[Value of nuclear medicine in preventive cardiology: the metabolic syndrome example]. / Apports de la médecine nucléaire en cardiologie préventive: l'exemple du syndrome métabolique.

Metabolic syndrome represents a grouping of risk factors closely linked to cardiovascular diseases and diabetes. At first, nuclear medicine has no direct application in cardiology at the level of primary prevention, but positron emission tomography is a non invasive imaging technique that can assess myocardial perfusion as well as the endothelium-dependent coronary vasomotion--a surrogate marker of cardiovascular event rate--thus finding an application in studying coronary physiopathology. As the prevalence of the metabolic syndrome is still unknown in Switzerland, we will estimate it from data available in the frame of a health promotion program. Based on the deleterious effect on the endothelium already observed with two components, we will estimate the number of persons at risk in Switzerland.

[How frequent are cardiovascular diseases a cause of work absenteeism and of disability in Switzerland?]. / Dans quelle mesure les maladies cardiovasculaires sont-elles la cause d'incapacité de travail et d'invalidité en Suisse?

Cardiovascular diseases (CVD) are a major cause of morbidity and mortality in industrialized countries, and also in Switzerland. In 2004/2005, CVD were in first line of all medical diagnosis by primary care physicians (12.4%) and of all causes of hospitalisation (9.6%). However, statistical data of work incapacity and disability related to CVD remain still insufficient. Based on medical publications and official Swiss statistics, CVD accountedfor only 2.3% among all medical causes of sickness certification for > 6 days established by primary care physicians in patients aged 15 to 64 years. Furthermore in 2006, CVD were involved only in 2.5% of women and 5.5% of men receiving a pension of Swiss disability insurance. Between 1987 and 2006, the proportion of diagnosis of CVD at medical office decreased from 14.6 to 12.4% (-15%), while during the same period, the reduction of the proportion of disability pension was more pronounced, from 9.6 to 4.1% (-57%). The magnitude of these changes reinforce the need for more detailed statistical data in order to evaluate the appropriateness between the expenditures devoted to the prevention and the therapy of CVD, and the economical consequences on work absenteeism and disability.

[Early detection of atherosclerosis]. / Détection précoce de la maladie athéroscléreuse.

According to the guidelines, the global assessment of cardiovascular risk is based on traditional risk factors. The emergence of new cardiovascular risk factors may be helpful. However, at every level of risk factor exposure, there is a substantial variation of atherosclerosis. Thus, subclinical disease measurements, representing the end result of risk exposure may be useful for improving cardiovascular risk prediction. In comparison to the ankle-brachial index, the high resolution B-mode ultrasound is a more promising tool to detect early atherosclerosis both on carotid and femoral arterial wall in asymptomatic patients. It appears as a new approach to predict the risk of cardiovascular disease and to monitor the cardiovascular therapy.

[Evolution of cardiac risk factors management among patients aged 65 years and older with coronary artery disease]. / Evolution du contrôle des facteurs de risque cardiovasculaire chez les patients coronariens de plus de 65 ans.

The aim of this retrospective study was to compare the appropriateness of cardiac risk factors (CV-RF) management in a Swiss cardiac rehabilitation center. The comparison of the control of CV-RF among 342 patients with coronary artery disease (CHD) aged > or =65 years was improved. The CV-RF management has globally improved during the two periods of observation (1994-95 and 1999-2000). Nevertheless, according to the recommendations published between 1994 and 1999, an underuse of the cardioprotective agents was still observed. Using a standardized protocol for the management of CHD which allows the benchmarking among the network of cardiac rehabilitation centers network could increase the quality of care for such high risk patients.

Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV Cohort Study.

BACKGROUND: Administration of protease inhibitors (PIs) to HIV-infected individuals has been associated with hyperlipidemia. In this study, we characterized the lipoprotein profile in subjects receiving ritonavir, indinavir, or nelfinavir, alone or in combination with saquinavir. METHODS AND RESULTS: Plasma lipoprotein levels were quantified in 93 HIV-infected adults receiving PIs. Comparison was done with pretreatment values and with 28 nonPI-treated HIV-infected subjects. An elevation in plasma cholesterol levels was observed in all PI-treated groups but was more pronounced for ritonavir (2.0+/-0.3 mmol/L [mean+/-SEM], n=46, versus 0.1+/-0.2 mmol/L in nonPI treated group, P<0.001) than for indinavir (0.8+/-0.2 mmol/L, n=26, P=0.03) or nelfinavir (1.2+/-0.2 mmol/L, n=21, P=0.01). Administration of ritonavir, but not indinavir or nelfinavir, was associated with a marked elevation in plasma triglyceride levels (1.83+/-0.46 mmol/L, P=0.002). Plasma HDL-cholesterol levels remained unchanged. Combination of ritonavir or nelfinavir with saquinavir did not further elevate plasma lipid levels. A 48% increase in plasma levels of lipoprotein(a) was detected in PI-treated subjects with pretreatment Lp(a) values >20 mg/dL. Similar changes in plasma lipid levels were observed in 6 children receiving ritonavir. CONCLUSIONS: Administration of PIs to HIV-infected individuals is associated with a marked, compound-specific dyslipidemia. The risk of pancreatitis and premature atherosclerosis due to PI-associated dyslipidemia remains to be established.

[Alcohol and risk of coronary heart disease]. / Alkohol und kardiovaskuläre Krankheiten.

More than 60 prospective cohort studies have shown a consistent association between regular and moderate alcohol consumption and decrease in risk of coronary heart disease, ischemic stroke and heart failure by 20 to 40% as compared to heavy alcohol intake or drinking no alcohol. Lower protective effects were found in young, in women and in men living outside the Mediterranean area. Moreover, some biological characteristics of alcohol, particularly red wine, could interfere with the athero-thrombotic process and contribute to increase the plausibility for the protective effects of alcohol on cardiovascular diseases. However, the results of meta-analyses also demonstrate harmful effects in relation with dose and pattern of alcohol consumption. In regard to the available scientific data, alcohol consumption cannot be include in the recommendations for the prevention of cardiovascular diseases. On the other hand alcohol should not be prohibited when consumption remains mild to moderate.

[Statins in older patients: limits to prescription?]. / Statines et personnes âgées: limites à la prescription?

Cardio-vascular diseases are a major contributor to mortality, morbidity and functional decline in the elderly population. Hypercholesterolemia remains a major risk factor in older persons, but treatment decisions are difficult because of the paucity of data specific to this segment of the population. While evidence seems strong enough to support treating patients with cardio-vascular diseases (secondary prevention) up to their eighties, the question remains open whether to treat asymptomatic older patients (primary prevention) or those in their nineties.

Premature atherosclerosis in HIV-infected individuals--focus on protease inhibitor therapy.

OBJECTIVE: Lipid disorders associated with the use of protease inhibitors may contribute to the premature development of atherosclerosis. The purpose of the present study was to determine whether the administration of a protease inhibitor-containing regimen to middle-aged (30-50 years) HIV-infected individuals for 6 months or longer is associated with an increased prevalence of atherosclerosis. METHODS: High-resolution B-mode ultrasound imaging was used to visualize the femoral and carotid arteries of 68 HIV-negative and 168 HIV-infected individuals, including 136 patients who had received protease inhibitors for 26.8 +/- 8.9 months (mean +/- SD). Atherogenic plaques were defined as a thickening of the intima-media > or = 1200 mm. RESULTS: The proportion of participants with one or more plaques was higher in the HIV-infected group in comparison with the HIV-negative group (55 versus 38%; P = 0.02), and so was the prevalence of cigarette smoking (61 versus 46%; P = 0.03) and hyperlipidaemia (56 versus 24%; P < 0.001). The presence of plaque was independently associated with age, male gender, plasma low-density lipoprotein cholesterol levels and smoking. In univariate logistic regression analysis, an association was also found with HIV infection. Among HIV-infected subjects protease inhibitor therapy was not associated with the presence of plaque. CONCLUSIONS: A large proportion of the middle-aged HIV-infected individuals examined during this study had one or more atherosclerotic plaques within the femoral or carotid arteries. The presence of peripheral atherosclerosis within this population is not associated with the use of protease inhibitors, but rather with 'classic' cardiovascular risk factors such as smoking and hyperlipidaemia, which are amenable to interventions.

Postischemic blood flow response in hypercholesterolemic patients.

We undertook this cross-sectional study to compare the mechanical behavior and postischemic response of the radial artery of 15 newly diagnosed hypercholesterolemic patients with those of 15 age- and sex-matched normocholesterolemic control subjects and 21 hypercholesterolemic patients treated for 2 years with an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (simvastatin, 10 to 20 mg/d). At the time of the study total cholesterol levels were at 7.9 +/- 0.2, 4.9 +/- 0.2, and 6.0 +/- 0.3 mmol/L in the three groups, respectively (mean +/- SEM, P < .001). High-resolution, noninvasive echotracking for assessment of internal arterial diameter was combined with measurements of blood flow velocity by Doppler and blood pressure by photoplethysmography. Radial cross-sectional compliance and distensibility were similar in all groups. Forearm blood flow and flow-mediated dilation were measured after a 5-minute upper arm occlusion. Flow was calculated from the vessel diameter and blood flow velocity recorded simultaneously at the same site. Flow-mediated dilation after ischemia was not significantly different among the three groups. However, forearm blood flow increase was markedly blunted (P < .01) in untreated hypercholesterolemic patients (211%) compared with the normocholesterolemic control subjects (411%) and treated patients (365%). These findings suggest that the distensibility of the radial artery, a muscular conduit vessel usually devoid of atherosclerotic lesions, and its flow-mediated dilation are preserved in hypercholesterolemic patients. In contrast, forearm resistance vessels exhibit a markedly reduced postischemic blood flow response that may be restored by prolonged lipid-lowering intervention.

Apolipoprotein E polymorphism and the distribution profile of very low density lipoproteins; an influence of the E4 allele on large (Sf > 60) particles.

Very low density lipoprotein (VLDL) distribution and composition have been examined as a function of apo E genotype (E2/2 + E2/3 vs. E3/3 vs. E3/4 + E4/4) in healthy, normolipaemic subjects. Apo E genotype had a marked impact on plasma concentrations of apo E rich VLDL, but no influence on concentrations of apo E free particles. Thus, there was a trend to lower concentrations of apo E rich total VLDL in apo E4 carriers (mg/dl; E2, 49.1 +/- 35.2; E3, 52.5 +/- 30.9; E4 35.2 +/- 22.3; ANOVA P = 0.16; when comparing E4 with E2 + E3, P = 0.06). Consequently, there were highly significant differences between apo E-defined subgroups in terms of the percentage distribution of bound and non-bound fractions (% total VLDL non-bound to apo E: E2, 44.0 +/- 12.7%; E3, 39.7 +/- 8.7%; E4 51.0 +/- 12.2%; ANOVA P = 0.007). Subfractionation of VLDL into density subclasses revealed that genotype differences were restricted to large VLDL (Sf > 60). Significantly lower concentrations of apo E-rich particles were observed in E4 carriers for VLDL-1 Sf 400-100 (ANOVA P = 0.004) and VLDL-2 (P = 0.009) but not for small VLDL-3 Sf 60-20 (P = 0.34). No differences in plasma concentrations of apo E free VLDL were observed between genotype subclasses across the density spectrum. Compositional differences between the apo E defined VLDL were also evident for the core lipids. Apo E containing VLDL was enriched in esterified cholesterol and depleted in triglycerides compared to apo E poor VLDL: the difference became more marked with increasing density of the particles. Lipoprotein composition was not modulated to any great extent by apo E genotype. In patients with familial hypercholesterolaemia, relative concentrations of apo E rich, large VLDL were significantly higher than in controls. Treatment lowered concentrations of both apo E rich and apo E free VLDL but led to a greater relative enrichment of large VLDL in apo E containing particles. Apo E polymorphism appears to influence plasma concentrations of VLDL particles. The data are consistent with more pronounced receptor-mediated elimination of apo E4 containing VLDL. This may be a contributory factor to the down regulation of receptor activity which is suggested to be of major importance in provoking higher cholesterol levels associated with the apo E4 isoform.

Phospholipids and other lipids in angiographically assessed coronary artery disease.

Lipoprotein subclasses and their composition in cholesterol, triglycerides and in 5 types of phospholipid as well as apolipoproteins A-I and B were determined in blood of 114 patients undergoing coronary angiography for suspected or confirmed myocardial ischaemia. Lipid concentrations of lipoproteins were measured after preparative ultracentrifugation; high performance thin-layer chromatography was used to separate phospholipid subfractions. Patients with angiographically defined coronary artery disease (CAD) significantly differed from those without CAD in 25 different lipid or phospholipid parameters. Using discriminative analysis, apo A-I/apo B ratio was the only parameter with more than 70% success in reclassifying the patients in the CAD group. When correlated with a coronary atheromatous score reflecting either the number and degree of stenoses (Jenkins score) or the number of diseased vessels alone, only LDL-cholesterol was found to correlate with the Jenkins score. We conclude that serum phospholipid fractions may differ significantly in CAD group as compared with controls, but they are, however, no better predictors of CAD than other lipids.

Comparison of serum lipoprotein(a) distribution and its correlates among black and white populations.

BACKGROUND: Epidemiological data on serum lipoprotein(a) (Lp(a)), a presumably strong risk factor for coronary artery disease in White populations, has mostly been derived, in Black populations, from small samples. This study compares the distribution and the determinants of serum Lp(a) in Blacks and in Whites using large representative samples and the same methods in both populations. METHODS: The distribution and the correlates of serum Lp(a) were investigated in population-based samples of 701 Blacks in the Seychelles and 634 Whites in Switzerland, aged 25-64 years. Serum Lp(a) was quantified using a commercial immunoradiometric assay. RESULTS: The distribution of serum Lp(a) was similarly skewed in both ethnic groups, but median Lp(a) concentration was about twofold higher in Blacks (210 mg/l) compared to Whites (100 mg/l). The proportions of individuals with elevated serum Lp(a) (> 300 mg/l) was about 50% higher in Blacks (37.5%) than in Whites (25.2%). In both ethnic groups, serum Lp(a) was found to correlate with total cholesterol, LDL-cholesterol and apoprotein B but not with HDL-cholesterol, alcohol intake, smoking, and body mass index. The variance in serum Lp(a) concentration explained by any combination of these factors was smaller than 5.3% in the two populations. CONCLUSIONS: The measured factors did not explain the higher levels of serum Lp(a) found in Blacks compared to Whites. These findings are consistent with the hypothesis that genetic factors account for much of the variation of serum Lp(a) in both populations.

Electronic monitoring of compliance to lipid-lowering therapy in clinical practice.

Nonadherence to treatment is a common problem in the clinical management of hypercholesterolemic patients. This study was carried out with the aim of monitoring the daily compliance to a 6-month course of lipid-lowering therapy, using a microelectronic device, the Medication Event Monitoring System (MEMS), versus pill count. Forty men with primary hypercholesterolemia were prescribed fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed the study. Total cholesterol and LDL cholesterol levels decreased significantly (18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of compliance was achieved by MEMS using the following three indexes--compliance to total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/- 19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of nonadherence to medication, undetectable by pill count alone, such as a drug holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9% of cases, and, conversely, use of more than the one prescribed daily dose in 47% of cases. A significant correlation between the rate of compliance and the decrease in LDL cholesterol was observed only when the compliance was assessed by MEMS. The results indicate that MEMS is a useful tool for monitoring compliance in clinical practice and may possibly increase adherence to long-term lipid-lowering therapy.

Hepatic de novo lipogenesis after liver transplantation.

BACKGROUND: The liver can synthesize fatty acids from carbohydrate (de novo lipogenesis [DNL]). We hypothesized that stimulation of this process may be involved in the development of obesity and dyslipidemia, 2 conditions frequently encountered after liver transplantation. METHODS: Hepatic fractional DNL and glucose metabolism were measured in 2 groups of 5 patients (age 36.8 +/- [SD] 14.9 years, BMI 26.3+/-5.3 kg/M2) 1 to 5 years after liver transplantation and 8 healthy subjects (age 28.1+/-5.3 years, BMI 27.2+/-4.5 kg/M2). Subjects were studied while receiving an isoenergetic nutrition (based on 1.1 x their basal energy expenditure) as hourly oral liquid formula during 10 hours. Their hepatic DNL was measured by infusing 1-13C acetate and measuring tracer incorporation in VLDL-palmitate. Their glucose metabolism was assessed by means of 6,6-2H2 glucose and indirect calorimetry. RESULTS: Two liver transplant recipients and 4 healthy subjects were obese, as defined by a BMI > 27 kg/M2. Fractional hepatic DNL was not different in the 2 groups of subjects: liver transplant recipients 3.1+/-1.7% vs 3.2+/-2.1% in healthy subjects. In both groups, DNL increased in proportion to BMI. When both groups were analyzed together, BMI was positively correlated with DNL (DNL = 0.28 x BMI - 4.28, r2 = .445, p < .05). Whole body glucose turnover was 15.0+/-4.4 micromol/kg per minute in liver transplant recipients and 15.8+/-4.1 micromol/kg per minute in healthy subjects (NS). Net carbohydrate oxidation tended to be lower in liver transplant recipients (8.1+/-2.6 micromol/kg per minute) than in healthy subjects (10.4+/-2.4 micromol/kg per minute; NS). Net nonoxidative glucose disposal (4.0+/-2.7 in liver transplant recipients vs 1.9+/-1.8 in healthy subjects, NS) and energy expenditure (0.065+/-0.01 vs 0.065+/-0.01 kJ/kg per minute) were similar in both groups. CONCLUSIONS: These results indicate that fractional hepatic DNL is not altered by liver transplantation during near continuous nutrition. The disposal of orally administered carbohydrate is also essentially unchanged. This strongly argues against a role of hepatic DNL in the pathogenesis of obesity and dyslipidemia after liver transplantation.

Compliance to live oral Ty21a typhoid vaccine, and its effect on viability.

BACKGROUND: Concerns have been expressed that in travelers the efficacy of the live oral Ty21a typhoid vaccine Vivotif could be lower than reported, maybe due to a lack of compliance. The purpose of this study was to examine the level of compliance with the recommendations regarding dosing, timing of dosing with respect to food intake, and storage. METHODS: Travelers were randomized into two groups: one received oral information only, and the second, a combination of oral and written information. Four criteria of compliance were applied to travelers: 3 capsules needed to be swallowed (criterion 1) on day 1, 3 and 5 (criterion 2), at least 1 hour before or 2 hours after a meal (criterion 3) and the vaccine had to be kept refrigerated (2-8 degrees C) (criterion 4). Compliance was evaluated using three different methods: a questionnaire, pill counting, and electronic monitoring using the Medication Event Monitoring System (MEMS). Storage conditions were checked by temperature tags, and viability of the vaccine was assessed by culturing the content of remaining capsules. RESULTS: The data of 115 travelers were analyzed. All the travelers took the 3 capsules. Compliance to all four criteria was complete in 68% of travelers according to the questionnaire, and 53% according to the MEMS (p =.05). Sixty-seven percent of all the doses intervals were of 48 hours +/- 6 hours, 12% being shorter than 36 hours and 7% longer than 60 hours. Eighty-seven travelers (76%) took their capsules on each alternate day. The method of information had no significant impact on compliance. Forty-two percent of tags showed exposure to temperature over 10 degrees C for more than 24 hours. Yet, no difference could be found in the viability of the vaccine compared with controls. CONCLUSIONS: Most travelers take their 3 capsules on alternate days, but many did not follow the other recommendations. Electronic monitoring of compliance provides more accurate results than questionnaires. Emphasis must be put on motivating the travelers to take the vaccine as recommended.

[Reference values of intima-medial thickness of carotid and femoral arteries in subjects aged 20 to 60 years and without cardiovascular risk factors]. / Valeurs de référence des épaisseurs intima-média des artères carotidiennes et fémorales chez des sujets âgés de 20 à 60 ans et sans facteur de risque cardiovasculaire.

Many studies have shown a close correlation between intima-medial thickness of the carotid artery measured by high resolution ultrasonography and the presence of coronary artery disease or atherogenic risk factors. However, reference values for the value of intima-medial thickness (IMT) in healthy subjects have not yet been established. The aim of this study was, therefore, to determine the reference values of carotid (C-IMT) and femoral intima-medial thickness (F-IMT) with respect to age and gender in healthy subjects (53 women and 45 men) aged 20 to 60, with no family or personal history of cardiovascular disease or atherogenic risk factors, underwent high resolution colour echo-Doppler examination. The mean C-IMT was 556 +/- 57 microns in women and 573 +/- 70 microns in men (NS), and the femoral equivalent was 543 +/- 63 microns in women and 562 +/- 74 microns in men (NS). Between the ages of 20 and 60, the C-IMT increased by 1.8 microns per year (p < 0.03) in women and 3.4 microns (p < 0.001) in men, the variations being respectively 1.2 microns (NS) and 3.1 microns (p < 0.002) in the femoral artery. Multiple regression analysis including gender and individual values of age, body mass index and lipid profile confirmed that only age was significantly correlated to the increase in thickness. The authors conclude that the reference values of IMT do not differ with gender or site of analysis, but there is a slight influence with respect to age.

[Screening for cardiovascular disease risk factors among employees of a hospital]. / Dépistage des facteurs de risque des maladies cardiovasculaires chez les employés d'un hôpital.

A health promotion and screening program for the detection of the major risk factors for ischemic heart disease was carried out in 1990 among the employees (n = 4,521; 70% female) of the Centre Hospitalier Universitaire Vaudois (CHUV). The prevalence of risk factors among the 1,425 employees (73% female) who took part in the study (participation rate: males 29%, females 33%) was compared with the prevalence of risk factors within three other populations: 1) new CHUV employees, who are systematically screened (n = 424: 71% female); 2) a representative sample of the general population; and 3) a group of employees from 44 companies located in the same region. Smoking was the most common of the three main risk factors; its prevalence was lowest among CHUV employees and highest among employees of the 44 firms. The prevalence of hypercholesterolemia and high blood pressure was variable among the different populations. These variations could partly be due to differences in methodologies and measurement conditions, but could not totally be explained in this way.

[Survey of the recommendations given to travelers to tropical zones]. / Enquête sur les recommandations prodiguées aux voyageurs en zone tropicale.

This inquiry, conducted with the collaboration of 250 doctors, 150 pharmacists and 76 travel agencies in the Canton de Vaud was set up to assess the prophylactic advice given against tropical diseases. Replies concerning major affections are discussed. It appears that in a high proportion of cases the recommendations available to travellers are inadequate, due in part to lack of precise, standardised and up to date information.

[Vaccinations for travel abroad]. / Impfungen für Auslandreisen.

Travel to the developing world by Swiss citizens has been increasing. Vaccine-preventable diseases challenges the physician to provide pre-travel advice. Each traveler's itinerary, duration of stay and medical history, including previous immunization, should be reviewed. Vaccinations are required or recommended according to the requirements and the epidemiology of countries being visited. This article summarizes updated recommendations to individual vaccines and immunoglobulins.

[Prevention for travel to the tropics]. / Prophylaxe für Tropenreisen.

The Swiss Working Group for Health Advice to Travellers regularly publishes its recommendations for malaria prophylaxis and vaccination as supplement to the 'Bulletin' of the Federal Office of Public Health. In this review the strategy with respect to information, to clever behavior abroad, to chemoprophylaxis and immunization prophylaxis is analyzed. A critical evaluation of emergency self-therapy describes remaining questions in particular.