Influence of the timing of low-dose aspirin on tolerability of prolonged-release nicotinic acid in patients at elevated cardiovascular risk.

OBJECTIVES: To investigate the effect of low-dose aspirin administered in the morning or evening on the rate of discontinuation of prolonged-release nicotinic acid (Niaspan) due to flushing in patients at elevated cardiovascular risk. RESEARCH DESIGN AND METHODS: This was an observational, non-interventional study in patients at elevated cardiovascular risk due to cardiovascular disease or type 2 diabetes. Patients received prolonged-release nicotinic acid and aspirin under the usual care of their physician for 15 weeks. MAIN OUTCOME MEASURES: The main outcome measure was the rate of treatment discontinuation for flushing. Other adverse drug reactions (ADRs) were also recorded. Lipid parameters were also measured. RESULTS: The patient population included 539 subjects (70% male); 36% had type 2 diabetes, 80% had prior cardiovascular disease, and 37% had a family history of cardiovascular disease. The rate of treatment discontinuation due to flushing did not differ (p = 0.3375) between the morning aspirin group (10.6%) and the evening aspirin group (13.8%). The overall incidence of flushing was 57%. Most flushes were of mild or moderate severity and decreases occurred over time in both frequency and intensity. ADRs unrelated to flushing occurred in 6.6% of the morning aspirin group and 7.4% of the evening aspirin group. HDL-cholesterol increased by +21.3% in the overall population, together with moderate improvements in other lipid parameters. CONCLUSIONS: Flushing was the most common ADR with prolonged-release nicotinic acid treatment, as expected. The timing of aspirin administration did not influence the rate of treatment discontinuations for flushing. Marked increases in HDL-cholesterol were observed.

[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.

[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.

[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.

[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.

[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.

[Homocystein and cardiovascular risk: is dosage useful?]. / Homocystéine et risque cardiovasculaire: de l'utilité du dosage?

Hyperhomocysteinemia represents an independent risk factor for atherothrombotic disease. Physiopathological mechanisms of accelerated progression of atherosclerosis in presence of hyperhomocysteinemia are complex. Herein we report a clinical case which emphasis the importance of screening elevated homocystein in the absence of conventional risk factors in patients who suffer from premature atherosclerosis.

Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic joints.

Extravascular coagulation and diminished fibrinolysis are processes that contribute to the pathology of both inflammatory arthritis and atherosclerosis. We hypothesized that, given its homology with plasminogen, apolipoprotein (apo) (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be equally implicated in inflammatory arthritis. We detected the presence of apo(a) as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in synovial fluid rose in proportion to plasma apo(a) levels and was higher in inflammatory arthritides than in osteoarthritis. In addition, apo(a) immunoreactive material, but not apo(a) transcripts, was detected in inflammatory arthritic synovial tissues. These data indicated that synovial fluid apo(a) originates from circulating Lp(a) and that diffusion of Lp(a) through synovial tissue is facilitated in inflammatory types of arthritis. In synovial tissues, apo(a) co-localized with fibrin. These observations could be reproduced in a model of antigen-induced arthritis, using transgenic mice expressing human Lp(a). Although in this mouse model the presence of apo(a) did not change the severity of arthritis, the co-localization of apo(a) with fibrin in synovial tissue suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity and may thus contribute to the persistence of intra-articular fibrin in inflammatory arthritis.

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.

Epidemiology of cardiovascular risk factors among schoolchildren in Sousse, Tunisia.

BACKGROUND: In Tunisia, where the epidemiological transition phenomenon is well established, there are no data available at the population level on the cardiovascular disease (CVD) risk profile for children, although it is well known that risk factor development takes place in childhood. METHODS: We report an epidemiological survey based on a representative sample of 1569 urban schoolchildren of Sousse in Tunisia to assess the following CVD risk factors: hypertension, hypercholesterolaemia and other lipid disorders, obesity and tobacco consumption. RESULTS: The main results showed that girls had significantly higher levels of body mass index (BMI), diastolic blood pressure (DBP), total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol than boys, who however had significantly higher levels of systolic blood pressure (SBP). Total cholesterol was significantly correlated to BMI and decreased with age. Obesity (BMI = 27) was found in 7.9% of the study population and was significantly higher for girls (9.7%) than for boys (6%): chi 2 = 9.02, DF = 2, P = 0.011. Overweight (BMI = 25) was also significantly higher for girls (16%) than for boys (11.1%): chi 2 = 8.21, DF = 1, P = 0.0041. Smoking habit concerned 7.6% of the study population; it was significantly higher for boys (14.7%) than for girls (1.1%): chi 2 = 103.4, DF = 1, P < 0.00001. CONCLUSION: This study showed to some extent that Tunisia's urban population of schoolchildren is exposed early to CVD risk factors and all should be done to avoid the worsening of this profile. These results will serve as a baseline for assessment of future trends in the risk factors studied.

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.

Inactivated hepatitis A vaccine booster given >/=24 months after the primary dose.

We investigated what happens with the immune response when people come back for their booster dose of inactivated hepatitis A vaccine later than the recommended time of 6-12 months after the primary dose. We recruited a group of 124 travellers who received either the primary doses of Havrix 720 (two doses) or of Havrix 1440 (one dose) >/=24 months before study entry. They received a booster dose of Havrix 1440 and blood was drawn 1 month later. As a control group, we recruited a group of 125 travellers who followed a recommended schedule with a primary dose at month 0 and a booster dose at months 6-12. For both study groups, the GMTs increased dramatically and similarly upon the booster immunisation. Although significantly more late travellers (32%) had lost detectable antibodies than controls (11%) before administration of the booster dose, all these subjects showed an anamnestic response to the booster dose. Delaying the booster dose up to 66 months after primary vaccination did not seem to influence the immunogenicity of the booster dose. However, the recommended 6-12-month interval remains if detectable antibody titers are to be warranted constantly.

[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.

[Evaluating the efficacy and tolerance of atorvastatin in hyperlipidemia in general practice (SWITCH Study)]. / Prüfung der Wirksamkeit und Verträglichkeit von Atorvastatin bei Hyperlipidämie unter Praxisbedingungen (SWITCH-Studie).

Elevated levels of serum lipids and lipoproteins are known to play a major role in the development of atherosclerosis and subsequent coronary heart disease (CHD). In controlled clinical studies, atorvastatin (Sortis), a new 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA)-reductase inhibitor, proved to be a very effective and safe lipid-lowering agent. The aim of this open-label, multicentre study (without a control group) was to confirm the efficacy and safety of atorvastatin in a private practice group, including 181 Swiss cardiologists, internists, and general practitioners. A total of 877 hyperlipidaemic patients requiring treatment participated in this study. To evaluate the effectiveness of the treatment with atorvastatin over a period of 12 weeks, total plasma cholesterol (TC), HDL cholesterol, LDL cholesterol and triglycerides (TG) were determined every 4 weeks. The initial atorvastatin dose was 10 mg in 78% of patients and 20 mg in 22%. The dose was doubled every 4 weeks until the target values of TC < or = 5.2 mmol/l and TC/HDL < or = 5 were reached. After 12 weeks of treatment with atorvastatin the mean reduction in TC, TC/HDL, LDL and TG compared to baseline levels was 33, 37, 42, and 25% respectively. At the same time the HDL concentration was increased by 9%. These results were evidenced in patients with existing coronary heart disease, in high risk patients without manifest coronary heart disease and in patients with significantly elevated lipid levels (TC > 7.8 mmol/l, TC/HDL > 6.5). After treatment with atorvastatin for 12 weeks, 59% of patients had reached the therapeutic target of TC < or = 5.2 mmol/l. The target of TC/HDL < or = 5 was reached by 79%. Atorvastatin was almost without exception well tolerated, the most frequently reported side effects being nausea, myalgia, and headache. In this open-label multicentre study atorvastatin was found to be effective and well tolerated. The observed reduction in the lipid and lipoprotein concentration is in accordance with the results of published controlled studies. The lipid and lipoprotein concentrations were decreased significantly in patients with slight to moderate elevation of lipid levels as well as in those with significantly raised values.

[Pharmacoeconomic evaluation of pravastatin in coronary secondary prevention in patients with myocardial infarct or unstable angina pectoris. An analysis based on the LIPID Study]. / Pharmakoökonomische Bewertung von Pravastatin in der koronaren Sekundärprävention bei Patienten mit Myokardinfarkt oder instabiler Angina Pectoris. Eine Analyse auf der Grundlage der LIPID-Studie.

BACKGROUND: Secondary coronary prevention with lipid lowering drugs have become a major issue in health policy formulation due to the large upfront investment in drug therapy. The recently completed LIPID trial with pravastatin in secondary prevention immediately raise the question whether pravastatin might be cost-effective in Switzerland. METHODS: We conducted a cost-effectiveness analysis from the perspective of third party payers. The following costs were included in the analysis: daily treatment costs of pravastatin, non fatal myocardial infarction, coronary bypass operations and stroke. Life years gained was obtained by applying the declining exponential approximation of life expectancy. All calculations were standardized to 1000 treated patients. RESULTS: The net costs of treating 1000 patients (i.e. drug costs minus the costs of sequelae and interventions) are Fr. 3.6 Mio. In addition, a total of 430 life-years may be saved through treatment. The corresponding cost-effectiveness of pravastatin treatment is Fr. 8341 (nominal) Fr. 6985 (discounted). CONCLUSIONS: The results suggest that the cost-effectiveness of pravastatin in secondary prevention lie well within the threshold of other commonly accepted medical interventions and may be considered an economically viable approach for secondary coronary prevention.

Major reduction in plasma Lp(a) levels during sepsis and burns.

Plasma levels of lipoprotein(a) [Lp(a)], an atherogenic particle, vary widely between individuals and are highly genetically determined. Whether Lp(a) is a positive acute-phase reactant is debated. The present study was designed to evaluate the impact of major inflammatory responses on plasma Lp(a) levels. Plasma levels of C-reactive protein (CRP), low density lipoprotein cholesterol, Lp(a), and apolipoprotein(a) [apo(a)] fragments, as well as urinary apo(a), were measured serially in 9 patients admitted to the intensive care unit for sepsis and 4 patients with extensive burns. Sepsis and burns elicited a major increase in plasma CRP levels. In both conditions, plasma concentrations of Lp(a) declined abruptly and transiently in parallel with plasma low density lipoprotein cholesterol levels and closely mirrored plasma CRP levels. In 5 survivors, the nadir of plasma Lp(a) levels was 5- to 15-fold lower than levels 16 to 18 months after the study period. No change in plasma levels of apo(a) fragments or urinary apo(a) was noticed during the study period. Turnover studies in mice indicated that clearance of Lp(a) was retarded in lipopolysaccharide-treated animals. Taken together, these data demonstrate that Lp(a) behaves as a negative acute-phase reactant during major inflammatory response. Nongenetic factors have a major, acute, and unexpected impact on Lp(a) metabolism in burns and sepsis. Identification of these factors may provide new tools to lower elevated plasma Lp(a) levels.