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INTRODUCTION: We investigated the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on cardiovascular structure development in children. METHODS: We followed 1,356 children with the mean age of 6.6 years for 4.5 years in Beijing, China. We assessed the association of MASLD with cardiovascular structure (carotid intima-media thickness and left ventricular mass) outcomes at baseline and follow-up. RESULTS: Over follow-up, 59 children had persistent MASLD, 109 had incident MASLD (progression), and 35 had normalization of liver health. Children with MASLD normalization showed a significantly lower mean development in carotid intima-media thickness (0.161 vs 0.188 mm) and left ventricular mass (4.5 vs 12.4 g) than children with persistent MASLD. DISCUSSION: The control of MASLD was associated with improved cardiovascular structure development. [ABSTRACT FROM AUTHOR]

BACKGROUND: Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow, and stable flow (s-flow) protects against atherosclerosis by incompletely understood mechanisms. METHODS: Our single-cell RNA-sequencing data using the mouse partial carotid ligation model was reanalyzed, which identified Heart-of-glass 1 (HEG1) as an s-flow-induced gene. HEG1 expression was studied by immunostaining, quantitive polymerase chain reaction, hybridization chain reaction, and Western blot in mouse arteries, human aortic endothelial cells (HAECs), and human coronary arteries. A small interfering RNA-mediated knockdown of HEG1 was used to study its function and signaling mechanisms in HAECs under various flow conditions using a cone-and-plate shear device. We generated endothelial-targeted, tamoxifen-inducible HEG1 knockout (HEG1iECKO) mice. To determine the role of HEG1 in atherosclerosis, HEG1iECKO and littermate-control mice were injected with an adeno-associated virus-PCSK9 [proprotein convertase subtilisin/kexin type 9] and fed a Western diet to induce hypercholesterolemia either for 2 weeks with partial carotid ligation or 2 months without the surgery. RESULTS: S-flow induced HEG1 expression at the mRNA and protein levels in vivo and in vitro. S-flow stimulated HEG1 protein translocation to the downstream side of HAECs and release into the media, followed by increased messenger RNA and protein expression. HEG1 knockdown prevented s-flow-induced endothelial responses, including monocyte adhesion, permeability, and migration. Mechanistically, HEG1 knockdown prevented s-flow-induced KLF2/4 (Kruppel-like factor 2/4) expression by regulating its intracellular binding partner KRIT1 (Krev interaction trapped protein 1) and the MEKK3-MEK5-ERK5-MEF2 pathway in HAECs. Compared with littermate controls, HEG1iECKO mice exposed to hypercholesterolemia for 2 weeks and partial carotid ligation developed advanced atherosclerotic plaques, featuring increased necrotic core area, thin-capped fibroatheroma, inflammation, and intraplaque hemorrhage. In a conventional Western diet model for 2 months, HEG1iECKO mice also showed an exacerbated atherosclerosis development in the arterial tree in both sexes and the aortic sinus in males but not in females. Moreover, endothelial HEG1 expression was reduced in human coronary arteries with advanced atherosclerotic plaques. CONCLUSIONS: Our findings indicate that HEG1 is a novel mediator of atheroprotective endothelial responses to flow and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has long been hypothesized that the abnormal immune responses contribute to the essential hypertension (EH) and its subclinical target organ damage (STOD). However, the mechanism is unclear. This study aimed at exploring the potential association with abnormal T-cell responses and EH, STOD, and early atherosclerosis in patients with EH. METHODS: This cross-sectional study included 146 patients with EH and 73 age-matched normotensive individuals. The expressed peripheral TCR (T-cell receptor) β repertoire was analyzed by high through-put sequencing. RESULTS: The TCRβ repertoires of the patients with EH were significantly different, with significantly elevated certain TCR beta variable (TRBV) and joint (TRBJ) gene usages, significantly reduced TCRβ diversity indexes (diversity 50s) and numbers of total TCRβ clonal types, significantly elevated percentages of the biggest TCRβ clones and numbers of clones accounting >0.1% sequences, compared with those in the normotensive controls. Decreased diversity 50s and increased biggest TCRβ clone percentages were independently correlated with carotid intima-media thickness and subclinical carotid atherosclerosis (SCA) in the patients with EH. Moreover, the diversity 50s were further significantly reduced and the biggest TCRβ clone percentages were significantly increased in the patients with EH with SCA (n=89) comparing to the patients with EH/patients without SCA (n=57), and in patients with EH/SCA with carotid plaque (n=22) comparing to patients with EH/SCA/patients without carotid plaque (n=67). Importantly, specific TCRβ clones were identified in different subgroups of the patients with EH. CONCLUSIONS: These results reveal that abnormal T-cell responses may play important roles in the progression of EH and its SCA, especially the formation of carotid plaque. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100054414 [ABSTRACT FROM AUTHOR]

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined M H and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m27 [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long- term cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Target organ damage (TOD) such as left ventricular hypertrophy (LVH), abnormal pulse wave velocity, and elevated carotid intima-media thickness are common among adults with hypertension and are associated with overt cardiovascular events. The risk of TOD among children and adolescents with hypertension confirmed by ambulatory blood pressure monitoring is poorly understood. In this systematic review, we compare the risks of TOD among children and adolescents with ambulatory hypertension to normotensive individuals. Methods: A literature search was conducted to include all relevant English-language publications from January 1974 to March 2021. Studies were included if patients underwent 24-hour ambulatory blood pressure monitoring and ≥1 TOD was reported. Ambulatory hypertension was defined by society guidelines. Primary outcome was the risk of TOD, including LVH, left ventricular mass index, pulse wave velocity, and carotid intima-media thickness among children with ambulatory hypertension compared with those with ambulatory normotension. Meta-regression calculated the effect of body mass index on TOD. Results: Of 12 252 studies, 38 (n=3609 individuals) were included for analysis. Children with ambulatory hypertension had an increased risk of LVH (odds ratio, 4.69 [95% CI, 2.69–8.19]), elevated left ventricular mass index (pooled difference, 5.13 g/m2.7; [95% CI, 3.78–6.49]), elevated pulse wave velocity (pooled difference, 0.39 m/s [95% CI, 0.20–0.58]), and elevated carotid intima-media thickness (pooled difference, 0.04 mm [95% CI, 0.02–0.05]), compared with normotensive children. Meta-regression showed a significant positive effect of body mass index on left ventricular mass index and carotid intima-media thickness. Conclusions: Children with ambulatory hypertension have adverse TOD profiles, which may increase their risk for future cardiovascular disease. This review highlights the importance of optimizing blood pressure control and screening for TOD in children with ambulatory hypertension. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42020189359 [ABSTRACT FROM AUTHOR]

Background: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD).Methods: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression.Results: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data.Conclusions: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness. [ABSTRACT FROM AUTHOR]

Introduction: Atherosclerosis has been shown to impact cognitive impairment, with most of the evidence originating from European, African, or East Asian populations that have employed carotid intima-media thickness (cIMT) as a biomarker for atherosclerosis. Vascular disease is related to dementia/cognitive decline. There is no community-based study from India that has looked at the association of cIMT with cognitive performance. Methods: In this cross-sectional study between December 2014 and 2019, we recruited 7505 persons [(mean age 64.6 (9.2) y) and 50.9% women] from a community-dwelling population in New Delhi. These persons underwent carotid ultrasound to quantify cIMT and a cognitive test battery that tapped into memory, processing speed, and executive function. We also computed the general cognitive factor (g-factor), which was identified as the first unrotated component of the principal component analysis and explained 37.4% of all variances in the cognitive tests. We constructed multivariate linear regression models adjusted for age, sex, education, and cardiovascular risk factors. Additional adjustment was made for depression, anxiety, and psychosocial support in the final model. Results: We found a significant association of higher cIMT with worse performance in general cognition (β=−0. 01(95% CI: −0.01; −0.01); P <0.001), processing speed (β=−0.20; 95% CI: −0.34; −0.07); P =0.003), memory (β=−0.29; 95% CI: −0.53; −0.05); P =0.016), and executive function (β=−0.54; 95% CI: −0.75; −0.33); P =<0.001). There was no statistically significant association of cIMT with Mini-Mental Status Examination score (β=0.02; 95% CI: −0.34; 0.40; 0.89). Conclusion: The cross-sectional study found significant associations of increased cIMT with worse performance in global cognition, information processing, memory, and executive function. [ABSTRACT FROM AUTHOR]

Objective: This study aims to determine quantitatively the mediation effects of multiple cardiovascular risk factors on the associations of childhood body mass index (BMI) and its cumulative burden with adult carotid intima-media thickness (cIMT).Methods: The longitudinal cohort consisted of 1391 adults who had been examined for BMI 4-15 times over 35.0 years on average since childhood and had data on adult cIMT, systolic blood pressure, low-density lipoprotein cholesterol, atherogenic index of plasma, and serum glucose. The area under the curve was used as a measure of cumulative burden of BMI.Results: After adjusting for covariates, the total effects (standardized regression coefficient) of childhood BMI (0.138), adult BMI (0.111), and BMI area under the curve (0.150) on cIMT were all significant (P<0.001) without mediators included in the model. The mediation effects of adult systolic blood pressure, glucose, atherogenic index of plasma and low-density lipoprotein cholesterol were 8.0%, 4.3%, 3.6%, and 0.0%, respectively, in the model with childhood BMI as the predictor, 23.4%, 15.3%, 12.6%, and 7.2%, respectively, with adult BMI as the predictor, and 14.7%, 8.7%, 6.0%, and 2.0%, respectively, with BMI area under the curve as the predictor. The direct effects on cIMT were 0.117 (P<0.001) for childhood BMI, 0.046 (P=0.224) for adult BMI, and 0.103 (P<0.001) for BMI area under the curve after removing the mediation effects.Conclusions: The long-term deleterious impact of adiposity on subclinical changes in vascular structure begins early in life and is accumulated over lifetime. Excess adiposity and higher cIMT are linked partly through other cardiovascular risk factors in later life, especially elevated blood pressure and glucose. [ABSTRACT FROM AUTHOR]

Background: Stable angina pectoris, resulting from coronary artery atherosclerosis, significantly affects quality of life and carries a high risk of cardiovascular events. Despite modern therapies, managing this condition remains challenging. Traditional Chinese medicine (TCM) views it as a syndrome of heart meridian obstruction by phlegm and blood stasis, necessitating improved circulation and phlegm resolution. This study aims to evaluate the efficacy of Jiangzhi Mai'an Granules, a TCM formulation, in treating stable angina pectoris and carotid atherosclerosis, with the goal of integrating TCM with Western medicine to enhance clinical outcomes and patients' quality of life., Methods: A total of 120 patients diagnosed with stable angina pectoris and carotid atherosclerotic plaques of the phlegm and blood stasis types were randomly divided into 2 groups. The control group (n = 60) received standard Western medical treatment, whereas the treated group (n = 60) received JZMA in addition to the standard regimen. The treatment duration in both the groups was 3 months. The outcomes measured included carotid intima-media thickness (CIMT), carotid plaque dimensions, TCM syndrome scores, and serum lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], apolipoprotein B [Apo B], and non-HDL-C) and lipoprotein phospholipase A2 (Lp-PLA2) levels before and after treatment., Results: The treated group achieved a total efficacy rate of 93.3% (56/60), which surpassed the control group rate of 78.3% (47/60). The CIMT, carotid plaque thickness, and area in the treated group were significantly reduced posttreatment compared to baseline (P < .05) and were also lower than those in the control group (P < .05). Serum lipid levels, including TC, TG, LDL-C, ApoB and non-HDL-C were significantly decreased in both groups posttreatment (P < .05), and the treated group showed a further increase in HDL-C levels (P < .05). The treated group exhibited lower serum lipid levels than the control group posttreatment (P < .05). The TCM syndrome scores improved significantly in both groups after treatment (P < .05), with the treated group demonstrating a more pronounced reduction in scores than the control group (P < .05). The incidence of adverse events did not differ significantly between the 2 groups., Conclusions: JZMA combined with standard treatment effectively reduced CIMT, plaque size, and serum lipid levels, thereby enhancing clinical outcomes in patients with stable angina and carotid atherosclerosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aims to explore the risk factors for carotid plaque (CP) and carotid common artery intima-media thickening (CCAIMT) and clarify the relationship between the risk factors with the number of CPs and the side of CCAIMT in a high-stroke-risk population in Qujing, Yunnan, China. Carotid ultrasonography was performed in 430 participants with high stroke risk, who were divided into different groups according to their ultrasound results. The risk factors and blood biochemical indices were recorded for assessment. The prevalence rates of CP and CCAIMT were 88.1% and 70.5%, respectively. Multivariate logistic regression analysis identified age and lack of physical exercise as risk factors of CP. Compared to participants without CP, participants who performed little physical exercise were prone to have one CP, while participants with risk factors for smoking, older age, and physical inactivity were more likely to have several CPs. Risk factors for CCAIMT were older age, male, and the levels of low density lipoprotein cholesterol. Risk factors for left CCAIMT included a history of hyperlipidemia and low density lipoprotein cholesterol, while male sex was the sole risk factor for right CCAIMT. Finally, male sex and advanced age were identified as risk factors for dual CCAIMT. The research reveals the risk factors for CP and CCAIMT, also clarifies the relationship between the risk factors, CP numbers, and the side of CCAIMT., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Flavonoids may play a role in mitigating atherosclerotic cardiovascular diseases, with evidence suggesting effects may differ between vascular beds. Studies examining associations with subclinical markers of atherosclerosis between subpopulations with different underlying risks of atherosclerosis are lacking., Methods: Among 5599 participants from the MESA (Multi-Ethnic Study of Atherosclerosis), associations between dietary flavonoid intakes (estimated from a food frequency questionnaire) and subclinical measures of atherosclerosis (ankle-brachial index, carotid plaques and intima-media thickness, and coronary artery calcification) were examined using repeated measures models. Exposures and outcomes were measured at exam 1 (2000-2002) and exam 5 (2010-2011). Stratified analyses and interaction terms were used to explore effect modification by time, sex, race/ethnicity, and smoking status., Results: In the analytic population, at baseline, ≈46% were men with a median age of 62 (interquartile range, 53-70) years and total flavonoid intakes of 182 (interquartile range, 98-308) mg/d. After multivariable adjustments, participants with the highest (quartile 4) versus lowest (quartile 1) total flavonoid intakes had 26% lower odds of having an ankle-brachial index <1 (odds ratio, 0.74 [95% CI, 0.60-0.92]) and 18% lower odds of having a carotid plaque (odds ratio, 0.82 [95% CI, 0.69-0.99]), averaged over exams 1 and 5. Moderate (quartile 3) to high (quartile 4) intakes of flavonols, flavanol monomers, and anthocyanins were associated with 19% to 34% lower odds of having an ankle-brachial index <1 and 18% to 20% lower odds of having carotid plaque. Participants with the highest intakes of anthocyanins (quartile 4) at baseline had a marginally slower rate of carotid plaque progression than those with moderate intakes (quartiles 2 and 3). There were no significant associations with intima-media thickness or coronary artery calcification. Observed associations did not differ by sex, race/ethnicity, or smoking status., Conclusions: In this multi-ethnic population, higher dietary flavonoid intakes were associated with lower odds of peripheral and carotid artery atherosclerosis. Increasing intakes of healthy, flavonoid-rich foods may protect against atherosclerosis in the peripheral and carotid arteries., Competing Interests: None.

Background: REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with use of icosapent ethyl compared with pharmaceutical grade mineral oil. The mechanisms underlying this benefit remain uncertain. We explored whether treatment allocation in REDUCE-IT might affect a series of biomarkers in pathways known to associate with atherosclerosis risk.Methods: Serum levels of interleukin-1β, interleukin-6, high-sensitivity C-reactive protein, oxidized low-density lipoprotein cholesterol, homocysteine, lipoprotein(a), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured at baseline, at 12 months, at 24 months, and at the end-of-study visit among REDUCE-IT participants with triglyceride levels ≥135 mg/dL and <500 mg/dL who were randomly allocated to treatment with either 4 grams daily of icosapent ethyl or mineral oil used as a comparator.Results: At baseline, median levels of each biomarker were similar in the 2 treatment groups. The levels of biomarkers associated with atherosclerosis increased over time among those allocated to mineral oil treatment; in this group at 12 months, the median percent increases from baseline were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density lipoprotein cholesterol, 16.2% for interleukin-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein, and 28.9% for interleukin-1β (all P values <0.001), with similar changes at 24 months. In the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months. As such, at study conclusion, between-group treatment differences largely reflected increases in the mineral oil group with median percent differences of 2.4% for lipoprotein(a), 3.0% for homocysteine, 4.2% for oxidized low-density lipoprotein cholesterol, 19.8% for interleukin-6, 26.2% for Lp-PLA2, 38.5% for high-sensitivity C-reactive protein, and 48.7% for interleukin-1β (all P values ≤0.007). These data are consistent with previous REDUCE-IT results in which the median percent change for low-density lipoprotein cholesterol at 12 months was -1.2% among those allocated to icosapent ethyl and 10.9% among those allocated to the mineral oil comparator.Conclusions: Among participants in REDUCE-IT, allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels increased among those allocated to mineral oil. The effect of these findings on interpretation of the overall risk reductions in clinical events observed within REDUCE-IT is uncertain.Registration: URL: https://www.Clinicaltrials: gov; Unique identifier: NCT01492361. [ABSTRACT FROM AUTHOR]

Assessments of venous thrombi and atherosclerosis were performed in vivo using magnetic resonance imaging of the inferior vena cava and of the brachiocephalic artery (BCA).[2],[3] Next, we assessed whether removal of DVT would affect the plaque. Keywords: atherosclerosis; inflammation; magnetic resonance imaging; molecular imaging; monocytes; thromboinflammation; venous thrombosis EN atherosclerosis inflammation magnetic resonance imaging molecular imaging monocytes thromboinflammation venous thrombosis 1945 1947 3 06/16/23 20230620 NES 230620 Deep vein thrombosis (DVT) and atherosclerosis cause significant morbidity and can lead to death. Here, we hypothesized that an increase in arterial events after venous thrombosis occurs because DVT directly accelerates atherosclerosis through a process involving DVT-induced inflammation. [Extracted from the article]

For example, lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle with apolipoprotein B SB 100 sb covalently bound through a disulfide bond to apolipoprotein(a),[4] has been relatively understudied with respect to its value as a cardiovascular risk factor when measured in childhood. Keywords: Editorials; atherosclerosis; child; lipoprotein; risk factors EN Editorials atherosclerosis child lipoprotein risk factors 32 34 3 12/29/22 20230103 NES 230103 B Article, see p 23 b Studies of cardiovascular risk factors in childhood are often limited by an inability to demonstrate direct links with atherosclerotic cardiovascular disease (ASCVD) in adulthood. Moreover, Lp(a) acted in an additive manner to LDL cholesterol such that those with elevated Lp(a) (>=30 mg/dL) and LDL cholesterol >=3.36 mmol/L (>=130 mg/dL) in childhood had a hazard ratio of 4.30 (95% CI, 3.30-5.30) compared with those with normal Lp(a) and LDL cholesterol. [Extracted from the article]

Background: Evidence suggests marginal superiority of static aortic systolic blood pressure (aSBP) compared with brachial SBP (bSBP) regarding the association with organ damage and prognosis of cardiovascular disease (CVD). The noninvasive 24-hour aSBP assessment is feasible and associates better with presence of left ventricular hypertrophy compared with 24-hour bSBP. We aimed at comparing the association of 24-hour aSBP and 24-hour bSBP with indices of arterial damage and examining the role of 24-hour SBP amplification variability (within-subjects' SD) in this association.Methods: Consecutive subjects referred for CVD risk assessment underwent 24-hour aortic and brachial ambulatory BP monitoring using a validated oscillometric device (Mobil-O-Graph). Arterial damage was assessed by carotid intima-media thickness (IMT) and detection of carotid and femoral atheromatosis (plaque presence).Results: Cross-sectionally 501 individuals (aged 54±13 years, 57% men, 80% hypertensives) were examined. Multivariable analysis revealed superiority of 24-hour aSBP regarding the association with IMT, carotid hypertrophy and carotid-but not femoral-atheromatosis. In receiver operator characteristics analysis, 24-hour aSBP displayed a higher discriminatory ability-compared to 24-hour bSBP-for the detection of both carotid hypertrophy (area under the curve, 0.662 versus 0.624, P<0.05) and carotid atheromatosis (area under the curve, 0.573 versus 0.547, P<0.05). This effect was more prominent in individuals with above-median 24-hour SD of SBP amplification.Conclusions: Our results suggest that 24-hour aSBP assessment may be of significant value in clinical practice to detect site-specific arterial damage on the basis of pressure amplification variability and should be prospectively examined in clinical trials. [ABSTRACT FROM AUTHOR]

Background: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).Methods: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy.Results: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.Conclusions: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions. [ABSTRACT FROM AUTHOR]

Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objectives: Vascular ultrasound is commonly used to diagnose giant cell arteritis (GCA). Most protocols include the temporal arteries and axillary arteries, but it is unclear which other arteries should be included. This study investigated whether inclusion of intima media thickness (IMT) of the common carotid artery (CCA) in the ultrasound evaluation of GCA improves the accuracy of the examination., Methods: We formed a fast-track clinic to use ultrasound to rapidly evaluate patients with suspected GCA. In this cohort study, patients referred for new concern for GCA received a vascular ultrasound for GCA with the temporal arteries and branches, the axillary artery, and CCA., Results: We compared 57 patients with GCA and 86 patients without GCA. Three patients with GCA had isolated positive CCA between 1 and 1.49 mm, and 21 patients without GCA had isolated positive CCA IMT. At the 1.5-mm CCA cutoff, 4 patients without GCA had positive isolated CCA, and 1 patient with GCA had a positive isolated CCA. The sensitivity of ultrasound when adding carotid arteries to temporal and axillary arteries was 84.21% and specificity 65.12% at an intima media thickness (IMT) cutoff of ≥1 mm and 80.70% and 87.21%, respectively, at a cutoff of ≥1.5 mm., Conclusion: Measurement of the CCA IMT rarely contributed to the diagnosis of GCA and increased the rate of false-positive results. Our data suggest that the CCA should be excluded in the initial vascular artery ultrasound protocol for diagnosing GCA. If included, an IMT cutoff of higher than 1.0 mm should be used., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adverse cardiac events are common in older patients with non-ST elevation acute coronary syndrome (NSTEACS), yet prognostic predictors are still lacking. This study investigated the long-term prognostic significance of non-invasive measures including endothelial function, carotid intima-media thickness (CIMT), and vascular stiffness in older NSTEACS patients referred for invasive treatment., Methods: NSTEACS patients aged 75 years and older recruited to a multicentre cohort study (NCT01933581) were assessed for baseline endothelial function using endoPAT logarithm of reactive hyperemia index (LnRHI), CIMT using B-mode ultrasound, and vascular stiffness using carotid-femoral pulse wave velocity (cfPWV). Long-term outcomes included major adverse cardiovascular events (MACE), a composite of death, reinfarction, urgent revascularization, stroke/transient ischemic attack, and significant bleeding., Results: Recruitment resulted in 214 patients assessed for LnRHI, 190 patients assessed for CIMT and 245 patients assessed for cfPWV. For LnRHI group (median follow-up 4.73 years [IQR: 1.41-5.00]), Cox regression analysis revealed a trend towards increased risk of MACE (HR: 1.24 [95% CI: 0.80-1.93]; P  = 0.328) and mortality (HR: 1.49 [95% CI: 0.86-2.59]; P  = 0.157), but no significance was reached. No difference for other components of MACE was found. For CIMT group (median follow up 4.74 years [IQR: 1.55-5.00]), no statistically significant difference in MACE was found (HR: 0.92 [95% CI: 0.53-1.59]; P  = 0.754). Similarly, for cfPWV group (median follow-up 4.96 years [IQR: 1.55-5.00]), results did not support prognostic significance (for MACE, HR: 0.95 [95% CI: 0.65-1.39]; P  = 0.794)., Conclusion: Endothelial function, CIMT and vascular stiffness were proven unsuitable as strong prognostic predictors in older patients with NSTEACS., Clinical Trial Registration: NCT01933581., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk. [ABSTRACT FROM AUTHOR]

The same is found in atherosclerosis neointimal lesions (Figure [H and I]), suggesting that this pattern of vWF localization and I VWF/Vwf i transcription is a general characteristic of neointimal lesions in both the systemic and pulmonary vascular beds. Keywords: hypertension, pulmonary; models, animal; vascular remodeling; von Willebrand Factor EN hypertension, pulmonary models, animal vascular remodeling von Willebrand Factor 429 431 3 08/02/22 20220802 NES 220802 vWF (von Willebrand Factor) is a large, secreted, multimeric glycoprotein transcribed by vascular endothelial cells and, to a lesser extent, megakaryocytes throughout the body. [Extracted from the article]

Background: Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events., Methods: We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study., Results: A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P   =  0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate., Conclusions: IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The product of red cell distribution width (RDW) and mean corpuscular volume (MCV) has been identified as an indicator of target organ damage in cases of hypertension. However, the role of the RDW-MCV product in assessing carotid alteration, renal damage, and left ventricular hypertrophy in patients with hypertension has not been elucidated. In this cross-sectional study, a total of 1115 participants with hypertension were included. The RDW and MCV at admission were measured using an automated hematology analyzer. Organ damage was determined by the left ventricular mass index (LVMI), carotid intima-media thickness, and estimated glomerular filtration rate. The prevalence rates of carotid alteration and left ventricular hypertrophy were 57.0% and 18.0%, respectively. A higher RDW-MCV product and RDW were observed in hypertensive patients who developed carotid alteration. After adjusting for potential confounding factors, the correlations of the RDW-MCV product (P = .285) and RDW (P = .346) with carotid alteration were not significant. Moreover, the analysis of variance showed no significant correlation between RDW and LVMI (P = .186). However, the RDW-MCV product was higher in individuals with a high LVMI compared to those with a normal LVMI. Multivariable linear regression analysis revealed that the RDW-MCV product was independently associated with the LVMI (β = 2.519, 95% CI: 0.921-4.116; P = .002), but not the estimated glomerular filtration rate (β = -0.260, 95% CI: -2.031-1.511; P = .773). An elevated RDW-MCV product may be a predictor for left ventricular hypertrophy in patients with hypertension., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate if serum polyfluoroalkyl substances (PFAS) were associated with cardiometabolic markers. Methods: Serum PFAS were evaluated in 38 Arizona firefighters and 49 participants from the 2009 to 2010 National Health and Nutrition Exainination Survey (NHANES). Cardiometabolic markers including carotid intima-medial thickness (CIMT) were measured in the firefighters. Results: Firefighters had elevated perfluorohexane sulfonic acid (PFHxS) and lower perfiuorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) compared to NHANES participants; for nine of the other 12 PFAS the values were not significantly different. There were significant negative associations among firefighters between perfluorodecanoic acid (PFDeA) and total cholesterol and PFUA and interleukin-6. PFAS concentrations were not associated with CIMT. Conclusion: PFHxS levels were elevated in firefighters compared to NHANES subjects. Serum PFAS concentrations were not associated with increased cardiometabolic risk measures in this population of firefighters. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the relationship between job stress and subclinical cardiovascular disease at ELSA-Brasil. Methods: We considered job stress domains (demand, skill discretion, decision authority, and social support) as independent variables and coronary artery calcium {CAC more than 0) and carotid intima-media thickness (CIMT more than P75% as a continuous variable) as dependent ones. Odds ratio (OR) and 95% confidence interval (95% CI) were presented crude, with further adjustments for sociodemographic, cardiovascular risk factors, and lifestyle variables. Linear regression models were built for CIMT using the same covariates. Results: Although significant associations were observed in the crude models, after multivariate adjustment CAC and CIMT were not significantly associated with demand, skill discretion, decision authority, and social support. Conclusions: Our results did not support an association between job stress and subclinical cardiovascular disease measured by CAC or CIMT. [ABSTRACT FROM AUTHOR]

Background: The TST trial (Treat Stroke to Target) showed the benefit of targeting a low-density lipoprotein cholesterol (LDL-C) concentration of <70 mg/dL in terms of reducing the risk of major cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature. The impact on carotid atherosclerosis evolution is not known.Methods: TST-PLUS (Treat Stroke to Target-Plaque Ultrasound Study) included 201 patients assigned to an LDL-C concentration of <70 mg/dL and 212 patients assigned to a target of 100±10 mg/dL. To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe as needed. Ultrasonographers were certified and carotid ultrasound examinations were performed using M'Ath software at baseline and at 2, 3, and 5 years. All images were uploaded to the Intelligence in Medical Technologies database directly from the carotid ultrasound device. The central core laboratory performed all offline measurements of the intima-media thickness of both common carotid arteries blinded from the randomization arm. The main outcomes were newly diagnosed atherosclerotic plaque on carotid bifurcation or internal carotid artery using the Mannheim consensus definition and between-group comparison of common carotid arteries intima-media thickness change.Results: After a median follow-up of 3.1 years, the achieved LDL-C concentrations were 64 mg/dL (1.64 mmol/L) in the lower-target group and 106 mg/dL (2.72 mmol/L) in the higher-target group. Compared with the higher-target group, patients in the lower-target group had a similar incidence of newly diagnosed carotid plaque: 46/201 (5-year rate, 26.1%) versus 45/212 (5-year rate, 29.7%). The change in common carotid arteries intima-media thickness was -2.69 µm (95% CI, -6.55 to 1.18) in the higher-target group and -10.53 µm (95% CI, -14.21 to -6.85) in the lower-target group, resulting in an absolute between-group difference of -7.84 µm (95% CI, -13.18 to -2.51; P=0.004).Conclusions: In patients with ischemic stroke and atherosclerosis, an LDL-C target of <70 mg/dL (1.8 mmol/L) did not reduce the incidence of new carotid plaques but produced significantly greater regression of carotid atherosclerosis than an LDL-C target of 90 to 110 mg/dL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875. [ABSTRACT FROM AUTHOR]

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach.Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients.Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials. [ABSTRACT FROM AUTHOR]

Recent evidence links long-term (visit-to-visit) blood pressure (BP) variability to the risk of cardiovascular disease, independent of mean BP levels. Potential associations between long-term BP variability and cardiovascular disease risk may be reflected in early life course alterations in coronary artery calcium (CAC) and carotid intima-media thickness. We evaluated 2482 CARDIA study (Coronary Artery Risk Development in Young Adults) participants (mean [SD] age at the year 20 exam [2005-2006] was 45.4 [3.6] years, 43.2% men, and 41.3% black). We included participants with BP assessments across 20-years (year 0, 2, 5, 7, 10, 15, 20 exams) and carotid intima-media thickness and CAC data at the year 20 exam. BP variability was assessed using variability independent of the mean and SD. Adjusted multivariable linear or logistic regression models (as appropriate) were used to assess associations between long-term BP variability measures and carotid intima-media thickness. and CAC (ln [CAC+1] and prevalent CAC). Long-term systolic BP variability independent of the mean (per 1 SD) was positively associated with carotid intima-media thickness (β=10 μm, SE=3, P=0.002). Similarly, long-term diastolic BP variability independent of the mean was associated with carotid intima-media thickness (β=10 μm, SE (3), P=0.001). Long-term BP variability was not associated with either ln [CAC+1] or prevalent CAC. Long-term systolic and diastolic BP variability across early adulthood was positively associated with modest adverse midlife alterations in carotid intima-media thickness but not to CAC. Our findings provide further insights into pathophysiologic mechanisms that link long-term BP variability to cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Pulmonary endarterectomy (PEA) is the gold standard treatment for patients with operable chronic thromboembolic pulmonary hypertension. However, persistent pulmonary hypertension (PH) after PEA remains a major determinant of poor prognosis. A concomitant small-vessel arteriopathy in addition to major pulmonary artery obstruction has been suggested to play an important role in the development of persistent PH and survival after PEA. One of the greatest unmet needs in the current preoperative evaluation is to assess the presence and severity of small-vessel arteriopathy. Using the pulmonary artery occlusion technique, we sought to assess the presence and degree of small-vessel disease in patients with chronic thromboembolic pulmonary hypertension undergoing PEA to predict postoperative outcome before surgery.Methods: Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned pulmonary vascular resistance in larger arterial (upstream resistance [Rup]) and small arterial plus venous components (downstream resistance) in 90 patients before PEA. For validation, lung wedge biopsies were taken from nonobstructed and obstructed lung territories during PEA in 49 cases. Biopsy sites were chosen according to the pulmonary angiogram still frames that were mounted in the operating room. All vessels per specimen were measured in each patient. Percent media (%MT; arteries) and intima thickness (%IT; arteries, veins, and indeterminate vessels) were calculated relative to external vessel diameter.Results: Decreased Rup was an independent predictor of persistent PH (odds ratio per 10%, 0.40 [95% CI, 0.23-0.69]; P=0.001) and survival (hazard ratio per 10%, 0.03 [95% CI, 0.00-0.33]; p=0.004). Arterial %MT and %IT of nonobstructed lung territories and venous %IT of obstructed lung territories were significantly increased in patients with persistent PH and nonsurvivors. Rup correlated inversely with %MT (r=-0.72, P<0.001) and %IT (r=-0.62, P<0.001) of arteries from nonobstructed lung territories and with %IT (r=-0.44, P=0.024) of veins from obstructed lung territories. Receiver operating characteristic analysis disclosed that Rup <66% predicted persistent PH after PEA, whereas Rup <60% identified patients with poor prognosis after PEA.Conclusions: Pulmonary artery occlusion waveform analysis with estimation of Rup seems to be a valuable technique for assessing the degree of small-vessel disease and postoperative outcome after PEA in chronic thromboembolic pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of the combination of exercise training (ET) and statins in people living with human immunodeficiency virus. Methods: This was a randomized, double-blind, placebo-controlled clinical trial. Eighty-three people living with human immunodeficiency virus were assigned to either placebo (PL), statins (STA), PL + ET (PLET) or STA + ET (STAET) groups. Volunteers assigned to STA and STAET groups were administered 10 mg of rosuvastatin, whereas the PL and PLET groups were administered a placebo. The PLET and STAET groups performed ET three times a week. Before and after the 12-wk follow-up, the volunteers underwent to anthropometric assessment and blood collection to evaluate lipid profile, cardiovascular markers, inflammatory profile; a Doppler ultrasound examination, muscle strength (MS) and cardiorespiratory fitness (CF) tests were performed. Results: There was a decrease in total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, fibrinogen, interleukin (IL)-1β and right carotid intima-media thickness in the STA, PLET, and STAET groups compared with PL group (P < 0.001). Furthermore, there was a decrease in total cholesterol, triglycerides, low-density lipoprotein, IL-1β, IL-6, and IL-8 levels and in left and right carotid intima-media thickness and an increase in HDL-c levels in the STAET groups compared with the STA (P ≤ 0.001) and PLET groups (P ≤ 0.001). There was an increase in IL-10 levels, peak-systolic velocity, end-diastolic velocity, wall shear rate in the PLET and STAET groups compared with the PL (P ≤ 0.001) and STA groups (P ≤ 0.001). The PLET and STAET groups reduced body fat mass, body fat percentage and increased lean body mass, MS and CF compared with PL (P ≤ 0.001) and STA (P ≤ 0.001) groups. Conclusions: The combination of ET and statins is useful to enhance lipid and inflammatory profiles, reduce cardiovascular disease markers, and improve Doppler ultrasound findings, MS and CF in people living with HIV. [ABSTRACT FROM AUTHOR]

Background: Despite advances in the diagnosis and treatment of ankylosing spondylitis (AS), the risk of cardiovascular complications in AS patients is still higher than in the general population. Macrophages are at the intersection of the basic pathogenetic processes of AS and atherosclerosis. Although syndecan-4 (SDC4) mediates a variety of biological processes, the role of SDC4 in macrophage-mediated atherogenesis in AS patients remains unclear. Herein, we aimed to investigate the role of SDC4 in subclinical atherosclerosis in AS patients., Methods: Subjects were selected from eligible AS patients and control subjects without a prior history of AS who were referred to the rheumatology outpatient clinics. All participants' past medical records and clinical, and demographic characteristics were scanned. In addition, carotid intima-media thickness (CIMT) measurement and disease activity index measurement were applied to all patients., Results: According to our data, serum SDC4 level was significantly higher among AS patients compared with the control group (6.7 [1.5-35.0] ng/mL vs 5.1 [0.1-12.5] ng/mL, P < .001). The calculated CIMT was also significantly higher in AS patients than in the control group (0.6 [0.3-0.9] mm vs 0.4 (0.2-0.7), P < .001]. Additionally, serum C-reactive protein level and SDC4 level were independent predictors of AS and strongly associated with CIMT. Linear regression analysis showed that serum SDC4 level was the best predictor of CIMT (P = .004)., Conclusion: Our data indicate that serum SDC4 levels provide comprehensive information about the clinical activity of the disease and subclinical atherosclerosis in AS patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D., Methods: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program. We included first-order T2D interaction terms in each model to determine whether CAD loci were modified by T2D. The genetic main and interaction effects were assessed using a joint test to determine whether a CAD variant, or gene-based rare variant set, was associated with the respective subclinical atherosclerosis measures and then further determined whether these loci had a significant interaction test., Results: Using a Bonferroni-corrected significance threshold of P <1.6×10 -4 , we identified 3 genes ( ATP1B1 , ARVCF , and LIPG ) associated with CAC and 2 genes ( ABCG8 and EIF2B2 ) associated with carotid intima-media thickness and carotid plaque, respectively, through gene-based rare variant set analysis. Both ATP1B1 and ARVCF also had significantly different associations for CAC in T2D cases versus controls. No significant interaction tests were identified through the candidate single-variant analysis., Conclusions: These results highlight T2D as an important modifier of rare variant associations in CAD loci with CAC., Competing Interests: Disclosures Dr Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr Raffield is a consultant for the Trans-Omics for Precision Medicine (TOPMed) Administrative Coordinating Center (through WeStat). Dr Malhotra receives research funding from Aeglea BioTherapeutics and Amgen and serves as a consultant for Myokardia/Bristol Myers Squibb, Renovacor, Epizon Pharma, and Third Pole. The other authors report no conflicts.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a breakthrough in the treatment of hypercholesterolemia. The aim of this study was to perform a multicentre prospective analysis on the effects of PCSK9i since their distribution in Italy., Methods: During the study period (July 2017 to February 2022) 246 patients (mean age 61 ± 11 years, male 73%) who were evolocumab (142/246) or alirocumab (104/246) new users were enrolled in the CERTI (Costo Efficacia Regione Toscana Inibitori PCSK9) study. Lipid value, adverse events (AEs), major cardiovascular events (MACEs) and intima-media thickness were analysed., Results: PCSK9i therapy allowed a significant improvement in patients' lipid profile [total cholesterol -35%, P < 0.001; triglycerides -9%, P < 0.05; low-density lipoprotein (LDL) cholesterol -51%, P < 0.001; Lp(a) levels -4%, P < 0.05], maintained during the follow-up. No significant variations in intima-media thickness were observed. In the subgroup of patients with more than 1 year of PCSK9i therapy (165/246 patients) we highlighted: a 66% reduction in MACEs compared with the year before recruitment; a progressive increase in MACEs during the follow-up (MACEs event/rate at first year 0.08 vs. MACEs event/rate at year 5: 0.47); a patients cluster with late MACEs older, with higher prevalence of hypertension, smoking habit and peripheral vascular disease. During the follow-up, we recorded AEs in 31% of patients, which mainly resulted in reduction/discontinuation of lipid-lowering therapy for 50 patients or in discontinuation/shift of PCSK9i (respectively 8 and 6 cases)., Conclusion: Our data agree with the large evidence on the effectiveness/tolerability of PCSK9i therapy; however, although PCSK9i represents a good cholesterol-lowering therapeutic option, our study shows a progressive increase in MACEs during the late follow-up that deserve further research., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Potential associations between menopause, age at menopause, and clinical indicators related to cardiovascular disease (CVD) have not been elucidated. To identify the risk of CVD early and contribute to its prevention and intervention, the present study used relevant biomarkers to evaluate the risk of CVD among pre- and postmenopausal women. An overall population of 816 women (aged 40-60 y) was evaluated as premenopause, natural early menopause, or natural late menopause (ages ≤ 48 and ≥52 y), with ages 49-51 years as reference (natural menopause). High-sensitivity C-reactive protein, carotid intima-media thickness, and brachial-ankle pulse wave velocity were measured. Triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) of the postmenopausal group were each significantly higher than that of the premenopausal. However, the 3 menopausal groups were similar regarding hypertension, diabetes, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. In the logistic regression model, the CRP, brachial-ankle pulse wave velocity, and carotid intima-media thickness levels were similar among the premenopause and early and late menopause groups. These results were unchanged after further adjustment for multiple confounders including age, smoking, drinking, salt intake habits, presence of hypertension, or diabetes mellitus. Menopause itself is a more important risk factor for CVD compared with menopause that begins at early or late age., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Vascular aging is a major contributor to cardiovascular disease and can be quantified by higher carotid stiffness, intima-media thickness and diameter, and hypertension. Weight gain across the lifetime may be an important, modifiable determinant of vascular aging. We therefore aimed to assess lifetime body silhouette trajectories (a marker of weight change across the lifespan) in relation to vascular aging in late adulthood. We used cross-sectional data from a community-based cohort study (n=8243; age, 59.4; 38.7% women). A linear mixed model was used to assess trajectories of recalled body silhouettes from age 8 to 45 years. We assessed carotid artery properties (ultrasonography), resting hypertension (blood pressure ≥140/90 mm Hg or use of antihypertensives), and exaggerated exercise blood pressure, a marker of masked hypertension (systolic blood pressure ≥150 mm Hg during submaximal exercise) at study recruitment when the participants were 50 to 75 years of age. We identified 5 distinct body silhouette trajectories: lean stable (32.0%), lean increase (11.1%), moderate stable (32.5%), lean-marked increase (16.3%), and heavy stable (8.1%). Compared with individuals in the lean-stable trajectory, those in the moderate-stable, lean-marked increase, and heavy-stable trajectories had higher carotid stiffness, intima-media thickness and diameter (odds ratios between 1.23 and 2.10 for highest quartile versus lowest quartile of manifestations of vascular aging; P<0.05) and were more likely to have resting hypertension and exaggerated exercise blood pressure, after adjustment for potential confounders (odds ratios between 1.31 and 1.60; P<0.05). Vascular aging was most prominent among individuals who were lean in early life but markedly gained weight during young adulthood and among those who were heavy in early life and maintained weight. [ABSTRACT FROM AUTHOR]

In patients with chronic kidney disease, data on blood pressure (BP) pattern and its association with target organ damage, which indicates elevated cardiovascular risk, are sparse. In 305 treated hypertensive chronic kidney disease patients, we assessed BP pattern, left ventricular mass (magnetic resonance imaging), intima-media thickness (ultrasound), 24-hour-pulse wave velocity and 24-hour-central augmentation index (Mobil-O-Graph). Controlled hypertension (normal office and ambulatory BP) was found in 41% and sustained uncontrolled hypertension (elevated office and ambulatory BP) in 30% of patients. Misclassification of BP status occurred in 29%: white coat uncontrolled hypertension (elevated office but normal ambulatory BP) was detected in 11% and masked uncontrolled hypertension (normal office but elevated ambulatory BP) in 18% of patients. Left ventricular mass was increased in white coat uncontrolled hypertension (+11.2 g), masked uncontrolled hypertension (+9.4 g), and sustained uncontrolled hypertension (+16.6 g) compared with controlled hypertension. Intima-media thickness was similar across all 4 BP groups. Twenty-four hour-pulse wave velocity and 24-hour-central augmentation index were increased in masked uncontrolled hypertension (+0.5 m/sec and +2.5%) and sustained uncontrolled hypertension (+0.5 m/sec and +2.9%) compared with controlled hypertension. In conclusion, based on office BP measurements, misclassification of true BP status occurred in almost one-third of chronic kidney disease patients. Both types of misclassification (white coat uncontrolled hypertension and masked uncontrolled hypertension) were associated with parameters of target organ damage. Ambulatory BP monitoring should be used routinely to identify chronic kidney disease patients at high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Lecithin:cholesterol acyltransferase (LCAT) is the sole enzyme that esterifies cholesterol in plasma. Its role in the supposed protection from atherogenesis remains unclear because mutations in LCAT causing fish-eye disease (FED) or familial LCAT deficiency (FLD) have been reported to be associated with more or instead less carotid atherosclerosis, respectively. This discrepancy may be associated with the loss of cholesterol esterification on only apolipoprotein AI (FED) or on both apolipoprotein AI- and apolipoprotein B-containing lipoproteins (FLD), an aspect that has thus far not been investigated.Methods: Seventy-four heterozygotes for LCAT mutations recruited from Italy and the Netherlands were assigned to FLD (n=33) or FED (n=41) groups and compared with 280 control subjects. Subclinical atherosclerosis was assessed with carotid intima-media thickness.Results: Compared with control subjects, total cholesterol was lower by 16% (-32.9 mg/dL) and 7% (-14.9 mg/dL) and high-density lipoprotein cholesterol was lower by 29% (-16.7 mg/dL) and 36% (-20.7 mg/dL) in the FLD and FED groups, respectively. Subjects with FLD displayed a significant 18% lower low-density lipoprotein cholesterol compared with subjects with FED (101.9±35.0 versus 123.6±47.4 mg/dL; P=0.047) and control subjects (122.6±35.0 mg/dL; P=0.003). Remarkably, all 3 intima-media thickness parameters were lower in subjects with FLD compared with FED and control subjects (accounting for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids). After additional correction for nationality and ultrasonographic methods, average and maximum intima-media thickness remained significantly lower when subjects with FLD were compared with those with FED (0.59 versus 0.73 mm, P=0.003; and 0.87 versus 1.24 mm, P<0.001, respectively). In contrast, the common carotid intima-media thickness (corrected for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids) was higher in subjects with FED compared with control subjects (0.69 versus 0.65 mm; P=0.05), but this significance was lost after adjustment for nationality and ultrasonographic machine.Conclusions: In this head-to-head comparison, FLD and FED mutations were shown to be associated with decreased and increased atherosclerosis, respectively. We propose that this discrepancy is related to the capacity of LCAT to generate cholesterol esters on apolipoprotein B-containing lipoproteins. Although this capacity is lost in FLD, it is unaffected in FED. These results are important when considering LCAT as a target to decrease atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult nonlaboratory-based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a lipid model based on nonlaboratory risk factors plus lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood.Methods: The study comprised 2893 participants 12 to 18 years of age from 4 longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study), and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up, 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age and sex were included in each model.Results: In univariate models, all risk factors except for borderline high and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (relative risk [95% confidence interval]), male sex (2.7 [2.0-2.6]), prehypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3-2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high low-density lipoprotein cholesterol (1.6 [1.2-2.2]), high low-density lipoprotein cholesterol (1.6 [1.1-2.1]), and borderline low high-density lipoprotein cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT (P<0.05). The addition of lipids into the nonlaboratory risk model slightly but significantly improved discrimination in predicting high cIMT compared with nonlaboratory-based risk factors only (C statistics for laboratory-based model 0.717 [95% confidence interval, 0.685-0.748] and for nonlaboratory 0.698 [95% confidence interval, 0.667-0.731]; P=0.02).Conclusions: Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic-based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid-femoral (aortic) pulse wave velocity, augmentation index, and carotid intima-media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima-media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Keywords: cardiovascular risk; computed tomography; coronary artery disease EN cardiovascular risk computed tomography coronary artery disease 585 586 2 08/22/22 20220823 NES 220823 According to the American Heart Association (AHA) and the American College of Cardiology (ACC), coronary artery calcium (CAC) scanning is the best way to improve selection of patients for lipid-lowering drug treatment when the initial risk assessment by the Pooled Cohort Equations is inconclusive.[1] Similar recommendations have been issued by the Canadian Cardiovascular Society and the Cardiac Society of Australia and New Zealand. Cardiology organizations have recommended CAC as a reasonable test in intermediate risk primary prevention patients to improve selection of patients for more intensive and safe statin therapy for prevention. [Extracted from the article]

Middle aortic syndrome (MAS) is a narrowing of the abdominal aorta, often in conjunction with renal artery stenosis (RAS). Structure and function of the cardiovascular system are not well understood. In a prospective cross-sectional study, 35 children with MAS or RAS or both (MAS/RAS) were compared with 140 age-, sex-, and body surface area-matched healthy children. Vascular assessment included carotid intima-media thickness and carotid distensibility using B-mode ultrasound and central and peripheral pulse wave velocities using applanation tonometry. Left ventricular structure and function were assessed by 2-dimensional and speckle-tracking echocardiography. Children with MAS or RAS were 12.5±3.0 years old at enrollment, and 50% were men. Carotid intima-media thickness (0.54±0.10 versus 0.44±0.05 mm; P<0.001) and central pulse wave velocities (5.58±1.83 versus 5.00±0.90 m/s; P=0.01) were significantly higher in children with disease compared with healthy children; however, after adjustment for systolic blood pressure z score, only carotid intima-media thickness remained significantly higher in the MAS/RAS group compared with the controls (β=0.07 [0.03, 0.10]). Peripheral pulse wave velocities and carotid distensibility were normal. Children with disease had significantly increased left ventricular mass and changes in diastolic function (lower E/a ratio and lower e' velocities). Systolic parameters, including ejection fraction, global longitudinal and circumferential strain, were similar to controls. Our findings demonstrate that children with MAS or RAS have evidence of carotid and left ventricular remodeling, without peripheral arterial involvement, which suggests a localized disease process. Left ventricular systolic function is preserved; however, subtle changes in diastolic function are observed. Carotid vessel changes are consistent with a 5- to 10-year aging, which underscores the importance of blood pressure control. [ABSTRACT FROM AUTHOR]

Objectives: The presence of atherosclerotic plaque in the carotid arteries is a strong predictor of cardiovascular disease (CVD). Research and data on CVD risk have been derived primarily from individuals aged 55 years or older, and assessment of CVD risk among young and middle-aged adults seldom has been studied. The use of ultrasonography to measure carotid intima-media thickness (IMT) and carotid plaque appears to have utility to detect subclinical atherosclerosis in asymptomatic adults. This study evaluated the presence of carotid plaque using ultrasonography among healthy young and middle-aged adults.Methods: Participants were men and women recruited in Miami, Florida, and were 18 to 50 years old with no history of CVD. Participants underwent a general physical examination and carotid artery ultrasonography to evaluate carotid IMT and carotid plaque.Results: From a total of 173 participants with a mean age of 34 years (standard deviation 8.9), 21.0% (95% confidence interval [CI] 15.0-27.2) were identified as having carotid plaque. IMT values ranged from 0.49 to 1.03 mm, with a mean value of 0.70 mm (standard deviation 0.09). In multivariable logistic regression older age (adjusted odds ratio [AOR] 1.08, 95% CI 1.01-1.16, P = 0.024) and cigarette smoking (AOR 2.67, 95% CI 1.02-7.00, P = 0.045) were associated with plaque, after controlling for IMT (AOR 2.55, 95% CI 1.40-4.65, P = 0.002).Conclusions: Traditional CVD risk factors such as those evaluated in this study may fail to provide adequate predictive value of carotid atherosclerosis in younger populations with no history of CVD, because the majority of traditional risk factors identified in previous research were not associated with carotid plaque in this young sample. Further research assessing nontraditional risk factors among asymptomatic individuals is required, and the evaluation of IMT as an intervention tool to detect CVD risk in these asymptomatic populations is warranted. [ABSTRACT FROM AUTHOR]

Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular risk. We hypothesized that the number of cardiovascular risk factors determines the progression of vascular aging. One hundred forty-two subjects (mean age 51.9 years, 94 men) without established cardiovascular disease were investigated in 2 examinations over a 2-year period. Subjects were classified at baseline according to their number of risk factors (from 0 to 2 and more). Subjects had determinations of carotid-femoral pulse wave velocity, aortic augmentation index, brachial flow-mediated dilatation, and common carotid intima-media thickness and their annual absolute changes were calculated. Subjects with more risk factors had a gradual higher annual progression of pulse wave velocity (0.092 m/s/y for 0, 0.152 m/s/y for 1, and 0.352 m/s/y for 2 and more; P=0.007). Patients with both hypertension and dyslipidemia have 4× higher annual progression rate compared with subjects without these risk factors (0.398 m/s/y versus 0.102 m/s/y). When only subjects 55 years old and under were considered, the progression rate of augmentation index was higher in subjects with more risk factors (1.15%/y versus 1.50%/y versus 2.99%/y, respectively; P=0.037). No association was found with the annual change of flow-mediated dilatation or carotid intima-media thickness. In the general population, increasing number of risk factors is associated with accelerated deterioration of specific indices of vascular aging, such as pulse wave velocity and augmentation index; in contrast, flow-mediated dilatation and carotid intima-media thickness are insensitive to such changes. Accordingly, the former may be more useful for gauging vascular aging. [ABSTRACT FROM AUTHOR]

Background: Dickkopf-related protein 3 (DKK3) is a secreted protein that is involved in the regulation of cardiac remodeling and vascular smooth muscle cell differentiation, but little is known about its role in atherosclerosis.Methods: We tested the hypothesis that DKK3 is atheroprotective using both epidemiological and experimental approaches. Blood DKK3 levels were measured in the Bruneck Study in 2000 (n=684) and then in 2005 (n=574). DKK3-deficient mice were crossed with apolipoprotein E-/- mice to evaluate atherosclerosis development and vessel injury-induced neointimal formation. Endothelial cell migration and the underlying mechanisms were studied using in vitro cell culture models.Results: In the prospective population-based Bruneck Study, the level of plasma DKK3 was inversely related to carotid artery intima-media thickness and 5-year progression of carotid atherosclerosis independently from standard risk factors for atherosclerosis. Experimentally, we analyzed the area of atherosclerotic lesions, femoral artery injury-induced reendothelialization, and neointima formation in both DKK3-/-/apolipoprotein E-/- and DKK3+/+/apolipoprotein E-/- mice. It was demonstrated that DKK3 deficiency accelerated atherosclerosis and delayed reendothelialization with consequently exacerbated neointima formation. To explore the underlying mechanisms, we performed transwell and scratch migration assays using cultured human endothelial cells, which exhibited a significant induction in cell migration in response to DKK3 stimulation. This DKK3-induced migration activated ROR2 and DVL1, activated Rac1 GTPases, and upregulated JNK and c-jun phosphorylation in endothelial cells. Knockdown of the ROR2 receptor using specific siRNA or transfection of a dominant-negative form of Rac1 in endothelial cells markedly inhibited cell migration and downstream JNK and c-jun phosphorylation.Conclusions: This study provides the evidence for a role of DKK3 in the protection against atherosclerosis involving endothelial migration and repair, with great therapeutic potential implications against atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Heterozygous familial hypercholesterolemia (HeFH) is an autosomal dominant disorder leading to premature atherosclerosis. Children with HeFH exhibit early signs of atherosclerosis manifested by increased carotid intima-media thickness (IMT). In this study, we assessed the effect of 2-year treatment with rosuvastatin on carotid IMT in children with HeFH.Methods: Children with HeFH (age, 6-<18 years) and low-density lipoprotein cholesterol >4.9 mmol/L or >4.1 mmol/L in combination with other risk factors received rosuvastatin for 2 years, starting at 5 mg once daily, with uptitration to 10 mg (age, 6-<10 years) or 20 mg (age, 10-<18 years). Carotid IMT was assessed by ultrasonography at baseline and 12 and 24 months in all patients and in age-matched unaffected siblings. Carotid IMT was measured at 3 locations (common carotid artery, carotid bulb, internal carotid artery) in both the left and right carotid arteries. A linear mixed-effects model was used to evaluate differences in carotid IMT between children with HeFH and the unaffected siblings. P values were adjusted for age, sex, carotid artery site, and family relations.Results: At baseline, mean±SD carotid IMT was significantly greater for the 197 children with HeFH compared with the 65 unaffected siblings (0.397±0.049 and 0.377±0.045 mm, respectively; P=0.001). During 2 years of follow-up, the change in carotid IMT was 0.0054 mm/y (95% confidence interval, 0.0030-0.0082) in children with HeFH and 0.0143 mm/y (95% confidence interval, 0.0095-0.0192) in unaffected siblings (P=0.002). The end-of-study difference in mean carotid IMT between children with HeFH and unaffected siblings after 2 years was no longer significant (0.408±0.043 and 0.402±0.042 mm, respectively; P=0.2).Conclusions: In children with HeFH who were ≥6 years of age, carotid IMT was significantly greater at baseline compared with unaffected siblings. Rosuvastatin treatment for 2 years resulted in significantly less progression of increased carotid IMT in children with HeFH than untreated unaffected siblings. As a result, no difference in carotid IMT could be detected between the 2 groups after 2 years of rosuvastatin. These findings support the value of early initiation of statin treatment for low-density lipoprotein cholesterol reduction in children with HeFH.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01078675. [ABSTRACT FROM AUTHOR]

Background—Although HIV is associated with increased atherosclerotic cardiovascular disease (CVD) risk, it is unknown whether guidelines can identify HIV-infected adults who may benefit from statins. We compared the 2013 American College of Cardiology/American Heart Association and 2004 Adult Treatment Panel III recommendations in HIV-infected adults and evaluated associations with carotid artery intima-media thickness and plaque. Methods and Results—Carotid artery intima-media thickness was measured at baseline and 3 years later in 352 HIV-infected adults without clinical atherosclerotic CVD and not on statins. Plaque was defined as IMT >1.5 mm in any segment. At baseline, the median age was 43 (interquartile range, 39–49), 85% were men, 74% were on antiretroviral medication, and 50% had plaque. The American College of Cardiology/American Heart Association guidelines were more likely to recommend statins compared with the Adult Treatment Panel III guidelines, both overall (26% versus 14%; P<0.001), in those with plaque (32% versus 17%; P=0.0002), and in those without plaque (16% versus 7%; P=0.025). In multivariable analysis, older age, higher low-density lipoprotein cholesterol, pack per year of smoking, and history of opportunistic infection were associated with baseline plaque. Baseline IMT (hazard ratio, 1.18 per 10% increment; 95% confidence interval, 1.05–1.33; P=0.005) and plaque (hazard ratio, 2.06; 95% confidence interval, 1.02–4.08; P=0.037) were each associated with all-cause mortality, independent of traditional CVD risk factors. Conclusions—Although the American College of Cardiology/American Heart Association guidelines recommended statins to a greater number of HIV-infected adults compared with the Adult Treatment Panel III guidelines, both failed to recommend therapy in the majority of HIV-affected adults with carotid plaque. Baseline carotid atherosclerosis but not atherosclerotic CVD risk scores was an independent predictor of mortality. HIV-specific guidelines that include detection of subclinical atherosclerosis may help to identify HIV-infected adults who are at increased atherosclerotic CVD risk and may be considered for statins. [ABSTRACT FROM AUTHOR]

BACKGROUND: Remote ischemic preconditioning (RIPC) can inhibit recurrent ischemic events effectively in patients with acute or chronic cerebral ischemia. However, it is still unclear whether RIPC can impede ischemic injury after carotid artery stenting (CAS) in patients with severe carotid artery stenosis. METHODS: Subjects with severe carotid artery stenosis were recruited in this randomized controlled study, and assigned to RIPC, sham, and no intervention (control) groups. All subjects received standard medical therapy. Subjects in the RIPC and sham groups underwent RIPC and sham RIPC twice daily, respectively, for 2 weeks before CAS. Plasma neuron-specific enolase and S-100B were used to evaluate safety, hypersensitive C-reactive protein, and new ischemic diffusion-weighted imaging lesions were used to determine treatment efficacy. The primary outcomes were the presence of ≥1 newly ischemic brain lesions on diffusion-weighted imaging within 48 hours after stenting and clinical events within 6 months after stenting. RESULTS: We randomly assigned 189 subjects in this study (63 subjects in each group). Both RIPC and sham RIPC procedures were well tolerated and completed with high compliance (98.41% and 95.24%, respectively). Neither plasma neuron-specific enolase levels nor S-100B levels changed significantly before and after treatment. No severe adverse event was attributed to RIPC and sham RIPC procedures. The incidence of new diffusion-weighted imaging lesions in the RIPC group (15.87%) was significantly lower than in the sham group (36.51%; relative risk, 0.44; 96% confidence interval, 0.20-0.91; P<0.01) and the control group (41.27%; relative risk, 0.39; 96% confidence interval, 0.21-0.82; P<0.01). The volumes of lesions were smaller in the RIPC group than in the control and sham groups (P<0.01 each). Ischemic events that occurred after CAS were 1 transient ischemic attack in the RIPC group, 2 strokes in the control group, and 2 strokes and 1 transient ischemic attack in the sham group, but these results were not significantly different among the 3 groups (P=0.597). CONCLUSIONS: RIPC is safe in patients undergoing CAS, which may be able to decrease ischemic brain injury secondary to CAS. However, the mechanisms and effects of RIPC on clinical outcomes in this cohort of patients need further investigation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654666 [ABSTRACT FROM AUTHOR]