Polypharmacy is a frequent condition, but its prevalence and determinants in the Swiss mid-aged population are unknown. We aimed to evaluate the prevalence and determinants of polypharmacy in a large ...Swiss mid-aged population-based sample.
Data from 4938 participants of the CoLaus study (53% women, age range 40-81 years) were collected between 2009 and 2012. Polypharmacy was defined by the regular use of five or more drugs.
Polypharmacy was reported by 580 participants 11.8%, 95% confidence interval (10.9; 12.6). Participants on polypharmacy were significantly older (mean ± standard deviation: 66.0 ± 9.1 vs. 56.6 ± 10.1 years), more frequently obese (35.9% vs. 14.7%), of lower education (66.6% vs. 50.7%) and former smokers (46.7% vs. 36.4%) than participants not on polypharmacy. These findings were confirmed by multivariate analysis: odds ratio and (95% confidence interval) for age groups 50-64 and 65-81 relative to 40-49 years: 2.90 (2.04; 4.12) and 10.3 (7.26; 14.5), respectively, p for trend < 0.001; for low relative to high education: 1.56 (1.17; 2.07); for overweight and obese relative to normal weight participants: 2.09 (1.65; 2.66) and 4.38 (3.39; 5.66), respectively, p for trend < 0.001; for former and current relative to never smokers: 1.42 (1.14, 1.75) and 1.63 (1.25, 2.12), respectively, p for trend < 0.001.
One out of nine participants of our sample is on polypharmacy. Increasing age, body mass index, smoking and lower education independently increase the likelihood of being on polypharmacy.
The polypill has been advocated for cardiovascular disease (CVD) management. The fraction of the population who could benefit from the polypill in Switzerland is unknown. Assess (1) the prevalence of ...subjects (a) eligible for the polypill and (b) already taking a polypill equivalent; and (2) the determinants of polypill intake in the first (2009-2012) and second follow-ups (2014-2017) of a population-based prospective study conducted in Lausanne, Switzerland. The first and the second follow-ups included 5038 and 4596 participants aged 40-80 years, respectively. Polypill eligibility was defined as having a high CVD risk as assessed by an absolute CVD risk ≥ 5% with the SCORE equation for Switzerland and/or presenting with CVD. Four polypill equivalents were defined: statin + any antihypertensive with (A) or without (B) aspirin; statin + calcium channel blocker (CCB) (C); and statin + CCB + angiotensin-converting enzyme inhibitor (D). The prevalence of polypill eligibility was 20.6% (95% CI 19.5-21.8) and 27.7% (26.5-29.1) in the first and second follow-up, respectively. However, only around one-third of the eligible 29.5% (95% CI 26.7-32.3) and 30.4% (27.9-33.0) respectively, already took the polypill equivalents. All polypill equivalents were more prevalent among men, elderly and in presence of CVD. After multivariable adjustment, in both periods, male gender was associated with taking polypill equivalent A (OR: 1.93; 95% CI 1.45-2.55 and OR: 1.67; 95% CI 1.27-2.19, respectively) and polypill equivalent B (OR: 1.52; 95% CI 1.17-1.96 and OR: 1.41; 95% CI 1.07-1.85, respectively). Similarly, in both periods, age over 70 years, compared to middle-age, was associated with taking polypill equivalent A (OR: 11.71; CI 6.74-20.33 and OR: 9.56; CI 4.13-22.13, respectively) and equivalent B (OR: 13.22; CI 7.27-24.07 and OR: 20.63; CI 6.51-56.36, respectively). Former or current smoking was also associated with a higher likelihood of taking polypill equivalent A in both periods. A large fraction of the population is eligible for the polypill, but only one-third of them actually benefits from an equivalent, and this proportion did not change over time.
Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 ...European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.
Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic ...determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.
We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)).
We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.
Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association ...studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 × 10−18).
Low birth weight is associated with increased rates of obesity, insulin resistance and type 2 diabetes, but the precise mechanisms for this association remain unclear. We aimed to assess the ...relationships between birth weight and markers of glucose homeostasis or obesity in adults.
Cross-sectional population-based study on 1458 women and 1088 men aged 35-75 years living in Lausanne, Switzerland. Birth weight was self-reported and categorized into ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg. Body composition was assessed by bioimpedance. Leptin and adiponectin levels were measured by ELISA.
Women with low birth weight (≤ 2.5 kg) had higher levels of fasting plasma glucose, insulin, HOMA, diabetes and metabolic syndrome; a non significant similar trend was seen in men. In both genders, height increased with birth weight, whereas a U-shaped association was found between birth weight and body mass index, waist circumference and body fat percentage. After adjusting for age, smoking status, physical activity and fat mass, an inverse association was found between leptin and birth weight categories: adjusted mean ± standard error 17.3 ± 0.7, 16.2 ± 0.3, 15.6 ± 0.5 and 14.0 ± 0.8 ng/dL for birth weight categories ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg, respectively, in women (p < 0.05) and 9.8 ± 0.8, 9.1 ± 03, 7.8 ± 0.4 and 7.7 ± 0.5 ng/dL in men (p < 0.05). An inverse association was also found between reported birth weight and leptin to fat mass ratio: mean ± standard error 0.77 ± 0.04, 0.73 ± 0.02, 0.69 ± 0.03 and 0.62 ± 0.04 in women (p < 0.05); 0.46 ± 0.05, 0.45 ± 0.02, 0.39 ± 0.02 and 0.38 ± 0.03 in men (p < 0.05). No differences in adiponectin levels were found between birth weight groups.
Middle-aged adults born with a low weight present a higher prevalence of diabetes and obesity and also higher leptin levels and leptin to fat mass ratio than adults born with a normal weight. The higher leptin levels and leptin to fat mass ratio among adults born with a low weight might be related to nutritional factors during childhood or to the development of leptin resistance and/or higher leptin production by body fat unit. Subjects born with a low weight should be counselled regarding the risks of developing diabetes and/or cardiovascular disease.
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.
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).
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.
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.
Faculty of Biology and Medicine of the University of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, and Vaud Pulmonary League.
Recent data indicate a slight decrease in the prevalence of smoking in Switzerland, but little is known regarding the intention and difficulty to quit smoking among current smokers. Hence, we aimed ...to quantify the difficulty and intention to quit smoking among current smokers in Switzerland.
Cross-sectional study including 607 female and 658 male smokers. Difficulty, intention and motivation to quit smoking were assessed by questionnaire.
90% of women and 85% of men reported being "very difficult" or "difficult" to quit smoking. Almost three quarters of smokers (73% of women and 71% of men) intended to quit; however, less than 20% of them were in the preparation stage and 40% were in the precontemplation stage. On multivariate analysis, difficulty to quit was lower among men (Odds ratio and 95% confidence interval: 0.51 0.35-0.74) and increased with nicotine dependence and number of previous quitting attempts (OR=3.14 1.75-5.63 for 6+ attempts compared to none). Intention to quit decreased with increasing age (OR=0.48 0.30-0.75 for ≥65 years compared to <45 years) and increased with nicotine dependence, the number of previous quitting attempts (OR=4.35 2.76-6.83 for 6+ attempts compared to none) and among non-cigarette smokers (OR=0.51 0.28-0.92). Motivation to quit was inversely associated with nicotine dependence and positively associated with the number of previous quitting attempts and personal history of lung disease.
Over two thirds of Swiss smokers want to quit. However, only a small fraction wishes to do so in the short term. Nicotine dependence, previous attempts to quit or previous history of lung disease are independently associated with difficulty and intention to quit.
Abstract 24S- and 27-hydroxycholesterol are obligatory intermediates of cholesterol catabolism and play an important role in the maintenance of whole-body cholesterol homeostasis. Using an HPLC–MS ...method for oxysterol quantification, the distribution of esterified and unesterified oxysterols in lipoprotein subfractions as well as the influence of daytime, food intake and menstrual cycle on oxysterol concentrations were investigated in healthy volunteers. Moreover, reference intervals for 24S- and 27-hydroxycholesterol in plasma as well as the corresponding levels for 27-hydroxycholesterol in the HDL subfraction were established in 100 healthy volunteers. Both circulating oxysterols are mainly transported in association with HDL and LDL – primarily in the esterified form. No significant diurnal changes and no variations during menstrual cycle of either absolute or cholesterol-related plasma levels were detected. In contrast to 24S-hydroxycholesterol in plasma and 27-hydroxycholesterol in the HDL subfraction, the 95% reference intervals of 27-hydroxycholesterol both in plasma and the non-HDL subfraction were higher in males than in females. The concentrations of 27-hydroxycholesterol in plasma and the non-HDL subfraction showed strong positive correlations with the concentrations of cholesterol, non-HDL cholesterol and triglycerides. Our data on the lipoprotein distribution of oxysterols as well as on their intra- and inter-individual variation set the stage for future clinical studies.
Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, ...affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.
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