cIMT Progression Research Articles

Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia.

Children with heterozygous familial hypercholesterolaemia (HeFH) show greater carotid intima-media thickness (cIMT). Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody, substantially reduced low-density lipoprotein cholesterol (LDL-C) and modestly reduced lipoprotein(a) in children with HeFH. We investigated evolocumab's effect on cIMT progression. HAUSER-RCT was a randomised, placebo-controlled trial. 157 paediatric patients with FH (age: 10-17 years) and LDL-C >130mg/dL despite statin therapy received monthly evolocumab 420mg or placebo for 24 weeks. Patients who continued into an open-label extension (HAUSER-OLE; n=150) received 80 weeks of monthly evolocumab plus statins. cIMT was measured by B-mode ultrasound scanning of right and left common carotid artery at baseline; week 24 of RCT [day 1 OLE]; and weeks 24, 48, and 80 of OLE. Descriptive analysis of cIMT was a prespecified HAUSER secondary endpoint, and inferential tests reported here were post-hoc. 151 patients had evaluable cIMT summary scores at ≥1 visit. From RCT baseline to week 24, mean cIMT increased by 0.006mm (SD=0.05) with placebo (n=37) and decreased by 0.003mm (SD=0.05) with evolocumab (n=76). From RCT baseline to OLE week 80, mean cIMT summary score decreased by 0.019mm (SD=0.04) and 0.012mm (SD=0.05), respectively, in patients who initially received placebo (n=34, P=0.007) versus receiving evolocumab throughout (n=59, P=0.067). Across patients who received evolocumab in OLE, mean cIMT significantly decreased by 0.011mm (SD=0.05) from OLE day 1 to week 80 (n=94, P=0.034). In children with HeFH, evolocumab plus statin treatment up to 104 weeks led to regression in carotid arterial wall thickening.

Interaction between subclinical carotid atherosclerosis endotype and biological sex: a study from IMPROVE cohort

Abstract Background Carotid-intima media thickness (c-IMT) is a measure of subclinical carotid atherosclerosis and a predictor of future atherosclerotic cardiovascular events (ASCVD). We have recently generated, using an artificial intelligence approach, four endotypes (E) of subclinical atherosclerosis, i.e. subgroups of individuals predisposed to both c-IMT progression and ASCVD. Each E is defined by a set of demographic, clinical, and molecular data and characterize individuals with a low (E1), intermendiate (E2), high (E3) and very high (E4) cardiovascular risk profile. We observed an unbalanced distribution of males and females across the 4 endotypes, with a higher prevalence of female in the low risk E1. Purpose To estimate the interaction between biological sex and the 4 endotypes on measures of c-IMT progression and ASCVD risk. Methods We performed our study on 3121 individuals from the IMPROVE cohort, which includes participants with at least three ASCVD risk factors. We estimated the interaction between biological sex and the endotypes generated in the IMPROVE on (1) c-IMT and carotid plaque measurements after 30 months of follow-up (c-IMTfastest-progr, Area of plaquesbulb-progr) by linear regression (β, SE) and (2) with the 3-year ASCVD risk by Cox [hazard ratio (HR), 95% confidence interval (CI)] regression model. Crude estimates were adjusted by batch effect for biomarker measurement, geographical region and/or baseline ultrasonographic measures. Adjusted models further included ASCVD common risk factors. Results As shown in Figure 1, we did not observe any significant interaction between endotypes and biological sex on 30-month carotid ultrasound progression measures, and 3-year-ASCVD risk. In both the crude and adjusted models on c-IMTfastest-progr, Area of plaquesbulb-progr, and 3-year ASCVD, the p-value for interaction ranged from 0.18 to 0.98. While E4 was associated with the strongest cardiovascular risk profile in both males and females. Conclusions Our results indicate that the association between endotypes and progression of subclinical atherosclerosis and ASCVD risk mirrors a specific risk profile not entirely explained by differences in biological sex.

No accelerated progression of subclinical atherosclerosis with integrase strand transfer inhibitors compared to non-nucleoside reverse transcriptase inhibitors.

The role of integrase strand transfer inhibitors (INSTI) in the cardiovascular risk of people with HIV is controversial. To assess the association of INSTI to subclinical atherosclerosis progression measured with the carotid intima-media thickness (cIMT). Prospective study in virologically suppressed people with HIV receiving INSTI- or NNRTI-based regimens. cIMT was measured at baseline, 48 and 96 weeks. cIMT progression was analysed both as a continuous and categorical variable, defined as cIMT increase ≥ 10% and/or new carotid plaque. Adjustments through Cox proportional hazard regression and linear mixed models, and propensity score matching were conducted. 190 participants were recruited and 173 completed the 96 week follow-up. 107 (56.3%) were receiving an INSTI-containing, 128 (67.4%) a NNRTI-containing and 45 (23.7%) a NNRTI plus an INSTI-containing regimen. The overall median (IQR) 2-year change of cIMT was 0.029 (-0.041 to 0.124) mm; 87 (45.8%) participants experienced a cIMT increase ≥ 10%, of whom 54 (28.4%) developed a new carotid plaque. Adjusted Cox regression showed no differences between INSTI and NNRTI groups in the categorical 2-year progression of cIMT, both including or excluding participants receiving INSTI + NNRTI. Similar results were observed for the continuous cIMT increase through adjusted linear mixed models. Propensity score matching showed no significant differences in the 2 year cIMT change between treatment groups [0.049 mm (-0.031-0.103) in the INSTI group versus 0.047 mm (-0.023-0.115) in the NNRTI group; P = 0.647]. cIMT progression was associated with traditional cardiovascular risk factors. INSTI-based regimens are not associated with increased progression of subclinical atherosclerosis when compared to NNRTI.

The Effect of Statins on Carotid Intima-Media Thickness and C-Reactive Protein in Type 2 Diabetes Mellitus: A Meta-Analysis.

The effect of statins on CIMT progression and C-reactive protein (CRP) in T2DM patients is widely reported. However, some studies demonstrated no effect of statins on CIMT and CRP in T2DM patients, while others reported otherwise. Thus, the current study comprehensively and quantitatively analyzes data from previous studies to evaluate the overall effect of statins on CIMT and CRP in T2DM to rule out any inconsistencies observed in previous clinical evidence. Therefore, the aim of this meta-oanalysis was to evaluate the effect of statins on CIMT progression and CRP in T2DM. A comprehensive search for studies was performed using PubMed, Scopus, Web of Sciences, and the Cochrane Library, for publications from their inception to 16 July 2024. The meta-analysis was conducted using Jamovi (version 4.2.8) and Review Manager (version 5.4), with the overall effect sizes reported as standardized mean differences (SMD) and 95% confidence intervals (CI). Evidence from eleven studies (fifteen statin dosages) that met the inclusion criteria with a sample size of 983 T2DM patients on statin treatment was analyzed. The overall effect size from the random effect model meta-analysis showed a reduction in the CIMT status amongst T2DM patients post-statin treatment compared to at baseline [SMD = -0.47, 95%CI (-0.76, -0.18), p = 0.001]. Furthermore, there was a reduction in the level of CRP in T2DM patients post-treatment [SMD = -1.80, 95% CI (-2.76, -0.84), p < 0.001]. Evidence gathered in this study suggests that statin therapy effectively reduces CIMT and CRP levels among patients living with T2DM. Interestingly, this evidence suggests that 20 mg of atorvastatin is more effective in reducing CIMT and CRP. Therefore, we recommend conducting further trials with larger sample sizes and proper methodology for T2DM.

Distinct gut microbiota signatures associated with progression of atherosclerosis in people living with HIV.

The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with HIV (PWH) remains unknown. 96-week, prospective, longitudinal study in virologically-suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline, 48-week and 96-week visits. cIMT progression was defined as an increase >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal-RNA (V3-V4 variable regions) were carried out following the Illumina protocol. Sequencing was performed with MiSeq platform. 191, 190 and 167 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. 87 (43%) participants showed atherosclerosis progression, and 54 (26.7%) presented new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups defined by cIMT progression. Beta-diversity determined through principal coordinate analysis distances showed that the groups exhibited distinct microbial profiles (PERMANOVA p-value = 0.03). Longitudinal analysis with ANCOM-BC2 adjusted for traditional cardiovascular risk factors, MSM and nadir CD4 count revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus_2, while non-progression was consistently associated with Prevotella_7. Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.

Accelerometer-based sedentary time, light physical activity, and moderate-to-vigorous physical activity from childhood with arterial stiffness and carotid IMT progression: A 13-year longitudinal study of 1339 children.

We examined the longitudinal associations of sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous PA (MVPA) from childhood with carotid-femoral pulse wave velocity (cfPWV), a measure of arterial stiffness and carotid intima-media thickness (cIMT). We studied 1339 children, aged 11 years from Avon Longitudinal Study of Parents and Children, UK, followed up for 13 years. Accelerometer-based ST, LPA, and MVPA were assessed at ages 11, 15, and 24 years clinic visits. cfPWV and cIMT were measured with Vicorder and ultrasound, respectively, at ages 17 and 24 years. Among 1339 [56.4% female] participants, mean ST increased from ages 11 through 24 years, while mean LPA and MVPA decreased. Persistently high ST tertile from childhood was associated with increased cfPWV progression, effect estimate 0.047 m/s; [(95% CI 0.005 to 0.090); p = 0.030], but not cIMT progression. Persistently high LPA tertile category was associated with decreased cfPWV progression in males -0.022 m/s; [(-0.028 to -0.017); p < 0.001] and females -0.027 m/s; [(-0.044 to -0.010); p < 0.001]. Cumulative LPA exposure decreased the odds of progressively worsening cfPWV [Odds ratio 0.994 (0.994-0.995); p < 0.0001] and cIMT. Persistent exposure to ≥60 min/day of MVPA was paradoxically associated with increased cfPWV progression in males 0.053 m/s; [(0.030 to 0.077); p < 0.001] and females 0.012 m/s; [(0.002 to 0.022); p = 0.016]. Persistent exposure to ≥60 min/day of MVPA was inversely associated with cIMT progression in females -0.017 mm; [(-0.026 to -0.009); p < 0.001]. LPA >3 h/day from childhood may attenuate progressively worsening vascular damage associated with increased ST in youth.

Cumulative accelerometer-based light physical activity from childhood through young adulthood with arterial stiffness and carotid intima-media thickness progression: a 13-year longitudinal study

Abstract Background Arterial stiffness is a novel risk factor for elevated blood pressure and hypertension in adolescents and young adults. Arterial stiffness and carotid intima-media thickness (cIMT) progression have been associated with cardiovascular events in adult. It remains unclear whether engaging in light physical activity may attenuate arterial stiffness and cIMT progression. Purpose To investigate the longitudinal association of cumulative light physical activity from childhood through young adulthood with arterial stiffness and cIMT progression. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1399 children aged 11 years who had at least two follow-up time-points accelerometer-measured sedentary time over 13 years follow-up, and complete cardiac structural measures at age 17 years clinic visit were included. Light physical activity was assessed with ActiGraph accelerometer worn for 4-7 days at the 11-, 15-, and 24-year clinic visits and sex-categorized in tertiles as low (reference), moderate, and high. Carotid femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and cIMT were assessed with Vicorder and ultrasound, respectively at ages 17 and 24 years. Multivariable adjusted associations were examined using generalized linear mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sedentary time, and moderate to vigorous physical activity. Results Among 1339 participants (mean [SD] age, 11.75 [0.24] years; [54.6% females]) males spent on average 369, 289, and 150 mins/day engaging in light physical activity at ages 11, 15, and 24 years, respectively. Females spent 366, 270, and 154 mins/day engaging in light physical activity at ages 11, 15, and 24 years respectively. cfPWV was significantly higher among males than females at ages 17 and 24 years. cIMT was higher in males than females at 17 years but not at age 24 years. In a fully adjusted model, the highest tertile of light physical activity from ages 11 – 24 years was cumulatively associated with progressively decreased changes in cfPWV (effect estimate -0.024m/s [CI -0.028 – -0.017] p&amp;lt;0.001) from ages 17 – 24 years in the total cohort, males (-0.022m/s [CI -0.044 – -0.010] p&amp;lt;0.001), and females (-0.027m/s [CI -0.044 – -0.010] p=0.002). There was no statistically significant association between cumulative light physical activity and cIMT in the total cohort, males, and females. Conclusion Persistent highest tertile of light physical activity from childhood through young adulthood was associated with decreased arterial stiffness progression.

Cumulative accelerometer-based sedentary time from childhood through young adulthood with increased arterial stiffness and carotid intima-media thickness in youth: a 13-year longitudinal study

Abstract Background Arterial stiffness and carotid intima-media thickness (cIMT) progression have been associated with cardiovascular morbidity and mortality in adulthood. Arterial stiffness is a strong risk factor for elevated blood pressure and hypertension, and insulin resistance in adolescents and young adults. It remains unclear whether cumulative sedentary time independently worsens arterial health in the paediatric population. Purpose To investigate the longitudinal association of cumulative sedentary time from childhood through young adulthood with arterial stiffness and cIMT changes during post-pubertal growth. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1399 children aged 11 years who had at least two follow-up time-points accelerometer-measured sedentary time over 13 years follow-up, and complete cardiac structural measures at age 17 years clinic visit were included. Sedentary time was assessed with ActiGraph accelerometer worn for 4-7 days at the 11-, 15-, and 24-year clinic visits and sex-categorized in tertiles as low (reference), moderate, and high. Carotid femoral pulse wave velocity (cfPWV), a measure of arterial stiffness, and cIMT were assessed with Vicorder and ultrasound, respectively at ages 17 and 24 years. Multivariable adjusted associations were examined using generalized linear mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, light physical activity, and moderate to vigorous physical activity, Results Among 1339 participants (mean [SD] age, 11.75 [0.24] years; [54.6% females]) males spent on average 358, 461, and 536 minutes/day sedentary at ages 11, 15, and 24 years, respectively. Females spent 369, 484, and 525 minutes/day sedentary at ages 11, 15, and 24 years respectively. cfPWV was significantly higher among males than females at ages 17 and 24 years. cIMT was higher in males than females at 17 years but not at age 24 years. In a fully adjusted model, the highest tertile of sedentary time from ages 11 – 24 years was cumulatively associated with progressively increased changes in cfPWV (effect estimate 0.009m/s [CI 0.006 – 0.012] p&amp;lt;0.001) from ages 17 – 24 years in the total cohort and females (0.047m/s [CI 0.005 – 0.090] p=0.030), but not in males. There was no statistically significant association between cumulative sedentary time and changes in cIMT in the total cohort, males, and females. Conclusion Cumulative increase in sedentary time during growth from childhood through young adulthood was independently associated with progressively worsening arterial stiffness in youth.

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 &gt;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 ( &gt; 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.

Markers of terminally differentiated T-cells as predictors of vascular health in renal transplant recipients and healthy adults

Meta-analyses confirm a link between persistent human cytomegalovirus (HCMV) infections and cardiovascular disease, but the mechanisms are unclear. We assess whether proportions of T-cell populations are reliable predictors of subclinical atherosclerosis and/or reflect the burden of HCMV in healthy adults and renal transplant recipients (RTR). Samples were collected from healthy adults and RTR at baseline (T0) and after 32 (24–40) months (T1). Left carotid intima media thickness (cIMT) and proportions of T-cells expressing CD57, LIR-1 or the TEMRA phenotype increased in healthy adults and RTR. The T-cell populations correlated with levels of HCMV-reactive antibodies. Proportions of CD57+, LIR-1+ and TEMRA CD8+ T-cells correlated with left and right cIMT in healthy adults. Proportions of CD57+ and LIR-1+ CD8+ T-cells at T0 predicted left cIMT at T1 among healthy adults, but these associations disappeared after adjustment for covariates. We link LIR-1+ and CD57+CD8+ T-cells with the progression of cIMT in healthy adults.

Arterial stiffness but not carotid intima-media thickness progression precedes premature structural and functional cardiac damage in youth: A 7-year temporal and mediation longitudinal study

Background and aimsThe longitudinal relations of cardiac indices with the aorta and carotid vessel and the time sequence for early cardiac disease development are uncharacterized in youth. We examined the temporal longitudinal associations of carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) with left ventricular hypertrophy (LVH) and diastolic dysfunction (LVDD). MethodsFrom the Avon Longitudinal Study of Parents and Children, UK birth cohort, 1856 adolescents (1011 females) at a mean (SD) age 17.7 (0.3) years were followed up for 7 years. Vicorder-measured cfPWV and ultrasound-measured cIMT were grouped in tertiles as low (reference), moderate, and high. Echocardiography measured cardiac abnormalities are left ventricular mass indexed for height2.7 (LVMI2.7) ≥51 g/m2.7 as LVH; relative wall thickness ≥44 as hiRWT; LVD function E/A <1.5 as LVD dysfunction (LVDD); and LV filling pressure E/e’ ≥8 as hiLVFP. Data were analysed with generalized logit mixed-effect models, cross-lagged path, and mediation structural equation models adjusting for cardiometabolic and lifestyle factors. ResultsOver follow-up, LVH prevalence increased from 3.6% to 7.2% and LVDD from 11.1 to 16.3%. High cfPWV progression was associated with worsening LVH [Odds ratio 1.23 (1.13–1.35); p < 0.001] in the total cohort, males, overweight/obese, and normotensive. High cfPWV progression was associated with worsening hiLVFP in the total cohort, females, and normal weight. Likewise, high cIMT progression was associated with worsening LVH [1.27 (1.26–1.27); p < 0.0001] in the total cohort, overweight/obese and elevated BP/hypertensive. Neither cfPWV nor cIMT progression was associated with worsening hiRWT in the total cohort. In cross-lagged models, higher baseline cfPWV was associated with future LVMI2.7 (β = 0.06, SE, 5.14, p = 0.035), RWT, LVDF, and LVFP. However, baseline LVMI2.7, RWT, LVDF, and LVFP were not associated with follow-up cfPWV. Baseline cIMT was not associated with follow-up cardiac indices and vice versa. Cumulative increased systolic blood pressure (34.3% mediation) and insulin resistance (15.1% mediation) mediated the direct associations of cumulative cfPWV with cumulative LVMI2.7. ConclusionsArterial stiffness progression temporally preceded worsening structural and functional cardiac damage in youth with increased systolic blood pressure and insulin resistance partly mediating the relationships. Future interventions aimed at attenuating premature cardiac damage in adolescents and young adults may consider a simultaneous treatment of both arterial stiffness, elevated blood pressure and insulin resistance.

Relationship between the cholesterol and triglyceride content of lipoprotein subclasses and carotid intima-media thickness: A cross-sectional population-based study

BackgroundThe association between lipoprotein subclasses and carotid intima-media thickness (cIMT) progression has yet to be fully evaluated. We assessed which lipoprotein subclasses were associated with maximum cIMT levels in the general population. MethodsIn this study, cholesterol and triglyceride content of 20 lipoprotein subclasses were analyzed using gel permeation high-performance liquid chromatography (GP-HPLC) in 864 Japanese women and men (mean age 57 y, free of chronic liver or kidney diseases and off lipid-lowering, hormone replacement, or adrenocorticosteroid medications). Univariate and multivariate regression analyses and univariate and partial correlation analyses were performed to examine the relationships between lipoprotein subclasses and maximum cIMT levels. ResultsAfter adjusting for age, sex, systolic blood pressure, smoking, diabetes, and anti-hypertensive agents, elevated low-density lipoprotein (LDL)-2 and −3 cholesterol (particle diameter 25.5 nm and 23.0 nm, respectively; medium and small LDL) were associated with higher maximum cIMT levels in both women and men (all p for trend < 0.05). These associations were significant even after participants taking anti-diabetic or anti-hypertensive agents were excluded. No significant associations were found between any triglyceride subclasses and maximum cIMT levels. ConclusionsSmaller LDL particle cholesterol values are the most atherogenic lipoprotein parameter.

A machine learning based approach to identify carotid subclinical atherosclerosis endotypes.

To define endotypes of carotid subclinical atherosclerosis. We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (β, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (β, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.

Carotid intima-media thickness in adults with and without psoriasis - a nested case-control study from baseline data of ELSA-Brasil cohort.

There is a lack of consensus about the association between psoriasis (PSO) and carotid intima-media thickness (cIMT) in literature, since previous studies considered dermatologic clinic patients or general population. This study aimed to compare cIMT levels according to PSO in a sample of 10,530 civil servants form the ELSA-Brasil cohort study and analyze its association with the disease. The PSO cases and disease duration were identified by medical diagnosis self-reported at study enrollment. A paired group was identified by propensity score matching among all the participants without PSO. Mean cIMT values were considered for continuous analysis while cIMT above 75th percentile was considered for categorical analysis. Multivariate conditional regression models were used to analyze association between cIMT and PSO diagnosis, by comparing PSO cases against paired controls and overall sample without disease. A total of n = 162 PSO cases were identified (1.54%) and no difference in cIMT values was observed between participants with PSO and overall sample or control group. PSO was not associated with linear increment of cIMT (vs. overall sample: β = 0.003, p = 0.690; vs. matched controls: β = 0.004, p = 0.633) neither with increased chance of having cIMT above 75th percentile (vs. overall sample: OR = 1.06, p = 0.777; vs. matched controls: OR = 1.19, p = 0.432; conditional regression: OR = 1.31, p = 0.254). There was no relationship between disease duration and cIMT (β = 0.000, p = 0.627). Although no significant relationship between mild cases of psoriasis and cIMT was observed among a wide cohort of civil servants, longitudinal investigation about cIMT progression and severity of disease are still needed.

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.

Cumulative insulin resistance and hyperglycemia with arterial stiffness and carotid IMT progression in 1,779 adolescents: a 9-yr longitudinal cohort study.

In pediatric population with diabetes and obesity, insulin resistance (HOMA-IR) has been associated with worsening vascular outcomes, however, the cumulative role of HOMA-IR, hyperglycemia, and hyperinsulinemia on repeatedly measured vascular outcomes in asymptomatic youth is unknown. We examined the longitudinal associations of fasting glucose, insulin, and HOMA-IR with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT). From the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, UK 1,779, 15-yr-old participants were followed up for 9 yr. Glucose, insulin, and HOMA-IR assessed at 15, 17, and 24 yr and sex-specifically dichotomized as ≥75th percentile, indicating high category and <75th percentile as reference. cfPWV and cIMT were measured at ages 17 and 24 yr. Associations were examined using linear mixed-effect models adjusted for cardiometabolic and lifestyle covariates. Among 1,779 participants [49.9% female], glucose, insulin, and HOMA-IR had a J- or U-shaped increase from ages 15 through 24 yr. The cumulative exposures to hyperinsulinemia effect estimate -0.019 mU/L; [95% CI -0.019 to -0.002; P = 0.033] and high HOMA-IR: -0.021; [-0.039 to -0.004; P = 0.019] from 15 to 24 yr of age were negatively associated with the 7-yr cfPWV progression. Only cumulative hyperinsulinemia and high HOMA-IR from ages 15 to 17 yr but not from ages 17 to 24 yr was associated with decreased cfPWV progression. There were no associations between cumulative hyperglycemia and cfPWV or cIMT progression. Hyperinsulinemia and HOMA-IR were not associated with cIMT progression. In conclusion, late adolescence may be an optimal timing for intervention targeted at sustaining the protective effect of the decline of insulin and insulin resistance on arterial stiffness progression.NEW & NOTEWORTHY Fasting plasma glucose, insulin, and insulin resistance had a J- or U-shaped increase from 15 to 24 yr with the base of the curve at age 17 yr. Cumulative high insulin and high insulin resistance from 15 to 24 yr were negatively associated with arterial stiffness progression from ages 17 to 24 yr. Age 17 yr may be an optimal timing for intervention targeted at sustaining the protective effect of the decline of insulin and insulin resistance on arterial stiffness progression.

Effect of lifestyle interventions on carotid arterial structure – The DR's EXTRA study

No lifestyle-based interventions with medium-term duration on carotid atherosclerotic have been performed so far. We aimed to investigate whether guideline-based dietary and physical activity interventions slow the progression of atherosclerotic changes in the general elderly population.1410 Finnish men and women from a representative population sample were randomly assigned to one of six groups in the four-year intervention study: 1) reference, 2) aerobic training, 3) resistance training, 4) Nordic Diet, 5) aerobic training + Nordic Diet, 6) resistance training + Nordic Diet. The primary outcome was mean common carotid artery intima-media thickness (cIMT). The lumen diameter of the common carotid artery (cLD) was also analyzed.567 men and 565 women aged 57 to 78 years were included. None of the intervention groups significantly slowed cIMT progression compared to the reference group. A subgroup analysis showed that men in the diet group had significantly smaller cIMT progression than in the reference group (−0.078 mm, 95% CI: −0.146 to −0.009, p = 0.02) and no significant increase in cIMT (p = 0.23). No other group showed a slowed cIMT progression.Among guideline-based lifestyle interventions, only diet leads to a significantly smaller progression of cIMT in older men of a representative population sample. No other lifestyle intervention contributed to a slowing of the progression of structural carotid markers. It must be questioned whether the guideline-based recommendations for a lifestyle change that were in place until recently are adequate to decelerate the atherosclerotic process.

Carotid wall echogenicity at baseline associates with accelerated vascular aging in a middle-aged population

Ultrasonic echolucent carotid intima-media (IM) complex and accelerated progression of carotid intima mediathickness (cIMT) have both separately been shown to predict future cardiovascular events. The aim of this studywas to evaluate if the echogenicity of the IM-complex is associated with the 3-year progression of cIMT. B-modeultrasound images captured at baseline and 3-year follow-up in the ‘Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention’ (VIPVIZA) trial were included (n: 3154). The bilateral mean cIMT and IM-echogenicity by greyscale median (GSM) were measured in the common carotid artery. Associations between IM-GSM at baseline and the 3-year cIMT progression were investigated using linear regression models for the whole population and stratified by sex, age and VIPVIZA study group (intervention versus control). In addition, adjusted analyses for confounding factors were performed. Unadjusted analysis showed that decreased IM-GSM at baseline was associated with increased progression of cIMT (p < 0.001). Stratified by age, the association was significant among 40 (p < 0.001) and 60 years old (p < 0.001). The association was statistically significant in both sexes and on comparison of VIPVIZA study subgroups. Adjustments for confounding factors did not alter the estimated relationship between IM-GSM and cIMT progression. Echolucent carotid intima media at baseline associates with increased 3-year cIMT progression among an asymptomatic, middle-aged population. Echogenicity of the intima media may identify individuals at risk for accelerated vascular aging.

Statins in Children, an Update.

Since lipid abnormalities tend to progress from childhood to adulthood, it is necessary to early identify and treat children and adolescents with dyslipidemia. This is important in order to reduce the cardiovascular risk, delay the development of fatty streaks, slow the progression of atherosclerosis and reverse atherosclerotic plaques. Together with therapeutic lifestyle changes, statins are the most common lipid-lowering drugs. By inhibiting the endogenous cholesterol synthesis in the liver, statins increase the catabolism of LDL-C, reduce VLDL-C, IDL-C and TG and modestly increase HDL-C. Regardless of their lipid-lowering effect, statins have also pleiotropic effects. Statins have increasingly been prescribed in children and adolescents and mounting evidence suggests their beneficial role. As with adults, in children, several studies have demonstrated that statin therapy is efficient at lowering lipid levels and reducing CIMT progression and cumulative estimated atherosclerotic burden in children. Statins are generally very well-tolerated in both adults and children and adverse events are quite uncommon. When evaluating the need and the timing for statin treatment, the presence of several factors (secondary causes, familial history, additional risk factors) should also be considered. Before initiating statins, it is imperative for clinical practitioners to consult patients and families and, as with any new medication therapy, to monitor patients taking statins. Despite being safe and effective, many children with lipid disorders are not on statin therapy and are not receiving the full potential benefit of adequate lipid-lowering therapies. It is therefore important that clinicians become familiar with statins.

Cumulative dyslipidemia with arterial stiffness and carotid IMT progression in asymptomatic adolescents: A simulated intervention longitudinal study using temporal inverse allocation model

Background and aimsWe aimed to examine the longitudinal associations of total cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and low-density lipoprotein cholesterol (LDL-C) with carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (cIMT) progression. MethodsWe studied 1779, 15-year-old participants from the Avon Longitudinal Study of Parents and Children, UK birth cohort, followed up for 9 years. Fasting TC, non–HDL-C, HDL-C, triglyceride, and LDL-C were measured at 15, 17, and 24 years and age-categorized as normal, elevated, and dyslipidemia based on National Heart, Lung, and Blood Institute lipid guidelines. cfPWV and cIMT were measured at 17 and 24 years. Associations were examined using linear mixed-effect models. To simulate the treatment of dyslipidemia we conducted temporal inverse allocation model analyses. ResultsAmong 1779 [49.9% female] participants, mean lipid levels and proportions at elevated or dyslipidemia categories increased from ages 15 through 24 years. Persistently elevated TC: effect estimate 0.026 mm; [95% CI 0.004 to 0.049; p = 0.024], elevated non–HDL-C, and elevated LDL-C were cumulatively associated with cIMT progression. Persistent borderline-low HDL-C: −0.027 mm; [-0.050 to −0.005; p = 0.019] and very-low HDL-C −0.035 mm; [-0.057 to −0.013; p = 0.002] levels were associated with cIMT progression. A temporal inverse allocation of elevated and dyslipidemic levels with normal lipid levels at age 17 years attenuated the associations of cumulative elevated TC, non–HDL-C, LDL-C, and low HDL-C with cIMT progression. Cumulative elevated lipids or dyslipidemia were not associated with cfPWV progression. ConclusionsLate adolescence is key to preventing, halting, and reversing dyslipidemic-related preclinical atherosclerosis progression, warranting universal lipid screening in the general pediatric population.