Genetic Insights on the Relation of Vascular Risk Factors and Cervical Artery Dissection.

BACKGROUND: The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. OBJECTIVES: This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS. METHODS: This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections. RESULTS: Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for ß-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD. CONCLUSIONS: These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under ß-blockers. This may inform secondary prevention strategies and trial design for CeAD.

Riociguat real-world use in patients with chronic thromboembolic pulmonary hypertension: A retrospective, observational cohort study in France.

BACKGROUND: Riociguat is the first approved treatment for inoperable and persistent/recurrent post-surgery chronic thromboembolic pulmonary hypertension (CTEPH). The RetrospectIve Adempas® stuDy (RiAD) aimed to describe the real-world utilization of riociguat in France. METHODS: In this retrospective multicentric study in patients initiating riociguat, dosing regimen, co-treatments and clinical characteristics were collected over a 2-year follow-up period. RESULTS: A total of 173 patients (mean age, 71.4 years; female, 63.0%; NYHA II-III, 80.3%) were included from January 2015 to December 2016 in 18 centers. All patients were diagnosed with CTEPH (75.7% inoperable and 20.8% with persistent/recurrent pulmonary hypertension [pH] after surgery) with mean (SD) right atrial pressure 7.6 (4.2) mmHg, mean pulmonary artery pressure 43.0 (11.4) mmHg and mean cardiac output 4.1 (1.1) L/min. Before riociguat initiation, 32.4% of patients previously received at least one pH-specific therapy. At initiation, 93.1% of patients were receiving anticoagulants and 83.2% were not receiving pH-specific co-treatments. Riociguat was initiated at 1 mg three times daily (t.i.d.) in 85.5% of patients and 82.1% were receiving 2.5 mg dose t.i.d. at 24 months. The maximal daily dose of 7.5 mg was never exceeded. At 24 months, the estimated rate of patients still taking riociguat was 78.8% with an estimated mean (SD) time on treatment of 20.1 (0.5) months per patient. No new safety signals were recorded. CONCLUSIONS: The results of this real-world study show that riociguat is used in France in accordance with its therapeutic indication in patients with inoperable or persistent/recurrent post-operative CTEPH and confirm its long-term safety.

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.

Simple cardiovascular risk stratification by replacing total serum cholesterol with anthropometric measures: The MORGAM prospective cohort project.

To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19-97 years, without established cardiovascular disease, and not on antihypertensive treatment. While BMI was reported in all, WHR and EFM were reported in âˆ¼52,000 participants. Prognostic importance of anthropometric measurements and total-cholesterol was evaluated using adjusted Cox proportional-hazards regression, logistic regression, area under the receiver-operating-characteristic curve (AUCROC), and net reclassification improvement (NRI). The primary endpoint was MACE, a composite of stroke, myocardial infarction, or death from coronary heart disease. Age interacted significantly with anthropometric measures and total-cholesterol on MACE (P ≤ 0.003), and therefore age-stratified analyses (<50 versus ≥ 50 years) were performed. BMI, WHR, EFM, and total-cholesterol were independently associated with MACE (P ≤ 0.003) and resulted in significantly positive NRI when added to age, sex, smoking status, and systolic blood pressure. Only total-cholesterol increased discrimination ability (AUCROC difference; P < 0.001). In subjects < 50 years, the prediction model with total-cholesterol was superior to the model including BMI, but not superior to models containing WHR or EFM, while in those ≥ 50 years, the model with total-cholesterol was superior to all models containing anthropometric variables, whether assessed individually or combined. We found a potential role for replacing total-cholesterol with anthropometric measures for MACE-prediction among individuals < 50 years when laboratory measurements are unavailable, but not among those ≥ 50 years.

Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study.

AIM: To test the association of alcohol consumption with total and cause-specific mortality risk. DESIGN: Prospective observational multi-centre population-based study. SETTING: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. PARTICIPANTS: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). MEASUREMENTS: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. FINDINGS: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7-14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7-20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10-35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. CONCLUSIONS: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.

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.

Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults.

Background Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated. Methods and Results The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex-specific Cox models, stratified by cohort, with age as the time scale. Models included baseline categorical obesity measures, age, total and high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive drugs, smoking, and diabetes mellitus. A total of 9105 all-cause deaths were recorded during a median follow-up of 10 years. Hazard ratios for all-cause death presented J- or U-shaped associations with most obesity measures. With waist and hip circumference included in the same model, for all hip sizes, having a smaller waist was strongly associated with lower risk of death, except for men with the smallest hips. In addition, among those with smaller waists, hip size was strongly negatively associated with risk of death, with ≈20% more people identified as being at increased risk compared with waist circumference alone. Conclusions A more complex relationship between hip circumference, waist circumference, and risk of death is revealed when both measures are considered simultaneously. This is particularly true for individuals with smaller waists, where having larger hips was protective. Considering both waist and hip circumference in the clinical setting could help to best identify those at increased risk of death.

Does Estimated Pulse Wave Velocity Add Prognostic Information?: MORGAM Prospective Cohort Project.

The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, Setting, and Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main Outcomes and Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.

Prevalence and Treatment of Familial Hypercholesterolemia in France.

BACKGROUND: Familial hypercholesterolemia (FH) is known to be underdiagnosed and undertreated. The prevalence of heterozygous FH is estimated to be 1 in 500. Nevertheless, a recent meta-analysis of screening in the general population seems to show that the prevalence of FH is more likely to be 1 in 250. METHODS: Analysis was based on the third French MONICA and MONALISA population surveys. Participants were randomly recruited in 1995 and 2005 from the general population of 3 regions of France. FH was diagnosed using a modified version of the Dutch Lipid Clinic Network (DLCN) without genetic testing. RESULTS: The DLCN score was assessed in 7928 participants aged 35 to 74 years; 50% were men. The prevalence of definite or probable FH was 0.85% (95% CI, 0.63-1.06). Among patients with definite or probable FH, 12% had histories of premature cardiovascular disease (vs less than 1% among subjects without FH; P < 0.0001), 70% were treated (13% with high-intensity, 83% with moderate-intensity, and 4% with low-intensity statin therapy), 90% had cholesterol screening within the past 12 months, and 97% were aware of their hypercholesterolemia. None reached the recommended low-density lipoprotein cholesterol (LDL-C) target (< 2.5 or < 1.8 mmol/L for subjects in primary prevention vs in secondary prevention or with diabetes, respectively), with a mean distance to target of 3.0 mmol/L. CONCLUSIONS: In a sample from the French general population aged 35 to 74 years, the prevalence of FH was close to 1 in 120, and the patients with FH were undertreated.

Does the Mediterranean Diet Protect against Stress-Induced Inflammatory Activation in European Adolescents? The HELENA Study.

Stress increases inflammation but whether adherence to Mediterranean diet counteracts this association and how early can these effects be observed is not well known. We tested whether (1) cortisol is associated to inflammation, (2) cortisol is associated to the adolescent Mediterranean diet score (aMDS), (3) aMDS lessens inflammation, (4) aMDS associates with cortisol levels and inflammation. Two hundred and forty-two adolescents (137 females; 12.5⁻17.5 years old) provided salivary cortisol, blood and 2-day 24-h dietary recall from which aMDS was derived. Cortisol levels were associated with increased tumor necrosis factor (TNF-α B = 11.887, p = 0.001) when adjusted for age, gender, parental education and body mass index (BMI). Moreover, cortisol levels were inversely associated to adherence to the Mediterranean Diet (B = -1.023, p = 0.002). Adolescents with higher adherence to aMDS had lower levels of interleukins (IL) IL-1, IL-2, IL-6 and TNF-α, compared to those who did not adhere. The association between cortisol and TNF-α was no longer significant when aMDS was included in the model (B = 6.118, p = 0.139). In addition, comparing lower and higher aMDS groups, the association between cortisol and TNF-α was only observed in those with lower aMDS adherence. Our study suggests that adherence to the Mediterranean Diet may counteract the effect of stress on inflammatory biomarkers which may contribute to decreasing the risk of future mental health.

Identification of a functional FADS1 3'UTR variant associated with erythrocyte n-6 polyunsaturated fatty acids levels.

BACKGROUND: Blood polyunsaturated fatty acid (PUFA) levels are determined by diet and by endogenous synthesis via Δ5- and Δ6-desaturases (encoded by the FADS1 and FADS2 genes, respectively). Genome-wide association studies have reported associations between FADS1-FADS2 polymorphisms and the plasma concentrations of PUFAs, HDL- and LDL-cholesterol, and triglycerides. However, much remains unknown regarding the molecular mechanisms explaining how variants affect the function of FADS1-FADS2 genes. OBJECTIVE: Here, we sought to identify the functional variant(s) within the FADS gene cluster. METHODS: To address this question, we (1) genotyped individuals (n = 540) for the rs174547 polymorphism to confirm associations with PUFA levels used as surrogate estimates of desaturase activities and (2) examined the functionality of variants in linkage disequilibrium with rs174547 using bioinformatics and luciferase reporter assays. RESULTS: The rs174547 minor allele was associated with higher erythrocyte levels of dihomo-γ-linolenic acid and lower levels of arachidonic acid, suggesting a lower Δ5-desaturase activity. In silico analyses suggested that rs174545 and rs174546, in perfect linkage disequilibrium with rs174547, might alter miRNA binding sites in the FADS1 3'UTR. In HuH7 and HepG2 cells transfected with FADS1 3'UTR luciferase vectors, the haplotype constructs bearing the rs174546T minor allele showed 30% less luciferase activity. This relative decrease reached 60% in the presence of miR-149-5p and was partly abolished by cotransfection with an miR-149-5p inhibitor. CONCLUSION: This study identifies FADS1 rs174546 as a functional variant that may explain the associations between FADS1-FADS2 polymorphisms and lipid-related phenotypes.

Determinants and outcome of multiple and early recurrent cervical artery dissections.

OBJECTIVE: To assess putative risk factors and outcome of multiple and early recurrent cervical artery dissection (CeAD). METHODS: We combined data from 2 multicenter cohorts and compared patients with multiple CeAD at initial diagnosis, early recurrent CeAD within 3 to 6 months, and single nonrecurrent CeAD. Putative risk factors, clinical characteristics, functional outcome, and risk of recurrent ischemic events were assessed. RESULTS: Of 1,958 patients with CeAD (mean ± SD age 44.3 ± 10 years, 43.9% women), 1,588 (81.1%) had single nonrecurrent CeAD, 340 (17.4%) had multiple CeAD, and 30 (1.5%) presented with single CeAD at admission and had early recurrent CeAD. Patients with multiple or early recurrent CeAD did not significantly differ with respect to putative risk factors, clinical presentation, and outcome. In multivariable analyses, patients with multiple or early recurrent CeAD more often had recent infection (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.29-2.53), vertebral artery dissection (OR 1.82, 95% CI 1.34-2.46), family history of stroke (OR 1.55, 95% CI 1.06-2.25), cervical pain (OR 1.36, 95% CI 1.01-1.84), and subarachnoid hemorrhage (OR 2.85, 95% CI 1.01-8.04) at initial presentation compared to patients with single nonrecurrent CeAD. Patients with multiple or early recurrent CeAD also had a higher incidence of cerebral ischemia (hazard ratio 2.77, 95% CI 1.49-5.14) at 3 to 6 months but no difference in functional outcome compared to patients with single nonrecurrent CeAD. CONCLUSION: Patients with multiple and early recurrent CeAD share similar risk factors, clinical characteristics, and functional outcome. Compared to patients with single nonrecurrent CeAD, they are more likely to have recurrent cerebral ischemia at 3 to 6 months, possibly reflecting an underlying transient vasculopathy.

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.

Inflammation and insulin resistance according to body composition in European adolescents: the HELENA study.

INTRODUCTION: Inflammation is related to insulin resistance in adults, especially on those individuals with high levels of body composition. OBJECTIVES: The aim of this study is to assess the relationship between a set of inflammatory biomarkers and insulin resistance by levels of body composition in a sample of European adolescents. MATERIAL AND METHODS: Nine hundred and sixty-two adolescents (442 boys and 520 girls) from nine European countries met the inclusion criteria of having measurements for the homeostasis model assessment (HOMA) and a set of inflammation-related biomarkers: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors C3 and C4 and selected cell adhesion molecules. Body mass index (BMI), fat mass index (FMI) and waist circumference (WC) were categorized using tertiles. To assess the associations stratifying by body composition indexes, ANOVA and linear regression models were performed. RESULTS: Mean biomarkers' concentrations differed across BMI, FMI and WC tertiles (p < 0.05) by sex. In both sexes, insulin, HOMA, CRP, C3 and C4 were significantly different between categories (p < 0.001), always showing the highest mean concentration in the upper category of BMI, FMI and WC. The most consistent finding was an association between insulin resistance and C3 concentrations (p < 0.05), in the adolescents in the highest tertile of BMI, FMI and WC, except in the case of FMI in girls. CONCLUSION: Inflammatory and glucose metabolism markers differed by tertiles of body composition, being usually higher in the highest tertile. C3 complement factor was associated with insulin resistance in adolescents, especially those with high total and abdominal adiposity.

Score of Adherence to 2016 European Cardiovascular Prevention Guidelines Predicts Cardiovascular and All-Cause Mortality in the General Population.

BACKGROUND: Guidelines on cardiovascular (CV) disease prevention promote healthy lifestyle behaviours and CV risk factor control to reduce CV risk. The effect of adherence to these guidelines on CV and all-cause mortality is not well known. METHODS: We assessed the effect of baseline adherence to "2016 European Guidelines on CV Disease Prevention in Clinical Practice" on long-term CV and all-cause mortality in a sample recruited from the French general population. Analysis was on the basis of the Third French Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population-based survey (recruitment period: 1994-1997). We built an adherence score to European guidelines, considering adherence to recommendations for smoking, drinking, physical activity, body mass index, blood pressure, low-density and high-density lipoprotein cholesterol, fasting blood glucose, and diet at baseline. Vital status was obtained 18 years after inclusion. Statistical analysis was on the basis of multivariate Cox modelling. RESULTS: Adherence score was assessed in 1311 apparently healthy participants aged 35-64 years (73% men). During the follow-up, 186 deaths occurred (41 were due to a CV cause). Considering CV mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score (worse adherence) was 3.12 (95% confidence interval [CI], 1.62-6.01; P = 0.001), compared with subjects in the first, second, or third quartile (best adherence). Considering all-cause mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score was 2.27 (95% CI, 1.68-3.06; P < 0.001). CONCLUSIONS: Better baseline adherence to European guidelines on CV disease prevention was associated with a significantly reduced long-term CV and all-cause mortality in a sample from the French general population.

Changes over time in the prevalence and treatment of cardiovascular risk factors, and contributions to time trends in coronary mortality over 25 years in the Lille urban area (northern France).

BACKGROUND: The long-term collection of population-based data should improve our knowledge of the contribution of trend in cardiovascular risk factors to the steady fall in mortality associated with coronary heart disease in high-income countries. AIMS: To assess long-term time trends in the prevalence of cardiovascular risk factors, estimated coronary heart disease risk and mortality between 1986 and 2013 in the Lille urban area (northern France). METHODS: We studied representative samples of inhabitants of the Lille urban area (aged 40-64 years) in 1986-1988 (n=860), 1995-1996 (n=1021), 2005-2007 (n=1021) and 2011-2013 (n=1636), together with data from the Lille MONICA registry. RESULTS: In men, the age-standardized prevalence fell between 1986 and 2013 from 70.5% to 42.5% for hypertension, from 71.1% to 58.3% for dyslipidaemia and from 44.1% to 24.7% for smoking (all P<0.001). The prevalence of being overweight increased from 59.6% to 65.1% (P<0.05). In women, the prevalences decreased from 56.6% to 34.3% for hypertension and from 60.9% to 42.2% for dyslipidaemia (both P<0.001). The prevalences of smoking (17%) and being overweight (50%) were stable. The mean 10-year (95% confidence interval) predicted risk of fatal coronary heart disease (estimated with the Systematic Coronary Risk Evaluation equation) decreased by 2.02% (1.78-2.25%) per year for men and by 1.55% (1.32-1.78%) for women. The observed coronary mortality rate fell by 2.6% (2.2-3.0%) in men and 2.8% (1.9-3.6%) in women. CONCLUSIONS: Prevalences of main risk factors and estimated coronary mortality risk decreased concomitantly with the observed coronary mortality - indicating that primary prevention made a major contribution to the decrease in mortality.

Prevalence of ideal cardiovascular health in European adolescents: The HELENA study.

BACKGROUND: The ideal cardiovascular health (iCVH) construct consists of 4 health behaviours and 3 health factors and is strongly related to later cardiovascular disease. However, the prevalence of iCVH in European adolescents is currently unknown. METHODS: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study is a cross-sectional, multicentre study conducted in 9 European countries during 2006-2007 and included 3528 adolescents (1683 boys and 1845 girls) between 12.5 and 17.5years of age. Status (ideal vs. non-ideal) for the health behaviours (smoking status, body mass index, physical activity and diet) and health factors (total cholesterol, blood pressure and fasting glucose) were determined. RESULTS: Overall, the prevalence of ideal health behaviours was low; non-smoking (60.9% ideal), body mass index (76.8%), physical activity (62.1%), and diet (1.7%). The prevalence of ideal health factors was; total cholesterol (65.8%), blood pressure (62.0%) and plasma glucose (88.8%). CONCLUSIONS: The low prevalence of iCVH behaviours, especially diet and physical activity, identified in European adolescents is likely to influence later cardiovascular health which strongly motivates efforts to increase ideal health behaviours in this population.

Ideal cardiovascular health and liver enzyme levels in European adolescents; the HELENA study.

There is an increasing interest for the role of liver enzymes as predictors of non-liver-related morbidity and mortality. The American Heart Association (AHA) described the ideal cardiovascular health concept as a score of seven cardiovascular health behaviors and factors that can be used to monitor and predict ideal cardiovascular health over time. This study aimed to examine the association of the ideal cardiovascular health (ICH), as defined by the AHA, with liver enzyme levels in European adolescents. A total of 637 adolescents (54.6% females), aged 14.6 ± 1.2 years from nine European countries participated in this cross-sectional study. Blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase were measured and the AST/ALT ratio calculated. Ideal cardiovascular health was defined as meeting ideal levels of the following components: four behaviors (smoking, body mass index, physical activity, and diet) and three factors (total cholesterol, blood pressure, and glucose). A higher number of ideal cardiovascular health behaviors, factors, and ideal cardiovascular health index were associated with lower ALT (P < 0.05, P < 0.001, and P < 0.001, respectively) and gamma-glutamyltransferase (P < 0.001, P < 0.01, and P < 0.001, respectively) levels. Similarly, a higher number of ideal cardiovascular health behaviors (P < 0.01), factors (P < 0.01), and ideal cardiovascular health index (P < 0.001) were associated with a higher aspartate aminotransferase to alanine aminotransferase ratio. These findings reinforce the usefulness of the ICH index as an instrument to identify target individuals and promote cardiovascular health in adolescents, and it also extends these observations to the liver manifestation of the metabolic syndrome.

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.).