Additive Effect of APOE Rare Variants on the Phenotype of Familial Hypercholesterolemia.

BACKGROUND: Autosomal dominant hypercholesterolemia (ADH) is due to deleterious variants in LDLR, APOB, or PCSK9 genes. Double heterozygote for these genes induces a more severe phenotype. More recently, a new causative variant of heterozygous ADH was identified in APOE. Here we study the phenotype of 21 adult patients, double heterozygotes for rare LDLR and rare APOE variants (LDLR+APOE) in a national wide French cohort. METHODS: LDLR, APOB, PCSK9, and APOE genes were sequenced in 5743 probands addressed for ADH genotyping. The lipid profile and occurrence of premature atherosclerotic cardiovascular diseases were compared between the LDLR+APOE carriers (n=21) and the carriers of the same LDLR causative variants alone (n=22). RESULTS: The prevalence of LDLR+APOE carriers in this French ADH cohort is 0.4%. Overall, LDL (low-density lipoprotein)-cholesterol concentrations were 23% higher in LDLR+APOE patients than in LDLR patients (9.14±2.51 versus 7.43±1.59 mmol/L, P=0.0221). When only deleterious or probably deleterious variants were considered, the LDL-cholesterol concentrations were 46% higher in LDLR+APOE carriers than in LDLR carriers (10.83±3.45 versus 7.43±1.59 mmol/L, P=0.0270). Two patients exhibited a homozygous familial hypercholesterolemia phenotype (LDL-cholesterol >13 mmol/L). Premature atherosclerotic cardiovascular disease was more common in LDLR+APOE patients than in LDLR carriers (70% versus 30%, P=0.026). CONCLUSIONS: Although an incomplete penetrance should be taken into account for APOE variant classification, these results suggest an additive effect of deleterious APOE variants on ADH phenotype highlighting the relevance of APOE sequencing.

A retrospective analysis on optimal medical therapy for patients with symptomatic lower extremity peripheral artery disease: a French observational study.

OBJECTIVE: Patients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc < 0.55 g/l is unknown. Aims of this study were to: (i) describe the prevalence of patients with a LDLc < 0.55 g/l, (ii) describe the prevalence of patients with an optimal medical treatment; (iii) compare this management between patients with a vascular surgery history and those without a vascular surgery history; and (iv) evaluate the number of patients eligible for new lipid-lowering therapies according to FOURIER and REDUCE-IT criteria. METHODS: In this single-center retrospective study, prevalence is expressed as numbers and percentages. Comparison of the number of well managed patients between LEAD patients with a vascular surgery history and those without was performed. Number of patients who would be eligible for FOURIER and REDUCE-IT studies were calculated. RESULTS: Among the LEAD patients included in the analysis (n = 225), only 12.4% (n = 28) had a LDLc < 0.55 g/L. The prevalence of patients who received the optimal medical treatment was 50.7% (n = 114). There was no statistical difference in the prevalence of patients with and without vascular surgery history achieving the LDLc goal (n = 9 (10.6%) vs. n = 19 (13.6%); p = not significant). Ninety-three patients (46.0%) would be eligible for EVOLOCUMAB treatment according to the Fourier study design whereas 17 patients (8.4%) would be eligible for treatment with ICOSAPENT ETHYL according to the REDUCE-IT study design. CONCLUSION: A majority of LEAD patients did not reach the LDLc goals. LEAD patients with a vascular surgery history did not experience a better management whereas they had a more consistent follow-up.

An unfavorable dietary pattern is associated with symptomatic peripheral artery disease.

BACKGROUND AND AIMS: Diet has an essential role in primary and secondary cardiovascular prevention by modulating various cardiovascular risk factors. The need to have easily useable tools seems essential to facilitate the daily practice of clinicians in order to propose the most optimal management of their patients' diet. The aim of this study was to compare the diet assessed with a simple food frequency questionnaire (FFQ) between patients with symptomatic peripheral artery disease (PAD) and healthy subjects. MATERIALS AND RESULTS: In this ancillary study (ELECTRO-PAD study), we included symptomatic PAD patients and healthy participants. All participants filled a FFQ previously validated called Cardiovascular-Dietary-Questionnaire 2 (CDQ-2). CDQ-2 allows the calculation of different scores: global food score, saturated fatty acids score (SFA), unsaturated fatty acids score (UFA), fruit and vegetable score. The higher the score, the better the diet. We compared the different scores between PAD patients and healthy participants. We included 37 PAD patients and 40 healthy subjects. Mean global score was significantly lower in PAD patients compared to the healthy participants (5.35 ± 7.65 vs 10.60 ± 5.81; p = 0.0011). Similarly, the sub-scores concerning unsaturated fatty acids and fruits-vegetables were significantly lower in PAD patients (p < 0.010). Only the sub-score concerning saturated fatty acids was not significantly different (p = 0.8803) between PAD patients and healthy participants. CONCLUSION: CDQ-2 highlights that PAD patients have an unfavorable diet compared with healthy participants. CDQ-2 is a tool of interest to help the clinicians for dietary advice of PAD patients.

Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.

OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score >100, and/or stenosis of >50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P < .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.

APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia.

Primary hypercholesterolemia is characterized by elevated LDL-cholesterol (LDL-C) levels isolated in autosomal dominant hypercholesterolemia (ADH) or associated with elevated triglyceride levels in familial combined hyperlipidemia (FCHL). Rare APOE variants are known in ADH and FCHL. We explored the APOE molecular spectrum in a French ADH/FCHL cohort of 5743 unrelated probands. The sequencing of LDLR, PCSK9, APOB, and APOE revealed 76 carriers of a rare APOE variant, with no mutation in LDLR, PCSK9, or APOB. Among the 31 APOE variants identified here, 15 are described in ADH, 10 in FCHL, and 6 in both probands. Five were previously reported with dyslipidemia and 26 are novel, including 12 missense, 5 synonymous, 2 intronic, and 7 variants in regulatory regions. Sixteen variants were predicted as pathogenic or likely pathogenic, and their carriers had significantly lower polygenic risk scores (wPRS) than carriers of predicted benign variants. We observed no correlation between LDL-C levels and wPRS, suggesting a major effect of APOE variants. Carriers of p.Leu167del were associated with a severe phenotype. The analysis of 11 probands suggests that carriers of an APOE variant respond better to statins than carriers of a LDLR mutation. Altogether, we show that the APOE variants account for a significant contribution to ADH and FCHL.

Effect on blood lipids of two daily servings of Camembert cheese. An intervention trial in mildly hypercholesterolemic subjects.

As a concentrated source of saturated fat, cheese consumption is considered to be associated with increased cholesterolemia and generally forbidden in dietary guidelines for adults with hypercholesterolemia. The aim of this study was to evaluate the impact of saturated fatty acids on lipid parameters and blood pressure with regards to different types of dairy products: Camembert and full-fat yoghurt. One-hundred and fifty-nine moderate hypercholesterolemic subjects without treatment were instructed to consume two full-fat yoghurts (2 × 125 g) per day for 3 weeks (run-in period) and then for a further period of 5 weeks, either two full-fat yoghurts or two 30 g servings of Camembert cheese per day. We observed that over the 5-week daily consumption of two servings of Camembert cheese, blood pressure and serum lipids did not change in moderate hypercholesterolemic subjects. These results suggest that fermented cheese such as Camembert could be consumed daily without affecting serum lipids or blood pressure.

Treatment of pediatric heterozygous familial hypercholesterolemia 7 years after the EAS recommendations: Real-world results from a large French cohort.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8-10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking. OBJECTIVE: Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. METHODS: This was a retrospective and prospective multicenter cohort study (2015-2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD. RESULTS: We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (-44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal. CONCLUSION: Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed.

Management of lipid variables in primary cardiovascular prevention: A position paper from the Heart, Vessels and Metabolism Group of the French Society of Cardiology.

Low-density lipoprotein cholesterol has been established as a powerful cardiovascular risk factor; its reduction provides a clinical benefit in primary cardiovascular prevention, irrespective of the characteristics of the patients treated. It is useful to tailor low-density lipoprotein cholesterol targets according to the magnitude of cardiovascular risk (low, high or very high) in order to reduce the cardiovascular risk as fully as possible. In order to provide a uniform approach, it is necessary to propose recommendations for good practice, defining strategies for reducing low-density lipoprotein cholesterol. It is also necessary to know their merits, to analyse their practical limits and to propose adaptations, taking into account limitations and national specifics. This position paper aims to analyse the contribution and limits, as well as the adaptation to French practice, of 2019 and 2021 European Society of Cardiology recommendations for the management of lipid variables and cardiovascular prevention.

Impact of dietary intervention on eating behavior after ischemic stroke.

Objective: Ischemic stroke is a major health issue. Currently, the relationship between dietary patterns and the occurrence of cardiovascular diseases including stroke is established, but the effect of systematic dietary intervention on dietary changes in ischemic stroke patients is unknown. Our objective was to compare changes in the dietary pattern of ischemic stroke patients who received a systematic diet intervention with changes in the dietary pattern of ischemic stroke patients who did not receive a systematic dietary intervention during their hospitalization. Methods: In this before-and-after study, two groups of patients with ischemic stroke were compared: Group 1 included 34 patients admitted with an ischemic stroke without a systematic dietray intervention; Group 2 included 34 patients admitted with an ischemic stroke with a systematic dietary intervention. Dietary patterns were assessed by a validated food frequency questionnaire of 19 questions (from a previously validated questionnaire of 14 questions), at the onset of stroke and at 6 months after stroke. This questionnaire allows the calculation of different scores as follows: global food score, saturated fatty acids score (SFA), unsaturated fatty acids score (UFA), fruit and vegetable score, and alcohol score. Results: Score changes were more important in group 2 than in group 1 for the global food score (7.4 ± 7 vs. 1.9 ± 6.7, p = 0.0013), the fruit and vegetable score (2 ± 2.6 vs. 0.6 ± 2.2, p = 0.0047), and the UFA score (1.8 ± 2.7 vs. 0.1 ± 3.3, p = 0.0238), whereas no significant differences were observed for the SFA score (-3.9 ± 4.9 vs. -1.6 ± 6, p = 0.1779) and the alcohol score (-0.4 ± 1.5 vs. -0.3 ± 1.1, p = 0.6960). Conclusion: This study showed that systematic dietary intervention during hospitalization improves the dietary patterns of ischemic stroke patients. The impact on the recurrence of ischemic stroke or cardiovascular events after dietary pattern changes needs to be studied.

Effectiveness of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on total and cardiovascular mortality and morbidity in primary prevention: A nationwide study based on French Health Insurance Data (SNDS).

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) both inhibit the renin-angiotensin system (RAS) but have different sites of action. Whether clinically meaningful differences exist is still debated. The authors set up a population-based nationwide retrospective cohort study with at least 5 years of follow-up based on the comprehensive French Health Insurance Database linked to the French hospital discharge database. Patients aged 50 or above, identified as ARB or ACE inhibitor new users in 2009 (at least one delivery during the year and no such delivery in 2008) were eligible. Exclusion criteria included history of cancer, cardiovascular disease, or chronic renal insufficiency. Main outcome measure was overall mortality. Secondary outcomes were cardiovascular deaths, major cardiovascular events, and major or other cardiovascular events. Out of 407 815 eligible patients, 233 682 (57%) were ARB users; two-third had no previous exposure to antihypertensive drug. Based on propensity-score based Cox model, ARB new user group had a better overall (HR: .878, 95%CI, .854 to .902), and cardiovascular (HR: .841, 95%CI, .800 to .84) survival and had a lower risk for major cardiovascular events (HR: .886, 95%CI, .868 to .905). Statistically significant quantitative interactions were detected with diabetes. Considering subgroup analyses, ARBs had a better survival than ACE inhibitors in nondiabetic patients.

Validation and reproducibility of a short food frequency questionnaire for cardiovascular prevention.

BACKGROUND: Diet strongly influences cardiovascular risk. Dietary evaluation is a major issue in cardiovascular prevention, but few simple tools are available. Our team previously validated a short food frequency questionnaire; a new version of this questionnaire (Cardiovascular Dietary Questionnaire 2 [CDQ-2]) is easier to complete and more reliable. AIMS: To validate CDQ-2 in comparison with the original version, and to test its reproducibility. METHODS: CDQ-2 has 17 closed-ended questions; it provides a global dietary score that is a combination of specific scores for saturated, monounsaturated and omega-3 fatty acids, and fruit and vegetables. CDQ-2 was validated against the original version in two groups, who completed both questionnaires: 99 patients with cardiovascular risk factors and 50 healthy subjects. Reproducibility was assessed with 27 health professionals who completed the questionnaire twice, with a 1-month interval. RESULTS: The correlation coefficients of the scores between the two questionnaires ranged from 0.65 (monounsaturated fatty acids) to 0.93 (fruit and vegetables) (all P<0.001). The percentage of subjects classified in the same quartile by both questionnaires ranged from 56% (omega-3 fatty acids) to 78% (fruit and vegetables). The percentage of subjects classified in the same or adjacent quartile ranged from 91% to 99%. The intraclass correlation coefficients, which assessed reproducibility, ranged from 0.61 (fruit and vegetables) to 0.88 (saturated fatty acids) (P<0.001). CONCLUSIONS: This new version of the short dietary questionnaire shows good reproducibility and correlations with the original version; use and reliability are improved, which makes CDQ-2 a valuable tool for cardiovascular prevention.

An unfavorable dietary pattern is associated with symptomatic ischemic stroke and carotid atherosclerosis.

OBJECTIVE: Ischemic strokes represent more than 80% of total strokes in Western countries. The influence of dietary factors on ischemic stroke risk is debated mainly because available data are limited. Our objective was to compare the dietary pattern of symptomatic ischemic stroke patients under 65 years old with control subjects using a validated 14-item food frequency questionnaire (FFQ). We also compared symptomatic ischemic stroke patients with carotid atherosclerosis with those without according to the presence or the absence of carotid plaque defined by duplex scanning. METHODS: This was a case-control multi-center study that took place in one University hospital and two general hospitals in France. One hundred twenty-four symptomatic ischemic stroke patients (confirmation by a neurologist and imaging; 66% smokers) and 50 controls (34% smokers) without any known cardiovascular disease or previous nutritional advice were included. The main outcome measure(s) were intake scores for saturated (SFA), monounsaturated (MUFA), Omega-3 polyunsaturated (Omega-3 PUFA), and Omega-6 polyunsaturated fatty acids (Omega-6PUFA). Fruit and vegetables and an overall cardiovascular dietary score were evaluated with the FFQ. The overall cardiovascular score is calculated as (MUFA + Omega-3 PUFA + fruits and vegetables) - (SFA) scores. RESULTS: Compared with controls, ischemic stroke patients had a higher SFA score (6.6 +/- 3.0 vs 4.9 +/- 2.7; P < .001), lower scores of MUFA (0.8 +/- 0.9 vs 1.5 +/- 1.2; P < .001), Omega-3 PUFA (1.7 +/- 1.6 vs 2.2 +/- 1.5; P = .013), Omega-6PUFA (2.6 +/- 2.5 vs 3.9 +/- 2.7; P = .002), fruit and vegetables (2.9 +/- 1.7 vs 3.8 +/- 1.6; P = .005), and a lower overall dietary score (-1.2 +/- 5.0 vs 2.5 +/- 4.4; P < .001). These results remained statistically significant after adjustment for age, gender, and smoking status. Ischemic stroke patients with carotid atherosclerosis (n = 54) had a worse overall cardiovascular dietary score than those without (n = 68): -2.2 +/- 4.4 vs -0.2 +/- 5.2; P = .024. CONCLUSION: Compared with controls, ischemic stroke patients, especially those with carotid atherosclerosis, have an unfavorable dietary pattern (high SFA, low fruit and vegetables, and Omega-3 PUFA consumptions) that may have been a facilitating condition of the ischemic stroke. Dietary recommendations of a healthy diet should be useful in ischemic stroke prevention, especially in patients with cardiovascular risk factors.

Optimization of high intensity interval exercise in coronary heart disease.

High intensity interval training has been shown to be more effective than moderate intensity continuous training for improving maximal oxygen uptake (VO(2max)) in patients with coronary heart disease (CHD). However, no evidence supports the prescription of one specific protocol of high intensity interval exercise (HIIE) in this population. The purpose of this study was to compare the acute cardiopulmonary responses with four different single bouts of HIIE in order to identify the most optimal one in CHD patients. Nineteen stable CHD patients (17 males, 2 females, 65 +/- 8 years) performed four different bouts of HIIE, all with exercise phases at 100% of maximal aerobic power (MAP), but which varied in interval duration (15 s for mode A and B and 60 s for mode C and D) and type of recovery (0% of MAP for modes A and C and 50% of MAP for modes B and D). A passive recovery phase resulted in a longer time to exhaustion compared to an active recovery phase, irrespective of the duration of the exercise and recovery periods (15 or 60 s, p < 0.05). Time to exhaustion also tended to be higher with mode A relative to mode C (p = 0.06). Despite differences in time to exhaustion between modes, time spent at a high percentage of VO(2max) was similar between HIIE modes except for less time spent above 90 and 95% of VO(2max) for mode C when compared with modes B and D. When considering perceived exertion, patient comfort and time spent above 80% of VO(2max), mode A appeared to be the optimal HIIE session for these coronary patients.

Geographical variations in the prevalence of hypertension in France: Cross-sectional analysis of the CONSTANCES cohort.

AIMS: While international variations in the prevalence of hypertension are well described, less is known about intra-national disparities and their determinants. We wanted to describe the variations in hypertension prevalence within France and to determine how much lifestyle and socioeconomic factors contributed to explain these regional variations. METHODS: Participants (62,247 French adults aged 18 to 69 years) were recruited in the 16 centres of the CONSTANCES study between 2012 and 2015. Hypertension was defined as blood pressure higher than 140/90 mmHg and/or taking antihypertensive medications. The contribution of lifestyle and socioeconomic factors to hypertension prevalence variations among centres was examined using sequential hierarchical logistic models. RESULTS: Hypertension prevalence was 37.3% (95% confidence interval (CI) = 36.6-38.0) in men and 23.2% (95% CI = 22.7-23.8) in women. Hypertension prevalence rates varied by almost two-fold among centres (1.9 in men, 1.6 in women) with the highest prevalence in the north and the east of France. Body mass index was strongly associated with hypertension in women (odds ratio (OR)1-unit increase = 1.11 (95% CI = 1.11-1.12)) and was the highest contributor to between-centre variations (27% in women), followed by socioeconomic characteristics (e.g. ORhigh versus low education = 0.85 (95% CI = 0.83-0.87), contributing to 14% of variations in women). Together, family history of hypertension, body mass index, education, occupation and residential area socioeconomic level explained about 30% and 40% of between-centre variations in men and women, respectively. CONCLUSION: Hypertension prevalence greatly varies among French regions and this is partly explained by known lifestyle and socioeconomic factors. Nevertheless, these variations and all the hypertension determinants have not been fully deciphered yet.

Six-year survival study after myocardial infarction: The EOLE prospective cohort study. Long-term survival after MI.

BACKGROUND: Studies of survival after myocardial infarction (MI) are often based on intention to treat analyses of controlled trials. OBJECTIVES: Describe long-term survival after MI in France. METHODS: Six-year cohort study of patients recruited within 3 months after MI. Primary outcome was all-cause death. Vital status was verified in the national death registry. Analysis used Cox models with time-dependent variables and propensity scores. RESULTS: Five thousand five hundred and twenty-seven (5527) subjects were included, 62.1±13 years old, 77.6% male, 9.6% smokers, 16.7% diabetic, 13.3% with previous MI. Up to 99% of patients were initially prescribed secondary prevention drugs (aspirin and/or other antiplatelet agents, beta-blockers, statins or other lipid-lowering agents, angiotensin converting enzyme inhibitors or angiotensin receptor blockers); 73% had all four classes. Overall 6-year mortality was 13.1% [95% confidence interval 12.3 to 14.0%], 2.34 per hundred patient-years (% PY); 49% returned all or all but one of the possible questionnaires (compliant [C]), 50.8% did not (non-compliant [NC]). The main predictors for death were non-compliance with study protocol (death rates NC 2.98% PY, C 1.69%PY, hazard ratio (HR) 3.13 [2.63-3.57]); increasing age at inclusion (HR up to 15.7 [10.7-23.2] for age ≥80); diabetes (1.39 [1.17-1.65]); smoking at inclusion (1.76 [1.27-2.44]), previous MI (1.46 [1.22-1.75]). Beta-blockers (0.79 [0.64-0.96]), statins (0.68 [0.51-0.90]), and enrolment in physical rehabilitation programs (0.74 [0.62-0.89]) were associated with a lower death rate. CONCLUSION: Association of mortality with non-compliance to study protocol probably indicates general non-compliance with prevention. Analyses of treatment effects were hindered by paucity of events and of unexposed patients.

Effect of an educational program (PEGASE) on cardiovascular risk in hypercholesterolaemic patients.

BACKGROUND: Many studies have demonstrated a gap between guidelines for the prevention of cardiovascular disease (CVD) and their implementation in clinical practice. AIM: The PEGASE education program has been devised with an aim to improve the management of patients at high risk of CVD. METHODS: In a multicentre study carried out from 2001-2004 in France, 96 participating physicians were randomized into a "trained" group, which included 398 "educated" patients, and a "non-trained" group, which included 242 "non-educated" patients. Educated patients received six hospital-based educational sessions, four collective and two individual. Framingham score, smoking, lipid levels, glycaemia, blood pressure, dietary intake and drug compliance, as well as quality of life, were evaluated at baseline (M0) and 6 months (M6). The primary endpoint of the study was the efficacy of the PEGASE program in reducing global CVD risk in high-risk patients. RESULTS: The Framingham score was calculated for 473 patients. The Framingham score improved significantly at M6 vs M0 in the educated group (13.0 +/- 8.21 vs 13.6 +/- 8.48, d = -0.658, p = 0.016), but not in the non-educated group (12.5 +/- 8.19 vs 12.4 +/- 7.81, d = +0.064, p = 0.836); the mean change between the two groups did not reach significance. Quality of life, LDL-c level and diet scores improved in the "educated" group only. CONCLUSIONS: The PEGASE education program improved risk factors for CVD, although global assessment by Framingham score was not significantly different between groups. This program, aimed at meeting needs and expectations of patients and physicians, was easily implemented in all hospital centres.

Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an independent marker of triglyceridemia and abdominal adiposity.

BACKGROUND AND AIM: In an animal model VLDL-triglyceride secretion is highly dependent on stearoyl-coA desaturase (SCD) activity and could explain abdominal fattening. The aim was to assess the relationship of plasma palmitoleic acid content, a product of SCD activity, with triglyceridemia and abdominal adiposity in humans. METHODS: We evaluated 134 healthy men. Plasma palmitoleic acid content was used as an indirect measurement of SCD activity because that enzyme catalyzes the desaturation from saturated to monounsaturated fatty acids and palmitoleic acid intake is very small. RESULTS: Subjects with triglycerides > or =75th percentile had a higher palmitoleic acid content than those with triglycerides <75th percentile (3.8+/-0.8 vs 2.8+/-0.9%, p<0.0001). Triglyceridemia was strongly correlated with palmitoleic acid content (PAC) (r=0.533, p<0.001). Mean triglyceridemia was 114% higher (1.43+/-0.75 vs 0.67+/-0.22 mmol/l) in the fourth quartile than in the first quartile of palmitoleic acid content. In a stepwise logistic regression analysis, palmitoleic acid content was the most strongly and independently associated parameter with triglyceridemia, and also with waist circumference when triglyceridemia was not included in the analysis. CONCLUSION: Plasma palmitoleic acid content, a product of SCD activity, is an independent marker of triglyceridemia and abdominal adiposity in men. This enzyme (SCD) could represent a target for prevention and treatment of these metabolic disorders in particular in subjects at risk of developing a metabolic syndrome.

A minimal resting time of 25 min is needed before measuring stabilized blood pressure in subjects addressed for vascular investigations.

Blood pressure (BP) measurement is a central element in clinical practice. According to international recommendations 3 to 5 minutes of resting is needed before blood pressure measurement. Surprisingly, no study has modelled the time course of BP decrease and the minimum resting-time before BP measurement. A cross-sectional bicentric observational study was performed including outpatients addressed for vascular examination. Using two automatic BP monitors we recorded the blood pressure every minute during 11 consecutive minutes. The data was analyzed by non-linear mixed effect regression. Systolic (SBP) and diastolic BPs were studied and we tested the effect of covariates on its evolution through log-likelihood ratio tests. We included 199 patients (66+/-13years old). SBP was found to decrease exponentially. Simulations based on the final model show that only half the population reaches a stabilized SBP (defined as SBP + 5 mmHg) after 5 min of resting-time while it takes 25 min to ensure 90% of the population has a stabilized SBP. In conclusion, our results and simulations suggest that 5 minutes are not enough to achieve a stabilized SBP in most patients and at least 25 minutes are required. This questions whether the diagnosis of hypertension can be reliably made during routine visits in general practitioners' offices.

[Nutritional aspects of hypertension]. / Les mesures nutritionnelles dans l'hypertension artérielle.

Nutritional factors may explain 30-75% of cases of hypertension, depending on the population. Overweight alone can explain 11-25%. Nutritional measures are effective in reducing blood pressure or delaying the onset of hypertension. Globally, their impact is close to that of antihypertensive treatment with a single drug and they potentiate the drug's efficacy. The Dash diet, in particular, has been shown to be effective in lowering blood pressure. It is low in saturated fat and sodium, rich in fruit, vegetables and nonfat dairy products.

Wine drinking and risks of cardiovascular complications after recent acute myocardial infarction.

BACKGROUND: Scientific data on the clinical impact of moderate alcohol consumption after a recent acute myocardial infarction (AMI) are limited, and the specific effect of wine ethanol has not been studied. METHODS AND RESULTS: In survivors of a recent AMI, we analyzed the association between ethanol intake and the risk of recurrence. The patients were classified according to the amount of ethanol that they consumed regularly during follow-up. Major prognostic factors, including the severity of the prior AMI and drug treatment, were recorded and included in the analyses. Only patients with at least 2 reliable assessments of drinking (and dietary) habits were included (n=437). The average ethanol intake was 7.6% of the total energy intake, wherein wine ethanol represented 92% of the total. Among these patients, 104 cardiovascular complications occurred during a mean follow-up period of 4 years. In comparison with abstainers, the adjusted risk of complications was reduced by 59% (95% confidence interval: 17 to 80) in patients whose average ethanol intake was 7.7% of the total energy intake (about 2 drinks/day), and by 52% (95% confidence interval: 4 to 76) in those whose average ethanol intake was of 16% of energy (about 4 drinks/day). CONCLUSION: Whereas moderate wine drinking was associated with a significant reduction in the risk of complications in this homogenous population of coronary heart disease patients, further studies are required to confirm the data, define the clinical and biological profile of the patients who would most benefit from wine drinking after recent AMI, and examine whether the relations found are due to ethanol or other wine ingredients.