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Adopting policies that promote health for the entire biosphere (One Health) requires human societies to transition towards a more sustainable food supply as well as to deepen the understanding of the metabolic and health effects of evolving food habits. At the same time, life sciences are experiencing rapid and groundbreaking technological developments, in particular in laboratory analytics and biocomputing, placing nutrition research in an unprecedented position to produce knowledge that can be translated into practice in line with One Health policies. In this dynamic context, nutrition research needs to be strategically organised to respond to these societal expectations. One key element of this strategy is to integrate precision nutrition into epidemiological research. This position article therefore reviews the recent developments in nutrition research and proposes how they could be integrated into cohort studies, with a focus on the Swiss research landscape specifically. [ABSTRACT FROM AUTHOR]

BackgroundGenome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.MethodsWe performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.ResultsThe overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.ConclusionsIn this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

In this cross‐sectional study, the prevalences of tooth loss, prosthetic dental restorations, and probing pocket depths (PPD) ≥4 mm, and their relationship to sociodemographic factors, were investigated in older Swiss adults. There were up to 1,673 participants aged ≥55 yr in the fourth survey of the Swiss Cohort Study on Air Pollution And Lung And Heart Disease In Adults (SAPALDIA4). Missing teeth, prosthetic dental restorations, and PPD ≥4 mm were recorded in clinical examinations conducted by field workers and compared with self‐reported information from questionnaires. Examination data showed that participants were missing five teeth on average, 74.8% had a prosthetic dental restoration, and 21.1% had PPD of ≥4 mm. The mean number of missing teeth and the prevalences of tooth loss, fixed dental prostheses, and removable dental prostheses were associated with age, education level, smoking status, and time since last visit to a dentist. Comparison of data obtained by field workers and that from self‐reports show a high level of agreement for the number of missing teeth and the prevalence of removable dental prostheses, but a lower level of agreement for self‐reports of fixed dental prostheses and periodontitis. [ABSTRACT FROM AUTHOR]

Exposure during transport and at non-residential locations is ignored in most epidemiological studies of traffic-related air pollution. We investigated the impact of separately estimating NO2 long-term outdoor exposures at home, work/school, and while commuting on the association between this marker of exposure and potential health outcomes. We used spatially and temporally resolved commuter route data and model-based NO2 estimates of a population sample in Basel, Switzerland, to assign individual NO2-exposure estimates of increasing complexity, namely (1) home outdoor concentration; (2) time-weighted home and work/school concentrations; and (3) time-weighted concentration incorporating home, work/school and commute. On the basis of their covariance structure, we estimated the expectable relative differences in the regression slopes between a quantitative health outcome and our measures of individual NO2 exposure using a standard measurement error model. The traditional use of home outdoor NO2 alone indicated a 12% (95% CI: 11-14%) underestimation of related health effects as compared with integrating both home and work/school outdoor concentrations. Mean contribution of commuting to total weekly exposure was small (3.2%; range 0.1-13.5%). Thus, ignoring commute in the total population may not significantly underestimate health effects as compared with the model combining home and work/school. For individuals commuting between Basel-City and Basel-Country, ignoring commute may produce, however, a significant attenuation bias of 4% (95% CI: 4-5%). Our results illustrate the importance of including work/school locations in assessments of long-term exposures to traffic-related air pollutants such as NO2. Information on individuals' commuting behavior may further improve exposure estimates, especially for subjects having lengthy commutes along major transportation routes. [ABSTRACT FROM AUTHOR]

Summary Background Low concentrations of the anti-inflammatory protein CC16 (approved symbol SCGB1A1) in serum have been associated with accelerated decline in forced expiratory volume in 1 s (FEV 1 ) in patients with chronic obstructive pulmonary disease (COPD). We investigated whether low circulating CC16 concentrations precede lung function deficits and incidence of COPD in the general population. Methods We assessed longitudinal data on CC16 concentrations in serum and associations with decline in FEV 1 and incidence of airflow limitation for adults who were free from COPD at baseline in the population-based Tucson Epidemiological Study of Airway Obstructive Disease ([TESAOD] n=960, mean follow-up 14 years), European Community Respiratory Health Survey ([ECRHS-Sp] n=514, 11 years), and Swiss Cohort Study on Air Pollution and Lung Diseases in Adults ([SAPALDIA] n=167, 8 years) studies. Additionally, we measured circulating CC16 concentrations in samples from children aged 4–6 years in the Tucson Children's Respiratory Study (n=427), UK Manchester Asthma and Allergy Study (n=481), and the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (n=231) birth cohorts to assess whether low CC16 concentrations in childhood were predictive for subsequent lung function. Findings After adjustment for sex, age, height, smoking status and intensity, pack-years, asthma, and FEV 1 at baseline, we found an inverse association between CC16 concentration and decline in FEV 1 in adults in TESAOD (4·4 mL/year additional FEV 1 decline for each SD decrease in baseline CC16 concentration, p=0·0014) and ECRHS-Sp (2·4 mL/year, p=0·023); the effect in SAPALDIA was marginal (4·5 mL/year, p=0·052). Low CC16 concentration at baseline was also associated with increased risk of incident stage 2 airflow limitation (ratio of FEV 1 to forced expiratory volume [FEV 1 /FVC] less than 70% plus FEV 1 % predicted less than 80%) in TESAOD and ECRHS-Sp. In children, the lowest tertile of CC16 concentrations was associated with a subsequent FEV 1 deficit of 68 mL up to age 16 years (p=0·0001), which was confirmed in children who had never smoked by age 16 years (−71 mL, p<0·0001). Interpretation Low concentrations of CC16 in serum are associated with reduced lung function in childhood, accelerated lung function decline in adulthood, and development of moderate airflow limitation in the general adult population. Funding National Heart, Lung, and Blood Institute and European Union Seventh Framework Programme. [ABSTRACT FROM AUTHOR]

The Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), a population cohort study, used heated-wire spirometers in 1991 and 2002 and then ultrasonic spirometers in 2010 revealing measurement bias in healthy never smokers. To provide a practical method to control for measurement bias given the replacement of spirometer in long-term population studies, we built spirometer-specific reference equations from healthy never smokers participating in 1991, 2002, and 2010 to derive individualized corrections terms. We compared yearly lung function decline without corrections terms with fixed terms that were obtained from a quasi-experimental study and individualized terms. Compared with baseline reference equations, spirometer-specific reference equations predicted lower lung function .The mean measurement bias increased with age and height. The decline in forced expiratory volume in 1 second during the reference period of 1991-2002 was 31.5 (standard deviation (SD), 28.7) mL/year while, after spirometer replacement, uncorrected, corrected by fixed term, and individualized term, the declines were 47.0 (SD, 30.1), 40.4 (SD, 30.1), and 30.4 (SD, 29.9) mL/year, respectively. In healthy never smokers, ultrasonic spirometers record lower lung function values than heated-wire spirometers. This measurement bias is sizeable enough to be relevant for researchers and clinicians. Future reference equations should account for not only anthropometric variables but also spirometer type. We provide a novel method to address spirometer replacement in cohort studies. [ABSTRACT FROM AUTHOR]

Background: Exposure to particulate matter (PM) has been associated with an increase in many inflammatory markers, including interleukin 6 (IL6). Air pollution exposure has also been suggested to induce an imbalance in the autonomic nervous system (ANS), such as a decrease in heart rate variability (HRV). In this study we aimed to investigate the modifying effect of polymorphisms in a major proinflammatory marker gene, interleukin 6 (IL6), on the relationship between long-term exposure to traffic-related PM10 (TPM10) and HRV. Methods: For this cross-sectional study we analysed 1552 participants of the SAPALDIA cohort aged 50 years and older. Included were persons with valid genotype data, who underwent ambulatory 24-hr electrocardiogram monitoring, and reported on medical history and lifestyle. Main effects of annual average TPM10 and IL6 gene variants (rs1800795; rs2069827; rs2069840; rs10242595) on HRV indices and their interaction with average annual exposure to TPM10 were tested, applying a multivariable mixed linear model. Results: No overall association of TPM10 on HRV was found. Carriers of two proinflammatory G-alleles of the functional IL6 -174 G/C (rs1800795) polymorphism exhibited lower HRV. An inverse association between a 1 µg/m3 increment in yearly averaged TPM10 and HRV was restricted to GG genotypes at this locus with a standard deviation of normal-to-normal intervals (SDNN) (GG-carriers: −1.8%; 95% confidence interval −3.5 to 0.01; pinteraction(additive) = 0.028); and low frequency power (LF) (GG-carriers: −5.7%; 95%CI: −10.4 to −0.8; pinteraction(dominant) = 0.049). Conclusions: Our results are consistent with the hypothesis that traffic-related air pollution decreases heart rate variability through inflammatory mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Background: Household cleaning products are associated with adverse respiratory health outcomes, but the cardiovascular health effects are largely unknown. Objective: We determined if long-term use of household sprays and scented products at home was associated with reduced heart rate variability (HRV), a marker of autonomic cardiac dysfunction. Methods: We recorded 24-hr electrocardiograms in a cross-sectional survey of 581 Swiss adults, ≥ 50 years of age, who answered a detailed questionnaire regarding their use of household cleaning products in their homes. The adjusted average percent changes in standard deviation of all normal-to-normal intervals in 24 hr (24-hr SDNN) and total power (TP) were estimated in multiple linear regression in association with frequency [< 1, 1-3, or 4-7 days/week, unexposed (reference)] of using cleaning sprays, air freshening sprays, and scented products. Results: Decreases in 24-hr SDNN and TP were observed with frequent use of all product types, but the strongest reductions were associated with air freshening sprays. Compared with unexposed participants, we found that using air freshening sprays 4-7 days/week was associated with 11% [95% confidence interval (CI): -20%, -2%] and 29% (95% CI: -46%, -8%) decreases in 24-hr SDNN and TP, respectively. Inverse associations of 24-SDNN and TP with increased use of cleaning sprays, air freshening sprays, and scented products were observed mainly in participants with obstructive lung disease (p < 0.05 for interactions). Conclusions: In predominantly older adult women, long-term frequent use of household spray and scented products was associated with reduced HRV, which suggests an increased risk of cardiovascular health hazards. People with preexisting pulmonary conditions may be more susceptible. [ABSTRACT FROM AUTHOR]

Background: Reproductive characteristics play an aetiological role for many diseases, including reproductive cancers. They have been shown to vary internationally and nationally, but have not yet been described for the whole Swiss population. Aim: The study investigated the variability of reproductive characteristics, their patterns, and main determinants across a population-based female study population in Switzerland. Methods: Reproductive characteristics obtained from 3119 women (28-72 years) participating in the SAPALDIA cohort survey in 2001-2003 are described across birth cohorts, study areas, language regions, and levels of urbanization. Determinants of age at menopause were analysed by Cox regression. Results: Reported median age at menarche was 13 years and median age at natural menopause was 52 years. The prevalence of nulliparity was 27%, and the fertility rate 1.6. Across birth cohorts there was a decline of menarcheal age and fertility rates, and an increase of nulliparity and age at last pregnancy. All characteristics varied across study areas, language regions, and levels of urbanization. Smoking, parity, and physical exercise were stronger predictors of earlier (<52 years) than older (>52 years) menopausal age. Conclusion: Reproductive events show secular and geographic variation within Switzerland. Smoking, parity and physical activity significantly predict age at natural menopause, particularly before age 52. The secular trend of earlier menarche and increased nulliparity may result in a higher risk of reproductive cancers in younger generations. [ABSTRACT FROM AUTHOR]

Chronic pain is a major global health problem. Untreated pain causes particular suffering in marginalized communities. Most studies investigating chronic pain in sub-Saharan Africa stem from South Africa and Nigeria. Pastoralists are particularly underrepresented in pain research. The main objective of this study is to investigate the burden of chronic pain in adult pastoralists in the Somali Regional State of Ethiopia. We conducted a cross-sectional household survey among adult pastoralists (aged 18 years or older, N = 299) by face-to-face interviews. To randomly select households, we applied GPS-based household localization and recruitment. Chronic pain was self-reported by 17.0% (95% CI: 10.8-25.7) of male and 34.7% (95% CI: 28.4-41.5) of female adult pastoralists. The prevalence of chronic pain increased with age from 5.4% (95% CI: 0.8-30.1; 18-34 years) to 27.1% (95% CI: 15.1-43.7; 35-54 years) to 69.1% (95% CI: 53.7-81.1; 55 years and older). The body sites most commonly affected among those with chronic pain were knees (37.2%), followed by lower back (33.7%) and head (23.3%). The data for the first time provide insights into the burden of chronic pain among Somali pastoralists and reveal associated risk factors. The results support the planning of locally adapted health interventions for pastoralist-specific pain management considering the effects of chronic pain on pastoralists’ daily lives. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second \((FEV_1)\), and its ratio to forced vital capacity \((FEV_1/FVC)\). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on \(FEV_1\) and \(FEV_1/FVC\) across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest \(P_{JMA} = 5.00×10^{−11})\), HLA-DQB1 and HLA-DQA2 (smallest \(P_{JMA} = 4.35×10^{−9})\), and KCNJ2 and SOX9 (smallest \(P_{JMA} = 1.28×10^{−8})\) were associated with \(FEV_1/FVC\) or \(FEV_1\) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

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 subject's 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. [ABSTRACT FROM AUTHOR]

Long-term ultrafine particle (UFP) exposure estimates at a fine spatial scale are needed for epidemiological studies. Land use regression (LUR) models were developed and evaluated for six European areas based on repeated 30 min monitoring following standardized protocols. In each area; Basel (Switzerland), Heraklion (Greece), Amsterdam, Maastricht, and Utrecht ("The Netherlands"), Norwich (United Kingdom), Sabadell (Spain), and Turin (Italy), 160-240 sites were monitored to develop LUR models by supervised stepwise selection of GIS predictors. For each area and all areas combined, 10 models were developed in stratified random selections of 90% of sites. UFP prediction robustness was evaluated with the intraclass correlation coefficient (ICC) at 31-50 external sites per area. Models from Basel and The Netherlands were validated against repeated 24 h outdoor measurements. Structure and model R² of local models were similar within, but varied between areas (e.g., 38-43% Turin; 25-31% Sabadell). Robustness of predictions within areas was high (ICC 0.73- 0.98). External validation R² was 53% in Basel and 50% in The Netherlands. Combined area models were robust (ICC 0.93-1.00) and explained UFP variation almost equally well as local models. In conclusion, robust UFP LUR models could be developed on short-term monitoring, explaining around 50% of spatial variance in longer-term measurements. [ABSTRACT FROM AUTHOR]

Background Epidemiological studies have shown effects of long-term exposure to air pollution on cardiovascular and respiratory health. However, studies investigating the effects of air pollution on cognition and brain function are limited. We investigated if neurocognitive functions are associated with air pollution exposure and whether apolipoprotein E (ApoE) alleles modify the association of air pollution exposure with cognition. Methods We investigated 789 women from the SALIA cohort during the 22-year follow-up examination (2008–2009). Exposure to particulate matter (PM) size fractions and nitrogen oxides (NO x ) were assigned to home addresses. Traffic indicators were used to assess residential proximity to high traffic load. Level of cognitive performance was assessed using the CERAD-Plus test. Air pollution effects on cognitive functioning were estimated cross-sectionally using adjusted linear regression models. Results Air pollution was negatively associated with cognitive function and cognitive performance in the subtests for semantic memory and visuo-construction. Significant associations could be observed for figure copying with an interquartile range increase of NO 2 ( β =–0.28 (95%CI:–0.44;–0.12)), NO x ( β =–0.25 (95%CI:–0.40;–0.09)), PM 10 ( β =–0.14 (95%CI:–0.26;–0.02)) and PM 2.5 ( β =–0.19 (95%CI:–0.36;–0.02)). The association with traffic load was significant in carriers of one or two ApoE ɛ4 risk alleles. Conclusion In this study of elderly women, markers of air pollution were associated with cognitive impairment in the visuospatial domain. The association of traffic exposure is significant in participants carrying the ApoE ε4 risk allele. [ABSTRACT FROM AUTHOR]

Air pollution is an important risk factor for global burden of disease. There has been recent interest in its possible role in the etiology of diabetes mellitus. Experimental evidence is suggestive, but epidemiological evidence is limited and mixed. We therefore explored the association between air pollution and prevalent diabetes, in a population-based Swiss cohort. We did cross-sectional analyses of 6392 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults [SAPALDIA], aged between 29 and 73 years. We used estimates of average individual home outdoor PM 10 [particulate matter <10 μm in diameter] and NO 2 [nitrogen dioxide] exposure over the 10 years preceding the survey. Their association with diabetes was modeled using mixed logistic regression models, including participants' study area as random effect, with incremental adjustment for confounders. There were 315 cases of diabetes (prevalence: 5.5% [95% confidence interval (CI): 2.8, 7.2%]). Both PM 10 and NO 2 were associated with prevalent diabetes with respective odds ratios of 1.40 [95% CI: 1.17, 1.67] and 1.19 [95% CI: 1.03, 1.38] per 10 μg/m 3 increase in the average home outdoor level. Associations with PM 10 were generally stronger than with NO 2 , even in the two-pollutant model. There was some indication that beta blockers mitigated the effect of PM 10 . The associations remained stable across different sensitivity analyses. Our study adds to the evidence that long term air pollution exposure is associated with diabetes mellitus. PM 10 appears to be a useful marker of aspects of air pollution relevant for diabetes. This association can be observed at concentrations below air quality guidelines. [ABSTRACT FROM AUTHOR]

Premature atrial contractions (PACs) are independent predictors of atrial fibrillation, stroke, and death. However, little is known about PAC frequency in the general population and its association with other cardiovascular risk factors. We performed a cross-sectional analysis among participants of the population-based Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). 24-hour Holter electrocardiograms to assess PAC prevalence and frequency were performed in a random sample of 1742 participants aged ≽50 years. The median (interquartile range) number of PACs per hour was 0.8 (0.4-1.8), 1.1 (0.5-2.4), 1.4 (0.7-4.6), 2.3 (0.8-6.9), and 2.6 (1.2-6.5) among participants aged 50 to 55, 55 to 60, 60 to 65, 65 to 70, and ≽70 years, respectively (PcO.OOOl). Only 18 (1.0%) participants did not have at least 1 PAC during Holter monitoring. In multivariable negative binomial regression models, PAC frequency was significantly associated with age (risk ratio [RR] per SD 1.80; P<0.0001), height (RR per SD 1.52; PC0.0001), prevalent cardiovascular disease (RR 2.40; P<0.0001), log-transformed N-terminal pro B-type natriuretic peptides (RR per SD 1.27; P<0.0001), physical activity ≽2 hours per day (RR 0.69; P=0.002), and high-density lipoprotein cholesterol (RR per SD 0.80; /J=0.0002). Hypertension and body mass index were not significantly related to PAC frequency. our knowledge, this is the first study to assess risk factors for PAC frequency in the general population aged ≽50 years. PACs are common, and their frequency is independently associated with age, height, history of cardiovascular disease, natriuretic peptide levels, physical activity, and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships need to be addressed in future studies. [ABSTRACT FROM AUTHOR]