Current cardiovascular risk management patterns with special focus on lipid lowering in daily practice in Switzerland.

Background: There may be a considerable gap between LDL cholesterol (LDL-C) and blood pressure (BP) goal values recommended by the guidelines and results achieved in daily practice. Design Prospective cross-sectional survey of cardiovascular disease risk profiles and management with focus on lipid lowering and BP lowering in clinical practice. Methods: In phase 1, the cardiovascular risk of patients with known lipid profile visiting their general practitioner was anonymously assessed in accordance to the PROCAM-score. In phase 2, high-risk patients who did not achieve LDL-C goal less than 2.6 mmol/l in phase 1 could be further documented. Results: Six hundred thirty-five general practitioners collected the data of 23 892 patients with known lipid profile. Forty percent were high-risk patients (diabetes mellitus or coronary heart disease or PROCAM-score >20%), compared with 27% estimated by the physicians. Goal attainment rate was almost double for BP than for LDL-C in high-risk patients (62 vs. 37%). Both goals were attained by 25%. LDL-C values in phase 1 and 2 were available for 3097 high-risk patients not at LDL-C goal in phase 1; 32% of patients achieved LDL-C goal of less than 2.6 mmol/l after a mean of 17 weeks. The most successful strategies for LDL-C reduction were implemented in only 22% of the high-risk patients. Conclusion: Although patients at high cardiovascular risk were treated more intensively than low or medium risk patients, the majority remained insufficiently controlled, which is an incentive for intensified medical education. Adequate implementation of Swiss and International guidelines would expectedly contribute to improved achievement of LDL-C and BP goal values in daily practice.

Approche éducationnelle des patients à risque cardiovasculaire [Educational approach to patients with cardiovascular risk factors]

In the outpatient setting, the long-term management of cardiovascular risk factors is essential to prevent recurrent cardiovascular disease. Recent studies have shown an additional benefit of beginning cardiovascular secondary prevention during the hospital stay. Early, in-hospital initiation of proven beneficial medications, such as aspirin or blood lipid lowering drugs and therapeutic lifestyle change counseling, improves patients' long-term outcome, as long as there is continuity of care in the outpatient setting. A recent hospitalization may be a teachable moment, when patients are more likely to modify their health behaviors. The continuity of care between in-hospital medicine and the outpatient setting helps patients in the long-term management of their cardiovascular disease.

Paroxetine use in pregnancy and cardiovascular defects

Background: Paroxetine (Paxil,) is an SSRI, used for thetreatment of depression, obsessive compulsive disorder,anxiety disorders and premenstrual dysphoria. Untilrecently, no studies had associated SSRIs as a group withan increased risk for major malformations above the 1%-3% baseline rate. However, in the past year, several studiesnoted specifically, an increase risk of cardiovascular defectsassociated with paroxetine, compared to other antidepressantswithin its class.Objectives: To determine whether paroxetine increases therisk of cardiovascular defects in infants of women exposedduring the first trimester of pregnancy.Methods: We collected prospectively ascertained cases ofinfants from Teratogen Information Services throughout theworld, exposed to paroxetine in the first trimester of pregnancyand compared them to a non-exposed Motheriskcohort.We also contacted the authors of data base studies thathad been published on antidepressants as a class, to determinehow many of these women had been exposed to paroxetineand the rates of cardiovascular defects in their infants.Results: We were able to ascertain the outcomes of 1177infants from 9 services. The rate of heart defects in the paroxetineparoxetinegroup was 0.8% versus 0.7% non-exposed group.The combined rate in the data base studies was 1.5%.Conclusions: Paroxetine does not appear to be associated withan increase risk for cardiovascular defects following use inpregnancy, as the incidence in more than 3000 infants was wellwithin the population incidence of approximately 1%.

Association entre consommation d'alcool et facteurs de risque cardiovasculaire: une étude sur la population lausannoise. [Association between alcohol consumption and cardiovascular risk factors: a narrative review]

Alors que la consommation modérée d'alcool est liée à un risque plus faible de développer une maladie coronarienne, l'impact d'une consommation plus importante d'alcool sur les facteurs de risque cardiovasculaire (FRCV) et la maladie coronarienne est moins clair. Nous avons étudié l'association entre la consommation d'alcool, les FRCV et l'estimation du risque à dix ans de faire un événement cardiovasculaire dans l'étude populationnelle lausannoise CoLaus. Dans cette étude, 73% des participants consomment de l'alcool, 16% consomment de 14 à 34 unités d'alcool par semaine et 2% consomment 35 unités ou plus par semaine. Cet article montre notamment l'impact d'une consommation importante d'alcool sur les FRCVet passe en revue les liens entre la consommation d'alcool, le type de boissons et les FRCV. [Abstract] Moderate alcohol consumption has been associated with lower coronary heart disease (CHD) risk. However, the impact of higher alcohol consumption on cardiovascular risk factors (CVRFs) is conflicting. We examined the association between alcohol consumption, CVRFs and the estimated 10-year CHD risk in the population-based CoLaus study in Lausanne, Switzerland. Among 5'769 participants without cardiovascular disease, 73% of the participants were alcohol drinkers; 16% consumed 14-34 drinks/week and 2% consumed >= 35 drinks/week. This article shows the impact of high alcohol consumption on CVRFs and reviews the literature on the associations between alcohol consumption and CVRFs.

Computational analysis of the genetic and environmental contributions to disease-related human phenotypes: From predicting adverse lipid response of HIV patients receiving antiretroviral therapy to genome-wide association studies of cardiovascular and lipid related disorders

Genetic variants influence the risk to develop certain diseases or give rise to differences in drug response. Recent progresses in cost-effective, high-throughput genome-wide techniques, such as microarrays measuring Single Nucleotide Polymorphisms (SNPs), have facilitated genotyping of large clinical and population cohorts. Combining the massive genotypic data with measurements of phenotypic traits allows for the determination of genetic differences that explain, at least in part, the phenotypic variations within a population. So far, models combining the most significant variants can only explain a small fraction of the variance, indicating the limitations of current models. In particular, researchers have only begun to address the possibility of interactions between genotypes and the environment. Elucidating the contributions of such interactions is a difficult task because of the large number of genetic as well as possible environmental factors.In this thesis, I worked on several projects within this context. My first and main project was the identification of possible SNP-environment interactions, where the phenotypes were serum lipid levels of patients from the Swiss HIV Cohort Study (SHCS) treated with antiretroviral therapy. Here the genotypes consisted of a limited set of SNPs in candidate genes relevant for lipid transport and metabolism. The environmental variables were the specific combinations of drugs given to each patient over the treatment period. My work explored bioinformatic and statistical approaches to relate patients' lipid responses to these SNPs, drugs and, importantly, their interactions. The goal of this project was to improve our understanding and to explore the possibility of predicting dyslipidemia, a well-known adverse drug reaction of antiretroviral therapy. Specifically, I quantified how much of the variance in lipid profiles could be explained by the host genetic variants, the administered drugs and SNP-drug interactions and assessed the predictive power of these features on lipid responses. Using cross-validation stratified by patients, we could not validate our hypothesis that models that select a subset of SNP-drug interactions in a principled way have better predictive power than the control models using "random" subsets. Nevertheless, all models tested containing SNP and/or drug terms, exhibited significant predictive power (as compared to a random predictor) and explained a sizable proportion of variance, in the patient stratified cross-validation context. Importantly, the model containing stepwise selected SNP terms showed higher capacity to predict triglyceride levels than a model containing randomly selected SNPs. Dyslipidemia is a complex trait for which many factors remain to be discovered, thus missing from the data, and possibly explaining the limitations of our analysis. In particular, the interactions of drugs with SNPs selected from the set of candidate genes likely have small effect sizes which we were unable to detect in a sample of the present size (<800 patients).In the second part of my thesis, I performed genome-wide association studies within the Cohorte Lausannoise (CoLaus). I have been involved in several international projects to identify SNPs that are associated with various traits, such as serum calcium, body mass index, two-hour glucose levels, as well as metabolic syndrome and its components. These phenotypes are all related to major human health issues, such as cardiovascular disease. I applied statistical methods to detect new variants associated with these phenotypes, contributing to the identification of new genetic loci that may lead to new insights into the genetic basis of these traits. This kind of research will lead to a better understanding of the mechanisms underlying these pathologies, a better evaluation of disease risk, the identification of new therapeutic leads and may ultimately lead to the realization of "personalized" medicine.

Obesity markers and estimated 10 year fatal cardiovascular risk in Switzerland

Objective: To assess the effectiveness of obesity markers to detect high (>5%) 10- year risk of fatal cardiovascular disease (CVD) as estimated using the SCORE function. Methods: Cross-sectional study including 3,047 women and 2,689 men aged 35-75 years (CoLaus study). Body fat percentage was assessed by tetrapolar bioimpedance. CVD risk was assessed using the SCORE risk function and gender and age-specific cut points for body fat were derived. The diagnostic accuracy of each obesity marker was evaluated through receiver operating characteristics (ROC) analysis. Results: Body fat presented a higher correlation with 10-year CVD risk than waist/hip ratio (WHR), waist or BMI: in men, r=0.31, 0.22, 0.19 and 0.12 and for body fat, WHR, waist and BMI, respectively; the corresponding values in women were 0.18, 0.15, 0.11 and 0.05, respectively (all p<0.05). In both genders, body fat showed the highest area under the ROC curve (AUC): in men, the AUC (and 95% confidence interval) were 76.0 (73.8 - 78.2), 67.3 (64.6 - 69.9), 65.8 (63.1 - 68.5) and 60.6 (57.9 - 63.5) for body fat, WHR, waist and BMI, respectively. In women, the corresponding values were 72.3 (69.2 - 75.3), 66.6 (63.1 - 70.2), 64.1 (60.6 - 67.6) and 58.8 (55.2 - 62.4). The use of body fat percentage criterion enabled to capture three times more subjects with high CVD risk than BMI criterion, and almost twice as much as WHR criterion.. Conclusions: Obesity defined by body fat percentage is more accurate to detect high 10-year risk of fatal CVD than obesity markers based on WHR, waist or BMI.

Superior diagnostic performance of perfusion-cardiovascular magnetic resonance versus SPECT to detect coronary artery disease: The secondary endpoints of the multicenter multivendor MR-IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary Artery Disease Trial).

ABSTRACT: BACKGROUND: Perfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference. METHODS: In 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results. RESULTS: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). CONCLUSION: In this large multicenter, multivendor study the diagnostic performance of perfusion-CMR to detect CAD was superior to perfusion SPECT in the entire population and in sub-groups. Perfusion-CMR can be recommended as an alternative for SPECT imaging. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00977093.

Atherosclerosis screening by noninvasive imaging for cardiovascular prevention: a systematic review.

BACKGROUND: Noninvasive imaging of atherosclerosis is being increasingly used in clinical practice, with some experts recommending to screen all healthy adults for atherosclerosis and some jurisdictions mandating insurance coverage for atherosclerosis screening. Data on the impact of such screening have not been systematically synthesized. OBJECTIVES: We aimed to assess whether atherosclerosis screening improves cardiovascular risk factors (CVRF) and clinical outcomes. DESIGN: This study is a systematic review. DATA SOURCES: We searched MEDLINE and the Cochrane Clinical Trial Register without language restrictions. STUDY ELIGIBILITY CRITERIA: We included studies examining the impact of atherosclerosis screening with noninvasive imaging (e.g., carotid ultrasound, coronary calcification) on CVRF, cardiovascular events, or mortality in adults without cardiovascular disease. RESULTS: We identified four randomized controlled trials (RCT, n=709) and eight non-randomized studies comparing participants with evidence of atherosclerosis on screening to those without (n=2,994). In RCTs, atherosclerosis screening did not improve CVRF, but smoking cessation rates increased (18% vs. 6%, p=0.03) in one RCT. Non-randomized studies found improvements in several intermediate outcomes, such as increased motivation to change lifestyle and increased perception of cardiovascular risk. However, such data were conflicting and limited by the lack of a randomized control group. No studies examined the impact of screening on cardiovascular events or mortality. Heterogeneity in screening methods and studied outcomes did not permit pooling of results. CONCLUSION: Available evidence about atherosclerosis screening is limited, with mixed results on CVRF control, increased smoking cessation in one RCT, and no data on cardiovascular events. Such screening should be validated by large clinical trials before widespread use.

Developmental and metabolic brain alterations in rats exposed to bisphenol A during gestation and lactation.

In recent years, considerable research has focused on the biological effect of endocrine-disrupting chemicals. Bisphenol A (BPA) has been implicated as an endocrine-disrupting chemical (EDC) due to its ability to mimic the action of endogenous estrogenic hormones. The aim of this study was to assess the effect of perinatal exposure to BPA on cerebral structural development and metabolism after birth. BPA (1mg/l) was administered in the drinking water of pregnant dams from day 6 of gestation until pup weaning. At postnatal day 20, in vivo metabolite concentrations in the rat pup hippocampus were measured using high field proton magnetic resonance spectroscopy. Further, brain was assessed histologically for growth, gross morphology, glial and neuronal development and extent of myelination. Localized proton magnetic resonance spectroscopy ((1)H MRS) showed in the BPA-exposed rat a significant increase in glutamate concentration in the hippocampus as well as in the Glu/Asp ratio. Interestingly these two metabolites are metabolically linked together in the malate-aspartate metabolic shuttle. Quantitative histological analysis revealed that the density of NeuN-positive neurons in the hippocampus was decreased in the BPA-treated offspring when compared to controls. Conversely, the density of GFAP-positive astrocytes in the cingulum was increased in BPA-treated offspring. In conclusion, exposure to low-dose BPA during gestation and lactation leads to significant changes in the Glu/Asp ratio in the hippocampus, which may reflect impaired mitochondrial function and also result in neuronal and glial developmental alterations.

Seasonality of cardiovascular risk factors: an analysis including over 230 000 participants in 15 countries.

OBJECTIVE: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies. METHODS: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed. RESULTS: In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m(2) for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol. CONCLUSIONS: CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.

The p22phox C242T gene polymorphism is associated with a reduced risk of angiographically verified coronary artery disease in a high-risk Finnish Caucasian population. The Finnish Cardiovascular Study.

American Heart Journal Vol. 152, Issue 3, pp 538-542, 2006

Effects of polymorphisms in beta1-adrenoceptor and alpha-subunit of G protein on heart rate and blood pressure during exercise test. The finnish cardiovascular study.

J Appl Physiol vol 100, no 2, pp 507-511, 2006