Use of Nonhuman Sera as a Highly Cost-Effective Internal Standard for Quantitation of Multiple Human Proteins Using Species-Specific Tryptic Peptides: Applicability in Clinical LC-MS Analyses.

Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically relevant analyses, stable isotope-labeled (SIL) internal standards (ISs) represent the "gold standard" for quantitation due to their similar physiochemical properties to the analyte, wide availability, and ability to multiplex to several peptides. However, the purchase of SIL-ISs is a resource-intensive step in terms of cost and time, particularly for screening putative biomarker panels of hundreds of proteins. We demonstrate an alternative strategy utilizing nonhuman sera as the IS for quantitation of multiple human proteins. We demonstrate the effectiveness of this strategy using two high abundance clinically relevant analytes, vitamin D binding protein [Gc globulin] (DBP) and albumin (ALB). We extend this to three putative risk markers for cardiovascular disease: plasma protease C1 inhibitor (SERPING1), annexin A1 (ANXA1), and protein kinase, DNA-activated catalytic subunit (PRKDC). The results show highly specific, reproducible, and linear measurement of the proteins of interest with comparable precision and accuracy to the gold standard SIL-IS technique. This approach may not be applicable to every protein, but for many proteins it can offer a cost-effective solution to LC-MS/MS protein quantitation.

A 2-year follow-up to a randomized controlled trial on resistance training in postmenopausal women: vasomotor symptoms, quality of life and cardiovascular risk markers.

BACKGROUND: Most women experience vasomotor symptoms (VMS) during the menopausal transition. A 15-week resistance training intervention (RTI) significantly reduced moderate-to-severe VMS (MS-VMS) and improved health-related quality of life (HRQoL) and cardiovascular risk markers in postmenopausal women. Whether a short RTI could have long-term effects is unknown. We aimed to investigate whether there were intervention-dependent effects two years after a 15-week RTI on MS-VMS frequency, HRQoL, and cardiovascular risk markers in postmenopausal women. METHODS: This observational prospective cohort study is a follow-up to a randomized controlled trial (RCT) on a 15-week RTI in postmenopausal women (n = 57). The control group had unchanged low physical activity during these first 15 weeks. At the follow-up contact two years post-intervention, 35 women agreed to participate in an additional physical visit at the clinic with clinical testing, blood sampling, and magnetic resonance imaging, identical to the protocol at the baseline visit at the start of the RCT. RESULTS: Although all women showed reduced MS-VMS and increased moderate-to-vigorous physical activity (MVPA) over the 2-year follow-up compared to baseline, the groups from the original RCT (intervention group; IG, control group; CG) changed differently over time (p < 0.001 and p = 0.006, respectively) regarding MS-VMS. The IG maintained a significantly lower MS-VMS frequency than the CG at the 6-month follow-up. At the 2-year follow-up, there was no significant difference between the original RCT groups. No significant changes over time or differences between groups were found in HRQoL or cardiovascular risk markers. However, significant interactions between original RCT groups and time were found for visceral adipose tissue (p = 0.041), ferritin (p = 0.045), and testosterone (p = 0.010). CONCLUSIONS: A 15-week resistance training intervention reduced MS-VMS frequency up to six months post-intervention compared to a CG, but the effect was not maintained after two years. The RTI did neither contribute to preserved improvements of cardiovascular risk markers nor improved HRQoL after two years compared to a CG. TRIAL REGISTRATION: Clinical trials.gov registered ID: NCT01987778, trial registration date 2013-11-19.

Classification of Common Food Lipid Sources Regarding Healthiness Using Advanced Lipidomics: A Four-Arm Crossover Study.

Prospective studies have failed to establish a causal relationship between animal fat intake and cardiovascular diseases in humans. Furthermore, the metabolic effects of different dietary sources remain unknown. In this four-arm crossover study, we investigated the impact of consuming cheese, beef, and pork meat on classic and new cardiovascular risk markers (obtained from lipidomics) in the context of a healthy diet. A total of 33 young healthy volunteers (23 women/10 men) were assigned to one out of four test diets in a Latin square design. Each test diet was consumed for 14 days, with a 2-week washout. Participants received a healthy diet plus Gouda- or Goutaler-type cheeses, pork, or beef meats. Before and after each diet, fasting blood samples were withdrawn. A reduction in total cholesterol and an increase in high density lipoprotein particle size were detected after all diets. Only the pork diet upregulated plasma unsaturated fatty acids and downregulated triglycerides species. Improvements in the lipoprotein profile and upregulation of circulating plasmalogen species were also observed after the pork diet. Our study suggests that, within the context of a healthy diet rich in micronutrients and fiber, the consumption of animal products, in particular pork meat, may not induce deleterious effects, and reducing the intake of animal products should not be regarded as a way of reducing cardiovascular risk in young individuals.

Effects of changing from a diet with saturated fat to a diet with n-6 polyunsaturated fat on the serum metabolome in relation to cardiovascular disease risk factors.

PURPOSE: Replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers. METHODS: In an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25-70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups. RESULTS: PLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia. CONCLUSION: The serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT01679496 on September 6th 2012.

Occupational exposure to particles and biomarkers of cardiovascular disease-during work and after vacation.

OBJECTIVE: Ambient particle matter is a risk factor for cardiovascular disease (CVD). However, little is known about associations between particles in occupational settings and risk of CVD. We investigated associations between occupational dust exposure and biomarkers of CVD, and potential recovery effects after vacation. METHODS: Personal dust exposure measurements (respirable silica, respirable dust < 4 µm, and particles of 0.1-10 µm (PM 0.1-10) were conducted once, and biological sampling were performed twice on non-smoking, male construction workers in Stockholm county, Sweden; during work and immediately after summer vacation. Linear regressions with adjustments for confounders and covariates were performed evaluating associations between occupational dust exposure and biomarkers. Paired t tests were performed evaluating changes before and after vacation. RESULTS: Sixty-five workers participated. Homocysteine concentrations were significantly higher with increasing concentrations (mg/m3) of respirable silica, respirable dust, and PM 0.1-10, and pulse rate with higher levels of respirable dust and dust of PM 0.1-10. Homocysteine levels were also positively correlated to number of years of dust exposure, as were low-density lipoprotein (LDL) levels. A clear recovery effect was present for LDL after vacation, but not for homocysteine. CONCLUSIONS: Occupational dust exposure was associated with some CVD risk markers, even at mean exposure concentrations below the Swedish occupational exposure limits for respirable silica and respirable dust, respectively. Vacation resulted in recovery for some risk markers. However, the change of the homocysteine and LDL levels suggest a long-term effect. Reduction of occupational exposure to dust may decrease the risk of CVD among exposed workers.

Hypertension among South African children in disadvantaged areas and associations with physical activity, fitness, and cardiovascular risk markers: A cross-sectional study.

Childhood hypertension drives hypertension in later life; hence, assessing blood pressure in children is an important measure to determine current and future cardiovascular health. There is, however, a paucity of childhood blood pressure data, particularly for sub-Saharan Africa. This study explores blood pressure and associations with age, sex, socioeconomic status, physical activity, fitness, and cardiovascular risk markers. In the 'Disease, Activity and Schoolchildren's Health' (DASH) study, a cross-sectional analysis was conducted in disadvantaged neighbourhoods in the Eastern Cape province of South Africa. Assessments included blood pressure, accelerometer-measured physical activity, physical fitness, and cardiovascular risk markers. The study consisted of 785 children (383 boys, 402 girls, M = 12.4±0.9 years). Overall, 18% of the children were classified as hypertensive, while 20% were either overweight/obese, and almost four out of ten children did not meet global daily physical activity recommendations. Hypertensive children were more likely to be overweight/obese, χ2 (2,785) = 14.42, p < 0.01, but only if they did not meet physical activity recommendations, χ2 (2,295) = 11.93, p < 0.01. Considering the moderating effect which sufficient activity has on the relationship between hypertension and body weight, more emphasis should be placed on early primary health intervention and education strategies.

Exposure-response relationships of dapagliflozin on cardiorenal risk markers and adverse events: A pooled analysis of 13 phase II/III trials.

AIMS: Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor that has been developed as oral glucose lowering drug. The original dosefinding studies focused on optimal glycaemic effects. However, dapagliflozin also affects various cardiorenal risk markers and provides cardiorenal protection. To evaluate whether the currently registered doses of 5 and 10 mg are optimal for cardiorenal efficacy and safety, we characterized the relationship between dapagliflozin exposure and nonglycaemic cardiorenal risk markers as well as adverse events. METHODS: Data were obtained from a pooled database of 13 24-week randomized controlled clinical trials of the clinical development programme of dapagliflozin. The exposure-response relationship was quantified using population pharmacodynamic and repeated time-to-event models. RESULTS: A dose of 10 mg dapagliflozin resulted in an average individual exposure of 638 ng h/mL (95% prediction interval [PI]: 354-1061 ng h/mL), which translated to 71.2% (95% PI: 57.9-80.5%), 61.1% (95% PI: 58.0-64.8%), 91.3% (95% PI: 85.4-94.6%) and 25.7% (95% PI: 23.5-28.3%) of its estimated maximum effect for fasting plasma glucose, haematocrit, serum creatinine and urinary albumin-creatinine ratio, respectively. CONCLUSION: We demonstrate that doses higher than 10 mg could provide additional beneficial effects in haematocrit, systolic blood pressure, urinary albumin-creatinine ratio and uric acid, without obvious increases in the rate of adverse events. These results raise the question whether future outcome studies assessing the benefits of higher than currently registered dapagliflozin doses are merited.

Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study.

BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. CONCLUSION: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.

Markers of Subclinical Cardiovascular Disease in Patients with Adrenal Incidentaloma.

Due to the growing availability of imaging examinations the percentage of patients with incidentally diagnosed adrenal tumors has increased. The vast majority of these lesions are benign, non-functioning adenomas, although according to various estimates even up to 30%-50% of patients with adrenal incidentaloma may present biochemical hypercortisolemia, without typical clinical features of Cushing's syndrome. Adrenal adenomas secreting small amounts of glucocorticoids may cause morphological and functional changes in the myocardium and blood vessels. Early stages of cardiovascular remodeling may be observed among asymptomatic patients with adrenal adenoma. Vascular changes precede the development of cardiovascular diseases and can increase morbidity and mortality in patients with adrenal incidentaloma. This risk may result not only from the traditional risk factors. Seemingly hormonally inactive adrenal tumors can indeed produce small amounts of glucocorticoids that have metabolic implications. Therefore, evaluation of patients with incidental adrenal findings presenting with subclinical cardiovascular disease seems of particular importance.

Daily Supplementation with 4000 IU Vitamin D3 for Three Years Does Not Modify Cardiovascular Risk Markers in Patients with Advanced Heart Failure: The Effect of Vitamin D on Mortality in Heart Failure Trial.

BACKGROUND/AIMS: We aimed to investigate the effect of a moderately high vitamin D dose on lipid parameters and biochemical markers of vascular calcification (VC) in patients with established cardiovascular disease. METHODS: We included in this pre-specified secondary analysis of a randomized controlled trial 161 patients with advanced heart failure and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L (vitamin D group: n = 80; placebo group: n = 81), who received a daily vitamin D3 supplement of 4,000 IU for 3 years. We assessed between-group differences of the lipid parameters total-cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides, and the VC markers fetuin-A and non-phosphorylated undercarboxylated matrix gla protein (MGP) at study termination, with adjustment for baseline values. RESULTS: Lipid parameters, the percentage of patients with dyslipoproteinemia, and VC markers did not differ significantly between groups at study termination (p values: 0.395-0.939). Likewise, vitamin D achieved no significant treatment effect on these markers in subgroup analyses in patients with 25OHD concentrations < 30 nmol/L, nonusers of lipid-lowering drugs, or diabetic patients (p values: 0.245-0.998). CONCLUSION: Our data indicate that vitamin D does not improve the lipid profile and does not influence the calcification inhibitors fetuin-A and non-phosphorylated undercarboxylated MGP in patients with advanced heart failure.

Weight Gain and Height Growth during Infancy, Childhood, and Adolescence as Predictors of Adult Cardiovascular Risk.

OBJECTIVES: To investigate independent relationships of childhood linear growth (height gain) and relative weight gain to adult cardiovascular disease (CVD) risk traits in Asian Indians. STUDY DESIGN: Data from 2218 adults from the Vellore Birth Cohort were examined for associations of cross-sectional height and body mass index (BMI) and longitudinal growth (independent conditional measures of height and weight gain) in infancy, childhood, adolescence, and adulthood with adult waist circumference (WC), blood pressure (BP), insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR]), and plasma glucose and lipid concentrations. RESULTS: Higher BMI/greater conditional relative weight gain at all ages was associated with higher adult WC, after 3 months with higher adult BP, HOMA-IR, and lipids, and after 15 years with higher glucose concentrations. Taller adult height was associated with higher WC (men ß = 2.32 cm per SD, women ß = 1.63, both P < .001), BP (men ß = 2.10 mm Hg per SD, women ß = 1.21, both P ≤ .001), and HOMA-IR (men ß = 0.08 log units per SD, women ß = 0.12, both P ≤ .05) but lower glucose concentrations (women ß = -0.03 log mmol/L per SD P = .003). Greater height or height gain at all earlier ages were associated with higher adult CVD risk traits. These positive associations were attenuated when adjusted for adult BMI and height. Shorter length and lower BMI at birth were associated with higher glucose concentration in women. CONCLUSIONS: Greater height or weight gain relative to height during childhood or adolescence was associated with a more adverse adult CVD risk marker profile, and this was mostly attributable to larger adult size.

The relationship between food insecurity with cardiovascular risk markers and metabolic syndrome components in patients with diabetes: A population-based study from Kerman coronary artery disease risk study.

BACKGROUND: We sought the prevalence of food insecurity and whether cardiovascular risk markers and metabolic syndrome components are significantly different in categories of food insecurity in patients with type 2 diabetes. MATERIALS AND METHODS: In this cross-sectional study, 520 patients with type 2 diabetes from the Kerman coronary artery disease risk study aged between 23 and 87 years (60.8 ± 11.4) who selected by one-stage cluster sampling were assigned into four groups of "food secure" and "mild," "moderate," and "severe" food insecure. Household food insecurity was assessed by a 9-item household food insecurity access scale questionnaire. RESULTS: The prevalence of food security and mild, moderate, and severe food insecurity in patients with diabetes was 24.4%, 33.1%, 28.9%, and 13.6%, respectively. There was a significant difference among the food-secure/insecure sex groups (P = 0.001). The prevalence of food insecurity and risk factors such as total cholesterol, high low-density lipoprotein cholesterol, and visceral obesity in mild food-insecure females was significantly higher than males (P < 0.001, 0.001, and 0.001, respectively). The fasting blood sugar significantly increased (P = 0.020) in diabetic females with food security than the other female groups. Diastolic blood pressure significantly increased (P = 0.028) in diabetic females with severe food insecurity than the other female groups. The glycosylated hemoglobin significantly increased (P = 0.013) in diabetic males with severe food insecurity than the other male groups. Food insecurity odds ratio in females was 1.74 (95% confidence interval [CI]: 1.10-2.70), 2.39 (95% CI: 1.48-3.88), and 2.73 (95% CI: 1.49-5.01) times higher than in males for mild, moderate, and severe food insecurity, respectively. CONCLUSION: Food insecurity may deteriorate some cardiometabolic biomarkers in type 2 diabetes. Improving food security in patients with diabetes may help reduce cardiovascular disease.

The Impact of a Nutritional Intervention on Glycemic Control and Cardiovascular Risk Markers in Type 2 Diabetes.

INTRODUCTION: Nutritional management plays a crucial role in treating patients with type 2 diabetes (T2D), working to prevent and control the progression of chronic non-communicable diseases. OBJECTIVES: To evaluate the effects of individualized nutritional interventions on weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting blood glucose (FBG), hemoglobin A1c (HbA1c), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)} over 12 months and subsequently at follow-up (15 months). METHODS: This longitudinal experimental study (without randomization and blinding) enrolled 84 sedentary participants with T2D (both sexes, aged 18-80 years). They were divided into a control group of 40 participants who received only medical consultations, and an intervention group of 44 participants who received the same medical care along with a nutritional assessment. Consultations occurred quarterly from August 2020 to November 2022 (first-twelfth month), with six to nine patients per session. Subsequently, a follow-up was conducted from December 2022 to November 2023, during which the intervention group had only medical care (during the 12th-15th months). Personalized dietary planning was inspired by the Mediterranean/DASH diets adapted to Brazilian foods and socioeconomic cultures. STATISTICAL ANALYSIS: Normal variables were compared between groups for each time point and also within each group across different time points using a two-way ANOVA (repeated measures for intragroup) followed by the Sídák post hoc test. Non-normal variables were compared between groups for each time point using Kruskal-Wallis followed by the Dunn post hoc test, and within each group across different time points using Friedman followed by the Dunn post hoc test. Data with a Gaussian distribution were presented as mean ± standard deviation (SD), and data with a non-Gaussian distribution were presented as median ± interquartile range (IQR). For all cases, α < 0.05 and p < 0.05 were adopted. RESULTS: In the intervention group, significant reductions were observed between the first and twelfth month for all parameters (p < 0.05), (except for TC), along with an increase in HDL-C (p = 0.0105). Conversely, in the control group, there was a significant increase in HbA1c, weight, BMI, FBG, and WHR (p < 0.05) between the first and twelfth months. Regarding the comparison between groups, there was a significant difference for all analyzed parameters (p < 0.05) from the first to the twelfth month. In the follow-up, differences were also observed (p < 0.05), except for BMI (p > 0.05). CONCLUSION: The individualized nutritional intervention improved eating habits, anthropometric, biochemical, and cardiovascular markers in T2D over 12 months, with sustained results during follow-up. The dietary plan inspired by the Mediterranean and DASH diets demonstrated good adaptation to the Brazilian food culture and the patients' socioeconomic contexts. Consistent monitoring and personalized nutritional management are essential for optimizing long-term outcomes. However, more clinical trials are necessary in order to optimize the level of evidence for longitudinal interventions.

Sedentary Behaviour-A Target for the Prevention and Management of Cardiovascular Disease.

Cardiovascular disease (CVD) is highly prevalent and can lead to disability and premature mortality. Sedentary behaviour, defined as a low energy expenditure while sitting or lying down, has been identified as an independent risk factor for CVD. This article discusses (1) the association of total sedentary time and patterns of accumulating sedentary time with CVD risk markers, CVD incidence and mortality; (2) acute experimental evidence regarding the acute effects of reducing and breaking up sedentary time on CVD risk markers; and (3) the effectiveness of longer-term sedentary behaviour interventions on CVD risk. Findings suggest that under rigorously controlled laboratory and free-living conditions, breaking up sedentary time improves cardiovascular risk markers in individuals who are healthy, overweight or obese, or have impaired cardiovascular health. Breaking up sedentary time with walking may have the most widespread benefits, whereas standing breaks may be less effective, especially in healthy individuals. There is also growing evidence that sedentary behaviour interventions may benefit cardiovascular risk in the longer term (i.e., weeks to months). Reducing and breaking up sedentary time may, therefore, be considered a target for preventing and managing CVD. Further research is needed to determine the effectiveness of sedentary behaviour interventions over the long-term to appropriately inform guidelines for the management of CVD.

Circulating Extracellular Vesicles Are Strongly Associated With Cardiovascular Risk Markers.

Background: Extracellular vesicles (EVs) are submicron membrane-bound vesicles released from various cells, which are emerging as a potential novel biomarker in cardiovascular diseases (CVDs) due to their procoagulatory and prothrombotic properties. However, there is little information about the relationships between circulating EVs and conventional and thrombogenic risk markers of CVDs. Objective: To investigate the relationships between circulating EVs, conventional cardiovascular risk markers and thrombogenic markers in subjects with moderate risk of CVDs. Design: Subjects (n = 40) aged 40-70 years with moderate risk of CVDs were recruited and assessed for body mass index, blood pressure and plasma lipid profile, as well as platelet aggregation, clot formation, thrombin generation and fibrinolysis. Numbers of circulating EVs were assessed by Nanoparticle Tracking Analysis and flow cytometry. A range of assays were used to assess the procoagulatory activity of plasma and circulating EVs. Results: Circulating EV numbers were positively associated with body mass index, blood pressure, plasma triacylglycerol concentration and overall CVD risk. Higher circulating EV numbers were also associated with increased thrombin generation and enhanced clot formation, and EVs isolated from subjects with moderate CVD risk promoted thrombin generation ex vivo. Higher numbers of endothelial-derived EVs were associated with a greater tendency for clot lysis. Plasma triacylglycerol concentration and diastolic blood pressure independently predicted circulating EV numbers, and EV numbers independently predicted aspects of thrombin generation and clot formation and 10-year CVD risk. Conclusion: Circulating EVs were strongly associated with both conventional and thrombogenic risk markers of CVDs, and also with overall CVD risk, highlighting a potentially important role for EVs in CVDs.

Mediterranean diet components are linked to greater endothelial function and lower inflammation in a pilot study of ethnically diverse women.

The Mediterranean Diet, characterized by higher intakes of plant foods including plant proteins, monounsaturated fat, fish, and lower consumption of animal products and saturated fat, has long been associated with reduced cardiovascular risk, but the molecular mechanisms underlying these associations have not been fully elucidated. We conducted a pilot study to evaluate associations of an Alternate Mediterranean Diet Score, reflective of adherence to this diet pattern and adapted for US populations, and its components, with markers of endothelial inflammation directly measured in endothelial cells harvested from a diverse sample of women (n = 25, mean ±â€¯SD age 33 ±â€¯10.5y, 68% racial/ethnic minorities). Cardiovascular risk markers including nuclear factor kappa B (NF-κB)-a marker of inflammation, as well as oxidative stress and endothelial nitric oxide synthase (eNOS) gene expression-markers of endothelial function, were evaluated in harvested endothelial cells. We hypothesized that the Mediterranean diet pattern would be associated with lower inflammation and oxidative stress and higher eNOS expression in endothelial cells. Results showed that lower oxidative stress was associated with higher plant-based protein (Exp(ß) = 0.96; P = .007), overall protein (Exp(ß) = 0.99; P = .007), and red and processed meat intake (Exp(ß) = 0.93; P = .012). Lower NF-κB was associated with higher legume (Exp(ß) = 0.79; P = .045) intake, and higher eNOS was associated with higher red and processed meat intake (Exp(ß) = 1.13; P = .005). Our findings suggest potential novel mechanisms through which certain Mediterranean dietary components may influence pre-clinical vascular alterations that may be associated with cardiovascular risk through lower endothelial oxidative stress, lower inflammation, and greater endothelial functioning. These findings warrant confirmation, prospectively in a larger sample.

N1-methylnicotinamide as a possible modulator of cardiovascular risk markers in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease, which is resulted from the three common features, hyperandrogenism (HA), ovulatory dysfunction (OD), and polycystic ovarian morphology (PCOM). The environmental inducers (like diet, lifestyle, chemicals, drugs, and ageing) and cardiometabolic risk factors (such as insulin resistance, metabolic syndrome, and obesity) are involved in pathogenesis of PCOS. The growing body of evidence has been shown that there exist endothelial cell dysfunction (ECD) in women with PCOS independent of age, weight and metabolic abnormalities. It has been shown that a broad spectrum of cardiovascular risk markers are involved in ECD- induced cardiovascular disease. It is well described that there are no worldwide treatments for PCOS and all of pharmacological treatments are off -label without any approval. MNAM is one of potential therapeutic factor, which produced by nicotinamide N-methyltransferase (NNMT) via consumption of S-adenosyl methionine (SAM) and nicotinamide. Only one study has shown higher expression of its producer enzyme, NNMT, in the cumulus cells of women with PCOS. Therefore, we reviewed beneficial effects of MNAM on modulation of cardiometabolic risk factors, which are associated to PCOS and try to describe possible mode of action of MNAM in the regulation of these markers.

The Inflammatory and Hemostatic Cardiovascular Risk Markers During Acute Hyperglycemic Crisis in Type 1 and Type 2 Diabetes.

BACKGROUND: We analyzed cardiovascular inflammatory (C-reactive protein (CRP), interleukin 6 (IL-6)), haemostatic (homocysteine) risk markers in lean and obese patients at admission and acute hyperglicemic crisis (AHC) resolving, involving diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). METHODS: In that context, we included group A: N = 20 obese, B: N=20 lean patients with DKA; C: N = l0 obese, D: N=10 lean patients with HHS; E: N = 15 obese, F: N=15 lean controls. CRP IL-6, homocysteine were determined by ELISA. RESULTS: Our results showed that CRP IL-6, and homocysteine levels decreased in all groups: (A: p<0.001; B: p<0.001, C: p<0.05; D: p<0.001 mg/L), (A: p<0.001 B: p<0.001, C: p<0.001, D: p<0.01 pg/mL), (A: p<0.001, B: p <0.001; C: p<0.05, D: p=0.001 µmol/L), respectively, at resolving AHC. However, CRP persisted higher (p<0.001, p<0.01), IL-6 lower (p<0.05, p<0.001), while homocysteine levels turned out to be similar to controls. CONCLUSIONS: AHC is associated with increased inflammatory and hemostatic cardiovascular risk markers. Also, insulin therapy in AHC has had more pronounced favorable effect on IL-6 and homocystein than on CRP.

The impact of lifestyle Physical Activity Counselling in IN-PATients with major depressive disorders on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers: study protocol for a randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a widespread and burdensome psychiatric issue. Physical activity counselling may increase lifestyle physical activity and cardiorespiratory fitness in this specific and particularly vulnerable population, which often suffers from both mental and physical health problems. Therefore, this study will examine the impact of a lifestyle physical activity counselling intervention on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers among in-patients diagnosed with MDD compared to controls. Secondary purposes are to examine the acceptability and perceived usefulness of the intervention among these patients, to find out whether the effectiveness of the intervention is moderated by genetic factors, and to compare baseline values with an age- and gender-matched group of healthy controls. METHODS: The study is designed as a multi-centric two-arm randomized clinical trial including an intervention group and a placebo control group, allocation concealment, single-blinding, and intention-to-treat analysis. Participants (N = 334) will be continuously recruited from four clinics specialized in the treatment of MDD. The intervention builds on a standardized, theory-based, low-cost lifestyle physical activity counselling programme, which was specifically designed for an in-patient rehabilitation setting. The placebo control condition consists of general instructions about health-enhancing physical activity. Data assessments will take place 2-3 weeks after admission to in-patient treatment (baseline), and 6 weeks (post) and 12 months (follow-up) after discharge from in-patient treatment. The primary outcome is objectively assessed physical activity at follow-up. DISCUSSION: Because regular physical activity has proven to be an important predictor of long-term response and remission in patients with major depression, we believe that our planned study may lay important groundwork by showing how individually tailored lifestyle physical activity counselling can be integrated into given clinical structures. Improving physical activity may have important implications for tackling metabolic and cardiovascular disease and increasing mood and cognitive functioning in this at-risk population, hence limiting the future burden of multiple chronic conditions. Increased physical activity may also reduce the likelihood of future depressive episodes. By moving towards the primary prevention of chronic physical conditions, much can be done to enhance the quality and quantity of life of people with MDD. TRIAL REGISTRATION: ISRCTN, ISRCTN10469580 . Registered on 3 September 2018.

Non-alcoholic fatty liver disease: Relationship with cardiovascular risk markers and clinical endpoints.

Non-alcoholic fatty liver disease (NAFLD) is a common diagnosis and is increasing in prevalence worldwide. NAFLD is usually asymptomatic at presentation; progression of the disease is unpredictable, leading to the development of a variety of techniques for screening, diagnosis and risk stratification. Clinical methods in current use include serum biomarker panels, hepatic ultrasound, magnetic resonance imaging, and liver biopsy. NAFLD is strongly associated with the metabolic syndrome, and the most common cause of death for people with the condition is cardiovascular disease. Whether NAFLD is an independent cardiovascular risk factor needs exploration. NAFLD has been associated with surrogate markers of cardiovascular disease such as carotid intima-media thickness, the presence of carotid plaque, brachial artery vasodilatory responsiveness and CT coronary artery calcification score. There is no effective medical treatment for NAFLD and evidence is lacking regarding the efficacy of interventions in mitigating cardiovascular risk. Health care professionals managing patients with NAFLD should tackle the issue with early identification of risk factors and aggressive modification. Current management strategies therefore comprise lifestyle change, with close attention to known cardiovascular risk factors.