Seraina Caviezel

Carotid intima-media thickness as a biomarker of subclinical atherosclerosis

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.

An Automated, Interactive Analysis System for Ultrasound Sequences of the Common Carotid Artery

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.

Particulate matter and subclinical atherosclerosis : associations between different particle sizes and sources with carotid intima-media thickness in the SAPALDIA study

Background: Subclinical atherosclerosis has been associated with long-term exposure to particulate matter (PM), but the relevance of particle size and sources of exposure remains unclear. Objectives: We investigated the association of long-term exposure to PM10 (≤ 10 μm), PM2.5 (≤ 2.5 μm: total mass, vehicular, and crustal sources), and ultrafine particles [UFP < 0.1 μm: particle number concentration (PNC) and lung-deposited surface area (LDSA)] with carotid intima-media thickness (CIMT). Methods: We used data from 1,503 participants ≥ 50 years old who participated in the third examination of the Swiss SAPALDIA cohort. Exposures were obtained from dispersion models and land-use regression models. Covariate information, including previous cardiovascular risk factors, was obtained from the second and third SAPALDIA examinations. Results: The adjusted percent difference in CIMT associated with an exposure contrast between the 10th and 90th percentile was 1.58% (95% CI: –0.30, 3.47%) for PM10, 2.10% (95% CI: 0.04, 4.16%) for PM2.5, 1.67% (95% CI: –0.13, 3.48%) for the vehicular source of PM2.5, –0.58% (95% CI: –3.95, 2.79%) for the crustal source of PM2.5, 2.06% (95% CI: 0.03, 4.10%) for PNC, and 2.32% (95% CI: 0.23, 4.40%) for LDSA. Stronger associations were observed among diabetics, subjects with low-educational level, and those at higher cardiovascular risk. Conclusions: CIMT was associated with exposure to PM10, PM2.5, and UFP. The PM2.5 source-specific analysis showed a positive association for the vehicular source but not for the crustal source. Although the effects of PNC and LDSA were similar in magnitude, two-pollutant and residual-based models suggested that LDSA may be a better marker for the health relevance of UFP. Citation: Aguilera I, Dratva J, Caviezel S, Burdet L, de Groot E, Ducret-Stich RE, Eeftens M, Keidel D, Meier R, Perez L, Rothe T, Schaffner E, Schmit-Trucksäss A, Tsai MY, Schindler C, Künzli N, Probst-Hensch N. 2016. Particulate matter and subclinical atherosclerosis: associations between different particle sizes and sources with carotid intima-media thickness in the SAPALDIA study. Environ Health Perspect 124:1700–1706; http://dx.doi.org/10.1289/EHP161

Long-term transportation noise annoyance is associated with subsequent lower levels of physical activity.

Noise annoyance (NA) might lead to behavioral patterns not captured by noise levels, which could reduce physical activity (PA) either directly or through impaired sleep and constitute a noise pathway towards cardiometabolic diseases. We investigated the association of long-term transportation NA and its main sources (aircraft, road, and railway) at home with PA levels. We assessed 3842 participants (aged 37-81) that attended the three examinations (SAP 1, 2, and 3 in years 1991, 2001 and 2011, respectively) of the population-based Swiss cohort on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Participants reported general 24-h transportation NA (in all examinations) and source-specific NA at night (only SAP 3) on an ICBEN-type 11-point scale. We assessed moderate, vigorous, and total PA from a short-questionnaire (SAP 3). The main outcome was moderate PA (active/inactive: cut-off≥150min/week). We used logistic regression including random effects by area and adjusting for age, sex, socioeconomic status, and lifestyles (main model) and evaluated potential effect modifiers. We analyzed associations with PA at SAP 3 a) cross-sectionally: for source-specific and transportation NA in the last year (SAP 3), and b) longitudinally: for 10-y transportation NA (mean of SAP 1+2), adjusting for prior PA (SAP 2) and changes in NA (SAP 3-2). Reported NA (score≥5) was 16.4%, 7.5%, 3%, and 1.1% for 1-year transportation, road, aircraft, and railway at SAP 3, respectively. NA was greater in the past, reaching 28.5% for 10-y transportation NA (SAP 1+2). The 10-y transportation NA was associated with a 3.2% (95% CI: 6%-0.2%) decrease in moderate PA per 1-NA rating point and was related to road and aircraft NA at night in cross-sectional analyses. The longitudinal association was stronger for women, reported daytime sleepiness or chronic diseases and it was not explained by objectively modeled levels of road traffic noise at SAP 3. In conclusion, long-term NA (related to psychological noise appraisal) reduced PA and could represent another noise pathway towards cardiometabolic diseases.

Long-term physical activity is associated with reduced arterial stiffness in older adults: longitudinal results of the SAPALDIA cohort study

BACKGROUND longitudinal analyses of physical activity (PA) and arterial stiffness in populations of older adults are scarce. We examined associations between long-term change of PA and arterial stiffness in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). METHODS we assessed PA in SAPALDIA 2 (2001-03) and SAPALDIA 3 (2010-11) using a short questionnaire with a cut-off of at least 150 min of moderate-to-vigorous PA per week for sufficient activity. Arterial stiffness was measured oscillometrically by means of the brachial-ankle pulse wave velocity (baPWV) in SAPALDIA 3. We used multivariable mixed linear regression models adjusted for several potential confounders in 2,605 persons aged 50-81. RESULTS adjusted means of baPWV were significantly lower in persons with sufficient moderate-to-vigorous PA (i) in SAPALDIA 2 but not in SAPALDIA 3 (P = 0.048) and (ii) in both surveys (P = 0.001) compared with persons with insufficient activity in both surveys. There was a significant interaction between sex and the level of change in PA concerning baPWV (P = 0.03). The triples of parameter estimates describing the association between level of PA change and baPWV were not significantly different between the two sex-specific models (P = 0.07). CONCLUSIONS keeping up or adopting a physically active lifestyle was associated with lower arterial stiffness in older adults after a follow-up of almost a decade. Increasing the proportion of older adults adhering to PA recommendations incorporating also vigorous PA may have a considerable impact on vascular health at older age and may contribute to healthy ageing in general.

Variability and reproducibility of carotid structural and functional parameters assessed with transcutaneous ultrasound - results from the SAPALDIA Cohort Study

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, Petersons elastic modulus and Youngs 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 Petersons elastic modulus and 1.2(27.9)% for Youngs 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.

Reproducibility of oscillometrically measured arterial stiffness indices: Results of the SAPALDIA 3 cohort study

Abstract Background. There is an increasing interest in oscillometric arterial stiffness measurement for cardiovascular risk stratification. We assessed reproducibility of the cuff-based arterial stiffness measures cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV) and peripheral augmentation index (pAI) in a subsample of the second follow-up of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA 3). Methods. CAVI, baPWV and pAI were measured twice within 90 days in a representative subsample (n = 105) of SAPALDIA 3 with a mean age of 63 years (52.4% female). Results. The mean coefficient of variation for CAVI was 4.4%, baPWV 3.9%, and pAI 7.4%. The intraclass correlation coefficient ranged from 0.6 for pAI to 0.8 for CAVI, and 0.9 for baPWV. The mixed linear model revealed that 68.7%/80.1%/55.0% of the CAVI/baPWV/pAI variance was accounted for by the subject, 5.2%/8.1%/ < 0.01% by the fieldworker, 6.7%/7.8%/28.5% by variation between measurement days, and 19.4%/4%/16.5% by measurement error. Bland-Altman plots showed no particular dispersion patterns except for pAI. Conclusions. Oscillometric arterial stiffness measurement by CAVI and baPWV has proved to be highly reproducible in Caucasians. Results of the pAI showed lower reproducibility. CAVI and baPWV can be implemented as easy-to-apply arterial stiffness measures in population wide cardiovascular risk assessment in Caucasians.

Is physical activity a modifier of the association between air pollution and arterial stiffness in older adults: The SAPALDIA cohort study

INTRODUCTION AND OBJECTIVES Air pollution and insufficient physical activity have been associated with inflammation and oxidative stress, molecular mechanisms linked to arterial stiffness and cardiovascular disease. There are no studies on how physical activity modifies the association between air pollution and arterial stiffness. We examined whether the adverse cardiovascular effects of air pollution were modified by individual physical activity levels in 2823 adults aged 50-81 years from the well-characterized Swiss Cohort Study on Air Pollution and Lung and Heart Diseases (SAPALDIA). METHODS We assessed arterial stiffness as the brachial-ankle pulse wave velocity (baPWV [m/s]) with an oscillometric device. We administered a self-reported physical activity questionnaire to classify each subjects physical activity level. Air pollution exposure was estimated by the annual average individual home outdoor PM10 and PM2.5 (particulate matter <10μm and <2.5μm in diameter, respectively) and NO2 (nitrogen dioxide) exposure estimated for the year preceding the survey. Exposure estimates for ultrafine particles calculated as particle number concentration (PNC) and lung deposited surface area (LDSA) were available for a subsample (N=1353). We used mixed effects logistic regression models to regress increased arterial stiffness (baPWV≥14.4m/s) on air pollution exposure and physical activity while adjusting for relevant confounders. RESULTS We found evidence that the association of air pollution exposure with baPWV was different between inactive and active participants. The probability of having increased baPWV was significantly higher with higher PM10, PM2.5, NO2, PNC and LDSA exposure in inactive, but not in physically active participants. We found some evidence of an interaction between physical activity and ambient air pollution exposure for PM10, PM2.5 and NO2 (pinteraction=0.06, 0.09, and 0.04, respectively), but not PNC and LDSA (pinteraction=0.32 and 0.35). CONCLUSIONS Our study provides some indication that physical activity may protect against the adverse vascular effects of air pollution in low pollution settings. Additional research in large prospective cohorts is needed to assess whether the observed effect modification translates to high pollution settings in mega-cities of middle and low-income countries.

Carotid Stiffness and Physical Activity in Elderly—A Short Report of the SAPALDIA 3 Cohort Study

Introduction Regular physical activity has been shown to reduce cardiovascular disease risk in the general population. While smaller studies in specified groups (highly trained versus untrained individuals) indicate a certain dose-dependent effect of physical activity on the reduction of carotid stiffness (an indicator of subclinical vascular disease), it is unclear whether this association is present in a representative sample. Thus, we investigated this question cross-sectionally in participants from the population-based Swiss Cohort Study on Air Pollution And Lung and Heart Diseases In Adults (SAPALDIA). Methods Self-reported total, moderate and vigorous physical activity and distensibility as a measure of local arterial stiffness among 1636 participants aged 50 to 81 years without clinically manifest diseases were evaluated. Mixed regression models were used to examine associations of physical activity intensity with distensibility. Results Vigorous physical activity, but not total nor moderate physical activity, was significantly associated with increased distensibility (= reduced carotid stiffness) in univariate analyses (percent change in the geometric mean and 95% confidence interval per 1 standard deviation increment in vigorous physical activity = 2.54 (0.69; 4.43), p<0.01; in total physical activity = 1.62 (-0.22; 3.50), p = 0.08; in moderate physical activity = 0.70 (-1.12; 2.56), p = 0.45). These associations disappeared when we additionally adjusted for age. Conclusion After adjustment for the most important confounders and risk factors, we found no evidence for an association of physical activity with carotid stiffness in the general middle aged to elderly population.

Associations of Novel and Traditional Vascular Biomarkers of Arterial Stiffness: Results of the SAPALDIA 3 Cohort Study

Background and Objectives There is a lack of evidence concerning associations between novel parameters of arterial stiffness as cardiovascular risk markers and traditional structural and functional vascular biomarkers in a population-based Caucasian cohort. We examined these associations in the second follow-up of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA 3). Methods Arterial stiffness was measured oscillometrically by pulse wave analysis to derive the cardio-ankle vascular index (CAVI), brachial-ankle (baPWV) and aortic pulse wave velocity (aPWV), and amplitude of the forward and backward wave. Carotid ultrasonography was used to measure carotid intima-media thickness (cIMT) and carotid lumen diameter (LD), and to derive a distensibility coefficient (DC). We used multivariable linear regression models adjusted for several potential confounders for 2,733 people aged 50–81 years. Results CAVI, aPWV and the amplitude of the forward and backward wave were significant predictors of cIMT (p < 0.001). All parameters were significantly associated with LD (p < 0.001), with aPWV and the amplitude of the forward wave explaining the highest proportion of variance (2%). Only CAVI and baPWV were significant predictors of DC (p < 0.001), explaining more than 0.3% of the DC variance. Conclusion We demonstrated that novel non-invasive oscillometric arterial stiffness parameters are differentially associated with specific established structural and functional local stiffness parameters. Longitudinal studies are needed to follow-up on these cross-sectional findings and to evaluate their relevance for clinical phenotypes.