Ischemic stroke subtypes: risk factors, treatments, and 1-month prognosis - The Lille, France Stroke Registry.

OBJECTIVES: First, this registry-based study aimed to comprehensively analyze patients' medical histories and treatments based on ischemic strokes' etiology. We focused on the management of atrial fibrillation among patients diagnosed with cardioembolic stroke. Then, our objective was to identify prognostic factors associated with 28-day mortality. MATERIALS AND METHODS: All ischemic strokes occurring in adults between 2014 and 2021 in Lille, France, were categorized using the TOAST classification. Comparative analyses of patients' medical characteristics were conducted across subtypes. Survival rates within 28 days post-stroke were assessed, and factors influencing mortality were identified using a multivariate Cox model. RESULTS: 1912 ischemic strokes were recorded, due to cardioembolism (36%), large-artery atherosclerosis (9%), small-artery occlusion (9%), other determined causes (6%), or undetermined causes (39%). The median NIHSS score after cardioembolic stroke (6, IQR: 3-13) was twice that after small-artery occlusion (3, IQR: 2-5). Among patients with cardioembolic stroke, 26% were diagnosed post-admission with atrial fibrillation. For the 42% diagnosed pre-admission, only 54% had prior prescriptions for oral anticoagulants. Reperfusion therapies were administered in 21% of cases, with significant variations across subtypes. Mortality rates were higher after cardioembolic strokes (17%) than after small-artery occlusions (3%). Prognostic factors included etiology, high NIHSS score, atrial fibrillation, and previous heparin prescription. CONCLUSIONS: While atrial fibrillation was underdiagnosed and undertreated, patients with cardioembolic stroke exhibited high severity and elevated mortality rates. Etiology emerged as an independent predictor of early mortality, regardless of NIHSS score upon admission. These findings underscore the importance of targeted prevention to improve patient outcomes after ischemic stroke.

Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort.

BACKGROUND: Cerebral microbleeds (CMBs) have been observed in healthy elderly people undergoing systematic brain magnetic resonance imaging. The potential role of acute triggers on the appearance of CMBs remains unknown. We aimed to describe the incidence of new CMBs after transcatheter aortic valve replacement (TAVR) and to identify clinical and procedural factors associated with new CMBs including hemostatic measures and anticoagulation management. METHODS: We evaluated a prospective cohort of patients with symptomatic aortic stenosis referred for TAVR for CMBs (METHYSTROKE [Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly]). Standardized neurologic assessment, brain magnetic resonance imaging, and analysis of hemostatic measures including von Willebrand factor were performed before and after TAVR. Numbers and location of microbleeds on preprocedural magnetic resonance imaging and of new microbleeds on postprocedural magnetic resonance imaging were reported by 2 independent neuroradiologists blinded to clinical data. Measures associated with new microbleeds and postprocedural outcome including neurologic functional outcome at 6 months were also examined. RESULTS: A total of 84 patients (47% men, 80.9±5.7 years of age) were included. On preprocedural magnetic resonance imaging, 22 patients (26% [95% CI, 17%-37%]) had at least 1 microbleed. After TAVR, new microbleeds were observed in 19 (23% [95% CI, 14%-33%]) patients. The occurrence of new microbleeds was independent of the presence of microbleeds at baseline and of diffusion-weighted imaging hypersignals. In univariable analysis, a previous history of bleeding (P=0.01), a higher total dose of heparin (P=0.02), a prolonged procedure (P=0.03), absence of protamine reversion (P=0.04), higher final activated partial thromboplastin time (P=0.05), lower final von Willebrand factor high-molecular-weight:multimer ratio (P=0.007), and lower final closure time with adenosine-diphosphate (P=0.02) were associated with the occurrence of new postprocedural microbleeds. In multivariable analysis, a prolonged procedure (odds ratio, 1.22 [95% CI, 1.03-1.73] for every 5 minutes of fluoroscopy time; P=0.02) and postprocedural acquired von Willebrand factor defect (odds ratio, 1.42 [95% CI, 1.08-1.89] for every lower 0.1 unit of high-molecular-weight:multimer ratio; P=0.004) were independently associated with the occurrence of new postprocedural microbleeds. New CMBs were not associated with changes in neurologic functional outcome or quality of life at 6 months. CONCLUSIONS: One out of 4 patients undergoing TAVR has CMBs before the procedure and 1 out of 4 patients develops new CMBs. Procedural or antithrombotic management and persistence of acquired von Willebrand factor defect were associated with the occurrence of new CMBs. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02972008.

Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1-10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74-1.02), 11% (HR = 0.89; 0.84-0.95) and 5% (HR = 0.95; 0.89-1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82-1.25), 10% (HR = 1.10; 1.02-1.19) and 17% (HR = 1.17; 1.09-1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

Large disparities in 28-day case fatality by stroke subtype: data from a French stroke registry between 2008 and 2017.

BACKGROUND AND PURPOSE: The objectives of the present analysis were to assess 28-day stroke case fatality according to the stroke aetiology and to identify associated factors. METHODS: All stroke events in adults aged ≥35 years between 2008 and 2017 were collected in a population-based stroke registry in northern France. RESULTS: Out of a total of 2933 strokes, there were 479 (16%) haemorrhagic strokes and 2454 (84%) ischaemic strokes; the 28-day case fatality rates were 48% and 15%, respectively. Three-quarters of the 28-day case fatalities occurred within 6 days of the event for haemorrhagic strokes and within 16.5 days for ischaemic strokes. After an ischaemic stroke, the case fatality rate was higher for women (18%) than for men (12%, p < 0.0001); however, this difference disappeared after adjustment for age. Cardioembolic strokes (34%) and strokes of undetermined cause (33%) were the most common ischaemic subtypes, with case fatality rates of 16% and 18%, respectively. Large artery atherosclerosis (11%) and lacunar strokes (10%) were less common, and both types had a case fatality rate of 3%. Age at the time of the event and stroke severity were both significantly associated with case fatality. For some types of stroke, a history of cardiovascular events and residence in a nursing home were associated with a poor prognosis. Medical care in a neurology ward was inversely associated with case fatality, for all stroke subtypes. CONCLUSIONS: In northern France, post-stroke case fatality remains high, especially for haemorrhagic stroke. Being treated in a neurology ward improved survival by around 80%.

Association between overall fruit and vegetable intake, and fruit and vegetable sub-types and blood pressure: the PRIME study (Prospective Epidemiological Study of Myocardial Infarction).

Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50-59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.

Association of low plasma antioxidant levels with all-cause mortality and coronary events in healthy middle-aged men from France and Northern Ireland in the PRIME study.

BACKGROUND: The main underlying risk factors associated with coronary heart disease (CHD) are modifiable and oxidative injury and systemic inflammatory damage represent key aetiological factors associated with the development and progression of CHD and premature mortality. OBJECTIVE: To examine associations of plasma antioxidant status with all-cause mortality and fatal or non-fatal cardiovascular events. DESIGN: The PRIME study prospectively evaluated 9709 men aged 50-59 years between 1991 and 1993 in Northern Ireland and France who were free of CHD at recruitment and followed annually for deaths and cardiovascular events for 10 years. Serum concentrations of vitamin C, retinol, two forms of vitamin E (α- and γ-tocopherol) and six carotenoids were quantified by high-performance liquid chromatography. Baseline conventional risk factors were considered, as well as socioeconomic differences and lifestyle behaviours including diet, smoking habit, physical activity, and alcohol consumption through Cox regression analyses. RESULTS: At 10 years, there were 538 deaths from any cause and 440 fatal or non-fatal cardiovascular events. After adjustment for country, age, systolic blood pressure, diabetes, body mass index, cholesterol, high density lipoprotein cholesterol, triglycerides, height, total physical activity, alcohol consumption and smoking habit, higher levels of all antioxidants were associated with significantly lower risk of all-cause mortality, with the exception of γ-tocopherol. Only retinol was significantly associated with decreased risk of cardiovascular events in a fully adjusted model. CONCLUSIONS: Low antioxidant levels contribute to the gradient of all-cause mortality and cardiovascular incidence independent of lifestyle behaviours and traditional cardiovascular and socioeconomic risk factors.

Reduced dose of rivaroxaban and dabigatran vs. vitamin K antagonists in very elderly patients with atrial fibrillation in a nationwide cohort study.

AIMS: The real-life benefits and risks of the non-vitamin K antagonist oral anticoagulants for stroke prevention in very elderly patients with atrial fibrillation (AF) are still debated. METHODS AND RESULTS: Cohorts of new users of rivaroxaban 15 mg, dabigatran 110 mg, or vitamin K antagonists (VKA) for AF ≥85 years old in 2013 or 2014 were identified in the nationwide French claims database and followed-up for 1 year. Cohorts were compared after 1:1 matching using high-dimensional propensity score. Compared to VKA use and considering 1-year cumulative incidences, risk of stroke, and systemic embolism was not different with rivaroxaban use [hazard ratio 1.14, 95% confidence interval (CI): 0.93-1.40] and lower with dabigatran use (0.77, 95% CI: 0.60-0.99), risk of major bleeding was not different with rivaroxaban use (0.91, 95% CI: 0.74-1.11) and with dabigatran use (0.81, 95% CI: 0.64-1.03), risk of all-cause death was borderline to significance lower with rivaroxaban use (0.91, 95% CI: 0.83-1.00), and lower with dabigatran use (0.87, 95% CI: 0.78-0.97). The risk for a composite of all events above was not different with rivaroxaban use (0.96, 95% CI: 0.88-1.04) and lower with dabigatran use (0.87, 95% CI: 0.79-0.96) as compared with VKA use. The risk for the composite of all events was not different with rivaroxaban use as compared with dabigatran use (1.09, 95% CI: 0.97-1.23). CONCLUSION: This study shows for the first time in more than 25 000 new real-life anticoagulant users for AF aged ≥85 years a neutral overall benefit-risk of rivaroxaban 15 mg vs. VKA and a favourable overall benefit-risk of dabigatran 110 mg vs. VKA on relevant clinical events. STUDY REGISTRATION: European Medicines Agency EUPAS14567 (www.encepp.eu) and Clinicaltrials.gov id NCT02864758.

Effectiveness and Safety of Rivaroxaban 15 or 20 mg Versus Vitamin K Antagonists in Nonvalvular Atrial Fibrillation.

Background and Purpose- We compared the 1-year safety and effectiveness of rivaroxaban 15 mg (R15) or rivaroxaban 20 mg (R20) to vitamin K antagonists (VKAs) in patients with nonvalvular atrial fibrillation. Methods- New user cohort study of patients dispensed R15 or R20 versus VKA in 2013 or 2014 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million people). R15 and R20 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing, and high-dimensional propensity score. Hazard ratios (95% CIs) for stroke and systemic embolism, major bleeding, and death were computed using Cox proportional hazards or models by Fine and Gray during exposure. Results- In 31 171 matched R20 and VKA, mean age, 71; 62% men; 76% with CHA2DS2-VASc ≥2; 5% HAS-BLED >3 (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol); incidence rates for stroke and systemic embolism were 1.5% and 1.9% (hazard ratio, 0.79 [0.69-0.90]); major bleeding, 1.5% and 2.2% (0.67 [0.59-0.77]); death, 3.9% and 5.8% (0.67 [0.61-0.73]). In 23 314 matched R15 and VKA patients, mean age, 80; 47% men; 93% with CHA2DS2-VASc ≥2 and 9% with HAS-BLED >3; incidence rates of stroke and systemic embolism were 2.3% and 2.1% (1.05 [0.92-1.21]); major bleeding, 2.4% and 2.9% (0.84 [0.74-0.96]); death, 9.1% and 10.8% (0.85 [0.79-0.90]). Numbers needed to treat to observe one fewer death (NNT) were 46 for R15 and 61 for R20. Conclusions- In real life in France over 2013 to 2015, R15 and R20 were at least as effective and safer than VKA. Clinical Trial Registration- URL: http://www.encepp.eu. Unique identifier: EUPAS14567.

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS: We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS: After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS: The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).

Dietary Patterns and Their Relationship With the Perceptions of Healthy Eating in European Adolescents: The HELENA Study.

Objective: The aim of this study was to identify dietary patterns (DPs) in European adolescents and to examine the association between perceptions of healthy eating and the obtained DPs.Method: A multinational cross-sectional study was carried out in adolescents aged 12.5 to 17.5 years and 2,027 (44.9% males) were considered for analysis. A self-reported questionnaire with information on food choices and preferences, including perceptions of healthy eating, and two 24-hour dietary recalls were used. Principal component analysis was used to obtain sex-specific DPs, and linear analyses of covariance were used to compare DPs according to perceptions of healthy eating.Results: Three and four DPs for boys and girls were obtained. In boys and girls, there were significant associations between some perceptions about healthy food and the Breakfast-DP (p < 0.05). In boys, Breakfast-DP and Healthy Beverage-DP were associated with the perception of the own diet as healthy (p < 0.05). Healthy Beverage-DP was associated with those disliking fruits and vegetables (p < 0.05). Girls considering the own diet as healthy were associated with Mediterranean-DP, Breakfast-DP, and Unhealthy Beverage and Meat-DP (p < 0.05). The perception of snacking as a necessary part of a healthy diet was associated with Breakfast-DP in both genders (p < 0.05).Conclusions: In European adolescents, perceptions of healthy eating were mainly associated with a DP characterized by foods consumed at breakfast. Future studies should further explore these findings in order to implement health promotion programs to improve healthy eating habits in adolescents.

Relative validation of the adapted Mediterranean Diet Score for Adolescents by comparison with nutritional biomarkers and nutrient and food intakes: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

OBJECTIVE: To investigate whether adherence to the adapted Mediterranean Diet Score for Adolescents (MDS_A) and the adapted Mediterranean Diet Quality Index for Adolescents (KIDMED_A) is associated with better food/nutrient intakes and nutritional biomarkers. DESIGN: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study is a cross-sectional study aiming to obtain comparable data on a variety of nutritional and health-related parameters in European adolescents aged 12·5-17·5 years. SETTING: Nine European countries. PARTICIPANTS: European adolescents (n 2330) recruited to the HELENA study. Dietary intake was obtained with 24 h dietary recalls, an FFQ and a Food Choices and Preferences questionnaire. MDS_A was calculated as a categorical variable using cut-offs (MDS_A), as a continuous variable (zMDS_A) and with energy adjustments (zEnMDS_A). The KIDMED_A score was also calculated. RESULTS: Multilevel linear regression analysis showed positive associations for zMDS_A and KIDMED_A with serum levels of vitamin D, vitamin C, plasma folate, holo-transcobalamin, ß-carotene and n-3 fatty acids, while negative associations were observed with trans-fatty acid serum levels. For categorical indices, blood biomarkers showed few significant results. zMDS_A and KIDMED_A showed positive associations with vegetables and fruits intake, and negative associations with energy-dense and low-nutritious foods. zMDS_A and KIDMED_A were positively associated with all macronutrients, vitamins and minerals (all P < 0·0001), except with monosaccharides and PUFA for KIDMED_A and cholesterol for both indices (P < 0·05). CONCLUSIONS: zMDS_A and KIDMED_A have shown the strongest associations with the dietary indicators and biomarkers that have been associated with the Mediterranean diet before, and are therefore considered the most appropriate and valid Mediterranean diet scores for European adolescents.

Sex Differences in Stroke Attack, Incidence, and Mortality Rates in Northern France.

BACKGROUND: Age and sex have a major impact on stroke onset. AIMS: We aimed to compare the attack, incidence, and 28-day mortality rate for stroke as well as risk factors in men and women aged 35 and over. METHODS: Data were obtained between 2008 and 2015 from the stroke population-based registry covering the city of Lille (northern France). RESULTS: A total of 2426 strokes (1917 incident strokes) were recorded. The number of strokes was lower in women than in men when considering individuals under the age of 75 but was twice as high when considering individuals aged 75 or over. Overall, there were 25% more strokes in women than in men. The age-adjusted attack (P = .017) and incident (P = .027) rates of stroke were ~30% lower in women than in men (a ~30% lower risk of ischemic stroke (P = .02) and a ~40% lower risk of intracerebral hemorrhage (ICH) (P = .004)). The age-adjusted mortality rate after ICH was ~35% lower in women than in men (P = .014). With regard to cardiovascular risk factors, women with stroke were older, smoked less, and were more likely to have a history of migraine or atrial fibrillation than the men. CONCLUSION: The risk of stroke is lower in women than in men under the age of 75 but is similar when comparing women and men after that age. Nevertheless, the age structure of the population (with more elderly women than elderly men) translates into a higher absolute number of strokes in women than in men.

Xafran, a drug utilization study of rivaroxaban in stroke prevention in atrial fibrillation in France using a claim database.

BACKGROUND: Little is known about the utilization of rivaroxaban in real life treatment settings in France. AIMS: Objectives of this study were to describe the conditions of use and treatment persistence in patients with atrial fibrillation and treated with rivaroxaban for stroke prevention (SP-AF). METHODS: A cohort study was performed using a representative sample of the French nationwide database. All adults who initiated rivaroxaban for SP-AF between 01/08/2012 and 31/12/2014 were included and followed for one year. Inappropriate use of rivaroxaban's was defined as use inconsistent with the summary of product characteristics. RESULTS: In this study, 1278 patients were included, 687 (53.8%) were men and the mean age was 73.4years; 123 patients (9.6%) had a stroke and 78 (6.1%) a major bleeding event in the three years before rivaroxaban initiation. At treatment initiation 236 (18.5%) had chronic congestive heart failure, 991 (77.5%) hypertension, 247 (19.3%) diabetes and 9 (0.7%) HIV, hepatitis B or C infection. No anticoagulant had been administered in the six previous months for 777 patients (60.8%); 160 patients (12.5%) had an inappropriate use of rivaroxaban in SP-AF. At 6 and 12 months after the first delivery with rivaroxaban, 62.8%, and 51.7% (68.5% and 60.5% in sensitivity analyses) of the patients were still treated with rivaroxaban. The proportion of patients with a continuous medication availability above 80% was 96.1%. CONCLUSION: The characteristics of patients in this study are similar to patients treated with this drug in other observational studies. Adherence and persistence with rivaroxaban can be considered good.

Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study.

BACKGROUND: Atherogenic dyslipidemia is associated with poor cardiovascular outcomes, yet markers of this condition are often ignored in clinical practice. Here, we address a clear evidence gap by assessing the prevalence and treatment of two markers of atherogenic dyslipidemia: elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. METHODS: This cross-sectional observational study assessed the prevalence of two atherogenic dyslipidemia markers, high triglyceride levels and low high-density lipoprotein cholesterol levels, in the study population from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; N = 7641; of whom 51.6% were female and 95.6% were White/Caucasian). The EURIKA population included European patients, aged at least 50 years with at least one cardiovascular risk factor but no history of cardiovascular disease. RESULTS: Over 20% of patients from the EURIKA population have either triglyceride or high-density lipoprotein cholesterol levels characteristic of atherogenic dyslipidemia. Furthermore, the proportions of patients with one of these markers were higher in subpopulations with type 2 diabetes mellitus or those already calculated to be at high risk of cardiovascular disease. Approximately 55% of the EURIKA population who have markers of atherogenic dyslipidemia are not receiving lipid-lowering therapy. CONCLUSIONS: A considerable proportion of patients with at least one major cardiovascular risk factor in the primary cardiovascular disease prevention setting have markers of atherogenic dyslipidemia. The majority of these patients are not receiving optimal treatment, as specified in international guidelines, and thus their risk of developing cardiovascular disease is possibly underestimated. TRIAL REGISTRATION: The present study is registered with ClinicalTrials.gov (ID: NCT00882336).

Comparison of definitions for the metabolic syndrome in adolescents. The HELENA study.

Various definitions are used to define metabolic syndrome in adolescents. This study aimed to compare, in terms of prevalence and differences, five frequently used definitions for this population: International Diabetes Federation, National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP) modified by Cook, pediatric American Heart Association (AHA), World Health Organization, and Jolliffe and Janssen. A sample of 1004 adolescents (12.5-17.0 years) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study was considered. The components of the definitions (waist circumference/BMI, plasma lipids, glycemia, and blood pressure) were applied, and definitions were compared by using crosstabs, sensitivity, specificity, and kappa coefficient. The prevalence of metabolic syndrome varied from 1.6 to 3.8% depending on the used definitions. Crosstabs comparing the definitions showed the fewest cases being misclassified (having metabolic syndrome or not) between NCEP-ATP and AHA. Analyses for kappa coefficient, sensitivity, and specificity confirmed this finding. CONCLUSION: The different definitions do not classify the same adolescents as having MS and prevalence varied between diagnostic methods. The modified NCEP-ATP and the AHA definitions were most analogous in defining subjects as having metabolic syndrome or not. What is known? • Metabolic syndrome is not only a problem of adulthood but is already present in children and adolescents. • Several diagnostic methods are used to define metabolic syndrome in adolescents. What is new? • Comparing the most frequently used definitions of metabolic syndrome in adolescents showed that they do not indicate the same adolescents as having metabolic syndrome. • The modified National Cholesterol Education Program Adult Treatment Panel III and the pediatric American Heart Association definitions were most analogous in defining subjects as having metabolic syndrome or not.

Correlates of dietary energy misreporting among European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

This study examined the correlates of dietary energy under-reporting (UR) and over-reporting (OV) in European adolescents. Two self-administered computerised 24-h dietary recalls and physical activity data using accelerometry were collected from 1512 adolescents aged 12·5-17·5 years from eight European countries. Objective measurements of height and weight were obtained. BMI was categorised according to Cole/International Obesity Task Force (IOTF) cut-off points. Diet-related attitudes were assessed via self-administered questionnaires. Reported energy intake (EI) was compared with predicted total energy expenditure to identify UR and OV using individual physical activity objective measures. Associations between misreporting and covariates were examined by multilevel logistic regression analyses. Among all, 33·3 % of the adolescents were UR and 15·6 % were OV when considering mean EI. Overweight (OR 3·25; 95 % CI 2·01, 5·27) and obese (OR 4·31; 95 % CI 1·92, 9·65) adolescents had higher odds for UR, whereas underweight individuals were more likely to over-report (OR 1·67; 95 % CI 1·01, 2·76). Being content with their own figures (OR 0·61; 95 % CI 0·41, 0·89) decreased the odds for UR, whereas frequently skipping breakfast (OR 2·14; 95 % CI 1·53, 2·99) was linked with higher odds for UR. Those being worried about gaining weight (OR 0·55; 95 % CI 0·33, 0·92) were less likely to OV. Weight status and psychosocial weight-related factors were found to be the major correlates of misreporting. Misreporting may reflect socially desirable answers and low ability to report own dietary intakes, but also may reflect real under-eating in an attempt to lose weight or real over-eating to reflect higher intakes due to growth spurts. Factors influencing misreporting should be identified in youths to clarify or better understand diet-disease associations.

The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents.

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings.

Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry.

BACKGROUND: There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. METHODS AND RESULTS: The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. CONCLUSION: This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

Postprocedural aortic regurgitation in balloon-expandable and self-expandable transcatheter aortic valve replacement procedures: analysis of predictors and impact on long-term mortality: insights from the FRANCE2 Registry.

BACKGROUND: Significant postprocedural aortic regurgitation (AR) is observed in 10% to 20% of cases after transcatheter aortic valve replacement (TAVR). The prognostic value and the predictors of such a complication in balloon-expandable (BE) and self-expandable (SE) TAVR remain unclear. METHODS AND RESULTS: TAVR was performed in 3195 consecutive patients at 34 hospitals. Postprocedural transthoracic echocardiography was performed in 2769 (92%) patients of the eligible population, and these patients constituted the study group. Median follow-up was 306 days (Q1-Q3=178-490). BE and SE devices were implanted in 67.6% (n=1872) and 32.4% (n=897). Delivery was femoral (75.3%) or nonfemoral (24.7%). A postprocedural AR≥grade 2 was observed in 15.8% and was more frequent in SE (21.5%) than in BE-TAVR (13.0%, P=0.0001). Extensive multivariable analysis confirmed that the use of a SE device was one of the most powerful independent predictors of postprocedural AR≥grade 2. For BE-TAVR, 8 independent predictors of postprocedural AR≥grade 2 were identified including femoral delivery (P=0.04), larger aortic annulus (P=0.0004), and smaller prosthesis diameter (P=0.0001). For SE-TAVR, 2 independent predictors were identified including femoral delivery(P=0.0001). Aortic annulus and prosthesis diameter were not predictors of postprocedural AR for SE-TAVR. A postprocedural AR≥grade 2, but not a postprocedural AR=grade 1, was a strong independent predictor of 1-year mortality for BE (hazard ratio=2.50; P=0.0001) and SE-TAVR (hazard ratio=2.11; P=0.0001). Although postprocedural AR≥grade 2 was well tolerated in patients with AR≥grade 2 at baseline (1-year mortality=7%), it was associated with a very high mortality in other subgroups: renal failure (43%), AR

Expired-air carbon monoxide as a predictor of 16-year risk of all-cause, cardiovascular and cancer mortality.

BACKGROUND: Measurement of expired-air carbon monoxide (EACO) is commonly used to ascertain non-smoking status, although it can also reflect exposures not related to smoking. Our aim was to assess 16-year mortality according to EACO measured at baseline, in a general population. METHODS: Our analysis was based on the Third French MONICA population survey (1994-1997). Causes of death were obtained 16 years after inclusion, and assessment of determinants of mortality was based on Cox modeling. RESULTS: EACO was measured in 2232 apparently healthy participants aged 35-64. During follow-up, 195 deaths occurred (19% were due to cardio-vascular (CV) causes and 49% to cancer). At baseline, the mean EACO was 11.8 (±7.4)ppm, 4.6 (±2.5)ppm, 4.3 (±2.2)ppm for current, former and never smokers, respectively (P<0.001). After adjustment for main mortality risk factors and smoking, the hazard ratio (HR) for total mortality was 1.03[95% confidence interval: 1.01-1.06] per 1-unit increase in EACO, and it was 1.04[1.01-1.07] for cancer mortality. Adjusted HR for CV mortality was 1.05[1.01-1.10] but did not remain significant after additional adjustment for smoking (0.98[0.91-1.04]). Interactions between EACO and smoking were not significant. CONCLUSIONS: In a general population, baseline EACO is an independent predictor of 16-year all-cause and cancer mortality, after adjustment for confounders including smoking. Given that the effect of EACO is similar among smokers and non-smokers, EACO is probably not solely related to smoking but could also be a marker of inhaled ambient carbon monoxide and/or endogenous production. Besides, smoking better predicts CV mortality than EACO.