Markers Of Subclinical Cardiovascular Disease Research Articles

Exploring the Association between Mediterranean Diet Adherence and Arterial Stiffness in Healthy Adults: Findings from the EvasCu Study.

(1) Background: Previous evidence has indicated a connection between a Mediterranean diet and cardiovascular disease. However, evidence for subclinical markers of cardiovascular disease, such as arterial stiffness, is limited. Therefore, the aim of this study was to assess the associations between adherence to the Mediterranean diet (MD), as assessed by the MEDAS-14 questionnaire, and arterial stiffness, as assessed by aortic pulse wave velocity, in healthy adults and according to sex. (2) A cross-sectional study including 386 healthy participants was performed in the EVasCu study. Adjusted and unadjusted differences in adherence to the MD and arterial stiffness were determined using Student's t test and ANCOVA for the total sample and according to sex. (3) Results: Our results showed that individuals with a high adherence to the MD had a greater arterial stiffness, both in the total sample and in females, although this difference was not significant after adjusting for possible confounding variables, such as age. (4) Conclusions: Our findings indicated that, in the unadjusted analyses, healthy subjects with a high adherence to the MD showed a greater arterial stiffness. When these analyses were adjusted, no significant differences were shown in a-PWv according to the categories of MD adherence.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries

AimsThe clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). MethodsWe analyzed data from 34,224 youths (51.0 % boys, aged 6–18 years) with CMRFs, 5004 (49.5 % boys, aged 6–18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6–17 years) with PWV measurement from 20 pediatric samples across 14 countries. ResultsWHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75–0.78) to 0.78 (0.76–0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74–0.79) to 0.77 (0.74–0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64–0.71) to 0.70 (0.66–0.73) for high cIMT (≥P95 values) and from 0.60 (0.58–0.66) to 0.62 (0.58–0.66) for high PWV (≥P95 values). ConclusionsOur findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.

357 Effects of Dietary Nitrate Supplementation on Vascular Function in Individuals with Prediabetes

OBJECTIVES/GOALS: Impaired vascular function, a subclinical marker of cardiovascular disease, has been identified in prediabetes. Dietary nitrate supplementation has been shown to improve vascular function. However, this has not been studied in prediabetes. The purpose was to determine the effects of dietary nitrate on vascular function in prediabetes. METHODS/STUDY POPULATION: Five individuals with prediabetes (4 men, 1 woman; 55 ± 17 yr; HbA1c = 5.8 ± 0.2) participated in a double-blind, placebo-controlled, repeated measures study. Participants were randomly assigned to a 3-day nitrate supplementation (nitrate-rich beetroot juice, 12.9 mmol, 140 mL), or a placebo supplementation (nitrate-depleted beetroot juice, 0.05 mmol, 140 mL). Following supplementation, participants reported to the lab for measures of vascular function in the lower limb. Doppler ultrasonography was used to measure flow-mediated dilation (FMD) and post-occlusive reactive hyperemia (RH) of the superficial femoral artery in response to a 5-min bout of leg ischemia. RESULTS/ANTICIPATED RESULTS: FMD did not differ between the nitrate-rich (2.87 ± 2.01%) and placebo (2.24 ± 1.69%) conditions (p = 0.48; d = 0.35). Furthermore, peak RH did not differ between the nitrate-rich (1503 ± 443 ml/min) and placebo (1762 ± 414 ml/min) conditions (p = 0.36; d = 0.46). DISCUSSION/SIGNIFICANCE: These preliminary results suggest that dietary nitrate supplementation in the form of beetroot juice does not improve vascular function in individuals with prediabetes.

Abstract 11: Biological Age as a Predictor of Arterial Stiffness in Midlife Women

Introduction: Black women develop hypertension (HTN) earlier in life and experience higher cardiovascular disease (CVD) morbidity and mortality rates at younger ages compared to White women. Growing evidence suggests this may be due to Black women experiencing premature physiological deterioration and accelerated biological aging, true global state of an aging organism. Yet, the relationship between biological aging and arterial stiffness, a precursory marker of subclinical CVD, in Black women has not been studied. We investigated the association between biological age (BA) and arterial stiffness in Black and White women. Hypothesis: BA will be associated with arterial stiffness and this association will be modified by race. Methods: In 219 women (n=140 White, n=79 Black) enrolled in the Morehouse-Emory Center for Health Equity and Predictive Health Institute cohorts (age range 25-49), arterial stiffness was assessed using carotid-femoral pulse wave velocity (CFPWV), measured by applanation tonometry (SphygmoCor®). BA was estimated using the Klemera-Doubal method from 10-select clinical biomarkers (BUN, Creatinine, Total Cholesterol, Alkaline Phosphatase, MCV, RDW, Albumin, Lymphocytes, WBC, CRP) and chronological age. Overall and race-specific associations between BA and arterial stiffness adjusting for demographics (race, education, income, marital status), lifestyle (alcohol, smoking), clinical (body mass index, HTN, diabetes history, SBP), and mental health factors (depressive symptoms) were estimated using multiple linear regression. Results: Mean chronological and BA age was 40 (SD=6.1) and 43 (SD=7.2) years, respectively. Black women had a BA that was 3.4 (SD=5.7) years older than their chronological age, while the difference was 1.3 (SD=4.8) years older for White women. Thus, Black women’s BA was 2.1 (95%CI: -3.5, -0.6) years older than White women. Mean (SD) CFPWV was 7.3 (1.1) in Black women and 6.3 (0.8) in White women. Overall, BA was associated with higher (worse) CFPWV in the minimal (β=0.06 m/s per year, 95%CI: 0.03, 0.08) and fully adjusted models (β=0.04 m/s, 95%CI: 0.01, 0.08). There was no significant interaction between race and BA in the association with arterial stiffness. Conclusions: Black women had older BA and worse CFPWV than White women. BA may partially account for the higher arterial stiffness in Black women.

(159) Characteristics and Hypertension Management Trends in Hypertensive Men With and Without Erectile Dysfunction

Abstract Introduction Hypertension, defined as a blood pressure (BP) ≥ 130/80 mmHg and/or use of BP lowering medications, affects 47% of the U.S. population and is the most important modifiable risk factor for cardiovascular disease (CVD) prevention. Prevalence of BP control appears to be decreasing in the U.S. and currently only 1 in 4 adults with hypertension have controlled BP. Erectile dysfunction (ED), an early marker of subclinical CVD, often accompanies hypertension. Most BP lowering medications have been shown to not affect sexual function, but the drug class of angiotensin receptor blockers (ARBs) have generally been found to have favorable effects on erectile function through their inhibition of angiotensin II. Therefore, exploring the relationship between hypertension management and ED is advantageous for the ultimate control and treatment of these two common and highly prevalent diseases. Objective Assess the demographics of hypertensive men with and without ED and examine associations of ED with hypertension management and BP control outcomes Methods All men presenting for an initial visit for hypertension (ICD-10 codes I10, I11.0, and I11.9) between January 2017-December 2022 at an academic medical center were included for analysis. The electronic health record was queried for patient demographics, the diagnosis of ED, cardiovascular comorbidities, major drug classes of antihypertensives, and major PDE5-inhibitors. Descriptive statistics was used to describe patient characteristics by ED status. Chi-squared, t-test, and Mann-Whitney U tests was used to compare characteristics of patients by presence of ED. Results Of 24,723 hypertensive men in our health system during the study period, only 1,119 men (4.5%) were noted to have ED (Table 1). Hypertensive men with ED were younger (56 ± 11), than those without ED (61±15). There was no statistically significant difference in the use of ARBs amongst hypertensive men with and without ED. Initial systolic and diastolic BP was significantly higher amongst men with ED. After pooling all outpatient clinic visits prior to and after the diagnosis of ED, BP control did improve mildly over the study period, but this was coupled with a decrease in BP medication use across all drug classes. Finally, there was a significant increase in hypertensive males who were on a either sildenafil or tadalafil after their ED diagnosis (Table 2). Conclusions This study elucidates several key points in conceptualizing the ED and hypertension problem and lays a foundation for the next phase in addressing critical gaps in care. This research further validates the underdiagnoses and thus undertreatment of ED overall, with a significantly lower than expected number of men with ED. Despite the well-established benefits of ARBs in hypertensive men with ED, we observed a trend of underutilization of this beneficial BP medication option. Improvements in BP control over time for hypertensive men with ED emphasize the role ED could play in hypertension management. Leveraging ARBs and education on the interplay of ED and hypertension could lead to improved rates and control of both diseases. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals, ForHims.

Estrogen-Based Gender-Affirming Hormone Therapy and Subclinical Cardiovascular Disease in Transgender Women with HIV.

Purpose: Transgender women (TW) are disproportionately affected by HIV infection and cardiovascular disease (CVD). This study evaluated whether estrogen-based gender-affirming hormone therapy (GAHT) in TW with HIV (TWH-GAHT) is associated with indices of subclinical CVD. Methods: Of the 40 HIV-seropositive persons enrolled, 20-60 years of age, on antiretroviral treatment with undetectable viral load, assessments were performed on 15 TWH; of these persons, 11 were GAHT treated. These TWH-GAHT were matched with HIV+ cisgender men and women based on age, ethnicity/race, body mass index, and antihypertensive medication use. Sex hormones, and cardiometabolic (waist circumference, blood pressure, insulin resistance, lipid profile, and C-reactive protein), vascular (flow-mediated dilation [FMD] and arterial stiffness), and proinflammatory measures were obtained. Results: TWH-GAHT displayed elevated estradiol and suppressed testosterone levels relative to normative ranges. Analyses indicated the TWH-GAHT displayed lower low-density lipoprotein compared with cisgender groups (p < 0.05). Although no difference was seen on FMD, the central augmentation index of aortic stiffness was higher in cisgender HIV+ women than cisgender HIV+ men (p < 0.05). No other group difference on subclinical CVD markers was observed. For TWH, partial correlations indicated associations of certain sex hormones with selected cardiometabolic outcomes and the inflammatory cytokine, interleukin-8. Conclusion: When well matched to HIV+ cisgender men and women, subclinical CVD pathophysiology did not appear elevated in TWH-GAHT, although tendencies emerged suggesting that some subclinical CVD indices may be higher, but others lower than cisgender groups. Longitudinal studies of TWH are needed to more precisely evaluate the moderating effect of GAHT on cardiometabolic pathophysiology.

Abstract 49: The Effects of Vitamin D Supplementation on Subclinical Cardiovascular Disease: Results From the Sturdy Trial

Background: In observational studies, older adults with insufficient or deficient serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation. This is possibly because the doses of vitamin D supplements tested were too low. Objective: To determine if higher doses of vitamin D supplementation lower high sensitivity cardiac troponin level (hs-cTnI) and N-terminal pro b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD. Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, and 4000 IU/day) on fall risk in adults aged ≥70 years old with low serum 25-hydroxyvitamin D levels (10-29 ng/ml). Hs-cTnI and NT-proBNP levels were measured at baseline and at 3-, 12- and 24-month follow-up visits. For analysis, participants were divided into low (200 IU/day) and high dose (1000+ IU/day) vitamin D treatment groups. The effects of vitamin D dose on hs-cTnI and NT-proBNP were assessed via mixed effects tobit models. Results: Among 688 participants (mean age of 77 ± 5 years, 44% were women, and 18% were Black), 50.7% were in the high-dose treatment group (1000+ IU/day). Hs-cTnI increased in both the low and high dose groups by 5.1% and 5.8%, respectively; likewise, NT-proBNP increased in both groups by 11.3% and 9.3%, respectively ( Figure). Compared to the low-dose group, high-dose vitamin D treatment did not affect hs-cTnI (1.7 % difference; 95% CI: -5.3, 9.3) or NT-proBNP (-1.8 % difference; 95% CI: -9.3, 6.3). Conclusions: Compared to low dose vitamin D supplementation, a higher dose did not affect markers of subclinical CVD in older adults with low serum vitamin D levels. These findings do not support higher doses of vitamin D as an intervention to reduce the risk of CVD in this population.

Association Between Measures of Body Composition and Coronary Calcium: Findings From the Multi-Ethnic Study of Atherosclerosis.

Background Obesity, as measured by body mass index, is widely recognized as a risk factor for the development of cardiovascular disease. However, the role of body composition components such as fat and lean mass is not well studied. Methods and Results A total of 3129 patients who underwent computed tomography scans for quantification of coronary artery calcification and had bioelectrical impedance analysis of body composition (fat mass and fat-free mass) during exam 5 of MESA (Multi-Ethnic Study of Atherosclerosis) were included in this cross-sectional analysis. Multivariable adjusted linear regression analysis was performed to assess the relationship between both fat mass and fat-free mass to prevalent coronary artery calcification, a marker of subclinical coronary artery disease quantified by both the coronary artery calcification (CAC) Agatston score and the spatially weighted calcium score. CAC and spatially weighted calcium score were natural log-transformed for analysis as continuous variables. Fat-free mass, but not fat mass, was independently associated with CAC. There was a 7.6% prevalence risk difference for CAC>0 per 10 kg. Fat-free mass was also significantly associated with natural log of CAC (coefficient=0.272, P<0.001). Both fat-free mass and fat mass were positively associated with natural log of spatially weighted calcium score, with risk difference coefficients of 0.729 and 0.359, respectively (P<0.001). Conclusions In this cross-sectional study, higher lean mass by bioelectrical impedance analysis and, to a lesser extent, higher fat mass by bioelectrical impedance analysis were significantly associated with higher coronary calcium, a marker of subclinical cardiovascular disease. Further exploration of the relationship between components of body composition and the development of cardiovascular disease is warranted.

Large-Scale Metabolomics and the Incidence of Cardiovascular Disease.

Background The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population. Methods and Results In 2278 individuals free from CVD in the EpiHealth study (aged 45-75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow-up of 8.6 years, 107 individuals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age- and sex-adjusted analyses and P<0.05 for adjustment for traditional CVD risk factors, 37 metabolites were significantly related to incident CVD. These metabolites belonged to multiple biochemical classes, such as amino acids, lipids, and nucleotides. Top findings were dimethylglycine and N-acetylmethionine. A lasso selection of 5 metabolites improved discrimination when added on top of traditional CVD risk factors (+4.0%, P=0.0054). Thirty-five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1-carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery. Conclusions Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.

Subclinical Cardiovascular Disease Markers in Relation to Serum and Dietary Magnesium in Individuals from the General Population: The KORA-MRI Study.

Several studies have implied a role of magnesium in the development of cardiovascular disease (CVD). Thus, magnesium might serve as a potential risk marker for early CVD. Therefore, we investigated the association of serum magnesium and dietary magnesium intake with markers of subclinical CVD in a population-based study. We used cross-sectional data from the sub-study of the Cooperative Health Research in the Region of Augsburg (KORA-FF4). Markers of subclinical CVD, namely, left and right ventricular structure and function and carotid plaque and carotid wall thickness, were derived by magnetic resonance imaging (MRI). Multivariable-adjusted regression models were applied to assess the relationship between serum and dietary magnesium and MRI-derived subclinical CVD markers. Among 396 included participants (mean age: 56.3 ± 9.2 years; 57.8% male), 181 (45.7%) had low serum magnesium levels (<2.07 mg/dL). Among 311 subjects with complete dietary data (mean age: 56.3 ± 9.1 years; 56.3% male), 154 (49.5%) had low dietary magnesium intake (≤155.2 mg/1000 kcal/day). Serum and dietary magnesium were not correlated (p-value = 0.5). Serum magnesium was significantly associated with presence of carotid plaque (OR 1.62, p-value 0.033). Dietary magnesium was associated with higher left ventricular end-systolic and end-diastolic volume (0.04 mL/m2, 0.06 mL/m2; p-value 0.011, 0.013, respectively), and also with a decrease in left ventricular remodeling index and mean diastolic wall thickness (−0.001 g/mL/m2, −0.002 mm/m2; p-value 0.004, 0.029, respectively). In summary, there was no consistent association of serum and dietary magnesium with imaging markers of subclinical CVD.

Abstract 12239: Objectively Measured Physical Activity Decreases the Risk of Subclinical Cardiovascular Disease: A Systematic Review

Introduction: Physical activity (PA) decreases the risk of cardiovascular events, but to what degree this is related to effects on surrogate markers of subclinical cardiovascular disease (CVD) is unclear. Clarifying the relationship between objectively measured PA and subclinical CVD would provide justification for using measures of subclinical CVD in clinical trials of PA interventions. Hypothesis: We hypothesized that higher levels of objectively measured PA are associated with less subclinical CVD. Methods: We performed a systematic review using Medline, Embase, CINAHL and Cochrane (January 1, 2000 - January 12, 2022). Studies of adult populations that examined the relationship between objectively measured PA (accelerometry) and subclinical CVD were included. Markers for subclinical CVD included: ankle brachial index ( n =4 studies); arterial stiffness ( n =31); carotid artery plaque/stenosis and intima media thickness ( n =9); coronary artery atherosclerosis ( n =4); endothelial function ( n =8); measures of cardiac structure and function ( n =4); and eight studies included multiple of the aforementioned outcomes. For those studies, we considered results on each outcome separately. Risk of bias was also assessed. Results: PA was inversely associated with subclinical CVD in 60 of 78 included analyses (76.9%). Of these, five studies (6.4%) found only an association with higher levels of PA. In six studies (7.7%), PA was no longer associated with subclinical CVD after adjustment for confounders. Seven analyses (9.0%) demonstrated mixed results but demonstrated an inverse relationship between PA and subclinical CVD in specific circumstances. Only 18 studies (23.1%) suggested that PA was not associated with decreased subclinical CVD. Conclusions: Increased PA is associated with less subclinical CVD across diverse populations. Interventions to increase PA have the potential to reduce the burden of subclinical CVD and, therefore, clinical CVD events.

Cardiovascular Risks of Hypertension: Lessons from Children with Chronic Kidney Disease.

Hypertension is the most common complication of chronic kidney disease (CKD) in children, having a strong association with subsequential cardiovascular disease (CVD). In pediatric CKD, a considerable percentage of children with hypertension are undiagnosed or undertreated. Prior research has evaluated structural and functional markers of subclinical CVD and biomarkers in adults with CKD, while ideal biomarkers in pediatrics are still insufficiently studied. The ultimate goal of this review is to summarize what is currently known about state of hypertension, cardiovascular risk factors, and potential CVD markers/biomarkers in children with pre-dialysis CKD. We discuss omics-related biomarkers and the pathophysiologic processes of endothelial dysfunction, kidney injury, oxidative stress and inflammation that are classified by specific biomarkers. Moreover, we illustrate the existing challenges and highlight the paucity of pediatric CKD research to evaluate these CVD biomarkers for future clinical pediatric practice. Thus, achieving clinical utility of CVD biomarkers for use in pediatric CKD remains a significant challenge requiring additional efforts.

Pre-Frailty Phenotype and Arterial Stiffness in Older Adults Free of Cardiovascular Diseases.

Purpose: Arterial stiffness is a subclinical marker of cardiovascular disease (CVD). The pre-frailty phenotype is associated with a higher risk for CVD. This study investigated the association between the pre-frailty phenotype and arterial stiffness in community-dwelling older adults without diagnosed CVD. Methods: In total, 249 community-dwelling older adults aged 60–80 years were included in this cross-sectional study. The pre-frailty phenotype was defined by the standardized Fried criteria (muscle weakness; slow walking speed; low physical activity; unintentional weight loss; self-reported exhaustion). Participants with one or two standardized Fried criteria were classified as pre-frail and those with zero criteria as robust. Arterial stiffness was measured by aortic pulse wave velocity (aPWV). The data were analyzed using the generalized linear model. Results: From 249 participants (66.1 ± 5.3 years; 79.5% females), 61.8% (n = 154) were pre-frail and 38.2% (n = 95) robust. Pre-frail older adults had a higher aPWV (β = 0.19 m/s; p = 0.007) compared to their robust peers. Conclusions: The pre-frailty phenotype was associated with higher arterial stiffness in community-dwelling older adults aged 60–80 years. Pre-frail older adults may have a higher risk for CVD.

Circulating anti-Müllerian hormone levels and markers of subclinical cardiovascular disease in middle-aged and older men

ContextRecent research suggests that higher circulating anti-Müllerian hormone (AMH) levels are associated with less frequent occurrence of (subclinical) cardiovascular disease (CVD) in women, but evidence in men is limited. ObjectiveWe investigated whether circulating AMH levels are associated with measures of subclinical CVD in middle-aged and older men. DesignProspective cohort study with a median follow-up time of 8.7 years. Serum AMH was measured at baseline. We assessed both cross-sectional and longitudinal associations using linear regression models adjusted for confounders. SettingDutch middle-aged and older men from the community. Participants394 men (aged 40–80 years) with an available AMH measurement at baseline. Main outcome measuresAt baseline (2001−2002): carotid intima-media thickness (CIMT), pulse wave velocity (PWV), abdominal aortic diameter, and Framingham risk score (FRS) predictions. At follow-up (2010−2011): CIMT, mean carotid aortic plaque score, PWV, and FRS predictions. All outcomes were transformed using rank-based inverse normal transformation to meet the normality assumption. ResultsHigher AMH levels were associated with lower CIMT at baseline (β = −0.04; 95%CI = 0.07, −0.01), but not with the other measures of subclinical CVD at baseline. Longitudinal analyses suggested that higher baseline AMH levels were associated with lower mean plaque scores at follow-up (β = −0.03, 95%CI = −0.07, 0.00), but not with the other follow-up outcomes. ConclusionsOur results suggest that AMH is associated with current CIMT and future carotid aortic plaque burden in men, implying that circulating AMH levels are potentially associated with local atherosclerosis rather than with total aortic stiffness.

Aortic arch calcification: A simple but powerful marker of subclinical cardiovascular disease

The burden of cardiovascular disease (CVD) worldwide remains high despite advances in diagnosis and management.1 Risk factor modification has become the cornerstone of CVD prevention. Because the burden of CVD remains high throughout the world, it is important to identify subclinical markers of CVD, in addition to traditional clinical risk factors, to aid in risk stratification and prognostication. Coronary artery calcification (CAC), as well as calcifications in extracoronary vascular beds, have provided great insights into the risk of developing clinical CVD.

MO977: Circulating CD14++CD16+MONocytes, NK Cells and LYMPHOcyte Subsets Correlate with Conventional and Novel Deformation Related Indices of Left Ventricular Function in Kidney Transplant Recipients with no Established Cardiovascular Disease

Abstract BACKGROUND AND AIMS Kidney transplant recipients (KTRs) carry a significant burden of cardiovascular disease (CVD), despite improvement of patterns of left ventricular (LV) remodeling following kidney transplantation. Kidney allograft dysfunction and the immunosuppressed milieu play a major adverse role in myocardial structural changes in asymptomatic KTRs. An intricate relationship exists between immune system responses with heart failure syndromes, manifesting among others with aberrant activity and counts of proinflammatory CD16+monocytes, of natural killer (NK) cells and T regulatory cells (Tregs). The associations of immune cell subpopulations with subclinical markers of CVD remain to be determined in KTRs. The aim of our study was to investigate potential correlations between blood levels of specific immune cells subsets with conventional and novel deformation related indices of LV function in KTRs. METHOD 31 stable KTRs (mean age 58 ± 9.28 years, 67% males, 13% diabetics) without established CVD were enrolled. Control population included 17 chronic kidney disease (CKD) stage 3 patients without history of CVD. Additional exclusion criteria were history of malignancy, autoimmune disease and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+B lymphocytes, CD3+CD4+T cells, CD3+CD8+T cells and Tregs (CD4+CD25+FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry. Simultaneously, conventional (left atrial volume index (LAVI), LV mass index (LVMI), E/E’) and novel 2D speckle tracking (2DST) echocardiographic indices of LV function [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), TWIST AND UNTWIST] were assessed. RESULTS KTRs had a mean eGFR of 58 ± 18 mL/min/1.73 m2 (CKD-EPI) and mean 24-h proteinuria (PER) 707 ± -1185 mg/24 h. Total lymphocytes, B-cells, T-cells and CD8+T cells counts correlated positively with eGFR (P &amp;lt; 0.05). Increased non-classical CD14+CD16++ monocytes were associated with proteinuria levels (P &amp;lt; 0.01) whereas an inverse correlation was observed between the percentage of classical CD14++CD16- monocytes with PER (P &amp;lt; 0.05). When compared with CKD patients, KTRs displayed higher CD14++CD16- and lower CD14+CD16++ monocytes counts, a lower percentage of NK cells and T cells and lower Tregs (significant differences presented in Table 1). Regarding classical indices of LV function, increased total monocytes were associated with elevated LAVI (P &amp;lt; 0.05), whereas an increased percentage of the intermediate CD14++CD16+monocytes correlated positively with an increased E/E’ value. Increased NK cells were associated with more negative GCS values (P &amp;lt; 0.05). No significant correlations were observed between the rest immune cells with the classical or novel LV dysfunction indices. CONCLUSION Alterations of immune cells subsets correlate with subclinical markers of LV dysfunction in KTRs with no established CVD. Future research is required to evaluate the role of immune subpopulations as tools to identify KTRs who are at the highest risk for complications and guide interventions.

Transient elastography and serum markers of liver fibrosis associate with epicardial adipose tissue and coronary artery calcium in NAFLD

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.

Abstract 040: Sleep Regularity And Subclinical Markers Of Cardiovascular Disease: The Multi Ethnic Study Of Atherosclerosis (MESA)

Background: Sleep irregularity has been linked to incident cardiovascular disease (CVD). Less is known about sleep regularity and associations with atherosclerosis. Our objective was to examine associations of sleep regularity with measures of atherosclerosis in the diverse MESA cohort. Methods: Participants from the MESA Sleep Study (2010-2013; N=2,032, Mean age: 68.6 ± 9.2 years; 53% Female, 38% White, 28% Black or African American, 23% Hispanic, 11% Chinese) completed 7-days of actigraphy. At the same exam, coronary artery calcium (CAC) was derived from computed tomography, carotid plaque presence and carotid intima-media thickness (cIMT) were derived from ultrasonography, and the ankle brachial index (ABI) was calculated from extremity measured systolic blood pressure. Sleep regularity was quantified by standard deviations in sleep durations and sleep onset time across wear days and categorized in 30 minute (mins) increments. Adjusted relative risk regression models were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI) for associations of measures of sleep regularity with each subclinical marker of CVD. Models adjusted for demographics, CVD risk factors, and objectively-assessed obstructive sleep apnea. Results: After multivariable adjustment, and compared to those with regular sleep durations (SD≤60 mins), participants with greater sleep duration irregularity (SD&gt;120 mins) were more likely to have high CAC burden [CAC &gt;300; PR (95% CI): 1.36 (1.03-1.78)], carotid plaque [1.10 (1.00-1.22)] and an abnormal ABI [ABI &lt;0.9; 1.74 (1.00-3.02)]. Compared to participants with regular sleep timing (SD≤30 mins), those with irregular sleep timing (SD&gt;90 mins) were 1.38 (1.04-1.83) times more likely to have high CAC burden. Associations did not vary by age or sex. Conclusion: Sleep regularity, particularly sleep duration regularity, was associated with measures of subclinical CVD in this diverse cohort. Sleep regularity is a modifiable sleep dimension worthy of further investigation.

Abstract P149: The Relationship Between Daytime Sleepiness, Exhaustion, Fatigue, And Arterial Stiffness. The Atherosclerosis Risk In Communities (ARIC) Study

Background: Excessive Daytime Sleepiness (EDS) is positively associated with the risk of cardiovascular disease (CVD) events and CVD mortality. However, the association between EDS and subclinical markers of CVD, such as arterial stiffness, is not fully understood and could have implications for CVD screening. EDS is multifactorial in origin, thus we incorporated measures of exhaustion and fatigue in order to comprehensively assess the association of lethargy and central artery stiffness. We examined the separate relationships between EDS, exhaustion, fatigue, and aortic stiffness via carotid-femoral pulse wave velocity (cfPWV) in a large population-based study. Methods: A cross-sectional analysis of ARIC Study participants (n=2500, mean age: 79.7, 57.2% female) who underwent arterial stiffness measurements (cfPWV) and completed the Epworth Sleep Scale (ESS) questionnaire in 2016-2019. EDS was defined as ESS 11. Exhaustion was derived from the Center for Epidemiological Study’s Depression (CES-D) scale, with positive exhaustion corresponding to increased effort in daily activities and noticeable difficulty in getting “going’. Fatigue was assessed at annual follow up calls in 2012-2013 and calculated as a summary score with participants responses about feeling tired in various scenarios in the past 7 days noted as a numeric value (1-5: never, rarely, sometimes, often or always). We used multivariable linear regression to estimate the association between ESS, exhaustion, and fatigue with cfPWV, adjusting for age, race-study center, body mass index, diabetes, heart rate, mean arterial pressure, and blood-pressure medication use. We evaluated potential effect modification by race, sex, diabetes, and hypertension. Results are presented as unstandardized beta coefficients (β) and 95% confidence intervals (CI). Results: A total of 14.2% participants reported EDS, 17.2% reported exhaustion, and the average fatigue score was 8.0. ESS was not associated with cfPWV when adjusting for covariates (β; 95% CI: -1.4; -4.7, 1.9). Similarly, EDS was not associated with cfPWV (β; 95% CI: -4.9; -40.4, 30.6), nor was there an association between ESS quartiles and cfPWV. However, both exhaustion (β; 95% CI: 40.4; 7.8, 73.0) and fatigue (β; 95% CI: 5.4; 0.6, 10.3) were positively associated with cfPWV after adjusting for covariates. There was no evidence of effect modification by race, sex, diabetes, or hypertension. Conclusion: EDS was not associated with arterial stiffness. A (positive) association was observed for both exhaustion and fatigue with cfPWV, suggesting a need for further investigation of fatigue related conditions and arterial stiffness in older adults.

Defining the effects of traffic-related air pollution on the human plasma proteome using an aptamer proteomic array: A dose-dependent increase in atherosclerosis-related proteins

BackgroundTraffic-related air pollution (TRAP) is a critical risk factor and major contributor to respiratory and cardiovascular disease (CVD). The effects of TRAP beyond the lungs can be related to changes in circulatory proteins. However, such TRAP-mediated changes have not been defined in an unbiased manner using a controlled human model. ObjectiveTo detail global protein changes (the proteome) in plasma following exposure to inhaled diesel exhaust (DE), a paradigm of TRAP, using controlled human exposures. MethodsIn one protocol, ex-smokers and never-smokers were exposed to filtered air (FA) and DE (300 μg PM2.5/m3), on order-randomized days, for 2 h. In a second protocol, independent never-smoking participants were exposed to lower concentrations of DE (20, 50 or 150 μg PM2.5/m3) and FA, for 4 h, on order-randomized days. Each exposure was separated by 4 weeks of washout. Plasma samples obtained 24 h post-exposure from ex-smokers (n = 6) were first probed using Slow off-rate modified aptamer proteomic array. Plasma from never-smokers (n = 11) was used for independent assessment of proteins selected from the proteomics study by immunoblotting. ResultsProteomics analyses revealed that DE significantly altered 342 proteins in plasma of ex-smokers (n = 6). The top 20 proteins therein were primarily associated with inflammation and CVD. Plasma from never-smokers (n = 11) was used for independent assessment of 6 proteins, amongst the top 10 proteins increased by DE in the proteomics study, for immunoblotting. The abundance of all six proteins (fractalkine, apolipoproteins (APOB and APOM), IL18R1, MIP-3 and MMP-12) was significantly increased by DE in plasma of these never-smokers. DE-mediated increase was shown to be concentration-dependent for fractalkine, APOB and MMP-12, all biomarkers of atherosclerosis, which correlated with plasma levels of IL-6, a subclinical marker of CVD, in independent participants. ConclusionThis investigation details changes in the human plasma proteome due to TRAP. We identify specific atherosclerosis-related proteins that increase concentration-dependently across a range of TRAP levels applicable worldwide.