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Purpose: Cardiovascular risk factors are widespread among children and adolescents and may lead to accelerated vascular aging in middle adulthood. However, data are scarce on shorter-term consequences, for example, on associated distinctive vascular properties before age 30 years. This study analyzes the association of childhood exposure to cardiovascular risk factors with carotid properties in adolescents and young adults., Methods: Four thousand thirty one participants from the population-based German Health Interview and Examination Survey for Children and Adolescents cohort (aged 3-17 years) had carotid intima-media thickness (CIMT) and distensibility coefficient (DC) measurements at the second follow-up (aged 14-28 years). The assessment of cardiovascular risk factors at baseline included information about arterial hypertension, obesity, dyslipidemia, and passive smoking., Results: Single risk factors and the exposure to multiple cardiovascular risk factors were associated with elevated CIMT and decreased DC. Relative risks for CIMT ≥ 90th centile and/or DC ≤ 10th centile were increased in participants exposed to two (RR CIMT  = 1.45 [95% confidence interval 1.11-1.91], p < .05; RR DC  = 1.37 [1.02-1.84], p < .05) and ≥ three risk factors (RR CIMT  = 1.66 [1.05-2.62], p < .05; RR DC  = 1.25 [0.71-2.21], p > .05)., Discussion: Exposure to multiple cardiovascular risk factors starting in childhood is associated with measurably increased CIMT and carotid stiffness in late adolescence and early adulthood. These findings underline the importance of population-wide preventive measures to promote optimal cardiovascular health., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The association of childhood blood pressure (BP) and heart rate (HR) with intermediate markers of cardiovascular disease several decades later has been shown, but studies on more short-term outcomes are scarce. Using population-based data, this study investigates the association of four BP parameters and HR in childhood with three carotid markers for vascular remodeling one decade later., Methods: At the 11-year follow-up, 4607 participants of the nationwide KiGGS cohort aged 14 to 28 years had semi-automated sonographic carotid intima media thickness (CIMT) measurements. We investigated associations of baseline (age 3-17 years) and follow-up SBP, DBP, mean arterial pressure (MAP), pulse pressure (PP) and resting heart rate (RHR), with CIMT and lumen diameter at or above the 90th percentile and distensibility coefficient at or below the tenth percentile in logistic regressions. Analyses were further adjusted using a composite cardiovascular risk (CVR) score of BMI, triglycerides, total/HDL-cholesterol-ratio and HbA1c., Results: SBP, DBP, MAP and RHR were significantly and similarly associated with all carotid measures 11 years later, for example an odds ratio (OR) of 1.17 [confidence interval (CI) 1.06-1.29] for one standard deviation SBP increase with elevated CIMT when adjusting for sex, age and CVR score. Cross-sectionally, the strongest association was found for MAP with reduced distensibility coefficient (OR 1.76; CI 1.59-1.94)., Conclusion: This population-based cohort study shows robust and consistent associations between childhood BP and RHR and three carotid measures of vascular remodeling only one decade later, clearly underscoring the potential importance of preventing high BP already early in the life course., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

No lifestyle-based interventions with medium-term duration on carotid atherosclerotic have been performed so far. We aimed to investigate whether guideline-based dietary and physical activity interventions slow the progression of atherosclerotic changes in the general elderly population. 1410 Finnish men and women from a representative population sample were randomly assigned to one of six groups in the four-year intervention study: 1) reference, 2) aerobic training, 3) resistance training, 4) Nordic Diet, 5) aerobic training + Nordic Diet, 6) resistance training + Nordic Diet. The primary outcome was mean common carotid artery intima-media thickness (cIMT). The lumen diameter of the common carotid artery (cLD) was also analyzed. 567 men and 565 women aged 57 to 78 years were included. None of the intervention groups significantly slowed cIMT progression compared to the reference group. A subgroup analysis showed that men in the diet group had significantly smaller cIMT progression than in the reference group (-0.078 mm, 95% CI: -0.146 to -0.009, p = 0.02) and no significant increase in cIMT (p = 0.23). No other group showed a slowed cIMT progression. Among guideline-based lifestyle interventions, only diet leads to a significantly smaller progression of cIMT in older men of a representative population sample. No other lifestyle intervention contributed to a slowing of the progression of structural carotid markers. It must be questioned whether the guideline-based recommendations for a lifestyle change that were in place until recently are adequate to decelerate the atherosclerotic process., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular health scores, such as Life's Simple 7 from the American Heart Association, and the assessment of arterial properties are independently used to determine cardiovascular risk. However, evidence of their association remains scarce, especially in healthy, middle-aged to older populations., Methods: A healthy sample of the Swiss population aged 50-91 years as part of the COmPLETE cohort study was included. Carotid intima-media thickness (cIMT), carotid lumen diameter (cLD), carotid distensibility coefficient (DC), flow-mediated dilation (FMD), and brachial-ankle pulse wave velocity (baPWV) were used to determine arterial properties. The Life's Simple 7 cardiovascular health score was calculated using seven categories (body-mass index, cholesterol, systolic blood pressure, hemoglobin A1c, smoking status, physical activity, and diet). In accordance with the American Heart Association, for each category, two points were given for an ideal health metric level, intermediate scores one point, and poor scores zero points. Intermediate and ideal health scores corresponded to a total of 5-9 and 10-14 points, respectively., Results: A total of 280 participants (50.7% male) were included. After adjusting for age and sex, an ideal health score was associated with lower cIMT (-0.038 mm, 95% CI: -0.069 mm--0.007 mm, p = 0.017), lower cLD (-0.28 mm, 95% CI: -0.46 mm--0.11 mm, p = 0.002), and lower baPWV (-0.05 m/s, 95% CI: -0.08 m/s--0.02 m/s, p = 0.003). No differences were found for FMD and DC., Conclusions: Even in a healthy sample of middle-aged and older adults, individuals with an ideal cardiovascular health score showed more favorable biomarkers of vascular aging than those with an intermediate score. This stresses the relevance of promoting an optimal lifestyle, even among the healthy population.

Background: This study aimed to derive carotid intima media thickness (CIMT) percentiles from a population-based sample of adolescents and young adults using improved technology, standardization and quality control, and to investigate the association of CIMT with hypertensive blood pressure (BP) and obesity., Methods: Four thousand seven hundred nine 14- to 28-year-old participants of the German KiGGS cohort 11-year follow-up, which was based on a nationwide population sample, had B-mode ultrasound CIMT measurement with semi-automated edge-detection and automatic ECG-gated real-time quality control. CIMT percentiles were estimated from far wall CIMT during 2 to 6 heart cycles using the GAMLSS statistical model. Hypertensive BP, overweight, obesity, and a risk score from added Z scores of triglycerides, total/HDL (high-density lipoprotein)-cholesterol ratio, and glycated hemoglobin were based on standardized measurements at baseline and follow-up., Results: CIMT differed by sex at all ages, furthermore by age and height in a nonlinear fashion. Percentiles were estimated simultaneously by age and height. Hypertensive BP and obesity were associated cross-sectionally and longitudinally with a higher risk of CIMT ≥75th percentile in log-binomial regression models adjusted for age, sex, height, current smoking, and cardiovascular risk score. For CIMT ≥90th percentile, the relative risk effect estimates were consistently >1 but often had large confidence intervals including 1, largest adjusted relative risk 3.37 (95% CI, 1.41-8.04) for the combination of hypertensive BP and obesity at follow-up., Conclusions: Based on state-of-the-art measurements and statistical techniques, these population-based CIMT percentiles by sex, age and height add unbiased evidence for the association of subclinical atherosclerosis with hypertensive BP and obesity in the young.

Carotid intima-media thickness (cIMT) and carotid stiffness (CS) are important markers of atherosclerotic risk in the young. We assessed a novel third-generation method for its applicability in large population-based epidemiologic studies to determine strengths, limitations, completeness and predictors of unsuccessful measurement. Four thousand seven hundred ninety-eight 14- to 31-y-old participants of the German KiGGS cohort, which is based on a nationally representative sample with 11-y follow-up, underwent B-mode ultrasound examinations of the left and right common carotid artery with semi-automatic edge detection and automatic electrocardiogram-gated real-time quality control based on a sophisticated snake algorithm and subpixel interpolation. Overall completeness was 98% for far wall cIMT and 89% for CS parameters. Plane-specific completeness varied from 92%-96% for far wall and from 64%-69% for near-wall cIMT. Obesity independently predicted unsuccessful cIMT and CS measurements with odds ratios of 12.67 (95% confidence interval: 5.50-29.19) and 7.30 (4.87-10.94) compared with non-overweight after adjustment for blood pressure, cholesterol, smoking, hazardous drinking, age, sex and sonographer. Inter- and intra-rater reliabilities of cIMT and CS parameters in a sample of 15 young adults were good or excellent. Third-generation cIMT and CS measurements in the young with semi-automatic edge-detection and automatic real-time quality control has been successfully standardized with high reliability and very high completeness in a national survey setting. This provides a strong methodological foundation for further validation of the predictive value of cIMT and CS for atherosclerotic risk in the young., Competing Interests: Conflict of interest disclosure The authors report no conflicts of interest., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Respiratory diseases are associated with increased cardiovascular risk in adults, but little is known on the early impact on the vasculature in youth. The SAPALDIA Youth study, the offspring study of the Swiss Study on Air Pollution and Lung and Heart Disease In Adults (SAPALDIA), investigated the association between physician-diagnosed asthma status and common carotid artery intima media thickness (CIMT). Offspring underwent standardized clinical protocols and provided information on early life factors, health, and lifestyle. The association between per subject averages of CIMT and asthma was estimated using mixed linear regression analyses adjusting for main confounders, testing for interaction with gender and age. Of 257 offspring (mean age 15 years, 53% female), 11.5% reported doctor-diagnosed asthma (male 17%, female 7%). Mean CIMT was significantly different by gender (male 0.53 mm (± 0.045), female 0.50 mm (± 0.048); p < 0.001). Interaction was highly significant by gender (p = 0.001) with significantly increased CIMT in asthmatic vs. non-asthmatics boys (difference 0.023 mm, 95% CI 0.003; 0.043), as compared to girls., Conclusion: Our study suggests an increased risk for early vascular change in adolescent asthmatic boys. Whereas the small number of girls limits the interpretation, the result necessitates further research into sex-specific atherosclerotic burden related to respiratory health in adolescence. What is Known: • Evidence points to a significant impact of adult respiratory disease on cardiovascular health indicators as well as on endpoints. • Inflammation is a key pathway in vascular change across the life course. What is New: • We observe an adverse association between physician-diagnosed asthma and carotid intima media thickness in adolescent boys. • Albeit a limited number of asthmatic girls, we hypothesize the gender typical timing of asthma or a higher male cardiovascular vulnerability as possible explanations for the gender-specific results.

Background and Aims: Subclinical atherosclerosis assessed by sonographic intima-media-thickness measurement of the carotid artery (cIMT) is considered to be an early precursor of cardiovascular disease already in childhood. Structural analysis of the carotid intimal layer (carotid intima-media-roughness, cIMR) improves cardiovascular risk profiling for the adult patient and has been shown to be increased also in paediatric patients with elevated cardiovascular risk. To date, normal values for the paediatric age are lacking. Thus, we present normative data for a paediatric age group., Methods: 602 healthy German school children (age 8-18 y) were studied, and cIMT and cIMR calculated; reference values were given for three age groups (group 1: 8-10.99 years; group 2: 11-13.99 years; group 3: 14-17.99 years)., Results: cIMT values were: 0.48 ± 0.03 mm for girls and boys in age group 1, 0.49 ± 0.03 mm for girls and boys in age group 2; and 0.45 ± 0.03 mm for girls and 0.49 ± 0.03 mm for boys in age group 3; cIMR was 0.04 ± 0.01 mm for both sexes in age group 1 and 3; while in age group 2, both sexes showed a cIMR of 0.03 ± 0.01 mm. Physical fitness was significantly negatively correlated with cIMR (r = - 0.212, p < 0.0001) and a strong predictor for cIMR increase., Conclusions: The normative data of cIMR for a paediatric age group presented here allow for the identification of patients at elevated cardiovascular risk. By including cIMR as surface analysis of the arterial wall, the individual risk stratification may be improved compared to thickness-analysis of the Intima-Media-Layer (cIMT) also at a paediatric age., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objective: Inflammatory risk factors in childhood, e.g. obesity, impact on carotid artery intima media thickness (CIMT), an early indicator of atherosclerosis. Little is known on potential infectious origins in childhood. We investigated the association between number of reported different childhood infectious diseases and CIMT in adolescence., Study Design: 288 SAPALDIA offspring (8-21years) underwent a clinical examination in 2010-2011: anthropometry, blood pressure, CIMT, blood draw (cardiovascular biomarkers, cotinine). Offspring and parents gave information on individuals' and family health, child's vaccination status, infectious diseases and other early life factors. Life-time prevalence of bronchitis, pneumonia, tonsillitis, otitis, mononucleosis, meningitis, appendicitis, and scarlet fever were investigated, separately, and as cumulative infectious disease score. Multilevel adjusted linear regression analysis on the association between subjects' CIMT average and infectious diseases score was performed, stratifying by sex., Results: Youth (mean age 14.8 yrs; 53% female) reported on average 1.3 of the listed infectious diseases; 22% boys and 15% girls reported ≥3 infectious diseases (p = 0.136). Two-thirds were vaccinated according to recommendations (boys 56%, girls 61.5%, p = 0.567). Sex-stratified analyses yielded significantly increased CIMT in boys with ≥3 infectious diseases vs. none (0.046 mm, 95%CI 0.024; 0.068). In girls, the effect was of same direction but statistically non-significant (0.011 mm, 95%CI -0.015; 0.036)., Conclusion: The SAPALDIA Youth study complements current evidence on infectious origins of atherosclerosis in adults. The larger effects observed in boys may relate to a higher vulnerability of the vasculature and/or to infectious pathogens. Our data are suggestive of an early impact of childhood infectious diseases on vascular health., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Questions Under Study: As the burden of cardiovascular disease (CVD) increases globally, its prevention and risk assessment becomes ever more important. We thus investigated the longitudinal association of the cardiovascular risk scores in the population-based cohort SAPALDIA with carotid intima media thickening (CIMT), an indicator of sub-clinical disease, and CVD incidence., Methods: In 2,832 SAPALDIA participants, the Swiss and ESC heart risk score (AGLA, SCORE) were calculated based on 2001 data and CIMT was measured in 2010/11. We ran multi-level linear regression analyses between scores and CIMT, stratified for CVD status and gender, and logistic analyses for doctor-diagnosed CVD incidence. Path analyses investigated direct and indirect effects on CIMT., Results: AGLA and SCORE were positively associated with increasing CIMT in both healthy and CVD diagnosed subjects and men and women. Participants in highest risk categories showed a significant CIMT difference of >0.20 mm compared to the reference risk category (<1%), even larger in CVD healthy subjects and men. With increasing risk the odds of CVD incidence increased (Ref. <1%; 10 yr. risk AGLA >10% OR 2.1, >20% OR 3.7). Path analyses yield risk factors' direct and indirect effects through blood pressure., Conclusion: The positive longitudinal association between risk estimations and CIMT confirms the use of risk scores in assessing individuals and populations at risk. Systolic blood pressure appears to be a main pathological mechanism, underscoring the importance of optimal blood pressure control and the importance of prevention strategies of risk factors, indirectly affecting CIMT through the haemodynamic pathway.

Background: Cigarette smoking is a prevalent risk behavior among adolescents and tracks into adulthood. Little is known on the early impact of smoking on the vasculature in adolescence, although smoking is considered highly atherogenic in adults. We investigated the association between active smoking and Carotid artery Intima Media Thickness (CIMT), an early indicator of atherosclerosis., Methods and Results: The SAPALDIA Youth Study is a nested study involving 356 offspring (8-20 yrs) of the Swiss SAPALDIA cohort who reported on early life, health and lifestyle, smoking habits and disease history. 288 youth underwent clinical examination. Mean average and maximum CIMT were calculated across all images of right and left common carotid. Multi-level linear regression was performed with weekly smoking, daily number of cigarettes and serum cotinine, adjusting for participant's and parental confounders. Valid CIMT data was available in 275 offspring (mean age 15 yrs, 53% girls). Weekly smoking was reported by 10% and current parental smoking by 24%. Individual mean and maximal CIMT averaged to 0.52 mm (sd 0.05) and 0.60 mm (sd. 0.05), respectively. Regression analyses yielded significant increase in average CIMT (mm) in weekly smokers (0.025, 95% CI 0.006; 0.045), per cigarette/day (0.003, 95% CI 0.001; 0.005) and serum cotinine level (0.008/100 μg/l, 95% CI 0.002; 0.015), which remained consistent after adjusting for parental confounders., Conclusion: Our study yields evidence of an early adverse impact of active tobacco exposure on atherogenesis in adolescents, independent of parental smoking, underlining the public health importance of prevention of adolescent smoking., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Intima-media thickness of the carotid artery (CIMT) and its increase is associated with several cardiovascular risk factors and manifest cardiovascular diseases. CIMT is suggested to be an important biomarker of subclinical atherosclerosis. CIMT is measured in B-mode ultrasound images of the carotid tree as a typical double line of the arterial wall. CIMT is best visible in the measurement segment of the distal common carotid artery with lowest measurement variability. The measurement is most reliable over a one centimeter-segment with automatic or semi-automatic reading methods, which minimises reading errors. Further structured training of sonographer and reader is important for valid and reproducible results. CIMT is an accepted predictor for future cardiovascular events independent of age, gender and cardiovascular risk factors. Measurement seems to be best applicable in patients with intermediate risk in order to readjust cardiovascular risk. Plaques in the carotid tree and thickening of the CIMT are different atherosclerotic processes. From childhood to early adulthood CIMT is the only atherosclerotic marker of the carotid tree; plaques occur later in life. Both parameters contribute independently to risk assessment for future cardio-vascular events. Aims of this review are to outline measurement procedures, reproducibility, prognostic value and ability to discriminate healthy subject and patients with manifest disease in a practical and scientifically contemporary manner.

Structural parameters of the common carotid artery (CCA) have shown to correlate with the risk of cardiovascular disease, but their precise measurement is challenging. We developed an automatic detection system with manual interaction capabilities that can reliably analyze B-mode ultrasound sequences of the CCA over several heart cycles. We evaluated 3824 frames from 40 sequences in two data qualities. Two readers measured the intima media thickness (IMT) and the lumen diameter at two evaluation times (T1/T2). A Bland-Altman analysis of the average IMT showed a bias ± SD of 0.002 ± 0.010 mm (T1), -0.004 ± 0.008 mm (T2) for completely automatic detections and -0.004 ± 0.010 mm (T1), -0.003 ± 0.010 mm (T2) for clips with manual corrections. The combination of automated analysis and manual intervention provides precise parameters as biomarkers for the atherosclerotic process and makes the system suitable for large scale epidemiological research, diagnostic and clinical practice., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: To improve screening and quantification of subclinical atherosclerosis in children and adolescents with type 1 diabetes (T1D), we investigated the distribution of cardiovascular risk factors (cRFs) and carotid intima-media thickness (cIMT) percentiles with regard to sex-specific differences., Methods: This cross-sectional analysis included clinical parameters, blood lipids, and B-mode ultrasound examination of the bilateral mean cIMT using an automatic contour identification procedure combined with computerized analysis., Results: A total of 270 patients were eligible for evaluation (126 females, mean age 13.7 yr; 144 males, mean age 13.8 yr). In the total group, cIMT was significantly related to sex and diabetes duration but not to age. In males, cIMT was significantly higher than in females and sex-specific cIMT percentiles were calculated. Both pulse pressure and diabetes duration in boys and low-density lipoprotein (LDL)-cholesterol, hemoglobin A1c (HbA1c), and diabetes duration in girls showed a significant association with cIMT., Conclusions: On the basis of sex differences of cRFs and cIMT in pediatric T1D, the assessment of sex-specific IMT percentiles facilitates a differentiated interpretation of subclinical atherosclerosis. The underlying diabetes and additional cRFs seem to be more important determinants of intima-media thickening than age. To improve the comparability of IMT measurements of relevant studies, the international harmonization of IMT measurements should be aimed for., (© 2011 John Wiley & Sons A/S.)

Background: Kawasaki Disease (KD) is a generalized vasculitis in childhood with possible long-term impact on cardiovascular health besides the presence of coronary artery lesions. Standard vascular parameters such as carotid intima–media thickness (cIMT) have not been established as reliable markers of vascular anomalies after KD. The carotid intima–media roughness (cIMR) representing carotid intimal surface structure is considered a promising surrogate marker for predicting cardiovascular risk even beyond cIMT. We therefore measured cIMR in patients with a history of KD in comparison to healthy controls to investigate whether KD itself and/or KD key clinical aspects are associated with cIMR alterations in the long-term. Methods: We assessed cIMR in this case-control study (44 KD, mean age in years (SD); 13.4 (7.5); 36 controls, mean age 12.1 (5.3)) approximately matched by sex and age. Different clinical outcomes such as the coronary artery status and acute phase inflammation data were analyzed in association with cIMR values. Results: When comparing all patients with KD to healthy controls, we detected no significant difference in cIMR. None of the clinical parameters indicating the disease severity, such as the persistence of coronary artery aneurysm, were significantly associated with our cIMR values. However, according to our marginally significant findings (p = 0.044), we postulate that the end-diastolic cIMR may be rougher than the end-systolic values in KD patients. Conclusions: We detected no significant differences in cIMR between KD patients and controls that could confirm any evidence that KD predisposes patients to a subsequent general arteriopathy. Our results, however, need to be interpreted in the light of the low number of study participants. [ABSTRACT FROM AUTHOR]

Cardiovascular health scores have emerged as a simple way to assess the risk to suffer from a cardiovascular disease. The American Heart Association's Life's Simple 7 constitutes of modifiable lifestyle factors to reduce cardiovascular risk. Its association with carotid properties is yet inconclusive. The aim of this study is to determine the association between the adherence to Life's Simple 7 and carotid properties in middle-aged to elderly Finns. A representative sample of Finnish men and women aged 55–74 years was included in the present study. Carotid intima-media thickness (cIMT), lumen diameter (cLD), and carotid distensibility were measured by transcutaneous ultrasound using state-of-the-art wall contour detection techniques. The Life's Simple 7 cardiovascular health score was calculated using seven categories (body mass index, cholesterol, systolic blood pressure, fasting plasma glucose, smoking status, physical activity, and diet). In accordance to the American Heart Association, for each category, an ideal score was given 2 points, intermediate scores 1 point, and poor scores 0 points. In total, 1400 (49.4% male) subjects were included in the analyses. After adjusting for age and sex, we found that subjects with a an ideal cardiovascular health score had lower cLD than those with an intermediate score (−0.21 mm, 95% CI: 0.37 to −0.05 mm, p= 0.005) and a poor score (−0.39 mm, 95% CI: 0.65 to −0.12 mm, p= 0.001). Similarly, subjects with an ideal health score had higher carotid distensibility than those with an intermediate score (0.0032 1/kPa, 95% CI: 0.009–0.0055 1/kPa, p= 0.002) and a poor score (0.0018 1/kPa, 95% CI: 0.0005–0.0032 1/kPa, p= 0.004). We found no differences regarding cIMT. In middle-aged to elderly Finns, higher adherence to the Life's Simple 7 is associated with lower cLD and higher distensibility, but not with cIMT. Adherence to healthy lifestyle habits is therefore associated with better carotid structure and carotid function in middle-aged to elderly Finns. [Display omitted] • Adherence to the Life's Simple 7 is associated with lower carotid lumen diameter. • Higher cardiovascular health is linked with higher carotid distensibility. • Even reaching some lifestyle goals protects carotid structure and function. [ABSTRACT FROM AUTHOR]

Background and aims Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today. Methods Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design. Mutations Pi-S and Pi-Z were coded as ordinal genotype score (MM, MS, MZ/SS, SZ and ZZ), according to their progressive biological impact. Results Serum A1AT concentration presented a u-shaped association with CIMT. At the lower end of the A1AT distribution, an analogous, linear association between SERPINA1 score and higher CIMT was observed, resulting in an estimated 1.2% (95%-confidence interval -0.1-2.5) increase in CIMT per unit ( p  = 0.060). Genotype score was significantly associated with arterial hypertension with an odds ratio (OR) of 1.2 (1.0–1.5) per unit ( p  = 0.028). The association with cardiovascular disease was not significant (OR 1.3 (0.9–1.9)). Conclusions Our results support a possible causal relationship between genetic A1AT deficiency and increased cardiovascular risk, which needs to be better taken into account for the management of affected patients and first-degree relatives. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Carotid intima media thickness (CIMT) and local stiffness are vascular biomarkers of atherosclerotic burden. We investigated the variability and reproducibility of clinically relevant structural (CIMT, lumen diameter) and functional parameters (strain, distensibility, compliance, β-stiffness index, Peterson's elastic modulus and Young's elastic modulus) measured in B-mode ultrasound sequences of the common carotid artery in the second follow up of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases In Adults (SAPALDIA3). Methods: Ultrasound sequential images were examined twice over a 1 cm segment across at least one heart cycle in 165 SAPALDIA3 participants. To assess variability and reproducibility of structural and functional parameters, individual coefficients of variation (CV), intraclass correlation (ICC), Bland–Altman plots and mixed effect regressions were used. Results: ICCs of repeated examinations ranged between 0.67 and 0.77 for blood pressure indices, between 0.87 and 0.97 for structural properties and between 0.75 and 0.79 for functional parameters. CV was lowest in structural parameters (1.6–4.6%), followed by blood pressure (5.1–7.9%) and functional indices (11.0–13.1%). Variations in all parameters were predominantly explained by subjects (>74% in functional, >82% in structural properties). Bland–Altman plots for functional indices showed mean and standard deviation of the respective mean value of 4.2(19.6)% for strain, 1.9(24.4)% for distensibility, 2.4(22.2)% for compliance, 3.0(24.4)% for β-stiffness index, 0.9(25.7)% for Peterson's elastic modulus and 1.2(27.9)% for Young's elastic modulus. Conclusion: The results show that SAPALDIA3 measurements of transcutaneous ultrasound examinations have an excellent reproducibility of structural parameters and a good reproducibility of functional indices. [Copyright &y& Elsevier]