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Drug type and dosing recommendation have been designed and optimized based on average response in the general population. Yet, there is significant inter-individual variability in drug response, which results in treatment inefficacy or adverse drug reactions in a subset of patients. This is partly due to genetic factors that typically affect drug metabolism or clearance. To verify the relevance and applicability of international pharmacogenetic guidelines in the Swiss population, we genotyped 1533 patients from a hospital-based biobank who received at least 30 different drugs, as documented in their electronic health record. We then assessed the prevalence of clinically actionable variants in 13 high-risk pharmacogenes. We compared the allele frequencies obtained in the hospital-based cohort with those of a Swiss population-based cohort of 4791 individuals. The prevalence of clinically actionable variants was comparable between the two cohorts, with most study participants (97.3%) carrying at least one actionable pharmacogenetic variant. We then assessed the frequency of high-risk prescriptions due to actionable gene-drug interactions and observed that 31% of patients in the hospital-based cohort were prescribed at least one drug for which they carried a high-risk variant, and for which international guidelines recommend a change of drug or dosage. Our analysis confirms the high prevalence of actionable pharmacogenetic variants in the Swiss population. It also shows that a substantial minority of patients are exposed to drugs for which they carry potentially problematic variants. Implementing a genetically informed approach to drug prescribing could have a positive impact on the quality of healthcare delivery.

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BACKGROUND: Only few previous cohort studies examined simultaneously predictors of chronic pain (CP) onset and recovery. Furthermore, these studies used various sociodemographic and pain-related characteristics, without standardized measures of sleep and depression. The present study aimed at expanding and strengthening these findings in a large Swiss population. METHODS: We analysed data from a longitudinal cohort (n = 4602) collected at two time points separated by 5 years in Lausanne, Switzerland. We studied through two independent multivariable logistic regression models, the predictors of CP onset and recovery, including socio-demographic data as well as standardized measures of sleep and mood. RESULTS: Chronic pain was reported by 43.1% and 44.4% of participants, with 11.6% at the second follow-up reporting moderate or intense pain. Neuropathic pain, regardless of intensity, had a more negative impact on quality of life. An inferential model (n = 1331) identified the male sex as predictive for recovering from CP. Older age, being overweight or obese (compared to normal weight), higher depression scores and pain medication intake were predictive for sustained pain at the second follow-up. A second model (n = 1886) identified being overweight or obese (compared to normal weight), low quality of sleep and being a former smoker (compared to a non-smoker) as predictive for developing CP, while the male sex was lowering the risk. CONCLUSIONS: While sex and weight are associated with both recovery and new CP onset, separate variables also need to be considered in these processes, underlining specific factors to be addressed, depending on the context, whether preventive or therapeutic. SIGNIFICANCE STATEMENT: Multivariable models in a Swiss cohort (N = 4602) associate male sex, not taking pain medication, normal weight, lower depression scores and younger age with recovery from chronic pain, while females, obese or overweight, having worse sleep and former smokers are associated with onset of new chronic pain. These common and separate factors need to be considered in treatment and prevention efforts.

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Importance: Accelerometry has been increasingly used as an objective index of sleep, physical activity, and circadian rhythms in people with mood disorders. However, most prior research has focused on sleep or physical activity alone without consideration of the strong within- and cross-domain intercorrelations; and few studies have distinguished between trait and state profiles of accelerometry domains in major depressive disorder (MDD). Objectives: To identify joint and individual components of the domains derived from accelerometry, including sleep, physical activity, and circadian rhythmicity using the Joint and Individual Variation Explained method (JIVE), a novel multimodal integrative dimension-reduction technique; and to examine associations between joint and individual components with current and remitted MDD. Design, Setting, and Participants: This cross-sectional study examined data from the second wave of a population cohort study from Lausanne, Switzerland. Participants included 2317 adults (1164 without MDD, 185 with current MDD, and 968 with remitted MDD) with accelerometry for at least 7 days. Statistical analysis was conducted from January 2021 to June 2023. Main Outcomes and Measures: Features derived from accelerometry for 14 days; current and remitted MDD. Logistic regression adjusted for age, sex, body mass index, and anxiety and substance use disorders. Results: Among 2317 adults included in the study, 1261 (54.42%) were female, and mean (SD) age was 61.79 (9.97) years. JIVE reduced 28 accelerometry features to 3 joint and 6 individual components (1 sleep, 2 physical activity, 3 circadian rhythms). Joint components explained 58.5%, 79.5%, 54.5% of the total variation in sleep, physical activity, and circadian rhythm domains, respectively. Both current and remitted depression were associated with the first 2 joint components that were distinguished by the salience of high-intensity physical activity and amplitude of circadian rhythm and timing of both sleep and physical activity, respectively. MDD had significantly weaker circadian rhythmicity. Conclusions and Relevance: Application of a novel multimodal dimension-reduction technique demonstrates the importance of joint influences of physical activity, circadian rhythms, and timing of both sleep and physical activity with MDD; dampened circadian rhythmicity may constitute a trait marker for MDD. This work illustrates the value of accelerometry as a potential biomarker for subtypes of depression and highlights the importance of consideration of the full 24-hour sleep-wake cycle in future studies.

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Sleep disturbances are well-known symptoms of major depressive disorder (MDD). However, the prospective risk of MDD in the presence of sleep disturbances in a general population-based cohort is not well known. This study investigated associations between both polysomnography (PSG)-based or subjective sleep features and incident MDD. Participants representative of the general population who had never had MDD completed sleep questionnaires (n = 2000) and/or underwent PSG (n = 717). Over 8 years' follow-up, participants completed psychiatric interviews enabling the diagnosis of MDD. Survival Cox models were used to analyze associations between sleep features and MDD incidence. A higher Epworth Sleepiness Scale and presence of insomnia symptoms were significantly associated with a higher incidence of MDD (hazard ratio [HR] [95 % confidence interval (CI)]: 1.062 [1.022-1.103], p = 0.002 and 1.437 [1.064-1.940], p = 0.018, respectively). Higher density of rapid eye movements in rapid eye movement (REM) sleep was associated with a higher incidence of MDD in men (HR 1.270 [95 % CI 1.064-1.516], p = 0.008). In women, higher delta power spectral density was associated with a lower MDD incidence (HR 0.674 [95 % CI 0.463-0.981], p = 0.039). This study confirmed the associations between subjective and objective sleep features and the incidence of MDD in a large community dwelling cohort.

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IMPORTANCE AND OBJECTIVE: Self-reported caffeine consumption has been widely used in research while it may be subject to bias. We sought to investigate the associations between self-reported caffeine consumption and plasma levels of caffeine and its two main metabolites (paraxanthine and theophylline) in the community. METHODS: Data from two population-based studies (SKIPOGH1 and 2 (N = 1246) and CoLaus|PsyCoLaus (N = 4461)) conducted in Switzerland were used. Self-reported caffeine consumption was assessed using questionnaires. Plasma levels of caffeine and its metabolites were quantified by ultra-high performance liquid chromatography coupled to a tandem quadrupole mass spectrometer. RESULTS: In both studies, mean log plasma levels of caffeine and its two metabolites were over 6.48 (plasma levels = 652 ng/ml) when no caffeine consumption was reported. Subsequently, nonlinear associations between log plasma levels and self-reported caffeine consumption were observed in SKIPOGH, with a change of the slope at 3-5 cups of espresso per day in SKIPOGH1 but not SKIPOGH2. In CoLaus|PsyCoLaus, increased daily consumption of caffeinated beverages was associated with increased log plasma levels with a change of the slope at 3 cups. In both studies, declared caffeine consumption higher than 3-5 cups per day was not associated with higher plasma levels of caffeine and its metabolites. CONCLUSION: Self-reports of no or low caffeine consumption and consumption of more than 3-5 cups of coffee should be interpreted with caution, with possible under- or over-estimation. Quantifying plasma levels of caffeine and its metabolites may contribute to a better estimation of caffeine intake.

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Introduction: In 2020, the European Society of Cardiology (ESC) recommends 150 min of moderate or 75 min of vigorous-intensity PA per week. While general population PA adherence is suboptimal, its status among those with previous ASCVD or high ASCVD risk remains unknown. We aimed to assess objective adherence to ESC PA recommendations using accelerometer-based measurement among these populations. Methodology: We used data from the Swiss CoLaus|PsyCoLaus cohort study (2014-2016). PA was measured using a 14-day wrist accelerometer. Adherence was defined as > 80 % of recommended PA achievement. Adherence was investigated separately among participants with previous ASCVD and among cardiovascular risk groups (based on the Systematic Coronary Risk Evaluation SCORE-1 and more recent SCORE2) with simple and multivariable logistic regressions. Participants' characteristics were also evaluated as independent factors after adjustment. Results: We studied 1867 participants (median age: 61.2 years, 51.3 % female). ESC PA Adherence reached 55.5 % overall, and 37 % in those with previous ASCVD. Multivariable analysis showed no significant association between previous ASCVD or high cardiovascular risk and PA adherence (Odds ratio adjusted [ORa] 0.9, 95 % Confidence Interval [CI] 0.6-1.4 and ORa 0.7, 95 % CI 0.4-1.2, respectively). Age (≥60 years old), obesity, smoking, chronic renal disease, hypertension, diabetes and benzodiazepine use were significantly associated with lower likelihood of PA adherence in multivariable logistic regression. Conclusion: Adherence to ESC PA guidelines, particularly in participants with higher cardiovascular risk, was poor. Since PA adherence was associated with modifiable risk factors (e.g., obesity, smoking, and benzodiazepine use), maintained efforts to implement the ESC recommendations are advised.

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Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

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Despite major advances, our understanding of the neurobiology of life course socioeconomic conditions is still scarce. This study aimed to provide insight into the pathways linking socioeconomic exposures-household income, last known occupational position, and life course socioeconomic trajectories-with brain microstructure and cognitive performance in middle to late adulthood. We assessed socioeconomic conditions alongside quantitative relaxometry and diffusion-weighted magnetic resonance imaging indicators of brain tissue microstructure and cognitive performance in a sample of community-dwelling men and women (N = 751, aged 50-91 years). We adjusted the applied regression analyses and structural equation models for the linear and nonlinear effects of age, sex, education, cardiovascular risk factors, and the presence of depression, anxiety, and substance use disorders. Individuals from lower-income households showed signs of advanced brain white matter (WM) aging with greater mean diffusivity (MD), lower neurite density, lower myelination, and lower iron content. The association between household income and MD was mediated by neurite density (B = 0.084, p = 0.003) and myelination (B = 0.019, p = 0.009); MD partially mediated the association between household income and cognitive performance (B = 0.017, p < 0.05). Household income moderated the relation between WM microstructure and cognitive performance, such that greater MD, lower myelination, or lower neurite density was only associated with poorer cognitive performance among individuals from lower-income households. Individuals from higher-income households showed preserved cognitive performance even with greater MD, lower myelination, or lower neurite density. These findings provide novel mechanistic insights into the associations between socioeconomic conditions, brain anatomy, and cognitive performance in middle to late adulthood.

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INTRODUCTION: Mental health disorders figure among the many comorbidities of obstructive respiratory diseases. The multisystemic characteristics of chronic respiratory disease and its impact on quality of life could affect depressive and/or anxiety disorders. We aimed to evaluate the association of spirometric indices, ventilatory disorders, and self-reported respiratory diseases with psychiatric disorders considering potential confounders. METHODS: We analysed data from CoLaus|PsyCoLaus, a Swiss population-based cohort study, consisting of 2'774 participants (56% women; mean age: 62.3 (standard deviation = ±9.9) years) who performed spirometry and completed semi-structured psychiatric interviews. We defined ventilatory disorders using GLI-2012 references. Major depressive episode (MDE) and anxiety disorders were defined using the DSM-IV (Diagnostic and Statistical Manual). RESULTS: 630 subjects (22.7%) presented a recent MDE. Reversible obstructive ventilatory disorders were associated with recent MDE (OR = 1.94, 95% confidence interval (95% CI) 1.10-3.43) and recent anxiety disorders (2.21 [1.16-4.22]) only in unadjusted model. Self-reported chronic obstructive pulmonary (COPD) and asthma were associated with MDE with ORs of 2.49 (95% CI, 1.19-5.27) and 1.56 (95% CI, 1.04-2.35) after adjustment, respectively. Possible restrictive ventilatory impairment was positively associated with recent anxiety disorders (OR = 2.46, 1.10-5.51). Z-scores of FEV1, FVC, and maximal mid-expiratory flow were not associated with psychiatric disorders. There was no association between ventilatory disorders and MDE in adjusted models. CONCLUSIONS: In this cross-sectional population-based study, the association between respiratory disorders and depressive disorders was observed for self-reported COPD and asthma, but not with objective diagnoses based on spirometry. Lung volumes are not associated with psychiatric disorders. Further prospective studies will be necessary to understand the significance of the association.

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BACKGROUND: High blood pressure (BP) is a major risk factor for cardiovascular disease (CVD). Adequate treatment of high BP should reduce the risk of CVD, but this association has seldom been assessed in a general population setting. METHODS: Population-based prospective study conducted in Lausanne, Switzerland, with a follow-up between 2003 and 2021. Participants were categorised as normal BP, untreated high BP, treated and uncontrolled BP and treated and controlled BP. Total and CVD mortality as well as any CVD event were assessed. RESULTS: 5341 participants (65% normal, 17.4% untreated, 8.8% treated and uncontrolled and 8.8% treated and controlled) were included. After a median follow-up of 14 years (IQR: 11-15), 575 CVD events occurred. Relative to participants with normal BP, multivariable-adjusted HRs (and 95% CI) for total CVD were 1.38 (1.11 to 1.72) for untreated, 1.35 (1.04 to 1.76) for treated and uncontrolled and 1.50 (1.15 to 1.95) for treated and controlled. The corresponding HRs for CVD mortality (112 events) were 0.94 (0.52 to 1.70), 1.77 (1.00 to 3.12) and 2.52 (1.50 to 4.23), respectively. For total mortality (677 events), the HRs were 1.24 (1.01 to 1.52), 1.26 (0.99 to 1.60) and 1.27 (0.99 to 1.62), respectively. Sensitivity analysis using BP status during a 5-year period and categorising participants as always normal, always treated and uncontrolled, always treated and controlled and other led to similar findings. CONCLUSION: Over a long follow-up period of 14 years, BP control was not associated with reduction of CVD events, CVD-related or total mortality. This finding should help define further studies on factors affecting CVD and mortality in people treated for hypertension in the general population.

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OBJECTIVE: We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy. DESIGN: Secondary analysis of a prospective population-based cohort study. PARTICIPANTS: We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland. MEASUREMENTS: The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes. METHODS: Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up. RESULTS: Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (-3% to 26.5%)] and eggs [18% (2.3%-33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes. CONCLUSION: We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results.

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Whether cardiovascular risk scores geographically aggregate and inform on spatial development of atherosclerotic cardiovascular diseases (ASCVD) remains unknown. Our aim is to determine the spatial distribution of 10-year predicted cardiovascular risk and ASCVD, and to compare the overlap of the resulting spatial distributions. Using prospective data from the CoLaus|PsyCoLaus cohort study (2003-2021) we computed SCORE2 in participants free from ASCVD. Geographical distributions of predicted risk and events were determined using the Gi* Getis-Ord autocorrelation statistic. 6203 individuals (54% women, mean age 52.5 ± SD 10.7, ASCVD incidence rate 5.7%) were included. We identified clusters of high versus low predicted risk (4%, 6%, respectively) and ASCVD (5%, 5% respectively) at baseline. They persisted at follow-up. Overlap of SCORE2 and ASCVD clusters was marginal. Body-mass index and alcohol consumption explained most of the predicted risk distribution. For ASCVD, high clusters persisted or were reinforced after multivariate adjustment, while low incidence clusters were reduced, multifactorial determinants. Incidence rate of ASCVD was 2.5% higher (IC 95%, 1.4-3.7) in clusters of higher incidence of ASCVD. To develop up-to-date, geographically targeted prevention strategies, there is a need to study novel geographically risk factors affecting ASCVD and to update commonly used prediction models for a population approach.

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INTRODUCTION: The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate.  Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex. METHOD: Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003-2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex,  age and gender-related factors were also tested. RESULTS: Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41-0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated a decreased risk of MetS compared to males. Conversely smoking and unemployment were significant risk factors for MetS development among male adults. CONCLUSIONS: Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people.

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BACKGROUND: Pharmacologic thromboprophylaxis (pTPX) might exacerbate the risk of clinically relevant bleeding (CRB) and hospital-acquired anemia (HAA) in older multimorbid inpatients. OBJECTIVES: We aimed to evaluate the association of pTPX use with CRB and HAA. METHODS: We used data from a prospective cohort study conducted in 3 Swiss university hospitals. Adult patients admitted to internal medicine wards with no therapeutic anticoagulation were included. pTPX use was ascertained during hospitalization. Outcomes were in-hospital CRB and HAA. We calculated incidence rates by status of pTPX. We assessed the association of pTPX with CRB using survival analysis and with HAA using logistic regression, adjusted for infection, length of stay, and the International Medical Prevention Registry on Venous Thromboembolism bleeding risk score. RESULTS: Among 1305 patients (mean age, 63.7 years; 44% women, 90% at low risk of bleeding), 809 (62%) received pTPX. The incidence of CRB was 2.4 per 1000 patient-days and was not significantly higher in patients with pTPX than in those without. We found no significant association between pTPX and CRB. HAA was frequent (20.2%) and higher in patients with pTPX than in those without (23.2% vs 15.3%). The incidence of HAA was 21.2 per 1000 patient-days and did not significantly differ between patients with pTPX and those without. We found an association between pTPX and HAA (adjusted odds ratio, 1.4; 95% CI, 1.0-2.1). CONCLUSION: Our study confirmed the safety of pTPX in medical inpatients at low risk of bleeding but identified an association between pTPX and HAA. Adherence to guidelines that recommend administering pTPX to medical inpatients at increased venous thromboembolism risk and low bleeding risk is necessary.

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BACKGROUND: Lack of physical activity (PA) and high sedentary behavior (SB) may enhance mental health problems, including depression, and are associated with increased mortality. Aside from a large body of research on major depressive disorder (MDD) assessed as an entity and either PA or SB, few studies have examined associations among subtypes of MDD and both PA and SB simultaneously derived from wrist-worn accelerometers. Accordingly, our aim was to explore the associations among MDD subtypes (atypical, melancholic, combined atypical-melancholic and unspecified) and four actigraphy-derived behaviors combining the levels of PA and SB. METHODS: The sample stemmed from CoLaus|PsyCoLaus, a population-based cohort study, consisting of 2375 participants (55.1% women; mean age: 62.4 years) who wore an accelorometer for 14 days after a physical exam and subsequently completed a semi-structured psychiatric interview. Activity behaviors were defined according to the combination of the levels of moderate-to-vigorous intensity PA and SB. Associations of remitted MDD subtypes, current MDD and physical inactivity behaviors were assessed using multinomial logistic regression, adjusted for socio-demographic characteristics, a history of anxiety, alcohol and drug use disorders and cardiovascular risk factors. RESULTS: In the fully adjusted model, participants with the remitted combined atypical-melancholic subtype had a higher risk of being more physically inactive. CONCLUSIONS: Our findings suggest that low PA and high SB are not restricted to the duration of depressive episodes in people with atypical and melancholic episodes. The lack of PA and high SB in this group of depressive patients exposes them to an additional long-term cardiovascular risk and measures to increase PA may be particularly fruitful in this MDD subgroup.

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AIMS: Outcomes reported for patients with hospitalization for acute heart failure (AHF) treatment vary worldwide. Ethnicity-associated characteristics may explain this observation. This observational study compares characteristics and 1-year outcomes of Kyrgyz and Swiss AHF patients against the background of European Society of Cardiology guidelines-based cardiovascular care established in both countries. METHODS AND RESULTS: The primary endpoint was 1 year all-cause mortality (ACM); the secondary endpoint was 1 year ACM or HF-related rehospitalization. A total of 538 Kyrgyz and 537 Swiss AHF patients were included. Kyrgyz patients were younger (64.0 vs. 83.0 years, P < 0.001); ischaemic or rheumatic heart disease and chronic obstructive pulmonary disease were more prevalent (always P < 0.001). In Swiss patients, smoking, dyslipidaemia, hypertension, and atrial flutter/fibrillation were more frequent (always P ≤ 0.035); moreover, left ventricular ejection fraction (LVEF) was higher (47% vs. 36%; P < 0.001), and >mild aortic stenosis was more prevalent (P < 0.001). Other valvular pathologies were more prevalent in Kyrgyz patients (P < 0.001). At discharge, more Swiss patients were on vasodilatory treatment (P < 0.006), while mineralocorticoid receptor antagonists (P = 0.001), beta-blockers (P = 0.001), or loop diuretics (P < 0.001) were less often prescribed. In Kyrgyz patients, unadjusted odds for the primary and secondary endpoints were lower [odds ratio (OR) 0.68, 95% confidence interval (CI): 0.51-0.90, P = 0.008; OR 0.72, 95% CI: 0.56-0.91, P = 0.006, respectively]. After adjustment for age and LVEF, no difference remained (primary endpoint: OR 1.03, 95% CI: 0.71-1.49, P = 0.894; secondary endpoint: OR 0.82, 95% CI: 0.60-1.12, P = 0.206). CONCLUSIONS: On the background of identical guidelines, age- and LVEF-adjusted outcomes were not different between Central Asian and Western European AHF patients despite of large ethnical disparity.

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Research on the relationship between obstructive sleep apnea and cognitive functioning has yielded conflicting results, particularly in the older population, and moderators of this association have rarely been studied. Here we investigated the cross-sectional association between obstructive sleep apnea and cognitive functioning as well as the moderating effect of age, sex, apolipoprotein E4, and obesity on this association among community-dwelling older people. We analysed data from 496 participants (71.4 ± 4.4 years; 45.6% men) of the HypnoLaus study who underwent polysomnography and a battery of neuropsychological tests. The sample was categorised as no-to-mild obstructive sleep apnea (apnea-hypopnea index 0-14.9/h; reference), moderate obstructive sleep apnea (apnea-hypopnea index 15.0-29.9/h), or severe obstructive sleep apnea (apnea-hypopnea index ≥30/h). Regression and moderation analyses were performed with adjustment for confounders. Apolipoprotein E4 and obesity moderated the association between severe obstructive sleep apnea and processing speed, whereas no moderating effects were found for age and sex. In apolipoprotein E4 carriers only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.13, p = 0.024). In obese participants only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.02, p = 0.025) and Stroop condition 2 (B = 3.30, p = 0.034). Severe obstructive sleep apnea was also associated with lower executive function in the whole sample according to Stroop condition 3 (B = 3.44, p = 0.020) and Stroop interference score (B = 0.24, p = 0.006). Our findings support associations of severe obstructive sleep apnea (but not moderate obstructive sleep apnea) with lower performance in processing speed and executive function in the older general population. Apolipoprotein E4 and obesity appear to be vulnerability factors that strengthen the association between severe obstructive sleep apnea and lower performance in processing speed.

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