Endothelial Dysfunction as a Link Between Cardiovascular Risk Factors and Peripheral Neuropathy in Diabetes

Abstract Context: Cardiovascular risk factors are well-known predictors of the development of diabetic peripheral neuropathy (DPN), which has traditionally been considered as a manifestation of diabetes-associated microangiopathy. Because endothelial dysfunction is strongly associated with all cardiovascular risk factors, we hypothesized that it may be a link between cardiovascular risk factors and DPN. Objective: The primary objective of this study was to test whether endothelial dysfunction is a predictor of DPN. Design and Setting: This is a cross-sectional analysis of a cohort composed of patients followed at the Microcirculatory Laboratory, Beth Israel Deaconess Medical Center. Patients: Participants with diabetes without DPN (n = 192) and with DPN (n = 166), subjects with prediabetes (n = 75), and nondiabetic controls (n = 59) were included. Interventions: Endothelial function was assessed with flow-mediated dilation (FMD) of the brachial artery. Inflammatory cytokines and biomarkers of endothelial function (soluble intercellular and vascular cell adhesion molecules) were quantified using a multiplex bead-based immunoassay. Neurological assessment included the neuropathy disability score (NDS). Main Outcome Measure: The relationship between FMD and NDS assessed using multiple linear regression. Results: In addition to already known risk factors of DPN, FMD was strongly associated with NDS (β = −0.24; P < .001). Sensitivity analysis that removed FMD from the model provided similar results for soluble intercellular cell adhesion molecule-1, another biomarker of endothelial function. Confirmatory factor analysis further showed that endothelial dysfunction is a significant mediator between glycosylated hemoglobin and diabetes duration and diabetic complications. Conclusions: This study shows that endothelial dysfunction occurs early in the pathophysiology of diabetes and is a link between cardiovascular risk factors and DPN.

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Abstract 13062: Epicardial Fat Associates With Endothelial Dysfunction, but Not With Coronary Calcium Score: From the Elsa-brasil Cohort Study

Circulation ◽

10.1161/circ.142.suppl_3.13062 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Karina P Martins ◽

Sandhi Barreto ◽

Daniel Bos ◽

JESIANA PEDROSA ◽

Douglas Mesquita ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Coronary Artery ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Cardiovascular Risk Factors ◽

Subcutaneous Fat ◽

Epicardial Fat ◽

Fat Deposits ◽

Multivariable Analyses

Introduction: Epicardial fat has been related to coronary artery disease (CAD) independent of visceral or subcutaneous fat. The mechanism responsible for this association has not yet been elucidated. Our objective was to evaluate the association between automatically measured epicardial fat volume (EFV), cardiovascular risk factors, coronary artery calcium (CAC) and endothelial function in participants of ELSA-Brasil. Methods and Results: The sample comprised 470 (mean age 55± 8y, 52.3% men) participants from ELSA-MG, one of the Investigation Centers of the cohort, who had valid computed tomography scans and endothelial function evaluated by peripheral arterial tonometry (PAT). The mean EFV was 111 (IQ 86-144) mL. CAC=0 was detected in 55% of participants. In the multivariable analyses between cardiovascular risk factors and EFV, the following associations were observed with higher EFV: female sex; and increased age, waist circumference and triglycerides (p <0.001 for all). In multivariable analyses, higher EFV remained associated with worse endothelial function - basal pulse amplitude (q2=1.22, CI95% 1.07-1.40, p=0.004; q3=1.50, CI95% 1.30-1.74, p<0.001; q4=1.50, CI95% 1.28-1.79, p<0.001) and PAT ratio (q2=0.87, CI95% 0.81-0.95, p<0.001; q3=0.86, CI95% 0.79-0.94, p<0.001; q4=0.80, CI95% 0.73-0.89, p<0.001), but not with CAC. Conclusions: Higher EFV was associated with impaired endothelial function, but not with higher CAC. Our results suggest that the mechanism by which epicardial fat deposits relates to CAD may be different from the pathway of CAC, which relates to calcified plaques. A possible mechanism may be through the enhancement of endothelial dysfunction, microvascular disease and predominantly lipidic non-calcified plaques.

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A single Mediterranean meal does not impair postprandial flow-mediated dilatation in healthy men with subclinical metabolic dysregulations

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0490 ◽

2016 ◽

Vol 41 (8) ◽

pp. 888-894 ◽

Cited By ~ 9

Author(s):

Sébastien Lacroix ◽

Christine Des Rosiers ◽

Mathieu Gayda ◽

Anna Nozza ◽

Éric Thorin ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Risk ◽

Fatty Acid ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Cardiovascular Risk Factors ◽

Omega 3 ◽

Vascular Effect ◽

Metabolic Markers ◽

Flow Mediated Dilatation

Cardiovascular risk factors are known to exacerbate high-saturated fatty acid meal (HSFAM)-induced endothelial dysfunction, but the influence of subclinical metabolic dysregulations and the acute impact of a single mixed Mediterranean-type meal (MMM) remains unknown. Thus, this study has the objective to evaluate the metabolic and vascular effect of such meals in healthy subjects with or without subclinical fasting metabolic dysregulations. Twenty-eight healthy males without overt cardiovascular risk factors randomly ingested 1 of 2 isocaloric meals on separate days. Plasma metabolic markers, fatty acid (FA) profile, and endothelial function (flow-mediated dilatation; FMD) were assessed at baseline and 2 and 4 h after meal ingestion. Unsupervised hierarchical clustering identified 2 subgroups of participants (n = 11 and 17) differing by their baseline metabolic profiles. The MMM did not significantly alter postprandial endothelial function in all subjects, irrespective of baseline metabolic parameters. In contrast, the HSFAM induced postprandial endothelial dysfunction (Δ%FMDabsolute = −5.28 ± 2.54, p < 0.01 vs. MMM) in a subgroup of individuals with significantly greater body mass index, fasting insulinemia, and lipid parameters (n = 11). Finally, the postprandial plasma FA profiles were differentially enriched by the HSFAM and MMM, notably with saturated FAs and omega-3 polyunsaturated FAs, respectively. Collectively, our results highlight the detrimental impact of a single HSFAM on endothelial function in healthy individuals displaying subclinical fasting metabolic dysregulations. Such individuals could benefit from MMM, demonstrated herein to be without any acute detriment to endothelial function.

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Association of cardiovascular risk factors with markers of endothelial dysfunction in middle-aged men and women

Thrombosis and Haemostasis ◽

10.1160/th05-08-0552 ◽

2006 ◽

Vol 95 (01) ◽

pp. 134-141 ◽

Cited By ~ 24

Author(s):

Barbara Thorand ◽

Jens Baumert ◽

Angela Döring ◽

Andrea Schneider ◽

Lloyd Chambless ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Cardiovascular Risk ◽

Endothelial Dysfunction ◽

Alcohol Consumption ◽

Cardiovascular Risk Factors ◽

Linear Regression Analysis ◽

High Body Mass Index ◽

Moderate Alcohol Consumption ◽

Men And Women

SummaryEndothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases and diabetes mellitus. However, the causes underlying endothelial dysfunction are not fully understood. Therefore, the aim of the present study was to investigate associations of cardiovascular risk factors with soluble adhesion molecules (sE-Selectin, sICAM-1), soluble thrombomodulin (sTM) and von Willebrand factor (vWF) as markers of endothelial dysfunction. The study population consisted of a subcohort of 2,168 men and women aged 35 to 74 years randomly drawn from three cross-sectional population-based MONICA/ KORA Augsburg surveys conducted between 1984 and 1995. In multivariable linear regression analysis, current smoking, high (versus moderate) alcohol consumption, ratio of total cholesterol/HDL-cholesterol (TC/HDL-C) and C-reactive protein (CRP) were significantly associated with elevated levels of sEselectin and sICAM-1. Increased levels of sE-selectin were also found in subjects with actual hypertension, high body mass index and prevalent diabetes mellitus. In addition, low physical activity and no (versus moderate) alcohol consumption were significantly associated with elevated concentrations of sICAM-1. Levels of sTM were higher in subjects with actual hypertension, no or high amounts of alcohol intake and a high ratio of TC/ HDL-C, but were lower in subjects witha history of myocardial infarction. VWF was significantly associated with CRP only. In conclusion, sE-selectin and sICAM-1 are more strongly associated with traditional cardiovascular risk factors than sTM and vWF.

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Endothelial Function and Insulin Resistance in Early Postmenopausal Women with Cardiovascular Risk Factors: Importance of ESR1 and NOS3 Polymorphisms

PLoS ONE ◽

10.1371/journal.pone.0103444 ◽

2014 ◽

Vol 9 (7) ◽

pp. e103444 ◽

Cited By ~ 7

Author(s):

Ruth Clapauch ◽

André Felipe Mourão ◽

Anete S. Mecenas ◽

Priscila A. Maranhão ◽

Ana Rossini ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Cardiovascular Risk ◽

Endothelial Function ◽

Cardiovascular Risk Factors ◽

Postmenopausal Women ◽

Early Postmenopausal Women

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Cardiovascular Risk Factors and their Relationship with Endothelial Dysfunction in Rural and Urban South African Children

10.21203/rs.3.rs-54162/v1 ◽

2020 ◽

Author(s):

Edna N. Matjuda ◽

Godwill Azeh Engwa ◽

Samuel Nkeh Chungag Anye ◽

Benedicta N. Nkeh Chungag ◽

Nandu Goswami

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Cardiovascular Risk ◽

Endothelial Dysfunction ◽

Cardiovascular Risk Factors ◽

High Blood Pressure ◽

Urban Children ◽

Urban Settings ◽

Arterial Blood ◽

Rural And Urban

Abstract Background: Endothelial dysfunction is known to be an initiator to the development and progression of atherosclerotic cardiovascular disease (CVD). However, there is paucity o knowledge on its relationship with cardiovascular risk factors in children. More so, some of these cardiovascular risk factors are known to be influenced by feeding habits and life style changes which often vary between rural and urban settings. This study was aimed to investigate the relationship between cardiovascular risk factors and endothelial function in rural and urban children. Methods: A cross-sectional study on 6-9 years old children in randomly selected rural and urban schools of the Eastern Cape Province of South Arica was conducted. General anthropometric indices were measured followed by blood pressure (BP) measurements. The pulse wave velocity (PWV) was measured using a Vicorder. Urine sample was collected for the determination of albumin, creatinine, asymmetric dimethylarginine (ADMA), 8-hydroxy-2deoxyguanosine (8-OHdG) and thiobarbituric acid reactive substance (TBARS). Albumin to creatinine ratio (ACR) was calculated.Results: Children from urban settings (10.8%) had a higher prevalence of overweight/obesity than their rural counterparts (8.5%) while the prevalence of elevated/high blood pressure was higher in rural children (23.2%) than in urban children (19.0%). Diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) significantly (p<0.005) increased with increasing quartiles of PWV. ADMA positively associated with HR in rural girls and showed a weak risk for elevated SBP and MAP. Body mass index (BMI) increased with increasing PWV and predicted endothelial dysfunction. 8-OHdG significantly (p<0.005) increased with increasing quartiles of ADMA and positively correlated with ADMA. Creatinine, albumin and ACR significantly (p<0.005) increased with increasing ADMA and ADMA associated positively with creatinine. Conclusion: Endothelial dysfunction was associated with obesity, high blood pressure, oxidative stress and microalbuminuria in children, and this relationship varied between rural and urban children.

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