Biomarkers Of Cardiovascular Disease Risk Research Articles

Evaluation of ABO blood group in subjects with CVD risk factors in a population sample from northeastern Iran

Background and aimsThe ABO blood group system is a genetic polymorphism which can affect the clearance of von Willebrand factor. We aimed to assess the levels of newer biomarkers of cardiovascular disease (CVD) risk; pro-oxidant-antioxidant balance (PAB), high sensitivity C-reactive protein (hs-CRP) and anti-heat-shock protein27 (anti-Hsp27) antibody titers in subjects with various blood groups (A, B, AB and O) and with or without traditional CVD risk factors. MethodsThe cross-sectional study comprised 6910 subjects. Antigen-antibody agglutination was evaluated by the slide test method for identification of ABO blood groups. ResultsAmong three markers, only Serum anti-Hsp27 titers significantly differed between the four blood groups and showed the highest and lowest values in AB and O blood groups (0.26 ± 0.22 and 0.23 ± 0.18 OD, respectively; P < 0.05). Serum anti-Hsp27 was higher in individuals with an AB blood group with metabolic syndrome (MetS), dyslipidemia, hypertension (HTN) and obesity and it was lower in subjects with O blood group; though, two other biomarkers, serum PAB and hs-CRP, were not significantly different between the ABO blood groups. However, they were not different among blood groups in participants with or without diabetes mellitus (DM) (P > 0.05). ConclusionIndividuals with an AB blood group and high levels of anti-Hsp27 antibody titers may be predisposed to CVDs that can be mediated through the traditional CVD risk factors among middle-aged subjects from northeastern Iran. The fact that differences in anti Hsp27 are only found in the subgroup with other risk factors suggest that the difference between ABO blood groups is a consequence rather than a cause.

Shortened Relative Leukocyte Telomere Length Is Associated With Prevalent and Incident Cardiovascular Complications in Type 2 Diabetes: Analysis From the Hong Kong Diabetes Register.

Several studies support potential links between relative leukocyte telomere length (rLTL), a biomarker of biological aging, and type 2 diabetes. This study investigates relationships between rLTL and incident cardiovascular disease (CVD) in patients with type 2 diabetes. Consecutive Chinese patients with type 2 diabetes (N = 5,349) from the Hong Kong Diabetes Register for whom DNA obtained at baseline was stored and follow-up data were available were studied. rLTL was measured by using quantitative PCR. CVD was diagnosed on the basis of ICD-9 code. Mean follow-up was 13.4 years (SD 5.5 years). rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA1c, and urine albumin-to-creatinine ratio (ACR), and positively with estimated glomerular filtration rate (eGFR) (all P < 0.001). Subjects with CVD at baseline had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than did subjects without CVD (4.6 ± 1.2 ΔΔCt) (P < 0.001). Of the 4,541 CVD-free subjects at baseline, the 1,140 who developed CVD during follow-up had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than those who remained CVD-free after adjusting for age, sex, smoking, and albuminuria status (4.7 ± 1.2 ΔΔCt) (P < 0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (for each unit decrease, hazard ratio 1.252 [95% CI 1.195-1.311], P < 0.001), which remained significant after adjusting for age, sex, BMI, systolic blood pressure, LDL cholesterol, HbA1c, eGFR, and ACR (hazard ratio 1.141 [95% CI 1.084-1.200], P < 0.001). rLTL is significantly shorter in patients with type 2 diabetes and CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in patients with type 2 diabetes.

Increased levels of the cardiovascular disease risk biomarkers GDF15 and myostatin in patients with chronic lymphocytic leukemia

Individuals suffering from cancer, including hematological malignancies, are at increased risk of cardiovascular disease (CVD). Elevated levels of several biomarkers in blood are associated with an increased risk of CVD. The aim of this study was to investigate whether a subset of such CVD risk biomarkers was elevated in patients with untreated chronic lymphocytic leukemia (CLL). Blood plasma and serum from 139 CLL patients and 71 healthy age-matched controls were analyzed for 11 proposed CVD risk biomarkers. The CLL cohort displayed a more heterogeneous pattern of biomarker expression compared to controls. The majority, eight out of 11, analyzed CVD risk biomarkers differed significantly in concentrations between CLL patients and controls. Increased levels of the biomarkers GDF15 and myostatin have not previously been reported in CLL. Further prospective studies are warranted to investigate whether these biomarkers predict future cardiovascular events in patients with CLL.

Association of Dietary Phytosterols with Cardiovascular Disease Biomarkers in Humans.

Cardiovascular disease (CVD) is a leading cause of death worldwide. Elevated concentrations of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are major lipid biomarkers that contribute to the risk of CVD. Phytosterols well known for their cholesterol-lowering ability, are non-nutritive compounds that are naturally found in plant-based foods and can be classified into plant sterols and plant stanols. Numerous clinical trials demonstrated that 2 g phytosterols per day have LDL-C lowering efficacy ranges of 8-10%. Some observational studies also showed an inverse association between phytosterols and LDL-C reduction. Beyond the cholesterol-lowering beneficial effects of phytosterols, the association of phytosterols with CVD risk events such as coronary artery disease and premature atherosclerosis in sitosterolemia patients have also been reported. Furthermore, there is an increasing demand to determine the association of circulating phytosterols with vascular health biomarkers such as arterial stiffness biomarkers. Therefore, this review aims to examine the ability of phytosterols for CVD risk prevention by reviewing the current data that looks at the association between dietary phytosterols intake and serum lipid biomarkers, and the impact of circulating phytosterols level on vascular health biomarkers. The clinical studies in which the impact of phytosterols on vascular function is investigated show minor but beneficial phytosterols effects over vascular health. The aforementioned vascular health biomarkers are pulse wave velocity, augmentation index, and arterial blood pressure. The current review will serve to begin to address the research gap that exists between the association of dietary phytosterols with CVD risk biomarkers.

Effect of short-acting exenatide administered three times daily on markers of cardiovascular disease in type 1 diabetes: A randomized double-blind placebo-controlled trial.

To investigate the effect of adding the short-acting glucagon-like peptide 1 receptor agonist (GLP-1RA) exenatide to insulin treatment on markers of cardiovascular risk in type 1 diabetes. In a randomized, double-blind, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on multiple daily injection therapy with a body mass index >22.0 kg/m2 and glycated haemoglobin concentration of 59 to 88 mmol/mol (7.5%-10.0%) were randomized (1:1) to preprandial subcutaneous injection of 10 μg exenatide (Byetta®) or placebo three times daily over 26 weeks as add-on treatment to existing insulin therapy. Reported markers of cardiovascular risk were secondary endpoints and were analyzed in a baseline-adjusted linear mixed model in the intention-to-treat population. The primary results of this study, the MAG1C (Meal-time Administration of exenatide for Glycaemic control in type 1 diabetes Cases) trial, were previously reported. Exenatide changed total fat mass by -2.6 kg (95% confidence interval [CI] -3.6; -1.6; P < 0.0001) and lean body mass by -1.1 kg (95% CI -1.9; -0.4; P = 0.01) compared with placebo, as assessed by dual-energy X-ray absorptiometry. Fat mass reductions were similar for central and peripheral fat mass. Exenatide did not change levels of interleukin-2 or -6; tumour necrosis factor-α; C-reactive protein; N-terminal prohormone of brain natriuretic peptide; or 8-oxo-7,8-dihydroguanosine (RNA oxidation marker) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (DNA oxidation marker). Exenatide added to insulin therapy in type 1 diabetes for 26 weeks resulted in body weight loss primarily from fat mass reduction, but had no effect on biomarkers of cardiovascular disease risk.

Association of a genetic variant in the AKT gene locus and cardiovascular risk factors

Cardiovascular disease (CVDs) is the leading cause of morbidity and death worldwide. Most genetic variants could be identified by several genome-wide-association-studies (GWAS), including within genes encoding proteins involved in the AKT/PI3K pathways that are related with an increased risk of metabolic syndrome and CVDs. Therefore, due to the importance of genetic variants in the prognosis of diseases, we examined the genetic polymorphism of AKT-rs1130233 located on chromosome 14 with cardiovascular risk factors. In this cross-sectional study, 721 subjects recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort study. The participants including 257 subjects with metabolic syndrome, 144 subjects with cardiovascular disease and 320 subjects as a control group. Anthropometric, biochemical and demographic information measures were prepared. Dietary assessment was managed by 24h dietary recall. DNA extraction and genotyping were carried out by using the TaqMan real-time-PCR based method. The association of AKT rs1130233 locus with dietary intakes, metabolic syndrome and cardiovascular risk factors were assessed. Data were analyzed by using SPSS 21 software. Frequencies of genotypes AA, AG and GG of the AKT rs1130233 polymorphism were 12.6%, 44.5% and 42.9% in subjects with metabolic syndrome and 9.7%, 39.6% and 50.7% in subjects with cardiovascular disease, respectively. The frequency of allele A and G in cardiovascular disease and metabolic syndrome population were 29.5%, 70.5% and 34.8%, 65.2%, respectively. We have found no significant association between the AKT rs1130233 polymorphism with cardiovascular risk factors and metabolic syndrome. The results of dietary intake showed that the levels of phosphorus intake (p=0.008), calcium intake (p=0.007) and iodine intake (p=0.04) were different in subjects with and without metabolic syndrome. And also, energy intake was significantly different in subjects with cardiovascular disease (p=0.01) compared to the control group. Our findings suggest that AKT rs1130233 was not associated with the risk of metabolic syndrome and cardiovascular disease in the Iranian population. More studies are needed to validate our results. We did functional analysis, due to certify our investigation about value of this genetic biomarker for CVD risk.

DNA methylation and incident cardiovascular disease.

DNA methylation is an epigenetic mark that reflects both genetic and environmental influences over the life course and has the potential to be a robust biomarker for cardiovascular disease (CVD) risk. However, standard association studies linking DNA methylation and CVD are susceptible to reverse causation and may not directly translate into useful biomarkers of future disease. Studies of incident CVD represent a crucial tool for improving this evidence base. Recent investigations have started to provide links between DNA methylation and incident CVD. Epigenome-wide association studies have suggested individual genetic loci in which differential methylation exists prior to disease onset, while multivariate predictive modeling approaches have made progress towards realizing the potential for DNA methylation as a predictive biomarker of CVD risk. Meanwhile, complementary analysis strategies such as Mendelian randomization have provided clues as to the causality of these epigenomic associations. Taken together, this wave of studies provides the basis for a better understanding of CVD pathophysiology and the development of more confident biomarkers of CVD risk.

Fasting blood triglycerides vary with circadian phase in both young and older people.

Daily rhythms in several physiological processes are important for cardiometabolic health. The lipid panel is used clinically to assess cardiovascular disease risk, but previous attempts to demonstrate circadian variation in lipids have failed to uncouple the endogenous circadian rhythm from the effects of meals and wake duration. Changes in basal lipid levels and dampening of circadian rhythms have been reported with aging, but it is unknown whether aging is also associated with changes in the rhythmic variation of lipids. We measured fasting lipid panels (triglycerides, total cholesterol, high‐density lipoprotein, and low‐density lipoprotein) in blood at wake time in 21 healthy adults using a specialized laboratory protocol that uncouples sleep–wake and activity‐related effects from the endogenous circadian rhythm. Young and older adults exhibited endogenous circadian variations in fasting triglycerides, with both groups peaking in the early biological morning. Young adults also exhibited significant circadian rhythmicity in total cholesterol and low‐density lipoprotein, while older adults did not exhibit circadian rhythmicity in any other lipids. These results reveal that triglyceride metabolism may be regulated by the central circadian pacemaker. Moreover, our findings may have clinical implications in assessing cardiovascular risk in shift workers and younger adults, since routine measurement of morning/fasting lipids may not fully and reliably assess triglyceride‐ and other lipid‐related biomarkers of cardiovascular disease risk in these groups.

1094-P: Short-Acting Exenatide and Markers of Cardiovascular Disease in Type 1 Diabetes: A Randomized, Double-Blinded, Placebo-Controlled Trial

In type 2 diabetes, some glucagon-like peptide 1 receptor agonists (GLP-1RAs) reduce the risk of major adverse cardiovascular events. Whether GLP-1RAs have any effect on cardiovascular disease risk in patients with type 1 diabetes remains to be elucidated. We tested the effect of adding the short-acting GLP-1RA exenatide to insulin treatment on markers of cardiovascular risk in type 1 diabetes. In a randomized, double-blinded, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on multiple daily insulin injection therapy with body mass index &amp;gt;22.0 kg/m2 and HbA1c 7.5-10.0% (59-88 mmol/mol) were randomized (1:1) to preprandial subcutaneous injection of 10 µg exenatide (Byetta®) or placebo three times daily over 26 weeks as add-on treatment to existing insulin therapy. Reported data were secondary endpoints and analyzed in a baseline-adjusted linear mixed model in the intention-to-treat population. Exenatide changed total fat mass by -2.6 kg (95% CI -3.6;-1.6, P&amp;lt;0.0001) and lean body mass by -1.1 kg (95% CI -1.9;-0.4, P=0.01) compared to placebo as assessed by dual-energy X-ray absorptiometry. Central and peripheral fat mass reductions were similar. Exenatide did not change levels of interleukin 2 or 6; tumor necrosis factor alpha; C-reactive protein; N-terminal prohormone of brain natriuretic peptide; or 8-oxo-7,8-dihydroguanosine (RNA oxidation marker) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (DNA oxidation marker). Exenatide added to insulin therapy in type 1 diabetes for 26 weeks resulted in body weight loss primarily from fat mass reduction but had no effect on circulating biomarkers of cardiovascular disease risk. Disclosure N.J. Johansen: Research Support; Self; AstraZeneca. T.F. Dejgaard: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. A. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. C. Schlüntz: None. E. Larsen: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H.E. Poulsen: Research Support; Self; Boehringer Ingelheim International GmbH. J.P. Gøtze: None. H. Møller: None. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp &amp; Dohme Corp., Sanofi. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Norgine B.V., Novo Nordisk A/S. Funding AstraZeneca

Sociodemographic and metabolic risk characteristics associated with metabolic weight categories in the Women's Health Initiative.

The Women's Health Initiative enrolled 161 808 postmenopausal women ages 50-79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n = 19 412). Normal weight was defined as a BMI ≥18.5 and <25 kg/m2 and waist circumference <88 cm and overweight/obesity as a BMI ≥25 kg/m2 or waist circumference ≥88 cm. Metabolically healthy was based on <2 and metabolically unhealthy ≥2 traits: triglycerides ≥150 mg/dl, systolic blood pressure (BP) ≥130 mmHg or diastolic BP ≥85 mmHg or antihypertensives or diuretics, fasting glucose ≥100 mg/dl or diabetes medication, and high-density lipoprotein cholesterol <50 mg/dl. Polytomous multinomial logistic regression with generalized link logit function provided the odds of metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) according to demographic and risk factor measures. Among the 19 412 postmenopausal women, 2369 (12.2%) participants had prevalent diabetes. Advanced age was associated with an increased odds of MUHNW as compared with the MHNW after adjusting for covariates [odds ratio (OR) 1.04, P < 0.0001]. Black/African American ethnicity was associated with a decreased odds of MUHNW (OR 0.64, P < 0.0001) and MUHO (OR 0.77, P = 0.0004), while an increased odds for MHO (OR 1.50, P < 0.0001) as compared with White MHNW. Advanced age and ethnicity are important indicators of metabolic weight categories among postmenopausal women.

Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts.

Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and humans, little is known about the nature of the interaction and the underlying molecular mechanisms at the cellular level. We used an untargeted metabolomics approach to study the impact of AA on the metabolome of C2C12 myoblast cells. Compared to untreated cells, treatment of C2C12 cells with AA at 100 µM resulted in enhanced concentrations of folic acid (2.5-fold) and 5-methyl-tetrahydrofolate (5-methyl-THF, 10-fold increase) whereas the relative concentrations of 10-formyl-tetrahydrofolate decreased by >90% upon AA pretreatment, indicative of increased utilization for the biosynthesis of active THF metabolites. The impact of AA on the folate-mediated one-carbon cycle further manifested itself as an increase in the levels of methionine, whose formation from homocysteine is 5-methyl-THF dependent, and an increase in thymidine, whose formation from deoxyuridine monophosphate (dUMP) is dependent on 5,10-methylene-THF. These findings shed new light on the interaction of AA with the folate-mediated one-carbon cycle and partially explain clinical findings that AA supplementation enhances erythrocyte folate status and that it may decrease serum levels of homocysteine, which is considered as a biomarker of cardiovascular disease risk.

Abstract P285: Sociodemographic and Metabolic Risk Characteristics Associated with Metabolic Weight Categories in the Women's Health Initiative

Introduction: To identify sociodemographic and metabolic correlates of weight categories in postmenopausal women. Hypothesis: We assessed the hypothesis that postmenopausal women with metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) were more likely to have adverse risk factors as compared to those with metabolically healthy normal weight (MHNW). Methods: The Women’s Health Initiative (WHI) enrolled 161,808 postmenopausal women ages 50-79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n=19,412). Normal weight was defined as a body-mass index (BMI) ≥18.5 and &lt;25 kg/m 2 and waist circumference (WC) &lt;88 cm and overweight/obesity as a BMI &gt; 25 kg/m 2 or WC &gt; 88 cm. Metabolically healthy was based on &lt;2 and metabolically unhealthy &gt; 2 traits: triglycerides &gt; 150 mg/dl, systolic blood pressure (BP) &gt; 130 mmHg or diastolic BP &gt; 85 mmHg or antihypertensives or diuretics, fasting glucose &gt; 100 mg/dl or diabetes medication, and HDL-cholesterol &lt;50 mg/dl. Multinomial logistic regression with generalized link logit function provided the odds ratio (ORs) of MHNW, MUHNW, MHO and MUHO. Results: The table shows the ORs of risk factors and biomarkers. Among the 19,412 participants, 2,369 (12.2%) had prevalent diabetes and a mean age of 63.3 ± 0.05 (SEM). Advanced age was associated with a greater odds of MUHNW and a lower odds of MHO as compared to the MHNW after adjusting for covariates. African-Americans were associated with a decreased likelihood of MUHNW and MUHO, while Hispanics were associated with a decreased likelihood of MHO and MUHO as compared to MHNW. Low-income had a greater odds of MUHNW, yet high-income had a lower odds of MHO or MUHO. Total cholesterol, insulin and C-reactive protein were associated with a greater odds of MUHNW, MUHO or MHO. Conclusions: Advanced age, ethnicity, income and biomarkers are important indicators of metabolic weight categories among postmenopausal women.

High Serum Adipocyte Fatty Acid-Binding Protein Is Associated With Peripheral Artery Disease in Peritoneal Dialysis Patients

BACKGROUND: Peripheral arterial disease (PAD) is a vascular disorder wherein peripheral ischemia is caused by arterial obstruction and results in increased events of cardiovascular disease (CVD). Peritoneal dialysis (PD) is an independent predictor of subclinical PAD and the subsequent mortality in patients with end-stage renal disease. Adipocyte fatty acid-binding protein (A-FABP) is a potential biomarker for CVD risk, especially in patients with overt atherosclerosis. This study was conducted to determine the relationship between PAD and fasting serum levels of A-FABP in patients undergoing PD. METHODS: Fasting blood samples were obtained from 66 PD patients. A-FABP levels were measured using a commercially available enzyme immunoassay kit. Ankle-brachial index (ABI) values were measured using the automated oscillometric method. Serum left or right ABI values of ＜ 0.9 were included in the low ABI group. RESULTS: There were 14 patients (21.2%) in the low ABI group. Compared with patients in the control group, those in the low ABI group had a higher prevalence of diabetes (P = 0.045) and higher serum C-reactive protein (P ＜ 0.001) and A-FABP (P ＜ 0.001) levels but lower weekly Kt/V (P = 0.014) and lower normalized protein equivalent of nitrogen appearance (P = 0.034) values. Multivariate logistic regression analysis of the factors that were significantly associated with PAD revealed that A-FABP (odds ratio, 1.038; 95% confidence interval [CI], 1.004-1.074; P = 0.030) was an independent predictor of PAD in PD patients. The area under the curve plotted to estimate the optimal level of A-FABP predicting PAD in PD patients by the receiver operating characteristic curve analysis was 0.757 (95% CI, 0.636-0.854; P = 0.0004). CONCLUSION: This study demonstrated that a higher serum A-FABP level is an independent predictor of PAD in patients undergoing PD.

Childhood Adversities as Determinants of Cardiovascular Disease Risk and Perceived Illness Burden in Adulthood: Comparing Retrospective and Prospective Self-Report Measures in a Longitudinal Sample of African Americans.

A large body of evidence suggests that exposure to childhood adversities increases risk for poor quality physical health in adulthood. Much of this evidence is based on retrospective measures which are believed to be contaminated by the limitations and biases of autobiographical memory. Using longitudinal data on 454 African Americans (61 percent female) this study examines the corroboration between prospective and retrospective measures of childhood adversities gathered approximately two decades apart, and the relative ability of the measures to predict self-reported illnesses and a biomarker of 30-year cardiovascular disease risk. Comparisons indicated that the retrospective and prospective measures demonstrated weak convergence and did not provide completely equivalent information about self-reported adverse childhood experiences. A series of regression models indicated that the two measures of adversities exhibited similar associations with the cardiovascular disease biomarker but divergent associations with self-reported illnesses. Furthermore, both the prospective and retrospective measures simultaneously predicted cardiovascular disease risk in adulthood. That the prospective measure did not significantly predict perceived illnesses after adjusting for the retrospective measure is evidence that childhood adversities predict self-reported health burden insofar as respondents remember those adversities as adults. The findings provide evidence that retrospective self-report measures of childhood adversities do not closely converge with prospective measures, and that retrospective measures may not provide valid estimates of the association between childhood adversities and perceived illnesses in adulthood.

Low-density granulocytes and monocytes as biomarkers of cardiovascular risk in systemic lupus erythematosus.

The aim was to evaluate the most relevant cell populations involved in vascular homeostasis as potential biomarkers of SLE-related cardiovascular disease (CVD). Low-density granulocytes (LDGs), monocyte subsets, endothelial progenitor cells, angiogenic T(Tang) cells, CD4+CD28null and Th1/Th17 lymphocytes and serum cytokine levels were quantified in 109 SLE patients and 33 controls in relationship to the presence of subclinical carotid atheromatosis or cardiovascular disease. A second cohort including 31 recent-onset SLE patients was also included. Raised monocyte and LDG counts, particularly those LDGs negative for CD16/CD14 expression (nLDGs), in addition to the ratios of monocytes and nLDGs to high-density lipoprotein-cholesterol (HDLc) molecules (MHR and nLHR, respectively), were present in SLE patients with traditional risk factors or subclinical atheromatosis but not in those who were CV-free, thus revealing their value in the identification of patients at risk of CVD, even at the onset of disease. Accordingly, nLDGs were correlated positively with carotid intima-media thickness (cIMT) and with inflammatory markers (CRP and IL-6). A bias towards more differentiated monocyte subsets, related to increased IFN-α and IL-17 serum levels, was also observed in patients. Intermediate monocytes were especially expanded, but independently of their involvement in CVD. Finally, CD4+CD28null, Th17 and Th1 lymphocytes were increased, with CD4+CD28null and Th17 cells being associated with cIMT, whereas endothelial progenitor and Tang cell levels were reduced in all SLE patients. The present study highlights the potential use of MHR and nLHR as valuable biomarkers of CVD risk in SLE patients, even at diagnosis. The increased amounts of nLDGs, monocytes, Th17 and senescent-CD28null subsets, coupled with reduced pro-angiogenic endothelial progenitor cells and Tang cells, could underlie the development of atheromatosis in SLE.

Myokines as biomarkers of frailty and cardiovascular disease risk in females.

Frailty is a risk factor for cardiovascular disease (CVD). Biomarkers have the potential to detect the early stages of frailty, such as pre-frailty. Myokines may act as biomarkers of frailty-related disease progression, as a decline in muscle health is a hallmark of the frailty phenotype. This study is a secondary analysis of 104 females 55years of age or older with no previous history of CVD. Differences in systemic myokine concentrations based on frailty status and CVD risk profile were examined using a case-control design. Propensity matching identified two sets of 26 pairs with pre-frailty as the exposure variable in low or elevated CVD risk groups for a total 104 female participants. Frailty was assessed using the Fried Criteria (FC) and CVD risk was assessed using the Framingham Risk Score (FRS). Factorial ANOVA compared the main effects of frailty, CVD risk, and their interaction on the concentrations of 15 myokines. Differences were found when comparing elevated CVD risk status with low for the concentrations of EPO (384.76±1046.07 vs. 206.63±284.61pg/mL, p=.001), FABP3 (2772.61±3297.86 vs. 1693.31±1019.34pg/mL, p=.017), FGF21 (193.17±521.09 vs. 70.18±139.51pg/mL, p=.010), IL-6 (1.73±4.97 vs. 0.52±0.89pg/mL, p=.023), and IL-15 (2.62±10.56 vs. 0.92±1.25pg/mL, p=.022). Pre-frail females had lower concentrations of fractalkine compared to robust (27.04±20.60 vs. 103.62±315.45pg/mL, p=.004). Interaction effects between frailty status and CVD risk for FGF21 and OSM were identified. In elevated CVD risk, pre-frail females, concentrations of FGF21 and OSM were lower than that of elevated CVD risk, robust females (69.10±62.86 vs. 317.24±719.69, p=.011; 1.73±2.32 vs. 24.43±69.21, p=.018, respectively). These data identified specific biomarkers of CVD risk and biomarkers of frailty that are exacerbated with CVD risk.

The Effect of Physical Activity on cTNI, Visceral Fat, and Plasma Biomarkers of Cardiovascular Risk in Shift Workers of Sarir Plast Industrial Group

Background: Shift work can be considered a cause of health problems and a risk factor for developing cardiovascular diseases. Objectives: The purpose of the present study was to evaluate the effect of aerobic physical activity on cTNI, visceral fat and plasma biomarkers of cardiovascular disease risk among shift workers of Sarir Plast Industrial Group. Methods: The present research is a semi-experimental research that was carried out on the shift workers of the Sarir Plast Industrial Group. Thirty workers, with an average of 5 years of shift work history, were selected through judgmental sampling technique and were then randomly assigned to the two groups of aerobic physical activity (n = 15) and control group (n = 15). Based on the schedule, the experimental group performed 8 weeks, 3 sessions per week with 50% - 70% THR intensity. Both before and immediately after the plan, the activity, height, BW, VF, cTNI, TC, TG, HDL, LDL, vLDL and VO2, max were measured. For data analysis, Kolmogorov-Smirnov test, Levene’s test, Mbox-test, and ANCOVA were employed (P < 0.05). Results: The BW, VF, TC, TG, and LDL significantly decreased in the post-test for the experimental group, while the value of HDL and VO2, max increased. However, cTNI and vLDL did not change significantly (P < 0.05). Conclusions: Aerobic physical activity was effective in reducing the risk factors of CVD in shift workers. It appeared that aerobic physical activity could be used as a non-pharmacological approach to prevent CVD in shift workers.

Bone Metabolism Analytes as Biomarkers of Pre-Frailty and Cardiovascular Disease Risk in Females

Background: Frailty and cardiovascular disease (CVD) share common pathophysiology in their progression. Declines in bone health often occur concomitantly with frailty and CVD. Therefore, analytes of bone metabolism may be useful biomarkers of pre-frailty and CVD risk. The aim of this study was to identify the effects of pre-frailty and CVD risk on the systemic concentrations of bone metabolism and inflammatory analytes in middle-aged and older females. Method: This case-control study is a secondary analysis of data from 1030 females with no self-reported history of CVD. Frailty was measured using the Fried Criteria, and females were stratified into low and elevated CVD risk using the Framingham risk score. Greedy matching with pre-frailty as the exposure variable identified 26 matched pairs in the low and elevated CVD risk groups for a total of 104 females. Factorial ANOVA compared differences in the log transformed concentrations of 15 bone metabolism analytes based on pre-frailty status, CVD risk, and the interaction. Results: Differences in the systemic concentrations of IL-6 (5.25 ± 14.30 vs 1.35 ± 1.74 pg/mL, p = 0.001), TNFα (1.41 ± 1.83 vs 0.89 ± 0.40 pg/mL, p = 0.06), and leptin (12628.48 ± 10472.90 vs 7562.96 ± 4972.25 pg/mL, p = 0.023) were found in elevated CVD risk status compared to low. No differences in the concentrations of bone metabolism analytes were found based on pre-frailty status, nor were any interaction effects. Conclusion: Differences were found in the concentrations of cytokines involved in bone metabolism based on CVD risk; however, no differences were found based on pre-frailty status. IL-6, TNFα, and leptin may act as biomarkers of CVD risk, but this study does not support the use of the examined analytes involved in bone metabolism as biomarkers of pre-frailty.

Association of daily nitrate consumption with blood pressure and other risk factors for cardiovascular diseases in a representative UK population

AbstractDietary inorganic nitrate has been shown to lower blood pressure (BP) and improve endothelial function(1). The main sources of dietary nitrate are vegetables (root and green leafy varieties) as well as drinking water but data available on dietary analysis software on nitrate levels in vegetables and vegetable-based foods is very limited. To date, very few studies have investigated the relationship between the level of consumption of dietary nitrate on BP and other cardiovascular disease (CVD) risk factors in a representative UK population. The aim of the study was to address this knowledge gap using data from the National Diet and Nutrition Survey (NDNS) years 1–8, a cross-sectional study conducted in 3339 men and women aged 19–64 y between 2008/09–2011/12. A comprehensive database was first developed to evaluate the nitrate and nitrite levels in vegetables, cured meats and composite dishes to more accurately estimate the dietary nitrate intakes of the NDNS participants. The population was then classified into quartiles of daily nitrate intake, with quartile 1 (Q1: 26–106 mg/d) and quartile 4 (Q4: 183–559 mg/d) representing diets with the lowest and highest intakes, respectively. ANCOVA analysis was performed to determine the relationship between the level of daily nitrate intake with available data on biomarkers of CVD risk (including BP (systolic, diastolic and pulse pressure), lipid profile, (total, high-density lipoprotein and low-density lipoprotein (LDL-C) cholesterol), C-reactive protein, anthropometric measures (body mass index and waist to hip ratio) and glycaemic control (glucose and glycated haemoglobin). There were significant differences in systolic (P-trend = 0.008) and diastolic (P-trend = 0.025) BP across increasing quartiles of dietary nitrate intake, with BP significantly lower in Q3 than all other quartiles. Pulse pressure (calculated as systolic–diastolic BP) was also found to be significantly different across quartiles (P-trend = 0.001), with diets of participants in Q3 and Q4 being associated with significantly lower pulse pressures than those in Q1 (P-Q1 vs. Q3 = 0.005, P-Q1 vs. Q4 = 0.007). All of the other CVD risk markers were not different between quartile groups. Our preliminary results suggest that the level of dietary nitrate intake may be significantly associated with BP, a key independent CVD risk factor. There is an urgent need to more accurately estimate the dietary nitrate intake in the UK population and to determine whether the source of dietary nitrate (vegetables vs cured meats) impacts on the significant relationship with BP.

Higher dose of resveratrol elevated cardiovascular disease risk biomarker levels in overweight older adults - A pilot study.

Older adults are at high risk of developing cardiovascular disease (CVD). Pre-clinical studies indicate that resveratrol (RSV), a polyphenol commonly found in grapes and red wine, may help prevent development of CVD. Based on our previous reports where the 300mg and 1000mg doses appeared safe and improved psychomotor function in a dose-dependent manner, our hypothesis was that RSV would reduce biomarkers of CVD risk in overweight, but otherwise healthy older adults and that 1000mg would lower CVD biomarkers >300mg. This analysis was performed on samples from older participants (65years and older) who were randomized to a 90day RSV treatment with 300mg (n=10), 1000mg (n=9) or placebo (n=10). We measured levels of CVD risk biomarkers i.e. oxidized low-density lipoprotein (oxLDL), soluble E-selectin-1 (sE-selectin), soluble Intercellular Adhesion Molecule-1 (sICAM-1), Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), total plasminogen activator inhibitor (tPAI-1). Statistical significance was set at p<0.05. Both sVCAM-1 and tPAI increased significantly more in the 1000mg vs. 300mg and placebo groups. Other biomarkers (300mg vs. 1000mg vs. placebo: oxLDL, sEselectin-1 and sICAM-1) followed the same trend toward higher levels in the 1000mg group compared to the 300mg and placebo groups, without reaching statistical significance. This pilot project suggests that a higher dose of RSV may increase the levels of CVD risk biomarkers in overweight older adults. Given no change in the CVD risk biomarkers in response to a lower dose, future studies should test the effects of different doses of RSV to evaluate potential detrimental effects of higher doses on CVD biomarkers and measures of cardiovascular function in older adults at risk for CVD.