Preclinical Atherosclerosis Research Articles

The impact of prediabetes on preclinical atherosclerosis in general apparently healthy population: A cross-sectional study

Background The hypothesis that not only diagnosed diabetes (DM), but also milder dysglycemia may affect the development of atherosclerosis still requires further study. In our population-based study, we aimed to evaluate the impact of prediabetic state on preclinical atherosclerosis and whether it may affect the cardiovascular risk (CVR) in the general population. Methods The analysis was a part of the Bialystok PLUS cohort study and represented a random sample of Bialystok (Poland) residents aged 20–79 years at the time of sampling (July 2017-January 2023). The cross-sectional analysis included 1431 participants of a population-based study (mean age 46.82 years). Comprehensive biochemical assessments were performed. An Oral Glucose Tolerance Test (OGTT) was performed on fasting patients who did not report having a DM. Results The population with prediabetes, based on HbA1c and OGTT, accounted for more than half of the study participants (n = 797, 55.7%). Atherosclerotic plaques in the carotid arteries were significantly more common in individuals with prediabetes considering all CVR categories. Prediabetes was associated with the occurrence of more advanced preclinical atherosclerosis, especially in the low to moderate CVR category. Serum glucose concentration after 1h and HbA1c proved to be statistically significant indicators of the presence of atherosclerotic plaques in ultrasound (respectively, AUC = 0.73 and 0.72). In multivariate logistic regression, prediabetes was independently associated with significantly increased risk of preclinical atherosclerosis (OR = 1.56, 95% CI 1.09–2.24), along with CVR categories, pulse wave velocity and central blood pressure augmentation index. Conclusions Prediabetes is associated with the occurrence and progression of the preclinical atherosclerosis. Importantly, many of those patients are in the low to moderate cardiovascular risk category, hence may have a severely underestimated risk. Inclusion of prediabetes into CVR assessment may improve risk stratification. An early identification of dysglycemic population is necessary to effectively implement the cardiovascular and metabolic prevention measures.

Early-Life Risk Factors for Carotid Intima-Media Thickness and Carotid Stiffness in Adolescence

ImportanceAtherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease later in life.ObjectiveTo identify early-life risk factors for preclinical atherosclerosis in adolescence.Design, Setting, and ParticipantsThis cohort study is part of the ongoing Wheezing Illness Study in Leidsche Rijn (WHISTLER) prospective birth cohort study, which includes 3005 healthy newborns born between December 2001 and December 2012 in the Leidsche Rijn area of Utrecht, the Netherlands. Eligible participants included those from the WHISTLER cohort who visited the clinic between March 2019 and October 2020 for adolescent follow-up. This study’s analyses were performed in January 2024.ExposuresEarly-life growth was assessed at birth to 6 months, 5 years, and 12 to 16 years. Abdominal ultrasonography determined abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depth. Blood pressure (BP) percentiles and body mass index (BMI) z scores were used.Main Outcomes and MeasuresCarotid ultrasonography was performed at age 12 to 16 years to assess carotid intima-media thickness (cIMT) and the distensibility coefficient (DC), established measures of preclinical atherosclerosis. Multivariable linear regression models were used to identify early-life risk factors for cIMT and DC in adolescence.ResultsIn total, 232 adolescents (median [IQR] age, 14.9 [13.7-15.8] years; 121 female [52.2%]) were included. More postnatal weight gain (B = 12.34; 95% CI, 2.39 to 22.39), higher systolic BP at 5 years (B = 0.52; 95% CI, 0.02 to 1.01), more VAT at 5 years (B = 3.48; 95% CI, 1.55 to 5.40), and a larger change in VAT between 5 and 12 to 16 years (B = 3.13; 95% CI, 1.87 to 4.39) were associated with a higher cIMT in adolescence. A higher BMI (B = −2.70, 95% CI,−4.59 to −0.80) and VAT at 5 years (B = −0.56; 95% CI, −0.87 to −0.25), as well as a larger change in BMI between 5 and 12 to 16 years (B = −3.63; 95% CI, −5.66 to −1.60) were associated with a higher carotid stiffness in adolescence. On the contrary, a larger change in SAT between 5 and 12 to 16 years (B = 0.37; 95% CI, 0.16 to 0.58) was associated with a higher carotid DC in adolescence.Conclusions and RelevanceIn this cohort study of 232 participants, early-life growth parameters, and particularly abdominal VAT development, were associated with a higher cIMT and carotid stiffness in adolescence. These findings suggest that assessment of adipose tissue development during childhood can aid characterization of lifetime risk trajectories and tailoring of cardiovascular prevention and risk management strategies.

Association between metabolically healthy obesity and carotid intima-media thickness in Korean adolescents with overweight and obesity.

Data regarding the association between metabolically healthy obesity (MHO) and preclinical atherosclerosis in childhood are lacking. Carotid intima-media thickness (cIMT) is a noninvasive method used to assess cardiovascular risk. This study examined the relationships among cIMT, metabolic phenotypes, and cardiometabolic risk factors (CMRFs) in overweight and obese adolescents. Anthropometric, biochemical, and cIMT data were collected. The study participants were categorized as MHO or metabolically unhealthy obesity (MUO) based on insulin resistance. CMRFs were assessed using blood pressure (BP); levels of triglycerides, high-density lipoprotein cholesterol (HDL-C), and fasting plasma glucose; or a diagnosis of diabetes mellitus. Differences in cIMT values were evaluated according to the metabolic phenotype and factors associated with cIMT. Among the 111 participants (80 boys, 72.1%), 23 (20.7%) were classified as MHO and 88 (79.3%) as MUO. The MHO group exhibited lower glycated hemoglobin and triglyceride levels and higher HDL-C levels compared to those exhibited by the MUO group (all P<0.01). The cIMT values did not differ significantly between the MHO and MUO groups. The high cIMT tertile group revealed higher systolic BP compared to that exhibited by the low cIMT tertile group (123.7±2.1 mmHg vs. 116.9±1.6 mmHg, P=0.028). Mean cIMT was positively correlated with age (β=0.009) and body mass index (BMI) (β=0.033) after adjusting for covariates (both P<0.05). In overweight and obese Korean adolescents, cIMT was associated with age and BMI but not with metabolic phenotype or CMRFs. Further research is warranted to determine the relationship between cIMT during adolescence and cardiovascular outcomes during adulthood.

Cardiovascular risk and preclinical atherosclerosis are associated with white matter hyperintensities in apparently healthy adults: the population-based cross-sectional BIALYSTOK PLUS study.

White matter hyperintensities, present in patients and asymptomatic individuals, have been previously shown to be associated with atherosclerosis risk factors, such as high blood pressure, hypercholesterolemia, smoking, and diabetes. Our aim was to examine the associations between the volume of white matter hyperintensities and cardiovascular risk factors in the general, apparently healthy population. The analysis includes 735 participants (aged 20 to 79 years) without neurological or severe cardiac diseases. The participants underwent detailed clinical examination, including medical history, biochemical analyses, carotid arteries ultrasound, and brain magnetic resonance imaging, followed by white matter hyperintensities segmentation using the FreeSurfer tool. The participants were divided into 3 cardiovascular risk (CVR) categories based on the 2021 European Society of Cardiology guidelines. The median volume of white matter hyperintensities was 95.2 mm3 (interquartile range, 2.1-482 mm3). Multivariable analysis revealed positive independent association between the volume of white matter hyperintensities and CVR categories, glycated hemoglobin concentration, presence of carotid plaques, and central systolic blood pressure. An analysis including individuals without hypertension or diabetes revealed mean intima‑media thickness and high or very high cardiovascular risk class as independent predictors of white matter hyperintensities percentile. The cardiovascular risk class, presence of carotid plaques, increased intima‑media complex thickness, and diabetes are the main risk factors for white matter hyperintensities in apparently healthy adults. People without hypertension or diabetes but with higher CVR are also at a risk for developing white matter hyperintensities, which emphasizes the importance of CVR assessment for prediction of neurodegenerative changes.

Subclinical Atherosclerosis and Endothelial Dysfunction in Cases of Systemic Lupus Erythematosus: A Hospital-Based Case-Control Study.

Background Women are more likely to be affected with systemic lupus erythematosus (SLE), a chronic multisystem inflammatory autoimmune illness. It is well established that SLE increases the risk of cardiovascular (CV) events. This study aimed to determine the prevalence of endothelial dysfunction and subclinical atherosclerosis in patients with SLE. If these conditions are identified early, suitable preventative measures may be advocated to lessen the burden of future CV events. Aim This study aims to calculate the frequency of endothelial dysfunction and subclinical atherosclerosis in SLE patients using the flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thickness (c-IMT). Results There were 50 confirmed cases of SLE. Compared to healthy controls, SLE patients' c-IMT readings were higher, suggesting subclinical atherosclerosis. Thirty-three patients with c-IMT values >0.06 (p<0.00269) out of 50 SLE cases were found to have a high prevalence of subclinical atherosclerosis. Five SLE patients showed FMDs of less than 4.5% (p<0.021) compared to healthy controls, indicating preclinical atherosclerosis with endothelial dysfunction. It was discovered that endothelial dysfunction exhibited a positive linear connection with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) when contrasted with traditional inflammatory indicators such as ESRand CRP. Conclusion Patients with SLE face a higher risk of CV events and mortality compared to those without the condition. They are also more prone to developing endothelial dysfunction and subclinical atherosclerosis. Detecting these issues early can help in implementing primary and secondary prevention strategies effectively.

Evaluation of Cardiovascular Risk in People with Type 1 Diabetes: A Comprehensive and Specific Proposed Practical Approach.

People living with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in this population. CVD risk increases with each uncontrolled risk factor, even in individuals with good glycaemic control. Recommendations for assessing CVD risk in the T1D population are extended from those for type 2 diabetes (T2D) even though the physiopathology and underlying mechanisms of atherosclerosis in T1D are poorly understood and differ from those in T2D. Unlike the assessment of microvascular complications, which is well established in T1D, this is far from being the case for the comorbidities and risk associated with CVD. Aside from classical cardiovascular comorbidities, carotid ultrasound can be useful to stratify CVD risk. The utilization of specific risk scales such as the Steno Type 1 Risk Engine can help to more accurately classify cardiovascular risk in these individuals. The cornerstones of the management of cardiovascular risk in T1D are the promotion of the Mediterranean diet, tight glycaemic control (glycated haemoglobin (HbA1c) < 7%), blood pressure < 130/80mmHg in most patients, and low-density lipoprotein (LDL) cholesterol < 100mg/dL in moderate-risk individuals, < 70mg/dL in high-risk individuals, and < 55mg/dL in very high-risk individuals. Conventional medical follow-up of patients with T1D should be individualized (approximately 2-3 visits per year), and a carotid ultrasound evaluation is recommended every 5 years in the absence of significant preclinical atherosclerosis or more often in those with severe preclinical atherosclerosis. Antithrombotic therapy is recommended in those receiving secondary prevention, those with stenosis > 50% in any arterial bed, and those with an impaired ankle-brachial index. This document is a proposal of a practical approach for the evaluation, classification, and management of CVD risk in individuals living with T1D.

AMPK-mediated regulation of endogenous cholesterol synthesis does not affect atherosclerosis in a murine Pcsk9-AAV model

Background and aimsDysregulated cholesterol metabolism is a hallmark of atherosclerotic cardiovascular diseases, yet our understanding of how endogenous cholesterol synthesis affects atherosclerosis is not clear. The energy sensor AMP-activated protein kinase (AMPK) phosphorylates and inhibits the rate-limiting enzyme in the mevalonate pathway HMG-CoA reductase (HMGCR). Recent work demonstrated that when AMPK-HMGCR signaling was compromised in an Apoe-/- model of hypercholesterolemia, atherosclerosis was exacerbated due to elevated hematopoietic stem and progenitor cell mobilization and myelopoiesis. We sought to validate the significance of the AMPK-HMGCR signaling axis in atherosclerosis using a non-germline hypercholesterolemia model with functional ApoE. MethodsMale and female HMGCR S871A knock-in (KI) mice and wild-type (WT) littermate controls were made atherosclerotic by intravenous injection of a gain-of-function Pcsk9D374Y-adeno-associated virus followed by high-fat and high-cholesterol atherogenic western diet feeding for 16 weeks. ResultsAMPK activation suppressed endogenous cholesterol synthesis in primary bone marrow-derived macrophages from WT but not HMGCR KI mice, without changing other parameters of cholesterol regulation. Atherosclerotic plaque area was unchanged between WT and HMGCR KI mice, independent of sex. Correspondingly, there were no phenotypic differences observed in hematopoietic progenitors or differentiated immune cells in the bone marrow, blood, or spleen, and no significant changes in systemic markers of inflammation. When lethally irradiated female mice were transplanted with KI bone marrow, there was similar plaque content relative to WT. ConclusionsGiven previous work, our study demonstrates the importance of preclinical atherosclerosis model comparison and brings into question the importance of AMPK-mediated control of cholesterol synthesis in atherosclerosis.

Predictability of Cardiovascular Risk Scores for Carotid Atherosclerosis in Community-Dwelling Middle-Aged and Elderly Adults.

Background: The assessment of future risk of cardiovascular diseases (CVD) is strongly recommended for all asymptomatic adults without CVD history. Carotid atherosclerosis (CA) is a preclinical phenotype of CVDs. However, data on estimated future CVD risks with respect to preclinical atherosclerosis are limited. This community-based study aimed to assess the relationships between predicted CVD risks and CA. Methods: We enrolled 3908 subjects aged 40-74 years without CVD history and calculated their 10-year CVD risks using the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). Carotid plaque (CP) at the extracranial carotid arteries was determined by high-resolution B-mode ultrasonography and further classified into mild or advanced CA. Results: The means of FRS for CP-negative and mild and advanced CA were 9.0%, 14.4%, and 22.1%, respectively (p-value < 0.0001). The corresponding values for PCE score were 4.8%, 8.8%, and 15.0%, respectively (p-value < 0.0001). The odds ratios (ORs) of having CP per 5.0% increase in FRS and PCE score were 1.23 (95% CI, 1.19-1.28) and 1.36 (95% CI, 1.28-1.44), respectively. The corresponding values of having advanced CA were 1.24 (95% CI, 1.19-1.29) and 1.38 (95% CI, 1.30-1.48), respectively. Among the models of FRS or PCE plus other conventional CVD risk factors, the FRS + age model had the highest discrimination for the presence of CP (AUROC, 0.7533; 95% CI, 0.7375-0.7691) as well as for the presence of advanced CA (AUROC, 0.8034; 95% CI, 0.7835-0.8232). The calibration of the FRS + age models for the presences of CP and advanced CA was excellent (χ2 = 8.45 [p = 0.49] and 10.49 [p = 0.31], respectively). Conclusions: Estimated future CVD risks were significantly correlated with risks of having CA. Both FRS and PCE had good discrimination for the presences of CP and advanced CA.

A Study of Assessment of Preclinical Atherosclerosis by Carotid Intima-media Thickness in Newly Diagnosed Patients with Rheumatoid Arthritis Younger than 50 Years of Age and Their Correlation with Disease Activity: A Comparative, Cross-sectional Study

Abstract Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition that has been linked to an increased risk of atherosclerosis and enhanced cardiovascular disease (CVD) risk. Most literature encompasses older age groups. Objectives: This study aimed to determine the carotid intima-media thickness (CIMT) in patients with newly diagnosed RA who are younger than 50 years of age and do not display the symptoms or traditional risk factors of CVD and compare it to the controls with same age and gender without RA. Furthermore, the correlation between CIMT and the disease activity Score -28 (Erythrocyte sedimentation rate) were examined. Subjects and Methods: The study enrolled 48 patients with RA and 51 healthy controls who met the study’s inclusion and exclusion criteria. All patients underwent CIMT by the ultrasound. Results: There was a significant increase in common carotid artery CIMT on both the right and left sides (P &lt; 0.001) in RA patients as compared to controls. The correlations between CIMT (right and left) and DAS 28 ESR were only poor and negative. Conclusion: Younger patients with RA showed higher CIMT than age- and sex-matched controls, indicating an increased risk of future cardiovascular events even in the young.

Development and Implementation of an Integrated Preclinical Atherosclerosis Database.

Basic scientists have used preclinical animal models to explore mechanisms driving human diseases for decades, resulting in thousands of publications, each supporting causative inferences. Despite substantial advances in the mechanistic construct of disease, there has been limited translation from individual studies to advances in clinical care. An integrated approach to these individual studies has the potential to improve translational success. Using atherosclerosis as a test case, we extracted data from the 2 most common mouse models of atherosclerosis (ApoE [apolipoprotein E]-knockout and LDLR [low-density lipoprotein receptor]-knockout). We restricted analyses to manuscripts published in 2 well-established journals, Arteriosclerosis, Thrombosis, and Vascular Biology and Circulation, as of query in 2021. Predefined variables including experimental conditions, intervention, and outcomes were extracted from each publication to produce a preclinical atherosclerosis database. Extracted data include animal sex, diet, intervention type, and distinct plaque pathologies (size, inflammation, and lipid content). Procedures are provided to standardize data extraction, attribute interventions to specific genes, and transform the database for use with available transcriptomics software. The database integrates hundreds of genes, each directly tested in vivo for causation in a murine atherosclerosis model. The database is provided to allow the research community to perform integrated analyses that reflect the global impact of decades of atherosclerosis investigation. This database is provided as a resource for future interrogation of sub-data sets associated with distinct plaque pathologies, cell type, or sex. We also provide the methods and software needed to expand this data set and apply this approach to the extensive repository of peer-reviewed data utilizing preclinical models to interrogate mechanisms of diverse human diseases.

Biochemical predictors of preclinical arteriosclerosis in patients with chronic obstructive pulmonary disease after COVID-19

This article presents the findings of an open, comparative, prospective study aimed to investigate the state of vascular endothelial function in patients with chronic obstructive pulmonary disease (COPD) who have recovered from COVID-19, and to assess the potential for long-term prediction of preclinical atherosclerosis development.Materials and methods. A total of 133 COPD patients were examined under outpatient conditions: the main group (n=90), with a history of COVID-19, and a comparison group (n=43). Participants were examined twice: V1 - initial examination from 3 weeks to three months post-infection, V2 - a follow-up examination 12 months after the first visit. Based on the CAVI index values at point V2, the main group was divided into 2 subgroups. The state of vascular endothelial function was assessed using volume sphygmomanometry and by determining the concentration of biochemical markers in the blood.Results. In the main group at point V2, the studied parameters of arterial stiffness were significantly higher compared to the comparison group (aortic pulse wave velocity, cardio-ankle vascular index (CAVI) on the right and left, augmentation indices on the brachial and carotid arteries). At point V1, in the 1st subgroup (R-CAVI≥8.5 units), the concentration of biomarkers such as endothelin-1, total homocysteine, monocyte chemoattractant protein, vascular endothelial growth factor, C-reactive protein, interleukin-6,10 was significantly higher than in the 2nd subgroup (R-CAVI&lt;8.5 units). Conclusion. Taking into account the results obtained, a mathematical model for predicting preclinical atherosclerosis in COPD patients 12 months after COVID-19 was developed, which can be applied by clinicians in the long-term assessment of cardiovascular risk. Key words: chronic obstructive pulmonary disease, COVID-19, sphygmomanometry, predictors, prognosis, CAVI index&gt; ˂ 8.5 units).Conclusion. Taking into account the results obtained, a mathematical model for predicting preclinical atherosclerosis in COPD patients 12 months after COVID-19 was developed, which can be applied by clinicians in the long-term assessment of cardiovascular risk.

Severe hypoglycemia and hypoglycemia awareness are associated with preclinical atherosclerosis in patients with type 1 diabetes without an estimated high cardiovascular risk.

To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D). Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40years, diabetic kidney disease, or ≥10years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated. We included 634 patients (52.4% men, age 48.3±10.8years, T1D duration 27.4±11.1years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p<0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n=192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n=436; ≥2 plaques: OR 1.2 [1.0-1.5], p=0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p=0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p=0.036). In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach.

Impact of Preeclampsia and Parity on Sex-based Discrepancies in Subclinical Carotid Atherosclerosis in Type 1 Diabetes.

The excess risk of fatal and nonfatal cardiovascular events is roughly twice as high in women than in men with type 1 diabetes. To evaluate the impact of preeclampsia and parity on sex-based discrepancies in preclinical atherosclerosis and on the diagnostic performance of a cardiovascular risk scale. Cross-sectional study. Single tertiary hospital. A total of 728 people with type 1 diabetes (48.5% women) without cardiovascular disease and age ≥40 years, nephropathy, and/or ≥10 years of diabetes duration with another risk factor. Standardized carotid ultrasonography. Carotid plaque determined by ultrasonography and cardiovascular risk estimated according to the Steno T1 Risk Engine (Steno-Risk). Nulliparous women and parous women without previous preeclampsia had a lower risk for carotid plaque than men (adjusted odds ratio: .48, 95% confidence interval [.28-.82]; adjusted odds ratio: .51 [.33-.79], respectively), without differences in the preeclampsia group. The prevalence of carotid plaque increased as the estimated cardiovascular risk increased in all subgroups except for preeclampsia group. The area under the curve of the Steno-Risk for identifying ≥2 carotid plaques was lower in the preeclampsia group (men: .7886; nulliparous women: .9026; women without preeclampsia: .8230; preeclampsia group: .7841; P between groups = .042). Neither the addition of parity nor preeclampsia in the Steno-Risk led to a statistically significant increase in the area under the curve. The risk for carotid plaque in women compared with men decreased as exposure to obstetric factors diminished. However, the addition of these factors did not improve the prediction of the Steno-Risk.

Evaluation of serum gamma-glutamyl transferase among patients with coronary artery disease in Erbil city

Background and objective: The leading cause of morbidity and mortality globally is coronary artery disease (CAD). One of the recent new parameters for evaluating CAD is Serum GGT, which has been shown to be a predictor of coronary artery status irrespective of the traditional cardiovascular risk variables. This study aimed to evaluate and assess the correlation between serum GGT and other variables among patients with CAD in comparison with healthy subjects. Methods: A case-control prospective study. Subjects were grouped into Group I (CAD patients-117 individuals) and Group II (healthy Subjects-83 individuals) based on their Coronary Angiographic profile at surgical specialty Hospital-Cardiac Center-Erbil/Iraq. Parameters of S. GGT, S. total cholesterol, S.HDL-C, S.LDL-C, S. VLDL-C, and S.TG, S. (25)OH vitamin D, serum troponin T, S.CK-MB, and CRP were assessed for both groups. Results: The study population included 58% of male and 42% of female participants, with an age range of 30-77, with a mean of 56.13± 10.5 years old. The Pearson’s correlation coefficient of serum GGT with other variables showed that the relation between serum GGT with VLDL-C, CRP, and Triglyceride among CAD patients was found to be a weakly positive correlation and statistically significant (r=0.3, P = 0.004), (r=0.2, P = 0.031), and (r=0.3, P = 0.007) respectively. Conclusion: The present study showed that S.GGT as a new potential biochemical marker for preclinical atherosclerosis, would be a useful and important marker for assessing and evaluating risk factors of coronary artery disease and to further evaluations for CAD.

Neutrophil-to-lymphocyte ratio is independently associated with carotid atherosclerosis burden in individuals with type 1 diabetes

Background and aimsRecent studies have identified a relationship between innate versus. Adaptative immunity and cardiovascular disease (CVD) in the general population, but information on type 1 diabetes (T1D) is lacking. We aimed to study the relationship between inflammatory biomarkers and preclinical atherosclerosis in this population. Methods and resultsCross-sectional study in T1D individuals without CVD and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of diabetes duration with classical CVD risk factors. Carotid plaques were evaluated by ultrasonography. C-reactive protein, total leukocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index were assessed as inflammatory markers. Multivariate-adjusted models including age, sex, and other CVD risk factors were constructed to test their independent associations with atherosclerosis burden. We included 602 subjects (52.8% men, 48.7 ± 10.2 years old and 27.0 ± 10.5 years of diabetes duration). Carotid plaques were found in 41.2% of the individuals (12.8%, ≥3 plaques). The number of carotid plaques (none, 1–2, ≥3 plaques), was directly associated with the leukocyte count (6570 [5445–8050], 6640 [5450–8470] and 7310 [5715–8935] per mm3, respectively; p for trend = 0.021) and the NLR (1.63 [1.28–2.13], 1.78 [1.38–2.25] and 2.14 [1.58–2.92], respectively; p for trend <0.001), but only the NLR remained directly associated in fully-adjusted models (presence of plaques; OR 1.285 [1.040–1.587]; ≥3 plaques, OR 1.377 [1.036–1.829]). ConclusionsThe NLR was independently and directly associated with carotid plaque burden in T1D individuals. Our data support the role of innate versus. Adaptative immunity in atherosclerosis also among the T1D population.

The inflammatory potential of diet is associated with future development of pre-clinical carotid atherosclerosis

The inflammatory potential of diet is associated with future development of pre-clinical carotid atherosclerosis

Spinal radiographic progression is correlated with preclinical atherosclerosis in spondyloarthritis.

A higher prevalence of cardiovascular risk was observed in spondyloarthritis (SpA). The relationship between disease-related factors structural damage and subclinical atherosclerosis is still unknown. The aim of our study was to evaluate the association of subclinical atherosclerosis with radiographic structural damage in patients with SpA. Forty-seven SpA patients who fulfilled the ASAS criteria were enrolled in a case-control study conducted over 12months and compared with 47 age and sex-matched healthy controls. None of the subjects had a previous history of cardiovascular diseases or cardiovascular risk factors. Demographic and disease characteristics were recorded. Structural lesions were evaluated using plain radiography, and two scoring tools were used to spine (BASRI and mSASSS). Subclinical atherosclerosis was assessed using ultrasound measurements of flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT). The median age of patients was 36 years. The sex ratio was 2.35. The median BASRI total score was 3 (IQR 2-4), median mSASSS score was 10 (IQR 415). cIMT was significantly increased in SpA patients compared to controls (p< 0.0001), and FMD was significantly lower in patients than in healthy subjects (p= 0.008). cIMT was significantly associated with ankylosis of the facet joints (p= 0.035) and Romanus spondylitis (p= 005). FMD was negatively associated with vertebral squaring (p= 0049), bridging syndesmophytes (p= 0031) and mSASSS score (p= 0.047). Our result supports the association of radiographic structural damage and subclinical atherosclerosis assessed using cIMT and FMD. This finding highlights the importance of earlier treatment in order to prevent radiographic damage progression and atherosclerotic events.

Role of Positron Emission Tomography Cardiac Perfusion Imaging in Clinical Management, Prognosis, and Risk Stratification of Cardiovascular Disease

Coronary artery disease (CAD) is an important cause of morbidity and mortality worldwide. Perfusion abnormalities precede wall motion abnormalities, ECG changes, and angina in the etiology of CAD. myocardial perfusion imaging (MPI) can detect perfusion alterations due to pathology at sites such as the endothelium, microvasculature, and epicardial coronary arteries. Thus, it measures the universal burden of ischemic heart disease (IHD). Nuclear medicine MPI is an important noninvasive imaging modality to evaluate the perfusion of the myocardium. Positron Emission Tomography (PET) and single-photon emission computed tomography (SPECT) with or without computed tomography (CT) are 2 primary modalities. PET is a highly sensitive modality with an inherent ability to quantify absolute myocardial blood flow (MBF) and variations in MBF due to various stress agents. PET has immense potential to change clinical management, prognosticate, and risk stratify patients presenting with clinical or preclinical CAD. Evidence shows that early PET detection of myocardial perfusion abnormalities, followed by aggressive intervention for cardiovascular risk factors, can reinstate myocardial perfusion. This may reduce morbidity and mortality. We shall be reviewing the clinical impact of PET in CAD and preclinical CAD patients.

Abstract 166: Memory Cd8 T Cells Contribute To Atherosclerosis In Aged Mice

Aging is a strong risk factor for atherosclerosis and aging significantly impacts immune cell populations and function. Immune cells are a major contributor to development of atherosclerosis; however, most preclinical atherosclerosis studies are performed in young mice. The role of aging on CD8 + T cells during atherogenesis remains unclear. Here we determined that depletion of CD8 + T cells attenuated atherogenesis in aged, but not young, mice. Furthermore, adoptive transfer of splenic CD8 + T cells from aged mice which contain a high proportion of memory T cells significantly enhanced atherosclerosis in young Cd8 -/- recipient mice compared with transfer of CD8 + T cells from young donor mice. Finally, we characterized T cells in healthy and atherosclerotic young and aged mice by single-cell RNA-sequencing (scRNAseq) and T cell receptor sequencing (TCR-seq). We found that with aging effector memory, central memory, and granzyme K + effector memory CD8 + T cells accumulate within atherosclerotic plaques, and aging induces transcriptomic changes related to CD8 + T cell activation, migration, cytotoxicity, and exhaustion. Overall, our study identifies memory CD8 + T cells as potential therapeutic targets for reducing atherosclerosis in older adults.

Advanced lipoprotein profile identifies atherosclerosis better than conventional lipids in type 1 diabetes at high cardiovascular risk

Background and aimsPeople with type 1 diabetes (T1D) present lipoprotein disturbances that could contribute to their increased cardiovascular disease (CVD) risk. We evaluated the relationship between lipoprotein alterations and atherosclerosis in patients with T1D. Methods and resultsCross-sectional study in subjects with T1D, without previous CVD, but high-risk (≥40 years, nephropathy, or ≥10 years of evolution of diabetes with another risk factor). The presence of plaque (intima-media thickness ≥1.5 mm) in the different carotid segments was determined by ultrasound. The advanced lipoprotein profile was analysed by magnetic resonance imaging (1H NMR). We included 189 patients (42% women, 47.8 ± 10.7 years, duration of diabetes 27.3 ± 10.1 years, HbA1c 7.5% [7–8]). Those with carotid plaques (35%) were older, with longer diabetes duration, had a higher prevalence of hypertension, and showed lower and smaller LDL particles (LDL-P) and HDL particles (HDL-P), but higher VLDL particles (VLDL-P). Some LDL, HDL and VLDL-related parameters were associated with atherosclerosis in sex, age and statin use adjusted models (p < 0.05), but after adjusting for multiple confounders, including conventional lipid parameters, only HDL-P (OR 0.440 [0.204–0.951]; p = 0.037), medium HDL-P (OR 0.754 [0.590–0.963]; p = 0.024), HDL-P cholesterol content (OR 0.692 [0.495–0.968]; p = 0.032), 1H NMR LDL-P number/conventional LDL-cholesterol (OR 1.144 [1.026–1.275]; p = 0.015), and 1H NMR non-HDL particle number/conventional non-HDL-cholesterol ratios (OR 1.178 [1.019–1.361], p = 0.026) remained associated with atherosclerosis. ConclusionsIn adults with T1D at high-risk, variables related to HDL, LDL and total atherogenic particle number are independently associated with preclinical atherosclerosis. Advanced lipoprotein profiling could be used to identify those at the highest risk of CVD.