Baseline Intima-media Thickness Research Articles

Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Intima-Media Thickness: Systematic Review and Meta-Analysis.

Beyond glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been proposed to reduce the risk of cardiovascular events. The aim of the present systematic review and meta-analysis is to demonstrate the effects of GLP-1 RA and SGLT2is on intima-media thickness (IMT). PubMed, EMBASE, Web of Science, SCOPUS, and Google Scholar databases were searched from inception to September 9, 2023. All interventional and observational studies that provided data on the effects of GLP-1 RAs or SGLT2is on IMT were included. Critical appraisal was performed using the Joanna Briggs Institute checklists. IMT changes (preintervention and postintervention) were pooled and meta-analyzed using a random-effects model. Subgroup analyses were based on type of medication (GLP-1 RA: liraglutide and exenatide; SGLT2i: empagliflozin, ipragliflozin, tofogliflozin, and dapagliflozin), randomized clinical trials (RCTs), and diabetic patients. The literature search yielded 708 related articles after duplicates were removed. Eighteen studies examined the effects of GLP-1 RA, and eleven examined the effects of SGLT2i. GLP-1 RA and SGLT2i significantly decreased IMT (MD = -0.123, 95% CI (-0.170, -0.076), P < 0.0001, I2 = 98% and MD = -0.048, 95% CI (-0.092, -0.004), P = 0.031, I2 = 95%, respectively). Metaregression showed that IMT change correlated with baseline IMT, whereas it did not correlate with gender, duration of diabetes, and duration of treatment. Treatment with GLP-1 RA and SGLT2i can lower IMT in diabetic patients, and GLP-1 RA may be more effective than SGLT2i.

O.2.3-11 Light standing work and high intensity occupational physical activities predict baseline and 8-year progression of carotid atherosclerosis among women

Abstract Purpose Recent reviews link higher levels of occupational physical activity (OPA) to cardiovascular disease (CVD). However, the evidence for women is inconsistent and studies of activity-limiting symptomatic CVD are prone to healthy worker selection effect. To address these limitations, this study investigated OPA effects on asymptomatic carotid artery intima-media thickness (IMT), a proxy for atherosclerosis, among women. Methods Participants include 905 women from the population-based Kuopio Ischemic Heart Disease Risk Factor Study with baseline (1998-2001) data on self-reported OPA and sonographic measurement of IMT. Linear mixed models with adjustment for 15 potential confounders estimated and compared mean baseline IMT and 8-year IMT progression for five levels of self-reported OPA. Analyses stratified by cardiovascular health and retirement status were planned because strong interactions between pre-existing CVD and OPA intensity have previously been reported. Results Light standing work, moderately heavy active work, and heavy or very heavy physical work were all consistently associated with greater baseline IMT and 8-year IMT progression than light sitting work, being hazardous for cardiovascular health. The greatest baseline IMT was observed for heavy or very heavy physical work (1.21 mm), and the greatest 8-year IMT progression for light standing work and moderately heavy active work (both 0.13 mm), 30% above sitting work (0.10 mm). Stratified analyses showed that these differences were driven by much stronger OPA effects among women with baseline carotid artery stenosis. Retired women experienced slower IMT progression than those still working at baseline. Conclusions Light standing work and higher levels of OPA intensity predict higher baseline IMT and 8-year IMT progression, especially among women with baseline stenosis. This study suggests that inconsistent findings regarding the effects of OPA on cardiovascular diseaes and mortality outcomes may be due to healthy worker selection and exposure misclassification biases including the failure to distinguish between standing and sitting work postures in many cohort studies. Funding Source This project is funded by the Danish taxpayers, via the Danish Work Environment Research Foundation, grant number 20195100247.

Occupational physical activity predicts baseline and 8-year progression of carotid atherosclerosis among women.

Recent reviews link higher levels of occupational physical activity (OPA) to cardiovascular disease (CVD). However, the evidence for women is inconsistent and studies of activity-limiting symptomatic CVD are prone to healthy worker survivor effect. To address these limitations, this study investigated OPA effects on asymptomatic carotid artery intima-media thickness (IMT) among women. Participants include 905 women from the population-based Kuopio Ischemic Heart Disease Risk Factor Study with baseline (1998-2001) data on self-reported OPA and sonographic measurement of IMT. Linear mixed models with adjustment for 15 potential confounders estimated and compared mean baseline IMT and 8-year IMT progression for five levels of self-reported OPA. Analyses stratified by cardiovascular health and retirement status were planned because strong interactions between preexisting CVD and OPA intensity have previously been reported. Light standing work, moderately heavy active work, and heavy or very heavy physical work were all consistently associated with greater baseline IMT and 8-year IMT progression than light sitting work. The greatest baseline IMT was observed for heavy or very heavy physical work (1.21 mm), and the greatest 8-year IMT progression for light standing work and moderately heavy active work (both 0.13 mm), 30% above sitting work (0.10 mm). Stratified analyses showed that these differences were driven by much stronger OPA effects among women with baseline carotid artery stenosis. Retired women experienced slower IMT progression than those working at baseline. Higher levels of OPA predict higher baseline IMT and 8-year IMT progression, especially among women with baseline stenosis.

OA40 Predicting cardiovascular disease risk in children and adolescents with juvenile-onset systemic lupus erythematosus using the APPLE (Atherosclerosis Prevention in Paediatric Lupus Erythematosus) clinical trial cohort

Abstract Background/Aims The risk of developing cardiovascular disease (CVD) through atherosclerosis in juvenile-onset systemic lupus erythematosus (JSLE) patients is significantly increased. This study aimed to stratify and characterise JSLE patients at elevated CVD risk using patient/disease-related factors and metabolomic data from patients recruited to the APPLE (Atherosclerosis Prevention in Paediatric Lupus Erythematosus) clinical trial, designed to assess atherosclerosis development. Methods Unsupervised hierarchical clustering was performed to stratify patients by arterial intima-media thickness (IMT) measurements at baseline (N = 151) and carotid (c)IMT progression over 36 months (placebo arm only, N = 60). Baseline metabolomic profiles (∼250 serum metabolites) were compared between clusters using conventional statistics, univariate logistic regression, sparse Partial Least-Squares Discriminant Analysis (sPLS-DA) and random forest classifier. An independent cohort (UCL-JSLE cohort, N = 89) with matching metabolomics, immunophenotyping and proteomics, was used to validate the discovered CVD risk-related signatures from the APPLE cohort. Results Baseline IMT stratification identified 3 clusters with high, intermediate, and low baseline IMT measurements and progression trajectories over 36 months, each having distinct racial/BMI/household education/income characteristics. Analysis of cIMT progression over 36 months identified 2 patient groups with high and low IMT progression. Unique metabolomic profiles differentiated high and low cIMT progression groups, with a good discriminatory ability (0.81 AUC in ROC analysis) using the top 6 metabolites (total cholesterol esters, total cholesterol, phospholipids in small LDL particles, total cholesterol in small LDL particles, free cholesterol in medium LDL particles, and total lipids in small LDL particles) selected from the analysis. cIMT progression over 36 months in the placebo group correlated positively with baseline disease activity (SLEDAI), damage score (SLICC), white blood cell count, serum complement C3, blood pressure (both systolic and diastolic) and BMI. Metabolomics signatures discovered from the APPLE cohort were applied to stratify JSLE patients in the validation cohort (UCL-JSLE), where 3 groups were identified with distinct metabolomics profiles indicating JSLE patients with high risk (N = 20), intermediate risk (N = 43) and low risk (N = 26) CVD-risk. Significant differences were observed in the frequency of classical monocytes (p = 0.015) and nonclassical monocytes (p = 0.005) when comparing the high and low CVD risk groups in the UCL-JSLE cohort. Conclusion Complex analysis of IMT patterns and progression in the APPLE trial cohort identified novel key determinants that could guide further research for CVD-risk stratification in JSLE. Disclosure J. Peng: None. G.A. Robinson: None. S.P. Ardoin: None. L.E. Schanberg: None. O. Carra: None. E. Jury: None. C. Ciurtin: None.

The Effect of Conventional and Distal Radial Access Techniques on Radial Artery Structure and Vascular Functions

Introduction: To compare radial artery (RA) diameters, intima-media thickness (IMT), and vascular functions before and after conventional and distal RA cannulation. It has been proposed that distal transradial (DTRA) cannulation can reduce RA complications. However, there has been no comparative study examining the effects of DTR and conventional transradial (CTRA) intervention on RA structure and function. Patients and Methods: Radial artery diameter, IMT, flow-mediated vasodilation (FMD) response were measured using conventional and Doppler RA ultrasonography before, and one day and one month after the procedure in patients who underwent CTRA or DTRA. Results: While baseline and first-day IMT values were similar between the groups, first-month IMT values in the CTRA group were found to be significantly increased compared to those in the DTRA group (CTRA= 0.39 ± 0.10 mm, DTRA= 0.32 ± 0.07 mm, p= 0.016). While proximal RA occlusion developed in three patients who underwent CTRA, it did not develop in any of the patients undergoing DTRA (p= 0.072). Conclusion: In patients who underwent CTRA, RA IMT increased significantly in the first month after the procedure, compared to patients who underwent DTRA. Proximal RAO was not observed in any of the patients who underwent DTRA.

Intima Media Thickness and Cognitive Function Among Adults: Meta-Analysis of Observational and Longitudinal Studies.

BackgroundCarotid structural changes measured by intima media thickness (IMT) have been related to cognitive complaints during aging. Therefore, the aims of this meta‐analysis were (1) to elucidate the relationship between vascular status, measured as IMT, and cognitive domains distinguishing between global cognition, executive functions, memory and attention; and (2) to explore whether demographic (ie, age and sex), clinical (ie, body mass index and IMT baseline values), and procedure characteristics influence this association.Methods and ResultsWe performed a systematic review of MEDLINE (via PubMed), Scopus, and Web of Science databases from their inception to June 2021. Studies meeting the following inclusion criteria were included: (1) the participants were adults; (2) the exposure was carotid IMT; (3) the outcome was cognitive function, including global cognition, executive function, memory, and attention measured using standardized tests; and (4) the study design was cross‐sectional or longitudinal including unadjusted and adjusted analyses. A total of 19 cross‐sectional and 15 longitudinal studies were included and demographic (age and sex), clinical (body mass index and baseline IMT values), and procedure characteristics were analyzed as potential mediator or moderators of the association.ConclusionsOur data support negative associations between IMT and cognitive function in cross‐sectional studies. The association between IMT and cognition lost significance in longitudinal studies and when controlling for covariates in cross‐sectional studies. Finally, the strength of these associations seems not to be modified by age, sex, body mass index, and baseline IMT values. This systematic review and meta‐analysis adds to the evidence supporting the use of IMT as a measure for identifying patients at risk of cognitive decline.

Carotid Artery Plaque Progression: Proposal of a New Predictive Score and Role of Carotid Intima-Media Thickness

Background: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. Methods: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6–34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30–49%; 2: in the range 50–69%; 3: in the range 70–99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. Results: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). Conclusion: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

Carotid artery plaque progression: Proposal of a new predictive score and role of carotid intima-media thickness

Longitudinal changes in carotid intima-media thickness (IMT) and plaque are considered markers of atherosclerosis progression and predictors of cardio and cerebrovascular events. However, a clinical predictive risk score of plaque progression is currently lacking. We aimed to investigate if a new proposed risk score (HAD2S score) composed by the sum of single vascular risk factors (Hypertension, Age ≥ 75 years, Diabetes, Dyslipidemia and Smoking) and baseline IMT were predictive of plaque progression.

Endothelial function in patients with critical and non-critical limb ischemia undergoing endovascular treatment.

Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease. CLI patients, compared to non-CLI, achieve worse treatment outcomes and generate higher costs. The aim of the study was to compare endothelial function and clinical outcomes in CLI and non-CLI patients after percutaneous transluminal angioplasty (PTA). In this prospective, follow-up study, 30 CLI patients and 40 non-CLI patients underwent PTA. Endothelial function was assessed based on flow mediated dilatation (FMD), reactive-hyperemia index (RHI), while the ankle-brachial index, toe-brachial index and the Rutherford scale were used for peripheral artery disease progression evaluation. The results were assessed before PTA, as well as 1, 3, 6 and 12 months after the procedure. There were no differences at the baseline regarding to endothelial function between both groups. Neither FMD nor RHI changed after PTA in any of the groups, although there was a difference in median RHI value between CLI and non-CLI patients regarding the 1st and 6th month of the follow-up (RHI6-RHI1 = 0.08 in CLI and -0.15 in non-CLI; P = 0.01). The larger baseline intima-media thickness (IMT) in the CLI group allowed to predict a greater number of re-intervention (P = 0.01) and major adverse event rates (P = 0.03). CLI patients presented larger decrease in the Rutherford scale compared to non-CLI (P <0.001). Baseline IMT was predictive for re-interventions and major adverse event rates. Although neither of groups exhibited significant changes in endothelial function, we proved differences between them regarding to changes in RHI.

The Gly82Ser polymorphism in the receptor for advanced glycation end products is associated with increased risk for coronary events in the general population

Abstract Background/Introduction Activation of the receptor for advanced glycation end products (RAGE) by AGEs and various immune mediators has pro-inflammatory and pro-atherogenic effects. RAGE also exists in a soluble form, sRAGE, that acts as a decoy receptor for RAGE ligands. Low plasma sRAGE has previously been found to be associated with a higher risk for major adverse coronary events (MACE) in the population. Purpose The purpose of our study was to examine the causality of the association, by exploring whether genetic variants that influence sRAGE are associated with atherosclerosis progression and incident MACE and mortality in the population. Methods We performed a genome-wide association study (GWAS) in 4192 individuals from a randomly selected subgroup of a population-based cohort. Subsequently, we explored the associations between the identified single nucleotide polymorphims (SNPs) associated with plasma sRAGE levels, baseline intima media thickness (IMT) and IMT progression in the common carotid artery during a median follow-up of 16.5 years. Further, we analyzed the prospective relationships between the sRAGE-associated SNPs, incident MACE and mortality in the entire population-based cohort of 29245 individuals. The median follow-up time from baseline was 21.2 years for MACE and 21.6 years for total mortality (time to event or end of follow-up). Results We found the minor alleles of two single nucleotide polymorphisms (SNPs), rs2070600 and rs204993, to be independently associated with lower plasma sRAGE. While rs204993 is a silent intronic mutation, rs2070600 is known to cause a Gly82Ser polymorphism in the ligand binding domain, enhancing RAGE propensity for activation. In Cox regression analyses, we found an association between the minor T (vs. C) allele of rs2070600 and increased risk for first-time MACE [HR 1.12 (1.02–1.23); P=0.023]. The association was independent of traditional cardiovascular risk factors, blood pressure-lowering medication and lipid-lowering medication at baseline. rs204993 was not associated with MACE. Neither SNP was associated with carotid IMT at baseline or with IMT progression. We did not identify any relationships with total mortality. Conclusions We demonstrate for the first time an independent link between a genetic RAGE determinant and the risk for MACE in the population. Despite both identified SNPs being associated with lower sRAGE levels, only the functional rs2070600 mutation was associated with MACE, suggesting that the link is probably due to the enhancement of RAGE function rather than to the sRAGE lowering effect. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This study was supported by grants from the Swedish Research Council and the Swedish Heart and Lung foundation.

Endothelial function indicators in patients with critical limb ischemia compared to patients with limb claudication – one-year follow-up period after endovascular revascularisation

Abstract Background Critical limb ischemia (CLI) is the most advanced stage of peripheral arterial disease. Limb revascularization is considered the first line of treatment. Purpose The aim of the study was to compare endothelial function and clinical outcomes in CLI and non-CLI patients during a 12-month follow-up period after endovascular treatment (PTA). Methods The study was conducted as a prospective, single-centre, follow-up evaluation. The authors recruited 30 CLI and 40 non-CLI patients. The following markers of endothelial dysfunction were evaluated: flow-mediated dilatation (FMD), reactive-hyperaemia index (RHI), arterial pulse-waveform analysis (aPWA) indices and clinical markers such as ankle-brachial index, toe-brachial index and Rutherford scale. Results Better clinical improvement may be observed in patients with CLI - the mean Rutherford grade significantly decreased in the CLI group (p&amp;lt;0.001). These patients also have better endothelial response to revascularization – CLI patients continue to have improved RHI up to 6 months after PTA, where in non-CLI patients, improvement was only noted during the first month. The mean FMD value did not change significantly during the follow-up in either of the groups. When comparing selected intervals, the FMD values in the CLI and non-CLI groups improved during the first month of observation and then decreased between the 1st and 6th month of follow-up. Finally, in CLI patients, baseline intima-media thickness predicts the number of reinterventions and major adverse events. Conclusions Patients with CLI differ significantly from patients with claudication based on clinical response and endothelial changes after revascularization. Figure 1. A) Kaplan-Meier survival curves according to CLI and non-CLI status for all study endpoints. B) Kaplan-Meier survival curves according to CLI and non-CLI status for reinterventions. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Collegium Medicum of Jagiellonian University - internal grant

Association of Viral Persistence and Atherosclerosis in Adults With Treated HIV Infection

Persons living with HIV (PLWH) have increased risk for cardiovascular disease, and inflammation is thought to contribute to this excess risk. Production of HIV during otherwise effective antiretroviral therapy (ART) has been associated with inflammation. To determine whether higher levels of viral persistence are associated with atherosclerosis as assessed by changes in carotid artery intima-media thickness (IMT) over time. In this cohort study, intima-media thickness, a validated marker of atherosclerosis, was assessed over time in a cohort of treated PLWH with viral suppression. Cell-associated HIV DNA and RNA and change in IMT, adjusted for demographics, cardiovascular risk factors, and HIV-related factors, were examined, as well as which factors were associated with viral persistence. One hundred fifty-two PLWH with undetectable viral loads for at least 6 months before study enrollment were recruited from HIV clinics affiliated with 2 hospitals in San Francisco, California, from January 1, 2003, to December 31, 2012. Data were analyzed from February 7, 2018, to May 12, 2020. Cell-associated HIV RNA and DNA were measured using enriched CD4+ T cells from cryopreserved peripheral blood mononuclear cells. Carotid IMT was measured at baseline and the last visit, with a mean (SD) follow-up of 4.2 (2.7) years, using high-resolution B mode ultrasonography. The main study outcomes were baseline IMT, annual IMT progression, and incident plaque, defined as a focal region of carotid IMT of greater than 1.5 mm. The analysis included 152 PLWH (140 [92.1%] male; median age, 48.5 [interquartile range {IQR}, 43.3-53.7] years). Older age, smoking, medications for hypertension, higher low-density lipoprotein levels, and higher interleukin 6 levels were associated with higher baseline mean IMT, whereas cell-associated HIV DNA (estimate, -0.07% [95% CI, -6.1% to 6.4%]; P = .98), and HIV RNA levels (estimate, -0.8% [95% CI, -5.9% to 4.4%]; P = .75) were not. Levels of HIV RNA (0.017 [95% CI, 0.000-0.034] mm/y; P = .047) and HIV DNA (0.022 [95% CI, 0.001-0.044] mm/y; P = .042) were significantly associated with annual carotid artery IMT progression in unadjusted models only. Both HIV RNA (incidence risk ratio [IRR], 3.05 [95% CI, 1.49-6.27] per IQR; P = .002) and HIV DNA (IRR, 3.15 [95% CI, 1.51-6.57] per IQR; P = .002) were significantly associated with incident plaque, which remained significant after adjusting for demographics, cardiovascular risk factors, and HIV-related factors (IRR for HIV RNA, 4.05 [95% CI, 1.44-11.36] per IQR [P = .008]; IRR for HIV DNA, 3.35 [95% CI, 1.22-9.19] per IQR [P = .02]). Higher C-reactive protein levels were associated with higher cell-associated HIV RNA (estimate, 20.7% [95% CI, 0.9%-44.4%] per doubling; P = .04), whereas higher soluble CD14 levels were associated with HIV DNA (estimate, 18.6% [95% CI, 3.5%-35.8%] per 10% increase; P = .01). Higher soluble CD163 levels were associated with a higher HIV RNA:DNA ratio (difference, 63.8% [95% CI, 3.5%-159.4%]; P = .04). These findings suggest that measurements of viral persistence in treated HIV disease are independently associated with incident carotid plaque development. The size and transcriptional activity of the HIV reservoir may be important contributors to HIV-associated atherosclerosis.

Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study.

BackgroundCarotid atherosclerosis is associated with subclinical ischemic cerebrovascular disease, but its role in hemorrhage‐prone small vessel disease—represented by cerebral microbleed (CMB)—is unclear, although vascular risk factors underlie both conditions. We hypothesized that persons with carotid atherosclerosis would have higher risk of CMB, particularly in deep regions.Methods and ResultsWe studied 1243 participants in the Framingham Offspring Study (aged 56.9±8.8 years; 53% women) with carotid ultrasound available on 2 occasions (1995–1998 and 2005–2008) prior to brain magnetic resonance imaging. Using multivariable logistic regression, we related baseline carotid stenosis, baseline intima–media thickness, and site‐specific carotid intima–media thickness progression (at internal and common carotid locations) to the prevalence and location (lobar or deep plus mixed) of CMB. In addition, we assessed effect modification by lipid levels and use of statin and antithrombotic medications. Carotid stenosis ≥25% (a marker of cerebrovascular atherosclerosis) was associated with presence of CMB overall (Odds Ratio 2.20, 95% CI 1.10–4.40) and at deep and mixed locations (odds ratio 3.60, 95% CI 1.23–10.5). Baseline carotid intima–media thickness was not associated with CMB. Progression of common carotid artery intima–media thickness among persons on hypertension treatment was associated with lower risk of deep and mixed CMB (odds ratio per SD 0.41, 95% CI 0.18–0.96).ConclusionsCumulative vascular risk factor exposure may increase the risk of CMB, especially in deep regions. The apparent paradoxical association of carotid intima–media thickness progression with lower risk of CMB may reflect benefits of intensive vascular risk factor treatment among persons with higher cardiovascular risk and deserves further investigation. If replicated, the results may have potential implications for assessment of preventive and therapeutic interventions for subclinical cerebral hemorrhage.

Coronary Artery Calcification Is Related to Inflammation in Rheumatoid Arthritis: A Long-Term Follow-Up Study.

Objective. A long-term follow-up of patients with rheumatoid arthritis (RA) to evaluate factors related to coronary artery calcification (CAC). Methods. All 22 eligible patients (4 males/18 females, mean age 65 years, and RA-duration 30–36 years) from the original (baseline; n = 39) study of atherosclerosis were included. Inflammation, cardiovascular risk factors, and biomarkers were measured at baseline. At follow-up 13 years later, CAC was assessed by computed tomography (CT) and the grade of inflammation was measured. Multivariate analysis of differences between patients with low (0–10) and high CAC (>10) was done by orthogonal projection to latent structures (OPLS). Results. Ten patients had CAC 0–10 and 12 had >10 (range 18–1700). Patients with high CAC had significantly higher ESR (24.3 versus 9.9 mm/h) and swollen joint count (2 versus 0). The OPLS models discriminated between patients having high or low CAC. With only baseline variables, the sensitivity was 73% and the specificity 82%. The model that also included inflammatory variables from follow-up had a sensitivity of 89% and a specificity of 85%. Exclusion of baseline intima media thickness and plaque from the latter model modestly reduced the accuracy (sensitivity 80% and specificity 83%). Conclusions. CAC is related to inflammation in patients with RA.

Abstract P056: Emerging Lifestyle Markers Predict Regression of Carotid Intima-Media Thickness Scores

Introduction: CVD remains the number one cause of mortality in the western world. Carotid intima-media thickness (IMT) is a safe &amp; reliable predictor of future CVD risk. This study assesses which lifestyle factors best predict a change in IMT over time. Hypothesis: We assessed the null hypothesis that all lifestyle changes are effective. Methods: A prospective cross-sectional analysis of 289 men &amp; women undergoing health &amp; cardiovascular risk screening every 1-2 years at an outpatient wellness center in Florida. This study reflects the first visit at the clinic, &amp; a second visit that occurred on average 2.8 years later. These subjects ranged in age from 23-65 (mean = 48.2). In addition to testing, subjects received nutrition, fitness, &amp; health coaching. Measurements were made of fitness using VO2max stress testing, diet intake using a 3-day dietary intake survey. Laboratory &amp; anthropometric measures were obtained fasting. Mean IMT scores used high resolution B-mode ultrasonography of the common carotid arteries. Each subject had ≥10 images collected from the far wall of both distal 1 cm of the common carotid arteries at end diastole. The carotid intimal thickness was measured as a continuous variable, using both multivariate &amp; bivariate linear regression, adjusting for age &amp; gender; as our site IMT precision was = 3%, we selected a 4% change as significant. Results: The average decrease in IMT score in this cohort was -0.018 mm over 2.8 years, a 2.04% reduction. The bivariate analyses showing a significant association with a ≥4% reduction in IMT in 62 of 288 subjects; they were a decrease in: Body mass index (BMI) (p=0.047), body fat (p=0.025), total cholesterol (TC) (p=0.031), LDL cholesterol (p=0.028), TC/HDL (0.002), or an increase in dietary intake of: magnesium (p=0.0001), fiber (p=0.017), vitamin D (p=0.016), vitamin K (p=0.001), potassium (p=0.001), &amp; calcium (p=0.024). In a multivariate analysis, starting a statin medication (p=0.0007), a decrease in BMI (p=0.042), baseline IMT, male gender, diastolic BP decrease, &amp; years of follow up were predictive of 4% IMT decline. Prior use of a statin medication was not significant. Conclusions: In conclusion, this study shows that a reduction in IMT score over 2.8 years is associated with a decrease in: BMI, body fat, TC, LDL, TC/HDL ratio, &amp; diastolic BP; or, an increase in intake of: magnesium, fiber, vitamins K &amp; D, potassium, &amp; calcium; or, starting a statin medication.

Significant Association between Serum Monokine Induced by Gamma Interferon and Carotid Intima Media Thickness.

The immune system may play an important role in the pathogenesis of cardiovascular disease. T cell-driven inflammation in human hypertension and atherosclerosis has recently been revealed. In the present study, we evaluated the association between serum levels of the C-X-C chemokine receptor type 3 chemokines and the carotid intima media thickness (IMT) in humans. One hundred sixty-four consecutive patients undergoing baseline and 2-year follow-up carotid IMT (110 men, 62.4±10.0 years) were enrolled. The maximum carotid IMT (max-IMT) and the mean carotid IMT (mean-IMT) were measured at baseline and after 24 months. Clinical and laboratory variables, including serum levels of the monokine induced by gamma interferon (MIG) and interferon gamma-induced protein 10 (IP-10), were analyzed at the time of initial enrollment. The baseline max- and mean-IMT were 0.992±0.235 and 0.793±0.191 mm, respectively. The serum levels of MIG and IP-10 significantly correlated with the carotid IMT. However, there was no significant correlation between the serum levels of MIG or IP-10 and IMT changes. A multivariate regression analysis revealed the serum MIG to be independently associated with the carotid IMT (max-IMT: β=0.194, p=0.010; mean-IMT: β=0.184, p=0.016) when controlled for age, sex, diabetes mellitus history, smoking history, body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and aspirin and statin medication. Circulating MIG levels are independently associated with the carotid IMT, after adjusting for confounding factors and medications. These findings indicate the potential clinical implication of MIG with respect to early atherosclerosis in humans.

The CD4:CD8 ratio is associated with IMT progression in HIV-infected patients on antiretroviral treatment.

IntroductionInversion of the CD4:CD8 ratio (<1) has been identified as a hallmark of immunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and intima-media thickness (IMT) progression in treated HIV-infected patients as a marker of early atherosclerosis.Materials and MethodsA longitudinal study during three years was conducted in 120 HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4:CD8 ratio, cardiovascular risk factor and antiretroviral (ARV) treatment and progression of subclinical atherosclerosis assessed using carotid IMT at baseline and after three years.ResultsFinally, 96 patients completed the study. Seventy-six (79.1%) patients were male, aged 44±10 years, 39 (40.6%) were on treatment with Protease inhibitors, 49 (51.04%) with non-nucleoside reverse transcriptase inhibitors (NNRTI), 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc and 2 (2.08%) only with nucleoside reverse transcriptase inhibitors (NRTI). The mean of ARV exposition was 6.9±5.9 years. Twenty six (27 %) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) hypertensive, 4 (4.16%) type 2 diabetes, 23 (23.9%) with dyslipidemia and 31 (32.3%) were infected with C hepatitis virus. Baseline IMT was significantly associated with age (rho=0.497; p<0.001), basal glucemia (rho=0.323; p=0.001), triglycerides (rho=0.232; p=0.023), Framingham score (rho=0.324; p=0.001), CD4:CD8 ratio (rho=−0.176; p=0.05) and dyslipidemia (0.72±0.16 mm vs 0.63±0.11 mm; p=0.029). In multivariable analysis where cardiovascular risk factor and ARV were included, IMT progression was inversely associated with CD4:CD8 ratio (OR=0.283; CI 95% 0.099–0.809; p=0.019) and treatment with NNRTI (OR=0.283; CI 95% 0.099–0.809; p=0.019).ConclusionsThe inversion of CD4:CD8 ratio in treated HIV-infected patients is independently associated with IMT progression, a marker of age-associated disease. Therefore, it might be clinically useful as predictor of cardiovascular events. Surprisingly, there was a positive correlation between receiving NNRTI and progression of IMT.

Abstract P343: Racial Differences In The Progression Of Carotid Intima-media Thickness In Middle-aged Men-the Era Jump Study

Introduction: Intima-media thickness (IMT) of the carotid artery is an independent predictor of future cardiovascular events. A few studies have examined the racial differences in IMT progression. We aimed to study the racial differences in IMT progression over 4-6 years among middle-aged Caucasian, African and Japanese American men. Methods: Population-based samples of 393 men (Caucasian=199, African Americans=39, Japanese Americans=155; aged 40-49 years at baseline) free of clinical cardiovascular disease and not on lipid lowering, anti-diabetic or anti-hypertension medications at baseline were examined for IMT at two time points (baseline (2004-07) and follow-up (2008-13). Measurements of IMT were standardized and performed by University of Pittsburgh. Progression of IMT was defined as (follow-up IMT [[Unable to Display Character: &amp;#8211;]] baseline IMT)/duration of follow-up (years). Multivariable linear regression analyses were used and models were adjusted for traditional cardiovascular risk factors (Table). Results: In the unadjusted analyses, IMT progression was significantly associated with age and race, and marginally significantly associated with systolic blood pressure and diabetes. The progression rate of IMT (mean ± SE) was the highest in Japanese American (16 ± 1.2μm/year) compared with Caucasian (10.3 ± 1.0μm/year; P &lt; 0.01) and African American men (3 ± 2μm/year; P &lt; 0.01). In the adjusted analyses, age and race remained significantly associated with IMT progression. Japanese Americans progressed significantly faster than Caucasians. African Americans progressed slower than Caucasians but this difference was not significant. Diabetes was marginally significantly associated with IMT progression. Conclusions: Age and race are the major determinants of IMT progression in these middle-aged men. Racial differences in progression are prominent with fastest progression in Japanese Americans.

Effect of cilostazol on carotid intima-media thickness in type 2 diabetic patients without cardiovascular event

We investigated the efficacy of cilostazol treatment for 2 years on the attenuation of carotid intima-media thickness (IMT) progression in type 2 diabetic patients without cardiovascular disease history, as compared with other antiplatelet agents. We recruited a total of 230 type 2 diabetic patients who had undergone IMT measurement twice within 1.5-2.5 years (mean 2.06 ± 0.32 years) interval. Among these participants, we classified them into three groups according to antiplatelet agent administration at baseline: Group I (n = 66), antiplatelet naïve; Group II (n = 75), other antiplatelet agent administration; and Group III (n = 50), cilostazol administration. We then analyzed the changes in clinical characteristics from baseline to 2 years. The changes in annual mean IMT at 2 years were 0.019 ± 0.045 mm/year, -0.001 ± 0.058 mm/year, and -0.019 ± 0.043 mm/year for Group I, II, and III, respectively (P < 0.001). Mean change in total cholesterol, low-density lipoprotein-cholesterol, and triglyceride compared with baseline decreased the most in Group III even after adjustment for statin use. We also observed that the odds ratio of carotid IMT progression at 2 years was the lowest in patients who were treated with cilostazol even after adjustment for change of metabolic parameters. When we categorized patients according to baseline carotid IMT tertile, the efficacy of cilostazol against carotid IMT progression was significant only when baseline IMT was over 0.662 mm (mean 0.801). Two-year treatment with cilostazol strongly inhibited carotid IMT progression compared to other antiplatelet agents in type 2 diabetic patients. This beneficial effect of cilostazol was significant when baseline IMT was thicker than 0.662 mm (mean 0.801 mm).

GW24-e1860 Association between Lipoprotein-Associated Phospholipase A2 Activity and the Progression of Subclinical Atherosclerosis: Results from the CMCS-Beijing Study

ObjectivesLipoprotein-associated phospholipase A2 (Lp-PLA2) has been shown to be associated with an increased risk of clinical cardiovascular events. We aimed to investigate whether Lp-PLA2 is also associated with the progression...