Change In cIMT Research Articles

Abstract 13313: Risk of Atherosclerosis in Thoracic Aortic Disease: A Study of Multi-Modal Imaging Data From 40,479 UK Biobank Participants

Background: Despite some shared risk factors, aortic aneurysms and atherosclerosis manifest differently across the aorta. While atherosclerosis commonly co-exists with descending and abdominal aortic aneurysms, some observations suggested a decreased risk of atherosclerosis in patients with ascending aortic aneurysms. This has led to the suggestion that drivers of ascending aortic aneurysms may be anti-atherogenic. Aim: Using carotid intima-media thickness (cIMT) as a surrogate for atherosclerosis and deep learning-derived estimates of aortic diameter, this study examines whether ascending aortic aneurysms are protective against atherosclerosis in a longitudinal analysis of UK Biobank participants. Methods: Individuals who underwent both carotid ultrasound and cardiovascular MRI in the UK Biobank (N=40,479) were identified. We derived ascending and descending aortic measurements from a previously developed deep learning model that was trained to quantify dimensions in >4 million MRI images and extract diameter during ventricular systole. Measures of mean cIMT at 2 standardized angles for bilateral carotid arteries were utilized. The relationship between cIMT and aortic diameter was assessed using univariable and multivariable linear regression. β was calculated as μm change in cIMT per cm of aortic diameter. Results: In individuals with an aneurysmal ascending aorta ( > 4.5cm), there was no significant association between aortic diameter and cIMT after accounting for age, sex, height, and weight (adjusted β=-15.4, P=0.26). There was also no significant correlation between ascending aortic diameter at baseline and cIMT progression in follow-up (adjusted β=-2.5; P=0.48). In the entire cohort, larger ascending aortic size was nominally associated with greater cIMT (adjusted β=5.0; P=0.005). As expected, larger diameter in the descending thoracic aorta was associated with higher cIMT (adjusted β=23.9; P=1.9x10 -16 ). Conclusion: Based on multi-modal imaging data from over 40K individuals, we find no evidence of an inverse relationship between ascending aortic aneurysmal disease and atherosclerosis.

Effect of Exercise on Carotid Artery Intima-Media Thickness in Adults: A Systematic Review and Meta-Analysis.

Carotid intima-media thickness (cIMT) is a validated surrogate marker of atherosclerosis that is independently associated with the risk for cardiovascular disease. Recent studies on the effect of exercise on cIMT have yielded conflicting results. Studies that were available up until October 30, 2021 from the PubMed, Cochrane Library, Embase, and Web of Science databases were included in the analysis. Subgroup analyses were performed to determine the effects of the type, intensity, and duration of exercise on cIMT. This review included 26 studies with 1370 participants. Compared with control participants, those who engaged in exercise showed a decline in cIMT (weighted mean difference [WMD] -0.02; 95% confidence interval [CI], -0.03 to -0.01; I2 = 90.1%). Participants who engaged in aerobic (WMD -0.02; 95% CI, -0.04 to -0.01; I2 = 52.7%) or resistance (WMD -0.01; 95% CI, -0.02 to -0.00; I2 = 38.5%) exercise showed lower cIMT compared with control participants. An exercise duration of >6months was associated with a 0.02mm reduction in cIMT. In participants with low cIMT at baseline (<0.7mm), exercise alone was not associated with a change in cIMT (WMD -0.01; 95% CI, -0.03 to 0.00; I2 = 93.9%). Exercise was associated with reduced cIMT in adults. Aerobic exercise is associated with a greater decline in cIMT than other forms of exercise. Large, multicenter, randomized controlled trials are required to establish optimal exercise protocols for improving the pathological process of atherosclerosis.

Abstract 9768: Relationship of Atherogenic Lipoproteins with Insulin Resistance and Carotid Intimal Thickness in Youth at Risk for Cardiovascular Disease

Introduction: Youth with obesity and abnormal glucose tolerance (AGT) have an atherogenic lipoprotein (Lp) profile (small dense HDL and small LDL) and an increased risk for atherosclerotic disease, but the relative contributions of hyperglycemia and insulin resistance to the development of subclinical atherosclerosis in youth are not well defined. Hypothesis: Atherogenic Lp concentrations (ApoB, small LDLp, small HDLp) are associated with lower insulin sensitivity (Si) and greater carotid intimal thickness (cIMT), irrespective of glycemic status. Methods: In 155 youth with obesity (14.5±1.4y (mean±SD), 50% female; 42 lean (LC: BMI 25-85%ile), 44 insulin sensitive (OIS, fasting insulin ≤20μM/mL, BMI≥95%ile), 35 insulin resistant (OIR; fasting insulin&gt;20μM/mL, BMI≥95%ile) and 34 with AGT (23 prediabetes, 11 type 2 diabetes) we compared a standard lipid panel and Lp size and number. Linear regressions were used to test the associations between lipids/ NMR-derived Lp with Si index derived from a minimal model during an intravenous glucose test. cIMT was determined by ultrasonography. In a subset of 56 youth (21 LC, 19 OIS, 10 OIR, and 7 AGT) we explored the change in Si with the change in Lp and cIMT after 2 years. Results: OIR and AGT had higher triglycerides and lower HDL compared to LC, P &lt;0.01. Total cholesterol, LDL, and cIMT were comparable among all youth. ApoB, total triglyceride-rich Lp, LDLp and small LDLp) were similar in OIS, OIR, and AbGT and higher compared to LC. Among adolescents with obesity, Si was inversely associated with ApoB (β=-0.016), total LDLp (β=-0.91), small HDLp (β=-0.11) and cIMT (β= -2.99), all P &lt;0.001. There was no effect modification by obesity group. LnSi was associated with total HDL (β=1.30), large HDLp (β= 0.23) and small HDLp (β=-0.11), all P &lt;0.01) with steeper associations between AGT vs OIR and AGT vs OIS. After 2 years, the change in insulin sensitivity was not associated with changes in lipoproteins or cIMT. Conclusions: Among youth with obesity, insulin resistance was associated with atherogenic lipoproteins and cIMT, regardless of glucose tolerance status. Alterations in HDL particle number and size were distinct early manifestations that were observed in youth with AGT compared to their peers.

Postprandial endothelial dysfunction and CIMT after oral fat challenge in patients with type 2 diabetes mellitus with and without macrovascular disease - A preliminary study

BackgroundVery few studies have reported on association of postprandial lipids and endothelial dysfunction among patients with diabetes. Whether endothelial dysfunction particularly postprandial FMD is worse in patients with T2DM with macrovascular disease compared to those without and whether this difference is related to postprandial hypertriglyceridemia (PPHTg) is unclear. Therefore, present study was aimed to assess the relationship between PPHTg and endothelial function in patients with T2DM with and without macrovascular disease. MethodEndothelial dysfunction by FMD and CIMT were compared in patients with T2DM with and without macrovascular disease (n = 13 each group) and 13 age, sex and BMI matched healthy individuals after an oral fat challenge. ResultsThere was significant postprandial deterioration of FMD 4-hr after fat challenge in patients with diabetes (P < 0.001) as well as healthy individuals (P = 0.004). Patients with diabetes with macrovascular disease had significantly lower fasting (5.7 ± 6.1% vs. 22.7 ± 10.0% and vs. 24.7 ± 5.3%) as well as postprandial (4-hr) (3.1 ± 5.0% vs. 15.3 ± 8.1% and vs. 15.4 ± 5.7%) FMD compared to other two groups. Fasting, postprandial as well as change in FMD and CIMT in patients with diabetes correlated significantly with fasting as well as postprandial triglycerides with stronger correlation in those with macrovascular disease. ConclusionStudy found significant endothelial dysfunction by FMD that shows substantial further deterioration postprandially following high fat meal in patients with diabetes with macrovascular disease compared to patients with diabetes without macrovascular disease and healthy individuals. Study also indicates that PPHTg is a contributor to endothelial dysfunction. However, more studies are required to corroborate these findings.

Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study.

BackgroundAlthough ≈70% of the world's population of people living with HIV reside in sub‐Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region.Methods and ResultsWe conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population‐based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3–4, range 1–5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non–high‐density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001–0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003–0.008 mm], HIV×time interaction P=0.25).ConclusionsIn rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub‐Saharan Africa.RegistrationURL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.

Waist circumference change and risk of high carotid intima-media thickness in a cohort of Chinese children.

Previous cross-sectional studies showed a positive association between waist circumference (WC) and carotid intima-media thickness (cIMT) among children and adolescents. We examined the association between change in WC and cIMT in a cohort study of Chinese children with 2-year follow-up. A school-based cohort study named 'Huantai Childhood Cardiovascular Health Cohort Study' was conducted in Zibo City, Shandong Province, China. WC and cIMT were measured in 2017 and 2019. Change in WC was categorized into four groups: persistently low WC, WC loss, WC gain and persistently high WC. We examined the association between WC change and cIMT during a 2-year follow-up. A total of 1183 children aged 6-11 years at baseline were included in this study. After adjustment for potential covariates, WC change was associated positively with cIMT change (linear regression coefficient = 5.92 μm/cm per 2 years, 95% confidence interval [CI]: 4.55-7.30). Among the 1072 children (out of 1183 children) with normal cIMT at baseline, compared with persistently low WC, WC gain (odds ratio [OR] = 3.23, 95% CI: 1.14-9.17) and persistently high WC (OR = 7.94, 95% CI: 3.81-16.51) were associated with high cIMT at the end of the follow-up period. In contrast, WC loss during follow-up was not associated with high cIMT (OR = 1.33, 95% CI:0.35-5.11). In this cohort of children, WC gain and persistently high WC were associated with increased cIMT whereas WC loss was not. These findings emphasize the importance of maintaining a normal WC in childhood to promote vascular health.

Abstract 080: A 15-year Cumulative High Exposure to Lean Mass and Blood Pressure but not Fat Mass predicts the 7-year change in Carotid-Femoral Pulse Wave Velocity and Carotid Intima-Media Thickness: The ALSPAC study

Introduction: Evidence on the associations of fat mass and lean mass with changes in carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT), markers of pre-clinical atherosclerosis, from adolescence through young adulthood is lacking. Previous studies have reported strong associations of body mass index (BMI), a measure of adiposity, with these markers. However, it is unclear if increased BMI in relation to these markers represents a pathological process or physiological adaptation. A knowledge gap also exists on the independent associations of blood pressure (BP) measured from childhood through young adulthood with changes in cfPWV and cIMT between ages 17 and 24.5 years. Hypothesis: We assessed the hypothesis whether lean mass and systolic BP, independent of fat mass, cardiometabolic and lifestyle factors, measured at age 9, 17, and 24.5 years drive a 7-year change in cfPWV and cIMT. Methods: We studied 3863 British children from the Avon Longitudinal Study of Parents and Children's birth cohort (56% females). fat mass and lean mass were measured by dual-energy Xray absorptiometry, systolic and diastolic BP by Omron BP/pulse monitor, cfPWV by Vicorder device, and cIMT by CardioHealth ultrasound scan. All exposures were categorized in tertiles of low, normal, and high, with the low category as the reference group. We conducted linear mixed effect model analyses and adjusted for age, sex, low-density lipoprotein, C-reactive protein, fasting blood glucose, moderate to vigorous physical activity, smoking status, family history of cardiometabolic diseases, time in years between measure at 9 and 24.5 years, and systolic BP, fat mass, and/or lean mass depending on the predictor. Results: Participants mean (SD) age in years at different time points were [9.83 (0.30); 17.72 (0.33); 24.54 (0.73)]. Over a 15-year follow-up period, persistent exposure to high lean mass effect estimate =0.006 (CI 0.001 - 0.010, p=0.022), high systolic BP 0.013 (0.009 - 0.017, p&lt;0.0001), and high diastolic BP 0.023 (0.019 - 0.027, p&lt;0.0001), were independently associated with a 7-year increase in cfPWV. Accumulated fat mass and BMI were not related to cfPWV changes. Cumulative exposure to high lean mass 0.012 (0.008 - 0.016, p&lt;0.0001), high BMI 0.007 (0.003 - 0.011, p=0.001) and high systolic BP 0.010 (0.006 - 0.014, p&lt;0.0001) were independently associated with a 7-year increase in cIMT. fat mass and Diastolic BP were not associated with cIMT changes. Conclusion: For the first time, we showed in a healthy cohort that persistent exposure to higher lean mass and BP from childhood independently drives arterial wall adaptation in early adulthood. These arterial changes are likely normal responses to growth and maturation rather than subclinical signs of arterial diseases. Thus, cumulative exposure to high BMI in relation to higher cfPWV and cIMT may not indicate a deleterious effect of adiposity.

Accelerated Early Vascular Aging Among Adolescents With Obesity and/or Type 2 Diabetes Mellitus.

BackgroundThe normal rate of subclinical vascular aging from adolescence to young adulthood has not been well‐characterized. We conducted a 5‐year longitudinal study among adolescents with normal‐weight, obesity, and/or type 2 diabetes mellitus to examine trajectories of early vascular aging.Methods and ResultsAdolescents (mean [SD] age 17.6 [3.5]; 35.3% male) had either normal weight (n=141), obesity (n=156), or type 2 diabetes mellitus (n=151) at baseline. Primary metrics used for early vascular aging included measures of vascular structure (carotid intima‐media thickness [cIMT]; common, internal, and bulb) and arterial stiffness (carotid‐femoral pulse wave velocity, and augmentation index). Longitudinal (5‐year) outcomes were examined using generalized estimating equations adjusting for baseline value, sex, race, and age. Compared with participants with normal weight, those with obesity had greater positive change in common cIMT (0.05 mm [0.03, 0.06]; P<0.001), bulb cIMT (0.02 mm [0.00, 0.05]; P=0.033), internal cIMT (0.03 mm [0.01, 0.05]; P<0.001), and pulse wave velocity carotid‐femoral (0.38 m/sec [0.14, 0.61]; P=0.001), and those with type 2 diabetes mellitus had greater positive change in common cIMT (0.05 mm [0.04, 0.07]; P<0.001), bulb cIMT (0.06 mm [0.04, 0.09]; P<0.001), internal cIMT (0.04 mm [0.02, 0.07]; P<0.001), augmentation index (4.67% [2.20, 7.13]; P<0.001), and pulse wave velocity carotid‐femoral (0.74 m/sec [0.46, 1.02]; P<0.001). Higher baseline systolic blood pressure was associated with greater positive change in common cIMT (0.007 mm [0.003, 0.011]; P<0.001), bulb cIMT (0.009 mm [0.002, 0.016]; P=0.01), internal cIMT (0.008 mm [0.003, 0.013]; P=0.001), and pulse wave velocity carotid‐femoral (0.066 m/sec [0.002, 0.130]; P=0.042).ConclusionsThese longitudinal data support the hypothesis that the presence of obesity, type 2 diabetes mellitus, and elevated baseline systolic blood pressure in early life accelerates the progression of risk factors key in the development of early vascular aging.

Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis

BackgroundCarotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression.MethodsWe conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes.ResultsData were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m2 [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) − 0.059 mm [95% CI − 0.099, − 0.020) followed by the calcium channel blockers (WMD − 0.055 mm [95% CI − 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD − 0.033 mm [95% CI − 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently.ConclusionPhosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.

Changes in Cardiovascular Health Following Exercise in Older Men and Women at Risk for Dementia

PURPOSE: To investigate the effects of a 24-week multiple-modality exercise intervention with additional mind-motor training on cardiovascular health and fitness. The secondary objective was to investigate whether the intervention had gender-specific effects on the study outcomes. METHODS: Community-dwelling older adults (n = 127, age = 67.5 [7.3] yr, 71% women) were randomized to a 45-min multiple-modality exercise intervention with additional 15 minutes of either mind-motor training (M4 group) or an active control intervention (15 minutes of balance, range of motion and breathing exercises, [M2 group]). Assessment occurred at: baseline, 24 weeks (intervention endpoint), and 52 weeks (after a 28-week no-contact follow-up). The study outcomes were: predicted maximal oxygen consumption (pVO2max), automated office blood pressure (BP), carotid atrial compliance (cAC), intima-media thickness (cIMT), as well as body weight. Mixed between-within ANOVA was used to examine: i) main effects of time (baseline vs 24 weeks), intervention group (M4 vs M2) and gender (men vs women); ii) interactions of time x intervention group, and time x gender. RESULTS: Results at 24 weeks: both M4 and M2 demonstrated improvements in pVO2max (p<.001), with no interaction effects for group or gender (all p>.05). For BP measures, both groups showed reduction in systolic (p<.001) and diastolic (p=.001) BP, with no interaction effect for intervention group; however, women showed greater reduction in diastolic BP compared to men (p=.02). No significant changes were observed in cIMT, cAC, or body weight. Results at 52 weeks: improvements in pVO2max were retained (p<.001), however, the M4 group showed higher pVO2max when compared to M2 (p=.005), with no interaction effects for gender. Significant reduction in systolic BP (p<.001) was observed for both M4 and M2, with no interaction effects for group or gender. For diastolic BP, M4 showed significant reduction compared to M2 (p=.04); women also demonstrated greater reduction compared to men (p=.02). There was no significant change in cIMT, cAC or body weight. CONCLUSION: Our results suggest that women may be more likely to benefit from group-based, multiple-modality exercise programs in measures of cardiovascular health.

Effect of statin on arginine metabolites in treated HIV-infection

Background and aimsAsymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide and an independent risk factor for cardiovascular disease. We examined the effect of statin on ADMA in HIV + patients on stable ART, and whether such an effect contributes to the favorable changes on carotid intima media thickness. MethodsThis is a secondary analysis of SATURN-HIV, in which HIV + adults on stable ART with HIV-1 RNA< 1000 copies/mL and LDL-cholesterol <130 mg/dL were randomized to 10 mg daily rosuvastatin or placebo. Arginine metabolites, ADMA, and markers of inflammation were assessed at baseline and 48 weeks. Carotid intima media thickness (c-IMT) was measured at baseline, 48 and 96 weeks. Spearman correlations, and linear mixed-effect models were used to study relationships among variables. ResultsOverall, 79% were male, 68% African Americans, with a median age of 46 years. In the statin arm, no change in ADMA levels was observed at 48 weeks (0.70%), whereas a trend towards an increase in ADMA levels (23.78%) was observed in the placebo group (p = 0.06). Elevated baseline ADMA (highest tertile) was associated with a 0.04 mm increase in c-IMT (p = 0.03) after adjusting for statin and study duration. No interaction was seen between baseline ADMA and statin randomization on change in c-IMT (p = 0.21). ConclusionsIn HIV + subjects on ART, rosuvastatin suppressed the increase over time in ADMA levels. Elevated baseline levels of ADMA were associated with increases in c-IMT, regardless of statin assignment. The favorable effect of rosuvastatin on c-IMT appears to be independent of the arginine pathway.

Radial artery intima-media thickness regresses after secondary prevention interventions in patients' post-acute coronary syndrome and is associated with cardiac and kidney biomarkers.

BackgroundRadial artery intima-media thickness (rIMT) measured by ultra-high-resolution ultrasound is associated with increased cardiovascular risk and predicts outcomes. We performed non-invasive high-resolution ultrasound of the radial artery to investigate vascular changes in subjects presenting with acute coronary syndrome (ACS) and who had undergone percutaneous coronary intervention (PCI).PurposeIn the present work, we aimed to follow rIMT change over time post-acute coronary syndrome as a tool to monitor potential response to intensified medical therapy.MethodsWe examined 256 subjects who underwent PCI due to ACS and healthy controls (n= 39) and we measured a number of biomarkers, which are known to be associated with cardiovascular disease. Images of radial artery were acquired bilaterally in the longitudinal view using a 50 MHz transducer (Vevo 2100 VisualSonics, Inc, Toronto, Ontario, Canada). Carotid IMT (cIMT) and rIMT were measured at <1 month after index PCI followed by a repeated measurement of rIMT at 4 months from the ACS in a sub-set (n=117).ResultsrIMT measured within 1 month post ACS was significantly higher than rIMT after 4 months from ACS, (p < 0.0001), mean ± SD (rIMT right 0.35 ± 0.08; rIMT left 0.37 ± 0.08) vs. (rIMT right 0.29 ± 0.08; rIMT left 0.31 ± 0.09) respectively. There was no statistically significant change in cIMT. In healthy controls there were no changes in rIMT or cIMT overtime. High levels of CX3CL1 and myeloperoxidase measured within one month post ACS are associated with increase of rIMT, r=0.38 (p< 0.0001) and r=0.41 (p< 0.0001) respectively.ConclusionsrIMT seem to decrease systemically after ACS and is accompanied with corresponding biomarker change. The cause and clinical implications of the observed decrement in rIMT after ACS need further studies.

Serum Ferritin Relates to Carotid Intima-Media Thickness in Offspring of Fathers With Higher Serum Ferritin Levels

Body iron status has been linked to atherosclerosis in adults. The purposes of our study were to determine (1) the association between circulating ferritin levels and carotid intima-media thickness (cIMT) in a cohort of apparently healthy children and (2) the association between cIMT and parental ferritin levels. Circulating ferritin levels (microparticle enzyme immunoassay), metabolic parameters, and cIMT (ultrasonography) were analyzed cross-sectionally in a cohort of 692 healthy white children with a mean age of 8 ± 2 years (52% girls and 48% boys). In consecutive 123 children from the cross-sectional sample, the same serum assessments were also performed at baseline in their parents, and the cIMT was repeated after 3 years of follow-up in the children at a mean age of 11 ± 2 years (53% girls and 47% boys). Weak but significant positive associations were evident between children's circulating ferritin levels and cIMT (r=0.123; P=0.001) and with the change in cIMT 3 years later a tendency was also observed (r=0.185; P=0.048). In multiple regression analyses, circulating ferritin levels contributed independently to cIMT variance (β=0.090; P=0.026; R(2)=10%) and cIMT change variance (β=0.216; P=0.019; R(2)= 3.4%) after controlling for body mass index, high-sensitivity C-reactive protein, age, sex, and low-density lipoprotein-cholesterol levels. This association was, however, remarkably significant (β=0.509; P=0.001; R(2)= 20.4%) in children whose fathers had ferritin levels above the median value (122.5 ng/mL).The latter association remained significant after correction for multiple testing. Maternal's ferritin levels showed no interaction in this association. These results suggest a paternal-specific effect on cIMT partially reflected by father's ferritin levels.

Abstract 17913: Inhibition of CETP by Dalcetrapib Results in a Modest Increase in Cholesterol Efflux Capacity Associated With an Increase in Large HDL Particles, but Does Not Impact Carotid Intima-Media Thickness in a dal-PLAQUE-2 Substudy

Inhibition of cholesteryl ester transfer protein (CETP) is an approach aiming at raising HDL-cholesterol levels and reducing cardiovascular risk. The dal-PLAQUE-2 phase III study recruited 988 subjects with stable coronary artery disease. Its primary objective was to evaluate the effect of dalcetrapib on the progression of carotid atherosclerotic disease measured by intima-media thickness after one year of therapy. As dalcetrapib showed a neutral effect on cardiovascular risk in the dal-OUTCOMES study, our objective was to evaluate its effect on cIMT and markers of HDL mass, lipoprotein subclass distribution and HDL function. All subjects from dal-PLAQUE-2 who had provided serum samples at baseline and one year were included in our substudy of 193 subjects on placebo and 186 subjects on dalcetrapib. Comparisons between groups at one year were made by ANCOVA after adjustment for baseline levels. No significant differences between groups for all variables considered were observed at baseline. Dalcetrapib reduced CETP activity as measured by a fluorescent method by 30% after 1 year (p&lt;0.001), which resulted in increases in HDL-cholesterol and apoA-I levels by 32% and 11%, respectively (both p&lt;0.001). Dalcetrapib markedly increased the concentration of large HDL particles measured by NMR profiling (+59%, p&lt;0.001), at the expense of small HDL particles (-9.5%, p&lt;0.001). Cholesterol efflux capacity of serum was measured from J774 macrophages under basal conditions and after cAMP stimulation. Dalcetrapib increased basal and stimulated efflux by 7.1% and 5.5% (both p&lt;0.001), but was without effect on the ABCA1-dependent component (p=0.26). Despite these effects, dalcetrapib had no impact on mean and maximal cIMT (p=0.98 and p=0.85). While the change in cIMT was inversely correlated with basal cholesterol efflux in the placebo group (Spearman r=-0.163, p&lt;0.05), such a relationship was not found in the dalcetrapib group. Moreover, the change in total HDL particles concentration was inversely correlated with change in cIMT (r=0.181, p&lt;0.05) in the placebo arm only. In conclusion, dalcetrapib raised HDL-C and larger HDL, but this had minimal effects on cholesterol efflux capacity of patients’ serum and had a neutral effect on carotid artery plaque burden.

Beneficial effect of high dose statins on the vascular wall in patients with repaired aortic coarctation?

BackgroundCarotid intima–media thickness (CIMT) is a marker for atherosclerosis. Adult post-coarctectomy patients (CoA) demonstrate an increased cardiovascular risk and increased CIMT compared to controls. This study evaluates the effect of high dose statins on the change in CIMT and cardiovascular risk. MethodsWe designed a multicenter, prospective, randomized, open label trial with blinded endpoint (PROBE design) to evaluate the effect of three year treatment with atorvastatin 80mg on CIMT and cardiovascular risk. Primary endpoint was CIMT measured by B mode ultrasonography. Secondary endpoints were mortality and morbidity due to cardiovascular disease and serum lipids. Results155 patients (36.3±11.8years, 96 (62%) male) were randomized (atorvastatin=80, no treatment=75). There was no significant effect of atorvastatin on the change in CIMT (treatment effect −0.005, 95% CI, −0.039–0.029; P=0.76). A significant effect on serum cholesterol and LDL levels was found (− 0.71, 95% CI, − 1.16 to − 0.26; P = 0.002 vs − 0.66, 95% CI − 1.06 to − 0.26; P = 0.001). There was no difference in secondary outcome measures. Baseline CIMT was higher in hypertensive compared to normotensive CoA. (0.69±0.16mm vs 0.61±0.98mm; P=0.002). Hypertension (ß=0.043, P=0.031) was the strongest determinant CIMT. ConclusionThree year treatment with atorvastatin does not lead to a reduction of CIMT and secondary outcome measures, despite a decrease in total cholesterol and LDL levels. Hypertensive CoA demonstrate the highest CIMT and the largest CIMT progression. Blood pressure control should be the main focus in CoA to decrease cardiovascular risk.

Do subclinical vascular abnormalities precede impaired physical ability and ADL disability?

Cardiovascular disease is an important cause of disability in activities of daily living (ADL) through its effect on physical functioning. However, it is unclear whether subclinical vascular abnormalities and rate of change in subclinical vascular abnormalities is also associated with an impaired physical ability and with ADL disability. In a longitudinal study, 490 middle-aged and older persons were included. Physical ability was measured using the Short Physical Performance Battery and ADL disability using a questionnaire on self-reported basic and instrumental ADL. Subclinical vascular abnormalities were measured by pulse wave velocity (PWV) and carotid intima media thickness (CIMT, in men only). Longitudinal associations between baseline markers of subclinical vascular abnormalities, their rate of change, and change in physical ability or ADL disability were assessed using generalized estimation equation models. After adjustment for confounders, higher baseline PWV, change in PWV, baseline CIMT (in men) and change in CIMT (in men) were associated with a higher rate of change in physical ability (regression coefficients 0.035, 95% CI [0.018; 0.052]; 0.047, 95% CI [0.024; 0.069]; 0.214, 95% CI [0.070; 0.358] and 0.148, 95% CI [0.019; 0.277], respectively). No relations were found for change in ADL disability. In subjects with incident cardiovascular disease, higher change in PWV was associated with a higher rate of change in ADL disability (regression coefficient 0.054, 95% CI [0.001; 0.106]). The present study showed that subclinical vascular abnormalities and rate of change were associated with higher rate of change in physical ability. The association between (change in) subclinical vascular abnormalities and ADL disability tended to be stronger in persons with incident and prevalent cardiovascular disease. These data may suggest that ADL decline is more a direct effect of experienced clinically manifest vascular events rather than the effect of progression of subclinical vascular abnormalities.

Effects of fenofibric acid on carotid intima-media thickness in patients with mixed dyslipidemia on atorvastatin therapy: randomized, placebo-controlled study (FIRST).

To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol, The Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) trial evaluated the effects of fenofibric acid (FA) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin. This multicenter, double-blind, placebo-controlled study was performed in patients with mixed dyslipidemia (fasting triglycerides, ≥150 mg/dL; high-density lipoprotein cholesterol, ≤45 [men] or 55 mg/dL [women]; low-density lipoprotein cholesterol, ≤100 mg/dL once and averaging ≤105 mg/dL) and a history of coronary heart disease or risk equivalent. Patients on background atorvastatin (continued on starting dose or titrated to 40 mg, if needed) were randomized to FA 135 mg or placebo. The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT, measured by ultrasound. In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy, rate of change in posterior-wall cIMT was similar with FA plus atorvastatin (-0.006 mm/y) versus atorvastatin monotherapy (0.000 mm/y; P=0.22). FA plus atorvastatin was favored (P<0.05) in 5 of 24 prespecified subgroups: age ≥60 years, history of coronary artery disease, cIMT >0.795 mm, triglycerides 170 to 235 mg/dL, and statin use at entry. Adverse events were consistent with the known safety profiles of both drugs; however, FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy (6.5% versus 0.9%). Compared with atorvastatin monotherapy, FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia.

Effects of resistance training on central blood pressure in obese young men

Central blood pressure is a predictor of the risk of cardiovascular disease (CVD), and the effects of resistance training (RT) on central blood pressure are largely unknown. This study explored the effects of high-intensity RT on central blood pressure, indices of arterial stiffness and wave reflection and inflammatory/atherogenic markers in overweight or obese, sedentary young men. Thirty-six participants were randomized to RT (12 weeks of training, 3/wk, n=28) or control groups (C, 12 weeks of no training, n=8) and assessed for changes in central and brachial blood pressures, augmentation index (AIx), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), body composition, lipids and inflammatory/atherogenic markers. High-intensity RT resulted in decreased central and brachial systolic/diastolic blood pressures (all P0.03), despite not altering AIx (P=0.34) or cfPWV (P=0.43). The vascular endothelial growth factor increased (P=0.03) after RT, without any change in cIMT, C-reactive protein, oxidized LDL (oxLDL) or other inflammatory markers (all P0.1). Changes in the central systolic blood pressure (cSBP) were positively correlated with changes in oxLDL (r=0.42, P=0.03) and soluble E-selectin (r=0.41, P=0.04). In overweight/obese young men, high-intensity RT decreases cSBP, independently of weight loss and changes in arterial stiffness. The cardioprotective effects of RT may be related to effects on central blood pressure.

Reversal of Early Atherosclerosis in Metabolic Syndrome by Yoga – A Randomized Controlled Trial

Metabolic syndrome (MetS) is a strong risk factor for Coronary Heart Disease (CHD) and type II Diabetes mellitus (DM). The aim of the present study was to determine whether yoga can regress early atherosclerosis in patients with MetS, as measured by carotid intima thickness (cIMT). 100 adult patients of MetS were randomized to yoga and control group and were followed for 1 year. 81% patients completed the study. At the end of 1 year, the yoga group showed a significant regression of cIMT (0.842 ± 0.176 to 0.808 ± 0.204, p<0.001) whereas there was no significant change in cIMT in the control group (0.831 ± 0.171 to 0.834 ± 0.131, p=NS). In addition the yoga group also showed greater reduction in Body Mass Index (BMI), Waist Circumference (WC), LDL cholesterol and Systolic Blood Pressure (SBP). On the basis of this randomized study, we conclude that practice of yoga can regress early atherosclerosis in MetS and has also beneficial effects on several metabolic parameters. The mechanisms of the improvement are not evident from the present study andneed further investigations.

Are Monocytes the Canary in the Coal Mine for HIV-Related Atherosclerosis?

In the era of well-controlled human immunodeficiency virus (HIV) infections with combination antiretroviral therapy (cART), serious non-AIDS events take center stage for people living with HIV infection. This has resulted in a greater focus on research to understand the pathogenesis of these conditions, to enable identification of those at most risk, and to investigate targeted interventions in order to successfully prevent them. Cardiovascular disease (CVD), which is one such non-AIDS event, is an increasing cause of morbidity and mortality in HIV-infected people, with a reported 2-fold heightened risk compared with the general community [1]. This increased risk is likely to result from interplays between the traditional cardiac risk factors, the effects of cART medications, and the pro-inflammatory actions of HIV. In this edition of the Journal of Infectious Diseases, Kelesidis et al [2 ]t ake us another step forward toward understanding the pathogenesis of CVD in HIV infection. In a prospective study of the progression of subclinical atherosclerosis, as measured by carotid intima media thickness (cIMT), the authors showed that baseline levels of lipopolysaccharide (LPS) and soluble CD14 (sCD14) predicted greater progression of cIMT in HIV-infected adults but not in the comparable HIV-uninfected group. This was despite the fact that neither HIV infection nor cART was associated with change in cIMT. Although immune activation and in