Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults.

BACKGROUND AND AIMS: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). METHODS: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. RESULTS: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 µm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. CONCLUSIONS: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

Remnant cholesterol trajectory and subclinical arteriosclerosis: a 10-year longitudinal study of Chinese adults.

We aimed to identify different trajectories of remnant cholesterol (RC) and investigate the association of RC trajectories with vascular endothelial function and atherosclerosis progression in a longitudinal cohort of the Chinese population. A total of 521 participants were included in the flow-mediated vasodilation (FMD) subcohort study, and 7775 participants were included in the brachial-ankle pulse wave velocity (baPWV) subcohort study. All participants had ≥ 3 medical examinations during the 10-year follow-up period. In the FMD subcohort study, three distinct RC trajectories were identified according to the RC range and changing pattern over time: "low" (57.58%), "moderate" (30.90%) and "high" (11.52%). The proportion of the three groups with vascular endothelial dysfunction (FMD < 7.0%) was 20.00%, 39.75% and 60.00% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.88 and 2.94 times the odds of vascular endothelial dysfunction (P = 0.048). In the baPWV subcohort study, three distinct RC trajectories were also identified: "low" (54.29%), "moderate" (38.97%) and "high" (6.74%). The proportion of the three groups with atherosclerosis (baPWV > 1400 cm/s) was 38.79%, 51.26% and 59.01% respectively. Taking the low group as a reference, participants in the moderate and high groups had over 1.46 and 2.16 times the odds of atherosclerosis (P < 0.001). The findings indicated that distinct RC trajectories are significantly associated with vascular endothelial function and atherosclerosis. Regular monitoring to identify persistent increases in RC may be more helpful in identifying individuals with a high risk of cardiovascular disease.

Detection of subclinical atherosclerosis using vascular ultrasound as a vascular risk assessment method. Simplified protocol. / Detección de aterosclerosis subclínica mediante ecografía vascular como método de evaluación de riesgo vascular. Protocolo simplificado.

Cardiovascular disease secondary to atherosclerosis is the main cause of morbidity and mortality in the world. Cardiovascular risk stratification has proven to be an insufficient approach to detect those subjects who are going to suffer a cardiovascular event, which is why for years other markers have been sought to help stratify each individual with greater precision. Two-dimensional vascular ultrasound is a excellent method for vascular risk assessment.

Ankle-Brachial Index and Risk of Sudden Cardiac Death in the Community: The ARIC Study.

BACKGROUND: Sudden cardiac death (SCD) is a significant global public health problem accounting for 15% to 20% of all deaths. A great majority of SCD is associated with coronary heart disease, which may first be detected at autopsy. The ankle-brachial index (ABI) is a simple, noninvasive measure of subclinical atherosclerosis. The purpose of this study was to examine the relationship between ABI and SCD in a middle-aged biracial general population. METHODS AND RESULTS: Participants of the ARIC (Atherosclerosis Risk in Communities) study with an ABI measurement between 1987 and 1989 were included. ABI was categorized as low (≤0.90), borderline (0.90-1.00), normal (1.00-1.40), and noncompressible (>1.40). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual and was adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Cox proportional hazards models were used to evaluate the associations between baseline ABI and incident SCD. Of the 15 081 participants followed for a median of 23.5 years, 556 (3.7%) developed SCD (1.96 cases per 1000 person-years). Low and borderline ABIs were associated with an increased risk of SCD (demographically adjusted hazard ratios [HRs], 2.27 [95% CI, 1.64-3.14] and 1.52 [95% CI, 1.17-1.96], respectively) compared with normal ABI. The association between low ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors (HR, 1.63 [95% CI, 1.15-2.32]). CONCLUSIONS: Low ABI is independently associated with an increased risk of SCD in a middle-aged biracial general population. ABI could be incorporated into future SCD risk prediction models.

Polygenic Scores and Preclinical Cardiovascular Disease in Individuals With HIV: Insights From the REPRIEVE Trial.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death among the 38.4 million people with HIV globally. The extent to which cardiovascular polygenic risk scores (PRSs) derived in non-HIV populations generalize to people with HIV is not well understood. METHODS AND RESULTS: PRSs for CAD (GPSMult) and lipid traits were calculated in a global cohort of people with HIV treated with antiretroviral therapy with low-to-moderate atherosclerotic cardiovascular disease risk enrolled in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV). The PRSs were associated with baseline lipid traits in 4495 genotyped participants, and with subclinical CAD in a subset of 662 who underwent coronary computed tomography angiography. Among participants who underwent coronary computed tomography angiography (mean age, 50.9 [SD, 5.8] years; 16.1% women; 41.8% African, 57.3% European, 1.1% Asian), GPSMult was associated with plaque presence with odds ratio (OR) per SD in GPSMult of 1.42 (95% CI, 1.20-1.68; P=3.8×10-5), stenosis >50% (OR, 2.39 [95% CI, 1.48-3.85]; P=3.4×10-4), and noncalcified/vulnerable plaque (OR, 1.45 [95% CI, 1.23-1.72]; P=9.6×10-6). Effects were consistent in subgroups of age, sex, 10-year atherosclerotic cardiovascular disease risk, ancestry, and CD4 count. Adding GPSMult to established risk factors increased the C-statistic for predicting plaque presence from 0.718 to 0.734 (P=0.02). Furthermore, a PRS for low-density lipoprotein cholesterol was associated with plaque presence with OR of 1.21 (95% CI, 1.01-1.44; P=0.04), and partially calcified plaque with OR of 1.21 (95% CI, 1.01-1.45; P=0.04) per SD. CONCLUSIONS: Among people with HIV treated with antiretroviral therapy without documented atherosclerotic cardiovascular disease and at low-to-moderate calculated risk in REPRIEVE, an externally developed CAD PRS was predictive of subclinical atherosclerosis. PRS for low-density lipoprotein cholesterol was also associated with subclinical atherosclerosis, supporting a role for low-density lipoprotein cholesterol in HIV-associated CAD. REGISTRATION: URL: https://www.reprievetrial.org; Unique identifier: NCT02344290.

Connections between Cognitive Impairment and Atrial Fibrillation in Patients with Diabetes Mellitus Type 2.

(1) Background: Cognitive decline (CD), considered a precursory state of dementia, is frequently encountered in patients with diabetes mellitus type 2 (DM-2) and might even have a higher prevalence in those with associated atrial fibrillation (AF). In this study, we aimed to research if the association of DM-2 and AF favors a precocious onset of CD. (2) Methods: This study was conducted on 160 patients, featuring 50 with DM-2, 54 with DM-2 and AF, and 56 subjects without DM-2 and AF, all evaluated clinically and with five neuropsychiatric scales. (3) Results: The Mini-Mental-State-Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living Score (ADL), Instrumental Activities of Daily Living Score (IADL), and Geriatric Depression Scale (GDS-15) were significantly altered in patients with DM-2 and AF in comparison to patients without these diseases. The logistic regression model indicated that, in patients with DM-2 and AF, an increase of one year in age is associated with a 7.3% augmentation of the risk of a precocious onset of CD (MMSE < 27). (4) Conclusions: CD is more frequent in patients with DM-2, especially when associated with AF, versus those without DM-2 and AF. Our findings suggest that an older age and associated dyslipidemia represent risk factors for CD in patients with DM-2.

Predicting the risk of subclinical atherosclerosis based on interpretable machine models in a Chinese T2DM population.

Background: Cardiovascular disease (CVD) has emerged as a global public health concern. Identifying and preventing subclinical atherosclerosis (SCAS), an early indicator of CVD, is critical for improving cardiovascular outcomes. This study aimed to construct interpretable machine learning models for predicting SCAS risk in type 2 diabetes mellitus (T2DM) patients. Methods: This study included 3084 T2DM individuals who received health care at Zhenhai Lianhua Hospital, Ningbo, China, from January 2018 to December 2022. The least absolute shrinkage and selection operator combined with random forest-recursive feature elimination were used to screen for characteristic variables. Linear discriminant analysis, logistic regression, Naive Bayes, random forest, support vector machine, and extreme gradient boosting were employed in constructing risk prediction models for SCAS in T2DM patients. The area under the receiver operating characteristic curve (AUC) was employed to assess the predictive capacity of the model through 10-fold cross-validation. Additionally, the SHapley Additive exPlanations were utilized to interpret the best-performing model. Results: The percentage of SCAS was 38.46% (n=1186) in the study population. Fourteen variables, including age, white blood cell count, and basophil count, were identified as independent risk factors for SCAS. Nine predictors, including age, albumin, and total protein, were screened for the construction of risk prediction models. After validation, the random forest model exhibited the best clinical predictive value in the training set with an AUC of 0.729 (95% CI: 0.709-0.749), and it also demonstrated good predictive value in the internal validation set [AUC: 0.715 (95% CI: 0.688-0.742)]. The model interpretation revealed that age, albumin, total protein, total cholesterol, and serum creatinine were the top five variables contributing to the prediction model. Conclusion: The construction of SCAS risk models based on the Chinese T2DM population contributes to its early prevention and intervention, which would reduce the incidence of adverse cardiovascular prognostic events.

Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged adults.

AIMS: Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. METHODS: A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrollment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed, and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). RESULTS: On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 (OR for 3rd tertile, 8.31; 95% CI 2.85-24.2; p<0.001; and 2.77; 95% CI, 1.02-7.51; p=0.045, respectively) and provided significant incremental diagnostic value over SCORE2. CONCLUSIONS: In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures.

Prevalence and Burden of Carotid and Femoral Atherosclerosis in Subjects Without Known Cardiovascular Disease in a Large Community Hospital in South-America.

INTRODUCTION: Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD). AIM: To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD. METHODS: We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries. RESULTS: Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF. CONCLUSIONS: We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA.

Ultrasound screening for abdominal aortic aneurysm in primary care. / Utilidad de la ecografía en el cribado del aneurisma de aorta abdominal en atención primaria.

INTRODUCTION: Abdominal aortic aneurysm (AAA) constitutes a pathology with high mortality. There is currently no screening program implemented in primary care in Spain. OBJECTIVES: To evaluate the usefulness of ultrasound in the detection of AAA in the at-risk population in primary care. Secondarily, to identify subjects whose vascular risk (VR) should be reclassified and to determine whether AAA is associated with the presence of carotid plaque and other risk factors. MATERIAL AND METHODS: Cross-sectional, descriptive, multicenter, national, descriptive study in primary care. SUBJECTS: A consecutive selection of hypertensive males aged between 65 and 75 who are either smokers or former smokers, or individuals over the age of 50 of both sexes with a family history of AAA. MEASUREMENTS: Diameter of abdominal aorta and iliac arteries; detection of abdominal aortic and carotid atherosclerotic plaque. VR was calculated at the beginning and after testing (SCORE). RESULTS: One hundred and fifty patients were analyzed (age: 68.3±5 years; 89.3% male). Baseline RV was high/very high in 55.3%. AAA was detected in 12 patients (8%; 95% CI: 4-12); aortic ectasia in 13 (8.7%); abdominal aortic plaque in 44% and carotid plaque in 62% of the participants. VR was reclassified in 50% of subjects. The detection of AAA or ectasia was associated with the presence of carotid plaque, current smoking and lipoprotein(a), p<0.01. CONCLUSIONS: The prevalence of AAA in patients with VR is high. Ultrasound in primary care allows detection of AAA and subclinical atherosclerosis and consequently reclassification of the VR, demonstrating its utility in screening for AAA in the at-risk population.

Screening for Subclinical Atherosclerosis and the Prediction of Cardiovascular Events in People with Type 1 Diabetes.

People with type 1 diabetes (T1D) have a high cardiovascular disease (CVD) risk, which remains the leading cause of death in this population. Despite the improved control of several classic risk factors, particularly better glycaemic control, cardiovascular morbidity and mortality continue to be significantly higher than in the general population. In routine clinical practice, estimating cardiovascular risk (CVR) in people with T1D using scales or equations is often imprecise because much of the evidence comes from pooled samples of people with type 2 diabetes (T2D) and T1D or from extrapolations of studies performed on people with T2D. Given that T1D onsets at a young age, prolonged exposure to the disease and its consequences (e.g., hyperglycaemia, changes in lipid metabolism or inflammation) have a detrimental impact on cardiovascular health. Therefore, it is critical to have tools that allow for the early identification of those individuals with a higher CVR and thus be able to make the most appropriate management decisions in each case. In this sense, atherosclerosis is the prelude to most cardiovascular events. People with diabetes present pathophysiological alterations that facilitate atherosclerosis development and that may imply a greater vulnerability of atheromatous plaques. Screening for subclinical atherosclerosis using various techniques, mainly imaging, has proven valuable in predicting cardiovascular events. Its use enables the reclassification of CVR and, therefore, an individualised adjustment of therapeutic management. However, the available evidence in people with T1D is scarce. This narrative review provides and updated overview of the main non-invasive tests for detecting atherosclerosis plaques and their association with CVD in people with T1D.

Association of Anthropometric and CT-Based Obesity Indices with Subclinical Atherosclerosis.

AIM: Few studies have compared the strength in the associations of anthropometric and computed tomography (CT)-based obesity indices with coronary artery calcification (CAC), aortic artery calcification (AoAC), and aortic valve calcification (AVC). METHODS: We assessed cross-sectcional associations of anthropometric and CT-based obesity indices with CAC, AoAC, and AVC. Anthropometric measures included body mass index (BMI), waist circumference, hip ircumference, waist-to-hip circumference ratio, and waist-to-height ratio in 931 men (mean age, 63.7 years) from a population-based cohort. CT images at the L4/5 level were obtained to calculate the areas of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), VAT-to-SAT ratio (VSR), and VAT-to-TAT ratio (VTR). CAC, AoAC, and AVC were quantified using the Agatston score based on CT scanning. RESULTS: CAC, AVC, and AoAC were present in 348 (62.6%), 173 (18.6%), and 769 (82.6%) participants, respectively. In multivariable models adjusting for age, lifestyle factors, and CT types (electron beam CT and multidetector row CT), anthropometric and CT-based obesity indices were positively associated with CAC (p＜0.01). Conversely, VAT-to-SAT ratio and VAT-to-TAT ratio were positively associated with AoAC (p＜0.01). Any obesity indices were not associated with AVC. CONCLUSIONS: The strength of the associations of obesity indices with subclinical atherosclerosis varied according to the anatomically distinct atherosclerotic lesions, among men.

Evaluation of subclinical cardiovascular risk in drug-naive pediatric patients with anxiety disorders.

OBJECTIVE: This study examined subclinical atherosclerosis in drug-naïve children with anxiety disorders using non-invasive measures to investigate the clinical features associated with subclinical atherosclerosis. METHOD: A total of 37 drug-naive children and adolescents with anxiety disorders and 37 healthy controls were included in the study. The Children's Depression Inventory (CDI) and the State-Trait Anxiety Inventory (STAI-T and STAI-S) were used to assess children's depression and anxiety levels. Carotid artery intima-media (cIMT), epicardial adipose tissue (EAT), and periaortic adipose tissue (PAT) thicknesses, which are indicators of subclinical atherosclerosis, were obtained by echocardiographic measurements. RESULTS: Multivariate analysis of covariance (MANCOVA) revealed a significant main effect on cIMT, EAT thickness, and PAT thickness, independent of confounding factors such as age, sex, body mass index, mean blood pressure, and family income (Pillai's Trace V = .76, F (1, 72) = 35.60, P < .001, ηp2 = .76). Analysis of covariance (ANCOVA) showed that cIMT, EAT thickness, and PAT thickness values were significantly higher in the anxiety disorder group compared to the the control group (P < .001). In partial correlation analysis, a positive correlation was observed between STAI-T and cIMT and EAT thickness. In linear regression analyses, age and STAI-T were significantly correlated with cIMT and EAT thickness levels. CONCLUSIONS: These results suggest that subclinical cardiovascular risk is significantly increased in children and adolescents with anxiety disorders.

The impact of diabetes and subclinical hypothyroidism association with coronary artery calcium: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: We aimed to analyze the association of diabetes and subclinical hypothyroidism with subclinical atherosclerosis measured by coronary artery calcium (CAC) in the baseline of the ELSA-Brasil study. Materials and methods: CAC was measured using a 64-detector computed tomographic scanner. The association of CAC > 0 was presented as an odds ratio (OR) and 95% confidence intervals (95%CI) in logistic models and as β (95%CI) in linear models after multivariable adjustment for confounders. Results: We analyzed 3,809 participants (mean-age (SD) 50.5 (8.8); 51.7% women). In the main analysis, we did not find an association of diabetes and subclinical hypothyroidism with CAC. However, in stratified analysis according to age strata, we found no significative interaction terms, an important heterogeneity between the groups, with the younger age strata showing an association of the group with both diseases and CAC > 0 (OR 7.16; 95%CI, 1.14; 44.89) with a wide but significative 95%CI, suggesting that the smaller number of participants in the younger group may influence the results. Our findings also showed an association of CAC > 0 and log (CAC+1) with diabetes in logistic (OR, 1.31; 95%CI, 1.05-1.63) and linear models (β, 0.24, 0.16, 0.40), respectively. Diabetes was independently associated with CAC > 0 in linear models. Discussion: In conclusion, our results showed a great heterogeneity in stratified analysis based on age in the younger age strata. Although we found no significant interaction factors, the smaller sample size for the analysis may influence the negative findings.

Cumulative Blood Pressure in Early Adulthood and Coronary Artery Calcium and Carotid Intima-Media Thickness in Middle Age Among Adults With Maintained Blood Pressure of <130/80 mm Hg: A Post Hoc Analysis.

BACKGROUND: To examine the association of blood pressure (BP) levels with coronary artery calcium and carotid intima-media thickness (CIMT) in people with maintained BP below the hypertension range based on current definitions. METHODS AND RESULTS: In this post hoc analysis of the CARDIA (Coronary Artery Risk Development in Young Adults) prospective observational cohort study conducted in 4 US cities, we examined 1233 study participants (mean [SD] age at year 20 examination was 45.3 [3.5] years; 65.4% women). Participants with BP assessments across 20 years and untreated BP of <130/80 mm Hg were included. Multivariable logistic or linear regression models, adjusted for age, sex, race, education, diabetes, body mass index, serum creatinine, smoking, alcohol intake, physical activity, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides, were used to examine the associations between cumulative BP measures with coronary artery calcium and CIMT. Higher long-term cumulative systolic BP and pulse pressure across early adulthood were associated with higher CIMT (both P<0.001) but not coronary artery calcium in the multivariable-adjusted model. The associations remained significant even after adjustment for a single BP measurement at year 0 or year 20. The odds ratio (OR) of a maximal CIMT >1.01 mm was ≈50% higher per 1-SD increase in systolic BP (OR, 1.50 [95% CI, 1.19-1.88]) and pulse pressure (OR, 1.46 [95% CI, 1.19-1.79]). Similar findings for CIMT were observed among individuals with a coronary artery calcium score of 0 as well as those with maintained BP of <120/80 mm Hg throughout young adulthood. CONCLUSIONS: Long-term cumulative systolic BP and pulse pressure across early adulthood within the nonhypertensive range were associated with adverse midlife alterations in CIMT.

Association of carotid wall shear stress measured by vector flow mapping technique with ba-PWV: a pilot study.

Objective: Arterial stiffness is an important tissue biomarker of the progression of atherosclerotic diseases. Brachial-ankle pulse wave velocity (ba-PWV) is a gold standard of arterial stiffness measurement widely used in Asia. Changes in vascular wall shear stress (WSS) lead to artery wall remodeling, which could give rise to an increase in arterial stiffness. The study aimed to explore the association between ba-PWV and common carotid artery (CCA) WSS measured by a newly invented vascular vector flow mapping (VFM) technique. Methods: We included 94 subjects free of apparent cardiovascular disease (CVD) and divided them into a subclinical atherosclerosis (SA) group (N = 47) and non subclinical atherosclerosis (NSA) group (N = 47). CCA WSS was measured using the VFM technique. Bivariate correlations between CCA WSS and other factors were assessed with Pearson's, Spearman's, or Kendall's coefficient of correlation, as appropriate. Partial correlation analysis was conducted to examine the influence of age and sex. Multiple linear stepwise regression was used for the analysis of independent determinants of CCA WSS. Receiver operating characteristic (ROC) analysis was performed to find the association between CCA WSS and 10-year CVD risk. Results: The overall subjects had a mean age of 47.9 ± 11.2 years, and males accounted for 52.1%. Average systolic CCA WSS was significantly correlated with ba-PWV (r = -0.618, p < 0.001) in the SA group. Multiple linear stepwise regression analysis confirmed that ba-PWV was an independent determinant of average systolic CCA WSS (ß = -0.361, p = 0.003). The area under the curve (AUC) of average systolic CCA WSS for 10-year CVD risk ≥10% was 0.848 (p < 0.001) in the SA group. Conclusions: Average systolic CCA WSS was significantly correlated with ba-PWV and was associated with 10-year CVD risk ≥10% in the SA group. Therefore, CCA WSS measured by the VFM technique could be used for monitoring and screening subjects with potential CVD risks.

Association of cardiorespiratory fitness level with vascular function and subclinical atherosclerosis in the elderly.

PURPOSE: Physical exercise is crucial for healthy aging and plays a decisive role in the prevention of atherosclerotic cardiovascular disease (ASCVD). A higher level of cardiorespiratory fitness (CRF) in the elderly is associated with lower cardiovascular and all-cause mortality. This study investigated the association of CRF level with vascular function and cardiovascular risk factors in the elderly. METHODS: We examined 79 apparently healthy and physically active subjects aged > 55 years (64 ± 4 years). Cardiovascular functional parameters assessed included brachial and central blood pressure (BP), pulse wave velocity (PWV), augmentation index (Aix), and ankle-brachial index. Sonography of the common carotid artery was performed. CRF level was determined by a cardiopulmonary exercise test, and everyday activity was quantified with an accelerometer. RESULTS: All participants had a higher CRF level than the reported age-specific normative values. Twenty-nine subjects had subclinical atherosclerosis of the common carotid artery. Compared with participants without atherosclerosis, they were older (p = 0.007), displayed higher brachial systolic BP (p = 0.006), and higher central systolic BP (p = 0.014). Lower brachial (p = 0.036) and central (p = 0.003) systolic BP, lower PWV (p = 0.004), lower Aix (p < 0.001), lower body fat percentage (< 0.001), and lower LDL cholesterol (p = 0.005) were associated with a higher CRF level. CONCLUSIONS: In this cohort of healthy and physically active individuals, subjects with subclinical atherosclerosis displayed higher systolic brachial and central BP. A higher CRF level was associated with enhanced vascular function, consistent with an influence of CRF on both BP and vascular function in the elderly.

DNA Methylation of the IL-17A Gene Promoter Is Associated with Subclinical Atherosclerosis and Coronary Artery Disease: The Genetics of Atherosclerotic Disease Mexican Study.

The interleukin-17 (IL-17) has a crucial role during inflammation and has been associated with cardiovascular diseases, but its role in epigenetics is still poorly understood. Therefore, the aim of this study was to evaluate the DNA methylation status of the IL-17A gene promoter to establish whether it may represent a risk factor for subclinical atherosclerosis (SA) or clinical coronary artery disease (CAD). We included 38 patients with premature CAD (pCAD), 48 individuals with SA, and 43 healthy controls. Methylation in the CpG region of the IL-17A gene promoter was assessed via methylation-specific polymerase chain reaction (MSP). Individuals with SA showed increased methylation levels compared to healthy controls and pCAD patients, with p < 0.001 for both. Logistic regression analysis showed that high methylation levels represent a significant risk for SA (OR = 5.68, 95% CI = 2.38-14.03, p < 0.001). Moreover, low methylation levels of the IL-17A gene promoter DNA represent a risk for symptomatic pCAD when compared with SA patients (OR = 0.16, 95% CI = 0.06-0.41, p < 0.001). Our data suggest that the increased DNA methylation of the IL-17A gene promoter is a risk factor for SA but may be a protection factor for progression from SA to symptomatic CAD.

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques, levels of LDL, and cardiorespiratory fitness in the elderly.

BACKGROUND: Atherosclerosis forms the pathological basis for the development of cardiovascular disease. Since pathological processes initially develop without clinically relevant symptoms, the identification of early markers in the subclinical stage plays an important role for initiating early interventions. There is evidence that regulatory T cells (Tregs) are involved in the development of atherosclerosis. Therefore, the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques (SAP). In addition, various lifestyle and risk factors, such as cardiorespiratory fitness, were investigated as associated signatures. METHODS: A cross-sectional study was performed in 79 participants (male: n = 50; age = 63.6 ± 3.7 years; body mass index = 24.9 ± 3.1 kg/m²; mean ± SD) who had no previous diagnosis of chronic disease and were not taking medication. Ultrasound of the carotids to identify SAP, cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed. Additionally, tests were conducted to assess blood lipids and determine glucose levels. Immunophenotyping of Tregs and their subtypes (resting (rTregs) and effector/memory (mTregs)) was performed by 8-chanel flow cytometry. Participants were categorized according to atherosclerotic plaque status. Linear and logistic regression models were used to analyze associations between parameters. RESULTS: SAP was detected in a total of 29 participants. The participants with plaque were older (64.5 ± 3.6 years vs. 62.9 ± 3.5 years) and had higher peripheral systolic blood pressure (133.8 ± 14.7 mmHg vs. 125.8 ± 10.9 mmHg). The participants with SAP were characterized by a lower percentage of rTregs (28.8% ± 10.7% vs. 34.6% ± 10.7%) and a higher percentage of mTregs (40.3% ± 14.7% vs. 30.0% ± 11.9%). Multiple logistic regression identified age (odds ratio (OR) = 1.20 (95% confidence interval (95%CI): 1.01-1.42)) and mTregs (OR = 1.05 (95%CI: 1.02-1.10)) as independent risk factors for SAP. Stepwise linear regression could reveal an association of peak oxygen uptake (ß = 0.441), low-density lipoprotein (LDL) (ß = -0.096), and SAP (ß = 6.733) with mTregs and LDL (ß = 0.104) with rTregs. CONCLUSION: While at an early stage of SAP, the total proportion of Tregs gives no indication of vascular changes, this is indicated by a shift in the Treg subgroups. Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators. This could be used to initiate lifestyle-based preventive measures at an early stage, which may have a protective effect against disease progression.

Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years.

BACKGROUND: Atherosclerosis is a systemic disease that frequently begins early in life. However, knowledge about the temporal disease dynamics (ie, progression or regression) of human subclinical atherosclerosis and their determinants is scarce. OBJECTIVES: This study sought to investigate early subclinical atherosclerosis disease dynamics within a cohort of middle-aged, asymptomatic individuals by using multiterritorial 3-dimensional vascular ultrasound (3DVUS) imaging. METHODS: A total of 3,471 participants from the PESA (Progression of Early Subclinical Atherosclerosis) cohort study (baseline age 40-55 years; 36% female) underwent 3 serial 3DVUS imaging assessments of peripheral arteries at 3-year intervals. Subclinical atherosclerosis was quantified as global plaque volume (mm3) (bilateral carotid and femoral plaque burden). Multivariable logistic regression models for progression and regression were developed using stepwise forward variable selection. RESULTS: Baseline to 6-year subclinical atherosclerosis progression occurred in 32.7% of the cohort (17.5% presenting with incident disease and 15.2% progressing from prevalent disease at enrollment). Regression was observed in 8.0% of those patients with baseline disease. The effects of higher low-density lipoprotein cholesterol (LDL-C) and elevated systolic blood pressure (SBP) on 6-year subclinical atherosclerosis progression risk were more pronounced among participants in the youngest age stratum (Pinteraction = 0.04 and 0.02, respectively). CONCLUSIONS: Over 6 years, subclinical atherosclerosis progressed in one-third of middle-age asymptomatic subjects. Atherosclerosis regression is possible in early stages of the disease. The impact of LDL-C and SBP on subclinical atherosclerosis progression was more pronounced in younger participants, a finding suggesting that the prevention of atherosclerosis and its progression could be enhanced by tighter risk factor control at younger ages, with a likely long-term impact on reducing the risk of clinical events. (Progression of Early Subclinical Atherosclerosis [PESA; also PESA-CNIC-Santander]; NCT01410318).