Vascular Organ Damage Research Articles

Association between cardiovascular risk and diastolic blood pressure in older adults with systolic blood pressure less than 130mmHg: a prospective cohort study from 2014 to 2022

BackgroundThe 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline lowered the diagnostic threshold for hypertension to a systolic/diastolic blood pressure (SBP/DBP) of 130/80 mmHg. However, the predictive value of DBP for cardiovascular (CV) risk assessment diminishes with aging. The study aimed to explore whether the new diagnostic threshold for diastolic hypertension is associated with increased risk of CV organ damage and major adverse cardiovascular events (MACEs) in older adults.Methods1181 individuals aged 65 years or older with SBP < 130 mmHg were enrolled a prospective cohort study. They were classified into Low (< 70 mmHg), Optimal (70 to < 80 mmHg), and High (80 to < 90 mmHg) DBP groups. Cardiac, vascular, and renal organ damage were measured at baseline. The endpoint of the study was MACEs.ResultsAmong 1181 participants (average age 71.9 years, 44.8% men), 172 MACEs were observed during an average follow-up of 6.4 years. We found no significant differences in CV organ damage or MACEs rates (Log-rank P = 0.73) among three groups. In multivariable Cox regression, compared to the Optimal DBP group, no significant increase in CV risk was observed in the Low DBP group (hazard ratio [HR] 1.02, [95% CI 0.68–1.52], P = 0.93) or the High DBP group (HR 1.04, [95% CI 0.72–1.49], P = 0.85). Propensity score matching showed consistent results.ConclusionIn older adults with SBP < 130 mmHg, DBP values 80–89 mmHg were not associated with higher risk of CV organ damage, events or mortality.

Age and blood pressure stratified healthy vascular aging, organ damage and prognosis in the community-dwelling elderly: insights from the North Shanghai Study

BackgroundThis study aimed to investigate the prognostic value of age and blood pressure stratified healthy vascular aging (HVA) defined in the North Shanghai Study (NSS), and illustrate its relationship with organ damage (OD).MethodsThis study enrolled 3590 community-dwelling elderly Chinese aged over 65 years and finally 3234 participants were included. 3230 individuals were included in the final analysis, with 4 participants lost to follow-up. NSS HVA was defined as low carotid-femoral pulse wave velocity (PWV) which had a higher cutoff value with advanced age and level of blood pressure. OD was thoroughly assessed and classified into vascular, cardiac and renal OD. Primary endpoints were major adverse cerebrocardiovascular events (MACCE) and all-cause mortality.ResultsNine hundred seventy-eight participants out of 3234 participants (43.1%) were identified as having NSS HVA. The NSS HVA group exhibited a younger age, lower blood pressure levels, lower body mass index, and milder OD compared to the non-NSS HVA group. Over follow-up of 5.7 ± 1.8 years, 332 MACCE (1.82 per 100 person-year) and 212 all-cause deaths (1.14 per 100 person -year) occurred. NSS HVA was associated with a reduced risk of MACCE (HR [95% CI] = 0.585, 0.454–0.754) and all-cause death (HR [95%CI] = 0.608 [0.445, 0.832]), especially in those subgroups without clinical diagnosed cardiovascular disease (CVD) or diabetes mellitus but with at least one type of OD. Moreover, NSS HVA exhibited improved prognostic value for MACCE, all-cause death and CVD death compared to other definitions of HVA.ConclusionsAge and blood pressure stratified NSS HVA could serve as an improved indicator against serious adverse events in the community-dwelling elderly Chinese.Trial registrationPrognosis in the Elderly Chinese: The Northern Shanghai Study (NSS), NCT02368938, https://clinicaltrials.gov/study/NCT02368938?cond=NCT02368938&rank=1.

What are the risk factors for ascending aorta dilatation in the non-diabetic normotensive population? A cross-sectional study in China

ObjectivesAscending aorta dilatation (AAD) has been suggested as a surrogate marker for vascular organ damage in the hypertensive population. However, limited data are available on AAD in normotensive individuals. This...

PRECLINICAL VASCULAR ORGAN DAMAGE AND VASCULAR AGEING ASSESMENT IN NON-ALCOHOLIC FATTY LIVER DISEASE AND METABOLIC ASSOCIATED FATTY LIVER DISEASE PATIENTS

Objective: Non-alcoholic fatty liver disease (NAFLD) and metabolic associated fatty liver disease (MAFLD) are a growing health problem, with a growing prevalence due to its association with metabolic syndrome and diabetes. It is known to be a risk factor for the development of cirrhosis and hepatocarcinoma, but it is also known to be an important cardiovascular risk factor. The aim of this study is to assess the burden of preclinical vascular organ damage. Design and method: The study enrolled 80 consecutive patients (mean age 63.3±15.0) who underwent hepatological evaluation in our department, with evaluation of liver fibrosis score (APRI score, FIB-4) and liver stiffness, and quantification of cardiovascular risk according to Guidelines (2021 ESC Guidelines on cardiovascular disease prevention in clinical practice). Carotid atherosclerotic burden was evaluated by B-mode ultrasound in each segment (common, bulb, internal), bilaterally, and expressed as mean of maximum IMT (M-MAX), right common carotid artery distensibility and stiffness (CardioVascular Suite 4, Quipu, Italy). Aortic stiffness was evaluated as carotid-femoral pulse wave velocity (PWV), measured by applanation tonometry (PulsePen DiaTecne, Italy), with calculation of vascular ageing. Results: We found no significant correlation between ultrasound or tonometry parameters and liver stiffness and fibrosis scores. VPWV was significantly above upper limit of normal of 10 m/s (11.6±6.0 m/s, p=0.02), and the percentiles for age were significantly higher than 50th (61.7±25.1, p&lt;0.001), with 52,5% of patients showing increased PWV. Similarly, M-MAX was higher than the upper normality level of 0.9 mm (1.09±0.30 mm, p&lt;0.001). 70% of patients had an increased M-MAX. Vascular age based on arterial stiffness resulted significantly higher than biological age (mean difference 4.6 years, p&lt;0.001). 76.2% (71/80) of the overall cohort and 45,2% (14/31) of patients classified as low risk showed at least one type of vascular organ damage. Conclusions: Patients with NAFLD or MAFLD showed a large prevalence of arterial stiffening and increased IMT and an enhanced vascular ageing, even among those classified at low cardiovascular risk according to Guidelines. Vascular organ damage evaluation could be useful to identify preclinical organ damage in these patients

Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis

Damage of the endothelial glycocalyx (eGC) plays a central role in the development of vascular hyperpermeability and organ damage during systemic inflammation. However, the specific signalling pathways for eGC damage remain poorly defined. Aim of this study was to combine sublingual video-microscopy, plasma proteomics and live cell imaging to uncover further pathways of eGC damage in patients with coronavirus disease 2019 (COVID-19) or bacterial sepsis. This secondary analysis of the prospective multicenter MICROCODE study included 22 patients with COVID-19 and 43 patients with bacterial sepsis admitted to intermediate or intensive care units and 10 healthy controls. Interleukin-6 (IL-6) was strongly associated with damaged eGC and correlated both with eGC dimensions (rs=0.36, p = 0.0015) and circulating eGC biomarkers. In vitro, IL-6 reduced eGC height and coverage, which was inhibited by blocking IL-6 signalling with the anti-IL-6 receptor antibody tocilizumab or the Janus kinase inhibitor tofacitinib. Exposure of endothelial cells to 5% serum from COVID-19 or sepsis patients resulted in a significant decrease in eGC height, which was attenuated by co-incubation with tocilizumab. In an external COVID-19 cohort of 219 patients from Massachusetts General Hospital, a previously identified proteomic eGC signature correlated with IL-6 (rs=-0.58, p < 0.0001) and predicted the combined endpoint of 28-day mortality and/or intubation (ROC-AUC: 0.86 [95% CI: 0.81–0.91], p < 0.001). The data suggest that IL-6 may significantly drive eGC damage in COVID-19 and bacterial sepsis. Our findings provide valuable insights into pathomechanisms of vascular dysfunction during systemic inflammation and highlight the need for further in vivo studies.

Therapeutics for sickle cell disease intravascular hemolysis.

Sickle cell disease (SCD) is a genetic disorder predominantly affecting individuals of African descent, with a significant global health burden. SCD is characterized by intravascular hemolysis, driven by the polymerization of mutated hemoglobin within red blood cells (RBCs), leading to vascular inflammation, organ damage, and heme toxicity. Clinical manifestations include acute pain crises, hemolytic anemia, and multi-organ dysfunction, imposing substantial morbidity and mortality challenges. Current therapeutic strategies mitigate these complications by increasing the concentration of RBCs with normal hemoglobin via transfusion, inducing fetal hemoglobin, restoring nitric oxide signaling, inhibiting platelet-endothelium interaction, and stabilizing hemoglobin in its oxygenated state. While hydroxyurea and gene therapies show promise, each faces distinct challenges. Hydroxyurea's efficacy varies among patients, and gene therapies, though effective, are limited by issues of accessibility and affordability. An emerging frontier in SCD management involves harnessing endogenous clearance mechanisms for hemolysis products. A recent work by Heggland et al. showed that CD-36-like proteins mediate heme absorption in hematophagous ectoparasite, a type of parasite that feeds on the blood of its host. This discovery underscores the need for further investigation into scavenger receptors (e.g., CD36, SR-BI, SR-BII) for their possible role in heme uptake and detoxification in mammalian species. In this review, we discussed current SCD therapeutics and the specific stages of pathophysiology they target. We identified the limitations of existing treatments and explored potential future developments for novel SCD therapies. Novel therapeutic targets, including heme scavenging pathways, hold the potential for improving outcomes and reducing the global burden of SCD.

Increased triglyceride independently associates with premature structural and functional cardiac damage progression in asymptomatic adolescents: a 7-year longitudinal study

Abstract Background High levels of triglyceride have been associated with poor cardiovascular health in adults. The relationships between triglyceride and early signs of vascular organ damage among adolescents and young adults are inconsistent. There is a scarcity of longitudinal evidence regarding the potentially deleterious effects of increased triglyceride on cardiac structure and function in apparently healthy youth. Purpose To investigate the longitudinal association of changes in triglyceride with structural and functional cardiac damage progression during growth from adolescence through young adulthood. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma triglyceride measured at 17- and 24-year clinic visits were included. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7), relative wall thickness (RWT), LV diastolic function from mitral E/A ratio (LVDF), and LV filling pressure from E/e´ ratio (LVFP) were available at baseline and follow-up. LVMI2.7 ≥51g/m2.7, RWT ≥0.44, LVDF&amp;lt;1.5, and LVFP ≥8 were categorised as LV hypertrophy, high RWT, LVD dysfunction, and high LVFP, respectively. Multivariable adjusted associations were examined using generalized linear mixed-effect models and generalized logit mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, sedentary time, light physical activity, moderate to vigorous physical activity, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) median triglyceride values increased in males from 0.72 mmol/L to 0.86 mmol/L and in females from 0.74 mmol/L to 0.80 mmol/L, over 7 years. The prevalence of LV hypertrophy increased in males from 3.6% to 11.9% and in females from 1.6% to 4% over 7 years. The prevalence of LVD dysfunction increased in males from 7.8% to 16.6% and in females from 10.3% to 15.4%. In a fully adjusted model, each 1 mmol increase in triglyceride was significantly associated with higher odds of LV hypertrophy progression (odds ratio 2.89; [95% CI, 1.54 – 5.43], p&amp;lt;0.001), LVD dysfunction (1.98 [1.86 – 3.71], p=0.032), and high LVFP (2.19; [1.29 – 3.70], p=0.004) but not high RWT (1.45; [0.77 – 2.73], p=0.245), over 7 years. Conclusion Increased triglyceride during growth from adolescence through young adulthood was independently associated with progressive structural and functional cardiac damage in asymptomatic youth.

Hypertension after the Menopause: What Can We Learn from Experimental Studies?

Hypertension is the most prevalent cardiovascular disease of the adult population and is closely associated with serious cardiovascular events. The burden of hypertension with respect to vascular and other organ damage is greater in women. These sex differences are not fully understood. The unique feature in women is their transition to menopause accompanied by profound hormonal changes that affect the vasculature that are also associated with changes of blood pressure. Results from studies of hormone replacement therapy and its effects on the cardiovascular system are controversial, and the timing of treatment after menopause seems to be important. Therefore, revealing potential sex- and sex hormone-dependent pathophysiological mechanisms of hypertension in experimental studies could provide valuable information for better treatment of hypertension and vascular impairment, especially in postmenopausal women. The experimental rat models subjected to ovariectomy mimicking menopause could be useful tools for studying the mechanisms of blood pressure regulation after menopause and during subsequent therapy.

Prevalence of microalbuminuria in patients with type 2 diabetes mellitus having diabetic retinopathy in a tertiary care hospital in eastern India: A cross-sectional study

Diabetic retinopathy is a common microvascular complication of diabetes mellitus and one of the leading causes of acquired blindness. Microalbuminuria reflects a pathophysiological state of vascular dysfunction and organ damage. It is noticed that a rise in urinary albumin excretion is seen in the early phase of diabetic retinopathy. The concordance of microalbuminuria and diabetic retinopathy has been well reported in type 1 diabetes; however, for type 2 diabetes, there is a paucity of data. To estimate the prevalence of microalbuminuria in diabetic retinopathy patients with type 2 diabetes attending the out-patient department (OPD) in a tertiary care center in eastern India and also to find out any association between microalbuminuria and severity of diabetic retinopathy. : The study included 200 patients with type 2 diabetic patients having diabetic retinopathy. The study populations were selected by thorough clinical examination and as per inclusion–exclusion criteria. Estimation of urinary albumin and albumin creatinine ratio was done by using Konelab 20 Autoanalyzer machine by the immunoturbidimetry method. Diabetic retinopathy was classified as per the International Clinical Diabetic Retinopathy Severity Scales into mild, moderate, severe, very severe non-proliferative as well as proliferative diabetic retinopathy. Data were analyzed with ratio, rate, percentage, and statistical significance was considered if p&amp;#60;0.5. : The prevalence of microalbuminuria was found in 36% (72 patients). The highest number of patients (88.24%) with microalbuminuria was found in severe NPDR. 93.06% of patients with microalbuminuria had clinically significant macular edema. A statistically significant correlation (p&amp;#60;0.001) was found between microalbuminuria and the degree of retinopathy in mild, moderate, and severe NPDR. A significant correlation was found between urinary microalbumin and the severity of diabetic retinopathy.

CARFILZOMIB-BASED REGIMEN AND CARDIOTOXICITY IN MULTIPLE MYELOMA: INCIDENCE OF CARDIOVASCU-LAR EVENTS AND ORGAN DAMAGE IN CARFILZOMIB-DEXAMETHASONE VERSUS CARFIL-ZOMIB-LENALIDOMIDE

Objective: Cardiotoxicity is a known adverse effect of Carfilzomib therapy, nevertheless few data are available on cardiovascular complications induced by different Carfilzomib-regimens in a real-life setting. The aim of this perspective study was to investigate the difference in incidence and time of onset of cardiovascular adverse events between Kd and KRd in MM patients in real-life conditions. Furthermore, we investigated differences in subclinical organ damage (both cardiac and vascular ) induced by the two regimens, and offer a discussion on how these data might support different follow up strategies for patients treated with Kd or KRd regimen Design and method: In this prospective study, adults with MM who had haematological indication to Kd or KRd, were consecutively enrolled. They underwent a baseline cardiovascular assessment before treatment initiation and a follow-up evaluation at 6 months, including office blood pressure measurements, ambulatory blood pressure monitoring, 12-leads EKG, trans-thoracic echocardiography with global longitudinal strain assessment (GLS), and estimation of arterial stiffness by the carotid-femoral pulse wave velocity (cfPWV) measurement. Results: A total of 109 patients were enrolled, 47 (43%) received Kd and 62 (57%) KRd. All-types of cardiovascular and hypertensive events occurred more frequently in Kd group compared to KRd (59% vs 40% and 55% vs 35.5% patients, respectively, p&lt;0.05), with higher incidence of hypertensive urgencies. Furthermore, the time of onset of all-type of CVAEs, major and hypertensive event was shorter in Kd regimen compared to KRd (3.6 vs. 10.2 months, 4.0 vs. 10.8 months and 8.6 vs. 14.6 months, respectively (p &lt; 0.05)). At follow-up, Kd patients developed more frequently signs of cardiac as decline of global longitudinal strain (-19.7 vs -21.3, p = 0.009) and vascular organ damage demonstrated by a rise of pulse wave velocity (8.5 vs 1.9, p = 0.009), with respect to KRd. Conclusions: In conclusion, Kd regimen showed greater cardiovascular toxicity with respect to KRd and earlier onset of events. Thus, a closer and careful follow-up should be considered.

Carfilzomib-Based Regimen and Cardiotoxicity in Multiple Myeloma: Incidence of Cardiovascular Events and Organ Damage in Carfilzomib-Dexamethasone versus Carfilzomib-Lenalidomide-Dexamethasone. A Real-Life Prospective Study.

Carfilzomib-mediated cardiotoxicity in multiple myeloma (MM) is a well-established adverse effect, however limited data are available on the comparison of cardiovascular complications in patients treated with Carfilzomib-dexamethasone (target dose of K 56 mg/m2) versus Carfilzomib-lenalidomide-dexamethasone (target dose of K 27 mg/m2) beyond controlled trials. A total of 109 patients were enrolled, 47 (43%) received Kd and 62 (57%) KRd. They then underwent a baseline and follow-up evaluation including trans-thoracic echocardiography and arterial stiffness estimation. All types of cardiovascular and hypertensive events occurred more frequently in the Kd group compared with the KRd (59% vs. 40% and 55% vs. 35.5% patients, respectively, p ≤ 0.05), with higher incidence of hypertensive. The time of onset of any type of CVAE, and of major and hypertensive events was shorter in the Kd regimen (p ≤ 0.05). At follow-up, Kd patients more frequently developed signs of cardiac (decline of global longitudinal strain) and vascular organ damage (rise of pulse wave velocity), as compared with KRd. Despite the older age, longer history of MM and longer period of pre-treatment of Kd patients, these factors did not increase the probability of incidence for all types of cardiovascular events at multivariate analysis (p > 0.05). In conclusion, the Kd regimen showed greater cardiovascular toxicity and earlier onset of events with respect to KRd. Thus, a closer and thorough follow-up should be considered.

JS-ECCR/HBPRCA-2: HOMOCYSTEINE AND LIPOPROTEIN (A) AS A DETERMINANT OF ARTERIAL STIFFNESS AND A PREDICTOR OF HYPERTENSION MEDIATED TARGET ORGAN DAMAGE (HMOD)

Background: Despite advances in modern medicine, cardiovascular disease (CVD) remains a leading cause of global mortality. Among the many CVD determinants, hypertension is a leading modifiable risk factor and blood pressure control and prevention of hypertension mediated target organ damage (HMOD) has become the hallmark of cardiovascular risk management. Homocysteine and lipoprotein (a) are independent CVD risk factors, proposed to contribute to vascular compromise by facilitating thrombogenesis and atherosclerosis. Aims: We sought to determine in a real-world clinical setting whether these risk factors interact to facilitate vascular organ damage in hypertension. Methods: We performed a cross-sectional analysis of prospectively collected data in 131 hypertensive patients referred to our tertiary hypertension clinic at Royal Perth Hospital. The Lipoprotein (a), homocysteine and other biochemical parameters studied were assayed in the central hospital laboratory. We analysed the effect of the interaction between Lipoprotein (a) and homocysteine (Lpa-Hcy) on markers of HMOD including arterial stiffness, as assessed by pulse wave velocity (PWV). Results: The average age of participants was 56 ± 0.9 years, and there was a greater proportion of males than females (62% vs. 38%). The regression analysis demonstrated that Lp(a)-Hcy interaction was significantly associated with PWV [beta = 0.33; 95% CI 0.12, 0.55; p &lt; 0.005], 24 h urinary protein excretion [beta = -10.9; 95% CI -14.5, -7.4; p &lt; 0 .001], and estimated glomerular filtration rate [beta = 103.9; 95% CI 93.9, 113.8; p &lt; 0.001], which persisted after adjusting for potential confounders such as age, sex, 24 h BP, inflammation, smoking, diabetes mellitus and other metabolic risk factors. Interaction analysis showed that increasing homocysteine and lipoprotein (a) concentration was associated with increasing arterial stiffness. Hcy levels does not affect the PWV if Lp(a) levels are normal and the knowledge of both Lp(a) and Hcy are necessary to determine arterial damage. Furthermore, Lp(a)-Hcy product exhibited a positive predictive relationship with every unit increase in Lp(a)-Hcy product associated with a 0.3 m/s increase in PWV which may represent a useful marker for cardiovascular risk stratification and may suggest the need for rigorous treatment to minimise HMOD progression. These clinical findings provide novel insights into the potential interaction between Lp(a) and Hcy in the pathogenesis of hypertension mediated vascular damage

The Complement System Mediates COVID-19 Endothelial Cell Injury, Modifying Cell Permeability

Background Coronavirus Disease 2019 (COVID-19) is a (SARS-CoV-2)-mediated respiratory disease. The severity of COVID-19 has been classified as mild, moderate, severe and critical per the WHO-China Joint Mission. Among a total of 72 314 case records from the Chinese Center for Disease Control and Prevention, approximately 81% of COVID-19 cases were defined as mild, 14% of as severe, and 5% as critical. The overall hospital mortality of COVID-19 cases is approximately 15-20%, but it is up to 40-49% among critical cases requiring intensive care unit admission. The complement system, is a key component of the innate immune response, consists of more than 50 soluble and membrane-bound proteins that provide defense against microbes and mediate inflammatory responses. The activation of the complement system involves a series of enzymatic transformations, where C3b acts as a mediator. The final step of the complement cascade is the formation of a membrane attack complex (MAC, C5b-9) on the plasma membrane (PM) of the cells. Several pathologies including thrombotic, inflammatory, autoimmune and age-related diseases are associated with abnormal complement activation. There is evidence linking the activation of the complement system and endothelial injury to organ damage and complications that increase the risk of mortality in COVID-19. We hypothesize that endothelial cell injury resulting from complement activation contributes to COVID-19-associated vascular injury and organ damage. Aims To identify differences in complement activation associated with mild and severe forms of COVID-19 To determine the role of differential complement activation by COVID-19 patient sera in mediating endothelial cell damage. Methodology Clinical information, and sera from SARS-CoV-2 positive patients with mild and severe COVID-19 were obtained from the Canadian COVID-19 Prospective Cohort Study (CANCOV) to identify complement activation and endothelial cell (EC) injury. Complement activation was determined using a previously established protocol (Noris et al., 2017). Briefly, primary human umbilical vein endothelial cells (HUVECs) were treated with adenosine diphosphate (ADP), followed by treatment with healthy control or COVID-19 patient serum. To confirm the biological activity of complement, we measured the deposition of C3b and C5b-9 on the plasma membrane of HUVECs via immunofluorescence (IF) on cells exposed to healthy or patient sera. In addition, a permeability assay using a transwell model was used to measure the changes in permeability induced by healthy or patient sera via complement activation. Briefly, HUVECs were seeded on the top part of the insert, allowing them to form a monolayer. Monolayer integrity was assessed by imaging cells stained with Hoechst (nuclear stain) and phalloidin (cytoskeleton stain) on the day of the experiment, as well as before and after incubation with healthy or patient sera. Results We were able to detect complement activation/deposition when exposing the cells to COVID-19 sera. As for C3b deposition, cells exposed to patient sera showed no difference compared to those treated with sera from healthy donors. However, we observed increased C5b-9 deposition on the PM of cells treated with patient sera compared to those treated with sera from healthy donors, with further increased deposition when cells are treated with deceased patient sera. We observed a trend demonstrating increased permeability when cells are treated with deceased COVID-19 patient sera compared to healthy donors. Cellular permeability is significantly lower in those cells treated sera from patients with mild or severe COVID-19. Conclusion There is a differential biological activity of complement on endothelial cells depending on the severity of COVID-19, this complement activation leads to an increase in cell permeability. While more research needs to be done, these results contribute to a better understanding of the consequences of complement activation on endothelium in COVID-19.

Cumulative muscle mass and blood pressure but not fat mass drives arterial stiffness and carotid intima-media thickness progression in the young population and is unrelated to vascular organ damage

We examined the longitudinal associations of fat mass, lean mass, and blood pressure (BP) from childhood through young adulthood with changes in carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT). We included 3863 participants from the Avon Longitudinal Study of Parents and Children birth cohort. Fat mass and lean mass, measured by dual-energy X-ray absorptiometry, and BP were measured at ages 9, 17 and 24 years and classified into low, moderate, and high tertiles. cfPWV and cIMT were measured at 17 and 24 years of age. Associations were examined via linear mixed effect models and adjusted for cardiometabolic and lifestyle factors. Among 1720 [44.5%] male and 2143 [55.5%] female participants, cumulative high exposures to lean mass (effect estimate 0.006 m/s [95% CI 0.001 to 0.010; p = 0.022]), systolic BP (0.013 m/s [0.009 to 0.017; p < 0.0001]) and diastolic BP (0.023 m/s [0.019 to 0.027; p < 0.0001]) from 9–24 years of age were positively associated with the 7-year increase in cfPWV. Persistent high exposures to lean mass (0.012 mm; [0.008 to 0.016; p < 0.0001]), body mass index (0.007 mm [0.003 to 0.011; p = 0.001]), and systolic BP (0.010 mm; [0.006 to 0.014; p < 0.0001]) from ages 9–24 years were positively associated with thicker cIMT at 17–24 years of age. Total fat and trunk fat mass from childhood had no association with cfPWV or cIMT progression. In conclusion, increased lean mass and BP but not fat mass from childhood drives arterial remodeling in young adulthood.

Association of Circulating Platelet Extracellular Vesicles and Pulse Wave Velocity with Cardiovascular Risk Estimation.

Elevated circulating platelet-derived extracellular vesicles (EVs) have been reported in conditions associated with thrombotic risk. The present study aimed to assess the relationship between circulating platelet-derived EV levels, cardiovascular risk stratification and vascular organ damage, as assessed by pulse wave velocity (PWV). A total of 92 patients were included in the present analysis. Platelet EV were evaluated by flow cytometry (CD41+/Annexin v+). The cardiovascular risk was determined using the 2021 ESC guideline stratification and SCORE2 and SCORE-OP. PWV was performed as a surrogate to assess macrovascular damage. Risk stratification revealed significant group differences in EV levels (ANOVA, p = 0.04). Post hoc analysis demonstrated significantly higher levels of EVs in the very high-risk group compared with the young participants (12.53 ± 8.69 vs. 7.51 ± 4.67 EV/µL, p = 0.03). Linear regression models showed SCORE2 and SCORE-OP (p = 0.04) was a predictor of EV levels. EVs showed a significant association with macrovascular organ damage measured by PWV (p = 0.01). PWV progressively increased with more severe cardiovascular risk (p < 0.001) and was also associated with SCORE2 and SCORE-OP (p < 0.001). Within the pooled group of subjects with low to moderate risk and young participants (<40 years), those with EV levels in the highest tertile had a trend towards higher nocturnal blood pressure levels, fasting glucose concentration, lipid levels, homocysteine and PWV. Levels of platelet-derived EVs were highest in those patients with very high CV risk. Within a pooled group of patients with low to moderate risk, an unfavourable cardiometabolic profile was present with higher EV levels.

Abstract P255: STUDY OF THE SEVERITY OF COVID-19 IN HYPERTENSIVE PATIENTS IN PRIMARY CARE, IN SPAIN. PRELIMINARY RESULTS.

Objective: Decision-making in the management of the COVID-19 pandemic has raised questions related to the disease progression in hypertensive patients according to their BP control and the presence of comorbidities or target organ involvement. It has been reported that HTN can worse the outcomes of patients infected by COVID-19. The aim of this study is to assess the clinical and sociodemographic parameters in this population of hypertensives treated in Primary Care, according to the severity of the disease progression (mild-asymptomatic or those who required hospital admission). Design and Methods: Multicentric, observational, cross-sectional, retrospective and analytical study. The patients were selected through a random sampling in 12 provinces in Spain, among patients older than 18y with treated hypertension and COVID-19 (PCR positive) under the primary care scope (119 investigators). Data collection time was 15 months (IQR= 5), from November 2020 to February 2022, outside the first wave. Results: 1372 patients were recruited (51% women, mean age 67yo), smoking 12.5%, obesity 43.9%, diabetes 27.5%, controlled arterial hypertension 55.9% (BP&lt;140/90). The severity of COVID-19 progression was: mild-asymptomatic 971 (71%), hospital admission 401 (29%), admission to ICU 74 (5%), death 48 (4%). Comparing the progression of the covid-19 disease of patients who requires hospital admission vs mild-asymptomatic, statistically significant differences were found between some comorbidities: COPD 21.7% vs 11.9%, p&lt;0.001; Diabetes 33.7% vs 24.9%, p&lt;0.05; Dyslipidemia 64.6% vs 57.9%, p&lt;0.05; CKD 21.5% vs 11.1%, p&lt;0.01; Stroke 9.5% vs 5.5%, p&lt;0.05; Atrial Fibrillation 17.7% vs 7.2%, p&lt;0.001; Heart Failure 17% vs 5.8%, p&lt;0.01; Ischemic Heart Disease 13.2% vs 4.6%, p&lt;0.001. As well as: GFR &lt;60 ml/min 110 (27%) vs 140 (14%), p&lt;0.001; ACR (median, IQR) 72 mg/g (10-118) vs 62 (7-115), p&lt;0.05 . Conclusions: Among Spanish hypertensive patients in Primary Care, Covid-19 mortality achieves 4%. Some comorbidities such as diabetes, ischemic heart disease, atrial fibrillation, heart failure, stroke, chronic kidney disease or dyslipidemia, in which hypertension itself develop obvious vascular organ damage, results in worsening the outcomes of this population.

Neuropilin Is a New Player in the Pathogenesis of COVID-19

—A family of glycoproteins called neuropilins is gaining attention as a new contributor to the pathogenesis of COVID-19. The concept of penetration of SARS-CoV-2 into host cells is traditionally associated with the receptor role of the ACE2 protein. New evidence suggests that it is possible to enhance pulmonary viral infection by involvement of neuropilins. Neuropilins have two prominent features: (a) a wide range of participation in cellular and tissue processes; (b) a concomitant enhancement of effects associated with the co-reception of regulatory proteins. These features determine the special role of functionally disseminated neuropilins in the pathogenesis of vascular system damage, immunothrombosis, and organ damage with comorbid manifestations during COVID-19. However, the presentation of neuropilins as a generalized therapeutic target that has a corrective effect on the affected areas is an ambiguous approach and requires a selective strategy.

Circulating platelet‐derived extracellular vesicles correlate with night‐time blood pressure and vascular organ damage and may represent an integrative biomarker of vascular health

Elevated office blood pressure (BP) has previously been associated with increased levels of circulating extracellular vesicles (EVs). The present study aimed to assess the relationship between levels of platelet derived EVs, ambulatory BP parameters, and pulse wave velocity as a marker of macrovascular organ damage. A total of 96 participants were included in the study. Platelet‐derived extracellular vesicles (pEVs) were evaluated by flow cytometry (CD41+/Annexin v+). BP evaluation included unobserved automated office BP and ambulatory BP monitoring. Carotid‐femoral pulse wave velocity (PWV) was measured as a marker of macrovascular damage. pEVs correlated with nocturnal systolic BP (r = 0.31; p = .003) and nocturnal dipping (r = ‐0.29; p = .01) in univariable analysis. Multivariable regression models confirmed robustness of the association of EVs and nocturnal blood pressure (p = .02). In contrast, systolic office, 24h‐ and daytime‐BP did not show significant associations with pEVs. No correlations were found with diastolic BP. Circulating pEVs correlated with pulse wave velocity (r = 0.25; p = .02). When comparing different hypertensive phenotypes, higher levels of EVs and PWV were evident in patients with sustained hypertension compared to patients with white coat HTN and healthy persons. Circulating platelet derived EVs were associated with nocturnal BP, dipping, and PWV. Given that average nocturnal BP is the strongest predictor of CV events, platelet derived EVs may serve as an integrative marker of vascular health, a proposition that requires testing in prospective clinical trials.

Circulating extracellular vesicles correlate with nocturnal blood pressure and vascular organ damage and may serve as an integrative biomarker of vascular health.

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Council on Science and Technology, Mexico (CONACYT). Background Elevated blood pressure (BP) has been associated with increased levels of circulating extracellular vesicles (EVs) which could potentially serve as a novel integrative biomarker for vascular health. Purpose The present study therefore aimed to assess the relationship between increased EV release, blood pressure and macrovascular organ damage. Methods A total of 83 patients with BP ranging from normal to high were included in the present analysis. Extracellular vesicles were evaluated by flow cytometry (CD41+/Annexin v+). BP evaluation included unobserved automated office BP (AOBP) and ambulatory BP monitoring (24hr-BP, day-BP and night-BP). Carotid-femoral pulse wave velocity (PWV) was measured by the SphygmoCor XCEL as a marker of macrovascular organ damage. Results Hypertensive patients (n = 73, BP 132.9 ± 17.4/79.4 ± 14.0) compared to normotensive patients (n = 10, BP 113.4 ± 10.4/71.3 ± 9.6) had higher levels of EVs (10.6 ± 8.2 vs 6.5 ± 4.5 EV/µL; p = 0.02). Circulating EVs were positively correlated with nocturnal systolic BP (r= 0.3; p = 0.01) and night-time dipping (r= -0.26; p = 0.02) in univariable analysis. In contrast, systolic AOBP, 24hr-BP and day-BP did not show significant associations. No significant correlations were found with diastolic BP. EVs were significantly correlated with PWV (r = 0.26 p = 0.02).While all BP measures were associated with PWV, average systolic night-time BP demonstrated the strongest correlation with PWV (r = 0.55; p &amp;lt; 0.001) compared to systolic AOBP (r = 0.51; p &amp;lt; 0.001), 24hr-BP (r = 0.46; p &amp;lt; 0.001), and average day-BP (r = 0.48; p &amp;lt; 0.001). Multivariable regression models confirmed robustness of the models. Conclusion We demonstrate a close positive relationship between a variety of BP measures and levels of circulating EVs as well as macrovascular damage assessed by PWV. The strongest correlation with EVs was found for average systolic nocturnal BP. Given that average nocturnal BP is the strongest predictor of CV events, EVs may serve as a useful integrative marker of vascular health and useful biomarker for CV risk assessment, a proposition that will need to be tested in prospective clinical trials. Abstract Figure.

Association of Novel Advanced Glycation End-Product (AGE10) with Complications of Diabetes as Measured by Enzyme-Linked Immunosorbent Assay.

Advanced glycation end-products (AGEs) contribute to vascular complications and organ damage in diabetes. The unique AGE epitope (AGE10) has recently been identified in human serum using synthetic melibiose-derived AGE (MAGE). We aimed at developing ELISA for AGE10 quantification, determining whether AGE10 is present in diabetic patients (n = 82), and evaluating its association with diabetic complications. In a competitive ELISA developed, the reaction of synthetic MAGE with anti-MAGE was inhibited by physiological AGE10 present in serum. In this assay, new murine IgE anti-MAGE monoclonal antibodies, which do not recognize conventional AGEs, a synthetic MAGE used to coat the plate, and LMW-MAGE (low molecular mass MAGE) necessary to plot a standard curve were used. AGE10 was significantly higher in patients with microangiopathy, in whom it depended on treatment, being lower in patients treated with aspirin. AGE10 levels were positively correlated with estimated glomerular filtration rate (eGFR) and negatively with creatinine. As a marker of stage ≥3 chronic kidney disease or microangiopathy, AGE10 displayed moderate overall accuracy (respectively, 69% and 71%) and good sensitivity (82.6% and 83.3%) but poor specificity (58.1% and 57.8%). In conclusion, newly developed immunoassay allows for AGE10 quantification. AGE10 elevation is associated with microangiopathy while its decrease accompanies stage ≥3 chronic kidney disease.