Biomarkers Of Cardiovascular Disease Risk Research Articles

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.

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<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<0.001), while shorter ACT-measured sleep duration was most strongly associated with time spent sedentary (B=-0.226, p<0.001). PSG-measured sleep apnea was most strongly associated with higher CRP (B=0.287, p<0.001) and IL-6 levels (B=0.260, p<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

AbstractPurposeWomen 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.MethodsWe 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.ResultsMedian 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).ConclusionsStructural 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.

Preliminary evidence of glycine as a biomarker of cardiovascular disease risk in children with obesity.

Glycine (GLY) is a substrate for a wide range of metabolic processes. Several preclinical and adult studies demonstrated inverse associations of GLY with obesity, cardiovascular disease (CVD) and diabetes. However, little evidence is available on relationships between GLY and CVD risk in children. We assessed links between circulating GLY and biomarkers of CVD in children with obesity. Participants included both male and females with normal weight (NW, n = 6) and obesity (OB, n = 15), with age 14-18 years and Tanner stage >IV. Concentrations of GLY, branched chain amino acids (BCAA), and 25-hydroxy vitamin-D [25(OH)D], glucose, insulin, adiponectin, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured using established techniques, and body composition by DXA. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Our study identified major relationships of GLY (p-value < 0.01 for all) of GLY with visceral fat (r2 = 0.40), BCAA (r2 = 0.44), HOMA-IR (r2 = 0.33), 25(OH)D (r2 = 0.48), IL-6 (r2 = 0.46) and adiponectin (r2 = 0.39). Given that CVD progression is a continuum and the disease itself is not present in children and biomarkers are typically used to monitor CVD in children, the links between GLY and biomarkers of CVD provide evidence for the first time of a potential role for GLY in CVD in children with obesity.

&lt;i&gt;Apium graveolens&lt;/i&gt; Aqueous Extract Reduced Cardiovascular Diseases and Inflammatory Biomarkers Expression in High-Fat Diet-Fed BALB/C Mice

Background and Aims: Cardiovascular disease prevention has always been a high goal. The goal of this study is to investigate if Apium graveolens has any influence on cardiovascular disease risk factors, biomarkers, and inflammatory biomarkers in male BALB/c mice that have been given a high-fat diet. Methods: Apium graveolens aqueous extract was given to male BALB/c mice, and they were either fed a standard pellet or a diet composed of cholesterol (0.15%), sodium cholate (0.5%), and pure coconut oil (21%) for 12 weeks. Serum fasting glucose, a lipid profile, liver function tests, and cardiac indicators were used to evaluate the extract’s anti-dyslipidemic, hypoglycemic, hepatoprotective, and cardioprotective characteristics. Antioxidant enzyme markers in tissues were also evaluated. To evaluate inflammatory and CVD biomarkers in cardiac tissue, RT-qPCR and ELISA were used. An unpaired t-test assessed group differences. P &lt; 0.05 showed significance. Results: The HFD control group exhibited considerably higher levels of blood glucose, lipid profile, hepatic indicators, inflammatory and cardiac markers, and lower levels of HDL-C and antioxidant enzymes. When administered orally, an aqueous extract of Apium graveolens significantly reduced blood glucose levels. Serum lipids and liver indicators returned to nearnormal levels. In addition to a considerable reduction in MDA levels, treated mice showed a large increases in catalase and reduced glutathione activities. Inflammatory and cardiovascular disease biomarker expression was reduced in the extract-treated groups. Conclusions: Apium graveolens consumption may help reduce the risk of cardiovascular disorders.

Detection of Undiagnosed Elevated Cardiovascular Risk Biomarkers among HIV-Positive Patients on Antiretroviral Therapy (ART) in Kigali-City, Rwanda

Background: Similar to other African countries, life expectancy of people living with HIV infection has improved due to access to antiretroviral therapy (ART) in Rwanda. However, both HIV infection and use of ART are associated with cardiovascular disease (CVD) risks, due to adverse changes in some biomarkers, causing dyslipidemia and other metabolic imbalances. Biomarkers for CVD risk in HIV-infected individuals taking ART, has not been well characterized in Rwanda. We evaluated the association between the use and duration of ART and biomarkers of CVD risk among HIV infected adults in Rwanda. Methods: A total of 150 participants (18-45 years) from HIV clinics in public Health Center in Kigali included n=30 HIV-uninfected (HIV-) and n=120 HIV-infected (HIV+) adults. Among the HIV+ adults, n=40 participants were ART-naïve. Cross-sectional data were collected on healthrelated behaviors and biochemical markers of CVD risk. We compared CVD-related biomarkers between HIV-, HIV+ ART-naïve, and HIV+ on ART groups. Results: The majority of participants were women (60%) and HIV- were younger (35 ± 6 vs. 31 ± 6 years). Total cholesterol and triglycerides concentrations were associated with ART usage. Serum triglycerides concentrations were lower in HIV+ ART-naïve compared to HIV+ on ART (76.6 ± 38.9 mg/dl vs. 85.0 ± 38.3 mg/dl; p&lt; 0.01). While total cholesterol concentrations were higher in HIV+ on ART than HIV+ ART-naïve (136.0 ± 45.1 mg/dl vs. 130.0 ± 36.5 mg/dl; p&lt;0.04), HDL-C was higher in those taking ART (68.7 ± 30.0 mg/dl vs. 55.0 ± 25.7 mg/dl; p=0.02) among HIV+ on ART for 0-6 months and 7-12 months respectively. Conclusion: Elevated levels of cardiovascular risk biomarker profiles (serum total cholesterol and triglycerides) were associated with use of ART in young adults with HIV in the present study. Although these values were within the upper limits of normal, our findings suggest early alterations in biomarkers of cardiovascular risk. These findings underscore the need for early evaluation of lipid profiles as biomarkers of CVD risk, to effectively monitor how ART may contribute to cardiovascular disease and deter treatment programs in Rwanda and other African countries.

Effect of modernized collaborative care for depression on depressive symptoms and cardiovascular disease risk biomarkers: eIMPACT randomized controlled trial

Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, Mage = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges’ g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results – 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93–7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers – i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, β-thromboglobulin, and platelet factor 4 (Hedges’ gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention – which harnessed technology to maximize access and minimize resources – produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches.Trial Registration:ClinicalTrials.gov Identifier: NCT02458690.

Calprotectin and CRP as biomarkers of cardiovascular disease risk in patients with chronic kidney disease: a follow-up study at 5 and 10 years

Chronic kidney disease (CKD) and low-grade inflammation are associated with increased risk of cardiovascular disease (CVD). Calprotectin, a protein mainly secreted by activated neutrophils during inflammatory conditions, has been linked to CVD risk in general populations. The aim of this study was to evaluate the association of calprotectin with CVD risk in CKD patients, relative to C-reactive protein (CRP). One hundred and fifty-three patients with moderate CKD were prospectively followed up at 5 and 10 years. We used Cox regression modelling with stepwise adjustments for other relevant covariates (age, sex, cystatin C, previous CVD, systolic blood pressure, HDL cholesterol and HbA1c) to assess the association of baseline calprotectin and CRP with the risk of fatal or non-fatal CVD events. Twenty-nine and 44 patients experienced a CVD event during median follow-up of 4.8 and 10.9 years, respectively. Higher calprotectin was associated with increased CVD risk at both time points, which remained statistically significant after multivariable adjustments, including adjustment for CRP. For CRP, the associations did not remain statistically significant after final multivariable adjustments. In conclusion, we have shown that in patients with CKD, calprotectin was independently associated with the risk of future CVD events, suggesting that calprotectin may provide prognostic information of CVD risk.

Polygenic risk for schizophrenia and bipolar disorder in relation to cardiovascular biomarkers

Individuals with schizophrenia and bipolar disorder are at an increased risk of cardiovascular disease (CVD), and a range of biomarkers related to CVD risk have been found to be abnormal in these patients. Common genetic factors are a putative underlying mechanism, alongside lifestyle factors and antipsychotic medication. However, the extent to which the altered CVD biomarkers are related to genetic factors involved in schizophrenia and bipolar disorder is unknown. In a sample including 699 patients with schizophrenia, 391 with bipolar disorder, and 822 healthy controls, we evaluated 8 CVD risk biomarkers, including BMI, and fasting plasma levels of CVD biomarkers from a subsample. Polygenic risk scores (PGRS) were obtained from genome-wide associations studies (GWAS) of schizophrenia and bipolar disorder from the Psychiatric Genomics Consortium. The CVD biomarkers were used as outcome variables in linear regression models including schizophrenia and bipolar disorder PGRS as predictors, age, sex, diagnostic category, batch and 10 principal components as covariates, controlling for multiple testing by Bonferroni correction for the number of independent tests. Bipolar disorder PGRS was significantly (p = 0.03) negatively associated with BMI after multiple testing correction, and schizophrenia PGRS was nominally negatively associated with BMI. There were no other significant associations between bipolar or schizophrenia PGRS, and other investigated CVD biomarkers. Despite a range of abnormal CVD risk biomarkers in psychotic disorders, we only found a significant negative association between bipolar disorder PGRS and BMI. This has previously been shown for schizophrenia PGRS and BMI, and warrants further exploration.

Impact of perinatal factors on biomarkers of cardiovascular disease risk in preadolescent children.

This review aims to summarize associations of the perinatal environment with arterial biophysical properties in childhood, to elucidate possible perinatal origins of adult cardiovascular disease (CVD). A systematic search of PubMed database was performed (December 2020). Studies exploring associations of perinatal factors with arterial biophysical properties in children 12 years old or less were included. Properties studied included: pulse wave velocity; arterial stiffness or distensibility; augmentation index; intima-media thickness of aorta (aIMT) or carotids; endothelial function (laser flow Doppler, flow-mediated dilatation). Two reviewers independently performed study selection and data extraction. Fifty-two of 1084 identified records were included. Eleven studies explored associations with prematurity, 14 explored maternal factors during pregnancy, and 27 explored effects of low birth weight, small-for-gestational age and foetal growth restriction (LBW/SGA/FGR). aIMT was consistently higher in offspring affected by LBW/SGA/FGR in all six studies examining this variable. The cause of inconclusive or conflicting associations found with other arterial biophysical properties and perinatal factors may be multifactorial: in particular, measurements and analyses of related properties differed in technique, equipment, anatomical location, and covariates used. aIMT was consistently higher in LBW/SGA/FGR offspring, which may relate to increased long-term CVD risk. Larger and longer term cohort studies may help to elucidate clinical significance, particularly in relation to established CVD risk factors. Experimental studies may help to understand whether lifestyle or medical interventions can reverse perinatal changes aIMT. The field could be advanced by validation and standardization of techniques assessing arterial structure and function in children.