Cardiovascular Risk In Subjects Research Articles

Risk of heart disease and stroke among individuals with prehypertension or blood pressure progression: a national population-based cohort study.

The purpose of our study was to analyze the association of blood pressure and blood pressure progression with heart disease and stroke among Chinese population. We included a total of 10 122 adults aged 45 years and above free of heart disease or stroke at baseline from the China Health and Retirement Longitudinal Study cohort. We used Cox proportional hazards models to analyze the relationship between cardiovascular risk and prehypertension in subjects with or without progression to hypertension. During a mean follow-up of 6.5 years, 1972 subjects were either diagnosed with heart disease or had a stroke (composite outcome). Compared with individuals with normotension at baseline, the fully adjusted hazard ratio (HR) [95% confidence interval (CI)] was 1.25 (1.10-1.42) and 1.52 (1.34-1.74) for composite outcome in individuals with prehypertension and hypertension at baseline, respectively. The subjects who progressed to hypertension had higher risk of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. The subjects who progressed from prehypertension to hypertension had 1.72 times higher risk [HR (95% CI): 1.72 (1.37-2.16)] of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. The cardiovascular risk of subjects with prehypertension is higher than that of subjects with normal blood pressure. After a diagnosis of hypertension, subjects who progressed from normal blood pressure to hypertension had an increased risk of heart disease and stroke.

Erythrocyte membrane fluidity: A novel biomarker of residual cardiovascular risk in type 2 diabetes.

Improving the composition of circulating fatty acids (FA) leads to a reduction in cardiovascular diseases (CVD) in high-risk individuals. The membrane fluidity of red blood cells (RBC), which reflects circulating FA status, may be a valid biomarker of cardiovascular (CV) risk in type 2 diabetes (T2D). Red blood cell membrane fluidity, quantified as general polarization (GP), was assessed in 234 subjects with T2D, 86 with prior major CVD. Based on GP distribution, a cut-off of .445 was used to divide the study cohort into two groups: the first with higher GP, called GEL, and the second, defined as lower GP (LGP). Lipidomic analysis was performed to evaluate FA composition of RBC membranes. Although with comparable CV risk factors, the LGP group had a greater percentage of patients with major CVD than the GEL group (40% vs 24%, respectively, p < .05). Moreover, in a logistic regression analysis, a lower GP value was independently associated with the presence of macrovascular complications. Lipidomic analysis showed a clear shift of LGP membranes towards a pro-inflammatory condition due to higher content of arachidonic acid and increased omega 6/omega 3 index. Increased membrane fluidity is associated with a higher CV risk in subjects with T2D. If confirmed in prospective studies, membrane fluidity could be a new biomarker for residual CV risk assessment in T2D.

Epicardial fat thickness in type 2 diabetes outpatient care

Background and aimVisceral fat is an independent predictor of the cardiovascular risk in subjects with type 2 diabetes (T2DM), but it is rarely assessed during an outpatient visit. Epicardial fat (EAT), the visceral fat of the heart, plays a role in coronary artery disease (CAD). EAT thickness can be clinically assessed with standard ultrasound. In this study we sought to evaluate the association of ambulatory ultrasound measured EAT thickness with CAD in asymptomatic well controlled T2DM subjects on metformin monotherapy during outpatient visits. Methods and resultsThis was single center, pragmatic study in 142 T2DM patients. Each subject underwent baseline ultrasound EAT thickness measurement, anthropometric and biomarkers. The incidence of CAD was detected after 1 year. At baseline, HbA1c was 6.7 % and BMI 34.9 kg/m2, EAT thickness was 8.3 ± 2.3 in women and 9.4 ± 2.4 mm in men, higher than threshold values for high cardiovascular risk. In multivariate models, EAT was the only statistically significant correlate of CAD at 1-year f/u (p = 0.04). ConclusionsPoint of care ultrasound measured EAT thickness is a good correlate of CAD in well controlled and asymptomatic T2DM subjects on metformin monotherapy. EAT thickness predicted CAD better than traditional risk factors, such as BMI, HbA1c, age, blood pressure or duration of diabetes.

Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and cardiovascular risk

BackgroundThe residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD). MethodsIL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n = 285). Incident clinical events were obtained through national registers. Plaques removed at surgery were analyzed by immunohistochemistry and biochemical methods. ResultsDuring 23.1 ± 7.0 years follow-up, 575 subjects in the MDC cohort suffered a first myocardial infarction. Subjects in the highest tertile of IL-6 had an increased risk compared to the lowest tertile (HR and 95% CI 2.60 [2.08–3.25]). High plasma IL-6 was also associated with more atherosclerosis, increased arterial stiffness, and impaired endothelial function in SUMMIT VIP, but IL-6 was only weakly associated with plaque inflammation in CPIP. sIL-6R showed no independent association with risk of myocardial infarction, atherosclerosis severity or vascular function, but was associated with plaque inflammation. ConclusionsOur findings show that sIL-6R is a poor marker of CVD risk and associated vascular changes. However, the observation that sIL-6R reflects plaque inflammation highlights the complexity of the role of IL-6 in CVD.

Family history screening for premature cardiovascular disease and hypercholesterolaemia in newborns: An economic, sustainable and fast strategy to identify high cardiovascular disease risk subjects

Family history screening for premature cardiovascular disease and hypercholesterolaemia in newborns: An economic, sustainable and fast strategy to identify high cardiovascular disease risk subjects

Renal hyperfiltration revisited—Role of the individual body surface area on mortality

BackgroundHigher than normal estimated glomerular filtration rate (eGFR), i.e. renal hyperfiltration (RHF), has been associated with mortality. MethodsA population-based screening program in Finland identified 1747 apparently healthy middle-aged cardiovascular risk subjects in 2005–2007. GFR was estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation indexed for 1.73 m2 and for the actual body surface area (BSA) of the subjects. This individually corrected eGFR was calculated as eGFR (ml/min/BSA m2) = eGFR (ml/min/1.73 m2) x (BSA/1.73). BSA was calculated by the Mosteller formula. RHF was defined as eGFR of more than 1.96 SD above the mean eGFR of healthy individuals. All-cause mortality was obtained from the national registry. ResultsThe higher the eGFR, the greater was the discrepancy between the two GFR estimating equations. During the 14 years of follow-up, 230 subjects died. There were no differences in mortality rates between the categories of individually corrected eGFR (p = 0.86) when adjusted for age, sex, body mass index, systolic BP, total cholesterol, new diabetes, current smoking, and alcohol use. The highest eGFR category was associated with increased standardized mortality rate (SMR) when CKD-EPI formula indexed for 1.73 m2 was used, but SMR was at the population level when individually corrected eGFR was applied. ConclusionsHigher than normal eGFR calculated by the creatinine-based CKD-EPI equation is associated with all-cause mortality when indexed to 1.73 m2, but not when indexed to actual BSA of a person. This challenges the current perception of the harmfulness of RHF in apparently healthy individuals.

DNA-Methylation Signatures of Tobacco Smoking in a High Cardiovascular Risk Population: Modulation by the Mediterranean Diet.

Biomarkers based on DNA methylation are relevant in the field of environmental health for precision health. Although tobacco smoking is one of the factors with a strong and consistent impact on DNA methylation, there are very few studies analyzing its methylation signature in southern European populations and none examining its modulation by the Mediterranean diet at the epigenome-wide level. We examined blood methylation smoking signatures on the EPIC 850 K array in this population (n = 414 high cardiovascular risk subjects). Epigenome-wide methylation studies (EWASs) were performed analyzing differential methylation CpG sites by smoking status (never, former, and current smokers) and the modulation by adherence to a Mediterranean diet score was explored. Gene-set enrichment analysis was performed for biological and functional interpretation. The predictive value of the top differentially methylated CpGs was analyzed using receiver operative curves. We characterized the DNA methylation signature of smoking in this Mediterranean population by identifying 46 differentially methylated CpGs at the EWAS level in the whole population. The strongest association was observed at the cg21566642 (p = 2.2 × 10-32) in the 2q37.1 region. We also detected other CpGs that have been consistently reported in prior research and discovered some novel differentially methylated CpG sites in subgroup analyses. In addition, we found distinct methylation profiles based on the adherence to the Mediterranean diet. Particularly, we obtained a significant interaction between smoking and diet modulating the cg5575921 methylation in the AHRR gene. In conclusion, we have characterized biomarkers of the methylation signature of tobacco smoking in this population, and suggest that the Mediterranean diet can increase methylation of certain hypomethylated sites.

Cardiovascular risk in subjects over 55 years of age and cognitive performance after five years. NEDICES2-RISK study. Study protocol.

Cognitive impairment and dementia have a high prevalence among the elderly and cause significant socio-economic impact. Any progress in their prevention can benefit millions of people. Current data indicate that cardiovascular risk (CVR) factors increase the risk of developing cognitive impairment and dementia. Using models to calculate CVR specific for the Spanish population can be useful for estimating the risk of cognitive deterioration since research on this topic is limited and predicting this risk is mainly based on outcomes in the Anglo-Saxon population. The aim of this study is to assess the relationship between CVR in the Spanish population, as calculated using the FRESCO (Función de Riesgo Española de acontecimientos Coronarios y Otros) and REGICOR (Registre Gironí del Cor) CVR tables, and the change in cognitive performance at a 5-year follow-up. Design: Observational, analytic, prospective cohort study, with a 5-year follow-up. Ambit: Population. Population: Subjects 55 to 74 years of age, included in the NEDICES2 (2014-2017) cohort, who did not present dementia and had undergone the neuropsychological evaluation (N = 962). Variables: Exposure factors (CVR factors and estimated risk according to the CVR predictors by REGICOR and FRESCO), dependent variables (change in the score of the brief neuropsychological test in the study NEDICES2 five years after the first evaluation), and clinical and socio-demographic variables. Statistical analysis: Analysis of data quality. Descriptive analysis: socio-demographic and clinical variables of subjects. Bivariate analysis: relationship between basal CVR and change in neuropsychological tests. Multivariate analysis: relationship between basal CVR and change in neuropsychological tests adjusted by co-variables. Analysis and comparison of the reliable change in independent samples. The Spanish population can benefit from determining if individuals with high CVR, which is commonly detected in usual clinical practice, will present decreased cognitive performance compared to subjects with lower CVR. This study can affect how to address CVR factors and the design of effective prevention strategies for cognitive deterioration. Clinicaltrials.gov, NCT03925844.

Effect of Obstructive Sleep Apnea and CPAP Treatment on the Bioavailability of Erythrocyte and Plasma Nitric Oxide.

Endothelial dysfunction resulting from decreased nitric oxide (NO) bioavailability is an important mechanism that increases cardiovascular risk in subjects with obstructive sleep apnea (OSA). NO is produced by nitric oxide synthase (NOS) in a reaction that converts L-arginine to L-citrulline. Asymmetric-dimethylarginine (ADMA) is created by L-arginine and is a naturally occurring competitive inhibitor of nitric oxide synthase (NOS). The aim of our study was to verify if erythrocytes could play a role in the storage and accumulation of ADMA in OSA patients. The crosstalk between erythrocyte-ADMA, SDMA, L-arginine, and L-citrulline levels and endothelial function was investigated in OSA subjects both at baseline and prospectively following 1-year CPAP (continuous positive airway pressure) treatment. A total of 46 subjects with OSA were enrolled in this study and divided into two groups: those with moderate-to-severe OSA and those with mild or no OSA. A physical examination was followed by blood collection for the assessment of biochemical cardiovascular risk factors and the nitric oxide bioavailability parameters both in plasma and erythrocytes. Vasodilative endothelial function was assessed using Laser Doppler Flowmetry (LDF). No significant changes regarding the NO pathway metabolites were noted apart from the plasma L-citrulline concentration, which was decreased in patients with OSA (26.9 ± 7.4 vs. 33.1 ± 9.4 μM, p < 0.05). The erythrocyte ADMA concentration was lower than in plasma irrespective of the presence of OSA (0.33 ± 0.12 vs. 0.45 ± 0.08 μM in OSA, p < 0.05 and 0.33 ± 0.1 vs. 0.45 ± 0.07 μM in the control, p < 0.05). No significant changes regarding the LDF were found. CPAP treatment did not change the levels of NO metabolites in the erythrocytes. The erythrocyte pool of the NO metabolic pathway intermediates does not depend on OSA and its treatment, whereas the erythrocytes could constitute a high-volume buffer in their storage Hence, the results from this prospective study are a step forward in understanding the role of the erythrocyte compartment and the intra-erythrocyte pathways regulating NO bioavailability and paracrine endothelial function in the hypoxia-reoxygenation setting, such as obstructive sleep apnea.

LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals

AimsAlthough adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. Data synthesisAvailable algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. ConclusionsThe accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk.

Baseline cardiovascular risk in subjects with type 2 diabetes and chronic kidney disease from the FLOW trial

Abstract Background Patients with chronic kidney disease and type 2 diabetes (T2D) have a high risk of progression to kidney failure as well as cardiovascular (CV) events. It is established that glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and reduce body weight. Some CV outcomes trials have shown that GLP-1RAs reduce CV risk in people with T2D at high CV risk; for example, the SUSTAIN 6 trial demonstrated that the GLP-1RA semaglutide significantly lowered the rate of major CV events (CV death, non-fatal myocardial infarction and non-fatal stroke) versus placebo. Some trials have also indicated that GLP-1RAs reduce albuminuria and estimated glomerular filtration rate (eGFR) decline. Based on these previous results indicating potential kidney-protective effects, the FLOW trial (NCT03819153) is evaluating once-weekly, subcutaneous semaglutide 1.0 mg versus placebo on kidney- and CV-related outcomes in participants with T2D. We describe the baseline characteristics and the calculated CV risk of this patient population using the atherosclerotic CV disease (ASCVD) and second manifestations of arterial disease (SMART) risk calculators. Methods FLOW is an ongoing, multicentre, randomised, double-blind, parallel-group, event-driven, phase 3b trial, with participants randomised 1:1 to semaglutide or placebo, each in addition to standard of care. Recruitment is complete and 3,535 participants with T2D, an eGFR ≥25–≤75 mL/min/1.73 m2, and urine albumin-to-creatinine ratio ≥100–≤5,000 mg/g have been enrolled. The primary endpoint is time to first occurrence of a kidney composite that includes ≥50% persistent eGFR reduction, kidney failure (persistent eGFR &amp;lt;15 mL/min/1.73 m2 or initiation of chronic dialysis or kidney transplantation), and kidney-related death, or CV death. Key secondary outcomes include time to first occurrence of CV death, myocardial infarction or stroke. Results The baseline clinical characteristics and demographics are shown (Table 1). Median age was 68 years, 30% were female, mean diabetes duration was 17 years, and 98% had a history of hypertension. Overall, 52% of participants had a previous CV event. The calculated 10-year risk for ASCVD events in those without prior ASCVD was 31% in males and 18% in females, and in those with previous CV events was 37–56% in males and 35–53% in females depending on the type of CV disease reported in the calculator (Table 2). Conclusions The FLOW trial has completed enrolment. Based on the ASCVD and SMART risk calculators, the enrolled population has a substantial risk for adverse CV outcomes. Event ascertainment is ongoing, and the FLOW trial will provide evidence for the potential of semaglutide to improve kidney and CV outcomes in the T2D population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk

Prolonged mean response time in older adults with cardiovascular risk compared to healthy older adults

BackgroundDuring incremental exercise (Inc-Ex), the mean response time (MRT) of oxygen uptake (V̇O2) represents the time delay before changes in muscle V̇O2 reflect at the mouth level. MRT calculation by linear regression or monoexponential (τ’) fitting of V̇O2 data are known to be highly variable, and a combination of incremental and constant load exercise (CL-Ex) is more reproducible.MethodsWe evaluated MRT in older adults using linear regression and combination methods. We recruited 20 healthy adults (male: 9, 69.4 ± 6.8 years) and 10 cardiovascular risk subjects (male: 8, 73.0 ± 8.8 years). On day 1, they performed Inc-Ex using a 10W/min ramp protocol, for determination of the ventilatory anaerobic threshold (VAT) using the V-slope method. On day 2, they performed Inc-Ex to VAT exercise intensity and CL-Ex for 25min total. The MRT was calculated from the CL-Ex V̇O2 average and the time at equivalent V̇O2 in the Inc-Ex. We also assessed the amount of physical activity using the International Physical Activity Questionnaire short form (IPAQ-SF).ResultsThe MRT of healthy participants and those at cardiovascular risk were 49.2 ± 36.3 vs. 83.6 ± 45.4s (p = 0.033). Total physical activity in the IPAQ-SF was inversely correlated with MRT.ConclusionThe MRT was significantly prolonged in cardiovascular risk participants compared to healthy participants, possibly related to the amount of daily physical activity. Individual MRT may be useful for adjustment of exercise intensity, but this should also be based on daily physical activity and individual condition during exercise.

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[18F]F PET-CT

BackgroundFluorine-18 sodium fluoride (Na[18F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[18F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients. Methods and ResultsThirty-four high CV risk individuals without previous CV events were scanned with Na[18F]F PET-CT. Cardiac Na[18F]F uptake was assessed through the global molecular calcium score (GMCS), which was calculated by summing the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. Mean age is 63.5 ± 7.8 years and 62% male. Median GMCS is 320.9 (240.8-402.8). Individuals with more than five CV risk factors (50%) have increased GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), P = 0.01], which is positively correlated with predicted fatal CV risk by SCORE (rs = 0.32, P = 0.04). There is a positive correlation between GMCS and weight (rs = 0.61), body mass index (rs = 0.66), abdominal perimeter (rs = 0.74), thoracic fat volume (rs = 0.47), and epicardial adipose tissue (rs = 0.41), all with P ≤ 0.01. There is no correlation between GMCS and coronary calcium score nor coronary artery wall Na[18F]F uptake. ConclusionsIn a high CV risk group, the global cardiac microcalcification burden is related to CV risk factors, metabolic syndrome variables and cardiac fat. Cardiac GMCS is a promising risk stratification tool, combining a straightforward and objective methodology with a comprehensive analysis of both coronary and valvular microcalcification.

Olive Pomace Oil versus High Oleic Sunflower Oil and Sunflower Oil: A Comparative Study in Healthy and Cardiovascular Risk Humans.

Olive pomace oil (OPO) is mainly a source of monounsaturated fat together with a wide variety of bioactive compounds, such as triterpenic acids and dialcohols, squalene, tocopherols, sterols and aliphatic fatty alcohols. To date, two long-term intervention studies have evaluated OPO’s health effects in comparison with high oleic sunflower oil (HOSO, study-1) and sunflower oil (SO study-2) in healthy and cardiovascular risk subjects. The present study integrates the health effects observed with the three oils. Two randomized, blinded, cross-over controlled clinical trials were carried out in 65 normocholesterolemic and 67 moderately hypercholesterolemic subjects. Each study lasted fourteen weeks, with two four-week intervention phases (OPO versus HOSO or SO), each preceded by a three-week run-in or washout period. Regular OPO consumption reduced total cholesterol (p = 0.017) and LDL cholesterol (p = 0.018) levels as well as waist circumference (p = 0.026), and only within the healthy group did malondialdehyde (p = 0.004) levels decrease after OPO intake versus HOSO. Contrarily, after the SO intervention, apolipoprotein (APO) B (p < 0.001) and Apo B/Apo A ratio (p < 0.001) increased, and to a lower extent APO B increased with OPO. There were no differences between the study groups. OPO intake may improve cardiometabolic risk, particularly through reducing cholesterol-related parameters and waist circumference in healthy and hypercholesterolemic subjects.

Noninvasive Measurement of Aortic Pressure and Evaluation of Arterial Stiffness in Patients with Hypertension: An Observational Study.

Arterial stiffness, a major marker of vascular impedance, has been identified as a predictor of adverse cardiac outcomes. The present study determined the relationship between blood pressure (BP) and arterial stiffness measured noninvasively using a periscope in hypertensive patients. It has also evaluated the usefulness of indices of arterial stiffness in cardiovascular (CV) risk stratification and the necessity to implement these aortic pressure parameters in clinical practice. The prospective, observational study involved patients with hypertension between the age of 18 and 80 years. The demographic and anthropometric measurements of all the participants were recorded and various central and peripheral (brachial) arterial pressure parameters were measured using a periscope. The clinical variables were compared separately for different CV risk grades and arterial stiffness index (ASI) using Kruskal-Wallis test for non-normal data and chi-square test for count data. The correlation of different parameters with CV risk grade and ASI were evaluated using Spearmen's correlation method. The agreement of different ASI indices with CV risk grades was assessed using Kappa method. The study recruited a total of 3,032 patients with hypertension. Classification of the subjects for CV risk grades had demonstrated that major proportion of the patients (n = 713) had moderate and severe CV risks (n = 708). The classification of hypertensive patients for arterial stiffness had shown that 1,037 subjects had severe arterial stiffness. Classification of arterial stiffness based on BP levels had demonstrated that 623 patients with severe arterial stiffness and 315 with borderline arterial stiffness had stage II hypertension, and 480 patients with normal BP had no arterial stiffness. Brachial ASI had a strong correlation with systolic BP (SBP). A very good agreement with K value 0.871 was noted for Kappa agreement of arterial stiffness indices with CV risk. The present study corroborates the use of central BP parameters as indicators of arterial stiffness in hypertensive subjects. Noninvasive measurement of these indices has wider implications in personalized risk assessment of CV risk in subjects with hypertension.

Advanced Glycations End Products in the Skin as Biomarkers of Cardiovascular Risk in Type 2 Diabetes.

The incidence and prevalence of diabetes are increasing worldwide, and cardiovascular disease (CVD) is the leading cause of death among subjects with type 2 diabetes (T2D). The assessment and stratification of cardiovascular risk in subjects with T2D is a challenge. Advanced glycation end products are heterogeneous molecules produced by non-enzymatic glycation of proteins, lipids, or nucleic acids. Accumulation of advanced glycation end products is increased in subjects with T2D and is considered to be one of the major pathogenic mechanism in developing complications in diabetes. Skin AGEs could be assessed by skin autofluorescence. This method has been validated and related to the presence of micro and macroangiopathy in individuals with type 2 diabetes. In this context, the aim of this review is to critically summarize current knowledge and scientific evidence on the relationship between skin AGEs and CVD in subjects with type 2 diabetes, with a brief reference to other diabetes-related complications.

Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study

BackgroundIn patients with type 2 diabetes mellitus (T2DM) an association between severe hypoglycaemic episodes and the risk of cardiovascular (CV) morbidity and mortality has been previously established.MethodsWe aimed to investigate the influence of hypoglycaemia on several diabetes-related and platelet-related miRNAs selected based on bioinformatic analysis and literature search, including hsa-miR-16, hsa-miR-34a, hsa-miR-129-2, hsa-miR-15a, hsa-miR-15b, hsa-miR-106a, miR-223, miR-126. Selected miRNAs were validated by qRT-PCR in 14 patients with T2DM on metformin monotherapy, without established CV disease and antiplatelet therapy during a stepwise hypoglycaemic clamp experiment and a follow-up 7 days after the clamp event. In order to identify which pathways and phenotypes are associated with validated miRNAs we performed target prediction on genes expressed with high confidence in platelets.ResultsCirculating levels of miR-106a-5p, miR-15b, miR-15a, miR-16-5p, miR-223 and miR-126 were increased after euglycaemic clamp followed by hypoglycaemic clamp, each with its distinctive time trend. On the contrary, miR-129-2-3p, miR-92a-3p and miR-34a-3p remained unchanged. MiR-16-5p was negatively correlated with interleukin (IL)-6, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) (p = 0.002, p < 0.001, p = 0.016, respectively), whereas miR-126 was positively correlated with VCAM (p < 0.001). There were negative correlations between miR-16-5p, miR-126 and coagulation factors, including factor VIII and von Willebrand factor (vWF). Among all studied miRNAs, miR-126, miR-129-2-3p and miR-15b showed correlation with platelet function. Bioinformatic analysis of platelet-related targets of analyzed miRNAs showed strong enrichment of IL-2 signaling. We also observed significant enrichment of pathways and diseases related to cancer, CV diseases, hyperglycemia, and neurological diseases.ConclusionsHypoglycaemia can significantly influence the expression of platelet-enriched miRNAs, with a time trend paralleling the time course of platelet activation. This suggests miRNAs could be exploited as biomarkers for platelet activation in response to hypoglycaemia, as they are probably released by platelets upon activation by hypoglycaemic episodes. Should they hold their promise in clinical endpoint studies, platelet-derived miRNAs might become helpful markers of CV risk in subjects with diabetes.Trial registration The study was registered at clinical trials.gov; Impact of Hypoglycaemia in Patients With DIAbetes Mellitus Type 2 on PLATElet Activation (Diaplate), trial number: NCT03460899

T097 Novel predictors of cardiovascular risk in subjects with type-2 diabetes mellitus: Evidence from a cross-sectional study

T097 Novel predictors of cardiovascular risk in subjects with type-2 diabetes mellitus: Evidence from a cross-sectional study

Innovative Approaches to Assess Intermediate Cardiovascular Risk Subjects: A Review From Clinical to Metabolomics Strategies.

Current risk stratification strategies for coronary artery disease (CAD) have low predictive value in asymptomatic subjects classified as intermediate cardiovascular risk. This is relevant because not all coronary events occur in individuals with traditional multiple risk factors. Most importantly, the first manifestation of the disease may be either sudden cardiac death or acute coronary syndrome, after rupture and thrombosis of an unstable non-obstructive atherosclerotic plaque, which was previously silent. The inaccurate stratification using the current models may ultimately subject the individual to excessive or insufficient preventive therapies. A breakthrough in the comprehension of the molecular mechanisms governing the atherosclerosis pathology has driven many researches toward the necessity for a better risk stratification. In this Review, we discuss how metabolomics screening integrated with traditional risk assessments becomes a powerful approach to improve non-invasive CAD subclinical diagnostics. In addition, this Review highlights the findings of metabolomics studies performed by two relevant analytical platforms in current use–mass spectrometry (MS) hyphenated to separation techniques and nuclear magnetic resonance spectroscopy (NMR) –and evaluates critically the challenges for further clinical implementation of metabolomics data. We also discuss the modern understanding of the pathophysiology of atherosclerosis and the limitations of traditional analytical methods. Our aim is to show how discriminant metabolites originated from metabolomics approaches may become promising candidate molecules to aid intermediate risk patient stratification for cardiovascular events and how these tools could successfully meet the demands to translate cardiovascular metabolic biomarkers into clinical settings.

Dietary sodium estimation methods: accuracy and limitations of old and new methods in individuals at high cardiovascular risk.

Accurate and easy to use methods for dietary Na intake estimation in population level are lacking. We aimed at (i) estimating the mean Na intake in the group level using a variety of dietary methods (DM) and urinary methods (UM) and correlating them with 24-h urine collection (24UCol) and (ii) improving the accuracy of the existing DM. The most common DM (three 24-h dietary recalls (24DR) and FFQ) and UM (24UCol and spot urine collection using common equations) were applied. To improve the existing: (i) 24DR, discretionary Na was quantified using salt-related questions or adding extra 15 % in total Na intake and (ii) FFQ, food items rich in Na and salt-related questions were added in the standard questionnaire (NaFFQ). National and Kapodistrian University of Athens, Greece. Totally, 122 high cardiovascular risk subjects (56·0 ± 12·6 years; 55·7 % males). Mean 24 h Na excretion (24UNa) was 2810 ± 1304 mg/d. Spot urine methods overestimated the 24UNa (bias range: -1781 to -492 mg) and were moderately correlated to 24UCol (r = 0·469-0·596, P ≤ 0·01). DM underestimated the 24UNa (bias range: 877 to 1212 mg) and were weakly correlated with 24UCol. The improved DM underestimated the 24UNa (bias range: 877 to 923 mg). The NaFFQ presented the smallest bias (-290 ± 1336 mg) and the strongest correlation with 24UCol (r = 0·497, P ≤ 0·01), but wide limits of agreement in Bland-Altman plots (-2909 mg; 2329 mg), like all the other methods did. The existing methods exhibit poor accuracy. Further improvement of the newly developed NaFFQ could be promising for more accurate estimation of mean dietary Na intake in epidemiological studies. Additional validation studies are needed.