Age and gender differences in the social patterning of cardiovascular risk factors in Switzerland: the CoLaus study.

OBJECTIVES: We examined the social distribution of a comprehensive range of cardiovascular risk factors (CVRF) in a Swiss population and assessed whether socioeconomic differences varied by age and gender. METHODS: Participants were 2960 men and 3343 women aged 35-75 years from a population-based survey conducted in Lausanne, Switzerland (CoLaus study). Educational level was the indicator of socioeconomic status used in this study. Analyses were stratified by gender and age group (35-54 years; 55-75 years). RESULTS: There were large educational differences in the prevalence of CVRF such as current smoking (Δ = absolute difference in prevalence between highest and lowest educational group:15.1%/12.6% in men/women aged 35-54 years), physical inactivity (Δ = 25.3%/22.7% in men/women aged 35-54 years), overweight and obesity (Δ = 14.6%/14.8% in men/women aged 55-75 years for obesity), hypertension (Δ = 16.7%/11.4% in men/women aged 55-75 years), dyslipidemia (Δ = 2.8%/6.2% in men/women aged 35-54 years for high LDL-cholesterol) and diabetes (Δ = 6.0%/2.6% in men/women aged 55-75 years). Educational inequalities in the distribution of CVRF were larger in women than in men for alcohol consumption, obesity, hypertension and dyslipidemia (p<0.05). Relative educational inequalities in CVRF tended to be greater among the younger (35-54 years) than among the older age group (55-75 years), particularly for behavioral CVRF and abdominal obesity among men and for physiological CVRF among women (p<0.05). CONCLUSION: Large absolute differences in the prevalence of CVRF according to education categories were observed in this Swiss population. The socioeconomic gradient in CVRF tended to be larger in women and in younger persons.

The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used.

BACKGROUND/OBJECTIVES: To assess the distribution of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO). SUBJECTS/METHODS: A total of 881 obese (body mass index (BMI) > or =30 kg/m2) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1β, IL-6 and TNF-α were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay. RESULTS: On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-α and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight+obese individuals (BMI > or =25 kg/m2, n=2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1β. Significantly lower IL-6 and TNF-α levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat. CONCLUSIONS: MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-α. Conversely, no association with IL-1β levels was found.

Chemical dispersants and pre-treatments to determine clay in soils with different mineralogy

Knowledge of the soil physical properties, including the clay content, is of utmost importance for agriculture. The behavior of apparently similar soils can differ in intrinsic characteristics determined by different formation processes and nature of the parent material. The purpose of this study was to assess the efficacy of separate or combined pre-treatments, dispersion methods and chemical dispersant agents to determine clay in some soil classes, selected according to their mineralogy. Two Brazilian Oxisols, two Alfisols and one Mollisol with contrasting mineralogy were selected. Different treatments were applied: chemical substances as dispersants (lithium hydroxide, sodium hydroxide, and hexametaphosphate); pre-treatment with dithionite, ammonium oxalate, and hydrogen peroxide to eliminate organic matter; and coarse sand as abrasive and ultrasound, to test their mechanical action. The conclusion was drawn that different treatments must be applied to determine clay, in view of the soil mineralogy. Lithium hydroxide was not efficient to disperse low-CEC electropositive soils and very efficient in dispersing high-CEC electronegative soils. The use of coarse sand as an abrasive increased the clay content of all soils and in all treatments in which dispersion occurred, with or without the use of chemical dispersants. The efficiency of coarse sand is not the same for all soil classes.

Socioeconomics status and quality of care in a population-based sample of swiss diabetic patients

Introduction: Low socioeconomic status (SES) is associated with higher prevalence of diabetes and worse outcomes; it has also been shown to be associated with worse quality of care. We aimed to explore the relationship between SES and quality of care in the Swiss context. Methods: We used data from a population-based survey including 519 adult diabetic patients living in the canton of Vaud. Self-reported data on patients' and diabetes characteristics, indicators of process and outcomes of care and quality of life were collected. Dependent variables included 6 processes of care (PoC) received during the last 12 months (HbA1C, lipid, microalbuminuria, fundoscopy, feet examination and influenza vaccination) and selected clinical outcomes (blood pressure, LDL, HbA1C, diabetes-specific (ADDQoL) and generic quality of life (SF-12)). Regression analyses were performed to assess the relationship between education and income, respectively, and quality of care as measured by PoC and clinical outcomes. Adjustment was made for age, gender and comorbidities. Results: Mean age was 64.5 years, 40% were women; 19%, 56% and 25% of the patients reported primary (I), secondary (II) and tertiary (III) education. Fundoscopy was the only PoC significantly associated with education, with III education patients more likely to get the exam than those with primary education (adjOR 1.8, 95% CI 1.0-3.3). Use of composite indicators of PoC showed that compared to patients with primary education, patients with III education were more likely to receive ≥5/6 PoC (adjOR 1.9, 95% CI 1.1-3.4), and that those with II or III education were more likely to receive 4/4 PoC (adjOR 1.9, 95% CI 1.0-3.3; adjOR 2.1, 95% CI 1.1-4.1, respectively). Quality of life was the only clinical outcome significantly associated with education, with II and III education patients reporting better quality of life compared to primary education patients, as measured by the ADDQoL (β 0.6, 95% CI 0.3-1.0, β 0.6, 95% CI 0.2-1.0, respectively) and the physical component score of the SF-12 (β 2.5, 95% CI 0.2-4.8, β 3.6, 95% CI 0.9-6.4, respectively). No associations were found between income and quality of care. Conclusion: Social inequalities have been demonstrated in Switzerland for global health indicators. Our results suggest that similar associations are found when considering quality of care measures in individuals with diabetes, but only for a few indicators.

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Metastable liquid-liquid phase transition in a single-component system with only one crystal phase and no density anomaly

We investigate the phase behavior of a single-component system in three dimensions with spherically-symmetric, pairwise-additive, soft-core interactions with an attractive well at a long distance, a repulsive soft-core shoulder at an intermediate distance, and a hard-core repulsion at a short distance, similar to potentials used to describe liquid systems such as colloids, protein solutions, or liquid metals. We showed [Nature (London) 409, 692 (2001)] that, even with no evidence of the density anomaly, the phase diagram has two first-order fluid-fluid phase transitions, one ending in a gas¿low-density-liquid (LDL) critical point, and the other in a gas¿high-density-liquid (HDL) critical point, with a LDL-HDL phase transition at low temperatures. Here we use integral equation calculations to explore the three-parameter space of the soft-core potential and perform molecular dynamics simulations in the interesting region of parameters. For the equilibrium phase diagram, we analyze the structure of the crystal phase and find that, within the considered range of densities, the structure is independent of the density. Then, we analyze in detail the fluid metastable phases and, by explicit thermodynamic calculation in the supercooled phase, we show the absence of the density anomaly. We suggest that this absence is related to the presence of only one stable crystal structure.

Finite-size scaling investigation of the liquid-liquid critical point in ST2 water and its stability with respect to crystallization.

The liquid-liquid critical point scenario of water hypothesizes the existence of two metastable liq- uid phases low-density liquid (LDL) and high-density liquid (HDL) deep within the supercooled region. The hypothesis originates from computer simulations of the ST2 water model, but the stabil- ity of the LDL phase with respect to the crystal is still being debated. We simulate supercooled ST2 water at constant pressure, constant temperature, and constant number of molecules N for N ≤ 729 and times up to 1 μs. We observe clear differences between the two liquids, both structural and dynamical. Using several methods, including finite-size scaling, we confirm the presence of a liquid-liquid phase transition ending in a critical point. We find that the LDL is stable with respect to the crystal in 98% of our runs (we perform 372 runs for LDL or LDL-like states), and in 100% of our runs for the two largest system sizes (N = 512 and 729, for which we perform 136 runs for LDL or LDL-like states). In all these runs, tiny crystallites grow and then melt within 1 μs. Only for N ≤ 343 we observe six events (over 236 runs for LDL or LDL-like states) of spontaneous crystal- lization after crystallites reach an estimated critical size of about 70 ± 10 molecules.

Divergent fifteen-year trends in traditional and cardiometabolic risk factors of cardiovascular diseases in the Seychelles.

OBJECTIVE: Few studies have assessed secular changes in the levels of cardiovascular risk factors (CV-RF) in populations of low or middle income countries. The systematic collection of a broad set of both traditional and metabolic CV-RF in 1989 and 2004 in the population of the Seychelles islands provides a unique opportunity to examine trends at a fairly early stage of the "diabesity" era in a country in the African region. METHODS: Two examination surveys were conducted in independent random samples of the population aged 25-64 years in 1989 and 2004, attended by respectively 1081 and 1255 participants (participation rates >80%). All results are age-standardized to the WHO standard population. RESULTS: In 2004 vs. 1989, the levels of the main traditional CV-RF have either decreased, e.g. smoking (17% vs. 30%, p < 0.001), mean blood pressure (127.8/84.8 vs. 130.0/83.4 mmHg, p < 0.05), or only moderately increased, e.g. median LDL-cholesterol (3.58 vs. 3.36 mmol/l, p < 0. 01). In contrast, marked detrimental trends were found for obesity (37% vs. 21%, p < 0.001) and several cardiometabolic CVD-RF, e.g. mean HDL-cholesterol (1.36 vs. 1.40 mmol/l, p < 0.05), median triglycerides (0.80 vs. 0.78 mmol/l, p < 0.01), mean blood glucose (5.89 vs. 5.22 mmol/l, p < 0.001), median insulin (11.6 vs. 8.3 micromol/l, p < 0.001), median HOMA-IR (2.9 vs. 1.8, p < 0.001) and diabetes (9.4% vs. 6.2%, p < 0.001). At age 40-64, the prevalence of elevated total cardiovascular risk tended to decrease (e.g. WHO-ISH risk score > or =10; 11% vs. 13%, ns), whereas the prevalence of the metabolic syndrome (which integrates several cardiometabolic CVD-RF) nearly doubled (36% vs. 20%, p < 0.001). Data on physical activity and on intake of alcohol, fruit and vegetables are also provided. Awareness and treatment rates improved substantially for hypertension and diabetes, but control rates improved for the former only. Median levels of the cardiometabolic CVD-RF increased between 1989 and 2004 within all BMI strata, suggesting that the worsening levels of cardiometabolic CVD-RF in the population were not only related to increasing BMI levels in the interval. CONCLUSION: The levels of several traditional CVD-RF improved over time, while marked detrimental trends were observed for obesity, diabetes and several cardiometabolic factors. Thus, in this population, the rapid health transition was characterized by substantial changes in the patterns of CVD-RF. More generally, this analysis suggests the importance of surveillance systems to identify risk factor trends and the need for preventive strategies to promote healthy lifestyles and nutrition.

Plasma lipoprotein-associated phospholipase A2 activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study.

ABSTRACT: INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA2 activity was reported as a risk factor for dementia in the Rotterdam study, no association between Lp-PLA2 mass and dementia or Alzheimer's disease (AD) was detected in the Framingham study. The objectives of the current study were to explore the relationship of plasma Lp-PLA2 activity with cognitive diagnoses (AD, amnestic mild cognitive impairment (aMCI), and cognitively healthy subjects), cardiovascular markers, cerebrospinal fluid (CSF) markers of AD, and apolipoprotein E (APOE) genotype. METHODS: Subjects with mild AD (n = 78) and aMCI (n = 59) were recruited from the Memory Clinic, University Hospital, Basel, Switzerland; cognitively healthy subjects (n = 66) were recruited from the community. Subjects underwent standardised medical, neurological, neuropsychological, imaging, genetic, blood and CSF evaluation. Differences in Lp-PLA2 activity between the cognitive diagnosis groups were tested with ANOVA and in multiple linear regression models with adjustment for covariates. Associations between Lp-PLA2 and markers of cardiovascular disease and AD were explored with Spearman's correlation coefficients. RESULTS: There was no significant difference in plasma Lp-PLA2 activity between AD (197.1 (standard deviation, SD 38.4) nmol/min/ml) and controls (195.4 (SD 41.9)). Gender, statin use and low-density lipoprotein cholesterol (LDL) were independently associated with Lp-PLA2 activity in multiple regression models. Lp-PLA2 activity was correlated with LDL and inversely correlated with high-density lipoprotein (HDL). AD subjects with APOE-ε4 had higher Lp-PLA2 activity (207.9 (SD 41.2)) than AD subjects lacking APOE-ε4 (181.6 (SD 26.0), P = 0.003) although this was attenuated by adjustment for LDL (P = 0.09). No strong correlations were detected for Lp-PLA2 activity and CSF markers of AD. CONCLUSION: Plasma Lp-PLA2 was not associated with a diagnosis of AD or aMCI in this cross-sectional study. The main clinical correlates of Lp-PLA2 activity in AD, aMCI and cognitively healthy subjects were variables associated with lipid metabolism.

Lipoprotéine(a): de l'athérosclérose à Alzheimer [Lipoprotein (a) in Alzheimer's atherosclerosis].

Lipoprotein(a) [Lp(a)] is an enigmatic lipoprotein particle present in the plasma from humans, great apes and hedgehogs. Plasma levels of Lp(a) vary widely between individuals and are largely determined by specific sequences within the gene encoding apo(a), the unique highly polymorphic glycoprotein attached to apoB of low density lipoprotein (LDL) to form Lp(a). Elevated plasma concentrations of LP(a) are associated with the premature development of atherosclerosis. A major goal of our laboratory is to better understand the metabolism of Lp(a) and its function in humans. We have identified unexpected and large variations in plasma Lp(a) levels during renal disease, HIV-infection and in sepsis. Moreover, we have observed an association between Lp(a) and Alzheimer disease. Taken together, our observations suggest that Lp(a) may constitute a novel target in our fight against cardiovascular and neurodegenerative disorders.

Prescription de statines en prévention primaire: quel score de risque cardiovasculaire faut-il utiliser en Suisse? [Statin prescription in primary prevention: which cardiovascular risk score should be used in Switzerland?]

La prévention primaire des maladies cardiovasculaires par les médecins s'effectue par une prise en charge individualisée des facteurs de risque. L'indication à un traitement par statines se base sur une estimation du risque de survenue d'une maladie cardiovasculaire et sur le taux de LDL-cholestérol. Trois scores de risque sont couramment utilisés: le score PROCAM, le score Framingham, et le SCORE européen. En Suisse, le Groupe Suisse Lipides et Athérosclérose (GSLA) recommande en première instance l'utilisation du score PROCAM avec une adaptation du niveau de risque pour la Suisse. Une enquête a aussi montré que c'est le score le plus utilisé en Suisse. Dans cet article, les particularités de ces scores et leurs applications pratiques en ce qui concerne la prescription de statines en prévention primaire sont discutées. Les conséquences et les bénéfices potentiels de l'application de ces scores en Suisse sont également abordés. [Abstract] Primary prevention of cardiovascular disease by physicians is achieved by management of individual risk factors. The eligibility for treatment with statins is based on both an estimate of the risk of developing cardiovascular disease and the LDL-cholesterol. Three risk scores are commonly used : the PROCAM score, the Framingham score, and the European score. In Switzerland, the Swiss Group Lipids and Atherosclerosis (GSLA) recommends to use the PROCAM score with an adjustment of the level of risk for Switzerland. A survey also showed that PROCAM is the most used in Switzerland. In this article, the differences of these scores and their practical applications regarding the prescription of statins in primary prevention are discussed. The consequences and potential benefits of applying these scores in Switzerland are also discussed.

Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases.

Elevated low-density lipoprotein (LDL) levels induce activation of the p38 mitogen-activated protein kinase (MAPK), a stress-activated protein kinase potentially participating in the development of atherosclerosis. The nature of the lipoprotein components inducing p38 MAPK activation has remained unclear however. We show here that both LDLs and high-density lipoproteins (HDLs) have the ability to stimulate the p38 MAPKs with potencies that correlate with their cholesterol content. Cholesterol solubilized in methyl-beta-cyclodextrin was sufficient to activate the p38 MAPK pathway. Liposomes made of phosphatidylcholine (PC) or sphingomyelin, the two main phospholipids found in lipoproteins, were unable to stimulate the p38 MAPKs. In contrast, PC liposomes loaded with cholesterol potently activated this pathway. Reducing the cholesterol content of LDL particles lowered their ability to activate the p38 MAPKs. Cell lines representative of the three main cell types found in blood vessels (endothelial cells, smooth muscle cells and fibroblasts) all activated their p38 MAPK pathway in response to LDLs or cholesterol-loaded PC liposomes. These results indicate that elevated cholesterol content in lipoproteins, as seen in hypercholesterolemia, favors the activation of the stress-activated p38 MAPK pathway in cells from the vessel wall, an event that might contribute to the development of atherosclerosis.

Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins.

Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding. Recent genome-wide association studies identified PNPLA3 to be associated with hepatic fat content and liver function, thus pointing to a possible involvement in the hepatic lipoprotein metabolism. The aim of this study was to examine the association between two common variants in the adiponutrin gene and parameters of lipoprotein metabolism in 23,274 participants from eight independent West-Eurasian study populations including six population-based studies [Bruneck (n = 800), KORA S3/F3 (n = 1644), KORA S4/F4 (n = 1814), CoLaus (n = 5435), SHIP (n = 4012), Rotterdam (n = 5967)], the SAPHIR Study as a healthy working population (n = 1738) and the Utah Obesity Case-Control Study including a group of 1037 severely obese individuals (average BMI 46 kg/m2) and 827 controls from the same geographical region of Utah. We observed a strong additive association of a common non-synonymous variant within adiponutrin (rs738409) with age-, gender-, and alanine-aminotransferase-adjusted lipoprotein concentrations: each copy of the minor allele decreased levels of total cholesterol on average by 2.43 mg/dl (P = 8.87 x 10(-7)), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 x 10(-6)) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 x 10(-4)). These associations remained significant after correction for multiple testing. We did not observe clear evidence for associations with HDL cholesterol or triglyceride concentrations. In conclusion, our study suggests that adiponutrin is involved in the metabolism of apoB-containing lipoproteins.

The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity.

Proteins secreted from adipose tissue are increasingly recognized to play an important role in the regulation of glucose metabolism. However, much less is known about their effect on lipid metabolism. The fasting-induced adipose factor (FIAF/angiopoietin-like protein 4/peroxisome proliferator-activated receptor gamma angiopoietin-related protein) was previously identified as a target of hypolipidemic fibrate drugs and insulin-sensitizing thiazolidinediones. Using transgenic mice that mildly overexpress FIAF in peripheral tissues we show that FIAF is an extremely powerful regulator of lipid metabolism and adiposity. FIAF overexpression caused a 50% reduction in adipose tissue weight, partly by stimulating fatty acid oxidation and uncoupling in fat. In addition, FIAF overexpression increased plasma levels of triglycerides, free fatty acids, glycerol, total cholesterol, and high density lipoprotein (HDL)-cholesterol. Functional tests indicated that FIAF overexpression severely impaired plasma triglyceride clearance but had no effect on very low density lipoprotein production. The effects of FIAF overexpression were amplified by a high fat diet, resulting in markedly elevated plasma and liver triglycerides, plasma free fatty acids, and plasma glycerol levels, and impaired glucose tolerance in FIAF transgenic mice fed a high fat diet. Remarkably, in mice the full-length form of FIAF was physically associated with HDL, whereas truncated FIAF was associated with low density lipoprotein. In human both full-length and truncated FIAF were associated with HDL. The composite data suggest that via physical association with plasma lipoproteins, FIAF acts as a powerful signal from fat and other tissues to prevent fat storage and stimulate fat mobilization. Our data indicate that disturbances in FIAF signaling might be involved in dyslipidemia.

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.