Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies.

BACKGROUND: Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults. METHODS: We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D. RESULTS: The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40-1.49]). The association was weaker in individuals aged ≥75 years versus 65-74 years (HR 1.32 [1.19-1.46] vs. 1.56 [1.50-1.62]; p-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85-1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59-0.98]). CONCLUSIONS: T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.

How ambient temperature affects mood: an ecological momentary assessment study in Switzerland.

BACKGROUND: Recent research has suggested that an increase in temperature can negatively affect mental health and increase hospitalization for mental illness. It is not clear, however, what factors or mechanisms mediate this association. We aimed to (1) investigate the associations between ambient temperatures and bad daily mood, and (2) identify variables affecting the strength of these associations (modifiers) including the time, the day of the week and the year of the mood rating, socio-demographic characteristics, sleep quality, psychiatric disorders and the personality trait neuroticism in the community. METHODS: Data stemmed from the second follow-up evaluation of CoLaus|PsyCoLaus, a prospective cohort study conducted in the general population of Lausanne (Switzerland). The 906 participants rated their mood level four times a day during seven days using a cell phone app. Mixed-effects logistic regression was used to determine the association between daily maximum temperature and mood level. Participant ID was inserted as a random effect in the model, whereas the time of the day, the day of the week and the year were inserted as fixed effects. Models were controlled for several confounders (socio-demographic characteristics, sleep quality, weather parameters and air pollutants). Stratified analyses were conducted based on socio-demographic characteristics, sleep quality, presence of psychiatric disorders or a high neuroticism. RESULTS: Overall, the probability of having a bad mood for the entire day decreased by 7.0% (OR: 0.93: 95% CI 0.88, 0.99) for each 5 °C increase in maximum temperature. A smaller and less precise effect (-3%; OR: 0.97: 95% CI 0.91, 1.03) was found when controlling for sunshine duration. A higher association was found in participants with bipolar disorder (-23%; OR: 0.77: 95% CI 0.51, 1.17) and in participants with a high neuroticism (-13%; OR: 0.87 95% CI 0.80, 0.95), whereas the association was reversed for participants with anxiety (20%; OR: 1.20: 95% CI 0.90, 1.59), depression (18%; OR: 1.18 95% CI 0.94, 1.48) and schizophrenia (193%; OR: 2.93 95% CI 1.17, 7.73). CONCLUSIONS: According to our findings, rising temperatures may positively affect mood in the general population. However, individuals with certain psychiatric disorders, such as anxiety, depression, and schizophrenia, may exhibit altered responses to heat, which may explain their increased morbidity when exposed to high temperatures. This suggests that tailored public health policies are required to protect this vulnerable population.

Prevalence of atrial fibrillation : The Swiss population-based CoLaus|PsyCoLaus study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with increased morbi-mortality. The prevalence of AF in the Western world is increasing; however, reports on the prevalence of AF in the past decade are scarce, and whether the prevalence of AF increased during the last decade in Switzerland remains uncertain. Therefore, using data from a Swiss population-based sample, we aimed to assess the point prevalence of AF from 2014 to 2017 and to investigate determinants of AF. METHODS: A cross-sectional analysis of 4616 Caucasian participants aged 45-86 years (55% women) from a population-based sample was designed to explore the point prevalence and determinants of cardiovascular risk factors in the population of Lausanne, Switzerland. AF was assessed using electrocardiography (ECG) between 2014 and 2017. RESULTS: Overall, the point prevalence of AF was 0.9% (95% confidence interval [95% CI]: 0.7-1.2%) and the combined AF + atrial flutter (AFL) point prevalence was 1.1% (95% CI: 8.4-1.5%). The point prevalence of AF was higher among men (81% vs. 19% in women) and increased with age, reaching 3.1% in participants aged ≥ 80. In multivariable analysis, male gender (odds ratio and 95% CI: 4.98 [1.01-24.6]) and increasing age (2.86 [1.40-5.87] per decade) were associated with AF. CONCLUSION: The point prevalence of AF and of AF + AFL, assessed between 2014 and 2017 in the city of Lausanne (Switzerland), was low but increased with age and in men.

[Do we all suffer from imposter syndrome?] / Souffrons-nous toutes et tous d'un syndrome d'imposture?

Imposture syndrome is widespread among physicians and medical students. It is defined as a psychological experience in which people doubt their own skills and achievements despite proven successes and thus have an unfounded fear of being found out. This can have serious consequences, such as anxiety and/or depressive disorders, and can lead to burn-out. The Clance scale is a self-assessment tool used to measure the level of imposture experienced and, when appropriate, to assess the suffering caused. The aim of this article is to help recognise this syndrome, which is one way of preventing it.

Le syndrome d'imposture est largement répandu chez les médecins et les étudiant-e-s en médecine. Il est défini comme une expérience psychologique où l'individu, malgré des succès démontrés, doute de ses compétences et réussites et, ainsi, éprouve une crainte infondée d'être démasqué. D'importantes conséquences comme des troubles anxieux et/ou dépressifs associés à un burnout peuvent en découler. L'échelle de Clance est un outil d'autoévaluation permettant de mesurer le niveau d'imposture ressenti et, le cas échéant, d'en évaluer la souffrance engendrée. Le but de cet article est d'aider à reconnaître ce syndrome, ce qui constitue l'un des axes de sa prévention.

Investigating acceptability of a training programme in precision medicine for frontline healthcare professionals: a mixed methods study.

BACKGROUND: Precision Medicine offers tailored prevention, diagnosis, treatment and management to patients that considers genomics, lifestyle and environmental factors. If implementation of Precision Medicine is to advance, effective, focused upskilling of frontline healthcare professionals through quality continuing professional development is needed. This study reports on an evidence-based approach to needs assessment to investigate the current level of knowledge of Precision Medicine, acceptable content for training, the perceived potential of a more precision approach to patient care and motivation to participate in a training programme among pharmacists, advanced practice nurses and general practitioners. Investigating perceived needs can avoid a top-down approach and support a design that is fit for purpose to targeted professions. METHODS: This study reports on 2 focus groups (n = 12) delivered in French and German with equal professional participation of the targeted professions. The research objectives were investigated in two phases. During the first phase, a literature review and expert consultations were conducted to develop a definition of PM, patient cases and content for training. In a second phase, these investigations were further explored using focus groups to investigate acceptable learning objectives, the potential of PM to relevant professions and motivation of participants. Quantitative investigations using rating scales and visual analogues were incorporated. The focus groups were audio recorded, transcribed by intelligent verbatim and translated to English. NVivo was used for data analysis and interpretation following a hybrid approach using the Framework Method and thematic analysis. The analytical framework, Implementation Science, was applied to organise and present research data. RESULTS: Precision Medicine is considered a new topic area, largely unfamiliar to frontline healthcare professionals.. There was acceptance of a more precision approach to care among all participants with perceived positive implications for patients. Valuable insight was gathered on acceptable content and form for training. All participants expressed concerns on readiness within their professions which included an insufficient system infrastructure, a lack of time to attend needed training, a lack of clarity for use in practice and the time needed to build a support network. CONCLUSIONS: A precision approach to patient care is on the horizon for health care professionals not only in hospital settings but also at the community level. Our results conclude that an adaptable and flexible training programme in PM is timely, contextually relevant and conducive to the needs of targeted health professions for successful implementation. A training programme in PM will require support across sectors and stakeholders, supporting insurance models, educated patients and integrated care supported by innovative technology. Implementation Science outcomes are a useful strategy towards design of an effective training programme that can have measurable impact in practice.

[Teaching and learning during attending rounds in internal medicine: an anthropological study]. / Enseigner et apprendre lors des grandes visites en médecine interne hospitalière : Une étude anthropologique.

This anthropological research aims to highlight the educational approaches in action during attending rounds. The goal is to understand how specific learning domains, professional socialization and learning environments are influenced by the different ways of conducting attending rounds. Two formats of rounds were noted: the IN format, when the patient case is presented in the patient room, and the OUT format. Six educational approaches were identified. The attending round format has an impact on the approaches used. The latter contribute to the development, to varying degrees, of knowledge, skills and attitudes. Attending rounds remain a space for "top-down" transmission and supervision, even though some approaches involve learner initiatives and peer group logic.

Notre recherche anthropologique vise à mettre en lumière les approches pédagogiques à l'œuvre durant les grandes visites. Comment les domaines d'apprentissages visés, la socialisation professionnelle et l'environnement d'apprentissage sont-ils influencés par les différentes manières de les conduire ? Deux formes de visites sont retrouvées : la forme IN (le cas est présenté au lit du patient) et la forme OUT. Six approches pédagogiques ont été identifiées. La forme de grande visite influence les approches pédagogiques mobilisées. Celles-ci contribuent à développer, à des degrés variables, des savoirs, savoir-faire et savoir-être. Les grandes visites restent un espace de transmission « top-down ¼ et de surveillance, même si certaines approches encouragent les initiatives des apprenants ainsi que les logiques de groupes de pairs.

Diurnal Salivary Cortisol in Sarcopenic Postmenopausal Women: The OsteoLaus Cohort.

Sarcopenia, similar to hypercortisolism, is characterized by loss of muscle mass and strength. Cortisol circadian rhythm changes with aging (blunted late-day nadir values) were suggested to contribute to this decline. We aimed to explore the relationship between diurnal salivary cortisol values and sarcopenia diagnosis and its components in postmenopausal women. This is a cross-sectional study within the OsteoLaus population-based cohort in Lausanne (Switzerland). Participants had a body composition assessment by dual X-ray absorptiometry (DXA), a grip strength (GS) measure, and salivary cortisol measures (at awakening, 30 min thereafter, 11 AM (sc-11AM) and 8 PM (sc-8PM)). Associations between salivary cortisol and sarcopenia diagnosed by six different criteria (based on appendicular lean mass (ALM) assessed by DXA, and muscle strength by GS), and its components, were analyzed. 471 women aged > 50 years (63.0 ± 7.5) were included. Various definitions identified different participants as sarcopenic, who consistently presented higher salivary cortisol at 11 AM and/or 8 PM. There were no associations between salivary cortisol levels and ALM measures, either absolute or after correction to height squared (ALM index) or body mass index. GS was inversely correlated to sc-11AM (r = - 0.153, p < 0.001) and sc-8PM (r = - 0.118, p = 0.002). Each 10 nmol/l increase of sc-11AM, respectively sc-8PM, was associated with a GS decrease of 1.758 (SE 0.472) kg, respectively 2.929 (SE 1.115) kg. In postmenopausal women, sarcopenia is associated with higher salivary cortisol levels at 11 AM and 8 PM. An increase of daily free cortisol levels in the physiological range could participate to sarcopenia development by decreasing muscle function in postmenopausal women.

Risk factors of excessive daytime sleepiness in a prospective population-based cohort.

Although excessive daytime sleepiness is commonly evaluated in clinical and research settings using the Epworth Sleepiness Scale, few studies have assessed the factors associated with its incidence in the general population. We prospectively investigated the predictors of incident and persistent excessive daytime sleepiness in 2,751 subjects (46.1% men, mean age 56.0 ± 9.8 years) from the CoLaus-PsyCoLaus population-based cohort (Lausanne, Switzerland) over 5 years. Participants completed the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index, and underwent a full clinical evaluation at baseline and 5 years afterwards. Ambulatory polysomnography was performed at baseline in a sub-sample of 1,404 subjects. Among the 2,438 subjects without excessive daytime sleepiness (Epworth Sleepiness Scale ≤ 10) at baseline, the 5-year incidence of excessive daytime sleepiness was 5.1% (n = 124). Multivariate logistic regression revealed that male sex, depressive symptoms, reported poor sleep quality and moderate to severe obstructive sleep apnea were independent predictors of incident excessive daytime sleepiness, while older age, moderate coffee consumption, periodic leg movement during sleep and hypertension were independent protective factors. Stratified analysis according to sex and age showed some distinctive associations. Among the 313 patients with excessive daytime sleepiness at baseline, 137 (43.8%) had persistent excessive daytime sleepiness 5 years later. Our findings provide new insights into the predictors of incident excessive daytime sleepiness, but interventional studies are needed to understand the impact of treating these risk factors on the incidence of excessive daytime sleepiness.

Trends in prevalence and outcomes of frailty in a Swiss university hospital: a retrospective observational study.

BACKGROUND: Frailty complicates management and worsens outcomes. We assessed the prevalence, determinants and consequences of frailty among elderly patients in a hospital setting. DESIGN: Retrospective observational study in a Swiss university hospital. METHODS: 22,323 patients aged ≥65 years hospitalized between January 2009 and December 2017 at the internal medicine ward were included. Frailty was defined by the Hospital Frailty Risk Score (HFRS) and patients were categorized as low (HFRS<5), intermediate (HFRS 5-15) and high (HFRS>15) risk. RESULTS: Overall prevalence of intermediate and high risk of frailty was 43% and 20%, respectively; prevalence was higher in women and increased with age. Prevalence of high risk of frailty increased from 11.4% in 2009 to 31% in 2012, and decreased to 19.2% in 2017. After multivariable adjustment, frailty was associated with increased length of stay: average and (95% confidence interval) 11.9 (11.7-12.1), 15.6 (15.4-15.8) and 19.7 (19.3-20.1) days for low, intermediate and high risk, respectively, and increased likelihood of ICU stay: odds ratio (OR) and (95% CI) 1.57 (1.41-1.75) and 2.10 (1.82-2.42) for intermediate and high risk, respectively, p for trend <0.001. Frailty was associated with increased likelihood of hospital costs >70,000 CHF: OR and (95% CI) 3.46 (2.79-4.29) and 10.7 (8.47-13.6) for intermediate and high risk, respectively, p for trend <0.001, and with a lower likelihood of complete cost coverage: OR and (95% CI) 0.70 (0.65-0.76) and 0.52 (0.47-0.58) for intermediate and high risk, respectively, p for trend<0.001. CONCLUSIONS: Frailty is a frequent condition among hospitalized patients and is associated with higher costs.

[Strategy diagnostic and therapeutic of an hypophosphatemia]. / Stratégie diagnostique et thérapeutique d'une hypophosphatémie.

Hypophosphatemia is an electrolyte disorder frequently faced in inpatient and outpatient practice. Associated symptoms are very variable but are often nonspecific. The consequence is that it might be overlooked. Yet, when severe, hypophosphatemia is associated with a significant morbi-mortality and, therefore, needs to be identified and treated appropriately. Treatment goes from identifying the cause to substitution according to whether it is symptomatic or not and its severity. Mild to moderate hypophosphatemia needs substitution only when symptomatic which will be administrated orally, while severe hypophosphatemia requires an intravenous substitution. We review here situations at risk of hypophosphatemia, its clinical manifestations and its management in terms of diagnostic and treatment.

L'hypophosphatémie est un désordre électrolytique fréquemment rencontré, tant en milieu hospitalier qu'ambulatoire. Sa symptomatologie est très variable et souvent aspécifique. De ce fait, elle peut parfois être manquée. Pourtant, lorsque sévère, elle est grevée d'une morbimortalité non négligeable. Le traitement passe par l'identification de sa cause, puis une substitution en fonction de la présentation clinique et de sa sévérité. Une hypophosphatémie légère à modérée nécessite une supplémentation en cas de symptômes et sera administrée par voie orale, tandis qu'une hypophosphatémie sévère justifie une supplémentation intraveineuse. Cet article intègre un rappel du métabolisme du phosphate, les situations associées à un risque d'hypophosphatémie, ses manifestations cliniques et sa gestion tant sur le plan diagnostique que thérapeutique.

Life worth living: cross-sectional study on the prevalence and determinants of the wish to die in elderly patients hospitalized in an internal medicine ward.

BACKGROUND: Elderly people frequently express the wish to die: this ranges from a simple wish for a natural death to a more explicit request for death. The frequency of the wish to die and its associated factors have not been assessed in acute hospitalization settings. This study aimed to investigate the prevalence and determinants of the wish to die in elderly (≥65 years) patients hospitalized in an internal medicine ward. METHODS: This cross-sectional study was conducted between 1 May, 2018, and 30 April, 2019, in an acute care internal medicine ward in a Swiss university hospital. Participants were a consecutive sample of 232 patients (44.8% women, 79.3 ± 8.1 years) with no cognitive impairment. Wish to die was assessed using the Schedule of Attitudes toward Hastened Death-senior and the Categories of Attitudes toward Death Occurrence scales. RESULTS: Prevalence of the wish to die was 8.6% (95% confidence interval [CI]: 5.3-13.0). Bivariate analysis showed that patients expressing the wish to die were older (P = .014), had a lower quality of life (P < .001), and showed more depressive symptoms (P = .044). Multivariable analysis showed that increased age was positively (odds ratio [OR] for a 5-year increase: 1.43, 95% CI 0.99-2.04, P = .048) and quality of life negatively (OR: 0.54, 95% CI 0.39-0.75, P < 0.001) associated with the likelihood of wishing to die. Participants did not experience stress during the interview. CONCLUSIONS: Prevalence of the wish to die among elderly patients admitted to an acute hospital setting is low, but highly relevant for clinical practice. Older age increases and better quality of life decreases the likelihood of wishing to die. Discussion of death appears to be well tolerated by patients.

[Pharmacogenomics : a toolbox to improve drug prescription]. / Pharmacogénomique et aide à la prescription médicamenteuse.

As a result of advances in pharmacogenomics (PGx), the paradigm that a single dose of a drug is extrapolated to an entire population is set to change. Personalising drug prescriptions according to individual genomic determinants would make it possible to increase the effectiveness and tolerance of treatments. In Switzerland, any doctor can prescribe validated PGx tests for five actionable drugs : abacavir, carbamazepine, thiopurines [azathioprine], fluoropyrimidines [5-FU, capecitabine] and irinotecan. Such an approach presupposes that PGx data are shared with trained clinicians and that prescribing aids can guide them.

Suite aux progrès de la pharmacogénomique (PGx), le paradigme qui veut qu'une dose unique d'un médicament soit extrapolée à l'ensemble d'une population est appelé à évoluer. Une personnalisation de la prescription médicamenteuse en fonction de déterminants génomiques individuels permettrait d'augmenter l'efficacité et la tolérance aux traitements. En Suisse, tout médecin peut réaliser des tests PGx validés pour cinq médicaments actionnables qui sont : l'abacavir, la carbamazépine, les thiopurines (azathioprine), les fluoropyrimidines (5-fluoro-uracile, capécitabine) et l'irinotécan. Une telle approche présuppose que les données PGx soient partagées avec des cliniciens formés et que des outils d'aide à la prescription puissent les orienter.

[Organizational Impacts and Clinical Challenges of the COVID-19 Pandemic on a Swiss Tertiary Internal Medicine Department]. / Impacts organisationnels et défis cliniques de la pandémie COVID-19 pour un service hospitalier de médecine interne universitaire.

The rapid progression of COVID-19 is an organizational challenge for all hospitals. To secure the patient overflow, the Department internal medicine of the University Hospital of Lausanne increased nurse and medical workforces as well as bed capacity by 65 %, with extraordinary help from other departments. The implemented crisis management stood upon three pillars : a crisis management team, steering documents and internal communication. In this new form, the Department had already taken care of 442 COVID-19 admissions by April 16, 2020. Alongside organizational challenges, clinical issues such as rapid respiratory distress, clinical suspicions with negative PCR and treatment uncertainties in the absence of sufficient evidence were overcome. Despite the peak of the pandemic appearing to have passed, the next phase could be just as complicated.

La progression rapide du COVID-19 constitue un défi organisationnel pour tous les hôpitaux. Pour anticiper un afflux important de patients, le service de médecine interne du CHUV a ainsi augmenté ses forces de travail médico-soignantes et son nombre de lits de 65 % avec un soutien extraordinaire de toute l'institution. Pour opérer ces changements majeurs, l'organisation de crise mise en place s'est appuyée sur trois piliers : une cellule de conduite, des documents de pilotage et une communication interne. Sous cette nouvelle forme, le service a pris en charge 442 hospitalisations COVID-19 jusqu'au 16 avril 2020. Si les enjeux organisationnels ont été majeurs, la gestion des situations complexes, comme les manifestations respiratoires et les multiples incertitudes cliniques diagnostiques et thérapeutiques, ont été également une gageure. Le pic de la pandémie semble passé, mais la prochaine phase pourrait constituer un nouveau défi organisationnel.

Genetic Factors Explain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns.

OBJECTIVE: Lp(a) (lipoprotein(a)) concentrations are widely genetically determined by the LPA isoforms and show 5-fold interpopulation differences. Two- to 3-fold differences have been reported even within Europe. Finns represent a distinctive population isolate within Europe and have been repeatedly reported to present lower Lp(a) concentrations than Central Europeans. The significance of this finding was unclear for a long time because of the difficult comparability of Lp(a) assays. Recently, a large standardized study in >50 000 individuals from 7 European populations confirmed this observation but could not provide insights into the causes. APPROACH AND RESULTS: We investigated Lp(a) concentrations, LPA isoforms, and genotypes of established genetic variants affecting Lp(a) concentrations (LPA variants, APOE isoforms, and PCSK9 R46L) in the Finnish YFS (Cardiovascular Risk in Young Finns Study) population (n=2281) and 3 Non-Finnish Central European populations (n=10 003). We observed ≈50% lower Lp(a) concentrations in Finns. The isoform distribution was shifted toward longer isoforms, and the percentage of low-molecular-weight isoform carriers was reduced. Most interestingly, however, Lp(a) was reduced in each single-isoform group. In contrast to the known inverse relationship between LPA isoforms and Lp(a) concentrations, especially very short isoforms presented unexpectedly low Lp(a) concentrations in Finns. The investigated genetic variants, as well as age, sex, and renal function, explained 71.8% of the observed population differences. CONCLUSIONS: The population differences in Lp(a) concentrations between Finnish and Central European populations originate not only from a different LPA isoform distribution but suggest the existence of novel functional variation in the small-isoform range.

Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.

Magnesium (Mg2+) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg2+, which is crucial for Mg2+ homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg2+ homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10-13) near TRPM6, which encodes an epithelial Mg2+ channel, and rs35929 (P=2.1×10-11), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg2+ regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg2+ wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg2+ deficiency to insulin resistance and obesity.

[The CoLaus/PsyCoLaus study†: 16 years of follow-up with some key messages end images]. / L'étude CoLaus/PsyCoLaus†: 16 ans de suivi en quelques messages et images clés.

The main aims of the CoLaus/PsyCoLaus cohort study are to better understand: 1) the personal, biologic, genetic end environmental determinants of cardiovascular risk factors and diseases, and 2) the existing association of mental disorders with cardiovascular diseases. The study was initiated in 2003 and over 6700 participants from the city of Lausanne were include and very rich phenotypic data were collected making the study unique worldwide. Numerous scientific articles were published in various fields such as epidemiology, public health, genetic, social and environmental determinants of cardiovascular diseases and their association with mental health. We briefly present here some key results obtained over the last 16 years.

L'étude de cohorte CoLaus/PsyCoLaus a pour but de mieux comprendre : 1) les déterminants personnels, biologiques, génétiques et environnementaux des facteurs de risque cardiovasculaire et des maladies cardiovasculaires, et 2) l'association existante entre les troubles mentaux et les maladies cardiovasculaires. Initiée en 2003, elle a suivi plus de 6700 participants de la ville de Lausanne en récoltant des phénotypes très riches qui la rendent unique au monde. Les très nombreuses publications scientifiques qui en découlent touchent des domaines aussi variés que l'épidémiologie, la santé publique, les déterminants génétiques, sociaux et environnementaux des maladies cardiovasculaires et mentales ainsi que leur association. Nous décrivons ici brièvement quelques résultats clés obtenus sur les 16 dernières années de suivi.

[Menopausal hormone therapy. Effects on bone and body composition]. / Traitement hormonal de la ménopause†: effets osseux et sur la composition corporelle.

Changes occurring at menopause can be mitigated by prescribing menopausal hormone replacement therapy (HRT). Recent publications from the CoLaus/OsteoLaus cohorts provide important insights into the effects of HRT and after its discontinuation on bone and body composition. HRT has a beneficial effect on bone mineral density, bone microarchitecture and fracture prevention. The benefits persist after treatment discontinuation, but not beyond 2 to 5 years. The effect of HRT on body composition is more controversial. HRT reduces the accumulation of fat mass, mainly abdominal and visceral fat mass. This is important from the perspective of diabetes and cardiovascular disease prevention. However, the benefits seem to disappear immediately after discontinuation.

Les changements survenant à la ménopause peuvent être atténués par le traitement hormonal de la ménopause (THM). Les résultats récents issus des cohortes CoLaus/OsteoLaus apportent un éclairage important sur les effets du THM et de son arrêt sur les paramètres osseux et de la composition corporelle. Le THM a un effet bénéfique sur la densité minérale osseuse, la microarchitecture osseuse et la prévention des fractures. Le bénéfice persiste à l'arrêt du traitement, mais pas au-delà de 2 à 5 ans. L'effet du THM sur la composition corporelle est plus controversé. Le THM diminue l'accumulation de masse grasse, essentiellement de masse grasse abdominale et intraviscérale. Ceci est important dans la perspective de la prévention du diabète et des maladies cardiovasculaires. Par contre, le bénéfice semble disparaître à son arrêt.

A genome-wide association meta-analysis on apolipoprotein A-IV concentrations.

Apolipoprotein A-IV (apoA-IV) is a major component of HDL and chylomicron particles and is involved in reverse cholesterol transport. It is an early marker of impaired renal function. We aimed to identify genetic loci associated with apoA-IV concentrations and to investigate relationships with known susceptibility loci for kidney function and lipids. A genome-wide association meta-analysis on apoA-IV concentrations was conducted in five population-based cohorts (n = 13,813) followed by two additional replication studies (n = 2,267) including approximately 10 M SNPs. Three independent SNPs from two genomic regions were significantly associated with apoA-IV concentrations: rs1729407 near APOA4 (P = 6.77 × 10 - 44), rs5104 in APOA4 (P = 1.79 × 10-24) and rs4241819 in KLKB1 (P = 5.6 × 10-14). Additionally, a look-up of the replicated SNPs in downloadable GWAS meta-analysis results was performed on kidney function (defined by eGFR), HDL-cholesterol and triglycerides. From these three SNPs mentioned above, only rs1729407 showed an association with HDL-cholesterol (P = 7.1 × 10 - 07). Moreover, weighted SNP-scores were built involving known susceptibility loci for the aforementioned traits (53, 70 and 38 SNPs, respectively) and were associated with apoA-IV concentrations. This analysis revealed a significant and an inverse association for kidney function with apoA-IV concentrations (P = 5.5 × 10-05). Furthermore, an increase of triglyceride-increasing alleles was found to decrease apoA-IV concentrations (P = 0.0078). In summary, we identified two independent SNPs located in or next the APOA4 gene and one SNP in KLKB1 The association of KLKB1 with apoA-IV suggests an involvement of apoA-IV in renal metabolism and/or an interaction within HDL particles. Analyses of SNP-scores indicate potential causal effects of kidney function and by lesser extent triglycerides on apoA-IV concentrations.

REM-associated sleep apnoea: prevalence and clinical significance in the HypnoLaus cohort.

This study determined the prevalence of rapid eye movement (REM) related sleep-disordered breathing (REM-SDB) in the general population and investigated the associations of REM-SDB with hypertension, metabolic syndrome, diabetes and depression.Home polysomnography (PSG) recordings (n=2074) from the population-based HypnoLaus Sleep Cohort (48.3% men, 57±11 years old) were analysed. The apnoea-hypopnoea index was measured during REM and non-REM sleep (as REM-AHI and NREM-AHI, respectively). Regression models were used to explore the associations between REM-SDB and hypertension, diabetes, metabolic syndrome and depression in the entire cohort and in subgroups with NREM-AHI <10 events·h-1 and total AHI <10 events·h-1The prevalence of REM-AHI ≥20 events·h-1 was 40.8% in the entire cohort. An association between increasing REM-AHI and metabolic syndrome was found in the entire cohort and in both the NREM-AHI and AHI subgroups (p-trend=0.014, <0.0001 and 0.015, respectively). An association was also found between REM-AHI ≥20 events·h-1 and diabetes in both the NREM-AHI <10 events·h-1 (odds ratio (OR) 3.12 (95% CI 1.35-7.20)) and AHI <10 events·h-1 (OR 2.92 (95% CI 1.12-7.63)) subgroups. Systolic and diastolic blood pressure were positively associated with REM-AHI ≥20 events·h-1REM-SDB is highly prevalent in our middle-to-older age sample and is independently associated with metabolic syndrome and diabetes. These findings suggest that an increase in REM-AHI could be clinically relevant.

Obstructive sleep apnoea as a risk factor for incident metabolic syndrome: a joined Episono and HypnoLaus prospective cohorts study.

Cross-sectional studies have demonstrated that obstructive sleep apnoea (OSA) and metabolic syndrome (MetS) are often associated, but whether a temporal relationship exists is unknown. We aimed to investigate the effect of OSA on the risk of developing MetS in the general population.A prospective study was conducted combining two population-based samples: Episono (Brazil) and HypnoLaus (Switzerland). MetS was assessed according to unified criteria. Polysomnography (PSG) was performed at baseline and follow-up in Episono, and at baseline in HypnoLaus. OSA was defined according to the apnoea-hypopnoea index as mild (≥5- <15 events h-1) and moderate-to-severe (≥15 events·h-1). We included 1853 participants (mean±sd age 52±13 years, 56% female) without MetS at baseline.After mean±sd 6±1 years, 318 (17.2%) participants developed MetS. Moderate-to-severe OSA was independently associated with incident MetS (OR 2.58, 95% CI 1.61-4.11) and increased the number of MetS components from baseline to follow-up through mediation of the percentage of time with arterial oxygen saturation <90%. Subset analysis in Episono confirmed that the increase in this parameter between baseline and follow-up PSGs represented a risk factor for incident MetS (OR 1.42, 95% CI 1.04-1.95, for each 10% increase).OSA is independently associated with an increased risk of developing MetS through mediation of nocturnal hypoxaemia in the general population.