepressant-related microstructural changes in the external capsule.

Several magnetic resonance imaging (MRI) studies have reported that antidepressant medications are strongly linked to brain microstructural alterations. Notably, external capsule alterations have been reported to be a biological marker for therapeutic response. However, prior studies did not investigate whether a change in the neurite density or directional coherence of white matter (WM) fibers underlies the observed microstructural alterations. This MRI-based case-control study examined the relationship between patients' current use of antidepressant medications and advanced measurements of external capsule WM microstructure derived from multishell diffusion imaging using neurite orientation dispersion and density imaging (NODDI). The study compared a group of thirty-five participants who were taking antidepressant medications comprising selective serotonin reuptake inhibitors (SSRIs) (n = 25) and serotonin and norepinephrine reuptake inhibitors (SNRIs) with a control group of thirty-five individuals matched in terms of age, sex, race, and atherosclerotic cardiovascular risk factors. All participants were selected from the Dallas Heart Study phase 2, a multi-ethnic, population-based cohort study. A series of multiple linear regression analyses were conducted to predict microstructural characteristics of the bilateral external capsule using age, sex, and antidepressant medications as predictor variables. There was significantly reduced neurite density in the bilateral external capsules of patients taking SSRIs. Increased orientation dispersion in the external capsule was predominantly seen in patients taking SNRIs. Our findings suggest an association between specific external capsule microstructural changes and antidepressant medications, including reduced neurite density for SSRIs and increased orientation dispersion for SNRIs.

Unclosing Premature Mortality Gap Among Patients With Gout in the US General Population, Independent of Serum Urate and Atherosclerotic Cardiovascular Risk Factors.

Gout flares are followed by transient major cardiovascular (CV) risk, implicating the role of inflammation; the aim of this study was to determine whether premature mortality rates in patients with gout and CV risk are independent of serum urate (SU) and atherosclerotic CV disease (ASCVD) risk factors. Using serial US nationwide prospective cohorts, we evaluated the independent association of prevalent gout with all-cause and CV mortality, adjusting for SU, ASCVD risk factors, comorbidities, medications, and kidney function and compared mortality rates between the early (1988-1994 baseline) and late cohorts (2007-2016 baseline). We replicated late cohort findings among patients with gout in a nationwide UK cohort (2006-2010 baseline). Adjusted hazard ratios (HRs) for mortality rates in patients with prevalent gout were similar in early and late US cohorts (1.20 [1.03-1.40] and 1.19 [1.04-1.37], respectively); HRs with further adjustment for SU were 1.19 (1.02-1.38) and 1.19 (1.03-1.37), respectively. Adjusted HR among patients with gout from the UK late cohort was 1.61 (1.47-1.75); these associations were larger among women (P = 0.04) and prominent among Black individuals. Adjusted HR for CV mortality rates in the late US cohort was 1.39 (1.09-1.78); those for circulatory, CV, and coronary heart disease deaths among UK patients with incident gout were 1.48 (1.24-1.76), 1.49 (1.20-1.85), and 1.59 (1.26-1.99), respectively. Patients with gout experience a persistent mortality gap in all-cause and CV deaths, even adjusting for SU and ASCVD risk factors, supporting a role for gout-specific pathways (eg, flare inflammation). These findings suggest gaps in current care, particularly in women and possibly among Black patients.

Left Ventricular Global Longitudinal Strain (LV GLS) assessed by Echocardiography predicts myocardial fibrosis and iron overload in transfusion dependent beta-thalassemia patients

Abstract Background Cardiac involvement represents the leading cause of death in transfusion dependent beta-thalassemia (TDT) patients. It is mainly related to cardiac iron overload and myocardial fibrosis, causing progressive damage and a deterioration of systolic and diastolic function. Moreover, myocardial fibrosis may not be directly related with the degree of cardiac iron deposition and it is associated with a higher risk of cardiovascular complications. To date, Cardiac Magnetic Resonance (CMR) is the gold standard for the evaluation of iron overload with T2* sequences and for the detection of myocardial fibrosis with late gadolinium enhancement (LGE). However, CMR is not always feasible. Left Ventricular Global Longitudinal Strain (LV GLS) with Speckle Tracking Echocardiography (STE) is a non-invasive imaging tool, which may play a key role in the early recognition of subclinical myocardial damage and dysfunction (figure 1). Purpose The aim of this study was the evaluation of the role of LV GLS with STE in the characterization of myocardial involvement in a population of TDT patients. Methods An observational, cross-sectional, monocentric study was conducted enrolling 44 patients with TDT from the outpatient clinic of hematology located in our teritary hospital from January 2022 to December 2022. Each patient underwent a thorough clinical evaluation, laboratory testing, transthoracic echocardiogram (TTE) with LV GLS-STE by a trained cardiologist and contrast enhanced CMR with T2* technique and LGE sequences. A T2* value &amp;lt; 20 msec was set to define the presence of iron overload. Results The mean age of patients was 39± 9 years with a slight prevalence of female sex (53% vs 47% respectively). Atherosclerotic cardiovascular risk factors were rarely present, the most common was arterial hypertension in about 12% of patients. The TTE pointed out a left ventricular ejection fraction within the normal range (mean value of 59 ± 5%). As regards LV GLS, the mean value was -21.1 ± 3.0%. Cardiac iron overload was observed in 18% of patients, while about 15% of patients had cardiac fibrosis. A clinical and statistically significant difference was observed between LV GLS values in patients with cardiac iron overload as compared to patients without (-18.2 ± 2.1% vs -20.6 ± 3.1%; p value=0.043). A clinical and statistically significant difference was documented, also, between LV GLS values in patient with cardiac fibrosis as compared to patient without LGE (-16.4 ± 1.7% vs -20.6 ± 2.8%; p value=0.002). As regards cardiac fibrosis, a LV GLS cut-off value of -18,3% was found by the analysis of ROC curve with an AUC of 0.931 (95% CI: 0.846-1.000) (figure 2). Conclusions In a small population of TDT patients we observed that LV GLS with STE may be a promising tool able to help clinicians in the early identification of cardiac iron overload and fibrosis, providing useful information for diagnostic workup and therapeutic approach.

Comparison of Atherosclerotic Cardiovascular Risk Factors and Cardiometabolic Profiles Between Current and Never Users of Marijuana.

The relationship between marijuana use and cardiovascular health remains uncertain, with several observational studies suggesting a potential association with increased adverse atherosclerotic cardiovascular disease (ASCVD) outcomes. This study examined the relationship between marijuana use, ASCVD risk factors, and cardiometabolic risk profiles. US adults (18-59 years) without cardiovascular disease were identified from the National Health And Nutrition Examination Survey (2005-2018) based on self-reported marijuana use. Current users (used within the past month) and never users were compared with assess the burden and control of traditional ASCVD risk factors and biomarkers, using inverse probability of treatment weighting to adjust for sociodemographic and lifestyle factors, including tobacco use. Of the 13 965 participants identified (mean age, 37.5; 51.2% female; 13% non-Hispanic Black), 26.6% were current users. Current users were predominantly male, low-income, and more likely to be concurrent tobacco users. Inverse probability of treatment weighting analysis showed no significant differences in the burden and control of hypertension (19.3% versus 18.8%, P=0.76; 79.8% versus 77.8%, P=0.75), dyslipidemia (24.0% versus 19.9%, P=0.13; 82% versus 75%, P=0.95), diabetes (4.8% versus 6.4%, P=0.19; 52.9% versus 50.6%, P=0.84), obesity (35.8% versus 41.3%, P=0.13), and physical activity levels (71.9% versus 69.3%, P=0.37) between current and never users. Likewise, mean 10-year ASCVD risk scores (2.8% versus 3.0%, P=0.49), 30-year Framingham risk scores (22.7% versus 24.2%, P=0.25), and cardiometabolic profiles including high-sensitivity C-reactive protein (3.5 mg/L versus 3.7 mg/L, P=0.65), neutrophil-lymphocyte ratio (2.1 versus 2.1, P=0.89), low-density lipoprotein (114.3 mg/dL versus 112.2 mg/dL, P=0.53), total cholesterol (191.2 mg/dL versus 181.7 mg/dL, P=0.58), and hemoglobin A1C (5.4% versus 5.5%, P=0.25) were similar between current and never users. This cross-sectional study found no association between self-reported marijuana use and increased burden of traditional ASCVD risk factors, estimated long-term ASCVD risk, or cardiometabolic profiles. Further studies are needed to explore potential pathways between adverse cardiovascular disease outcomes and marijuana use.

Relationship between modifiable atherosclerotic cardiovascular risk factors and coronary artery bifurcation lesion

Abstract Background: Modifiable atherosclerotic cardiovascular disease risk factors are hypertension, diabetes mellitus, dyslipidemia, cigarette smoking, and obesity; the term coronary artery bifurcation is used when a coronary artery divides into two hemodynamically important branches or when the main branch has a hemodynamic significant side branch, bifurcation lesion represent 20% or more of coronary artery stenoses undergoing angiography. Objectives: To evaluate the relationship of hypertension, diabetes, dyslipidemia, cigarette smoking, and obesity to coronary bifurcation disease. Materials and Methods: In a cross-sectional study conducted in the Iraqi Center for Heart Diseases from May 2020 to May 2021, a total of 140 adult patients (70 cases with coronary bifurcation lesions and 70 control cases with non-bifurcation lesions) with angiography-documented stenotic coronary artery disease (CAD) were defined. Case demographics and modifiable CAD risk factors were addressed. Results: In the bifurcation group, the non-bifurcation lesion was mostly an associated angiographic finding (82%). The most significantly correlated atherosclerotic risk factor with bifurcation lesion compared to non-bifurcation lesion was diabetes, followed by systemic hypertension. Dyslipidemia was the most common prevalent risk factor, equally distributed in both groups. Smoking and obesity were distributed nearly equally in both groups. Conclusion: There is a significant relationship between diabetes and hypertension with coronary bifurcation lesions compared to non-bifurcation lesions.

TyG index as a predictor of spontaneous coronary artery dissection in young women

ABSTRACT Objective Spontaneous coronary artery dissection (SCAD) is a rare but potentially life-threatening pathology and cases are especially seen in women under 50 years of age and with relatively fewer cardiovascular risk factors. Although risk factors facilitating the development of SCAD have been defined in the literature, modifiable risk factors remain unclear. In this study, it was aimed to investigate the relationship between the triglyceride glucose index (TyG) and the development of SCAD in the population of young women. Methods The results of 281 patients were analyzed and compared with each other in terms of clinical, demographic, laboratory parameters, and coronary angiography results. Results The mean age was 45 years and all of them were female. When the groups were compared, the TyG and inflammatory parameters were higher in the SCAD group (p < 0.001). When these two groups with low cardiovascular risk factors were compared in logistic regression analysis, high TyG was found to be an independent predictor of SCAD development in young women (p < 0.001). Conclusion As a result, our study shows that the development of these non-atherosclerotic conditions can be predicted by simple biochemical tests in young women with low atherosclerotic cardiovascular risk factors.

Severity of ischemic heart disease in relation to atherosclerotic cardiovascular risk score and individual atherosclerotic cardiovascular risk factor

Severity of ischemic heart disease in relation to atherosclerotic cardiovascular risk score and individual atherosclerotic cardiovascular risk factor

Uterine arcuate artery calcification as a potential marker of cardiovascular risk-a preliminary study.

Atherosclerotic cardiovascular disease is the most common cause of death in postmenopausal women. As this is a progressive disease, it is important to identify markers at an early stage during the subclinical period. Arterial calcifications are an indicator of overall atherosclerotic disease and therefore may be used as a marker for the estimation of future atherosclerotic cardiovascular events. The aims of this study are to investigate the relationship between uterine myometrial calcification (UMC) and carotid artery intima-media thickness (CIMT) and to evaluate whether UMC can be a predictive marker for the estimation of future atherosclerotic cardiovascular risk in asymptomatic postmenopausal women. In this cross-sectional study, we assessed 81 postmenopausal women without gynecological complaints for cardiovascular risk factors, UMC, and CIMT. Participants were divided into two risk groups according to their cardiovascular risk factors. The level of UMC was determined using a new scoring system, which was based on transvaginal ultrasonography. Demographic, clinical, and laboratory parameters, UMC scores, and measurements of CIMT were evaluated. A moderately positive correlation was detected between CIMT and UMC scores ( r = 0.62). There was a significant relationship between UMC scores and atherosclerotic cardiovascular risk; the risk of atherosclerosis was 15.4 times higher (OR: 15.4, 95% CI: 5.1-46.8; P = 0.001) in participants with a high UMC score (≥2). According to the multivariable logistic regression model adjusted by age and duration of menopause, the risk of cardiovascular atherosclerosis increased 27.8 fold for those with CIMT of 0.075 or greater (OR: 27.8, 95% CI: 5.3-147.1; P = 0.001) and 9.2 fold for those with a UMC score of 2 or greater (OR: 9.2, CI: 1.22-69.3; P = 0.032). The presence of UMC has been identified as an independent predictive factor for atherosclerotic risk. Accordingly, considering UMC as an atherosclerotic cardiovascular risk factor may provide an opportunity to identify cardiovascular disease in asymptomatic postmenopausal women. When UMC is detected, women should be assessed for cardiovascular risk.

The mean platelet volume and atherosclerotic cardiovascular-risk factors in adults with obesity: a systematic review and meta-analysis of observational studies

BackgroundObesity is a major risk factor for atherosclerotic cardiovascular disease (ASCVD) and is associated with altered platelet function. The mean platelet volume (MPV) is a rapid measure of platelet activation and a prognostic marker in patients with cardiovascular disease. However, no meta-analysis on the association between MPV and obesity has been conducted, and the value of monitoring the MPV in patients with obesity remains unclear.ObjectiveTo provide cumulative evidence on whether the mean platelet volume (MPV) is increased in individuals with obesity and to describe associations between the ASCVD-risk factors and the MPV in individuals with obesity.MethodsThis meta-analysis was prepared following the Meta-analysis Of Observational Studies (MOOSE) guidelines. We searched the PubMed and Embase database from inception until the 31st of March 2021. Studies were included when they reported the mean platelet volume in individuals with obesity and provided a suitable non-obese comparator group. The risk of bias was independently assessed by two reviewers using the Newcastle–Ottawa scale. The primary outcome of the meta-analysis was the MPV, while we considered the atherosclerotic risk profiles as a secondary outcome.ResultsWe identified 178 citations through the PUBMED and 255 citations through EMBASE database search. In all, 13 studies met the inclusion criteria. Firstly, we report an increased mean platelet volume in individuals with obesity compared to non-obese individuals (MD 0.79; [95%CI: 0.42 to 1.16], I2 = 93.4%). Moreover, the reported increase in the MPV was inversely associated with the body mass index (Coefficient: -0.57, standard error (SE): 0.18, p < 0.001) and directly related to changes in triglyceride levels (Coefficient: 4.99, standard error (SE): 1.14, p < 0.001).ConclusionThis meta-analysis and meta-regression showed an increased MPV in nondiabetic individuals living with obesity. Moreover, the MPV was associated with hypertriglyceridemia, an independent predictor of atherosclerotic cardiovascular disease. Overall, the findings suggest that MPV may be a valuable rapid marker for the monitoring and risk-stratification of individuals with obesity who may be at risk of developing cardiovascular disease.

Correlation between known atherosclerotic cardiovascular risk factors and the maximum carotid plaque height among executive check-up unit patients in a tertiary hospital

Abstract Funding Acknowledgements Type of funding sources: None. Background As the development of atherosclerotic cardiovascular disease (ASCVD) involves several traditional risk factors, such as age, sex, elevated blood glucose, dyslipidemia, hypertension, obesity, family history, and smoking, assessment based on conventional risk factors is recommended in identifying individuals who at risk for ASCVD. Estimating risk through these factors has performed poorly; thus, non-invasive and inexpensive methods for identifying the presence of subclinical atherosclerosis in these patients are warranted. Present data suggest that the simpler maximum carotid plaque height (MCPH) predicted cardiovascular events similar to the more comprehensive carotid plaque burden, whereas intima-media thickness (IMT) did not. This concept, however, has not yet been validated in the Philippine population. Purpose To determine if there is a significant correlation between known ASCVD risk factors and the MCPH among Executive Check-Up Unit (ECU) patients in a tertiary hospital from January to December 2019. Methods This is an analytical cross-sectional study done in a private tertiary hospital from January to September 2021. The clinical profile of patients along with identified risk factors were collated and tabulated. Previous carotid ultrasound studies retrieved were then examined by a high-resolution ultrasonographic unit with a linear array transducer. Clear images were captured digitally to allow electronic measurement of the MCPH by a clinical research fellow in peripheral vascular medicine. Results A total of 589 patients were included in the study. The mean age of the patients was 50.4 years old. Three hundred sixty-three were male, while 226 were female. One hundred fourteen were found to have diabetes, 22 patients had proteinuria and 79 patients had left ventricular hypertrophy. A total of 57 patients had only one risk factor, 142 patients had two risk factors, 175 patients had three risk factors, 129 patients had four risk factors, 47 had five risk factors, 8 patients had six risk factors and, only one patient had seven risk factors present. Eight-two patients were classified as having Grade I MCPH, 137 patients had Grade II MCPH, while 22 patients were classified as Grade III MCPH. Results showed that the number of risk factors and the MCPH are significantly correlated. The coefficient suggested that the correlation was positive. Conclusion Risk factors individually identified to positively correlate with the MCPH were age, fasting blood glucose, glycosylated hemoglobin, proteinuria, and left ventricular hypertrophy. On the other hand, there was no significant correlation between sex, body mass index, hypertension, low density lipoprotein, and the MCPH. Notably, there was a significant correlation between the number of ASCVD risk factors and the MCPH of the study population: as the number of risk factors increased, the maximum plaque height grade also increased.

We do not need more Guidelines, nor more Drugs, nor more Combinations! The priority is a Medical Ecosystem that favors Evidence-Based Medicine, Personalization, Empowerment, Access, and Reflection

A growing number of publications evidencing the poor achievement of the therapeutic goals of the so-called atherosclerotic cardiovascular risk factors (especially hypercholesterolemia, hypertension, and diabetes). Many authors propose therapeutic inertia as the most compelling cause of this situation. This article aims to provide a vision from a dedicated cardiovascular prevention physician's perspective, based on four pillars (in order of importance): "face-to-face" assistance with social responsibility, clinical research, teaching, and consulting. Beyond the bureaucratic vision, it proposes the necessary conditions to achieve an efficient medical ecosystem (evidence-based medicine, personalization, empowerment, access, and reflection). Likewise, the therapeutic failure palliatives, as called by the author (more guidelines, more high-tech drugs, and more combinations of drugs), are exposed. These palliatives feed into a vicious circle and are insufficient to mitigate a medical-social problem, as is the cardio-metabolic risk and diseases

Intersecting single-cell transcriptomics and genome-wide association studies identifies crucial cell populations and candidate genes for atherosclerosis

AimsGenome-wide association studies (GWASs) have discovered hundreds of common genetic variants for atherosclerotic disease and cardiovascular risk factors. The translation of susceptibility loci into biological mechanisms and targets for drug discovery remains challenging. Intersecting genetic and gene expression data has led to the identification of candidate genes. However, previously studied tissues are often non-diseased and heterogeneous in cell composition, hindering accurate candidate prioritization. Therefore, we analysed single-cell transcriptomics from atherosclerotic plaques for cell-type-specific expression to identify atherosclerosis-associated candidate gene–cell pairs.Methods and resultsWe applied gene-based analyses using GWAS summary statistics from 46 atherosclerotic and cardiovascular disease, risk factors, and other traits. We then intersected these candidates with single-cell RNA sequencing (scRNA-seq) data to identify genes specific for individual cell (sub)populations in atherosclerotic plaques. The coronary artery disease (CAD) loci demonstrated a prominent signal in plaque smooth muscle cells (SMCs) (SKI, KANK2, and SORT1) P-adj. = 0.0012, and endothelial cells (ECs) (SLC44A1, ATP2B1) P-adj. = 0.0011. Finally, we used liver-derived scRNA-seq data and showed hepatocyte-specific enrichment of genes involved in serum lipid levels.ConclusionWe discovered novel and known gene–cell pairs pointing to new biological mechanisms of atherosclerotic disease. We highlight that loci associated with CAD reveal prominent association levels in mainly plaque SMC and EC populations. We present an intuitive single-cell transcriptomics-driven workflow rooted in human large-scale genetic studies to identify putative candidate genes and affected cells associated with cardiovascular traits. Collectively, our workflow allows for the identification of cell-specific targets relevant for atherosclerosis and can be universally applied to other complex genetic diseases and traits.

Prevalence of atherosclerotic diseases and cardiovascular risk factors in military health care centres

The high burden of atherosclerotic diseases is attributable to preventable cardiovascular (CV) risk factors particularly hypertension (HPT), diabetes mellitus (DM), hyperlipidaemia and smoking.

Impact of early initiation of SGLT2 inhibitor on cardiovascular outcomes in diabetic patients with known atherosclerotic cardiovascular disease or risk factors: propensity score matched analysis

Abstract Purpose Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular benefits in patients with diabetes and atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the impact of early initiation of SGLT2 inhibitor on cardiovascular outcomes in diabetic patients with known and at risk of ASCVD. Methods We retrospectively analyzed 29,309 consecutive patients with type 2 diabetes prescribed empagliflozin (N=18,979, 64.8%) and dapagliflozin (N=10,330, 35.2%) between August 2015 and August 2020 in 16 public hospitals in Hong Kong. Patients with diagnosis of diabetes to first prescription of SGLT2 inhibitors (Dx-to-Rx time) ≤12 months were matched with &amp;gt;12 months using propensity score derived from logistic regression. 3,370 matched patients were divided into 4 groups: (i) patients with known ASCVD involving 1 territory (coronary artery, peripheral artery or cerebrovascular disease); (ii) known ASCVD involving &amp;gt;1 territories; (iii) CV risk factor(s) other than diabetes and (iv) no known ASCVD or additional CV risk factors. Incidence rates of 3-point major adverse cardiovascular events (MACE, including non-fatal stroke, non-fatal myocardial infarction and cardiovascular death) were compared between Dx-to-Rx time ≤12 months and &amp;gt;12 months across 4 subgroups during a median follow-up of 2.8 years (IQR 2.2 to 3.4). Results Of 29,309 patients (mean age 54.9±11.6 years, female 41.0%), 22.9% had single territory and 6.1% multi-territories ASCVD, 53.3% with additional CV risk factors and 17.7% neither risk factor nor ASCVD. Overall, 19.0% of patients had Dx-to-Rx time ≤12 month; 19.3%, 15.7%, 17.6% and 30.0% in each group, respectively. Overall, Dx-to-Rx time ≤12 months was associated with lower rates of MACE (hazard ratio (HR) =0.27, 95% CI: 0.17–0.42). Subgroup analysis showed similar results in patients with CV risk factors of or known ASCVD but not in patients with neither risk factor nor ASCVD (P for interaction=0.001, Table 1). Conclusion Early initiation of SGLT2 inhibitor was associated with significant lower MACE rates in diabetic patients with known ASCVD or additional CV risk factors. The impact was more marked in patients with additional CV risk factors. Our findings suggested early initiation in diabetic patients with known ASCVD and additional CV risk factors. Funding Acknowledgement Type of funding sources: None.

Cardiovascular susceptibility LOCI through the lens of single-cells in plaques: Discovery of crucial cell populations and candidate genes for atherosclerosis.

Background and Aims: We recently reported on the cellular landscape of advanced carotid atherosclerotic plaques, providing detailed insight on plaque pathology while creating a vast resource for further studies. Large-scale GWAS have identified hundreds of common variants for atherosclerotic disease and cardiovascular risk factors. One of the major challenges in the post-GWAS era remains decoding of susceptibility loci to targets that have the ability to translate into clinical care.

Clinical significance of subclinical atherosclerosis in retinal vein occlusion

Retinal vein occlusion (RVO) is associated with atherosclerotic cardiovascular risk factors; however, its association with the specific markers of subclinical atherosclerosis has not yet been established. To investigate this association, we compared 70 patients with RVO to 70 age- and sex-matched patients without RVO. Low-density lipoprotein cholesterol (LDL-C) levels and brachial-ankle pulse wave velocity (baPWV) were significantly higher in the RVO group than in the control group. Carotid plaques (54.3% vs. 28.6%, p = 0.004) were more frequent in the RVO group. Multivariate logistic regression analysis showed that the presence of carotid plaques (odds ratio [OR]: 3.15, 95% confidence interval [CI] 1.38–7.16, p = 0.006), as well as smoking, LDL-C level, and baPWV were associated with RVO. Additionally, a multinomial logistic regression model showed that the presence of carotid plaques (OR: 3.94, 95% CI 1.65–9.41, p = 0.002) and LDL-C level were associated with branch RVO, whereas smoking and baPWV were associated with central RVO. In conclusion, RVO was associated with subclinical atherosclerosis markers, including carotid plaques and baPWV. These results support the hypothesis that atherosclerosis contributes to the etiology of RVO and suggest the evaluation of subclinical atherosclerosis in patients with RVO.

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

DASH Diet Concordance Among Adults in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study (2010–2013)

Abstract Objectives South Asian Americans have a disproportionately higher risk of atherosclerotic cardiovascular disease (ASCVD) and risk factors, such as hypertension compared to non-Hispanic whites and other Asian American groups. Our objective was to investigate adherence to Dietary Approaches to Stop Hypertension (DASH), an established dietary pattern to reduce blood pressure, and association with sociodemographic, body composition, and ASCVD risk factors. Methods Baseline data from 893 adults (40–83y, 47% female) recruited between 2010–2013 for the MASALA Study were used in these analyses. We computed a DASH concordance score from the validated 163-item Study of Health Assessment and Risk in Ethnic groups food frequency questionnaire (FFQ), using an established method. We scored concordance based on 8 components: high intake of 1) fruit, 2) vegetables, 3) nuts/legumes, 4) low-fat dairy products, and 5) whole grains, and low intake of 6) sodium, 7) sugar-sweetened beverages, and 8) red/processed meats. The theoretical DASH score may range from 8 (low concordance) to 40 (high concordance). Results The DASH score in MASALA participants ranged 12–35 (mean ± SD, 24.4 ± 4.4). The average score was higher among women (25.4 ± 4.1) than men (23.6 ± 4.5; P &amp;lt; 0.001), higher among adults 65 and older than those ≤50 (24.9 ± 4.3 vs. 23.9 ± 4.6, P = 0.015), and higher among participants who had lived less than 50% of their life in the U.S. (24.9 ± 4.4 vs. 23.9 ± 4.4, p-0.0014). The score was also higher among participants who had a Bachelor's degree or greater (P = 0.0064), but there was no difference in the score based on annual family income (P = 0.07). The score was higher among vegetarians than non-vegetarians (26.7 ± 3.5 vs. 23 ± 4.4; P &amp;lt; 0.001). It was also inversely associated with indicators of central adiposity including waist circumference (P = 0.001) and waist-to-hip ratio (P &amp;lt; 0.001). Conclusions Our results indicate that adherence to the DASH dietary pattern is associated with select sociodemographic factors and body composition among South Asians in the U.S. The computed DASH score will be utilized in forthcoming analyses to determine its associations with risk factors for hypertension, central adiposity, and ASCVD among participants in the MASALA cohort. Funding Sources NHLBI, National Center for Research Resources, National Center for Advancing Translational Sciences, NIH, via UCSF-CTSI.

383-P: Comparative Study of Serum Testosterone Levels in Male T2DM and Nondiabetic Subjects as a Risk Marker for Atherosclerotic Coronary Artery Disease

Background: Historically, higher levels of serum testosterone were presumed deleterious to the cardiovascular system. cardiovascular disease (CVD) risk factors prevalence were increased due to low testosterone levels. Material and Methods: This was a prospective observational study, conducted among men with type 2 diabetes with documented CAD (n = 60) and controls healthy men (n = 50). Pearson correlation between sex hormones and CAD risk factors was done. The association between sex hormones and CAD risk factors among patients was analyzed by multiple logistic regression. The statistical significance was set at the 0.05 level. Result: Mean age of diabetics was 44.5 ±7.9 years and non diabetics was 42.54 ± 5.63 years. 56% of Diabetics and 20 % non diabetics had lower levels of total testosterone. 68% of Diabetics and 26 % non diabetics had lower levels of free testosterone. Mean SHBG levels in Diabetics and non - diabetics was 8.6 ± 1.8 and 16 ± 3.2. Prevalence of Hypogonadism was 22% in Diabetics and 10% in Non diabetics. Among the cases, a significant positive correlation was found between total testosterone/FTI and waist circumference, W/H ratio, triglyceride levels, hs-CRP, and CIMT (P &amp;lt; 0.01). In addition, a significant negative correlation was found between total testosterone and FTI with high-density lipoprotein-cholesterol levels (P &amp;lt; 0.01). The multiple logistic regression analysis showed that total testosterone levels (P &amp;lt; 0.01) and SHBG (P &amp;lt; 0.01) are independently associated with the occurrence of atherosclerotic CAD in T2DM men. Conclusion: We conclude that increased serum testosterone levels and low SHBG in T2DM men are associated with the development of atherosclerotic cardiovascular risk factors. Disclosure A. K. Das: None. A. Bhagat: None. N. Sinha: None.