Disease Risk Markers Research Articles

Serum Carboxylated and Undercarboxylated Osteocalcin association with Coronary Atherosclerosis Disease and Cardiovascular Risk Markers in: Analysis of a Syrian Male Cohort

Background: New assumption concerning association of osteocalcin and Vascular calcification has emerged in reaction to observations that the mechanism of vascular calcification resembles that of bone mineralization, thus linking bone and the vasculature. However, studies reported contrasting results about the association between osteocalcin and atherosclerosis. This study was designed to evaluate capacity relationships among different forms of circulating osteocalcin and cardiovascular risk markers in male with coronary atherosclerosis. Methods: A cross-sectional study was conducted on 58 male patients, divided into two groups according to the severity of coronary artery disease (CAD), as determined by coronary angiography assessment: Early coronary atherosclerosis (ECA), n=20, patients with mild CAD (<50% stenosis in any major epicardial arteries), and late coronary atherosclerosis (LCA), n=38, patients with severe, multivessel CAD (>50% stenosis in at least one or more major epicardial arteries). The healthy control (HC) group included 26 healthy male subjects. Carboxylated (cOC) and ucOC were measured using ELISA technique. Results: We observed significantly lower ucOC levels in both stages of cardiovascular disease (CVD) (ECA and LCA) compared to the HC group (2.34±2.23 and 2.48±1.60 vs 6.65±1.78ng/mL, P<0.01). ucOC was inversely correlated with an increasing number of cardiovascular risk factors (CVRFs). Moreover, ucOC levels were markedly reduced in high-fasting plasma glucose (FPG) groups (IFG and T2DM-threshold level), compared to the normal FPG group (NG). cOC levels were higher in the IFG group, compared to the normal FPG group (8.50±4.76 vs 7.13±3.13ng/mL, p=0.008) possibly predicting such condition. Conclusions: In the present study, patients with coronary atherosclerosis, regardless of the onset of stenosis, showed lower ucOC levels which were inversely correlated with an increasing number of CVRFs. Moreover, ucOC levels were markedly reduced in high-FPG groups. Serum ucOC may be considered as a potential biomarker for coronary atherosclerosis disease and therefore its measurement may help to establish preventive and therapeutic approaches. Moreover, cOC may be associated with a high alert for diabetes at the IFG stage, but not when the disease progresses to diabetes.

Anti-Phosphatidylethanolamine and Anti-Phosphatidylserine Antibodies-Association with Renal Involvement, Atherosclerosis, Cardiovascular Manifestations, Raynaud Phenomenon and Disease Activity in Polish Patients with Systemic Lupus Erythematosus.

Objective. To evaluate the association between anti-phosphatidylethanolamine (aPE) and anti-phosphatidylserine (aPS) antibodies and cardiovascular risk, organ involvement and disease activity in systemic lupus erythematosus (SLE) patients. Methods. We studied 93 SLE patients and 30 controls. We analyzed levels of anti-phospholipid antibodies, including aPS and aPE, the profiles of antinuclear, anti-neutrophil cytoplasmic (ANCA) and anti-endothelial antibodies, carotid intima-media thickness (cITM) and atherosclerotic plaque presence, ankle-brachial and high resistance indices, atherosclerotic risk factors, organ manifestations and treatment. Results. Levels of aPS and aPE were significantly higher in SLE patients in comparison with the controls (p = 0.038 and p = 0.044, respectively). aPS was associated with the risk of Raynaud’s phenomenon (p = 0.021) development. aPE increased the risk of renal involvement (p = 0.049), cerebral stroke (p = 0.050), high vlues of cIMT (p = 0.041) development as well as occurrence of selected serological markers associated with activity of the disease such as anti-double stranded DNA (p = 0.021). The long duration of regular smoking (p = 0.021) and the high number of cigarettes/day (p = 0.015) were significantly associated with the risk of aPE occurrence. Conclusions. Patients with aPS and aPE are at risk of vascular involvement. Especially the presence of aPE may significantly increase the risk of thrombotic complications development in SLE patients without classical serological markers of APS. Finally, aPE might be used as a marker of disease activity and risk of renal injury development in this patient group. The classical atherosclerotic markers including lipid indices play an important role in complex analysis of cardiovascular risk in lupus patients and enable to identify patients at the highest risk and implement effective preventive, diagnostic and therapeutic procedures.

Study on urine micro albuminuria as an isolated risk factor for cardiac morbitdity and mortality in non-diabetics and non-hypertensives

Background: There is a relative paucity of data on the link between urine micro albumin and IHD in non-diabetics as well as non-hypertensive’s compared to diabetics. This study was meant to look for the association between urine micro albumin and in cardiac morbidity and mortality among non-diabetic and non-hypertensive’s, which may further provide insight to the early diagnosis of micro albuminuria and its potential for predicting cardiac morbidity and thus needed inputs for better clinical management. Aims and objectives: To assess the relationship between micro albuminuria and proven risk factors and markers of cardiovascular disease in non-diabetic & non-hyper extensive ischaemic heart disease patients. Materials and methods: Among the 200 patients which were taken in the study, 141 (69.8%) were males and the rest29.2%were females. 34.5% each were from the age of 41-50 years and51-60 years respectively. Only 26 (13.0%) patients were from the age group of morethan60years. Results: The mean age of patients was 50.66 with a SDof 9.33. Majority of males were from the age group of 41-50 years (38.3%), while 42.4% of females were from the age group of 51-60 years. Mean age of male patients was found to be 49.41±9.16,while female patients was of 52.44±9.57.

Association between APOE Genotype with Body Composition and Cardiovascular Disease Risk Markers Is Modulated by BMI in Healthy Adults: Findings from the BODYCON Study.

Body mass index (BMI) has been suggested to play an important role in the relationship between the APOLIPOPROTEIN (APO)E genotype and cardiovascular disease (CVD) risk. Using data from the BODYCON cross-sectional study (n = 360 adults) we assessed the association between body composition and CVD risk markers according to APOE genotype, with examination of the role of BMI. In this study cohort, the APOE2/E3 group had lower fasting blood lipids than APOE4 carriers and APOE3/E3 group (p ≤ 0.01). After stratifying the group according to BMI, APOE4 carriers in the normal BMI subgroup had a higher lean mass compared with the APOE3/E3 group (p = 0.02) whereas in the overweight/obese subgroup, the android to gynoid percentage fat ratio was lower in APOE4 carriers than APOE3/E3 group (p = 0.04). Fasting lipid concentrations were only different between the APOE2/E3 and other genotype groups within the normal weight BMI subgroup (p ≤ 0.04). This finding was associated with a lower dietary fibre and a higher trans-fat intake compared with APOE4 carriers, and a lower carbohydrate intake relative to the APOE3/E3 group. Our results confirm previous reports that BMI modulates the effect of APOE on CVD risk markers and suggest novel interactions on body composition, with diet a potential modulator of this relationship.

Physical activity assessment and vascular function in adults with cystic fibrosis and their non-CF peers

ABSTRACT An understanding of physical activity (PA) and related health benefits remains limited in adults with Cystic Fibrosis (CF). Raw acceleration data metrics may improve the quality of assessment and further this understanding. The study aimed to compare PA between people with CF (pwCF) and non-CF peers and examine associations between PA, vascular function and health outcome measures. PA was assessed in 62 participants (31 pwCF) using ActiGraph accelerometers. Vascular function (a marker of cardiovascular disease risk) was assessed using flow-mediated dilatation (FMD) in sub-groups of pwCF (n = 12) and matched controls. Average Euclidean norm minus one (ENMO) (total PA) was significantly lower (p = 0.005) in pwCF (35.09 ± 10.60 mg), than their non-CF peers (44.62 ± 13.78 mg). PwCF had PA profiles (intensity gradient) indicative of more time in lower intensity activity (−2.62 ± 0.20, −2.37 ± 0.23). Vigorous activity was positively associated with lung function (rs = 0.359) and Quality of Life (r = 0.412). There were no significant differences (p = 0.313) in FMD% between pwCF (5.29 ± 2.76%) and non-CF peers (4.34 ± 1.58%) and no associations with PA. PwCF engaged in less moderate-to-vigorous PA and demonstrated a steeper PA profile than their non-CF peers.

Serum Uric Acid and Lipid Levels in Patients With Acute Ischemic Stroke: A Cross-Sectional Study.

Background and objectiveGiven the enormous public health burden posed by acute ischemic stroke (AIS), it becomes imperative to identify associated risk factors such as serum uric acid (SUA) and lipid profile that can be tangibly assessed. This could potentially provide useful markers for disease risk or progression, facilitating timely diagnosis and management of AIS. This study aimed to evaluate the SUA and lipid levels in patients with AIS.MethodThis cross-sectional study enrolled 66 AIS patients aged >18 years, from both genders. After a thorough medical history and clinical examination, each patient was subjected to SUA analysis and lipid profiling using an auto-analyzer with dedicated reagents. Results were statistically analyzed using Chi square test, and p-value ≤0.05 indicated statistical significance.Results and interpretationThe study cohort showed a mean age of 61.17 ± 14.01 years and male to female (M:F) ratio of 1.7:1, with mean blood levels of SUA, triglyceride, and high-density lipoprotein (HDL) reaching 5.68 ± 1.71 g/dL, 205.42 ± 105.08 g/dL, and 29.80 ± 8.45 g/dL, respectively. Most patients suffered from hypertension (81.82%), diabetes (77.27%), and alcoholism (24.24%). Cerebrovascular Doppler findings revealed the combined presence of plaque and stenosis (24.24%). Male AIS patients showed a significantly greater association with alcohol and smoking/nicotine use (p<0.001). Gender showed no significant association with SUA, lipid profile, hypertension, and diabetes (p>0.05).ConclusionAIS is associated with hyperuricemia and dyslipidemia, with no significant gender differences.

Cohort profile: The PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension (PEACH) Study.

Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal morbidity and mortality worldwide, with implications for maternal and neonatal well-being in the short term and for long-term maternal cardiovascular health. Although the mechanisms behind HDP remain incompletely understood, evidence suggests that preeclampsia in particular is a syndrome with more than one distinct subtype. The PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction, Hypertension) Study was established to identify new HDP subtyping systems reflecting aetiology and prognosis and to find markers of later cardiovascular disease risk associated with preeclampsia. The PEACH Study recruited pregnant women referred to two Copenhagen-area hospitals with suspected preeclampsia (mean gestational age at enrolment: 36.7 weeks) and a group of frequency-matched pregnant women planning delivery at the same hospitals and healthy when enrolled mid-pregnancy. Prospective, longitudinal pregnancy cohort. Participants underwent repeated third-trimester blood sample collection, longitudinal cardiac function assessments using the USCOM-1A during the third trimester and at 1 year postpartum and collection of placental samples immediately after delivery. Medical information was abstracted from medical records and hospital databases. During 2016-2018, we recruited 1149 pregnant women, of whom 1101 were followed to delivery. Among 691 women enrolled with suspected preeclampsia, 310 and 172 developed preeclampsia and gestational hypertension respectively. Among 410 women with healthy pregnancies when enrolled mid-pregnancy, 37 later developed hypertensive disorders of pregnancy. Of 1089 women still in the cohort 1year postpartum, 578 (53.1%) participated in the follow-up assessment. The PEACH Study's rich data from women with and without HDP will enable us to identify new, clinically useful HDP subtypes to aid in decision-making regarding monitoring and treatment. Continued postpartum follow-up will help us develop algorithms to identify women at risk of persistent postpartum cardiac dysfunction and later cardiovascular disease after pregnancies complicated by HDP.

Impact of bariatric surgery on circulating PCSK9 levels as a marker of cardiovascular disease risk: a meta-analysis.

IntroductionThis systematic review and meta-analysis focuses on PCSK9 changes in obese patients following bariatric surgery.MethodsA systematic literature search in four databases was performed. Comprehensive Meta-Analysis (CMA) V2 software used to conduct the meta-analysis. Studies were evaluated regarding heterogeneity in design, populations under investigation, and treatment duration using a random-effects model and the generic inverse variance weighting approach. A random-effect meta-regression approach was used to investigate the association with the estimated effect size.ResultsThe results of the meta-analysis on 4 trials including 260 individuals demonstrated a remarkable decline of PCSK9 after bariatric surgery (WMD = –57.34 ng/ml, 95% CI: –87.97, –26.71, p < 0.001; I2 = 96.25%). Consistently, a significant decrease of LDL-C after bariatric surgery (WMD = –22.57 mg/dl, 95% CI: –27.5, –17.574, p < 0.001; I2 = 86.35%) was observed.ConclusionsPCSK9 is reduced significantly after bariatric surgery. The decrease of PCSK9 might be utilized as an independent surrogate marker of improvement of atherosclerotic cardiovascular disease risk after bariatric surgery.

Association between phase angle and coronary artery calcium score in patients on peritoneal dialysis.

IntroductionThe phase angle (PhA) has been used as a nutritional marker and predictor of mortality in patients on peritoneal dialysis (PD). The coronary artery calcium (CAC) score has shown to predict the incidence of acute myocardial infarction and death from cardiovascular disease in these patients. However, the association between PhA and CAC score in patients with PD is not well-established, which is the objective of this study.Materials and methodsCross-sectional study with patients on PD, followed up at a University Hospital, between March 2018 and August 2019. PhA was evaluated by unifrequency bioimpedance (BIA). The CAC score was calculated based on cardiovascular computed tomography, considering positive when greater than or equal to 100 Agatston and negative when less than 100 Agatston.ResultsWe evaluated 44 patients on dialysis, with a mean age of 56 years and median time on dialysis therapy was 11.7 months. In the statistical analysis, a significant association was only observed between the CAC score and the PhA.ConclusionThe PhA is associated with a positive CAC score in patients with PD, and despite other factors, may be useful as a risk marker for coronary artery disease in this population.

Evaluation of arterial stiffness in patients with familial hypercholesterolemia

Background and Aims : Patients with familial hypercholesterolemia (FH) are at increased risk of early cardiovascular events, and its main characteristic is the increase in LDL-cholesterol (LDL-c), leading to arterial atherosclerosis, which leads to increased risk for acute myocardial infarction and stroke. The main treatment is done with high potency statins. Arterial stiffness (AS) is an important risk marker for cardiovascular disease, which can be assessed by the patient's pulse wave velocity (PWV) and central systolic blood pressure (CSBP).

High-Resolution Digital Phenotypes From Consumer Wearables and Their Applications in Machine Learning of Cardiometabolic Risk Markers: Cohort Study.

BackgroundConsumer-grade wearable devices enable detailed recordings of heart rate and step counts in free-living conditions. Recent studies have shown that summary statistics from these wearable recordings have potential uses for longitudinal monitoring of health and disease states. However, the relationship between higher resolution physiological dynamics from wearables and known markers of health and disease remains largely uncharacterized.ObjectiveWe aimed to derive high-resolution digital phenotypes from observational wearable recordings and to examine their associations with modifiable and inherent markers of cardiometabolic disease risk.MethodsWe introduced a principled framework to extract interpretable high-resolution phenotypes from wearable data recorded in free-living conditions. The proposed framework standardizes the handling of data irregularities; encodes contextual information regarding the underlying physiological state at any given time; and generates a set of 66 minimally redundant features across active, sedentary, and sleep states. We applied our approach to a multimodal data set, from the SingHEART study (NCT02791152), which comprises heart rate and step count time series from wearables, clinical screening profiles, and whole genome sequences from 692 healthy volunteers. We used machine learning to model nonlinear relationships between the high-resolution phenotypes on the one hand and clinical or genomic risk markers for blood pressure, lipid, weight and sugar abnormalities on the other. For each risk type, we performed model comparisons based on Brier scores to assess the predictive value of high-resolution features over and beyond typical baselines. We also qualitatively characterized the wearable phenotypes for participants who had actualized clinical events.ResultsWe found that the high-resolution features have higher predictive value than typical baselines for clinical markers of cardiometabolic disease risk: the best models based on high-resolution features had 17.9% and 7.36% improvement in Brier score over baselines based on age and gender and resting heart rate, respectively (P<.001 in each case). Furthermore, heart rate dynamics from different activity states contain distinct information (maximum absolute correlation coefficient of 0.15). Heart rate dynamics in sedentary states are most predictive of lipid abnormalities and obesity, whereas patterns in active states are most predictive of blood pressure abnormalities (P<.001). Moreover, in comparison with standard measures, higher resolution patterns in wearable heart rate recordings are better able to represent subtle physiological dynamics related to genomic risk for cardiometabolic disease (improvement of 11.9%-22.0% in Brier scores; P<.001). Finally, illustrative case studies reveal connections between these high-resolution phenotypes and actualized clinical events, even for borderline profiles lacking apparent cardiometabolic risk markers.ConclusionsHigh-resolution digital phenotypes recorded by consumer wearables in free-living states have the potential to enhance the prediction of cardiometabolic disease risk and could enable more proactive and personalized health management.

A Comparative Study of the Right and Left Carotid Arteries in Relation to Age for Patients With Diabetes and Hypertension

Introduction: Age, hypertension, and diabetes can cause significant alterations in arterial structure and function, including changes in lumen diameter (LD), intimal-medial thickness (IMT), flow velocities, and arterial compliance. These are also considered risk markers of atherosclerosis and cerebrovascular disease. A difference between right and left carotid artery blood flow and IMT has been reported by some researchers, and a difference in the incidence of nonlacunar stroke has been reported between the right and left brain hemispheres. The aim of this study was to determine whether there are differences between the right and left common carotid arteries and internal carotid arteries in patients with hypertension and diabetes for 2 age groups. Methods: We studied 250 patients with both diabetes and hypertension. Patients were divided into 2 age groups with the old age group being 56 to 75 years and the young age group 35 to 55 years. The bilateral common carotid and internal carotid arteries were evaluated with B-mode ultrasound and Doppler examinations. The LD and IMT were measured for both common carotid arteries, and spectral waveform parameters and indices were recorded for both internal carotid arteries. Results: The difference in LD between the left and right common carotid arteries for the old age group was 11.64% and for the young age group was 6.42%, with significant P values of &lt;.05 for both age groups. The difference in IMT between the left and right common carotid arteries was 18.27% in the old age group compared with 15.38% in the young age group, with significant P values of &lt;.05. There was a difference in peak systolic velocity between the left and right internal carotid arteries of 4.85% in the old age group which was not significant, compared with 14.28% in the young age group with a significant P value &lt;.05, whereas the difference in end-diastolic velocity between the left and right internal carotid arteries was not significant for both age groups. Differences between the right and left internal carotid arteries for resistive index, pulsatility index, and pressure gradient were significant only in the young age group. Conclusion: We found significant differences between the right and left common carotid and internal carotid arteries in patients with diabetes and hypertension which were more prominent in the young age group. Values for common carotid IMT and LD were significantly higher in the left common carotid artery versus the right common carotid artery in both age groups. Differences between the 2 carotid sides may be attributed to anatomic variations in the common carotid artery origins which lead to differences in stress between the 2 sides.

Aortic calcification is associated with coronary artery calcification and is a potential surrogate marker for ischemic heart disease risk: A cross-sectional study.

Coronary artery calcification, an established marker of atherosclerotic plaque burden associated with increased risk of coronary artery disease, is routinely evaluated using electron beam computerized tomography or multidetector computed tomography (CT). However, aortic calcification, which is also a risk factor for adverse cardiac events, is not frequently assessed, despite being easily detected via standard chest radiography. We therefore sought to clarify the association between aortic calcification and significant coronary artery calcification to determine the feasibility of performing chest radiography to evaluate the risk of future cardiovascular events.Data from 682 consecutive patients who underwent cardiac CT scanning at our institution from May to September 2012 were included in this cross-sectional analysis. Electrocardiographic-gated CT was used to qualitatively evaluate calcification in 6 aortic segments. Cardiac contrast-ehnanced CT was performed to identify significant calcification of the coronary artery. Calcification was quantified by calculating the Agatston score, and the relationship between significant coronary artery calcification and calcification at each aortic site was evaluated.Among the aortic sites, calcification was most commonly observed in the aortic arch (77.4% of patients). Significant coronary artery calcification was observed in 267 patients (39.1%). Calcification in the ascending aorta, aortic arch, descending aorta, abdominal aorta, and aortic valve were significantly associated with the presence of coronary artery calcification after adjustment for cardiovascular risk factors and statin use (odds ratios [95% confidence intervals] 4.21 [2.55, 6.93], 1.65 [1.01, 2.69], 2.14 [1.36, 3.36], 2.87 [1.83, 4.50], and 3.32 [2.02, 5.46], respectively). Mitral valve calcification was weakly but nonsignificantly associated with coronary artery calcification (odds ratio 1.84 [95% confidence interval 0.94, 3.62]). Calcification of each aortic segment assessed was significantly associated with Agatston score ≥ 100.Aortic calcification was associated with coronary artery calcification. Calcification of the aortic arch, which can be readily detected by routine chest radiography, may be associated with coronary artery calcification and its assessment should therefore be considered to identify patients at increased risk of cardiovascular events. Further studies are warranted to confirm these findings.

Soluble urokinase-type plasminogen activator receptor (suPAR) is elevated in caregivers of patients with parkinsonism

Caregivers are integral to the care of those with neurological disorders such as Parkinson's Disease (PD), but are often burdened by stress, anxiety, and depression. Previous research has suggested that the foundation of such stress is low-grade systemic inflammation, as evidenced by increased interleukin 6 (IL-6) and C-reactive protein (CRP) levels. Soluble urokinase-type plasminogen activator receptor (suPAR) is a kidney disease risk factor and marker of chronic inflammation that integrates psycho-social stress and organ dysfunction. Caregivers of PD experience an extraordinary amount of stress and suPAR's role as prognostic marker has not yet been assessed in caregivers of PD. The aim of this study was to determine the relationship between suPAR levels and PD caregiver burden. Healthy volunteers who accompanied patients with parkinsonism (n = 35) donated blood samples, and complete blood counts (CBC), CRP, and suPAR levels were measured. Participants were then interviewed by telephone and stratified into primary and non-primary caregiver groups. Their caregiver burden was quantified through the Zarit Caregiver Burden Short Form (ZBI-12). The resultant data demonstrated higher plasma levels of suPAR and ZBI-12 scores for the primary caregiver group relative to the non-primary caregiver group (suPAR level: 3.73 vs. 2.72 ng/mL, p = 0.01; ZBI-12: 18.57 vs. 5.4, p < 0.0001; Table). The data also revealed a moderate positive correlation between suPAR and ZBI-12 scores. These findings not only demonstrate a correlation between elevated suPAR and caregiving burden in PD, but also further support and raise awareness for the overall psychosocial burden and stress experienced by those caregivers.

Recommendation on an updated standardization of serum magnesium reference ranges.

PurposeSerum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members’ hospitals and laboratories, presenting an urgent need for standardization.MethodsWe gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide.ResultsSerum magnesium levels designating “hypomagnesemia” differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from “normal” populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used “normal” ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD.ConclusionsWidely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

N-3 index is associated with cardiometabolic risk factors but is not improved by walnut intake in free-living elderly: a single-blind, randomised controlled trial.

n-3 index, the erythrocyte proportion of the EPA + DHA fatty acids is a clinical marker of age-related disease risk. It is unclear whether regular intake of α-linolenic acid (ALA), a plant-derived n-3 polyunsaturated fatty acid, raises n-3 index in older adults. Of the 356 participants at the Loma Linda, CA centre from the original study, a randomly selected subset (n 192) was included for this secondary analysis (mostly Caucasian women, mean age 69 years). Participants were assigned to either the walnut (15 % of daily energy from walnuts) or the control group (usual diet, no walnuts) for 2 years. Erythrocyte fatty acids were determined at baseline and 1-year following intervention. No differences were observed for erythrocyte EPA, but erythrocyte DHA decreased albeit modestly in the walnut group (-0·125 %) and slightly improved in the control group (0·17 %). The change in n-3 index between the walnut and control groups was significantly different only among fish consumers (those who ate fish ≥ once/month). Longitudinal analyses combining both groups showed significant inverse association between the 1-year changes of the n-3 index and fasting plasma TAG (ß = -10), total cholesterol (ß = -5·59) and plasma glucose (ß = -0·27). Consuming ALA-rich walnuts failed to improve n-3 index in elders. A direct source of EPA/DHA may be needed to achieve desirable n-3 index, as it is inversely associated with cardiometabolic risk. Nevertheless, incorporating walnuts as part of heart healthy diets is still encouraged.

A stronger association of diabetes mellitus with impaired hyperaemia using a novel ECG-gated device compared with peripheral arterial tonometry

PurposeImpaired digital reactive hyperaemia and flicker-stimulated retinal vascular response are commonly reported risk markers of cardiovascular disease. This is the first study to determine the correlation of these risk markers with diabetes mellitus by comparing our novel flicker-modulated ECG-gated fundoscope with the EndoPAT2000 system.MethodsIn total, 119 controls and 120 participants with diabetes mellitus partook in this cross-sectional study. The EndoPAT2000 system assessed digital reactive hyperaemia under fasting conditions. A mydriatic ECG-gated fundoscope with a novel flicker module acquired digital retinal images of the left eye before, during and after flicker stimulation. An inhouse semi-automated software measured retinal vessel diameters using a validated protocol with two observers repeating measurements in a subset of 10 controls and 10 participants with diabetes mellitus. Intra- and inter-observer reliability analyses occurred by the interclass correlation coefficient. A receiver operating characteristic curve established associations of variables with diabetes mellitus.ResultsDiabetes mellitus was more strongly associated with flicker-stimulated retinal arteriolar calibre change from baseline (AUC 0.81, 95% CI 0.75–0.87, p < 0.0001) than reactive hyperaemia index. Median flicker-stimulated arteriolar calibre change from baseline (controls: 2.74%, IQR 1.07 vs diabetes mellitus: 1.64%, IQR 1.25, p < 0.0001) and reactive hyperaemia index (controls: 1.87, IQR 0.81 vs diabetes mellitus: 1.60, IQR 0.81, p = 0.003) were lower in diabetes mellitus than controls. Intra- and inter-observer reliability coefficients were high from 0.87 to 0.93.ConclusionsImpaired flicker-stimulated retinal arteriolar calibre change from baseline is more highly correlated with diabetes mellitus in this study than a reduced reactive hyperaemia index.

Dynamic epigenetic age mosaicism in the human atherosclerotic artery.

Accelerated epigenetic ageing, a promising marker of disease risk, has been detected in peripheral blood cells of atherosclerotic patients, but evidence in the vascular wall is lacking. Understanding the trends of epigenetic ageing in the atheroma may provide insights into mechanisms of atherogenesis or identify targets for molecular therapy. We surveyed DNA methylation age in two human artery samples: a set of donor-matched, paired atherosclerotic and healthy aortic portions, and a set of carotid artery atheromas. The well-characterized pan-tissue Horvath epigenetic clock was used, together with the Weidner whole-blood-specific clock as validation. For the first time, we document dynamic DNA methylation age mosaicism of the vascular wall that is atherosclerosis-related, switches from acceleration to deceleration with chronological ageing, and is consistent in human aorta and carotid atheroma. At CpG level, the Horvath epigenetic clock showed modest differential methylation between atherosclerotic and healthy aortic portions, weak association with atheroma histological grade and no clear evidence for participation in atherosclerosis-related cellular pathways. Our data suggest caution when assigning a unidirectional DNA methylation age change to the atherosclerotic arterial wall. Also, the results support previous conclusions that epigenetic ageing reflects non-disease-specific cellular alterations.

17-OR: ADA Presidents' Select Abstract: Effects of Tirzepatide vs. Insulin Glargine 100 U/mL on Kidney Outcomes in Participants with Type 2 Diabetes in SURPASS-4

Tirzepatide (TZP, 5, 10, 15 mg/week) , a dual GIP/GLP-1 receptor agonist, reduced HbA1c levels more than titrated daily insulin glargine (iGlar) in people inadequately controlled on oral diabetes treatments with type 2 diabetes (T2D) and high cardiovascular risk (median study duration 85 weeks) . Here, we compared progression to pre-specified kidney endpoints between TZP and iGlar. Composite kidney outcomes in SURPASS-4 were analysed: endpoint 1 (eGFR [CKD-EPI] decline ≥40% from baseline, renal death, progression to ESRD, new onset macroalbuminuria) and endpoint 2 (endpoint 1 without new onset macroalbuminuria) . Data were examined within the entire study population, and in subgroups defined by baseline SGLT2i use, UACR ≥30 mg/g, eGFR &amp;lt;60 mL/min/1.73m2 and in those at high risk for kidney related outcomes, defined as eGFR &amp;lt;75 mL/min per 1.73 m2 and macroalbuminuria, or eGFR &amp;lt;45 mL/min per 1.73 m2. At baseline, participants (N=1995, age 63.6 years, HbA1c, 8.5%) had a mean eGFR of 81.3 mL/min per 1.73 m2; 17% had eGFR &amp;lt;60 mL/min per 1.73 m2, 28% microalbuminuria (UACR 30-300 mg/g) and 8% macroalbuminuria (UACR &amp;gt;300 mg/g) . During the follow-up to 1weeks, TZP participants experienced significantly fewer renal outcomes, especially new onset of macroalbuminuria versus iGlar (Table) . In people with T2D and high cardiovascular risk, TZP reduced markers of diabetic kidney disease risk. Disclosure H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research &amp; Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. N.Sattar: Consultant; Afimmune Limited, Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novartis Pharmaceuticals Corporation, Roche Diagnostics. I.Pavo: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. K.L.Duffin: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company, Pfizer Inc. Z.Yang: Employee; Eli Lilly and Company. R.Wiese: Employee; Eli Lilly and Company. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Funding Eli Lilly and Company

Effects of weight-loss on adipokines, total and regional body composition and markers of metabolic syndrome in women who are overweight and obese

Obesity among aging women is associated with increased risk for metabolic and cardiovascular diseases. Weight-loss has been shown to reduce disease risk; however, it remains unclear how changes in adipokines following weight-loss are associated with markers of metabolic and cardiovascular health in women. The aim of this study was to determine the effects of a 3-month intensive lifestyle management-focused weight-loss program on the interactions between adipokines, total and regional body composition, and biomarkers of cardiovascular and metabolic health. Women who were overweight or obese (n = 43, age = 49.2 ± 1.5 years, body mass index (BMI) = 34.5 ± 0.9 kg/m2; waist circumference (WC) = 99.8 ± 2.2 cm) completed a 3-month weight-loss program consisting of a reduced energy intake to 1200–1500 kcals/day combined with a progressive walking program targeting 300 min/wk. At 3-months, average body mass was reduced 8.3 % (ΔBMI −8.0 %; ΔWC −6.6 %). Weight-loss lowered fasting glucose (−12.1 %), insulin (−23.2 %), total cholesterol (−11.0 %), and LDL-C (−12.2 %) concentrations, and HOMA-IR (−32.4 %). Leptin was decreased 32.6 %, high molecular weight (HMW) adiponectin increased 25.0 %, and adiponectin:leptin ratio increased 1.27-fold. The change in fat mass was positively correlated with Δleptin (r = 0.527) and inversely correlated with Δadiponectin:leptin ratio (r = −0.547). The ΔHMW adiponectin inversely correlated with Δinsulin (r = −0.360) and ΔHOMA-IR (r = −0.304), and ΔLDL-C (r = −0.305), whereas Δleptin correlated with Δtriglyceride (r = 0.366) and Δtotal cholesterol (r = 0.402). Weight-loss in women who were overweight and obese was associated with a reduction in leptin and increase in HMW adiponectin and adiponectin:leptin ratio. Correlations revealed that changes in these adipokines were uniquely associated with improvements in select markers of metabolic and cardiovascular disease risk.