Marker Of Cardiovascular Disease Research Articles

Early Diagnosis of Subclinical Atherosclerosis in Asymptomatic Type 2 Diabetic Normotensive Menopausal Women: A Global Pulse Wave Velocity Study

AbstractArterial stiffness serves as a cardiovascular disease marker, aiding in the early identification of high-risk patients. We aimed to evaluate the prevalence of arterial stiffness, measured by global pulse wave velocity (gPWV), among diabetic normotensive menopausal women (DPMW) and its correlation with levels of glycosylated hemoglobin (HbA1c). We recruited 641 consecutive DPMW diagnosed with type 2 diabetes over 5 years. The control group (CG) consisted of 300 normotensive, normoglycemic menopausal women. Normal gPWV was defined as a velocity ≤7.1 m/s. We enrolled 641 DPMW with a mean age of 57 ± 12 years. The CG comprised 300 normotensive, normoglycemic postmenopausal women with a mean age of 56 ± 4 years. Among DPMW, 29 (4.5%) exhibited increased gPWV compared with 4 (1.3%) in the CG (p < 0.01). Of the 225 (35.1%) DPMW with HbA1c > 7.5%, 23 (10.2%) had increased gPWV. In contrast, among the 416 (64.9%) DPMW with HbA1c < 7.5%, only 6 (1.4%) had increased gPWV (p < 0.0001). Electrocardiographic (ECG) abnormalities were detected in 208 (32.4%) DPMW, with 11 (5.3%) of them exhibiting increased gPWV (p = 0.6). There was a higher prevalence of increased gPWV in asymptomatic normotensive DPMW, with a significant association between increased gPWV and elevated HbA1c levels. However, there was no correlation between increased gPWV and abnormal ECG findings, despite ECG being the sole test recommended by current guidelines for all diabetic patients. Early detection of elevated HbA1c levels and increased gPWV may identify asymptomatic DPMW at higher cardiovascular risk, highlighting the inadequacy of a simple ECG in assessing cardiovascular risk in this population.

Association between perceived discrimination and pulse wave velocity: a scoping review

Racial discrimination is a chronic stressor that may contribute to cardiovascular disease (CVD) disparities in non-Hispanic Black (NHB) adults. NHB adults experience greater perceived discrimination (PD) and CVD risk compared with non-Hispanic White adults. Although the association between PD and some subclinical CVD markers has been examined, the relationship between PD and arterial stiffness has not been established, limiting our understanding of the impact of PD on CVD.ObjectiveThe objective of this review was to summarise the literature on the relationship between PD and arterial stiffness.DesignSystematic scoping review.Data sourcesPubMed, Embase, SPORTDiscus with full text and CINALH+ with full text databases were searched from inception to 10 July 2023.Eligibility criteriaAdults (≥18 years), arterial stiffness measured as pulse wave velocity (PWV), PD assessment, and randomised control trial or observational study designs.Data extraction and synthesisOf 453 articles identified, four studies were included. Two studies were cross-sectional (United States, Brazil), one was longitudinal (United Kingdom), and another was a randomized control trial (United States).ResultsThe age of the study populations ranged from 18 years to 75 years and one study evaluated a clinical population. All studies used different PWV devices and PD assessments. Associations between PD and PWV varied by geographical region, sex, clinical status and study design.ConclusionResearch evaluating the association between PD and PWV is scarce and heterogeneous in PD and PWV assessments. There is an inconclusive association between PD and PWV.

Effect of Lactobacillus plantarum supplementation on trimethylamine-N-oxide levels in 30 patients with atherosclerotic cardiovascular disease: A double-blind randomized controlled trial

Introduction: Trimethylamine-N-oxide (TMAO) is a metabolite produced by intestinal microbiota. It is well recognized as an independent risk marker for cardiovascular and renal diseases and mortality. Aim: The aim of the present study was to investigate the effect of Lactobacillus plantarum GLP3 supplementation on TMAO levels in 30 patients with a history of atherosclerotic cardiovascular disease after 12 weeks of treatment. Materials and methods: Thirty consecutive male patients with a history of clinical atherosclerotic cardiovascular disease were randomized in the study. TMAO levels were evaluated in human plasma samples using high-performance liquid chromatography with triple quadrupole tandem mass spectrometry and results were presented as the median (interquartile range). Microbiome sequencing analysis, focusing on bacteria from the genus Lactobacillus, was performed in 21 patients. Results: Patients receiving probiotic treatment showed a significant decrease in the TMAO levels [from 284 (139) µg/L to 202.5 (96.7) µg/L; p=0.044], with no significant change apparent in the placebo group after the treatment [from 176 (120) µg/L to 178 (150) µg/L; p=0.258]. Lactobacillus spp. % in the probiotic group was significantly increased after the interventional procedures [0.6 (0.14) before and 0.79 (0.6) after the treatment; p=0.041]. Conclusion: Probiotic supplementation with Lactobacillus plantarum GLP3 reduced the TMAO levels in very high-risk patients for cardiovascular diseases.

Serum Levels of Trace Elements (Magnesium, Iron, Zinc, Selenium, and Strontium) are Differentially Associated with Surrogate Markers of Cardiovascular Disease Risk in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD), which is attributed to inflammatory processes that accelerate atherosclerosis. Therefore, the exploration of novel biomarkers association is needed. This study investigated the associations between serum trace elements (Fe, Zn, Mg, Se, and Sr) and surrogate markers of CVD in 219 RA patients and compared them with those with metabolic disorders (MetD, n = 82) and control participants (n = 64). Surrogate markers included carotid intima-media thickness (cIMT), carotid plaque presence (cPP), pulse wave velocity (PWV), distensibility (DIST), and the augmentation index (AIx). RA patients displayed heightened inflammatory markers, increased arterial stiffness and thickness, and elevated CV risk factors. Compared with those in control participants, Se levels in RA patients were lower, regardless of sex. Women and men with RA had lower Sr and Mg levels than those with MetD, respectively. Backward regression models demonstrated inverse associations of Sr and Zn with cIMT in men with RA and those with MetD, respectively. In RA patients, Sr and Zn were predictors of an increased AIx, with sex-specific associations. Increased Fe levels were associated with an increased AIx in women with MetD. Fe and Zn were predictors of increased cIMT in control participants, with sex-specific associations. Serum trace elements are independently associated with surrogate markers of CVD in patients with RA, highlighting their potential role in CV risk assessment. Prospective studies are essential for validating these associations and establishing optimal trace element levels for managing CVD risk in patients with RA.

Assessment and Predictors of Metabolic Syndrome in Patients With Xanthelasma Palpebrarum: An Observational Study

Introduction: Xanthelasma palpebrarum is considered to be a cutaneous marker for cardiovascular diseases, and there is a known association with hypertension, insulin resistance, diabetes mellitus, obesity and stroke. Objectives: Our aim was to study the association and identify the predictors of Metabolic Syndrome in patients of xanthelasma palpebrarum. Methods: An observational study was conducted on 55 patients in which patients of both sexes between the ages of 20-70 years without any other skin condition were included after written informed consent. After history and examination, blood pressure and waist circumference were measured in all the subjects. Investigations were sent for fasting blood sugar levels and serum lipid profile. The 2006 IDF Definition of Metabolic Syndrome was used as assessment criteria. Results: Among the 55 patients, metabolic syndrome was present in 23 patients (41.82%). There was a statistically significant (p<0.05) difference in the values of waist circumference (100% vs. 59.38%, P=0.0003), elevated blood pressure (82.61% vs. 9.38%, P<.0001), raised fasting blood sugar (47.83% vs. 18.75%, P=0.021), and raised triglyceride levels (56.52% vs. 25%, P=0.018) between patients with metabolic syndrome and those without. However, HDL cholesterol levels (34.78% vs. 50%, P=0.262) were comparable between both groups. Also, a patient aged 41 years or more with even a single xanthelasma of more than 1 year’s duration has 76.1% chance of developing metabolic syndrome. Conclusions: Metabolic syndrome develops in a sizeable number of xanthelasma palpebrarum patients and therefore this gives us an opportunity for early diagnosis and intervention to prevent the development of cardiovascular complications.

Amyloid beta, a marker of vascular aging and cardiovascular disease, is associated with accelerated progression of renal dysfunction

Abstract Background Amyloid-beta (1-40) (Αb1-40), a proinflammatory and pro-atherosclerotic peptide, is involved in Alzheimmer’s disease and vascular aging and is considered an emerging prognostic marker of atherosclerotic cardiovascular disease (ASCVD) and heart failure. Because Ab1-40 clearance is largely dependent on renal function while clinical data consistently associate this peptide with renal function, we hypothesized that Ab1-40 circulating levels would serve as a predictor of progression of renal dysfunction. Purpose To examine the potential cross-sectional and prospective bidirectional association of Ab1-40 levels with renal function in a population with a wide range of ASCVD risk. Methods In the settings of the Athens Cardiometabolic registry, data from consecutively recruited subjects with (n=137) and without clinically overt ASCVD (n=674) with available both Ab1-40 plasma levels and GFR values (total n=811) were analyzed. Αb1-40 was measured by enzyme-linked immunosorbent assay and renal function was assessed by estimation of glomerular filtration rate (GFR). Of these subjects, 182 individuals consented to be followed up and re-assessed after a minimum period of 12 months in order to examine a potential bidirectional link between changes in Ab1-40 levels and GFR. Results Patients with increased Ab1-40 levels at baseline had significantly worse renal function, reflected as lower GFR values, compared with their counterparts with lower Ab1-40 levels (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p<0.001). Elevated Ab1-40 levels were associated with chronic kidney disease (CKD) stage 2 [odds ratio (OR)=2.29, 95% confidence intervals (CI)= 1.58-3.31, p<0.001] and CKD stage 3 (OR=3.67, 95% CI=2.37-5.70, p<0.001) at baseline. Furthermore, increased Ab1-40 at baseline was prospectively associated with accelerated progression of renal dysfunction as assessed by changes in GFR values between baseline and follow-up [mean adjusted rate of decrease=-7.20 (95% CI=-1.33, -13.07) for higher vs lowest tertiles of Ab1-40 levels across a follow-up period of 12 months, p=0.017 for interaction). On the contrary, baseline GFR values were not prospectively associated with Ab1-40 levels at follow-up visits (p>0.05). Conclusion In a population with a wide range of ASCVD risk, high Αb1-40 levels at baseline were associated both with renal function at baseline and with accelerated rate of progression of GFR deterioration at follow-up irrespective of its baseline levels. These findings suggest a mechanistic background for the established association of Ab1-40 with renal function and warrant further research to clarify the clinical value of monitoring its circulating levels as a novel biomarker which could reflect enhanced risk for renal dysfunction.

Correlation between LDL/HDL-cholesterol ratio and long term prognosis after acute coronary syndrome and severity of coronary artery disease

Abstract Introduction Dyslipidaemia is an important correctable risk factor for coronary artery disease (CAD). Many studies have confirmed that the lower the low-density lipoprotein cholesterol (LDL-C) levels are, the lower is the CAD morbidity and mortality rates (1). However, many patients who achieved low levels of LDL-C still experience a major adverse cardiovascular event (MACE) because of the other residual risk factors. Therefore, there is a constant need for better stratification of patients who are at higher risk for novel MACE following their first acute coronary syndrome (ACS). Evidence increasingly suggests that the ratio of LDL-C/HDL-C might be a new and better marker of cardiovascular disease, as it simultaneously evaluates the levels of both LDL-C and HDL-C (2). Purpose The aim of this study was to investigate the prediction value of LDL-C/HDL-C ratio for long term prognosis after ACS as well as its correlation with CAD severity. Methods We included patients hospitalized at out centre with ACS from January 2017 to January 2024. Demographic data, data on LDL-C and HDL-C levels on admission and calculated Syntax score were used. Syntax score is a comprehensive angiographic scoring system which determines complexity by using coronary anatomy and lesion characteristics (3). Follow-up data were collected either by clinical follow-up visits or by telephone interviews. The MACE was defined as the composite of cardiovascular death, acute coronary syndrome and need for elective or urgent percutaneous or surgical revascularization. Results This registry-based study included 2471 patients with ACS, median age of 64 (interquartile range 56-73) years, 31% female. Total of 1099 patients (44%) had non-ST elevation ACS and 1372 (54%) had ST elevation myocardial infarction (STEMI). Median Syntax score was 13 (IQR 7-20.5), with 1494 (61%) patients having low Syntax score (≤16), 508 (21%) patients medium (16-22), and 448 (18%) high score (>22), respectively. Median follow up was 17 (3-27) months. LDL-C/HDL-C ratio correlated significantly with cardiovascular death, with weak coefficient (2.94 vs. 2.54 p<0.001; rho=0.102, p<.0001), however did not correlate with MACE (2.88 vs. 2.92, p=0.188, rho=0.06, p=0.77). This remained identical when tested for patients with STEMI and non-STE ACS. In addition, LDL-C/HDL-C ratio did not correlate with CAD severity as assessed with Syntax score (low 2.92 vs. medium 2.83 vs. high 2.86, p=0.597; rho=0.4, p=0.09). Conclusion Our data suggest that LDL-C/HDL-C ratio cannot be used as a relevant predictor of post-ACS long-term MACE or cardiovascular death, nor it can be correlated with CAD severity. Further studies are needed to establish the real value of LDL-C/HDL-C ratio as a post-ACS predictor.

High prevalence of coronary artery calcium and aortic calcification in adults with repaired coarctation of the aorta and interrupted aortic arch

Abstract Background There is a high rate of late cardiovascular mortality in patients with repaired coarctation of the aorta (CoA) and interrupted aortic arch (IAA). Coronary artery calcium (CAC) is a marker of cardiovascular disease and there is growing evidence for aortic calcification as a predictor. Recent research in the general population suggests any CAC in males <35 years old and females ≤45 years places them at ≥90th percentile. Aims We aimed (1) to determine the prevalence of CAC, thoracic aorta calcification (TAC), and abdominal aorta calcification (AAC) in patients with CoA or IAA repair, and (2) to compare patients to a control group of Tetralogy of Fallot (TOF) patients, a condition with no known increased risk of atherosclerotic cardiovascular disease. Methods Retrospective cohort study of adult survivors of CoA/IAA repair followed up at an adult congenital heart disease (ACHD) clinic. Patients with at least 1 chest, abdomen, or pelvis computerised tomography (CT) scan for any indication were included. The presence/absence of calcification in the coronary arteries or aorta was assessed qualitatively. Patients on antihypertensive and statin therapy were considered hypertensive and hypercholesterolaemic, respectively. Patients were compared to adult survivors of TOF repair with CT scans for any indication (controls). Results Ninety-three CoA/IAA patients (87% CoA/13% IAA, median age at latest follow-up 34 years) had a total of 169 chest and 37 abdomen/pelvis CTs; 82, 93, and 37 patients had at least 1 CT suitable for CAC, TAC, and AAC review, respectively. CAC was present in 22% (18/82), TAC in 33% (31/93), and AAC in 23% (5/22) of CoA/IAA patients. CAC was present in 12% (18/153) and TAC in 11% (18/158) of TOF patients. CoA/IAA patients were more likely to have CAC and TAC than TOF patients (p=0.04 and p<0.0001; respectively) and be younger at the time of diagnosis (CAC p=0.03, TAC p=0.0001) despite TOF patients being older at time of latest CT scan (p=0.0003) (Table 1). Males aged <35 years and females ≤45 years represented 44% (8/18) of CoA/IAA patients with CAC. CoA/IAA patients with CAC were more likely to be hypertensive and hypercholesterolaemic than those without (78% [14/18] vs 48% [31/64], p=0.03; and 28% [5/18] vs 0% [0/64], p<0.0001; respectively) and was similar for TAC (hypertension p=0.005, hypercholesterolaemia p=0.04) but not AAC. After a mean follow-up of 11±7 years from first ACHD clinic, of the 93 patients, 2 patients died, 5 had coronary artery disease (at least mild stenosis on invasive angiography), 3 had a stroke, and 70% (65/93) were considered hypertensive at latest follow-up. Conclusions There is a high prevalence of CAC, aortic calcification, and hypertension in young adults with repaired CoA/IAA. Coronary and thoracic aortic calcification occurs at a younger age compared to controls. Further studies are warranted to assess the impact of aggressive cardiovascular risk reduction in this high-risk group.

Lipoprotein(a) and atherosclerotic cardiovascular disease in a Brazilian tertiary hospital population

Abstract Background/Introduction Elevated levels of lipoprotein(a) [Lp(a)] are a strong risk marker of atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction (MI), ischemic stroke, and peripheral arterial disease, as well as of aortic valve calcification and stenosis. However, few studies have assessed the prevalence of high Lp(a) levels in patients followed at a tertiary hospital specialized in cardiovascular diseases (CVD). In addition, there is scant information about Lp(a) concentrations in Brazilian individuals. Purpose The aim of the study was to describe the demographic characteristics and comorbidities of patients with at least one measure of Lp(a) at a tertiary treatment center for CVD in our city – Brazil. Methods Patients treated at a heart institute had their data extracted between the years 1999 and 2021. Data were obtained through direct electronic extraction of patients' medical records. The patients were categorized according to different Lp(a) cutoff levels (> 50 and < 70, > 70 and < 90, and > 90 mg/dL) and by quartiles. Results Of 4,970 unique patients included in the study, the mean age at baseline was 59.9 years (SD ± 14.5), 2,634 (53%) were male, and the median Lp(a) was 23.2 mg/dL (interquartile range 8.9 - 56.8 mg/dL). In the whole cohort, 460 (9.3%) had Lp(a) > 50 and < 70, 344 (6.9%) > 70 and < 90, 612 (12.3%) > 90 mg/dl and 138 (2.8%) > 150 mg/dL. Established ASCVD was reported in 1,223 (24%) of the individuals, with a progressively higher prevalence across the Lp(a) categories above (31.2%, 33.8%, 34.2%, respectively) (table 1). Moreover, the Lp(a) median (interquartile range) in mg/dL was significantly higher in those with baseline history of ASCVD (31.4 [10.8-71.2] vs 21.2 [8.3-52]), MI (27.8 [10.6-65.9] vs 22.3 [8.5-54.7]) and stroke (24.9 [10-69.5] vs 23.1 [8.9-56.5]), all p < 0.05 (table 2). Lp(a) was also significantly higher among those with LDL-C ≥ 100 mg/dL relative to LDL-C < 100 mg/dl (25.5[9.5-63.2] vs 21.4[8.4 vs 52.2] p < 0.05). Conclusions In this cohort of patients followed at a tertiary center specialized in CVD, approximately a third had Lp(a) levels above 50 mg/dL, a cutoff robustly associated with ASCVD. This finding likely represents an important source of cardiovascular residual risk, particularly in those with established ASCVD, exposing the need of further therapies.

Assessment of body composition in young adulthood and its associations to early changes in cardiovascular phenotypes: a cross-sectional study

Abstract Introduction Obesity in young adulthood is associated with various cardiovascular structural and functional changes, commonly used as markers of early subclinical cardiovascular disease. Whether these changes occur predominantly in relation to increased fat mass (FM) or are instead more closely related to simultaneous increases in underlying fat-free mass (FFM) that are known to occur in obesity, is incompletely understood. Purpose To investigate associations between both FM and FFM and a wide range of cardiac (left ventricular mass, LVM; end-diastolic volume, EDV; cardiac output, CO; stroke volume, SV), vascular (systolic blood pressure, SBP; diastolic blood pressure, DBP; mean arterial pressure, MAP; systemic vascular resistance, SVR) and autonomic (heart rate variability triangular index, HRVTI; baroreceptor reflex sensitivity, BRS) phenotypes commonly used to monitor the early evolution of subclinical CVD. Methods The study used data from extensive adipose and cardiovascular phenotyping of 408 healthy young adults (mean age 21 years) participating in a sub-study of the long-running ALSPAC birth cohort. We performed cross-sectional analysis using multiple imputation, multivariable linear regression and interaction testing to assess the association between both FM and FFM and cardiovascular phenotypes. Results Our study revealed that FFM resulted in a much greater increase in CO (difference in outcome per 1-SD difference in exposure β=0.58L/min, p<0.01, 95% CI=0.38, 0.77) than FM (β=0.20L/min, p=0.01, 95% CI=0.05, 0.36), following adjustment for both tissue types. FFM was also associated with an increase in LVM (β=19.1g, p<0.01, 95% CI=16.61, 21.58), EDV (β=22ml, p<0.01, 95% CI=18.18, 25.13) and SV (β=13ml, p<0.01, 95% CI=10.96, 15.75). FFM was also associated with improved autonomic and peripheral vascular function, including lower HR (β=-4bpm, p<0.01, 95% CI=-6.12, -1.95), higher HRVTI (β=2.1, p<0.01, 95% CI=0.72, 3.48) and lower SVR (β=-1.1, p<0.01, 95% CI=-2.12, -1.07), resulting in unchanged MAP despite elevations in CO. On the contrary, FM was not associated with LVM (β=-0.91g, p=0.35, 95% CI=-2.85, 1.02), and was associated with lower EDV (β=-4.62ml, p<0.01, 95% CI=-7.34, -1.88) and reduced autonomic function, as seen with HRVTI (β=-1.83, p<0.01, 95% CI=-3.02, -0.64) and BRS (β=-2.47, p=0.01, 95% CI=-4.27, -0.67). FM was also associated with increased HR (β=3.26bpm, p<0.01, 95% CI=1.57, 4.94) and increased SBP (β=2.14mmHg, p<0.01, 95% CI=1.01, 3.27) DBP (β=2.68mmHg, p<0.01, 95% CI=1.60, 3.77), and MAP (β=2.34mmHg, p<0.01, 95% CI=1.34, 3.34). Conclusion In young adults, changes in surrogate clinical markers of cardiac, vascular, and autonomic function commonly attributed solely to increases in fat mass should be interpreted with caution as they may be associated with underlying changes in FFM. Future work should focus on longitudinal studies of this cohort to confirm remodelling patterns based on these clinical markers.

Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction

Abstract Background Endothelial dysfunction is an integrated index of risk factor burden and a marker of atherosclerotic cardiovascular disease. Air pollution is widely acknowledged as a significant non-traditional risk factor for cardiovascular disease. However, the impact of air pollutants at varying concentrations and exposure durations on endothelial function in different populations remains unclear. Purpose We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction. Methods We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter <2.5 μm aerodynamic diameter (PM2.5), inhalable particulate matter <10 μm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. We used the moving average 7- and 14-day exposures before the date of FMD measurements to estimate the short-term exposure effects and the moving average 12-month exposures before the date of FMD measurements to estimate the long-term exposure effects. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratified by age and sex. Results This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 μg/m³ increase in 12-month exposure to PM10 and NO2 was significantly and linearly associated with -0.20% (95% CI: -0.37 to -0.03) and -0.58% (95% CI: -0.99 to -0.18) changes in FMD in all participants. 12-month exposure to gaseous pollutants was also significantly but nonlinearly associated with lower FMD. 7-day exposure to Quartile 4 of SO2 was significantly associated with a 0.70% decrease in FMD compared to Quartile 1 (β = -0.70, 95% CI: -1.40 to -0.008). No relationships were observed between 7- and 14-day exposure to PM2.5, PM10, NO2, CO, and endothelial dysfunction. Although interaction effects were limited to SO2 and sex, significant associations with different air pollutants were only found in men and those younger than 65 years after stratified. Conclusions Long-term exposure to air pollution is strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex. Further identification of different susceptible populations and proactive measures to mitigate air pollution may be beneficial in reducing the burden of cardiovascular disease.

Investigating lifestyle determinants of carotid intima-media thickness: cross-sectional insights from the UK biobank cohort

Abstract Background/Introduction Carotid intima-media thickness (CIMT) is recognised as a crucial marker for cardiovascular disease (CVD) risk, inherently associated with vascular ageing and influenced by biomarkers such as elevated levels of HbA1c, dyslipidaemia, and hypertension. The significance of CIMT lies in its potential to act as a surrogate marker for CVD risk, bridging a gap in understanding the progression of vascular health. Purpose This study aims to investigate the correlation between CIMT and a composite biomarker score to enhance risk assessment and guide the prevention and treatment strategies for CVD. By examining this relationship, the study seeks to underline the importance of CIMT progression as an indicative marker for cardiovascular health. Methods A subset of participants from the UK Biobank, with valid CIMT measurements taken in 2014, was selected for this analysis. CIMT was measured through ultrasound techniques and considered the primary outcome variable, treated as continuous in the analysis. A linear regression model was used to examine the correlation between CIMT and lifestyle risk factors, with a focus on the moderating effects of sex. Results The study included 29,292 UK Biobank participants (48% female, mean age 64 years), with a mean CIMT of 687.11µm (SD 124.28). Significant predictors of CIMT were age (β=6.05) and male gender (β=13.02). Lifestyle factors such as body weight (β=0.84) and high physical activity (β=10.66) were positively correlated with CIMT. Current smokers showed a stronger association with CIMT (β=14.47) compared to former smokers (β=9.21). In females, age (β=6.07), body weight (β=0.71), CRBI score (β=9.95), and previous smoking (β=6.64) positively correlated with CIMT, while high CRP levels were negatively associated (β=-0.61). In males, significant factors included age (β=6.04), body weight (β=0.95), CRBI score (β=10.79), and smoking history, with previous smokers showing a stronger effect (β=11.67) and high physical activity notably associated with increased CIMT (β=18.73). Conclusion(s) The study's findings highlight the impact of lifestyle choices on vascular health, demonstrating that active living, maintaining a healthy weight, and abstaining from smoking can positively affect CIMT and thereby reduce CVD risk. The results confirm the importance of weight management for arterial health across all demographics and highlight the role of abnormal biomarker levels in increasing CIMT. This study contributes to a deeper understanding of the factors affecting CIMT and, by extension, cardiovascular health, advocating for targeted lifestyle interventions to mitigate CVD risk.

A Study of the Relationship Between Objective Tests to Diagnose Erectile Dysfunction and Markers of Cardiovascular Disease

Background: Erectile dysfunction (ED) can stem from various organic and functional causes but is often linked to vascular health and cardiovascular disease. Limited data exist on how cardiovascular disease markers correlate with objective ED tests like the Nocturnal Penile Tumescence and Rigidity (NPTR) test and Penile Color Doppler Ultrasound (PCDU). Methods: A prospective observational study was performed, and 58 men with ED were assessed using the International Index of Erectile Function-15 (IIEF-15), NPTR test, and PCDU. Peripheral vascular health was evaluated through carotid intima-media thickness (cIMT) and brachial flow-mediated dilation (FMD). Results: Out of the participants, 44 had normal NPTR results, while 14 had abnormal results. The group with abnormal NPTR results was significantly older and had higher rates of hypertension and diabetes. Although the IIEF-15 scores were similar between the two groups, those with abnormal NPTR results had a lower peak systolic velocity (PSV) and a higher prevalence of impaired PSV. Correlations between the IIEF, NPTR, PCDU, and peripheral vascular markers lost significance after the age adjustment. Conclusions: This study suggests that abnormal NPTR results, combined with cardiovascular risk factors, may signal vascular ED and generalized vasculopathy, highlighting the need for cardiovascular assessment. An accurate ED diagnosis should integrate clinical evaluation with multiple tests while considering aging as a key risk factor.

Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals.

The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer's disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels.

Transient changes in L-arginine, asymmetric and symmetric dimethyl arginine in triathletes following Norseman Xtreme Triathlon.

Arterial vasodilation is dependent on nitric oxide synthesized from L-arginine by endothelial nitric oxide synthase. Triathletes are reported to display altered serum concentrations of nitric oxide metabolites such as L-arginine, asymmetric dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) shortly after completing long-distance triathlon races. In other populations, similar changes to nitric oxide metabolites are established risk markers of cardiovascular disease. The objective of this study was to assess serum concentrations of metabolites for endothelial nitric oxide synthesis in triathletes one week following a long-distance triathlon race. In this prospective observational study, we used high-performance liquid chromatography to measure circulating concentrations of L-arginine, ADMA, and SDMA in triathletes. Venous blood samples were collected before, immediately after, day one, and one week following the triathlon race. Serum concentrations and L-arginine/ADMA ratio were determined for each time-point and compared to baseline. L-arginine/ADMA ratio was reduced on day one (147 ± 32 vs 163 ± 40, p < 0.02). ADMA was reduced immediately after and increased at day one and remained elevated at oneweek (0.29 ± 0.05μM, p < 0.001, 0.44 ± 0.08μM, p < 0.001 and 0.42 ± 0.07μM, p = 0.04, respectively vs 0.40 ± 0.05μM). SDMA was increased at all time-points when compared to baseline (0.48 ± 0.10μM, p < 0.001, 0.53 ± 0.11μM, p < 0.001 and 0.42 ± 0.08μM, p = 0.048 vs 0.38 ± 0.05μM). L-arginine was only decreased immediately after (46.0 ± 9.3μM vs. 64.6 ± 16.1μM, p < 0.001). Long-distance triathlon racing induces altered levels of metabolites for endothelial nitric oxide production that mostly normalizes within one week following racing. The clinical relevance of these transient changes has yet to be elucidated in the athletic population.

Reduced circulating CD63+ extracellular vesicle levels associate with atherosclerosis in hypercholesterolaemic mice and humans

AimsThe association and co-isolation of low-density lipoproteins (LDL) and extracellular vesicles (EVs) have been shown in blood plasma. Here we explore this relationship to better understand the role of EVs in atherogenesis.Methods and resultsWild type (WT), PCSK9−/−, and LDLR−/− C57BL/6 mice were used in this study. Eleven week-old male mice were fed high-fat diet (HFD) for 12 weeks or kept on normal diet until old age (22-months). Cardiac function was assessed by ultrasound, cholesterol was quantified with a colorimetric kit and circulating EVs were measured using flow cytometry. Plaques were analysed post-mortem using Oil-Red-O staining of the aortic arch. EVs were measured from platelet free blood plasma samples of normal and hypercholesterolaemic clinical patients. Based on annexin V and CD63 staining, we found a significant increase in EV levels in LDLR−/− and PCSK9−/− mice after HFD, but CD81 showed no significant change in either group. There was no significant change in plaque formation after HFD. PCSK9−/− mice show a favourable cardiac function after HFD. Blood cholesterol levels progressively increased during HFD, with LDLR−/− mice showing high levels while PCSK9−/− were significantly lowered compared to WT animals. In mice at old age, similar cholesterol levels were observed as in young mice. In old age, LDLR−/− mice showed significantly increased plaques. At old age, ejection fraction was decreased in all groups of mice, as were CD63+ EVs. Similarly to mice, in patients with hypercholesterolaemia, CD63+ EVs were significantly depleted.ConclusionsThis research demonstrates an inverse relationship between circulating EVs and cholesterol, making EVs a potential marker for cardiovascular disease (CVD). HFD causes reduced cardiac function, but atherosclerotic development is slowly progressing in hypercholesterolaemic models and only observed with old animals. These results also bring further evidence for the benefit of using of PCSK9 inhibitors as therapeutic agents in CVD.

Assessing the Influence of Long-Term Gender-Affirming Hormone Therapy on Cardiovascular Risk in Transgender Men through Carotid Intima-Media Thickness.

Background: Transgender men use exogenous androgen for male pattern virilization. Hysterectomy and bilateral salpingo-oophorectomy (HBSO) is performed to stop the endogenous estrogen secretion. Cardiovascular disease (CVD) risk has been shown to increase with long-term use of androgens and the removal of estrogen. We aimed to investigate the CVD risk in these individuals by measuring internal and common carotid artery intima-media thicknesses (CIMT). Methods: In this cohort study, data were collected from transgender men who had undergone HBSO and used androgens for at least two years (median treatment duration was 5 years in our research). Cisgender women in the same age range were selected as the control group. Demographics, vital signs, and hematological values of transgender patients and cisgender women subjects in the control group were noted. CVD markers were compared with sonographically measured CIMT values. Results: The mean age and body mass index (BMI) of the study group were 32.6 and 25.3, respectively. Weight, systolic-diastolic blood pressure, hemoglobin, hematocrit, low-density lipoprotein (LDL), serum triglyceride (TG), HbA1c levels, internal CIMT, and common CIMT values of the study group were higher, while the high-density lipoprotein (HDL) level was significantly lower compared the control group (p1 = 0.025, p2 = 0.010, p3 = 0.002, p4 = 0.001, p5 = 0.001, p6 = 0.012, p7 = 0.008, p8 = 0.007, p9 = 0.013, and p10 = 0.001). There was also an increase in the body weight, BMI, LDL, and TG levels of the study group after the testosterone treatment (p1 = 0.025, p2 = 0.019, p3 = 0.001, p4 = 0.001, and p5 = 0.001). Conclusions: We demonstrated that the use of testosterone therapy in transgender men is associated with higher CIMT values. While further investigation is needed to assess morbidity and mortality rates, we recommend that regular clinical and radiological examinations be performed in these individuals to accurately evaluate the risk of CVD.

Oral Disease and Atherosclerosis May Be Associated with Overlapping Metabolic Pathways.

Dental caries and periodontitis are among the most prevalent chronic diseases worldwide and have been associated with atherosclerotic cardiovascular diseases (ASCVD). This study aimed to determine (1) the independent associations between subclinical ASCVD markers (carotid intima media thickness [CIMT] and coronary artery calcification [CAC]) and quantitative indices of oral disease including the decayed, missing, and filled teeth (DMFT) index, gingivitis parameters, periodontal status, and number of teeth lost and (2) the extent to which metabolites altered in individuals with oral disease overlapped with those altered in individuals with ASCVD. We used data from 552 participants recruited through the Dental Strategies Concentrating on Risk Evaluation project. Oral examinations were conducted, and CIMT and CAC were measured. Multiple linear regression models were constructed with CIMT and CAC as dependent variables in the epidemiologic analysis. In the metabolomic analysis, logistic or linear regression was used to test 1,228 metabolites for association with each phenotype adjusted for age, sex, race, blood pressure, smoking, diabetes, cholesterol, high-sensitivity C-reactive protein, and interleukin-6. None of the oral disease markers were significant predictors of ASCVD markers in the fully adjusted models. However, critical lipid and lipid-signaling pathway metabolites were significantly associated with gingivitis, periodontitis, and DMFT: the lysophospholipid pathway (odds ratio [OR] = 2.29, false discovery rate [FDR]-adjusted P = 0.038) and arachidonate with gingivitis (OR = 2.35, FDR-adjusted P = 0.015), the sphingolipid metabolism pathway with periodontitis (OR = 2.09, FDR-adjusted P = 0.029), and borderline associations between plasmalogen and lysophospholipid pathways and DMFT (P = 0.055). Further, the same metabolite from the sphingolipid metabolism pathway, sphingomyelin (d17:1/14:0, d16:1/15:0), was inversely associated with both CIMT (β = -0.14, FDR-adjusted P = 0.014) and gingivitis (OR = 0.04, FDR-adjusted P = 0.033). The discovery of a common sphingomyelin metabolite in both disease processes is a novel finding suggesting that gingivitis and periodontitis may be associated with some overlapping metabolic pathways associated with ASCVD and indicating potential shared mechanisms among these diseases. The same metabolites may be altered in atherosclerosis and oral disease. Specifically, a common sphingomyelin metabolite was inversely associated with gingivitis and carotid intima media thickness, a subclinical marker of atherosclerotic cardiovascular disease. These findings can provide valuable insights for future mechanistic studies to establish potential causal relationships, with the hope of influencing disease prevention and targeted early treatment.

High-density lipoprotein functionality in cholesterol efflux in early childhood is related to the content ratio of triglyceride to cholesterol

Cholesterol efflux capacity (CEC), commonly measured as a useful risk marker of atherosclerotic cardiovascular disease, depends on high-density lipoprotein (HDL) functionality and its concentration. We defined the relative HDL functionality in cholesterol efflux, not influenced by HDL concentration, as the ratio of measured CEC to standardized CEC (stCEC) based on HDL-cholesterol (HDL-C) of each individual using the curve regression equation obtained from the correlation. HDL-C, CEC, and CEC/stCEC levels in the < 28-day-old participants (neonates) were significantly low compared to those of the ≥ 28-day-old participants, indicating that the low CEC levels in the neonates depend on not only lower HDL-C but also lower HDL functionality. The low level of CEC/stCEC was remarkable in neonates born at < 34 weeks of gestation and did not improved to the reference level (1.000) until the infantile period. The relatively low or high CEC/stCEC ratios in neonates and infants were associated with lower or higher HDL-TG and HDL-TG/HDL-C ratio, respectively. However, no apparent effect of HDL-TG and HDL-TG/HDL-C ratio on CEC/stCEC was observed in the ≥ 1-year-old participants, indicating that HDL functionality in cholesterol efflux could be associated with the various HDL particles with various lipid compositions, but not just with HDL-TG and HDL-TG/HDL-C ratio.

6934 Nutritional Factors and Endothelial Dysfunction in Women with Functional Hypothalamic Amenorrhea

Abstract Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a common form of secondary amenorrhea that results in hypoestrogenemia and hypercortisolemia. The underlying cause of FHA is due to a mismatch between energetic intake and expenditure that often manifests as disordered eating, excessive exercise, and psychosocial stress. Previous research identified that 1 in 3 women with FHA had endothelial dysfunction, a preclinical marker for cardiovascular disease. We sought to evaluate the nutrition content in young women with FHA compared to eumenorrheic controls and further assess the relationship to endothelial dysfunction. Methods: We enrolled 30 women with FHA and 29 eumenorrheic controls, not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol &amp;lt;50 pg/mL, FSH&amp;lt;10 mIU/L, and LH&amp;lt;10 mIU/L, and exclusion of polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, and pregnancy. Eumenorrheic controls had monthly menses with ovulation (progesterone ≥4 ng/mL). Vascular function was measured using EndoPAT 2000 (Itamar® Medical Ltd) to calculate the reactive hyperemic index (RHI). An RHI ≤1.67 indicates endothelial dysfunction. Nutritional intake was collected using a 3-day food diary and analyzed using ESHA Research Food Processor® Nutrition Analysis. Percent (%) recommendation values for nutrition content comparison were calculated based on height, weight, and age. Statistical analysis included Analysis of Variance and Kruskal Wallis test with nonparametric variables reported as median [IQR]. Results: The mean age and BMI of FHA and controls were 26.4 ± 6.2 yrs and 30.3 ± 3.7 yrs (p=0.008), and 21.6 ± 6.2 and 21.8 ± 2.0 kg/m2 (p=0.16), respectively. The median months of FHA amenorrhea was 12 months [5.0, 34.0]. After adjusting for age, there was no difference in caloric intakes in women with FHA compared to controls (1783.9 [1465, 2011] kcal vs. 1731.9 [1578, 1982] kcal, p=0.73); however FHA has higher intake of grams of protein (84.2 [74, 112] g vs. 74 [59, 92] g, p=0.0036), and higher grams of dietary fiber (30.1 [22, 43] g vs. 17.3 [15, 23] g, p=0.0037), respectively. In women with FHA, endothelial dysfunction was associated with a higher % recommended calories (p=0.0098), calories from fat (p=0.02), grams of saturated fat (p=0.03), and grams of carbohydrates (p=0.049). Conclusions: Our results demonstrate that women with FHA consumed similar daily calories, although more grams of protein and dietary fiber than controls. In women with FHA, higher calories, calories from fat, grams of saturated fat and carbohydrates were associated with endothelial dysfunction. Future studies should aim to identify other factors related to endothelial dysfunction among women with FHA and whether some FHA phenotypes are associated with more endothelial dysfunction than others. Presentation: 6/1/2024