Marker Of Cardiovascular Disease Research Articles

Abstract 14427: Subclinical Age- and Sex-Differences in Ventricular Strain in the Community: A Framingham Heart Study Cardiac Magnetic Resonance Study

Introduction: Myocardial strain is a measure of deformation and a marker of cardiovascular disease (CVD). The subclinical age- and sex-associations of left and right ventricular (LV, RV) strain by feature tracking cardiovascular magnetic resonance (FT-CMR) are not well established in the community. Methods: Framingham Heart Study Offspring cohort participants (n=1077) without prevalent CVD, hypertension, diabetes, or use of treatment for these conditions underwent 1.5T CMR. Steady-state free precession cine images spanning the entirety of both ventricles were acquired in the short-axis, 2-chamber, and 4-chamber views. Global longitudinal (GLS), circumferential (GCS), and radial (GRS) strains were measured by FT-CMR (Circle cvi42 v.5.11.1). Comparisons among age groups (<45 years, 45-54 years, 55-65 years, and >65 years) were performed by one-way analysis of variance and between sexes by independent samples t -test. Results: Clinical characteristics, CMR measures, and LV and RV strain by age and sex for the cohort are presented in the Table . Across increasing age groups, we observed more favorable LV GLS, GCS, and GRS (p=0.010, p<0.001, and p<0.001, respectively). Similar trends were present for RV strain for GCS and GRS (both p<0.001) but not GLS (p=0.22). Compared with men, women had greater magnitude (more favorable) LV and RV strain values for GLS, GCS, and GRS (all p≤0.013). Conclusions: In this large community based study of individuals without CVD, LV and RV strains by FT-CMR were greater (more favorable) with increasing age and in women. The associations and long-term implications of these differences in myocardial mechanics between groups require further investigation.

Daily breakfast: will skipping a morning meal become a new prognostic marker?

The increase in the prevalence of dietary risk factors and non-communicable diseases over the past decades has led to the search for new predictors, one of which is skipping breakfast. The article examines the potential of using the "daily breakfast"/"skipping breakfast" criterion as a prognostic marker. The results of studies on the correlation of daily breakfast with dietary risk factors (obesity and hypertension), type 2 diabetes, cardiovascular diseases and the risk of cardiovascular death are presented and analyzed. The effect of breakfast on the depression risk, which is an independent marker of cardiovascular diseases, is being studied. Also, possible pathogenetic mechanisms linking skipping breakfast with increased blood pressure are discussed. Research data is provided confirming the importance of morning meals for health. The article presents data on the prevalence of daily breakfast in the Russian population and in the populations of other countries with developed economies. Information is provided on the history of studying the effect of daily breakfast on health. Also, controversial scientific data is provided on the effect of skipping breakfast on body weight and its effective control. The role of morning meals in weight reduction programs is fully discussed. The issues of connection between the morning meal and daily calorie intake, the nutritional value of consumption of total protein, vitamins and minerals, as well as the uniform meal distribution across the day are considered. Data from a scientific discussion on the criteria for an "ideal" breakfast are presented, and general recommendations on the energy and nutritional value of a morning meal and the optimal composition of food are outlined.

80 The Association between Periodontal Disease and Self-Reported Cognitive and Functional Decline at Age 60 in a Large, Multicultural Cohort Study

Objective:We assess the association between self-reported history of periodontal disease diagnosis with self-reported cognitive and functional decline at age ∼60. We also investigate (1) the roles of social background, demographic characteristics, education, and adolescent test scores in confounding that association and (2) the role of cardiovascular disease in mediating that association.Participants and Methods:We use data from a nationally representative sample of 13,525 people who participated in the 2021 wave of the High School & Beyond (HSB) cohort study. HSB began in 1980 with a nationally-representative sample of American 10th and 12th grade students; these students have been followed up on six occasions since 1980, yielding extraordinary and prospectively-collected life course data on all key measures for a large, multicultural sample.In 2021, HSB sample members were evaluated with neuropsychological tests that evaluated list learning and memory, semantic and letter fluency, and working memory. They were also asked to self-report memory and functional decline using the AD8, using a cutoff of 2 or more items for significant concerns. Mild Cognitive Impairment will be identified using an algorithm validated in a similar sample of middle aged participants.Sample members were also asked in 2021 whether a medical professional had ever diagnosed them with periodontal disease; those responding affirmatively were then asked the years in which they started and stopped having periodontal disease.Measures of social and economic background; demographic characteristics; and educational contexts, opportunities, and attainments were measured prospectively—and in great detail—in the surveys administered in the 1980s. Critically, almost all sample members completed a series of cognitive tasks during adolescence, allowing us to address a key set of confounders in the relationship between periodontal disease and MCI. Markers of cardiovascular disease were measured in both 2013 and 2021.We estimate logistic regression models predicting significant cognitive and functional concerns as a function of periodontal disease history; we also estimate models that account for confounders, including social background, demographic characteristics, education, and cognitive skills during adolescence; finally, we estimate models that account for the mediating role of cardiovascular disease. All models account for the clustered sampling design of HSB and employ sampling weights to account for HSB’s complex sampling design and selective attrition from the panel.Results:About 15% of the cohort has been diagnosed with periodontal disease, and nearly one in five had significant cognitive and functional concerns.People with a history of periodontal disease were more likely to report significant cognitive and functional concerns. This association remains substantive and statistically significant after adjusting for confounders. All else equal, the odds of people with a history of periodontal disease having an AD8 score of 2 or higher were about 60% greater than the odds of those not reporting periodontal disease. Very little of this association can be attributed to cardiovascular disease as a mediating pathway.Conclusions:People with a history of periodontal disease are at greatly elevated risk of self-reported cognitive and functional concerns at age ∼60. This supports evidence— never before collected at this scale in a long-term, representative cohort study—that oral pathogens may contribute to cognitive well-being over the life course.

Reticulated Platelets: A Promising Prognosis Marker in Cardiovascular Diseases.

No Abstract.

Carbon-based light addressable potential sensor based on nitrogen-doped graphene quantum dots for detection of low-density lipoprotein

Cardiovascular diseases have become the number one killer of human health. Early diagnosis and treatment of cardiovascular diseases can effectively improve the treatment effect and reduce the disease death rate. As an important marker of cardiovascular disease, Low-Density Lipoprotein (LDL) can be used for the early detection of cardiovascular disease. In this study, a novel carbon-based Light Addressable Potentiometric Sensor (C-LAPS) for determination LDL has been constructed based on o-phenylenediamine modified nitrogen-doped graphene quantum dots/reduce graphene oxide (OPD@NGQDs/rGO) photosensitive layer. The OPD@NGQDs/rGO photosensitive layer has excellent photoelectric conversion efficiency, large specific surface area and good biocompatibility to enhance the response signal. For the determination LDL by the C-LAPS system, LDL binding to LDL aptamer causes a change in the surface potential of the photosensitive layer, producing a response signal that can be detected by the I-V curve. Under optimal conditions, the C-LAPS had a good linear relationship with LDL concentration in the range of 0.01 μg/mL- 0.15 μg/mL. The sensitivity was 1819 mV/µg·mL−1 and the limit of detection (LOD) was 6.43 ng/mL (S/N = 3). In addition, the C-LAPS showed good specificity, reproducibility, stability and satisfactory relative error for detecting LDL in human serum samples. Therefore, the C-LAPS has good performance and demonstrates potential clinical value.

Amino acid profile in overweight and obese prepubertal children - can simple biochemical tests help in the early prevention of associated comorbidities?

It is accepted that plasma branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are closely related to metabolic risk. Arterial hypertension, metabolic syndrome, endothelial dysfunction, inflammation, and metabolic dysfunction-associated fatty liver disease (MAFLD) are frequently seen in obese patients. Many attempts have been made to find biochemical indicators for the early detection of metabolic complications in children. It is not known if different amino acid profiles and BCAA and AA concentrations in overweight and obese children correlate with chemerin, proinflammatory, and simple biochemical markers. Thus, the study aimed to find out the early markers of cardiovascular disease and MAFLD in overweight and obese children. The study included 20 overweight and obese children (M/F 12/8; mean age 7.7 ± 2.3 years; BMI 26.8 ± 5.0 kg/m2) and 12 non-obese children (control group) (M/F 4/8; mean age 6.5 ± 2.2 years; BMI 14.8 ± 1.5 kg/m2). The following plasma amino acids were measured: aspartic acid, glutamic acid, serine, asparagine, glycine, glutamine, taurine, histidine, citrulline, threonine, alanine, arginine, proline, tyrosine, methionine, valine, isoleucine, leucine, phenylalanine, tryptophan, ornithine, and lysine. Chemerin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and basic biochemistry parameters were measured. The mean plasma levels of leucine, isoleucine, valine, phenylalanine, tyrosine, glutamic acid, and alanine were significantly higher in overweight and obese children than in the control group (p<0.03-p<0.0004). Conversely, the mean values of serine, asparagine, glutamine, and citrulline were significantly lower in overweight and obese children than in the control group (p<0.03-p<0.0007). Isoleucine, leucine, valine (BCAAs) tyrosine, and phenylalanine (AAAs) levels showed a positive correlation with uric acid, ALT, hs-CRP, and chemerin (r=0.80-0.36; p<0.05-p<0.00001), but not with IL-6. The mean values of glucose, IL-6, hs-CRP, chemerin, uric acid, and ALT were significantly higher in overweight and obese children than in the control group (p<0.03-p<0.00002). In contrast, the lipid profile did not differ between groups. An abnormal amino acid profile in overweight and obese pre-pubertal children, accompanied by elevated ALT and UA observed in the studied cohort, may suggest early metabolic disturbances that can potentially lead to metabolic syndrome, or MAFLD, and increased cardiovascular risk.

The Atherogenic Index of Plasma is a Predictor for Chronic Total Occlusion and Coronary Collateral Circulation Formation in CTOs Patients.

The atherogenic index of plasma (AIP), determined by the logarithmic transformation of the ratio of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), was found to be a marker of cardiovascular disease. We sought to investigate the correlation between the atherogenic AIP and coronary collateral circulation (CCC) formation in chronic total occlusive (CTOs) patients. This retrospective cohort study included 665 non-CTOs and 345 CTOs patients. CTOs were divided into 206 CCC poor formation patients and 139 CCC good formation patients according to the Cohen-Rentrop grade. Spearman correlation analysis was carried out to obtain the relationship between AIP and the Rentrop grade. We used multivariate logistic regression analysis to assess CTOs and CCC poor formation risk factors. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold for AIP to predict CTOs and CCC poor formation. The predicted increment of AIP on CTOs and CCC poor formation was evaluated by calculating the Net Reclassification Index (NRI) and the Integrated Discriminant Index (IDI). AIP in CTOs was significantly elevated compared to non-CTOs patients [(1.55 (1.02, 2.59)) vs (1.26 (0.82, 1.90)), p 0.001] AIP in the CCC poor formation group was significantly higher than that in the CCC good formation group [(1.73 (1.12, 2.90)) vs (1.37 (0.84, 2.13)), p = 0.002]. There was a negative correlation between AIP and the Rentrop grade (r = -0.145, p = 0.007). The results of multivariate logistic regression revealed that AIP was an independent predictor of CTOs (OR = 4.371, 95% CI: 2.436-7.844, p 0.001) and CCC poor formation (OR = 3.749, 95% CI: 1.628-8.635, p = 0.002). In the ROC analysis, the area under the curve of AIP for identifying CTOs and CCC poor formation was 0.596 (OR = 3.680, 95% CI: 1.490-9.090, p = 0.005) and 0.597 (95% CI: 0.535-0.658, p = 0.002), respectively. Contrary to previous research, we found that AIP is a moderate but not powerful indicator for detecting both CTO patients and poor CCC formation.

Body Composition and Cardiovascular Risk: A Study of Polish Military Flying Personnel.

(1) Background: Military personnel worldwide exhibit high rates of obesity. Obesity, and especially visceral obesity, contribute to various health issues, including type 2 diabetes and cardiovascular diseases (CVD). While BMI is commonly used to diagnose obesity, it has limitations and does not consider factors like fat distribution or muscle mass. This study aims to assess the relationship between BMI, percent body fat, waist circumference (WC), waist-to-height ratio (WHtR), and cardiovascular risk factors in Polish military flying personnel. Methods: This study involved 200 men from the Polish Air Force aged 38.8 ± 8.5 years. Anthropometric tests, body composition tests, and tests of biochemical markers of CVD were conducted. (2) Results: The prevalence of overweight and obesity varied based on the evaluation criterion; they were present in 63.5% of soldiers by BMI and in 52.5% by percent body fat; abdominal obesity was present in almost half (47%) of the surveyed soldiers according to WC and in 62.5% according to WHtR. All markers of obesity correlated positively with various biochemical markers of CVD, and 8.5% of subjects met the criteria for metabolic syndrome. (3) Conclusions: The prevalence of obesity in Polish military flying personnel, regardless of the evaluation criterion, is associated with significant metabolic complications in the form of lipid disorders and insulin resistance.

A case-control study of early-stage radiological markers of endothelial dysfunction and cardiovascular findings in patients with osteogenesis imperfecta: genotype-phenotype correlations.

Osteogenesis imperfecta (OI) is a disease caused by defective collagen synthesis. Collagen type 1 is found in many structures in the cardiovascular system. Endothelial dysfunction, which develops prior to the emergence of structural and clinical signs of atherosclerosis, isbelieved to play a key role in atherogenesis. Endothelial dysfunction may be detected presymptomatically by non-invasive radiologic methods, such as flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT). These modalities may provide early indicators of endothelial dysfunction. This cross-sectional comparative study aimed to investigate early-stage radiological markers of endothelial dysfunction and cardiovascular diseases in OI patients and healthy controls and to investigate the correlation of findings with OI genotype. Thirty patients diagnosed with OI were paired with thirty healthy age- and gender-matched controls and echocardiogram findings were compared. None of the patients had known underlying cardiovascular disease. The mean age was 13.18±2.91 years. According to Sillence classification, 15 patients had type 1 OI, 10 had type III, and 5 had type IV. Mean CIMT in the OI group was higher in the control group (OI group: 0.42±0.06 vs. healthy controls: 0.34±0.04mm, p<0.01), and mean FMD percent was lower in the patient group (p<0.01). Left ventricular ejection fraction was 78.97±10.32 vs. 77.56±8.50 %, (OI group: 7.00±3.06 vs. healthy controls: 12.14±1.99, p=0.56), and fractional shortening was 42.68±11.94 vs. 40.23±7.99 %, (p=0.35), in OI patients and controls, respectively. Pediatric patients with OI without clinical signs of cardiovascular abnormality had significantly worse CIMT and FMD findings than healthy controls. However, no difference was determined when comparing left ventricular ejection fraction or fractional shortening. OI patients may need to be screened for cardiovascular system complications starting from an early age.

The potential DNA methylation markers of cardiovascular disease in patients with type 2 diabetes

BackgroundDNA methylation is associated with cardiovascular (CV) disease. However, in type 2 diabetes (T2D) patients, the role of gene methylation in the development of CV disease is under-studied. We aimed to identify the CV disease-related DNA methylation loci in patients with T2D and to explore the potential pathways underlying the development of CV disease using a two-stage design.MethodsThe participants were from the Jinan Diabetes Cohort Study (JNDCS), an ongoing longitudinal study designed to evaluate the development of CV risk in patients with T2D. In the discovery cohort, 10 diabetic patients with CV events at baseline were randomly selected as the case group, and another 10 diabetic patients without CV events were matched for sex, age, smoking status, and body mass index as the control group. In 1438 T2D patients without CV disease at baseline, 210 patients with CV events were identified after a mean 6.5-year follow-up. Of whom, 100 patients who experienced CV events during the follow-up were randomly selected as cases, and 100 patients who did not have CV events were randomly selected as the control group in the validation cohort. Reduced representation bisulfite sequencing and Targeted Bisulfite Sequencing were used to measure the methylation profiles in the discovery and validation cohort, respectively.ResultsIn the discover cohort, 127 DMRs related to CV disease were identified in T2D patients. Further, we validated 23 DMRs mapped to 25 genes, of them, 4 genes (ARSG, PNPLA6, NEFL, and CRYGEP) for the first time were reported. There was evidence that the addition of DNA methylation data improved the prediction performance of CV disease in T2D patients. Pathway analysis identified some significant signaling pathways involved in CV comorbidities, T2D, and inflammation.ConclusionsIn this study, we identified 23 DMRs mapped to 25 genes associated with CV disease in T2D patients, of them, 4 DMRs for the first time were reported. DNA methylation testing may help identify a high CV-risk population in T2D patients.

New Trends in the Impact of Periodontal Treatment on Early Cardiovascular Diseases Outcomes: Insights and Future Perspectives.

Cardiovascular diseases represent the primary worldwide cause of mortality, and periodontitis is the main cause of tooth loss. The incidence of atherosclerotic disease has been reported to be higher in individuals affected by periodontitis than in individuals without, regardless of many common risk factors are present. Various pathogenetic models have been presented to clarify the close correlation between these two diseases. First, periodontal bacteria and their toxins can enter the circulation both during dental procedures and normal activities such as eating and teeth brushing. Periodontal bacteria may indirectly contribute to coronary artery disease (e.g., by causing immunological reactions) or directly by damaging coronary arteries. Periodontal treatment significantly reduces periodontal pathogens such as Porphyromonas gingivalis (Pg) or Actinobacillus actinomycetemcomitans (Aa) in deep periodontal pockets. Moreover, periodontal treatment may lower blood inflammatory mediators, enhance the lipid profile, and cause favourable changes in various surrogate markers for cardiovascular disease. The way in which oral bacteremia and periodontal inflammation cause atherosclerosis is still unclear and needs further studies. The real effectiveness of periodontal treatment in preventing cardiovascular events is a topic of current interest. In this regard, this review article explores new insights and provides an indication of future directions on the function of periodontal inflammation and oral bacteria in the incidence and progression of atherosclerosis and cardiovascular diseases, with the main focus on assessing the impact of periodontal treatment on cardiovascular disease outcome biomarkers.

Gender differences in cardiovascular disease risk: Adolescence to young adulthood

Background and aimsGender differences in cardiovascular disease (CVD) have been well documented but rarely for young adults and the extent to which gender related lifestyle differences may contribute to gender differences in CVD risk experienced by young adults have not been reported. Methods and resultsData are from a long-running cohort study, the Mater-University of Queensland Study of Pregnancy (MUSP). We track gender differences in CVD related behaviours at 21 and 30 years (consumption of a Western Diet/Health-Oriented Diet, cigarette smoking, vigorous physical exercise, heavy alcohol consumption). At 30 years we compare males and females for CVD risk, and the extent to which lifestyle behaviours at 21 and 30 years contribute to CVD risk.At both 21 and 30 years of age, males more frequently consume a Western Diet and less often a Health Oriented Diet. By contrast, males are also much more likely to report engaging in vigorous physical activity. On most CVD markers, males exhibit much higher levels of risk than do females at both 21 and 30 years. At 30 years of age males have about five times the odds of being at high risk of CVD. Some lifestyle behaviours contribute to this additional risk. ConclusionYoung adult males much more frequently engage in most CVD related risk behaviours and males have a higher level of CVD risk. Gender differences in CVD risk remain high even after adjustment for CVD lifestyles, though dietary factors independently contribute to CVD risk at 30 years.

The Role of Coronary Artery Calcium Score to Assess Risk of Cardiovascular Disease in Irradiated Esophageal Cancer Patients

Coronary artery calcium (CAC) score is an important predictive imaging marker of cardiovascular disease (CVD). While studies have found positive association between CAC score and cardiac toxicity in irradiated lung and breast cancer patients, there are no studies assessing CAC scores in esophageal cancer (EC). While a cardiac-gated CT is required for standard Agatston CAC score, visual assessment of CAC via ordinal scoring on non-gated CT has shown good concordance with Agatston score. In this study, we sought to examine whether visual assessment of CAC, measured on standard of care, non-contrast chest CT, predicts the development of adverse cardiovascular events (ACVE) in irradiated EC patients. This is a single institution retrospective study of EC patients treated with RT from 2010-2021. We included patients with available PET/CT at diagnosis or chest CT simulation scan without contrast, and excluded those with history of percutaneous coronary intervention, coronary bypass surgery, or prior thoracic RT. Pre-treatment characteristics, clinical factors, and grade ≥ 3 (G3+) adverse cardiovascular events (ACVE) (CTCAEv5.0) were evaluated. Visual assessment of CAC was performed using ordinal method (CAC scored from 0 to 12), by a thoracic radiologist. Fine and Gray regression was used to compute hazard ratios for time to first ACVE. Univariate analyses using Cox proportional hazards were used for overall survival (OS). ACVEs were recorded from start of oncologic treatment and OS calculated after completion of RT. A total of 118 patients were analyzed with a median follow-up of 16 months. Median age was 67 years, 65% male, 43% white, 59% with EC of distal esophagus, and 59% had squamous cell carcinoma. Median mean heart dose was 21.93 Gy (range 0.15-36.94). 24% developed G3+ ACVEs: atrial fibrillation 9%, stroke 6%, heart failure 4%, pulmonary embolism 4%, pericardial effusion 3%, myocardial infarction 2%, heart block 2%, and cardiac death 1%. On univariate analyses, CAC >1 vs. CAC ≤ 1 trended towards increased risk of ACVE (HR = 1.95, 95% CI = 0.89-4.26; p = 0.094), however it is not predictive of OS (HR = 1.31, 95% CI = 0.75-2.30; p = 0.343). Proportion of patients with ACVEs was greater in CAC>1 group (Table). When compared to patients with CAC ≤ 1, those with CAC >1 were older (median age 62 vs 72 years, p = 0.0015), less likely to be never smokers (38% vs 30%, p = 0.0437), and more likely to have hypertension (43% vs 64%, p = 0.0197), and hyperlipidemia (30% vs 47%, p = 0.0557). This is the first study to investigate the relationship between CAC score and ACVEs in EC. While the study was underpowered (likely due to low rates of recorded ACVEs), to detect a significant association between CAC score and ACVEs, there was a trend towards increased risk of ACVEs in patients with a CAC score >1 by visual ordinal scoring. Further prospective evaluation with a larger cohort is warranted.

Ceramides are decreased after liraglutide treatment in people with type 2 diabetes: a post hoc analysis of two randomized clinical trials

BackgroundSpecific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide has been shown to induce beneficial changes in the lipid profile and reduce the risk of CVD. Reducing lipotoxic lipids with an antidiabetic drug therapy could be a path towards precision medicine approaches for the treatment of complications to diabetes. In this post-hoc study, an investigation was carried out on the effect of liraglutide on CVD-risk associated ceramides in two randomized clinical trials including participants with type 2 diabetes (T2D).MethodsThis study analyzed plasma samples from two independent randomized placebo-controlled clinical trials. The first trial, Antiproteinuric Effects of Liraglutide Treatment (LirAlbu12) followed a crossover design where 27 participants were treated for 12 weeks with either liraglutide (1.8 mg/d) or placebo, followed by a four-week washout period, and then another 12 weeks of the other treatment. The second clinical trial, Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LiraFlame26), lasted for 26 weeks and followed a parallel design, where 102 participants were randomized 1:1 to either liraglutide or placebo. Heresix prespecified plasma ceramides were measured using liquid chromatography mass spectrometry and assessed their changes using linear mixed models. Possible confounders were assessed with mediation analyses.ResultsIn the LiraFlame26 trial, 26-week treatment with liraglutide resulted in a significant reduction of two ceramides associated with CVD risk, C16 Cer and C24:1 Cer (p < 0.05) compared to placebo. None of the remaining ceramides showed statistically significant changes in response to liraglutide treatment compared to placebo. Significant changes in ceramides were not found after 12-weeks of liraglutide treatment in the LirAlbu12 trial. Mediation analyses showed that weight loss did not affect ceramide reduction.ConclusionsIt was demonstrated that treatment with liraglutide resulted in a reduction in C16 Cer and C24:1 Cer after 26 weeks of treatment. These findings suggest the GLP-1RA can be used to modulate ceramides in addition to its other properties.Trial registrationClinicaltrial.gov identifier: NCT02545738 and NCT03449654.

Single-Cell RNA Sequencing Reveals That Adaptation of Human Aortic Endothelial Cells to Antiproliferative Therapies Is Modulated by Flow-Induced Shear Stress.

Endothelial cells (ECs) are capable of quickly responding in a coordinated manner to a wide array of stresses to maintain vascular homeostasis. Loss of EC cellular adaptation may be a potential marker for cardiovascular disease and a predictor of poor response to endovascular pharmacological interventions such as drug-eluting stents. Here, we report single-cell transcriptional profiling of ECs exposed to multiple stimulus classes to evaluate EC adaptation. Human aortic ECs were costimulated with both pathophysiological flows mimicking shear stress levels found in the human aorta (laminar and turbulent, ranging from 2.5 to 30 dynes/cm2) and clinically relevant antiproliferative drugs, namely paclitaxel and rapamycin. EC state in response to these stimuli was defined using single-cell RNA sequencing. We identified differentially expressed genes and inferred the TF (transcription factor) landscape modulated by flow shear stress using single-cell RNA sequencing. These flow-sensitive markers differentiated previously identified spatially distinct subpopulations of ECs in the murine aorta. Moreover, distinct transcriptional modules defined flow- and drug-responsive EC adaptation singly and in combination. Flow shear stress was the dominant driver of EC state, altering their response to pharmacological therapies. We showed that flow shear stress modulates the cellular capacity of ECs to respond to paclitaxel and rapamycin administration, suggesting that while responding to different flow patterns, ECs experience an impairment in their transcriptional adaptation to other stimuli.

Relationship between the structure, function and endothelial damage, and vascular ageing and the biopsychological situation in adults diagnosed with persistent COVID (BioICOPER study). A research protocol of a cross-sectional study.

Background: SARS-CoV-2 infection affects the vascular endothelium, which mediates the inflammatory and thrombotic cascade. Moreover, alterations in the endothelium are related to arterial stiffness, which has been established as a marker of cardiovascular disease. The objective of this study is to analyse how the structure, vascular function, vascular ageing and endothelial damage are related to the biopsychological situation in adults diagnosed with persistent COVID and the differences by gender. Methods: This cross-sectional, descriptive, observational study will be carried out in the Primary Care Research Unit of Salamanca (APISAL) and in the BioSepsis laboratory of the University of Salamanca. The sample will be selected from the persistent COVID monographic office at the Internal Medicine Service of the University Hospital of Salamanca, and from the population of subjects diagnosed with persistent COVID in the clinical history of Primary Care. Through consecutive sampling, the study will include 300 individuals diagnosed with persistent COVID who meet the diagnosis criteria established by the WHO, after they sign the informed consent. Endothelial damage biomarkers will be measured using ELLA-SimplePlexTM technology (Biotechne). Their vascular structure and function will be analysed by measuring the carotid intima-media thickness (Sonosite Micromax); the pulse wave and carotid-femoral pulse wave velocity (cfPWV) will be recorded with Sphygmocor System®. Cardio Ankle Vascular Index (CAVI), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index will be analysed with Vasera VS-2000®. The integral assessment of the subjects with persistent COVID will be conducted with different scales that evaluate fatigue, sleep, dyspnea, quality of life, attention, nutrition state, and fragility. We will also evaluate their lifestyles (diet, physical activity, smoking habits and alcohol consumption), psychological factors, and cognitive deterioration, which will be gathered through validated questionnaires; moreover, physical activity will be objectively measured using a pedometer for 7days. Body composition will be measured through impedance using an Inbody 230. Vascular ageing will be calculated with 10 and 90 percentiles of cfPWV and baPWV. Furthermore, we will analyse the presence of vascular injury in the retina, heart, kidneys and brain, as well as cardiovascular risk. Demographic and analytical variables will also be gathered. Discussion: Arterial stiffness reflects the mechanic and functional properties of the arterial wall, showing the changes in arterial pressure, blood flow, and vascular diameter that occur with each heartbeat. SARS-CoV-2 affects the endothelial cells that are infected with this virus, increasing the production of pro-inflammatory cytokines and pro-thrombotic factors, which can cause early vascular ageing and an increase of arterial stiffness. Persistent COVID is a complex heterogeneous disorder that affects the lives of millions of people worldwide. The identifications of potential risk factors to better understand who is at risk of developing persistent COVID is important, since this would enable early and appropriate clinical support. It is unknown whether vascular alterations caused by COVID-19 resolve after acute infection or remain over time, favouring the increase of arterial stiffness and early vascular ageing. Therefore, it is necessary to propose studies that analyse the evolution of persistent COVID in this group of patients, as well as the possible variables that influence it. Clinical Trial registration: ClinicalTrials.gov, identifier NCT05819840.

The association between atherogenic index of plasma and all-cause mortality and cardiovascular disease-specific mortality in hypertension patients: a retrospective cohort study of NHANES

BackgroundAtherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD), was related to the all-cause mortality and CVD-specific mortality in a U-shape in general population respectively. However, no studies have investigated these associations in hypertensive populations. Herein, this study aims to explore the relationship of AIP and all-cause mortality and CVD-specific mortality in patients with hypertension in order to provide some reference for the risk hierarchical management of hypertension.MethodsDemographic and clinical data of 17,382 adult patients with hypertension were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005–2018 in this retrospective cohort study. We used weighted univariate COX regression analysis to screen the covariates, and that weighted univariate and multivariate COX regression analyses to explore the association between AIP and all-cause mortality and CVD-specific mortality with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of age, gender, body mass index (BMI), CVD, diabetes mellitus (DM), antihyperlipidemic agents use, and hypotensive drugs use were also performed for further exploration of these relationships.ResultsThe average follow-up time was 97.10 months. A total of 2,844 patients died, and 971 of them died due to CVD. After adjusting for age, race, education level, marital status, poverty-income ratio (PIR), smoking, BMI, physical activity, antihyperlipidemic agents, DM, CVD, hypotensive drugs, estimated glomerular filtration rate (eGFR), and total energy intake, we found that both low [HR = 1.18, 95%CI: (1.07–1.32)] and high [HR = 1.17, 95%CI: (1.03–1.33)] levels of AIP were linked to an increased risk of all-cause mortality, and the U-shape association between AIP and CVD-specific mortality was also found [low AIP level: HR = 1.26, 95%CI: (1.05–1.51); high AIP level: HR = 1.26, 95%CI: (1.06–1.49)]. Furthermore, these relationships were existed in patients whose BMI > 25, were non-Hispanic White, with non-CVD, non-DM, non-antihyperlipidemic agents, and used hypertension drug (all P < 0.05).ConclusionAIP was associated with both all-cause mortality and CVD-specific mortality in patients with hypertension, but the specific role of AIP in prognosis in hypertensive populations is needed further exploration.

Antibodies against malondialdehyde among 60-year-olds: prediction of cardiovascular disease

Malondialdehyde (MDA) is generated in oxidized LDL. It forms covalent protein adducts, and is recognized by antibodies (anti-MDA). We previously studied IgM anti-MDA, and here we focus on IgG, IgG1 and IgG2 anti-MDA in predicting cardiovascular disease (CVD). We determined, by ELISA, anti-MDA in a 7-year follow-up of 60-year-old men and women from Stockholm County (2039 men, 2193 women). We identified 210 incident CVD cases (defined as new events of myocardial infarction (MI), and hospitalization for angina pectoris) and ischemic stroke, and 620 age- and sex-matched controls. IgG anti-MDA was not associated with CVD. Median values only differed significantly for IgG1 anti-MDA among men, with lower levels among cases than controls (p = 0.039). High IgG1 anti-MDA (above 75th percentile) was inversely associated with CVD risk after adjustment for smoking, body mass index, type 2 diabetes, hyperlipidemia, and hypertension, (OR and 95% CI: 0.59; 0.40–0.89). After stratification by sex, this association emerged in men (OR and 95% CI: 0.46; 0.27–0.77), but not in women. IgG2 anti-MDA were associated with protection in the whole group and among men though weaker than IgG1 anti-MDA. IgG2 anti-MDA above the 75th percentile was associated with an increased risk of MI/angina in women (OR and 95% CI: 2.57; (1.08–6.16)). IgG1 and less so IgG2 anti-MDA are protection markers for CVD and MI/angina in the whole group and among men. However, IgG2 anti-MDA was a risk marker for MI/angina among women. These findings could have implications for both prediction and therapy.

Vibrational spectroscopy identifies myocardial chemical modifications in heart failure with preserved ejection fraction

BackgroundVibrational spectroscopy can be a valuable tool to monitor the markers of cardiovascular diseases. In the present work, we explored the vibrational spectroscopy characteristics of the cardiac tissue in an experimental model of heart failure with preserved ejection fraction (HFpEF). The goal was to detect early cardiac chemical modifications associated with the development of HFpEF.MethodsWe used the Fourier-transform infrared (FTIR) and Raman micro-spectroscopic techniques to provide complementary and objective tools for the histological assessment of heart tissues from an animal model of HFpEF. A new sampling technique was adopted (tissue print on a CaF2 disk) to characterize the extracellular matrix.ResultsSeveral spectroscopic markers (lipids, carbohydrates, and glutamate bands) were recognized in the cardiac ventricles due to the comorbidities associated with the pathology, such as obesity and diabetes. Besides, abnormal collagen cross-linking and a decrease in tryptophan content were observed and related to the stiffening of ventricles and to the inflammatory state which is a favourable condition for HFpEF.ConclusionsBy the analyses of tissues and tissue prints, FTIR and Raman techniques were shown to be highly sensitive and selective in detecting changes in the chemistry of the heart in experimental HFpEF and its related comorbidities. Vibrational spectroscopy is a new approach that can identify novel biomarkers for early detection of HFpEF.

Endothelial Progenitor Cells in Autoimmune Disorders.

Circulating endothelial progenitor cells (EPCs) were first described in 1997 by Asahara et al. as "putative endothelial cells" from human peripheral blood. The study of endothelial progenitors is also intensifying in several pathologies associated with endothelial damage, including diabetes, myocardial infarction, sepsis, pulmonary arterial hypertension, obstructive bronchopneumopathy and transplantation. EPCs have been studied in several autoimmune diseases with endothelial involvement such as systemic lupus erythematosus, thrombotic thrombocytopenic purpura, antineutrophil cytoplasmic antibodies, vasculitis, rheumatoid arthritis, Goujerot-Sjögren and antiphospholipid syndrome. Factors involved in endothelial damage are due to overexpression of pro-inflammatory cytokines and/or autoantibodies. Management of these pathologies, particularly the long-term use of glucocorticoids and methotrexate, promote atherosclerosis. A lack of standardized assessment of the number and function of EPCs represents a serious challenge for the use of EPCs as prognostic markers of cardiovascular diseases (CVD). The objective of this review was to describe EPCs, their properties and their involvement in several autoimmune diseases.