Cardiovascular Disease Biomarkers Research Articles

Effects of Bariatric Surgery on Blood and Vascular Large Extracellular Vesicles According to Type 2 Diabetes Status.

Large extracellular vesicles (lEVs) enriched for endothelial and blood cell markers are increased in metabolic conditions such as obesity or type 2 diabetes (T2D), actively contribute to the atherosclerotic process, and have been identified as diagnostic and prognostic biomarkers for cardiovascular disease (CVD). Although bariatric surgery (BS) in individuals with obesity is related to decreased cardiovascular (CV) risk and increased life expectancy, after BS these subjects are still at higher CV risk than the general population. We aimed to compare the lEV profiles between individuals with obesity, with or without T2D, before and 1 year after BS, and normal-weight controls. Prospective longitudinal study with individuals eligible for BS, with or without T2D (T2D and OB groups, respectively) and healthy controls (HC group) matched by age and sex. The concentration and phenotype of lEVs were assessed by flow cytometry. The study cohort included 108 individuals (age 48.0 ± 10.5 years; 84.3% females). Before BS, the OB group presented higher concentrations of lEV enriched for endothelial and blood cell biomarkers than the HC group, but lower concentrations than those observed in the T2D group (P < .05). BS resulted in a significant reduction in most of the lEVs enriched for cell-specific markers in both subgroups. lEV differences between OB and T2D groups were no longer observed after BS (P > .05). However, compared with HC group, OB and T2D groups still showed increased concentrations of lEVs enriched for platelet and endothelial cell markers (P < .05). At 1 year after BS, lEV concentrations remain above the physiological range. These abnormalities might contribute to explaining the increased CV risk after BS and underscore the importance of long-term CV risk factor control in post-BS individuals.

Biomarkers of Adverse Cardiovascular Events in Kidney Disease

Based on domestic and international literature the review refers to the analysis of the research data on risk factors and biomarkers for the development of adverse cardiovascular events in patients with chronic kidney disease and acute kidney injury. Biomarker studies are important, especially in the early stages of chronic kidney disease, that is, in patients with creatinine clearance above 60 ml/min/1.73 m2, when preventive and therapeutic measures work more effectively. Among the potential predictors of adverse cardiovascular events, the biomarkers related to the following pathological processes (conditions) should be noted: oxidative stress (malondialdehyde, ischemic-modified albumin; superoxide dismutase), inflammation (interleukin-6, interleukin-18), acute kidney injury (kidney injury molecule 1; neutrophil gelatinase-associated lipocalin), cardiospecific biomarkers (highly sensitive troponin) and circulating microribonucleic acids (specific miRNA-133a, miRNA-21), as well as the prospects for further study of some biomarkers in cardionephrology are discussed. A separate emphasis is placed on the need to establish threshold values for various molecules in chronic kidney disease, depending on the degree of decline in kidney function, which will allow these indicators to be effectively used in clinical practice as diagnostic and prognostic biomarkers for cardiovascular diseases, since their usual reference values are used in the general population, will be higher in kidney disease. Currently, only for troponin and natriuretic peptides, certain reference values are established, which are less clear-cut in the population with chronic kidney disease than in the general population, and for all other biomarkers, cut-off values are not yet known.

Retinal Ischemic Perivascular Lesions in Individuals With Atrial Fibrillation.

Background We previously demonstrated that retinal ischemic perivascular lesions (RIPLs), which are indicative of ischemia in the middle retina, may be a biomarker of ischemic cardiovascular disease. In this study, we sought to determine the relationship between RIPLs and atrial fibrillation, a common source of cardiac emboli. Methods and Results In this case-control study, we identified individuals between the ages of 50 and 90 years who had undergone macular spectral domain optical coherence tomography imaging. Individuals with atrial fibrillation were identified, and age- and sex-matched individuals from the same pool, but without a diagnosis of atrial fibrillation, were selected as controls. Spectral domain optical coherence tomography scans were reviewed by 3 independent and masked observers for presence of RIPLs. The relationship between RIPLs and atrial fibrillation was analyzed using multivariable logistic regression models. There were 106 and 91 subjects with and without atrial fibrillation, respectively. The percentage of subjects with RIPLs was higher in the atrial fibrillation group compared with the control group (57.5% versus 37.4%; P=0.005). After adjusting for age, sex, smoking history, hypertension, diabetes, coronary artery disease, carotid stenosis, stroke, and myocardial infarction, the presence of RIPLs was significantly associated with atrial fibrillation, with an odds ratio of 1.91 (95% CI, 1.01-3.59). Conclusions RIPLs are significantly associated with atrial fibrillation, independent of underlying ischemic heart disease or cardiovascular risk factors. This association may inform the diagnostic cardiovascular workup for individuals with RIPLs incidentally detected on optical coherence tomography scan of the macula.

Protein Biomarkers of Early Menopause and Incident Cardiovascular Disease.

Background Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause with CVD remain poorly characterized. Methods and Results We measured 71 circulating CVD protein biomarkers in 1565 postmenopausal women enrolled in the FHS (Framingham Heart Study). We examined the association of early menopause with biomarkers and tested whether early menopause modified the association of biomarkers with incident cardiovascular outcomes (heart failure, major CVD, and all-cause death) using multivariable-adjusted linear regression and Cox models, respectively. Among 1565 postmenopausal women included (mean age 62 years), 395 (25%) had a history of early menopause. Of 71 biomarkers examined, we identified 7 biomarkers that were significantly associated with early menopause, of which 5 were higher in women with early menopauseincluding adrenomedullin and resistin, and 2 were higher in women without early menopauseincluding insulin growth factor-1 and CNTN1 (contactin-1) (Benjamini-Hochberg adjusted P<0.1 for all). Early menopause also modified the association of specific biomarkers with incident cardiovascular outcomes including adrenomedullin (Pint<0.05). Conclusions Early menopause is associated with circulating levels of CVD protein biomarkers and appears to modify the association between select biomarkers with incident cardiovascular outcomes. Identified biomarkers reflect several distinct biological pathways, including inflammation, adiposity, and neurohormonal regulation. Further investigation of these pathways may provide mechanistic insights into the pathogenesis, prevention, and treatment of early menopause-associated CVD.

Abstract P3021: Circulating Exosomal MicroRNAs As Biomarkers For Pulmonary Embolism

Pulmonary Embolism (PE) is the third leading cause of death worldwide. Current treatment for PE, including thrombolytics and anticoagulants, have serious side effects. Protein and RNA biomarkers presently used to diagnose PE do not have the necessary specificity or sensitivity. Therefore, discovery of predictive biomarkers for therapeutic effects and adverse outcomes is imperative. MicroRNAs (miRNAs) are known to regulate gene expression networks and their expression levels reflect the physiological state of their cell of origin. By investigating these circulating miRNAs, we can gain valuable insight into the state of the damaged cells or tissue. Here, we innovated a novel methodology to isolate exosomes from patient platelet-free plasma that provides better yield of both exosomes and their RNA content. We are the first to stratify the PE patient samples according to clinical severity (low-risk, sub-massive, massive PE) and analyze the correlations of the exosomal miRNA biomarkers with PE severity. We found that exosomes from PE patients are more heterogeneous, lower in concentration and larger in size compared to healthy controls. Further, exosomes from PE patient samples pack more RNA than healthy controls. With the results from ongoing miRNA sequencing, we will be able to identify miRNAs and other short non-coding RNAs as potential diagnostic biomarkers that best correlate with PE severity. Validation and predictive studies using qRT-PCR will push the frontiers on circulating small RNA biomarkers in PE and other cardiovascular diseases. Finally, network analysis on the potential RNA biomarkers will provide information for future studies on disease mechanisms and therapeutics development.

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.

Decoding of miR-7-5p in Colony Forming Unit-Hill Colonies as a Biomarker of Subclinical Cardiovascular Disease-A MERIT Study.

Colony forming unit-Hill (CFU-Hill) colonies were established to serve as a sensitive biomarker for vascular health. In animals, the overexpression of miR-7-5p was shown to be pro-atherogenic and associated with increased cardiovascular disease (CVD) risk. In a MERIT study, we aimed to explore the role of miR-7-5p expression in CFU-Hill colonies in type 1 diabetes mellitus (T1DM) and the effect of metformin in subclinical CVD. The expression of miR-7-5p in CFU-Hill colonies in 29 T1DM subjects without CVD and 20 healthy controls (HC) was measured. Metformin was administered to T1DM subjects for eight weeks. MiR-7-5p was upregulated in T1DM whereas metformin reduced it to HC levels. MiR-7-5p was positively correlated with c-reactive protein, and C-X-C motif chemokine ligand 10. The receiver operating characteristic curve revealed miR-7-5p as a biomarker of CVD, and upregulated miR-7-5p, defining subclinical CVD at a HbA1c level of 44.3 mmol/mol. Ingenuity pathway analysis predicted miR-7-5p to inhibit the mRNA expression of Krüppel-like factor 4, epidermal growth factor receptor, insulin-like growth factor 1 receptor, v-raf-1 murine leukemia viral oncogene homolog 1 and insulin receptor substrate ½, and insulin receptor, while metformin activated these miRNAs via transforming growth factor-β1 and Smad2/3. We proved the pro-atherogenic effect of miR-7-5p that maybe used as a prognostic biomarker.

Ceramides as risk markers for future cardiovascular events and all-cause mortality in long-standing type 1 diabetes.

Ceramides are lipid molecules involved in inflammation-related signaling. Recent studies have shown that higher amounts of specific circulating ceramides and their ratios are associated with future development of cardiovascular (CV) disease (CVD). We examined the associations between serum ceramide levels with CVD, kidney failure, and all-cause mortality in individuals with longstanding type 1 diabetes (T1D). We included 662 participants with T1D and 6-year follow-up, with a mean age of 55 years and mean diabetes duration of 33 years. Baseline serum samples were analyzed using liquid chromatography-mass spectrometry. Six predefined ceramide levels were measured, and predefined ratios were calculated. Adjusted Cox regression analyses on ceramide levels in relation to future CV events (CVE), kidney failure and all-cause mortality were performed, with and without adjustment for age, sex, BMI, LDL, triglycerides, systolic blood pressure, HbA1C, history of CVD, smoking status, statin use, eGFR and UAER. The ceramide ratio cer(d18:1/18:0)/cer(d18:1/24:0) was significantly associated with risk of CVE (HR = 1.33, P = 0.01) and all-cause mortality (HR = 1,48, P = 0.01) before and after adjustments. All five investigated ceramide ratios were associated with kidney failure, before adjusting for the kidney markers eGFR and UAER. In this study we demonstrate specific ceramides and ratios associated with 6-year cardiovascular risk and all-cause mortality in a T1D cohort. This highlights the strength of ceramide association with vascular complications and presents a new potential tool for early risk assessment if validated in other cohorts.

Low catestatin as a risk factor for cardiovascular disease - assessment in patients with adrenal incidentalomas.

Catestatin (Cts) is a peptide derived from proteolytic cleavage of chromogranin A, which exhibits cardioprotective and anti-inflammatory properties. Cts has been proposed as a potential biomarker for cardiovascular (CV) disease. examining Cts in patients with incidentally discovered adrenocortical adenomas (AI), and its associations with CV risk factors and blood pressure (BP). In this cross-sectional study, 64 AI patients without overt CV disease other than primary hypertension were recruited along with 24 age-, sex-, and body-mass-index (BMI)-matched controls with normal adrenal morphology. Laboratory, 24-h ambulatory BP monitoring, echocardiography, and common carotid artery sonography examinations were performed. Unadjusted Cts was higher in AI patients (median 6.5, interquartile range: 4.9-37 ng/ml) versus controls (4.5 (3.5 - 28)), p=0.048, however, the difference was insignificant after adjusting for confounding variables. Cts was lower in subjects with metabolic syndrome than in those without it (5.2 (3.9- 6.9) vs. 25.7 (5.8-115) ng/ml, p<0.01), and in men compared to women (4.9 (4-7.4) ng/ml vs. 7 (4.8-100), p=0.015). AI patients in the lower half of Cts levels compared to those in the upper had a higher prevalence of hypertension (OR 0.15, 95% CI: 0.041-0.5, p<0.001) and metabolic syndrome (OR 0.15, 95% CI 0.041-0.5, p<0.001). In AI patients Cts correlated positively with high-density lipoprotein cholesterol (Spearman's r=0.31), negatively with BMI (r=-0.31), and 10-year atherosclerotic CV disease risk (r=-0.42). Our data indicate associations between CV risk factors and Cts. More clinical research is needed to apply serum Cts as a biomarker.

Research progress of non-coding RNA in atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia in clinic, and its incidence is increasing year by year. In today's increasingly prevalent society, ageing poses a huge challenge to global healthcare systems. AF not only affects patients' quality of life, but also causes thrombosis, heart failure and other complications in severe cases. Although there are some measures for the diagnosis and treatment of AF, specific serum markers and targeted therapy are still lacking. In recent years, ncRNAs have become a hot topic in cardiovascular disease research. These ncRNAs are not only involved in the occurrence and development of AF, but also in pathophysiological processes such as myocardial infarction and atherosclerosis, and are potential biomarkers of cardiovascular diseases. We believe that the understanding of the pathophysiological mechanism of AF and the study of diagnosis and treatment targets can form a more systematic diagnosis and treatment framework of AF and provide convenience for individuals with AF and the society.

Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis.

Fewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases, tissue-entrapped EVs are associated with early mineralization, but their cargoes, functions, and contributions to disease remain unknown. Disease stage-specific proteomics was performed on human carotid endarterectomy specimens (n=16) and stenotic aortic valves (n=18). Tissue EVs were isolated from human carotid arteries (normal, n=6; diseased, n=4) and aortic valves (normal, n=6; diseased, n=4) by enzymatic digestion, (ultra)centrifugation, and a 15-fraction density gradient validated by proteomics, CD63-immunogold electron microscopy, and nanoparticle tracking analysis. Vesiculomics, comprising vesicular proteomics and small RNA-sequencing, was conducted on tissue EVs. TargetScan identified microRNA targets. Pathway network analyses prioritized genes for validation in primary human carotid artery smooth muscle cells and aortic valvular interstitial cells. Disease progression drove significant convergence (P<0.0001) of carotid artery plaque and calcified aortic valve proteomes (2318 proteins). Each tissue also retained a unique subset of differentially enriched proteins (381 in plaques; 226 in valves; q<0.05). Vesicular gene ontology terms increased 2.9-fold (P<0.0001) among proteins modulated by disease in both tissues. Proteomics identified 22 EV markers in tissue digest fractions. Networks of proteins and microRNA targets changed by disease progression in both artery and valve EVs revealed shared involvement in intracellular signaling and cell cycle regulation. Vesiculomics identified 773 proteins and 80 microRNAs differentially enriched by disease exclusively in artery or valve EVs (q<0.05); multiomics integration found tissue-specific EV cargoes associated with procalcific Notch and Wnt signaling in carotid arteries and aortic valves, respectively. Knockdown of tissue-specific EV-derived molecules FGFR2, PPP2CA, and ADAM17 in human carotid artery smooth muscle cells and WNT5A, APP, and APC in human aortic valvular interstitial cells significantly modulated calcification. The first comparative proteomics study of human carotid artery plaques and calcified aortic valves identifies unique drivers of atherosclerosis versus aortic valve stenosis and implicates EVs in advanced cardiovascular calcification. We delineate a vesiculomics strategy to isolate, purify, and study protein and RNA cargoes from EVs entrapped in fibrocalcific tissues. Integration of vesicular proteomics and transcriptomics by network approaches revealed novel roles for tissue EVs in modulating cardiovascular disease.

&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.

A universal boronate affinity capture-antibody-independent lateral flow immunoassay for point-of-care glycoprotein detection

Protein glycosylation and other post-translational modifications are involved in many biological processes including growth, development and immune responses, and glycoproteins are also known as biomarkers for cancer, diabetes and cardiovascular diseases. In traditional lateral flow immunoassay (LFIA) for glycoprotein detection, capture antibody (CA) is often required to label targets. However, the production of CA is complicated and expensive, restricting the wide application of LFIA. In this study, we developed a universal boronate affinity CA-independent LFIA method for glycoprotein detection. 4-Mercaptophenylboronic acid (4-MPBA)-modified Au nanoparticles (namely 4-MPBA-AuNPs) were used as LFIA labels, which could generate colorimetric signal and showed outstanding capability to bind glycoprotein. Compared with CA, 4-MPBA molecular as a glycoprotein recognition element had more prominent advantages, e.g., low cost, easy availability and good quality controllability. Take carcinoembryonic antigen (CEA) as model glycoprotein, the limit of detection of this CA-independent LFIA was 1.25 ng/mL by naked eyes, which was 8-fold lower than conventional CA-dependent sandwich LFIA. Significantly, the developed 4-MPBA-AuNPs-based CA-independent LFIA successfully detected 23 CEA-positive samples from 64 suspected human serum samples within 50 min in a nonlaboratory environment, with a 100% accuracy compared to clinical detection method. Therefore, this diagnostic platform could provide an effective tool for point-of-care glycoprotein detection with excellent reproducibility and high specificity.

Endothelial Glycocalyx Integrity in Treatment-Naïve People Living with HIV before and One Year after Antiretroviral Treatment Initiation.

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed EG at baseline, 24 (±4) and 48 (±4) weeks, by measuring the perfused boundary region (PBR, inversely proportional to EG thickness), in sublingual microvessels. In total, 66 consecutive PLWH (60 (90.9%) males) with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40(60.6%) received INSTI-based regimens. The mean (standard deviation) PBR decreased significantly from 2.17 (0.29) μm at baseline to 2.04 (0.26) μm (p = 0.019), and then to 1.93 (0.3) μm (p < 0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. PLWH on INSTIs had a significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low levels of viremia experienced the greatest PBR reduction. This study is the first to report the benefit of antiretroviral treatment on EG improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH.

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm.

Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of -0.092 (-0.148, -0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: -0.128 (-0.212, -0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD.ClinicalTrials.gov Identifier: NCT03703947.

Diabetes and associated cardiovascular complications: The role of microRNAs

Diabetes mellitus (DM) refers to a complex cluster of metabolic disorders characterized by hyperglycemia caused by inadequate insulin secretion, insulin resistance, or excessive glucagon secretion. If not correctly treated, the prolonged effects of DM-associated metabolic perturbations lead to systemic vascular complications and cardiovascular disease (CVD), the principal cause of mortality among patients with DM. Given the increase in the global prevalence of diabetes, novel diagnostic and therapeutic procedures are necessary for its effective identification and treatment. Recent findings point to an important role of microRNA (miRNAs) in DM initiation and progression, as well as the occurrence of associated cardiovascular complications. miRNAs are short, highly conserved, single-stranded, non-coding RNAs that contribute to the maintenance of physiological homeostasis through the regulation of crucial processes such as metabolism, cell proliferation, and apoptosis. The increased availability of high-throughput methodologies for identifying and characterizing non-coding RNAs has led to considerable interest in miRNAs as potential biomarkers and therapeutic agents for DM. In this review, we first comprehensively detail the regulatory miRNAs involved in the pathophysiology of DM and diabetic cardiomyopathy (DCMP). Subsequently, we summarize findings regarding the utility of several of these miRNAs as potential prognostic and diagnostic biomarkers for DM and DM-associated CVD. Finally, we evaluate the potential of miRNA-based therapeutic approaches for treating DM and DCMP in the clinical setting.

Evaluation of primary hemodynamic parameters using in-house developed flexible microstructured pressure sensor

Noninvasive measurement of arterial pulse provides information about the heart condition through the evaluation of primary hemodynamic parameters such as blood pressure (BP), pulse rate (PR), and pulse regularity. Moreover, BP is one of the most important biomarkers of cardiovascular disease, mainly hypertension. To prevent this, accurate measurement of BP becomes necessary. Currently, flexible pressure sensors have drawn a lot of interest due to their prospective applications in wearable devices for healthcare monitoring. We have collected the human oscillometric pulse by a polymer-based flexible capacitive pressure sensor and calculated the BP as well as PR using the maximum amplitude algorithm. The results are compared with a pre-calibrated oscillometric BP monitor available in the market. Based on the error criteria, the device followed the universal standard. In addition, the flexibility and high accuracy of the device result in the assessment of the possible medical applications, including abnormal pulse rates such as tachycardia or bradycardia and irregular heart rhythm such as cardiac arrhythmia.

Pre-diagnosis lipid levels and mortality after obesity-related cancer diagnosis in the Women's Health Initiative cardiovascular disease biomarker cohort.

Published studies have demonstrated inconclusive relationships between serum lipid levels and mortality after cancer. The primary objective was to evaluate the relationship between fasting lipid levels and mortality after cancer. Data were obtained on baseline lipids and outcomes after cancer from 1263 postmenopausal women diagnosed with 13 obesity-related cancers who were part of the Women's Health Initiative (WHI) lipid biomarkers cohort. Obesity-related cancers included incident invasive cancers of the breast, colorectum, endometrium, esophagus (adenocarcinoma), kidney, liver, gallbladder, pancreas, ovaries, small intestine, thyroid, stomach, as well as multiple myeloma. Baseline lipid measurements included high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and non-HDL-cholesterol. Outcomes were all cause, cancer-specific, and CVD mortality. Multivariable Cox proportional hazards models were used to measure associations between lipid levels and mortality (all cause, cancer, and CVD) after a cancer diagnosis, with lipids analyzed as continuous variables. Among women with obesity-related cancer, there were 707 deaths, of which 379 (54%) were due to cancer and 113 (16%) were due to CVD. Mean time from blood draw to cancer diagnosis was 5.1 years (range: 0.05-10 years). LDL-C values above the 95th percentile were associated with higher risk of all-cause mortality (p < 0.001), and cancer-specific mortality (p < 0.001), but not mortality due to CVD. Non-HDL-C values above the 65th percentile were associated with higher risk of all-cause mortality (p = 0.01) and mortality due to CVD (p = 0.003), but not cancer-specific mortality (p = 0.37). HDL-C values above the 95th percentile were associated with lower all-cause mortality (p = 0.002), and above the 65th percentile with lower cancer-specific mortality (p = 0.003), but no significant relationship with mortality due to CVD was observed. The relationship between pre-diagnosis fasting lipid levels and mortality after cancer diagnosis is complex. These results suggest that improved lipid control through lifestyle and anti-lipid medications could have a meaningful impact on outcomes after cancer.

1148-P: Glycoprotein Acetyls (GlycA) Associate with Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance (IR) in Youth with Type 1 Diabetes (T1D)

GlycA is a biomarker of systemic inflammation and cardiovascular disease, yet little is known about this biomarker in T1D. We examined the associations among GlycA, central adiposity, IR, and early kidney injury in adolescents with T1D. Glomerular filtration rate (GFR) and renal plasma flow (RPF) by iohexol and p-aminohippurate clearance, respectively, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry (DXA), and estimated insulin sensitivity (eIS) by the CACTI equation were assessed in youth with T1D (n=50, 16.0±3.0 years, 50% female, HbA1c 8.7±1.3%, T1D duration 5.7±2.6 years, UACR 6 [5-14] mg/g, GFR 189±40 mL/min). Intraglomerular pressure (PGLO) was estimated by the Gomez equations. Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. GlycA was higher in girls vs. boys (1.05±0.26 vs. 0.84±0.15 mmol/L, p=0.001), and in participants who were overweight or obese vs. normal weight (1.12±0.23 vs. 0.87±0.20, p=0.0004). GlycA correlated positively with estimated PGLO (r=0.52, p=0.001), UACR (r=0.53, p&amp;lt;0.0001) and trunk mass (r=0.45, p=0.001) and negatively with eIS (r=-0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and HbA1c. In youth with T1D, GlycA, a biomarker of inflammation, was found to be higher in girls with T1D and those of overweight/obese habitus, compared to boys with T1D. Additionally, GlycA associated with parameters of early kidney dysfunction, central adiposity, and IR. Disclosure T.Reinicke: None. S.Gross: None. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. T.B.Vigers: None. L.Pyle: None. L.Driscoll: None. F.H.Mahmud: None. A.Dart: None. M.E.Pavkov: None. R.G.Nelson: None. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. A.Caldwell-mcgee: None. C.Birznieks: None. D.Carrasco: None. M.Marcovecchio: None. K.J.Nadeau: None. K.L.Tommerdahl: None. M.Pauley: None. J.K.Snell-bergeon: None. Funding Junior Research Fellowship Award

Optical Nanobiosensor-Based Point-of-Care Testing for Cardiovascular Disease Biomarkers.

Cardiovascular disease is a global health threat, and detecting cardiac biomarkers is essential for early-stage diagnosis and personalized treatment. Traditional approaches have limitations, but optical nanobiosensors offer rapid, highly selective, and sensitive detection. Optical nanobiosensors generate biosignals that transfer light signals while analytes bind with the bioreceptors. Optical nanobiosensors have advantages such as ease of monitoring, low cost, a wide detection range, and high sensitivity without any interference. An optical nanobiosensor platform is a promising approach for point-of-care cardiac biomarker detection with a low detection limit. This review mainly focuses on the detection of cardiovascular disease biomarkers based on various optical nanobiosensor approaches that have been reported during the last five years, and we have categorized them based on optical signal readouts. A detailed discussion of the classification of cardiovascular disease biomarkers, design strategies of optical biosensors, types of optically active nanomaterials, types of bioreceptors, functionalization techniques, various assay types, and sensing mechanisms is presented. Then, we summarize the optical signaling readout-based various nanobiosensors systems for the detection of cardiovascular disease biomarkers. Finally, we summarize and conclude with the recent development of point-of-care testing (PoCT) for cardiovascular disease biomarkers used in various optical readout techniques.