Objective Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and anti-retroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine if HIV infection is associated with greater epicardial fat and if epicardial fat is associated with subclinical coronary atherosclerosis. Design We studied 579 HIV-infected and 353 HIV-uninfected men age 40 to 70 years with non-contrast computed tomography (CT) to measure epicardial adipose tissue volume (EAT) and coronary artery calcium (CAC). Total plaque score (TPS), and plaque subtypes (non-calcified, calcified and mixed) were measured by coronary CT angiography in 706 men. Methods We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race and serostatus and with additional cardiovascular (CV) risk factors and tested for modifying effects of HIV serostatus. Results HIV-infected men had greater EAT than HIV-uninfected men (p=0.001). EAT was positively associated with duration of antiretroviral therapy (p=0.02), specifically AZT (p<0.05). EAT was associated with presence of any coronary artery plaque (p=0.006) and non-calcified plaque (p=0.001), adjusting for age, race, serostatus and CV risk factors. Among men with CAC, EAT was associated with CAC extent (p=0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque. Conclusions Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV.
Background: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results: Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions: Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.
This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910.
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