Cyclic variation of the common carotid artery structure in relation to prior atherosclerotic burden and physical activity

Background and aims: Cardiovascular disease (CVD) accounts for the most deaths of non-communicable diseases worldwide. It begins with structural and functional changes of the arterial system commonly known as the atherosclerotic process, starting asymptomatically in early childhood, adapting arterial structure and function with advancing age depending on genetic and environmental exposures and finally resulting in CVD events such as myocardial infarction or stroke. CVD risk prediction today is generally based on risk scores, but substantial disadvantages occur since they account only for specific risk factors at one time point. Carotid structure and function (also called carotid stiffness) parameters measured by ultrasound may overcome this disadvantage, since they can provide information on structural and elastic carotid properties and reflect therefore vascular damage accumulated over time. Thus, the aims of this thesis were to summarize the state of the art of ultrasound measurements, to validate the new developed ultrasound analysis system, to assess the variability and reproducibility within the study sample and to investigate the long- and short-term associations of cardiovascular risk factors and carotid stiffness with main focus on physical activity in elderly participants of the SAPALDIA cohort. Methods: The SAPALDIA cohort study is an ongoing multicenter study with a population-based random sample of adults from eight rural and urban areas started in 1991 (SAPALDIA 1), with a first follow-up in 2001-2003 (SAPALDIA 2) and a second follow-up in 2010-2011 (SAPALDIA 3). In SAPALDIA 3, sequential B-mode ultrasound images of the common carotid artery were examined in 3489 participants (51% women) aged between 50-81 years at the time of examination. Expert readers analyzed these ultrasound images with a new analysis system called DYARA (DYnamic ARtery Analysis) according to the state of the art assessed in the review. Thereof, carotid structure parameters were measured and carotid stiffness indices were derived considering blood pressure at time of ultrasound assessment. Validation of the ultrasound analysis program DYARA and reproducibility of carotid parameters were performed in subgroup within the SAPALDIA 3 survey. The presented studies within this thesis comprise cardiovascular risk factor data from the first and second follow-up and therefore, long- and short-term associations with carotid stiffness could be investigated. Results: The intra- and inter-reader results of the validation study were highly consistent with slightly higher bias for analyses with manual interactions compared to the automatic detection. Among the carotid structure parameters, average values across heart cycle showed lower variability than single images in diastole and systole, whereby the relative difference was smaller in lumen diameter values compared to the carotid intima media thickness (CIMT). Based on different statistical approaches, reproducibility values within SAPALDIA 3 were consistently good to excellent for carotid structure and function indices. Findings additionally revealed that subjects itself were the greatest source of variability between two measurements. Multivariate regression analyses suggested that most single cardiovascular risk factors in SAPALDIA 2 were long-termly associated with increased carotid stiffness in SAPALDIA 3 except physical activity and high-density lipoprotein cholesterol (HDL-C). HDL-C was the only protective vascular determinant and no relation was observed for physical activity. Most carotid stiffness parameters were similar strong associated within each cardiovascular risk factor (except compliance showed main deviances among several risk factors). Estimating sex-specific associations of atherosclerotic risk factors and carotid stiffness indicated that increased heart rate was more strongly associated with stiffer arteries across all carotid stiffness parameters in men than in women. Low-density lipoprotein cholesterol (LDL-C) was significantly associated with carotid stiffness only in men and triglyceride only in women. Multifactorial pathway analyses of cardiovascular risk factors in SAPALDIA 3 showed that age was the strongest predictor of carotid stiffness, followed by mean arterial blood pressure and heart rate. Age strongly confounded the association of physical activity and carotid stiffness in multiple regression analyses and therefore, only an univariate association of physical activity and carotid stiffness could be observed. Conclusion: DYARA tackles the challenge of being able to analyze varying ultrasound image qualities with high precision. The high reproducibility and the feasible application in a large sample size suggest that this program can be recommended for epidemiological research, diagnostics and clinical practice. Long- and short-term cardiovascular exposures have added important information to the overall vascular damage assessed by carotid stiffness for both sexes. Although age was the strongest predictor, sex-differences in long-term associations may indicate a certain differentiated susceptibility to cardiovascular risk factors among men and women, which should be investigated in more detail. The presented studies within this thesis provide an important basis towards future investigations targeting the early and late consequences of atherosclerosis, its progression and possible implementations of preventive and/or personalized interventions

Patterns of cross-sectional and predictive physical activity in Swiss adults aged 52+: results from the SAPALDIA cohort

Non-communicable diseases (NCDs) account for the vast majority of deaths in Switzerland. Insufficient physical activity (PA) is an established NCD risk factor and PA is known to be beneficial for physical and mental wellbeing. Sedentary behaviour (SB) is an additional, independent risk factor and associated with frailty in older adults. This study aimed at describing cross-sectional PA patterns in a general population sample of subjects aged 52 years and older (52+) from eight areas across different language regions of Switzerland. Additionally, the predictive association of self-reported PA for objectively measured PA was tested.; Participants 52+ of the Swiss Cohort Study on Air Pollution And Lung and Heart Disease In Adults (SAPALDIA) who completed accelerometer data collection at the most recent follow-up (SAPALDIA4 in 2017/18) and provided information on determinants of interest (sex, age, body mass index [BMI], language region, education, employment status, civil status, smoking) were included in the analysis (n = 1314). The accelerometer-derived average time spent in different PA intensities (SB, light PA [LPA], moderate-to-vigorous PA [MVPA]) was estimated according to participant characteristics with control for season and wear time using multiple linear regressions. In further analyses, the predictive effect of changes in self-reported PA over roughly ten years between SAPALDIA2 (2001/02) and SAPALDIA3 (2010/11) (remaining inactive [RI]; becoming inactive [BI]; becoming active [BA]; remaining active [RA]) on the objectively measured SB, LPA and MVPA obtained seven years later by accelerometry (SAPALDIA4), was assessed using multiple linear regression models.; Overall, 21.7% of 52+ participants met the Swiss recommendations for subjectively assessed PA. Obese participants, 75+ year-olds, smokers and subjects living alone spent more time in SB and less time in LPA and MVPA compared with participants with a BMI below 25 kg/m2, between 52 and 64 years old, not smoking and being married, respectively. Residents living in the French-speaking part of Switzerland were less likely to engage in MVPA compared with residents from the German-speaking part and thus were less likely to meet the PA recommendations. A trend for increasing PA and decreasing SB was observed consistently across the four groups (RI, BI, BA, RA) of predictive self-reported PA patterns with participants remaining active over the course of roughly ten years showing highest levels of PA and lowest levels of SB measured objectively at SAPALDIA4.; The high proportion of SB points to the need of physical activity promotion for the older part of the population in Switzerland. According to our data, behavioural changes in PA are possible and sustainable as we can see in the group of participants becoming active and this is essential for health promotion recommendations

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

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).; 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.; 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.; 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

Association of Different Restriction Levels With COVID-19-Related Distress and Mental Health in Somatic Inpatients: A Secondary Analysis of Swiss General Hospital Data

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic and related countermeasures hinder health care access and affect mental wellbeing of non-COVID-19 patients. There is lack of evidence on distress and mental health of patients hospitalized due to other reasons than COVID-19-a vulnerable population group in two ways: First, given their risk for physical diseases, they are at increased risk for severe courses and death related to COVID-19. Second, they may struggle particularly with COVID-19 restrictions due to their dependence on social support. Therefore, we investigated the association of intensity of COVID-19 restrictions with levels of COVID-19-related distress, mental health (depression, anxiety, somatic symptom disorder, and mental quality of life), and perceived social support among Swiss general hospital non-COVID-19 inpatients. METHODS We analyzed distress of 873 hospital inpatients not admitted for COVID-19, recruited from internal medicine, gynecology, rheumatology, rehabilitation, acute geriatrics, and geriatric rehabilitation wards of three hospitals. We assessed distress due to the COVID-19 pandemic, and four indicators of mental health: depressive and anxiety symptom severity, psychological distress associated with somatic symptoms, and the mental component of health-related quality of life; additionally, we assessed social support. The data collection period was divided into modest (June 9 to October 18, 2020) and strong (October 19, 2020, to April 17, 2021) COVID-19 restrictions, based on the Oxford Stringency Index for Switzerland. RESULTS An additional 13% (95%-Confidence Interval 4-21%) and 9% (1-16%) of hospital inpatients reported distress related to leisure time and loneliness, respectively, during strong COVID-19 restrictions compared to times of modest restrictions. There was no evidence for changes in mental health or social support. CONCLUSIONS Focusing on the vulnerable population of general hospital inpatients not admitted for COVID-19, our results suggest that tightening of COVID-19 restrictions in October 2020 was associated with increased COVID-19-related distress regarding leisure time and loneliness, with no evidence for a related decrease in mental health. If this association was causal, safe measures to increase social interaction (e.g., virtual encounters and outdoor activities) are highly warranted. TRIAL REGISTRATION www.ClinicalTrials.gov, identifier: NCT04269005

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

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.; 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).; 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.; 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.; 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

Mortality monitoring in Switzerland

The Federal Statistical Office publishes weekly national and regional mortality reports online for Switzerland for the age groups 0 to <65 and 65+ years, which refer to deaths up to 9 days prior to the publication date. In addition to observed numbers of death events, expected numbers are reported, which allows  detection of periods of excess mortality and its quantification. As with previous periods of excess mortality, in 2020 the monitoring detected and quantified excess mortality during the two waves of the SARS-CoV-2 epidemic in Switzerland. During the year, the epidemic resulted in well over 10% more deaths than expected, mainly in individuals aged 65 years and above. Because of the profound impact of the epidemic, interest in the weekly mortality publication and its underlying methodology increased sharply. From inquiries and from newspaper and tabloid publications on the matter it became abundantly evident that the principles of the mortality monitoring were not well understood in general; mortality monitoring was even regularly confused with cause of death statistics. The present article therefore aims at elucidating the methodology of national mortality monitoring in Switzerland and at putting it into its public health context

Carotid stiffness and physical activity in elderly : a short report of the SAPALDIA 3 cohort study

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).; 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.; 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.; 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

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

Early detection of subjects at risk for vascular remodelling : results from the Swiss population-based study SAPALDIA

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.; 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.; 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 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.; 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