CVD Biomarkers Research Articles

Retina and Deep Learning-Based CVD Biomarker in Patients with Varying eGFR Levels: Data from the UK Biobank

Retina and Deep Learning-Based CVD Biomarker in Patients with Varying eGFR Levels: Data from the UK Biobank

Sphingomyelins of Local Fat Depots and Blood Serum as Promising Biomarkers of Cardiovascular Diseases.

The study analyzed samples of subcutaneous, epicardial, perivascular adipose tissue (SAT, EAT, PVAT, respectively) received from 30 patients with CAD and 30 patients with AVHD. Sphingomyelin spectrum of the blood serum was assessed using a high-resolution chromatography-mass spectrometric complex (liquid chromatograph of the Agilent 1200 series (Agilent Technologies, USA) with a maXis impact mass spectrometric detector (Bruker Daltonics, Germany)). Determination of the levels of sphingomyelins (SM) in adipose tissue samples was conducted by high performance liquid chromatography with mass spectrometric detection in the mass/charge ratio range from 100 to 1700. Consistent sphingomyelin spectrum of local fat depots and blood serum was revealed in CAD and AVHD. However, the content of SM varied: in CAD, a specific enhancement of SM in epicardial adipose tissue was observed compared to subcutaneous and perivascular localization. In AVHD, PVAT was characterized by a statistically significant increase in the levels of all SM relative to EAT. Almost all measured SM types in the serum of patients with CAD were higher than the levels in the AVHD group. Established associations of indicators of the sphingomyelin profile of adipose tissue and blood serum with clinical and instrumental indicators in CVD indicate the relationship between the metabolism of SM in adipose tissue of cardiac localization and disorders of systolic and diastolic function of the LV in patients with CVD, multivessel coronary disease in CAD and allow the use of SM as promising biomarkers of CVD. However, further research is needed to clarify the nature of these relationships.

A-374 Analytical Performance Assessment and Comparison of Point of Care Testing (POCT) Devices for Blood Lipids Measurements

Abstract Background Cardiovascular diseases (CVDs) are the leading cause of death in the U.S. and worldwide. According to the World Health Organization (WHO), worldwide, 85% of CVD deaths are due to heart disease and strokes, and over 75% occur in low- and middle-income countries (LMICs). Early detection and treatment are key to preventing the consequences of CVD. Point-of-care testing (POCT) devices offer alternatives to screening large populations for CVD risk. Although POCT are increasingly used for screening, only few information is available about their accuracy and reliability. Methods Eight POCT devices for blood lipids that previously successfully participated in the CDC CVD Biomarker Standardization Programs were used in this preliminary study. The analytical performance for all eight devices was assessed using split sample comparisons to the CDC reference measurement procedures for measurements performed in whole blood (WB) and serum. Specifically, the accuracy of total cholesterol (TC) was determined in WB and serum. The accuracy of high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c) was determined in serum. The precision of TC, HDL-c, LDL-c, and triglycerides (TG) was determined in WB and serum. Results The reference values of the specimens from 20 donors ranged between 154–279 mg/dL, 36.9–109 mg/dL, and 71.1–182 mg/dL for TC, HDL-c, and LDL-c in serum, and between 145–210 mg/dL for TC in WB. Preliminary assessments found that the mean bias for each instrument ranged from -7.86%–13.82% and from -11.90%–3.24% for TC in WB and serum, respectively. For serum HDL-c samples, the mean bias ranged from −6.81%–15.43%. The mean bias for serum LDL-c samples ranged from −22.40% to 3.08%. For three devices, approximately 30% of the WB measurements and approximately 50% of the serum measurements were reported as outside of the measurement range. The mean imprecision for each instrument ranged from 2.2%–13.75% and from 1.88%–11.76% for TC in WB and serum, respectively. For HDL-c, the mean imprecision ranged from 5.36%–23.21% and from 2.30% to 26.69% in WB and serum, respectively. The mean imprecision ranged from 4.82%–20.34% and from 3.06%–20.54% for LDL-c in WB and serum, respectively. For TG, the mean imprecision ranged from 5.78%–23.91% and from 1.71%–11.02% in WB and serum, respectively. Conclusion These preliminary findings about the analytical performance of POCT devices indicate notable differences in accuracy and precision for lipids measured in WB and serum, with serum measurements being more likely within performance requirements than WB measurements. Some devices appear to be more likely to report values outside the measurement range even though reference values are within the measurement range of the device. Further studies to verify these preliminary findings with more individual donor samples are underway.

<i>Apium graveolens</i> 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 < 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.

1813-PUB: Cardiorenal Effect of Dapagliflozin and Dapagliflozin-Saxagliptin Combination on CD34+ve Hematopoietic Stem Cells (HSCs) and Podocyte Specific Markers in Type 2 Diabetes Subjects

Introduction: Effect of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34+ HSCs as a cellular CVD biomarker. Both Dapa (a SGLT2 receptor inhibitor) and Saxagliptin (a DPP4 enzyme inhibitor) are T2DM meds, but the combo has not been evaluated for cardio-renal risk. Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial. Methods: 15 subjects were enrolled in 16 weeks, double-blind, three-arm, randomized placebo matched trial, with 10mg Dapa + Saxa placebo (n=4), 10 mg Dapa + 5 mg Saxa (n=5) Combo, And Dapa placebo + Saxa placebo (n=6), Placebo groups. T2DM (30-70 yrs) with HbA1c of 7-10%, were included. CD34+ HSC number, migration, mRNA expression along with biochemistry and urine exosomes were measured. Data were collected at wks 0, 8, and 16. For stats, a mixed model regression analysis was used. Results: Significant HbA1c (p=0.0357) reduction was noted in Combo group vs Dapa alone and Placebo. hsCRP levels (P=0.0317) and IL-6, two important inflammatory molecules, were significantly reduced in both Dapa and Combo vs Placebo. Leptin levels decreased significantly in both Dapa alone (p=0.035) and Combo group (p=0.015), vs Placebo, however the Adiponectin levels were higher in Dapa alone group. EPC migration improved significantly in both Dapa alone (p=0.05) and Combo group (p=0.05) vs Placebo. Interestingly, urine exosome-based podocyte specific protein such as podocalyxin was actually higher in Combo vs Control. Conclusions: Several parameters showed significant improvement with both Dapa and Combo vs placebo. However, other than glycemic control Combo didn’t offer any further benefit over Dapa alone in terms of HSC and biochemistry. Moreover, the Combo may have deleterious effect on renal podocyte inflammation which needs to be examined in a larger study. Disclosure S.Nandula: None. S.Sen: None.

Abstract 691: Cardio-renal Effect Of Dapagliflozin Alone Versus Dapagliflozin- Saxagliptin Combination In Type 2 Diabetes (t2dm) Subjects

Introduction: Effect of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34+ HSCs as a cellular CVD biomarker. Both Dapa (a SGLT2 receptor inhibitor) and Saxagliptin (a DPP4 enzyme inhibitor) are T2DM meds, but the combo has not been evaluated for cardio-renal risk. Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial. Methods: 15 subjects were enrolled in 16 weeks, double-blind, three-arm, randomized placebo matched trial, with 10mg Dapa + Saxa placebo (n=4), 10 mg Dapa + 5 mg Saxa (n=5) Combo, And Dapa placebo + Saxa placebo (n=6), Placebo groups. T2DM (30-70 yrs) with HbA1c of 7-10%, were included. CD34+ HSC number, migration, mRNA expression along with biochemistry and urine exosomes were measured. Data were collected at wks 0, 8, and 16. For stats, a mixed model regression analysis was used. Results: Significant HbA1c (p=0.0357) reduction was noted in Combo group vs Dapa alone and Placebo. hsCRP levels (P=0.0317) and IL-6, two important inflammatory molecules, were significantly reduced in both Dapa and Combo vs Placebo. Leptin levels decreased significantly in both Dapa alone (p=0.035) and Combo group(p=0.015), vs Placebo, however the Adiponectin levels were higher in Dapa alone group. EPC migration improved significantly in both Dapa alone (p=0.05) and Combo group (p=0.05) vs Placebo. Interestingly, urine exosome-based podocyte specific protein such as podocalyxin was actually higher in Combo vs Control. Conclusions: Several parameters showed significant improvement with both Dapa and Combo vs placebo. However, other than glycemic control the Combo didn’t offer any further benefit over Dapa alone in terms of HSC, biochemistry and podocyte markers. Of note, the combination may have deleterious effect on renal podocyte inflammation which needs to be examined in a larger study.

Clinical, nutritional, and quality assessment of flaxseeds and their supplemented muffins

ABSTRACT This study aimed to explore whether flaxseed could be used to ameliorate various CVD biomarkers. In the first phase, flaxseed’s nutritional composition was performed. In the second phase, a 32-day efficacy trial was conducted on 20 Sprague Dawley rats. All physical and biochemical tests were performed on the initial and final days. Results revealed that blood glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced, whereas high-density lipoprotein cholesterol, hematocrit, haemoglobin, red blood cells, and platelets were increased. Having significant clinical findings, a marketable flaxseed-supplemented muffin recipe was developed using flaxseed-supplemented flour at 0%, 5%, 10%, 12%, and 20%. Farinographic investigations of flaxseed-supplemented flour revealed its improved baking potential through more excellent water absorption and dough development time. The flaxseed-supplemented muffins revealed a significant rise of 15% in protein, 60% in fiber, 23% in ash, 60% in healthy vegetative fats and sensorial parameters.

Circulating Small Noncoding RNA Profiling as a Potential Biomarker of Atherosclerotic Plaque Composition in Type 1 Diabetes.

Cardiovascular disease (CVD) accounts for most deaths in patients with type 1 diabetes (T1D); however, the determinants of plaque composition are unknown. miRNAs regulate gene expression, participate in the development of atherosclerosis, and represent promising CVD biomarkers. This study analyzed the circulating miRNA expression profile in T1D with either carotid calcified (CCP) or fibrous plaque (CFP). Circulating small noncoding RNAs were sequenced and quantified using next-generation sequencing and bioinformatic analysis in an exploratory set of 26 subjects with T1D with CCP and in 25 with CFP. Then, in a validation set of 40 subjects with CCP, 40 with CFP, and 24 control subjects with T1D, selected miRNA expression was measured by digital droplet PCR. Putative gene targets enriched for pathways implicated in atherosclerosis/vascular calcification/diabetes were analyzed. The patients' main clinical characteristics were also recorded. miR-503-5p, let-7d-5p, miR-106b-3p, and miR-93-5p were significantly upregulated, while miR-10a-5p was downregulated in patients with CCP compared with CFP (all fold change >±1.5; P < 0.05). All candidate miRNAs showed a significant correlation with LDL-cholesterol, direct for the upregulated and inverse for the downregulated miRNA, in CCP. Many target genes of upregulated miRNAs in CCP participate in osteogenic differentiation, apoptosis, inflammation, cholesterol metabolism, and extracellular matrix organization. These findings characterize miRNAs and their signature in the regulatory network of carotid plaque phenotype in T1D, providing new insights into plaque pathophysiology and possibly novel biomarkers of plaque composition.

Cardiovascular biomarkers in pregnancy with diabetes and associations to glucose control

AimCardiovascular disease (CVD) is a leading cause of death in both men and women. Type 1 and 2 diabetes mellitus (DM1 and DM2) are well-known risk factors for CVD. In addition, gestational diabetes mellitus (GDM) is a female sex-specific risk factor for CVD. Here, we measure circulating concentrations of cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) during pregnancy—a window of time often referred to as a cardiovascular stress test for women.MethodsThis study utilized data from 384 pregnant women: 64 with DM1, 16 with DM2, 35 with GDM and 269 euglycemic controls. Blood was predominantly sampled within a week before delivery. Cardiovascular biomarker concentrations were measured in serum using electrochemiluminescence immunoassay.ResultCirculating cTnT levels were higher in women with DM1, DM2 and GDM as compared to controls, whereas NT-proBNP and GDF-15 levels were only increased in women with DM1. Glucose dysregulation, assessed by third trimester HbA1c levels, positively correlated with all three CVD biomarker levels, whereas pregestational body mass index correlated negatively with GDF-15.ConclusionsOur results support the presence of myocardial affection in women with diabetic disorders during pregnancy. Although pregestational DM1 in this study was associated with the most adverse CVD biomarker profile, women with GDM displayed an adverse cTnT profile similar to what we found in women with pregestational DM2. This supports that women with GDM should be offered long-term intensified cardiovascular follow-up and lifestyle advice following delivery, similarly to the well-established CV follow-up of women with pregestational DM.

Sexual dimorphism in testosterone programming of cardiomyocyte development in sheep.

Perturbed in utero hormone milieu leads to intrauterine growth retardation (IUGR), a known risk factor for left ventricular (LV) dysfunction later in life. Gestational testosterone (T) excess predisposes offspring to IUGR and leads to LV myocardial disarray and hypertension in adult females. However, the early impact of T excess on LV programming and if it is female specific is unknown. LV tissues were obtained at day 90 gestation from days 30-90 T-treated or control fetuses (n = 6/group/sex) and morphometric and molecular analyses were conducted. Gestational T treatment increased cardiomyocyte number only in female fetuses. T excess upregulated receptor expression of insulin and insulin-like growth factor. Furthermore, in a sex-specific manner, T increased expression of phosphatidylinositol 3-kinase (PI3K) while downregulating phosphorylated mammalian target of rapamycin (pmTOR)-to-mTOR ratio suggestive of compensatory response. T excess 1) upregulated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), markers of stress and cardiac hypertrophy and 2) upregulated estrogen receptors1 (ESR1) and 2 (ESR2), but not in androgen receptor (AR). Thus, gestational T excess upregulated markers of cardiac stress and hypertrophy in both sexes while inducing cardiomyocyte hyperplasia only in females, likely mediated via insulin and estrogenic programming.NEW & NOTEWORTHY The present study demonstrates sex-specific effects of gestational T excess between days 30 and 90 of gestation on the cardiac phenotype. Furthermore, the sex-specific programming is likely secondary to perturbation in both estrogen and insulin signaling pathways collectively. These findings are supportive of the role of androgen excess to serve as early biomarkers of CVD and could be critical in identifying therapeutic targets for LV hypertrophy and predict long-term CVD.

The association between plasma biomarkers, p‐tau181, glial fibrillary acidic protein, and neurofilament light and clinical AD risk: Results from prospective cohort study followed over 17 years

AbstractBackgroundPlasma biomarkers for Alzheimer’s disease (AD) have emerged as the future of AD prescreening measures and/or clinical risk assessment. In order to confirm clinical utility of plasma biomarkers, further validation in longitudinal cohort studies is necessary. Therefore, the aim of this study was to investigate the relationship between plasma biomarkers, phosphorylated tau (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) and incident clinical Alzheimer’s disease diagnosis in a community‐based cohort study prospectively followed over 17 years. Secondarily, disease specificity of these biomarkers was assessed with comparison to vascular (VD) and mixed dementia (MD), and the impact of fatal CVD risk on plasma biomarker prediction was explored.MethodP‐tau181, GFAP, and NfL concentration in plasma taken at baseline was measured using the SimoaTM HD‐X Analyzer and the 10‐year risk of fatal CVD using the Systematic Coronary Risk Evaluation (SCORE) was determined in 145 participants diagnosed with AD, 66 participants with VD, and 50 participants with MD during 17 years of follow‐up and 507 participants without dementia diagnosis. Cox regression models adjusted for age, sex, and education were used to assess the association between the plasma biomarker levels and risk of incident dementia subtypes.ResultHigher plasma levels of p‐tau181 and NfL were significantly associated to higher risk of AD development within the first nine years of follow‐up (p‐tau181, p=.02; NfL, p=.01) and were most elevated in AD cases in the first five years of follow‐up, however lacked associations between 9‐17 years. Contrastingly, GFAP levels were consistently elevated in AD cases and significant associations to higher AD risk were evident throughout the 17‐year follow‐up. NfL and GFAP levels additionally exhibited associations to a higher risk of VD and MD; while p‐tau181 did not. Significant interactions between fatal CVD risk and biomarker levels were evident for AD (p‐tau181, p=.03; NfL, p=.01).ConclusionHigher plasma p‐tau181 and NfL levels were associated with higher AD risk within nine years, while higher GFAP levels with higher AD risk consistently throughout 17 years. Plasma levels of p‐tau181 and NfL may be more suited to short‐term AD risk stratification; while GFAP may add important long‐term disease risk information.

MO009ROLE OF GDF-15, YKL-40, AND MMP-9 IN PATIENTS WITH ESKD: FOCUS ON SEX SPECIFIC ASSOCIATIONS WITH VASCULAR OUTCOMES AND ALL-CAUSE MORTALITY

Abstract Background and Aims This study was performed on behalf of the GOING-FWD Consortium. The importance of sex difference in the development of cardiovascular complications is well appreciated, however, further studies are warranted to assess if sex specific pathophysiological changes occur under uremic environment. Little is known about the relationship between the uremic phenotype and novel cardiovascular biomarkers like growth differentiation factor 15 (GDF-15), cartilage glycoprotein 39 (YKL-40), and matrix metalloproteinase 9 (MMP9), and if they have a sex specific effects in relation to inflammation, vascular remodelling, cardiovascular outcomes and all-cause mortality. Therefore, we hypothesise that there is a sex specific relationship between GDF-15, YKL-40, MMP9 and vascular outcomes defined as athero-/arteriosclerosis and vascular calcification. Method ESKD patients (n = 231), males (n = 152) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective CKD cohorts from the Division of Renal Medicine, Karolinska University Hospital, Sweden. Three putative CVD biomarkers, GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay (ELISA) kits. Biomarker level/activity was analysed in the context of gut microbiota derived TMAO, vascular calcification (determined as CAC score on CT scans, aortic valve calcification (AVC) and medial calcification on epigastric artery biopsies), inflammatory response, oxidative stress and all-cause mortality. Results The levels of investigated biomarkers have not differed between female and male patients with ESKD. However, GDF-15 correlated with TMAO in females from more severe cohort that are not receiving renal replacement therapy yet, whereas in males increased GDF-15 level was associated with higher Agatston score on CT-scans, inflammatory biomarker (IL-6) and oxidative stress biomarker 8-OHdG. None of biomarkers was related to intimal medial calcification assessed in epigastric artery biopsies. Comorbidity analysis revealed elevated GDF-15 levels in both females and males, while increased MMP-9 levels were observed only in females with diabetes mellitus, but not with CVD. When assessing death of any cause in our cohorts, both deceased males and females had higher GDF-15 concentration (p = 0.01 and p &amp;lt; 0.001, respectively), meanwhile only YKL-40 level was increased in deceased males (p = 0.02). Conclusion In summary, here we report that in males GDF-15 and YKL-40 were related to vascular calcification, inflammageing and oxidative stress, while in females the relationship of GDF-15 with TMAO was observed. Higher MMP-9 level was seen in males without diabetes and in females with confirmed diabetes mellitus. YKL-40 increase in males and GDF-15 in both males and females were associated with all-cause mortality. Our findings suggest that sex specific associations exist and those could have a potential to affect development of cardiovascular complications in patients with ESKD.

Comparing the educational gradients in three cardiovascular disease-specific health measures

Less-educated persons have worse cardiovascular health. We compare the educational gradients in three disease-specific health measures (biomarkers, self-reported doctors’ diagnoses and cause-specific mortality) in order to compare their relevance in different stages of the disease process. We study 14,102 people aged 50–89 from the US Health Retirement Study (HRS) in the period 2006–17. We use six CVD biomarkers (systolic/​diastolic blood pressure, ratio total/HDL cholesterol, C-reactive protein, body mass index, HbA1c) and two self-reported doctors’ diagnoses (stroke, heart attack). We estimate the gradient in biomarkers using log-binomial regression and the hazard of diagnoses and CVD mortality with Cox survival models. Among those without pre-diagnosed CVD conditions, the educational gradient in mortality is highest (RR 1.97), the gradient for those who receive a CVD diagnosis is in the middle (RR 1.46), and the gradient in biomarkers is lowest (RR 1.32). Among those with recent/​older diagnoses, the biomarker gradient is comparable to levels among the non-diagnosed, while the mortality gradient is much lower (RR 1.35). The gradients in diagnoses and mortality are only slightly explained by differences in biomarkers. The comparison of the three gradients and the mediation analysis suggest that in each of the steps to diagnosis and death there are social factors involved that increase the gradient and go beyond what biomarkers can predict. Having a CVD diagnosis leads to smaller mortality gradients, presumably because of the convergence of educational differences in behaviour and during treatment and monitoring. Our findings support prevention as a strategy against social inequalities in CVD.

Modification of vitamin B6 on the associations of blood lead levels and cardiovascular diseases in the US adults

BackgroundCardiovascular disease (CVD) is a leading cause of death in the US population. Lead exposure is an important risk factor of CVDs, as is associated with elevated homocysteine level and...

A community feasibility study of a cooking behavior intervention in African-American adults at risk for cardiovascular disease: DC COOKS (DC Community Organizing for Optimal culinary Knowledge Study) with Heart

BackgroundCooking interventions have increased in popularity in recent years. Evaluation by meta-analyses and systematic reviews show consistent changes in dietary quality reports and cooking confidence, but not of cardiovascular (CVD) biomarkers. Interventions evaluating or reporting behavioral mechanisms as an explanatory factor for these outcomes has been sparse. Moreover, evaluations of cooking interventions among communities with health disparities or food access limitations have received little attention in the literature.MethodsThis study will occur over two phases. Phase 1 will assess acceptability among the target population of African-American adults living within an urban food desert. Phase 2 will consist of a 6-week cooking intervention delivered at a community kitchen setting. Pre and post intervention visits for clinical examinations and biomarker collection will be conducted, as well as dietary and cooking skill assessments. Primary outcomes include cooking behavior and feasibility measures. Secondary outcomes are related to dietary quality, psychosocial factors, CVD biomarkers, and food environment measures.DiscussionThis study seeks to demonstrate feasibility of a community-based cooking intervention and to provide necessary information to plan future interventions that identify cooking behavior as an outcome of participation in cooking interventions among African-American adults, especially in relation to dietary and biomarker outcomes.Trial registrationThis study was registered at ClinicalTrials.gov (NCT04305431) on March 12, 2020.

Long-term whole-grain rye and wheat consumption and their associations with selected biomarkers of inflammation, endothelial function, and cardiovascular disease.

Whole-grain (WG) intake has been associated with a lowered risk of developing type 2 diabetes, cardiovascular disease, and some cancers in epidemiological studies. Reduced subclinical inflammation could be one important mechanism behind such associations. This study investigated whether high long-term WG rye and wheat intakes were associated with lower concentrations of biomarkers of inflammation, endothelial function, and protein biomarkers associated with cardiovascular disease. We assessed WG intake by food frequency questionnaire (FFQ) and by measuring alkylresorcinols (ARs) in plasma and adipose tissue, respectively. Selected biomarkers in free-living 109 women and 149 men were analyzed from two clinical subcohort studies (Swedish Mammography Cohort-Clinical (SMC-C) and Cohort of Swedish Men-Clinical (COSM-C), respectively. Total WG rye and wheat (WGRnW) and the ratio of WG rye to WG rye and wheat (WGR/WGRnW) were estimated from FFQs. ARs were measured in plasma and adipose tissue by gas chromatography-mass spectrometry (GC-MS) and the biomarkers by ELISA. We found no consistent associations between WG intake assessed by different methods and the selected biomarkers. However, WGRnW intake was inversely associated with cathepsin S (P-trend < 0.05) and total AR and C17:0/C21:0 in plasma were inversely associated with the endostatin concentration (P-trend < 0.05) adjusted for BMI, age, and sex. The results give limited support to the hypothesis that a high WG wheat and rye intake is associated with lower concentrations of common biomarkers of inflammation and CVD that have previously been reported inversely associated with WG intake or an overall healthy lifestyle.

Selected biomarkers of atherosclerosis - clinical aspects

Atherosclerosis is a inflammatory-immunological-degenerative process. Cardiovascular diseases account for 42% of premature deaths among men and 52% of premature deaths among woman. Identification of classical biomarkers of atherosclerosis, such as LDL, HDL and triglycerides may not be helpful in patients with moderate or unusual cardiovascular risk. Non-classical indicators of atherosclerosis include markers of the inflammatory proces, mar-kers of atherosclerotic plaque injury, acute phase proteins, ischemic markers, markers of tissue necrosis, markers of myocardial dysfunction. The identification of CVD biomarkers enables the classification of patients to appropriate cardiovascular risk groups. Knowledge about the CVD risk group makes it possible to take rapid therapeutic intervention aimed at limiting this risk. Pharmacotherapy for cardiovascular diseases is primarily based on lowering cholesterol’s level in the blood. Additional properties of statins (the most important lipid-lowering drugs) enable their pleiotropic effect by limiting the progression of atherosclerotic lesions by reducing the volume of atherosclerotic plaque. Further research on the pathogenesis of atherosclerosis will allow to learn new risk factors and new biomarkers of this disease.

Lipid levels and survival after obesity-related cancer in the Women’s Health Initiative CVD biomarker cohort.

e13618 Background: Previous investigations have demonstrated an inconclusive relationship between lipid biomarkers and mortality after cancer. Methods: We used data from 2,279 postmenopausal women diagnosed with 13 obesity-related cancers, who were part of the Women’s Health Initiative (WHI) lipid biomarkers cohort, to evaluate the relationship between lipid levels measured at study entry prior to cancer diagnosis, and mortality after cancer. Baseline lipid measurements consisted of HDL-Cholesterol, LDL-Cholesterol, and non-HDL-Cholesterol with ranges of measurement listed in the table. Obesity-related cancers included: meningioma, thyroid, adenocarcinoma of esophagus, breast, multiple myeloma, liver, kidney, gallbladder, stomach, uterus, pancreas, ovaries, and colorectal. The age adjusted relationship between baseline lipids and all-cause mortality as well as mortality due to cancer were estimated using Cox proportional hazards models and Fine-Gray models, respectively. Results: The majority of women in the cohort had either desirable or acceptable lipid levels (86% HDL-C, 30% LDL-C and 61% non-HDL-C. Low vs. desirable HDL-C levels were associated with higher risk of all-cause mortality (hazard ratio (HR) 1.54, 95% confidence interval [CI] [1.48, 1.60], p &lt;.001) and higher cancer mortality (sub-distribution hazard ratio (SHR)1.9, 95% CI [1.51, 2.3], p &lt;.001). High non-HDL-C vs desirable, was associated with higher all-cause mortality (HR 1.13, 95% CI [1.06, 1.21], p = .001) however no significant impact on cancer mortality (SHR 1.06, 95% CI [0.87, 1.30], p = 0.563). LDL-C levels demonstrated a more complex relationship with mortality, nevertheless, very high LDL-C levels were associated with higher risk of all-cause mortality (HR 1.63, 95% CI,1.21-2.2, p = ,0.001) and cancer-specific mortality (HR 1.78, 95% CI 1.22-2.63, p = 0.003). Conclusions: Elevated LDL-C and lower HDL-C may be associated with a lower risk of all-cause and cancer specific mortality in women diagnosed with obesity related cancers in the WHI. Results of multivariable adjustment for important predictors of mortality including race/ethnicity, medication use and other socio-demographic and clinical factors will be presented. [Table: see text]

Circulating miRNA-126, -145 and -155 levels in Mexican women exposed to inorganic arsenic via drinking water

The aim of this research was to investigate circulating expression levels of three miRNAs (miR-126, miR-155, and miR-145) proposed as predictive CVD biomarkers in Mexican women exposed to inorganic arsenic via drinking water. Mean UAs concentration of 19.5 ± 14.0 μg/g creatinine was found after urine samples were analyzed (n = 105). Significant associations between UAs levels and serum expression levels of miR-155 (p < 0.05) and miR-126 (p < 0.05) were observed after adjustment for assessed co-variables. Alterations in the serum expression levels of miR-155 and miR-126 may be associated with the onset and development of cardiovascular diseases, hence miRNAs could be proposed as prognostic CVD biomarkers. Data found in this study are of concern and risk reduction plans are necessary for the assessed communities to prevent cardiovascular events in this population of women.

Human Visceral Adipose Tissue Macrophages Are Not Adequately Defined by Standard Methods of Characterization.

Obesity is associated with a state of chronic low-grade inflammation both systemically and within specific tissues, including adipose tissue (AT). In murine models of obesity, there is a shift in the inflammatory profile of the AT immune cells, with an accumulation of proinflammatory M1 macrophages that surround the expanding adipocyte. However, much less is known about the immune cell composition and how to best define AT macrophages in humans. Objective. The goals of the current study were to determine the contribution of macrophages to the stromal vascular fraction (SVF) in lean versus obese human visceral AT (VAT); examine the expression of common M1, M2, and pan macrophage markers; and determine the association of specific macrophage types with known biomarkers of obesity-related cardiometabolic disease. Research Design and Methods. VAT biopsies were obtained from obese (n = 50) and lean (n = 8) patients during elective surgery. Adipocytes and SVF were isolated, and the SVF was subjected to flow cytometry analyses. Results. Our results indicate that VAT macrophages are increased in obesity and associate with biomarkers of CVD but that many macrophages do not fall into currently defined M1/M2 classification system based on CD206 receptor expression levels. Conclusions. VAT macrophages are increased in obese subjects, but the current markers used to define macrophage populations are inadequate to distinguish differences in human obesity. Further studies are needed to delineate the function of AT macrophages in the maintenance and progression of human AT inflammation in obesity.