Risk Of Subclinical Atherosclerosis Research Articles

Machine Learning-Assisted Analysis of Sublingual Microcirculatory Dysfunction for Early Cardiovascular Risk Evaluation and Cardiovascular-Kidney-Metabolic Syndrome Stage in Patients With Type 2 Diabetes Mellitus.

To examine whether sublingual microcirculation can be used as an effective and noninvasive method for assessing cardiovascular, kidney, and metabolic risks in patients with type 2 diabetes mellitus (T2DM). This cross-sectional observational study enrolled 186 patients with T2DM. All patients were evaluated using the Framingham General Cardiovascular Risk Score (FGCRS) and cardiovascular-kidney-metabolic (CKM) syndrome stage. Side-stream dark-field microscopy was used for sublingual microcirculation, including total and perfused vessel density (TVD and PVD). Multiple machine-learning prediction models have been developed for CKM risk and stage assessment in T2DM patients. Receiver operating characteristic (ROC) curves were generated to determine cutoff points. Compared to patients with T2DM, diabetic patients with subclinical atherosclerosis (SA) had a greater CV risk, as measured by the FGCRS, accompanied by markedly decreased microcirculation perfusion. Microcirculatory parameters (TVD and PVD), including carotid intima-media thickness (IMT), brachial-ankle pulse wave velocity (ba-PWV), and FGCRS, were closely associated with SA incidence. Microcirculatory parameters, Index (DMSA screen), and cut-off points were used to screen for SA in patients with T2DM. Furthermore, a new set of four factors identified through machine learning showed optimal sensitivity and specificity for detecting CKM risk in patients with T2DM. Decreased microcirculatory perfusion served as a useful early marker for CKM syndrome risk stratification in patients with T2DM without SA. Sublingual microcirculatory dysfunction is closely correlated with the risk of SA and CKM risk in T2DM patients. Sublingual microcirculation could be a novel tool for assessing the CKM syndrome stage in patients with T2DM.

Association Between Cardiovascular Health and Subclinical Atherosclerosis Among Young Adults Using the American Heart Association's "Life's Essential 8" Metrics.

This study investigated the association of American Heart Association's cardiovascular health guidelines Life's Essential 8 (LE8) and Life's Simple 7 (LS7) with carotid artery outcomes among young adults. This cross-sectional study included 240 young adults (age 24.2±1.6 years) who underwent a carotid ultrasound between 2018 and 2022. LE8 score was calculated from 4 health factors (body mass index, non-high-density lipoprotein cholesterol, fasting glucose, and blood pressure), and 4 health behaviors (dietary intake, physical activity, tobacco use, and sleep). LS7 was calculated from 7 metrics (all LE8 metrics, except for sleep) with a simpler algorithm. Higher LE8 and LS7 scores both indicate better health and better adherence to American Heart Association guidelines. Carotid artery outcomes included carotid artery intima-media thickness, arterial stiffness (eg, distensibility), and echogenicity determined by grayscale median of the intima media complex. Results of linear regression analyses, adjusting for age, sex, ethnicity, and parents' highest degree, indicated that a 1-SD increase in LE8 score was associated with 12.14 μm lower carotid artery intima-media thickness (95% CI, -20.93 to 3.35), 1.17 (10-6×m2/N) greater distensibility (95% CI, 0.09-2.24), suggesting less arterial stiffness, and 2.66 μm greater grayscale median of the intima media complex (95% CI, 0.58-4.75), suggesting less lipid deposition. Analyses using LS7 score demonstrated comparable findings. Health factor metrics demonstrated stronger association with carotid artery outcomes, as compared with behavior metrics. Greater adherence to the American Heart Association's cardiovascular health guidelines is associated with lower risk for subclinical atherosclerosis in young adults. LE8 and LS7 demonstrated comparable associations with carotid artery outcomes.

Selection scan in Native Americans of Mexico identifies FADS2 rs174616: Evidence of gene-diet interactions affecting lipid levels and Delta-6-desaturase activity

Searching for positive selection signals across genomes has identified functional genetic variants responding to environmental change. In Native Americans of Mexico, we used the fixation index (Fst) and population branch statistic (PBS) to identify SNPs suggesting positive selection. The 103 most differentiated SNPs were tested for associations with metabolic traits, the most significant association was FADS2/rs174616 with body mass index (BMI). This variant lies within a linkage disequilibrium (LD) block independent of previously reported FADS selection signals and has not been clearly associated with metabolic phenotypes. We tested this variant in two independent cohorts with cardiometabolic data. In the Genetics of Atherosclerotic Disease (GEA) cohort, the derived allele (T) was associated with increased BMI, lower LDL-C levels and a decreased risk of subclinical atherosclerosis in women. Significant gene-diet interactions affected lipid, apolipoprotein and adiponectin levels with differences according to sex, involving mainly total and complex dietary carbohydrate%. In the Genotype-related Effects of PUFA trial, the derived allele was associated with lower Δ-6 desaturase activity and erythrocyte membrane dihomo-gamma-linolenic acid (DGLA) levels, and with increased Δ-5 desaturase activity and eicosapentaenoic acid levels. This variant interacted with dietary carbohydrate% affecting Δ-6 desaturase activity. Notably, the relationship of DGLA and other erythrocyte membrane LC-PUFA indices with HOMA-IR differed according to rs174616 genotype, which has implications regarding how these indices should be interpreted. In conclusion, this observational study identified rs174616 as a signal suggesting selection in an independent linkage disequilibrium block, was associated with cardiometabolic and erythrocyte measurements of LC-PUFA in two independent Mexican cohorts and showed significant gene-diet interactions.

Re-Evaluation of Cardiovascular Disease Risk and Primary Prevention Treatments with Coronary Artery Calcium Scoring in Primary Prevention Patients.

Objective: The coronary artery calcium score (CACS) is used as a screening tool to identify the presence/absence of subclinical atherosclerosis in asymptomatic individuals. We evaluated the risk categories and medical therapy of asymptomatic individuals with subclinical atherosclerosis (CACS > 0) and applied the atherosclerotic cardiovascular disease (ASCVD) score and Framingham risk score (FRS) to assess those at a high risk of subclinical atherosclerosis (CACS ≥ 400). Methods: We retrospectively enrolled 218 asymptomatic individuals (65.6% women, and mean age 67.5 ± 10.3 years) who had their CACS evaluated at the cardiovascular department of our hospital between 2016 and 2020. Results: Among the 218 participants, 24.3% were classified as low-risk according to the FRS, and 19.3% had no subclinical atherosclerosis. However, only 12.8% and 27.5% of the study population were taking statins and aspirin, respectively. Furthermore, although more than half of the individuals without subclinical atherosclerosis were in the intermediate- and high-risk groups according to the risk scores, there were no considerable differences in the rates of taking aspirin and statins between the groups. When patients in the very-high-risk group according to the CACS and low-intermediate-risk patients were compared, there was no considerable difference in the rates of risk subgroups and taking statins, whereas high-risk patients took statistically significantly more aspirin. Conclusions: In primary prevention screening, CACS can be used as a reliable marker of subclinical ASCVD and help physicians optimize and improve adherence to medical therapy, including aspirin and statins, particularly for high-risk individuals.

Associations of genetically predicted vitamin D status and deficiency with the risk of carotid artery plaque: a Mendelian randomization study

Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (βCAC = − 0.14, P = 0.23; βcIMT = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.

Association of cardiovascular health with subclinical coronary atherosclerosis progression among five racial and ethnic groups: The MASALA and MESA studies

Background and aimsSouth Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups. MethodsWe assessed the distribution of CVH metrics (inadequate: score 0–8, average: 9–10, optimal: 11–14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study compared with other race/ethnic groups from the Multiethnic Study of Atherosclerosis (MESA). ResultsWe included 810 SA, 2622 Non-Hispanic White (NHW), and 4192 Other adults (collectively 1893 Black, 1496 Hispanic and 803 Chinese American participants, respectively). SA and White participants compared to Other race/ethnicity groups were more likely to have optimal CVH metrics (26% SA vs 28% White participants vs 21% Other, respectively, p < 0.001). Similar to NHW and the Other race/ethnic group, SA participants with optimal baseline CVH were less likely to develop incident CAC on follow-up evaluation compared to participants with inadequate CVH metrics, optimal CVH/CAC = 0: 24% SA, 28% NHW, and 15% Other (p < 0.01). In multivariable linear and logistic regression models, there was no difference in annualized CAC incidence or progression between each race/ethnic group (pinteraction = 0.85 and pinteraction = 0.17, respectively). Optimal blood pressure control was associated with lower CAC incidence among SA participants [OR (95% CI): 0.30 (0.14–0.63), p < 0.01] and Other race and ethnicity participants [0.32 (0.19–0.53), p < 0.01]. ConclusionsOptimal CVH metrics are associated with lower incident CAC and CAC progression among South Asians, similar to other racial groups/ethnicities. These findings underscore the importance of optimizing and maintaining CVH to mitigate the future risk of subclinical atherosclerosis in this higher risk population.

The ratio of systolic and diastolic pressure is associated with carotid and femoral atherosclerosis.

Although the impact of hypertension on carotid intima-media thickness (IMT) and plaques has been well established, its association with femoral IMT and plaques has not been extensively examined. In addition, the role of the ratio of systolic and diastolic pressure (SDR) in the subclinical atherosclerosis (AS) risk remains unknown. We assessed the relationship between SDR and carotid and femoral AS in a general population. A total of 7,263 participants aged 35-74 years enrolled from January 2019 to June 2021 in a southeast region of China were included in a cross-sectional study. Systolic and diastolic blood pressure (SBP and DBP) were used to define SDR. Ultrasonography was applied to assess the AS, including thickened IMT (TIMT) and plaque in the carotid and femoral arteries. Logistic regression and restricted cubic spline (RCS) models were the main approaches. The prevalence of TIMT, plaque, and AS were 17.3%, 12.4%, and 22.7% in the carotid artery; 15.2%, 10.7%, and 19.5% in the femoral artery; and 23.8%, 17.9% and 30.0% in either the carotid or femoral artery, respectively. Multivariable logistic regression analysis found a significant positive association between high-tertile SDR and the higher risk of overall TIMT (OR = 1.28, 95% CI = 1.10-1.49), plaques (OR = 1.36, 95%CI = 1.16-1.61), or AS (OR = 1.36, 95% CI = 1.17-1.57), especially in the carotid artery. RCS analysis further revealed the observed positive associations were linear. Further analyses showed that as compared to the low-tertile SDR and non-hypertension group, high-tertile SDR was associated with increased risks of overall and carotid TIMT, plaques, or AS in both groups with or without hypertension. SDR is related to a higher risk of subclinical AS, regardless of hypertension or not, suggesting that as a readily obtainable index, SDR can contribute to providing additional predictive value for AS.

Clinical and Serological Associations of Subclinical Atherosclerosis in Spondyloarthropathy

Background: Patients with spondyloarthropathy (SpA) have a higher risk of subclinical atherosclerosis (SCA). We assessed clinical and serological determinants of SCA in Indian SpA patients. Methods: Patients with SpA (fulfilling ASAS 2010 criteria; n = 104) attending our hospital were recruited; mean carotid intima-media thickness (CIMT) was performed by carotid ultrasonography, along with clinical assessment and traditional risk factor evaluation. Microparticles were extracted from plasma and total, as well as endothelial microparticles (EMP), platelet microparticles, T lymphocyte microparticles and B lymphocyte microparticles, were analysed by flow cytometry. Serum samples were analysed for inflammatory cytokines previously implicated in atherosclerosis, namely interleukin 1β (IL-1β), IL-6, IL-17, IL-27, IL-33 and tumour necrosis factor-alpha. Thirty-eight healthy controls were used for comparison. Subgroup analyses compared parameters between SpA with SCA (i.e., with carotid plaque or more than 75th percentile of CIMT for that age and sex in the Indian population) versus those without SCA. Ethical approval and written, informed consent were obtained. Results: Despite significantly younger age, lower body mass index and higher total cholesterol in controls compared to SpA, those with SpA had higher CIMT. Traditional cardiovascular risk factors (older age, higher waist-hip ratio) and novel markers of inflammation (serum IL-1β, IL-6) were associated with SCA. While total microparticles, EMP, T lymphocyte and B lymphocyte microparticles were increased in SpA than in healthy controls, they were not associated with SCA. Conclusions: Traditional risk factors and serum inflammatory cytokines IL-1β and IL-6 are associated with higher SCA in Indian SpA patients.

Clinical and Serological Associations of Subclinical Atherosclerosis in Systemic Sclerosis

Background: While patients with systemic sclerosis (SSc) are predisposed to cardiovascular events, data regarding this from India is sparse. We analysed correlates of subclinical atherosclerosis in Indian patients with SSc. Methods: Patients with SSc fulfilling the 2013 classification criteria ( n = 61) were recruited after obtaining written informed consent. Clinical risk factors for cardiovascular disease (CVD) were assessed. A carotid ultrasound was performed to assess the mean carotid intima-media thickness (CIMT). Total and endothelial microparticles (EMP, positive for CD31 and CD146) were estimated from plasma. Serum cytokines known to play a role in atherosclerosis (interleukin-1β [IL-1β], tumour necrosis factor-alpha, IL-6 and IL-17) were assessed. Forty-one age- and sex-similar healthy controls were recruited for comparison. Clinical and serological risk factors for CVD were compared between SSc with and without carotid plaque. Linear regression analyses were conducted to identify predictors of CIMT and carotid plaque in SSc. Results: Patients with SSc had lower body-mass index than healthy controls, however, had higher CIMT, higher serum IL-1β, IL-6, total microparticles and EMP than control subjects. SSc with carotid plaque ( n = 13) were older, and more likely to be male, but demonstrated no differences in serological markers of CVD. On multivariable-adjusted regression analyses, age was the only significant predictor of CIMT in SSc and male sex was the only significant predictor of carotid plaque in SSc. Conclusions: Carotid plaques were present in one-fifth of young patients with SSc. Older age and male sex predicted a higher risk of subclinical atherosclerosis in SSc.

Association of Higher Hemoglobin Level With Significant Carotid Artery Plaque in the General Population.

Serum hemoglobin (Hb) level affects the viscosity of blood. Several studies have reported that Hb level is associated with adverse cardiovascular outcome. However, there is a paucity of evidence on the association between serum Hb level and the risk of subclinical atherosclerosis. Thus, the objective of this study was to investigate the relationship between Hb level and risk of carotid plaque in a health checkup cohort. This retrospective study analyzed a total of 3,805 individuals without history of cardiovascular disease (CVD) who underwent carotid ultrasonography (USG) between January 2016 and June 2018. Participants were divided into 4 groups based on Hb quartiles in each of male and female. Carotid plaque score was calculated based on USG reports. Multivariable logistic regression analysis was performed for each index of quartile groups regarding the risk of carotid plaque. Of 3,805 individuals (mean age, 52.62±10.25 years; 2,674 [70.28%] males), mean Hb level was 15.11±0.75 g/dL in male and 13.35±0.74 g/dL in female. When the Q1 group was compared to the Q4, increasing quartile of Hb was associated with the presence of significant carotid plaque (plaque score ≥3) in male (adjusted odds ratio [OR], 1.538; 95% confidence interval [CI], 1.182-2.001; p=0.001) and female (adjusted OR, 1.749; 95% CI, 1.058-2.676; p=0.01). A high Hb level is associated with an increased risk of carotid plaques in individuals without history of CVD. This finding may support the need for early screening of CVD in individuals with high Hb levels.

Predicting the risk of subclinical atherosclerosis based on interpretable machine models in a Chinese T2DM population.

Cardiovascular disease (CVD) has emerged as a global public health concern. Identifying and preventing subclinical atherosclerosis (SCAS), an early indicator of CVD, is critical for improving cardiovascular outcomes. This study aimed to construct interpretable machine learning models for predicting SCAS risk in type 2 diabetes mellitus (T2DM) patients. This study included 3084 T2DM individuals who received health care at Zhenhai Lianhua Hospital, Ningbo, China, from January 2018 to December 2022. The least absolute shrinkage and selection operator combined with random forest-recursive feature elimination were used to screen for characteristic variables. Linear discriminant analysis, logistic regression, Naive Bayes, random forest, support vector machine, and extreme gradient boosting were employed in constructing risk prediction models for SCAS in T2DM patients. The area under the receiver operating characteristic curve (AUC) was employed to assess the predictive capacity of the model through 10-fold cross-validation. Additionally, the SHapley Additive exPlanations were utilized to interpret the best-performing model. The percentage of SCAS was 38.46% (n=1186) in the study population. Fourteen variables, including age, white blood cell count, and basophil count, were identified as independent risk factors for SCAS. Nine predictors, including age, albumin, and total protein, were screened for the construction of risk prediction models. After validation, the random forest model exhibited the best clinical predictive value in the training set with an AUC of 0.729 (95% CI: 0.709-0.749), and it also demonstrated good predictive value in the internal validation set [AUC: 0.715 (95% CI: 0.688-0.742)]. The model interpretation revealed that age, albumin, total protein, total cholesterol, and serum creatinine were the top five variables contributing to the prediction model. The construction of SCAS risk models based on the Chinese T2DM population contributes to its early prevention and intervention, which would reduce the incidence of adverse cardiovascular prognostic events.

Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

The role of coffee and potential mediators in subclinical atherosclerosis: insights from Mendelian randomization study.

Coffee contains many bioactive compounds, and its inconsistent association with subclinical atherosclerosis has been reported in observational studies. In this Mendelian randomization study, we investigated whether genetically predicted coffee consumption is associated with subclinical atherosclerosis, as well as the role of potential mediators. We first conducted a two-sample Mendelian randomization analysis to examine the causal effect of coffee and its subtypes on subclinical atherosclerosis inferred from coronary artery calcification (CAC). Next, the significant results were validated using another independent dataset. Two-step Mendelian randomization analyses were utilized to evaluate the causal pathway from coffee to subclinical atherosclerosis through potential mediators, including blood pressure, blood lipids, body mass index, and glycated hemoglobin. Mendelian randomization analyses were performed using the multiplicative random effects inverse-variance weighted method as the main approach, followed by a series of complementary methods and sensitivity analyses. Coffee, filtered coffee, and instant coffee were associated with the risk of CAC (β = 0.79, 95% CI: 0.12 to 1.47, p = 0.022; β = 0.66, 95% CI: 0.17 to 1.15, p = 0.008; β = 0.66, 95% CI: 0.20 to 1.13, p = 0.005; respectively). While no significant causal relationship was found between decaffeinated coffee and CAC (β = -1.32, 95% CI: -2.67 to 0.04, p = 0.056). The association between coffee and CAC was validated in the replication analysis (β = 0.27, 95% CI: 0.07 to 0.48, p = 0.009). Body mass index mediated 39.98% of the effect of coffee on CAC (95% CI: 9.78 to 70.19%, p = 0.009), and 5.79% of the effect of instant coffee on CAC (95% CI: 0.54 to 11.04%, p = 0.030). Our study suggests that coffee other than decaffeinated coffee increases the risk of subclinical atherosclerosis inferred from CAC. Body mass index mediated 39.98 and 5.79% of the causal effects of coffee and instant coffee on CAC, respectively. Coffee should be consumed with caution, especially in individuals with established cardiovascular risk factors, and decaffeinated coffee appears to be a safer choice.

DNA Methylation of the IL-17A Gene Promoter Is Associated with Subclinical Atherosclerosis and Coronary Artery Disease: The Genetics of Atherosclerotic Disease Mexican Study.

The interleukin-17 (IL-17) has a crucial role during inflammation and has been associated with cardiovascular diseases, but its role in epigenetics is still poorly understood. Therefore, the aim of this study was to evaluate the DNA methylation status of the IL-17A gene promoter to establish whether it may represent a risk factor for subclinical atherosclerosis (SA) or clinical coronary artery disease (CAD). We included 38 patients with premature CAD (pCAD), 48 individuals with SA, and 43 healthy controls. Methylation in the CpG region of the IL-17A gene promoter was assessed via methylation-specific polymerase chain reaction (MSP). Individuals with SA showed increased methylation levels compared to healthy controls and pCAD patients, with p < 0.001 for both. Logistic regression analysis showed that high methylation levels represent a significant risk for SA (OR = 5.68, 95% CI = 2.38-14.03, p < 0.001). Moreover, low methylation levels of the IL-17A gene promoter DNA represent a risk for symptomatic pCAD when compared with SA patients (OR = 0.16, 95% CI = 0.06-0.41, p < 0.001). Our data suggest that the increased DNA methylation of the IL-17A gene promoter is a risk factor for SA but may be a protection factor for progression from SA to symptomatic CAD.

Risk of subclinical atherosclerosis in primary Sjogren's syndrome: A systematic review and meta-analysis

BackgroundCurrently, the guidelines for prevention and management of atherosclerosis in patients with Sjogren's syndrome (SS) do not differentiate from those concerning the general population. ObjectivesThe present systematic review aimed to summarize evidence from primary studies assessing the risk of subclinical atherosclerosis in patients with primary SS (pSS). Methods and resultsLiterature was searched until June 2023. Eligible records were randomized controlled trials and observational studies comparing subclinical atherosclerosis markers between pSS patients and healthy controls. DerSimonian-Laird random effects models were used to calculate overall effect estimates. Totally, 19 observational studies comprising 1625 participants were included. Compared to healthy controls, pSS patients had significantly higher values of carotid-femoral intima-media thickness (cfIMT) (MD= 0.07 mm; 95 % CI= [0.04, 0.11]; p <0.001) and were more frequently diagnosed with atherosclerotic plaques (OR= 1.9; 95 % CI= [1.32, 2.74]; p <0.001). Moreover, pSS patients showed a decreased flow and nitrate-mediated dilation (MD = -2.48 %; 95 % CI= [-4.57, -0.39]; p = 0.02, MD= -2.11 %; 95 % CI= [-3.22, -1.01]; p <0.001, respectively). Similar results were observed for the pulse-wave velocity (MD= 0.7 m/s; 95 % CI= [0.36, 1.05]; p <0.001) and the ankle-brachial index (OR= 5.78; 95 % CI= [2.23, 14.99]; p = 0.003). Based on meta-regression analyses, only the disease duration and erythrocyte sedimentation rate were positively and significantly associated with higher cfIMT values. ConclusionPatients with pSS have an increased risk of subclinical atherosclerosis compared to healthy population and thus possibly require early and disease-specific intervention. Further research is warranted for more accurate cardiovascular risk management in SS.

Meta-analysis: increased risk of subclinical atherosclerosis in young women after preeclampsia

Abstract Background Preeclampsia leads to a two-to-eight fold increased risk of developing future cardiovascular disease (CVD). It is vital to identify the subgroup of high-risk women who will ultimately develop CVD. Preeclampsia is characterized by systemic endothelial dysfunction with a hyper inflammatory state. In combination with the pregnancy specific hypercholesteraemic state, this may trigger early onset atherosclerosis which could underlie future development of CVD. Purpose This meta-analysis aims to determine the prevalence of subclinical atherosclerosis at different age intervals, in young women after preeclamptic pregnancies compared to non-preeclamptic pregnancies. Methods A systematic search identified studies reporting prevalence of atherosclerosis. Only studies including a preeclamptic and non-preeclamptic group using CT or ultrasound scan were included. There was no restriction on follow up duration. All subtypes of atherosclerotic plaque in any maternal vessel were included. Quality of articles was assessed by the Newcastle-Ottawa scale. Odds ratios (OR) were calculated with logistic regression as a measure of effect size for the prevalence of any atherosclerotic plaque. The Random effects model pooled odds ratios to produce an overall odds ratio and also stratified data using maternal age and imaged artery. Results Nine studies included 4148 women in total: 1444 (35%) with preeclampsia and 2704 (65%) without preeclampsia. Prevalence of atherosclerosis was higher in women with previous preeclampsia. The overall OR of having atherosclerosis after preeclampsia was 1.67 (95% CI 1.38-2.02) with an I2 of 62%. The odds of atherosclerosis after preeclampsia &amp;lt;40 years of age was 0.64 (0.10-4.32), 40-49 was 1.59 (1.30-1.93) and &amp;gt;50 was 2.67 (1.84-3.89). Conclusion Women with preeclampsia have a significantly increased risk of early-onset atherosclerosis compared to women with healthy pregnancies. This elevated risk starts from 40 years onwards suggestive of accelerated atherosclerosis. Early lifestyle or pharmacological preventive measures should be considered and investigated to reduce CVD burden after preeclamptic pregnancies.Overall resultsTable of odds ratios

Abstract 11631: Subclinical Atherosclerosis Risk of Isolated Diastolic Hypertension in Young Adults

Aim: Hypertension among young adults is common. Little is known regarding subclinical atherosclerosis development associated with isolated diastolic hypertension (IDH) among young adults. This study aimed to assess the relationship between IDH and some surrogate markers of subclinical atherosclerosis in young adults. Methods: From January 2018 to December 2022, we consecutively enrolled 576 IDH individuals (aged 18 to 39 years) without cardiovascular complications and 576 normotensive subjects matched for age, sex and body mass index (BMI). Each participant underwent anthropometric measurements, serum biochemistry evaluation, 24-h ambulatory blood pressure (BP) monitoring, echocardiography, and carotid ultrasonography. Surrogate markers of subclinical atherosclerosis included carotid intima-media thickness (cIMT), ankle-brachial index (ABI), coronary calcification, and biochemical parameters. IDH was defined as diastolic BP ≥ 90 mmHg and systolic BP &lt; 140 mmHg. Results: Individuals with IDH had higher cIMT, greater ABI, and a higher frequency of coronary calcification and albuminuria (all P &lt; 0.05). IDH was correlated with cIMT, ABI, coronary calcification, and albuminuria (Pearson’s correlation coefficients: 0.471, 0.365, 0.411, and 0.268, respectively; all P &lt; 0.05). Compared with normotensive individuals, IDH was related to odds ratios of 2.09 (95% confidence interval [CI], 1.21-3.16), 2.72 (95% CI, 1.52-4.56), 1.78 (95% CI,1.15-2.89), and 1.26 (95% CI, 0.48-2.05) for cIMT, ABI, coronary calcification, and albuminuria, respectively. Conclusion: Our findings emphasize the importance of assessing IDH in young adults to identify high-risk individuals for preventing subclinical atherosclerosis complications.

Cardiometabolic Risk, Peripheral Arterial Disease and Cardiovascular Events in Polycystic Ovary Syndrome: Time to Implement Systematic Screening and Update the Management.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder in women of reproductive age. It presents with gynaecologic, metabolic, and psychologic manifestations. The dominant drivers of pathophysiology are hyperandrogenism and insulin resistance. Both conditions are related to cardiometabolic risk factors, such as obesity, hypertension, dyslipidaemia, hyperglycaemia, type 2 and gestational diabetes, nonalcoholic fatty liver disease and obstructive sleep apnoea. Women with PCOS of reproductive age consistently demonstrated an elevated risk of subclinical atherosclerosis, as indicated by different measurement methods, while findings for menopausal age groups exhibited mixed results. Translation of subclinical atherosclerosis into the increased incidence of peripheral arterial disease and major cardiovascular (CV) events is less clear. Although several expert groups have advised screening, the CV risk assessment and prevention of CV events are frequently underdiagnosed and overlooked aspects of the management of PCOS. A combination of lifestyle management and pharmacotherapy, including the promising new era of anti-obesity medicine, can lead to improvements in cardiometabolic health.

Metabolic health phenotype better predicts subclinical atherosclerosis than body mass index-based obesity phenotype in the non-alcoholic fatty liver disease population.

Non-alcoholic fatty liver disease (NAFLD), especially lean NAFLD is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). It is not currently known which clinical phenotypes of NAFLD contribute most to individual subclinical atherosclerosis risk. We examined the relationship between body mass index (BMI), the metabolically healthy status, and subclinical atherosclerosis in the NAFLD population. Data from asymptomatic NAFLD subjects who participated in a routine health check-up examination were collected. Participants were stratified by BMI (cutoff values: 24.0-27.9 kg/m2 for overweight and ≥28.0 kg/m2 for obesity) and metabolic status, which was defined by Adult Treatment Panel III criteria. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV) in 27,738 participants and by carotid plaque in 14,323 participants. Within each BMI strata, metabolically unhealthy subjects had a significantly higher prevalence of subclinical atherosclerosis than metabolically healthy subjects, whereas fewer differences were observed across subjects within the same metabolic category. When BMI and metabolic status were assessed together, a metabolically unhealthy status was the main contributor to the association of clinical phenotypes with the subclinical atherosclerosis burden (all p < 0.001). When BMI and metabolic abnormalities were assessed separately, the incidence of subclinical disease did not increase across BMI categories; however, it increased with an increase in the number of metabolic abnormalities (0, 1, 2 and ≥3). A metabolically healthy status in NAFLD patients was closely correlated with subclinical atherosclerosis, beyond that of the BMI-based obesity phenotype. The application of metabolic phenotyping strategies could enable more precise classification in evaluating cardiovascular risk in NAFLD.

Assessment of the risk of subclinical atherosclerosis in women with polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrinal disorders affecting women of reproductive age, which has been linked to an enlarged risk of cardiovascular disease and premature atherosclerosis. Atherosclerosis is a persistent inflammatory and lipid-depositing disease that starts from endothelial response to injury, ultimately leading to critical cardiovascular events. Podocalyxin, a cell surface sialomucin, is found on endothelial cells covering blood vessels. Objectives: Measuring serum podocalyxin to predict early atherosclerosis in PCOS women, also measuring lipid panel including the Atherogenic Index of Plasma (AIP), which is a powerful marker that can accurately predict the likelihood of developing the℮ risk of atherosclerosis even when other atherogenic risk factors appear within normal limits. Materials and Method: This case-control study included 124 age-matched women divided into 63 women diagnosed with PCOS (patients) and 61 healthy women (controls). Lipid panel and serum podocalyxin were measured. Results: There is a significant elevation in the mean value of serum podocalyxin (P=0.000), TG (P=0.39), TC (P=0.002), VLDL-C (P=0.039), LDL-C (P=0.001), a Risk ratio of TC/HDL-C (P=0.000), Risk ratio of LDL/HDL-C (P=0.000), and AIP (P=0.013) with significant decrease in mean value of HDL-C (P=0.000) in PCOS women as compared to healthy control. Conclusion: Higher levels of serum podocalyxin and atherogenic index of plasma were found in PCOS women; a positive correlation was also found between serum podocalyxin and atherogenic index of plasma. Therefore, serum podocalyxin appears to be a predictive marker to detect early atherosclerosis in women with PCOS. Keywords: polycystic ovary syndrome, atherosclerosis, podocalyxin, lipid profile, AIP.