Biomarkers Of Cardiovascular Disease Risk Research Articles

Biochemical markers and carotid intima-media thickness in relation to cardiovascular risk in young women.

Cardiovascular disease (CVD) is a major cause of death in the female population. The current study aimed to examine the relationship between CVD risk and novel endothelial dysfunction biomarkers [i.e., endocan, adiponectin and intercellular adhesion molecule (ICAM)-1] and carotid intima-media thickness (cIMT), respectively in a cohort of disease-free women of reproductive age. A total of 129 women were selected. Serum endocan, adiponectin and ICAM-1 were measured by a commercial enzyme-linked immunosorbent assay and cITM was determined by ultrasound. Cardiovascular risk score (CVRS) was calculated. The lowest endocan (p for trend = 0.051) and adiponectin (p for trend = 0.040) levels were found in a group of subjects with the highest CVRS. The cIMT values were the highest in second tertile subgroups, with the highest 75th percentile in a third tertile CVRS group, while the lowest cIMT values were detected in the lowest CVRS tertile group (p for trend = 0.001). A significant positive correlation between cIMT and CVRS (ρ = 0.307, p < 0.001), and a negative correlation between adiponectin and endocan with CVRS, respectively (ρ = - 0.252, p = 0.004; ρ = - 0.179, p = 0.043) were observed, but only endocan retained the independent association with CVRS (p = 0.030) in the multiple linear regression analysis. Endocan could be useful diagnostic tool in the estimation of cardiovascular risk in young women.

5123 Remission of Antibodies Blocking the Insulin Receptor Reduces Atherogenicity of LDL Particles but Increases HDL Particle Atherogenicity

Abstract Disclosure: M. Hwang: None. R. Shamburek: None. M. Lightbourne: None. M. Sampson: None. A. Remaley: None. B. Abel: None. R.J. Brown: None. Background: Type B insulin resistance syndrome (TBIR) is a rare autoimmune disorder defined by the presence of autoantibodies against the insulin receptor, usually in the context of systemic autoimmune diseases such as lupus. In TBIR, insulin signaling is disrupted at the receptor-level, resulting in failure of insulin to both suppress hepatic glucose production and to stimulate de novo lipogenesis. This leads to a phenotype of extreme insulin resistance (IR) and hyperglycemia without dyslipidemia. IR and hyperglycemia resolve when remission of the autoantibody is induced by immunosuppression. Given the known association between IR and cardiovascular disease (CVD), we sought to compare biomarkers of CVD risk using lipoprotein particles measured by Nuclear Magnetic Resonance (NMR) in patients with TBIR during their active disease state vs remission. Methods: Patients with TBIR (N=14) had fasting labs including NMR lipoprotein profiles (analyzed using LP4 deconvolution algorithm) during active disease (positive antibodies to the insulin receptor and severe IR) and remission (defined by discontinuation of insulin or amelioration of hyperglycemia). Particle size (nm) and concentration of subclasses by size were measured for low-density lipoprotein (LDL) particles (nmol/L) and high-density lipoprotein (HDL) particles (umol/L). Results: Upon remission from TBIR, there were large decreases in hemoglobin A1c (from 10.9±3.0% to 6.1±1.1%, p&amp;lt;0.001) and insulin (from 1000.0 (715.9, 1000.0) mcU/mL to 16.8 (8.1, 39.2) mcU/mL, normal 2.6-24.9 mcU/mL, p&amp;lt;0.001), and increases in BMI (from 21.8±3.5 to 28.6±7.4 kg/m2, p&amp;lt;0.01), C3 (from 76±27 to 114±20 mg/dL, normal 82-185 mg/dL, p&amp;lt;0.01), and C4 (from 16±8 to 25±9 mg/dL, normal 15-53 mg/dL, p&amp;lt;0.01). After remission of TBIR, LDL profiles became less atherogenic: small LDL particle concentration decreased (from 523.4±170.2 to 362.8±119.7, normal 63.8-1719.6, p&amp;lt;0.01) and LDL particle size increased (from 20.6±0.5 to 21.2±0.3, normal 19.9 -21.6, p&amp;lt;0.01). By contrast, HDL profiles became more atherogenic after remission of TBIR: small HDL particle concentration increased (from 4.6±2.6 to 8.2±4.3, normal 6.6-19.3, p&amp;lt;0.01); the largest HDL particle concentration decreased (from 1.5±0.8 to 0.7±0.7, normal 0-1.2, p&amp;lt;0.01), and HDL particle size decreased (from 10.3±0.4 to 9.6±0.5, normal 8.4-9.9, p&amp;lt;0.001). Conclusions: Active TBIR is a pro-inflammatory state characterized by excess consumption of C3 and C4. Inflammation may contribute to an unfavorable LDL particle profile that improves after remission. However, lack of insulin signaling through the insulin receptor during active TBIR likely leads to an anti-atherogenic HDL profile that returns to normal levels when insulin signaling is restored after remission. Future studies will further investigate the role of insulin resistance and inflammation in CVD risk. Presentation: 6/3/2024

The association of cardiovascular disease risk with coronary artery calcification and thoracic aortic dilation: a study in idiopathic inflammatory myopathies and systemic lupus erythematosus.

We aim to explore the prevalence of coronary artery calcification (CAC) and ascending/descending thoracic aorta (AA/DA) dilation in idiopathic inflammatory myopathies (IIM) and systemic lupus erythematosus (SLE) patients, and to assess associations between cardiovascular disease (CVD) risk factors and these imaging signatures. This study recruited 151 IIM patients, 140 SLE patients, and 195 controls. The CAC and AA/DA diameters were quantified using non-gated chest CT images. The independent samples t-test or Mann-Whitney test was chosen for comparisons of continuous variables between patients and healthy controls. For categorical data, comparisons were made using the chi-square test or Fisher's exact test. Multivariate regression or Spearman's correlation analysis was employed to probe the associations between CVD risk factors and Framingham risk score (FRS) with imaging signatures. The IIM and SLE patients showed significantly higher prevalence of CAC and AA/DA dilatation (P < 0.01). Age was a risk factor for both CAC and AA/DA dilatation in all cohorts (P < 0.01). In IIM patients, the AA/DA dilatation was associated with BMI (P = 0.05). In SLE patients, CAC was associated with the elevated CRP level (P = 0.05). Without CAC, both IIM and SLE patients showed significant correlations between AA/DA diameters and FRS (P < 0.01, P < 0.01). Only in SLE patients, the interleukin-6 (IL-6) level correlated with AA/DA diameters. The IIM and SLE patients more commonly exhibit CAC and AA/DA dilation. These subclinical atherosclerosis signs are associated with traditional CVD risk factors. For AID patients without CAC, AA/DA diameters could serve as a potential biomarker for early CVD risk. Key Points • The study characterized the manifestation of subclinical atherosclerosis imaging biomarkers (CAC, AA/DA dilation) in IIM and SLE patients. • AA/DA diameters could serve as an early imaging biomarker in clinical management for IIM and SLE patients with early-onset and no CAC present.

Relationship Between Weight Loss, Changes in Serum hs-CRP Levels and apo A-1 Lipoprotein, and High-Density Lipoprotein-Cholesterol Ratios as Predictors for Improved Cardiovascular Risk Factors After Laparoscopic Sleeve Gastrectomy

IntroductionObesity, a major global health concern, is a known risk factor for cardiovascular disease (CVD), often due to dyslipidemia and insulin resistance. Laparoscopic sleeve gastrectomy (LSG) is an effective weight reduction surgery that not only alters body metabolism and gastrointestinal physiology but also significantly lowers cardiovascular disease risk.MethodsThis study explores the impact of weight loss on serum high-sensitivity C-reactive protein (hs-CRP), an established inflammatory marker, and changes in cardiovascular risk factors, particularly high-density lipoprotein-cholesterol (HDL-C) ratios, serum apo A-1, lipid profile, and HOMA-IR in severe obesity undergoing LSG. Anthropometric measurements and blood samples were collected preoperatively and 6 months postoperatively to hs-CRP, HOMA-IR, lipid profile, apo A-1, and low- and high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratios, total cholesterol to HDL-C (TC/HDL-C) ratio, and monocyte to high-density lipoprotein-cholesterol ratio (MHR).ResultsIn total, 70 patients were analyzed after 6 months and reached %TWL 27.4 ± 9.5 and %EWL 62.0 ± 15.4. Significant improvements were noted in all measured biomarkers. Analysis showed that each unit reduction in BMI significantly affected hs-CRP and HDL-C. Furthermore, moderate associations between hs-CRP and various cardiovascular disease risk biomarkers, including a negative correlation with apo A-1 and positive correlations with total cholesterol (TC), TC/HDL-C, and LDL-C/HDL-C, along with a mild positive correlation with HOMA-IR.ConclusionWeight loss following LSG significantly reduced inflammation and improved atheroprotection. Improved inflammation markers were associated with favorable changes in cardiovascular risk factors, including HDL-C ratios particularly TC/HDL-C, LDL-C/HDL-C, and apo A-1.Graphical

Circadian misalignment disrupts biomarkers of cardiovascular disease risk and promotes a hypercoagulable state.

The circadian system regulates 24-h time-of-day patterns of cardiovascular physiology, with circadian misalignment resulting in adverse cardiovascular risk. Although many proteins in the coagulation-fibrinolysis axis show 24-h time-of-day patterns, it is not understood if these temporal patterns are regulated by circadian or behavioral (e.g., sleep and food intake) cycles, or how circadian misalignment influences these patterns. Thus, we utilized a night shiftwork protocol to analyze circadian versus behavioral cycle regulation of 238 plasma proteins linked to cardiovascular physiology. Six healthy men aged 26.2±5.6 years (mean ± SD) completed the protocol involving two baseline days with 8-h nighttime sleep opportunities (circadian alignment), a transition to shiftwork day, followed by 2days of simulated night shiftwork with 8-h daytime sleep opportunities (circadian misalignment). Plasma was collected for proteomics every 4h across 24 h during baseline and during daytime sleep and the second night shift. Cosinor analyses identified proteins with circadian or behavioral cycle-regulated 24-h time-of-day patterns. Five proteins were circadian regulated (plasminogen activator inhibitor-1, angiopoietin-2, insulin-like growth factor binding protein-4, follistatin-related protein-3, and endoplasmic reticulum resident protein-29). No cardiovascular-related proteins showed regulation by behavioral cycles. Within the coagulation pathway, circadian misalignment decreased tissue factor pathway inhibitor, increased tissue factor, and induced a 24-h time-of-day pattern in coagulation factor VII (all FDR <0.10). Such changes in protein abundance are consistent with changes observed in hypercoagulable states. Our analyses identify circadian regulation of proteins involved in cardiovascular physiology and indicate that acute circadian misalignment could promote a hypercoagulable state, possibly contributing to elevated cardiovascular disease risk among shift workers.

Precision Nutrition for Management of Cardiovascular Disease Risk during Menopause.

Women can spend up to 40% of their lives in the postmenopausal state. As women begin to transition into menopause, known as perimenopause, changes in hormonal concentrations and body composition dramatically increase overall cardiometabolic risk. Dietary patterns and interventions can be utilized to prevent and treat cardiovascular disease (CVD) and some dietary patterns over others may be more beneficial due to their specific effects on the health aspects of menopause. In this narrative review, we summarize key cardiovascular alterations that occur during the menopause transition and explore current dietary recommendations to address CVD risk as well as explore the new frontier of precision nutrition and the implications for nutrition prescription during menopause. Popular dietary interventions for CVD such as the Dietary Approaches to Stop Hypertension (DASH) diet and the Mediterranean diet (MED) have limited data in women following menopause. However, both diets improve CVD risk biomarkers of total cholesterol and low-density lipoprotein cholesterol as well as lower oxidative stress and inflammation and improve endothelial function. As the menopause transition increases the risk for developing metabolic syndrome, insulin insensitivity, and dyslipidemia, the DASH diet and MED may be impactful dietary strategies for mediating CVD risk in menopausal women. However, these are "one-size-fits-all" approaches that neglect individual characteristics such as genetic predisposition and environmental factors. Precision nutrition considers individual factors for nutrition prescription, spanning from evaluating food intake preferences and behaviors to deep phenotyping. Data from a large-scale investigation of the menopause transition suggests nutritional strategies that address postprandial glycemic responses, and the gut microbiome may attenuate some of the unfavorable effects of menopause on CVD risk factors. Considering menopause, women are a clinical population that would greatly benefit from precision nutrition. Future research should explore the use of machine learning and artificial intelligence in a precision nutrition framework to modify the DASH diet and MED to address adverse effects that occur during the menopause transition are vital for supporting women's health as they age.

Deep transfer learning for detection of breast arterial calcifications on mammograms: a comparative study

IntroductionBreast arterial calcifications (BAC) are common incidental findings on routine mammograms, which have been suggested as a sex-specific biomarker of cardiovascular disease (CVD) risk. Previous work showed the efficacy of a pretrained convolutional network (CNN), VCG16, for automatic BAC detection. In this study, we further tested the method by a comparative analysis with other ten CNNs.Material and methodsFour-view standard mammography exams from 1,493 women were included in this retrospective study and labeled as BAC or non-BAC by experts. The comparative study was conducted using eleven pretrained convolutional networks (CNNs) with varying depths from five architectures including Xception, VGG, ResNetV2, MobileNet, and DenseNet, fine-tuned for the binary BAC classification task. Performance evaluation involved area under the receiver operating characteristics curve (AUC-ROC) analysis, F1-score (harmonic mean of precision and recall), and generalized gradient-weighted class activation mapping (Grad-CAM++) for visual explanations.ResultsThe dataset exhibited a BAC prevalence of 194/1,493 women (13.0%) and 581/5,972 images (9.7%). Among the retrained models, VGG, MobileNet, and DenseNet demonstrated the most promising results, achieving AUC-ROCs > 0.70 in both training and independent testing subsets. In terms of testing F1-score, VGG16 ranked first, higher than MobileNet (0.51) and VGG19 (0.46). Qualitative analysis showed that the Grad-CAM++ heatmaps generated by VGG16 consistently outperformed those produced by others, offering a finer-grained and discriminative localization of calcified regions within images.ConclusionDeep transfer learning showed promise in automated BAC detection on mammograms, where relatively shallow networks demonstrated superior performances requiring shorter training times and reduced resources.Relevance statementDeep transfer learning is a promising approach to enhance reporting BAC on mammograms and facilitate developing efficient tools for cardiovascular risk stratification in women, leveraging large-scale mammographic screening programs.Key points• We tested different pretrained convolutional networks (CNNs) for BAC detection on mammograms.• VGG and MobileNet demonstrated promising performances, outperforming their deeper, more complex counterparts.• Visual explanations using Grad-CAM++ highlighted VGG16’s superior performance in localizing BAC.Graphical

Air Pollution and Blood Pressure: Evidence From Indonesia.

Indonesia faces significant air quality issues due to multiple emissions sources, including rapid urbanization and peatland fires associated with agricultural land management. Limited prior research has estimated the episodic shock of intense fires on morbidity and mortality in Indonesia but has largely ignored the impact of poor air quality throughout the year on biomarkers of cardiovascular disease risk. We conducted a cross-sectional study of the association between particulate matter less than 2.5 microns in diameter (PM2.5) and blood pressure. Blood pressure measurements were obtained from the fifth wave of the Indonesian Family Life Survey (IFLS5), an ongoing population-based socioeconomic and health survey. We used the GEOS-Chem chemical transport model to simulate daily PM2.5 concentrations at 0.5°×0.625° resolution across the IFLS domain. We assessed the association between PM2.5 and diastolic and systolic blood pressure, using mixed effects models with random intercepts for regency/municipality and household and adjusted for individual covariates. An interquartile range increase in monthly PM2.5 exposure was associated with a 0.234 (95% CI: 0.003, 0.464) higher diastolic blood pressure, with a greater association seen in participants age 65 and over (1.16 [95% CI: 0.24, 2.08]). For the same exposure metric, there was a 1.90 (95% CI: 0.43, 3.37) higher systolic blood pressure in participants 65 and older. Our assessment of fire-specific PM2.5 yielded null results, potentially due to the timing and locations of health data collection. To our knowledge, this is the first study to provide evidence for an association between PM2.5 and blood pressure in Indonesia.

Association of retinal image-based, deep learning cardiac BioAge with telomere length and cardiovascular biomarkers.

Our retinal image-based deep learning (DL) cardiac biological age (BioAge) model could facilitate fast, accurate, noninvasive screening for cardiovascular disease (CVD) in novel community settings and thus improve outcome with those with limited access to health care services. This study aimed to determine whether the results issued by our DL cardiac BioAge model are consistent with the known trends of CVD risk and the biomarker leukocyte telomere length (LTL), in a cohort of individuals from the UK Biobank. A cross-sectional cohort study was conducted using those individuals in the UK Biobank who had LTL data. These individuals were divided by sex, ranked by LTL, and then grouped into deciles. The retinal images were then presented to the DL model, and individual's cardiac BioAge was determined. Individuals within each LTL decile were then ranked by cardiac BioAge, and the mean of the CVD risk biomarkers in the top and bottom quartiles was compared. The relationship between an individual's cardiac BioAge, the CVD biomarkers, and LTL was determined using traditional correlation statistics. The DL cardiac BioAge model was able to accurately stratify individuals by the traditional CVD risk biomarkers, and for both males and females, those issued with a cardiac BioAge in the top quartile of their chronological peer group had a significantly higher mean systolic blood pressure, hemoglobin A 1c , and 10-year Pooled Cohort Equation CVD risk scores compared with those individuals in the bottom quartile (p<0.001). Cardiac BioAge was associated with LTL shortening for both males and females (males: -0.22, r2 = 0.04; females: -0.18, r2 = 0.03). In this cross-sectional cohort study, increasing CVD risk whether assessed by traditional biomarkers, CVD risk scoring, or our DL cardiac BioAge, CVD risk model, was inversely related to LTL. At a population level, our data support the growing body of evidence that suggests LTL shortening is a surrogate marker for increasing CVD risk and that this risk can be captured by our novel DL cardiac BioAge model.

Abstract 23: Multidimensional Association of Sleep With Health Behaviors and Cardiometabolic Risk in Adolescents

Introduction: Insufficient sleep has been recognized by AHA as part of Life’s Essential 8 in the prevention of cardiovascular disease (CVD). While sleep is a multidimensional phenomenon comprised of duration, efficiency, quality, timing, and regularity, prior epidemiological research in youth has predominantly focused on sleep duration. It is important to disentangle which sleep dimensions most associate with other health behaviors and biomarkers for CVD risk in adolescents. Hypothesis: We hypothesize that specific dimensions of insufficient, disturbed, and misaligned sleep will be differentially associated with nutrition, physical activity, and inflammation. Methods: We analyzed data from 421 population-based randomly-selected adolescents from the Penn State Child Cohort (median 16 years; 47% female; 21% racial/ethnic minority) who had at least 5-night at-home actigraphy (ACT), 1-night in-lab 9-h polysomnography (PSG), self-reported insomnia symptoms, daytimes sleepiness, sleep schedule, circadian preference, and dietary assessment, as well as fasting blood draw assayed for C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα). Linear regression models tested the independent association of each sleep dimension with caloric intake, ACT-derived sedentary behavior, and blood-based inflammatory biomarkers, while accounting for sex, age, race/ethnicity, and body mass index. Results: Higher ACT-measured night-to-night variability in sleep duration was most strongly associated with increased caloric intake, particularly carbohydrates (B=0.203, p&lt;0.001), while shorter PSG-measured sleep duration was also associated with carbohydrates but to a lesser extent (B=-0.150, p=0.002). Later bedtime on weekdays was most strongly associated with higher bouts of sedentary behavior (B=0.216, p&lt;0.001), while shorter ACT-measured sleep duration was most strongly associated with time spent sedentary (B=-0.226, p&lt;0.001). PSG-measured sleep apnea was most strongly associated with higher CRP (B=0.287, p&lt;0.001) and IL-6 levels (B=0.260, p&lt;0.001), while later bedtime on weekdays (B=0.136, p=0.025) and evening circadian preference (B=-0.124, p=0.017) were also associated with inflammation but to a lesser extent. Conclusions: The association of inadequate sleep with health behaviors and cardiometabolic risk in adolescents is in itself multidimensional. These data support that AHA guidelines should be updated to include insufficient, disturbed, and misaligned sleep as contributors to CVD risk.

Retinal oximetry and microvascular assessment after hypertensive pregnancy complications.

Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non-invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group. We examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non-parametric tests and multiple regression analyses, adjusted for age and body mass index. Median arteriolar oxygen saturation (SaO2; 94.2% vs. 93.0%), venular oxygen saturation (SvO2; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV-difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm2) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV-difference (R2 = 0.209) and negatively correlated with arteriolar diameter (CRAE; r2 = 0.382). Structural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV-difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women.

Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796.

Systemic and cerebral inflammatory responses are implicated in the pathogenesis of obesity and associated metabolic impairment. While the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to obesity-associated inflammation, whether it contributes to the development or maintenance of obesity is unknown. We provide support for a direct role of saturated fatty acids, such as palmitic acid, as NLRP3 activating stimuli in obese states. To investigate whether NLRP3 activation contributes to the pathogenesis of diet-induced obesity (DIO) in mice, we tested two different clinical-stage NLRP3 inflammasome inhibitors. We demonstrate a contributory role of this key inflammasome to established obesity and associated systemic and cerebral inflammation. By comparing their effects to calorie restriction, we aimed to identify specific NLRP3-sensitive mechanisms contributing to obesity-induced inflammation (as opposed to be those regulated by weight loss per se). In addition, a direct comparison of an NLRP3 inhibitor to a glucagon like peptide-1 receptor agonist, semaglutide (Wegovy), in the DIO model allowed an appreciation of the relative efficacy of these two therapeutic strategies on obesity, its associated systemic inflammatory response, and cerebral gliosis. We show that two structurally distinct, NLRP3 inhibitors, NT-0249 and NT-0796, reverse obesity in the DIO mouse model and that brain exposure appears necessary for efficacy. In support of this, we show that DIO-driven hypothalamic glial fibrillary acidic protein expression is blocked by dosing with NT-0249/NT-0796. While matching weight loss driven by semaglutide or calorie restriction, remarkably, NLRP3 inhibition provided enhanced improvements in disease-relevant biomarkers of acute phase response, cardiovascular inflammation, and lipid metabolism. SIGNIFICANCE STATEMENT: Obesity is a global health concern that predisposes individuals to chronic disease such as diabetes and cardiovascular disease at least in part by promoting systemic inflammation. We report that in mice fed a high-fat, obesogenic diet, obesity is reversed by either of two inhibitors of the intracellular inflammatory mediator NLRP3. Furthermore, NLRP3 inhibition reduces both hypothalamic gliosis and circulating biomarkers of cardiovascular disease risk beyond what can be achieved by either the glucagon like peptide-1 agonist semaglutide or calorie restriction alone.

Clinical Update: Ceramides As Novel Biomarkers of Cardiovascular Disease Risk

Historically, lipid panels have been used to predict cardiovascular risk. However, individuals with well-controlled lipid levels continue to have cardiac events. Recent advances in genomics and lipidomic technologies have identified a class of lipids known as ceramides, a minor subset of the lipidome that has a causative role in cardiometabolic conditions. Different genes and tissue distributions distinguish ceramides from other lipids. Nurse practitioners and other providers must be knowledgeable of the important role of ceramides in risk stratification for primary and secondary prevention beyond the standard lipid profile.

Abstract 12485: Cardiovascular Disease Risk, Cognitive Function, and Serum Biomarkers in Older Women Participating in a Lifestyle Intervention

Background: Cardiovascular disease (CVD), including atherosclerotic CVD (ASCVD) and stroke, increase risk of cognitive dysfunction. Serum biomarkers, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1) may be associated with elevated CVD risk and are also emerging as early indicators of cognitive dysfunction. Yet, few studies have investigated associations among all three: CVD risk, cognitive function, and serum biomarkers. Aims: We examined associations between CVD risk, cognitive function, and serum biomarkers in older women with CVD. Methods: Baseline data from an ongoing lifestyle intervention trial for the prevention of cognitive decline in older women with CVD (NCT04556305) were analyzed. Women ( N =253) aged ≥65 years were recruited from ambulatory cardiology clinics. At baseline, CVD risk factors, including blood pressure, body mass index (BMI), waist circumference, and step test (cardiorespiratory fitness) were assessed. ASCVD and CHA 2 DS 2 -VASc scores were calculated to estimate clinical ASCVD and stroke risk, respectively. Serum biomarkers included BDNF, VEGF, and IGF-1. Neurocognitive tests for global cognition, including episodic memory, executive function, semantic memory, and working memory domains, were administered. Linear regression models adjusted for age, education, and race or ethnicity were used to evaluate associations of individual CVD risk factors, ASCVD and CHA 2 DS 2 -VASc scores with cognitive function and serum biomarkers, separately. Results: Of CVD risk factors, waist circumference and BMI were associated with cognition: waist circumference with global cognition, episodic memory, and executive function ( β = -.14 - -.20); BMI with executive function ( β = -.13). ASCVD and CHA2DS2-VASc scores were associated with semantic memory ( β = -.23 and -.16, respectively). Only the ASCVD risk score was associated with BDNF ( β = .18) and VEGF ( β = .24) levels. Conclusion: In older women with CVD, body composition and CVD risk scores appear to be correlated with cognitive function. Future studies should explore associations prospectively and consider serum biomarkers as mediators of the relation of CVD risk to cognitive dysfunction.

Blackcurrant Anthocyanins Improve Blood Lipids and Biomarkers of Inflammation and Oxidative Stress in Healthy Women in Menopause Transition without Changing Body Composition.

Recent cell and animal studies suggest the potential of blackcurrants (BCs; Ribes nigrum) as a dietary agent that may reduce the risk of cardiovascular disease (CVD) by improving dyslipidemia, oxidative stress, and inflammation. This study aimed to examine the effects of BC anthocyanin (ACN) extract supplementation on biomarkers of CVD risk in healthy adult women in menopause transition. The effects of BC ACN supplementation on body composition, fasting blood lipids and biomarkers of inflammation and oxidative stress were evaluated using anthropometric measures and blood samples collected from a pilot randomized controlled clinical trial in peri- and early postmenopausal women. Thirty-eight eligible peri- and early postmenopausal women aged 45-60 completed the entire trial, in which they were randomly assigned into one of three treatment groups: placebo (control group), 392 mg/day (low BC group), or 784 mg/day (high BC group) for six months. The significance of differences in outcomes was tested using repeated-measures ANOVA. Overall, following six-month BC consumption, significantly decreased triglyceride (TG) levels were observed between treatment groups (p < 0.05) in a dose-dependent manner. Plasma interleukin-1β (IL-1β) was significantly reduced in a dose and time dependent manner (p < 0.05). Significant decreases in thiobarbituric acid reactive substances (TBARS) levels were also observed between treatment groups (p < 0.05) in a dose-dependent manner. Six-month change in oxidized LDL was inversely correlated with changes in catalase (CAT) and total antioxidant capacity (TAC) (p < 0.05), while C-reactive protein (hs-CRP) change was positively correlated with changes in TG and IL-1β (p < 0.01). Together, these findings suggest that daily BC consumption for six months effectively improved dyslipidemia, inflammation, and lipid peroxidation, thus potentially mitigating the risk of postmenopausal CVD development in study participants. Future studies with larger sample sizes and at-risk populations are warranted to confirm these findings.

Pivotal trial of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from CMERC-HI.

The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk. In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) according to Reti-CVD in prediction of CVD events. The cardiac computed tomography-measured coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial-ankle pulse wave velocity (baPWV) were compared to Reti-CVD. A total of 1106 participants were included, with 33 (3.0%) participants experiencing CVD events over 5years; the Reti-CVD-defined risk groups (low, moderate, and high) were significantly associated with increased CVD risk (HR trend, 2.02; 95% CI, 1.26-3.24). When all variables of Reti-CVD, CAC, CIMT, baPWV, and other traditional risk factors were incorporated into one Cox model, the Reti-CVD risk groups were only significantly associated with increased CVD risk (HR = 2.40 [0.82-7.03] in moderate risk and HR = 3.56 [1.34-9.51] in high risk using low-risk as a reference). This regulated pivotal study validated an AI-SaMD, retinal image-based, personalized CVD risk scoring system (Reti-CVD). These results led the Korean regulatory body to authorize Reti-CVD.

Pulse rate variability predicted cardiovascular disease in sleep disordered breathing: The Guangdong sleep health study

ObjectivesPulse rate variability (PRV) predicts stroke in patients with sleep disordered breathing (SDB). However, the relationship between PRV and cardiovascular disease (CVD) was unknown in SDB. MethodsThis was a cross-sectional study. Community residents in Guangdong were investigated. Sleep study were conducted with a type Ⅳ sleep monitoring. PRV parameters was assessed from the pulse waveforms derived from the sleep monitoring. Results3747 participants were enrolled. The mean age was 53.9 ± 12.7 years. 1149 (30.7%) were diagnosed as SDB. PRV parameters, except for the averages of pulse-to-pulse intervals (ANN), were higher in participants with SDB than those without. After adjusting for traditional CVD risk factors, deceleration capacity of rate (DC), ANN, and the percentage of pulse-to-pulse interval differences that were more than 50 ms (PNN50) were correlated with CVD risk in participants with SDB (OR were 0.826, 1.002, and 1.285; P were 0.003, 0.009, and 0.010), but not in participants without SDB. There was no interaction effect between DC, ANN, PNN50 and oxygen desaturation index. In hierarchical analysis, DC and ANN were predictors for CVD in SDB patients with age <60 years, male, overweight, diabetes, and normal lipid metabolism. PNN50 was predictor for CVD in the elderly SDB patients without overweight, diabetes or dyslipidemia. ConclusionsPRV parameters may be specific predictors for CVD in SDB. PNN50 was a potent biomarker for CVD risk in the elderly with SDB, event without traditional CVD risk factors.

Association of non-daily hookah tobacco smoking and cardiovascular disease-related exposure biomarkers among U.S. users: The Population Assessment of Tobacco and Health Study

Hookah smoking has grown to become a global tobacco epidemic. While cigarette smoking is a well-established cardiovascular disease (CVD) risk factor, the CVD risks of hookah smoking are unknown, particularly among regular U.S. adult hookah users who are predominantly non-daily users. Herein, we examined the association between hookah smoking and biomarkers of CVD risk among regular exclusive hookah smokers (n = 75), compared to regular exclusive cigarette smokers (n = 1773), dual hookah and cigarette smokers (n = 43) and never tobacco users (n = 757), using data from a nationally representative sample of adults from the Population Assessment of Tobacco and Health Study (2013–2014). Whereas 84% of cigarette smokers reported daily use, only 8% of hookahsmokers reported daily use, with more than a third reporting monthly use. Adjusting for age and sex and as compared to exclusive cigarette smokers, exclusive hookah smokers had significantly lower geometric mean concentrations in serum sICAM-1 and urinary F2-isoprostane (p < 0.05). Although not statistically significant, a signal of increased oxidative stress was observed among hookah smokers as compared to never tobacco users (urinary F2-isoprostane). CVD-related harm biomarkers appear to be lower among hookah smokers than cigarette smokers. These findings represent patterns of hookah smoking predominantly shared among adult U.S. users who report non-daily occasional use and do not reflect solitary, daily use as is common in the Middle East. Future studies with longer exposure and longitudinal hookah use are warranted to explore the association between hookah smoking and CVD risk.

Relation of forward and backward traveling pressure waves with subclinical carotid artery wall remodeling and central pulse pressure.

Central pulse pressure (PP) is the sum of forward and backward traveling pressure waves that have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding the importance of the forward versus the backward wave for CVD risk. Therefore, we sought to determine the degree to which the forward and backward pressure waves are associated with subclinical carotid artery wall remodeling and central PP in healthy adults. Using applanation tonometry, carotid pressure waveforms were acquired in 308 healthy individuals (aged 45 ± 17 years, range 19-80 years, 61% women), from which the time integral of the forward (PfTI) and backward (PbTI) pressure waves were derived via pressure-only wave separation analysis. Common carotid artery intima-media thickness (cIMT), a biomarker of subclinical CVD risk, was derived via B-mode ultrasonography measured ∼2 cm from the carotid bulb. Both PfTI (r = 0.31, P < 0.001) and PbTI (r = 0.40, P < 0.001) were correlated with cIMT. However, further analysis revealed that PbTI mediated the relation between PfTI and cIMT (proportion mediated = 156%, P < 0.001). The association between PbTI and cIMT remained after adjusting for age, sex, body mass index, blood glucose, low-density lipoprotein cholesterol, heart rate, brachial systolic pressure, and aortic stiffness (B = 0.02, 95% confidence interval = 0.01, 2.77, P < 0.001). Both PfTI (r = -0.58, P < 0.001) and PbTI (r = -0.50, P < 0.001) were correlated with central PP, however, PfTI fully mediated the association between PbTI and central PP (proportion mediated = 124%, P < 0.001). Although PfTI is correlated with higher central PP, it is PbTI that is directly associated with carotid artery wall remodeling.NEW & NOTEWORTHY The present study contributes to the growing body of evidence highlighting the physiological and clinical insight provided by the pulsatile hemodynamic components of central artery pulse pressure. The notable findings of this study are: 1) The reflected (backward) pressure wave is associated with carotid intima-media thickness independent of traditional cardiovascular risk factors, including systolic blood pressure and aortic stiffness. 2) The incident (forward) pressure wave, and not the reflected pressure wave, is associated with greater central pulse pressure.

Glycemic index, glycemic load, dietary insulin index, and dietary insulin load in relation to cardiometabolic risk factors among participants with atherosclerosis: a cross-sectional study

BackgroundWe examined the cross-sectional associations of dietary Glycemic Index (GI), Glycemic Load (GL), Dietary Insulin Index (DII), and Dietary Insulin Load (DIL) with cardiovascular disease (CVD) factors in subjects with atherosclerosis.MethodsThe present cross-sectional study was conducted on subjects with atherosclerosis. Regular dietary intake was assessed using a 168-item semi-quantitative food frequency questionnaire (FFQ) and GI, GL, DIL, and DII were also calculated. Odds Ratio (OR) and 95% Confidence Intervals (CIs) were estimated for general and central obesity according to the GI, GL, DII, and DIL.ResultsAccording to the continuous score of GL, there was a significant positive association between GL and central obesity for women in all models. Regarding the association between DIL score and biochemical variables, there was a significant positive association between Na and Aspartate transaminase (AST) with DII. Moreover, there was a significant positive association between LDL-c(p = 0.03) and AST (p = 0.04)with DIL score in all 3 models.ConclusionIn this study, GL was associated with greater odds of central obesity in women, but not in men. Neither dietary DII nor DIL was associated with BMI and central obesity. GI, GL, DII, and DIL were significantly associated with some CVD risk biomarkers in subjects with atherosclerosis.