Peter Vollenweider

Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study

BACKGROUND Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample. METHODS Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index. FINDINGS The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p<0·0001), and depression (1·92, 1·01-3·64; p=0·0292). INTERPRETATION The high prevalence of sleep-disordered breathing recorded in our population-based sample might be attributable to the increased sensitivity of current recording techniques and scoring criteria. These results suggest that sleep-disordered breathing is highly prevalent, with important public health outcomes, and that the definition of the disorder should be revised. FUNDING Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise.

The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study

BACKGROUND Diagnosis of sleep-disordered breathing requires overnight recordings, such as polygraphy or polysomnography. Considering the cost and low availability of these procedures, preselection of patients at high risk is recommended. We aimed to develop a screening tool allowing identification of individuals at risk of sleep-disordered breathing. METHODS We used the participants from the population-based HypnoLaus cohort in Lausanne, Switzerland, who had a clinical assessment and polysomnography at home, to build a clinical score (the NoSAS score) using multiple factor analysis and logistic regression to identify people likely to have clinically significant sleep-disordered breathing. The NoSAS score was externally validated in an independent sleep cohort (EPISONO). We compared its performance to existing screening scores (STOP-Bang and Berlin scores). FINDINGS We used the 2121 participants from the HypnoLaus cohort who were assessed between Sept 1, 2009, and June 30, 2013. The NoSAS score, which ranges from 0 to 17, allocates 4 points for having a neck circumference of more than 40 cm, 3 points for having a body-mass index of 25 kg/m(2) to less than 30 kg/m(2) or 5 points for having a body-mass index of 30 kg/m(2) or more, 2 points for snoring, 4 points for being older than 55 years of age, and 2 points for being male. Using a threshold of 8 points or more, the NoSAS score identified individuals at risk of clinically significant sleep-disordered breathing, with an area under the curve (AUC) of 0·74 (95% CI 0·72-0·76). It showed an even higher performance in the EPISONO cohort, with an AUC of 0·81 (0·77-0·85). The NoSAS score performed significantly better than did the STOP-Bang (AUC 0·67 [95% CI 0·65-0·69]; p<0·0001) and Berlin (0·63 [0·61-0·66]; p<0·0001) scores. INTERPRETATION The NoSAS score is a simple, efficient, and easy to implement score enabling identification of individuals at risk of sleep-disordered breathing. Because of its high discrimination power, the NoSAS score can help clinicians to decide which patients to further investigate with a nocturnal recording. FUNDING Faculty of Biology and Medicine of the University of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, and Vaud Pulmonary League.

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.

STUDY OBJECTIVES To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). METHODS Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. RESULTS 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. CONCLUSIONS Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function.

Association between parental history and genetic risk scores for coronary heart disease prediction: The population-based CoLaus study

BACKGROUND AND AIMS Parental history (PH) and genetic risk scores (GRSs) are separately associated with coronary heart disease (CHD), but evidence regarding their combined effects is lacking. We aimed to evaluate the joint associations and predictive ability of PH and GRSs for incident CHD. METHODS Data for 4283 Caucasians were obtained from the population-based CoLaus Study, over median follow-up time of 5.6 years. CHD was defined as incident myocardial infarction, angina, percutaneous coronary revascularization or bypass grafting. Single nucleotide polymorphisms for CHD identified by genome-wide association studies were used to construct unweighted and weighted versions of three GRSs, comprising of 38, 53 and 153 SNPs respectively. RESULTS PH was associated with higher values of all weighted GRSs. After adjustment for age, sex, smoking, diabetes, systolic blood pressure, low and high density lipoprotein cholesterol, PH was significantly associated with CHD [HR 2.61, 95% CI (1.47-4.66)] and further adjustment for GRSs did not change this estimate. Similarly, one standard deviation change of the weighted 153-SNPs GRS was significantly associated with CHD [HR 1.50, 95% CI (1.26-1.80)] and remained so, after further adjustment for PH. The weighted, 153-SNPs GRS, but not PH, modestly improved discrimination [(C-index improvement, 0.016), p = 0.048] and reclassification [(NRI improvement, 8.6%), p = 0.027] beyond cardiovascular risk factors. After including both the GRS and PH, model performance improved further [(C-index improvement, 0.022), p = 0.006]. CONCLUSION After adjustment for cardiovascular risk factors, PH and a weighted, polygenic GRS were jointly associated with CHD and provided additive information for coronary events prediction.

Current Genetic Data Do Not Improve the Prediction of Type 2 Diabetes Mellitus: The CoLaus Study

CONTEXT Several genetic risk scores to identify asymptomatic subjects at high risk of developing type 2 diabetes mellitus (T2DM) have been proposed, but it is unclear whether they add extra information to risk scores based on clinical and biological data. OBJECTIVE The objective of the study was to assess the extra clinical value of genetic risk scores in predicting the occurrence of T2DM. DESIGN This was a prospective study, with a mean follow-up time of 5 yr. SETTING AND SUBJECTS The study included 2824 nondiabetic participants (1548 women, 52 ± 10 yr). MAIN OUTCOME MEASURE Six genetic risk scores for T2DM were tested. Four were derived from the literature and two were created combining all (n = 24) or shared (n = 9) single-nucleotide polymorphisms of the previous scores. A previously validated clinic + biological risk score for T2DM was used as reference. RESULTS Two hundred seven participants (7.3%) developed T2DM during follow-up. On bivariate analysis, no differences were found for all but one genetic score between nondiabetic and diabetic participants. After adjusting for the validated clinic + biological risk score, none of the genetic scores improved discrimination, as assessed by changes in the area under the receiver-operating characteristic curve (range -0.4 to -0.1%), sensitivity (-2.9 to -1.0%), specificity (0.0-0.1%), and positive (-6.6 to +0.7%) and negative (-0.2 to 0.0%) predictive values. Similarly, no improvement in T2DM risk prediction was found: net reclassification index ranging from -5.3 to -1.6% and nonsignificant (P ≥ 0.49) integrated discrimination improvement. CONCLUSIONS In this study, adding genetic information to a previously validated clinic + biological score does not seem to improve the prediction of T2DM.

A Genetic Risk Score is Significantly Associated with Statin Therapy Response in the Elderly Population

The ability of statins to strongly reduce low‐density lipoprotein cholesterol (LDL‐C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population‐based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL‐C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population‐based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL‐C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL‐C reduction to a considerable extent in the older population.

Associations of specific phobia and its subtypes with physical diseases: an adult community study

BackgroundSpecific phobia is the most prevalent anxiety disorder in the community and is associated with substantial impairment. Comorbidity with physical diseases is assumed and has important implications for etiology, treatment, or prevention of the comorbid conditions. However, due to methodological issues data are limited and subtypes of specific phobia have not been investigated yet. We examined the association of specific phobia and its subtypes with physical diseases in a representative community sample with physician-diagnosed physical diseases and diagnostic criteria of specific phobia.MethodsData of the German Mental Health Survey from 4181 subjects aged 18–65 years were used. Specific phobia was diagnosed using M-CIDI/DIA-X interview; physical diseases were assessed through a self-report questionnaire and a medical interview. Logistic regression analyses adjusted for sex were calculated.ResultsSpecific phobia was associated with cardiac diseases, gastrointestinal diseases, respiratory diseases, arthritic conditions, migraine, and thyroid diseases (odds ratios between 1.49 and 2.53). Among the subtypes, different patterns of associations with physical diseases were established. The findings were partially replicated in the Swiss PsyCoLaus Study.ConclusionsOur analyses show that subjects with specific phobia have an increased probability for specific physical diseases. From these analyses etiological mechanisms of specific phobia and physical disease can be deduced. As subtypes differed in their patterns of associations with physical diseases, different etiological mechanisms may play a role. The findings are highly relevant for public health in terms of prevention and therapy of the comorbid conditions.

Cysteine-rich angiogenic inducer 61 (Cyr61): a novel soluble biomarker of acute myocardial injury improves risk stratification after acute coronary syndromes

Aims We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. Methods and results Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. Conclusion Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients.

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−1. The 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−1. REM-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. REM sleep-disordered breathing is highly prevalent and is associated with metabolic syndrome and diabetes http://ow.ly/u52H30kBh3u