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Background: Sudden cardiac death is responsible for 10% to 20% of all deaths in Europe. The current study investigates how well the risk of sudden cardiac death can be predicted. To this end, we validated a previously developed prediction model for sudden cardiac death from the Atherosclerosis Risk in Communities study (USA). Methods: Data from participants of the Copenhagen City Heart Study (CCHS) (n=9988) was used to externally validate the previously developed prediction model for sudden cardiac death. The model's performance was assessed through discrimination (C-statistic) and calibration by the Hosmer-Lemeshow goodness-of-fit (HL) statistics suited for censored data and visual inspection of calibration plots. Additional validation was performed using data from the Hoorn Study (N=2045), employing the same methods. Results: During ten years of follow-up of CCHS participants (mean age: 58.7 years, 56.2% women), 425 experienced SCD (4.2%). The prediction model showed good discrimination for sudden cardiac death risk (C-statistic: 0.81, 95% CI: 0.79-0.83). Calibration was robust (HL statistic: P=0.8). Visual inspection of the calibration plot showed that the calibration could be improved. Sensitivity was 89.8%, and specificity was 60.6%. The positive and negative predictive values were 10.1% and 99.2%. Model performance was similar in the Hoorn Study (C-statistic: 0.81, 95% CI: 0.77-0.85 and the HL statistic: 1.00). Conclusion: Our study showed that the previously developed prediction model in North American adults performs equally well in identifying those at risk for sudden cardiac death in a general North-West European population. However, the positive predictive value is low.

Background: Cardiovascular health may be used for prevention of cerebral vascular disease; however, data on the association of cardiovascular health across midlife and late-life with late-life cerebral vascular disease are lacking. Our aim was to examine whether midlife or late-life cardiovascular health as well as changes of cardiovascular health within midlife and between midlife and late-life were associated with prevalence of magnetic resonance imaging markers of cerebral vascular disease at late-life. Methods: Prospective cohort study including 1638 participants from the Atherosclerosis Risk in Communities Study who took part in 2 visits at midlife (mean ages, 53 and 59 years), and a late-life visit (mean age, 76 years). A cardiovascular health Life’s Simple 7 score (range, 0–12/0–14, depending on diet availability) including 6 out of 7 items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Participants underwent 3T brain magnetic resonance imaging scans in late-life visit. Outcomes were white matter hyperintensity volume, microbleeds, and lacunar, subcortical, and cortical infarcts at late-life. Linear and logistic regression models were used to assess the associations of cardiovascular health in midlife and late-life, and improvement of cardiovascular health within midlife, and from midlife to late-life with magnetic resonance imaging markers of cerebral vascular disease, adjusting for potential confounders. Results: A higher cardiovascular health in midlife, improvement of cardiovascular health within midlife, higher cardiovascular health at late-life, and improvement of cardiovascular health from midlife to late-life were associated with a lower prevalence of cerebral vascular disease markers. For example, improvement in cardiovascular health (per point) from midlife to late-life was associated with smaller white matter hyperintensity volume (β, −0.07 [95% CI, −0.10 to −0.04]) and lower odds of microbleeds (odds ratio, 0.93 [0.90–0.97]), lacunar (odds ratio, 0.93 [0.89–0.97]), subcortical (odds ratio, 0.93 [0.89–0.97]), and cortical infarcts (odds ratio, 0.92 [0.87–0.97]). Conclusions: Improving cardiovascular health within midlife and from midlife to late-life may prevent development of cerebral vascular disease.

Background: To examine the association of ultrasensitive cTnI (cardiac troponin I) with incident cardiovascular disease events (CVDs) in the primary prevention setting. Methods: cTnI was analyzed in the baseline plasma (2008–2012) of CVD-free volunteers from the Paris Prospective Study III using a novel ultrasensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection of 0.013 pg/mL. Incident CVD hospitalizations (coronary heart disease, stroke, cardiac arrhythmias, deep venous thrombosis or pulmonary embolism, heart failure, or arterial aneurysm) were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed SD increase of cTnI in Cox models using age as the time scale. Results: The study population includes 9503 participants (40% women) aged 59.6 (6.3) years. cTnI was detected in 99.6% of the participants (median value=0.63 pg/mL, interquartile range, 0.39–1.09). After a median follow-up of 8.34 years (interquartile range, 8.0–10.07), 516 participants suffered 612 events. In fully adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (hazard ratio, 1.18 [1.08–1.30]). Among all single risk factors, cTnI had the highest discrimination capacity for incident CVD events (C index=0.6349). Adding log cTnI to the SCORE 2 (Systematic Coronary Risk Evaluation) risk improved moderately discriminatory capacity (C index 0.698 versus 0.685; bootstrapped C index difference: 0.0135 [95% CI, 0.0131–0.0138]), and reclassification of the participants (categorical net reclassification index, 0.0628 [95% CI, 0.023–0.102]). Findings were consistent using the US pooled cohort risk equation. Conclusions: Ultrasensitive cTnI is an independent marker of CVD events in the primary prevention setting.

We evaluated whether better cardiovascular health at midlife and improvement of cardiovascular health within midlife were associated with dementia risk.Two longitudinal population-based studies were used: Atherosclerosis Risk in Communities (ARIC) (n = 11,460/visits at ages 54 and 60), and Age, Gene/Environment Susceptibility (AGES)-Reykjavik (n = 3907/visit at age 51). A cardiovascular health score (range 0-12/0-14, depending on diet availability) including six/seven items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Cardiovascular health was defined as low (score 0-4/0-5), intermediate (5-7/6-9), or high (8-12/10-14). Incident dementia was ascertained through linkage to health records and with neuropsychological examinations.Midlife high compared to low cardiovascular health (hazard ratios [HRs]: for ARIC: 0.60 [95% confidence interval: 0.52, 0.69]); for AGES-Reykjavik: 0.83 [0.66, 0.99] and improvement of cardiovascular health score within midlife (HR per one-point increase: ARIC: 0.94 [0.92, 0.96]) were associated with lower dementia risk.Better cardiovascular health at midlife and improvement of cardiovascular health within midlife are associated with lower dementia risk.Cardiovascular health and dementia were studied in two large cohort studies. Better cardiovascular health at midlife relates to lower dementia risk. Improvement of cardiovascular health within midlife relates to lower dementia risk. Promotion of cardiovascular health at midlife can help to reduce dementia risk.

Background: Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources. Methods: We present new cross-ancestry meta-analyzed GWAS results involving up to 81 669 VTE cases from 30 studies, with replication of novel loci in independent populations and loci characterization through in silico genomic interrogations. Results: In our genetic discovery effort that included 55 330 participants with VTE (47 822 European, 6320 African, and 1188 Hispanic ancestry), we identified 48 novel associations, of which 34 were replicated after correction for multiple testing. In our combined discovery-replication analysis (81 669 VTE participants) and ancestry-stratified meta-analyses (European, African, and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. A genetic risk score of the significantly associated loci in Europeans identified a 6-fold increase in risk for those in the top 1% of scores compared with those with average scores. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein quantitative-trait locus Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 GWAS loci provided insights to biological pathways contributing to VTE, with some loci contributing to VTE through well-characterized coagulation pathways and others providing new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis. Conclusions: Our cross-ancestry GWAS meta-analyses identified new loci associated with VTE. These findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.

Aims To investigate the impact of coronavirus disease 2019 lockdown on trajectories of arterial pulse-wave velocity in a large population of users of connected smart scales that provide reliable measurements of pulse-wave velocity. Methods and results Pulse-wave velocity recordings obtained by Withings Heart Health & Body Composition Wi-Fi Smart Scale users before and during lockdown were analysed. We compared two demonstrative countries: France, where strict lockdown rules were enforced (n = 26 196) and Germany, where lockdown was partial (n = 26 847). Subgroup analysis was conducted in users of activity trackers and home blood pressure monitors. Linear growth curve modelling and trajectory clustering analyses were performed. During lockdown, a significant reduction in vascular stiffness, weight, blood pressure, and physical activity was observed in the overall population. Pulse-wave velocity reduction was greater in France than in Germany, corresponding to 5.2 month reduction in vascular age. In the French population, three clusters of stiffness trajectories were identified: decreasing (21.1%), stable (60.6%), and increasing pulse-wave velocity clusters (18.2%). Decreasing and increasing clusters both had higher pulse-wave velocity and vascular age before lockdown compared with the stable cluster. Only the decreasing cluster showed a significant weight reduction (−400 g), whereas living alone was associated with increasing pulse-wave velocity cluster. No clusters were identified in the German population. Conclusions During total lockdown in France, a reduction in pulse-wave velocity in a significant proportion of French users of connected smart bathroom scales occurred. The impact on long-term cardiovascular health remains to be established.

Background A higher burden of cardiovascular disease risk factors has been reported in sexual minority populations. Primordial prevention may therefore be a relevant preventative strategy. The study's objectives are to estimate the associations of Life's Essential 8 (LE8) and Life's Simple 7 (LS7) cardiovascular health scores with sexual minority status. Methods and Results The CONSTANCES is a nationwide French epidemiological cohort study that recruited randomly selected participants older than 18 years in 21 cities. Sexual minority status was based on self‐reported lifetime sexual behavior and categorized as lesbian, gay, bisexual, or heterosexual. The LE8 score includes nicotine exposure, diet, physical activity, body mass index, sleep health, blood glucose, blood pressure, and blood lipids. The previous LS7 score included 7 metrics without sleep health. The study included 169 434 cardiovascular disease–free adults (53.64% women; mean age, 45.99 years). Among 90 879 women, 555 were lesbian, 3149 were bisexual, and 84 363 were heterosexual. Among 78 555 men, 2421 were gay, 2748 were bisexual, and 70 994 were heterosexual. Overall, 2812 women and 2392 men declined to answer. In multivariable mixed effects linear regression models, lesbian (β=−0.95 [95% CI, −1.89 to −0.02]) and bisexual (β=−0.78 [95% CI, −1.18 to −0.38]) women had a lower LE8 cardiovascular health score compared with heterosexual women. Conversely, gay (β=2.72 [95% CI, 2.25–3.19]) and bisexual (β=0.83 [95% CI, 0.39–1.27]) men had a higher LE8 cardiovascular health score compared with heterosexual men. The findings were consistent, although of smaller magnitudes for the LS7 score. Conclusions Cardiovascular health disparities exist in sexual minority adults, particularly lesbian and bisexual women, who may represent a priority population for primordial cardiovascular disease prevention.

Background: The burden of sudden cardiac death (SCD) in the general population is substantial and SCD frequently occurs among people with few or no known risk factors for cardiac disease. Reported incidences of SCD vary due to differences in definitions and methodology between cohorts. This study aimed to develop a method for adjudicating SCD cases in research settings and to describe uniform case definitions of SCD in an international consortium harmonizing multiple longitudinal study cohorts. Methods: The harmonized SCD definitions include both case definitions using data from multiple sources (eg, autopsy reports, medical history, eyewitnesses) as well as a method using only information from registers (eg, cause of death registers, ICD-10 codes). Validation of the register-based method was done within the consortium using the multiple sources definition as gold standard and presenting sensitivity, specificity, accuracy and positive predictive value. Results: Consensus definitions of “definite,” “possible” and “probable” SCD for longitudinal study cohorts were reached. The definitions are based on a stratified approach to reflect the level of certainty of diagnosis and degree of information. The definitions can be applied to both multisource and register-based methods. Validation of the method using register-information in a cohort comprising 1335 cases yielded a sensitivity of 74%, specificity of 88%, accuracy of 86%, and positive predictive value of 54%. Conclusions: This study demonstrated that a harmonization of SCD classification across different methodological approaches is feasible. The developed classification can be used to study SCD in longitudinal cohorts and to merge cohorts with different levels of information.

Person-centered cardiovascular health (CVH) may facilitate cardiovascular disease primordial prevention in low resources settings. The study aims to assess the validity of person-centered CVH compared to gold standard measured CVH by examining the concordance between person-centered vs. measured CVH together with their respective association with incident cardiovascular disease events (CVD). Life’s Simple 7 (LS7) CVH metrics, including non-smoking, Body Mass Index, diet, physical activity, blood glycemia, blood pressure, and blood cholesterol were collected from 19,473 adults participating in the e-cohort NutriNet-Santé study from 2011 to 2014 and were followed until September 2020. Clinical examinations and blood analyses defined the measured biological metrics, while diagnoses, medication, or treatment for type 2 diabetes, hypertension, and hypercholesterolemia defined person-centered biological metrics. Declared behavioral metrics were common for both measured and person-centered CVH. The study included 18,714 CVD-free participants (mean age 51 years, 73% women), among whom 16.52% and 38.75% had 5–7 ideal LS7 metrics according to measured and person-centered CVH, respectively. Weighted concordance of person-centered and measured CVH was 0.87 [0.86; 0.88]. Over median follow-up of 8.05 years, 749 CVD events occurred. There was a 7% (HR 0.93 [0.88; 0.99]) and 13% (HR 0.87 [0.83; 0.92]) risk reduction of CVD risk by additional measured and person-centered ideal metrics, respectively. In conclusion, person-centered CVH may represent a reliable alternative to measured CVH.

Background: Women represent a growing proportion of sports participants. Still, few original data regarding sudden cardiac arrest during sports (Sr-SCA) in women are available. Objectives: The authors sought to assess the incidence, characteristics, and outcomes of women presenting with Sr-SCA. Methods: Data were analyzed from 3 population-based European registries (ESCAPE-NET 2020 Horizon Program) that prospectively and exhaustively collect every case of SCA: SDEC (Paris-Sudden Death Expertise Center), ARREST (AmsteRdam REsuscitation Studies), and SRCR (Swedish Register for Cardiopulmonary Resuscitation). Sr-SCA was defined as SCA during or ≤1 hour after cessation of sports activity. Results: Of 34,826 SCA between 2006 and 2017, 760 Sr-SCA (2.2%) were identified, including 54 in women. The average annual incidence of Sr-SCA in women in the 3 registries ranged from 0.10 per million (95% CI: 0.01-0.71 per million) to 0.38 per million (95% CI: 0.14-1.04 per million). Overall, the average annual incidence rate of Sr-SCA in women was 0.19 per million (95% CI: 0.14-0.24 per million), >10-fold lower compared with men (2.63 per million [95% CI: 2.45-2.83 per million]; P < 0.0001). When extrapolating to the total European population and accounting for age and sex, this yields 98 cases per year (95% CI: 72-123 cases per year) in women and 1,350 cases per year (95% CI: 1,256-1,451 cases per year) in men. Subject characteristics and circumstances of occurrence were similar in women vs men. Bystander response, time to defibrillation, and survival rate at hospital admission (58.8% vs 58.5%; P = 0.99) and 30 days did not differ significantly between women and men. Conclusions: These findings emphasize the dramatically lower risk of Sr-SCA in women compared with men, despite similar subject characteristics. This should be considered in designing preparticipation screening strategies in the future.

Introduction: Evidence on the link between sleep habits and cardiovascular diseases (CVD) in the community predominantly relies on studies that have investigated only one sleep habit, measure at one timepoint. Therefore, this study examined the joint effect of five sleep habits at baseline and at follow-up with incident CVD events. Hypothesis: We assessed the hypothesis that change in sleep habits over time including improvement in sleep habits and maintenance of a high level of sleep habits are related to reduced CVD risk. Methods: We combined data from two large independent community-based cohorts, the Paris Prospective Study 3 (France) and the CoLaus/PsyCoLaus study (Switzerland), involving 11 347 participants in total, aged 53–64 and comprising 44.6% women, initially free from CVD at baseline (respectively 2008-2012 and 2003-2006). Information on participants’ sleep habits were collected twice (median time interval between the 2 time points=2.0; interquartile range [IQR]: 2.0-5.2) by validated questionnaires. A healthy sleep score (HSS) combining five sleep habits (early chronotype, sleep duration of 7-8 h/day, never/rarely insomnia, no sleep apnea, and no frequent excessive daytime sleepiness) was calculated at baseline and follow-up. Each sleep habit was scored 1 point if optimal, otherwise 0 point. The score ranged from 0 to 5, reflecting the number of optimal sleep habits. Associations of HSS at baseline and the change in the score over time with CVD events (coronary heart disease, CHD, or stroke) were examined using Cox proportional hazard models. Results: During a median follow-up of 8.9 years (IQR: 8.0-10.0), 499 first CVD events occurred (339 CHD and 175 stroke). In multivariate Cox analysis, the risk of CVD decreased by 18% per one-point increment in the HSS (hazard ratio, HR=0.82 [95% confidence interval, CI, 0.76-0.89]). At follow-up, 38% remained in stable high score (score≥3 at both time points, the median of the baseline HSS), 11% had a stable low HSS (score Conclusions: Higher HSS and increase in the HSS are associated with a lower risk of CHD and stroke in the community. This study supports the promotion of healthy sleep habits in the population and strong collaboration between sleep medicine and CVD medicine.

A higher burden of cardiovascular disease risk factors has been reported in sexual minority populations (SM), such as lesbian, gay, bisexual, and non-heterosexual, compared to heterosexual populations. Therefore, primordial prevention, i.e., preventing risk factor onset in the first place, may be a relevant preventative strategy in this population. This study aimed to quantify the associations of SM status in each sex with Life’s Simple 7 (LS7) and Life’s Essential 8 (LE8) cardiovascular health (CVH) scores. The CONSTANCES study is a multicentric study that recruited randomly selected adults in 24 health examination centers in 21 cities in the French European territory. Sexual minority status was based on self-reported lifetime sexual behavior and categorized as lesbian, gay, bisexual, or heterosexual. The study included 169,434 CVD-free participants (53.64% women, mean age: 46.00 years). Among 90879 women, 555 were lesbian, 3149 bisexual, and 84363 heterosexual. Among 78555 men, 2421 were gay, 2748 bisexual, and 70994 heterosexual. Overall, 2812 women and 2392 men declined to answer. In women, the prevalence of high LS7 scores (12-14) ranged from 9.00% (declined to answer) to 12.38% (bisexual), whereas in men, it ranged from 4.06% (declined to answer) to 9.17% (gay). In multivariate analyses (Table 1), lesbian and bisexual women had lower LS7 score compared to heterosexual women. However, this was observed only among those who had never been pregnant (p for interaction

Introduction: Cardiovascular health may be used for prevention of cerebral vascular disease. We evaluated whether improvement of cardiovascular health within midlife and from midlife to late-life were each associated with lower prevalence of MRI markers of cerebral vascular disease at late-life. Methods: 1,638 participants from the Atherosclerosis Risk in Communities (ARIC) Study took part in two visits at midlife (mean ages 53 at ARIC visit 1 and 59 at visit 3), and a late-life visit (mean age 76). A cardiovascular health Life’s Simple 7 score (range 0-12/0-14, depending on diet availability) including six/seven items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Participants underwent 3T brain MRI scans in 2011-2013 (late-life visit). Outcomes were white matter hyperintensity volume, microbleeds, and lacunar, subcortical, and cortical infarcts at late-life. Linear and logistic regression models were used to assess the associations of cardiovascular health with MRI markers of cerebral vascular disease. Results: Thirty nine percent of participants had high cardiovascular health at midlife visit 1, 32% at midlife visit 3, and 33% at late-life. Improvement of cardiovascular health within midlife and from midlife to late-life were each associated with a lower prevalence of cerebral vascular disease markers. For example, improvement in cardiovascular health (per point) from midlife to late-life was associated with smaller white matter hyperintensity volume (Beta:-0.07 [95%CI:-0.10,-0.04]), and lower odds of microbleeds (OR:0.93 [0.90,0.97]), lacunar (OR:0.93 [0.89,0.97)], subcortical (OR:0.93 [0.89,0.97])], and cortical infarcts (OR:0.92 [0.87,0.97)] (Figure). Conclusions: Improving cardiovascular health within midlife and from midlife to late-life may prevent development of cerebral vascular disease.

Background Studies reported a decrease in hospital admissions for myocardial infarction (MI) in early 2020 as a result of the coronavirus disease 2019 (COVID-19) crisis, mainly restricted to the beginning of the pandemic. Aims To describe national trends in hospital admissions for MI in 2020, and to compare patient characteristics, in-hospital prognosis and 90-day mortality between patients who had an MI in 2020 and those admitted in 2017–2019. Methods All patients hospitalized for MI in France from 2017 to 2020 were selected from the national hospital discharge database. Analyses compared temporal trends in MI admissions, in-hospital cardiac complications and mortality rates in 2020 versus 2017–2019. Results In 2020, 94,747 patients were hospitalized for MI, corresponding to a 6% decrease in MI admissions compared with 2017–19. This decrease was larger during the first lockdown (–24%; P

Depression is common in older individuals and is associated with high disability and mortality. A major problem is treatment resistance: >50% of older patients do not respond to current antidepressants. Therefore, new effective interventions for prevention and treatment of depression in older individuals need to be developed, which requires a better understanding of the mechanisms underlying depression. The pathophysiology of depression is multifactorial and complex. Microvascular dysfunction may be an early and targetable mechanism in the development of depression, notably depression that initiates in late life (late-onset depression). Late-onset depression commonly co-occurs with other diseases or syndromes that may share a microvascular origin, including apathy, cognitive impairment, dementia, and stroke. Together, these disabilities may all be part of one large phenotype resulting from global cerebral microvascular dysfunction. In this review, we discuss the pathophysiology of microvascular dysfunction-related late-onset depression, summarize recent epidemiological evidence on the association between cerebral microvascular dysfunction and depression, and indicate potential drivers of cerebral microvascular dysfunction. We also propose the hypothesis that depression may be a manifestation of a larger phenotype of cerebral microvascular dysfunction, highlight potential therapeutic targets and interventions, and give directions for future research.

ImportanceCardiovascular health may be used for prevention of depressive symptoms. However, data on the association of cardiovascular health across midlife with depressive symptoms are lacking.ObjectiveTo evaluate whether better baseline cardiovascular health and improvement of cardiovascular health over time are associated with a lower risk of both incident depressive symptoms and unfavorable trajectories of depressive symptoms.Design, Setting, and ParticipantsParticipants without depressive symptoms were included from a prospective community-based cohort in France (GAZEL cohort). Cardiovascular health examinations occurred in 1990 and 1997 and assessment of depressive symptoms in 1997 and every 3 years thereafter until 2015. Data were analyzed from January to October 2022.ExposuresNumber of cardiovascular health metrics (smoking, body mass index, physical activity, diet, blood pressure, glucose, and cholesterol) at an intermediate or ideal level in 1997 (range, 0-7) and 7-year change in cardiovascular health between 1990 and 1997.Main Outcomes and MeasuresPrimary outcome was incident depressive symptoms (20-item Center for Epidemiologic Studies–Depression Scale [CES-D] score of 17 or greater in men or 23 or greater in women); secondary outcome was trajectories of depressive symptoms scores. Trajectories included consistently low scores, moderately elevated scores, low starting then increasing scores, moderately high starting, increasing, then remitting scores, and moderately high starting then increasing scores.ResultsOf 6980 included patients, 1671 (23.9%) were women, and the mean (SD) age was 53.3 (3.5) years. During a follow-up spanning 19 years after 1997, 1858 individuals (26.5%) had incident depressive symptoms. Higher baseline cardiovascular health in 1997 and improvement in cardiovascular health over 7 years were each associated with lower risk of depressive symptoms (odds ratio [OR] per additional metric at intermediate or ideal level at baseline, 0.87; 95% CI, 0.84-0.91; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.91; 95% CI, 0.86-0.96). Also, better cardiovascular health was associated with lower risk of unfavorable depressive symptoms trajectories. Compared with the consistently low score trajectory, the lowest risks were observed for the low starting then increasing score trajectory (OR per additional metric at intermediate or ideal level at baseline, 0.70; 95% CI, 0.64-0.76; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.73; 95% CI, 0.68-0.79) and the moderately high starting then increasing score trajectory (OR per additional metric at intermediate or ideal level at baseline, 0.71; 95% CI, 0.64-0.79; OR per 1 higher metric at intermediate or ideal level over 7 years, 0.71; 95% CI, 0.64-0.77).Conclusions and RelevanceIn this prospective community-based cohort study of adults, higher cardiovascular health was associated with a lower risk of depressive symptoms over time. Elucidating which set of cardiovascular factors may affect depression risk could be important for prevention.

International audience; Importance Although hearing loss is common in the population worldwide, the prevalence of hearing loss and hearing aid use is not known.Objective To estimate the prevalence of hearing loss and hearing aid use in the adult French population.Design, Setting, and Participants This cohort study used data from the CONSTANCES cohort, a representative sample of the French population. Volunteers aged 18 to 75 years were recruited at 21 preventive health centers between January 1, 2012, and December 31, 2019. The present study included participants with audiometric data.Main Outcomes and Measures The main outcomes were prevalence of hearing loss and disabling hearing loss overall and by sex and age group and prevalence of self-reported hearing aid use among those with disabling hearing loss. Hearing loss was defined as a pure-tone average (PTA) in the better ear of 20 dB or higher, and disabling hearing loss was defined as a PTA in the better ear of 35 dB or higher.Results Of 200 870 participants in the CONSTANCES study, 186 460 had full audiometric data and were included in this study (mean [SD] age, 47.1 [13.5] years); 100 330 (53.8%) were female, and 86 130 (46.2%) were male. Of these participants, 24.8% (95% CI, 24.6%-25.0%) had hearing loss and 4.3% (95% CI, 4.2%-4.4%) had disabling hearing loss. The prevalence rates of hearing loss increased from 3.4% (95% CI, 2.8%-3.9%) at age 18 to 25 years to 73.3% (95% CI, 69.5%-77.2%) at age 71 to 75 years among men and from 4.4% (95% CI, 3.9%-5.0%) at age 18 to 25 years to 64.1% (95% CI, 59.7%-68.4%) at age 71 to 75 years among women. The prevalence of disabling hearing loss increased from 0.3% (95% CI, 0.2%-0.4%) among participants aged 18 to 25 years to 23.3% (95% CI, 20.7%-26.0%) among participants aged 71 to 75 years. Among the 8050 participants with disabling hearing loss, 36.8% (95% CI, 35.8%-37.9%) reported using hearing aids, including 56.7% (95% CI, 38.9%-74.4%) aged 18 to 25 years and 32.9% (95% CI, 26.8%-39.2%) aged 71 to 75 years.Conclusions and Relevance In this cohort study, hearing loss was prevalent in France, and the prevalence of hearing loss increased with age among both men and women. Hearing aids were underused, particularly among older individuals. These findings suggest that hearing loss prevention and screening in the French population are needed.

BACKGROUND Although sudden cardiac death (SCD) is recognized as a high-priority public health topic, reliable estimates of the incidence of SCD or, more broadly, out-of-hospital cardiac arrest (OHCA), in the population are scarce, especially in the European Union.OBJECTIVES The study objective was to determine the incidence of SCD and OHCA in the European Union.METHODS The study examined 4 large (ie, >2 million inhabitants) European population-based prospective registries collecting emergency medical services (EMS)-attended (ie, with attempted resuscitation) OHCA and SCD (OHCA without obvious extracardiac causes) for >5 consecutive years from January 2012 to December 2017 in the Paris region (France), the North Holland region (the Netherlands), the Stockholm region (Sweden), and in all of Denmark.RESULTS The average annual incidence of SCD in the 4 registries ranged from 36.8 per 100,000 (95% CI: 23.5-50.1 per 100,000) to 39.7 per 100,000 (95% CI: 32.6-46.8 per 100,000). When extrapolating to each European country and accounting for age and sex, this yields to 249,538 SCD cases per year (95% CI: 155,377-343,719 SCD cases per year). The average annual incidence of OHCA in the 4 registries ranged from 47.8 per 100,000 (95% CI: 21.2-74.4 per 100,000) to 57.9 per 100,000 (95% CI: 19.6-96.3 per 100,000), corresponding to 343,496 OHCA cases per year (95% CI: 216,472-464,922 OHCA cases per year) in the European Union. Incidence rates of SCD and OHCA increased with age and were systematically higher in men compared with women.CONCLUSIONS By combining data from 4 large, population-based registries with at least 5 years of data collection, this study provided an estimate of the incidence of SCD and OHCA in the European Union. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Pulse wave velocity is an established marker of early vascular aging but may also help identifying individuals with supernormal vascular aging. We tested the hypothesis that individuals with the largest difference (Δ-age) between chronological and vascular age show the lowest rate of cardiovascular events and may thus be defined as supernormal vascular aging. Vascular age was defined as the predicted age in the best fitting multivariable regression model including classical risk factors and treatment and pulse wave velocity, in a subset of the Reference Values for Arterial Stiffness Collaboration Database (n=3347). Δ-age was then calculated as chronological age minus vascular age, and the 10th and 90th percentiles were used to define early (Δ-age6.8 years). The risk for fatal and nonfatal cardiovascular events associated with vascular aging categories was investigated in the Malmö Diet and Cancer Study cohort (n=2642). In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events), Δ-age was significantly ( P

Background: Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient mortality. Little is known about the prototypes of CAV trajectories at the population level. We aimed to identify the different evolutionary profiles of CAV and to determine the respective contribution of immune and nonimmune factors in CAV development. Methods: Heart transplant recipients were from 4 academic centers (Pitié-Salpêtrière and Georges Pompidou Hospital, Paris, Katholieke Universiteit Leuven, and Cedars-Sinai, Los Angeles; 2004–2016). Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessments of clinical, histological, and immunologic parameters. The main outcome was a prediction for CAV trajectory. We identified CAV trajectories by using unsupervised latent class mixed models. We then identified the independent predictive variables of the CAV trajectories and their association with mortality. Results: A total of 1301 patients were included (815 and 486 in the European and US cohorts, respectively). The median follow-up after transplantation was 6.6 (interquartile range, 4–9.1) years with 4710 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years. The 4 trajectories were characterized by (1) patients without CAV at 1 year and nonprogression over time (56.3%), (2) patients without CAV at 1 year and late-onset slow CAV progression (7.6%), (3) patients with mild CAV at 1 year and mild progression over time (23.1%), and (4) patients with mild CAV at 1 year and accelerated progression (13.0%). This model showed good discrimination (0.92). Among candidate predictors assessed, 6 early independent predictors of these trajectories were identified: donor age ( P P P =0.001), recipient dyslipidemia ( P =0.009), class II anti–human leukocyte antigen donor-specific antibodies ( P =0.004), and acute cellular rejection ≥2R ( P =0.028). The 4 CAV trajectories manifested consistently in the US independent cohort with similar discrimination (0.97) and in different clinical scenarios, and showed gradients for overall-cause mortality ( P Conclusions: In a large multicenter and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 CAV trajectories and their respective independent predictive variables. Our results provide the basis for a trajectory-based assessment of patients undergoing heart transplantation for early risk stratification, patient monitoring, and clinical trials. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04117152.

Objective: Impaired baroreflex function is an early indicator of cardiovascular autonomic imbalance. Patients with type 2 diabetes mellitus (T2D) have decreased baroreflex sensitivity (BRS), however, whether the neural and/or mechanical component of the BRS (nBRS and mBRS, respectively) is altered in those with high metabolic risk (HMR, impaired fasting glucose and/or metabolic syndrome) or with overt T2D, is unknown. We examined this in a community-based observational study, the Paris Prospective Study III (PPS3). Approach and Results: In 7626 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and RR intervals [time intervals between successive R waves]) and mBRS were measured by high-precision carotid echotracking. The associations between overt T2D or HMR as compared with subjects with normal glucose metabolism (NGM) and nBRS or mBRS were quantified using multivariable linear regression analysis. There were 319 subjects with T2D (61±6 years, 77% male), 1450 subjects with HMR (60±6 years, 72% male), and 5857 subjects with NGM (59±6 years, 57% male). Compared with NGM subjects, nBRS was significantly lower in HMR subjects (β=−0.07 [95% CI, −0.12 to −0.01]; P =0.029) and in subjects with T2D (β=−0.18 [95% CI, −0.29 to −0.07]; P =0.002) after adjustment for confounding and mediating factors. Subgroup analysis suggests significant and independent alteration in mBRS only among HMR patients who had both impaired fasting glucose and metabolic syndrome. Conclusions: In this community-based study of individuals aged 50 to 75, a graded decrease in nBRS was observed in HMR subjects and patients with overt T2D as compared with NGM subjects.

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, ankle-brachial index, pulse wave velocity, and coronary artery calcium. the Prospective Studies of Atherosclerosis (Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. in summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. the consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences. (c) 2020 S. Karger AG, Basel, Austrian Science Fund (FWF)Austrian Science Fund (FWF) [P 32488]; Dr.-Johannes-and-Hertha-Tuba Foundation, This work was funded by the Austrian Science Fund (FWF) (P 32488) and the Dr.-Johannes-and-Hertha-Tuba Foundation. Funders of individual studies contributing to the present analysis arelisted onthe Proof-ATHERO webpage(https://clinicalepi.i-med.ac.at/research/proof-athero/studies/).

We examined the association between resting heart rate and life span using linear regression in the Paris Prospective Study I, the Whitehall I Study, and the Framingham Heart Study. We used Cox proportional hazards regression to relate change in heart rate over years to mortality risk. We confirmed the inverse relation between resting heart rate and life span, observed a shift to the right (an increase) in life span over the past 250 years in humans compared to other mammals, and observed that higher resting heart rate was associated with higher risk of mortality after adjustment for standard risk factors.

Aims Age and sex disparities in out-of-hospital cardiac arrest (OHCA) have been described. Reproductive age may have a protected effect on females vs. males, although results are conflicting. We aimed to clarify this using the Paris Sudden Death Expertise Centre (SDEC) registry. Methods and results The Paris SDEC registry collects OHCAs occurring in the Greater Paris Area. We included all OHCAs of presumed cardiac causes occurring between 2013 and 2018. Patients were divided into age groups: 1–13, 13–50, 50–75, and >75 years. Sex and age disparities in OHCA incidence and outcomes were analysed using multivariable negative binomial and logistic regression models. There were 19 782 OHCAs meeting inclusion criteria: 0.37% aged 1–13 years, 12.4% aged 13–50 years, 40.4% aged 50–75 years, and 46.9% aged >75 years. Adjusted incidence rate ratios (IRRs) in females vs. males were for the youngest to the older age groups: 1.29 [95% confidence interval (CI) 0.78–2.13], 0.54 [0.49–0.59], 0.60 [0.56–0.64], and 0.75 [0.67–0.84]. At reproductive age, females were more likely than males to have a return of spontaneous circulation [adjusted odds ratio (OR) 1.60 (1.27–2.02)], to be alive at hospital admission [OR: 1.49 (1.18–1.89)]. In both sexes, patients aged 13–50 years were more likely to survive at hospital discharge than those aged 50–75 years [males: OR 1.81 (1.49–2.20), females: 2.24 (1.54–3.25)]. However, at reproductive age, no sex disparity was observed in survival at hospital discharge [OR: 1.16 (0.75–1.80)]. Conclusion Incidence rate ratios were similar between pre- and post-menopausal aged patients. At reproductive age, no sex disparity in survival at hospital discharge was observed, suggesting that menopausal status may not influence OHCA occurrence and prognosis.

Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2, are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess.

Aims To evaluate the association of basic life support with survival after sports-related sudden cardiac arrest (SR-SCA). Methods and results In this systematic review and meta-analysis, a search of several databases from each database inception to 31 July 2021 without language restrictions was conducted. Studies were considered eligible if they evaluated one of three scenarios in patients with SR-SCA: (i) bystander presence, (ii) bystander cardiopulmonary resuscitation (CPR), or (iii) bystander automated external defibrillator (AED) use and provided information on survival. Risk of bias was evaluated using Risk of Bias in Non-randomized Studies of Interventions. The primary outcome was survival at the longest follow up. The meta-analysis was conducted using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach was used to rate certainty in the evidence. In total, 28 non-randomized studies were included. The meta-analysis showed significant benefit on survival in all three groups: bystander presence [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.48–4.37; I2 = 25%; 9 studies—988 patients], bystander CPR (OR 3.84, 95% CI 2.36–6.25; I2 = 54%; 23 studies—2523 patients), and bystander AED use (OR 5.25, 95% CI 3.58–7.70; I2 = 16%; 19 studies—1227 patients). The GRADE certainty of evidence was judged to be moderate. Conclusion In patients with SR-SCA, bystander presence, bystander CPR, and bystander AED use were significantly associated with survival. These results highlight the importance of witness intervention and encourage countries to develop their first aid training policy and AED installation in sport settings.

Supplemental Digital Content is available in the text., Objective: The aim with the present study was to evaluate the association between pubertal body mass index (BMI) change and adult coronary artery calcification (CAC) score and risk of acute coronary events. Approach and Results: We included 37 672 men from the BMI Epidemiology Study and calculated their pubertal BMI change (BMI at 20 years−BMI at 8 years). Coronary artery computed tomography analysis of CAC score, midlife BMI, and major risk factors for coronary heart disease were available for a sub-cohort through linkage with the SCAPIS (Swedish Cardio Pulmonary Bioimage Study) cohort (n=922). Information on first acute coronary events was retrieved from Swedish national registers (n=37 672, events n=1873). Pubertal BMI change (odds ratio per SD increase, 1.32 [1.14–1.52]), but not childhood BMI, was associated with middle age CAC score ≥1. This association for pubertal BMI change was maintained after adjustment for midlife BMI at CAC analysis and in a model including major cardiovascular risk factors. Individuals who became overweight during puberty (hazard ratio, 2.11 [1.79–2.49]), but not those overweight at 8 years who normalized their weight during puberty, had substantially increased risk of acute coronary events compared with men who were never overweight. Among subjects with an acute coronary event, individuals with pubertal onset overweight were at increased risk of death due to the event. Conclusions: Pubertal BMI change is an independent predictor of CAC score and risk of acute coronary events in adult men. Excessive BMI increase during puberty may initiate the coronary atherosclerotic process, thereby increasing the risk and severity of adult acute coronary events.

OBJECTIVE Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) have used a single measure of CVH, and none have investigated the association with impaired fasting glucose (IFG). We examined the association between changes in CVH and incident T2D and IFG. RESEARCH DESIGN AND METHODS Within the Whitehall II study, CVH was examined every 5 years from 1991/93 until 2015/16. Subjects with 0–2, 3–4, and 5–6 ideal metrics of CVH from the American Heart Association were categorized as having low, moderate, or high CVH, respectively. RESULTS There were 6,234 participants (mean age 49.8 ± 6.0 years, 70% male) without prior cardiovascular disease and T2D, including 5,015 who were additionally free from IFG at baseline. Over a median follow-up of 24.8 (interquartile range 24.0–25.2) years, 895 and 1,703 incident cases of T2D and IFG occurred, respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4,464 participants free from CVD and T2D and among 2,795 participants additionally free from IFG. In multivariate analysis, compared with those with stable low CVH, risk of T2D was lower in those with initially high CVH (hazard ratio [HR] 0.21; 95% CI 0.09, 0.51), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR 0.53; 95% CI 0.41, 0.69), low-moderate/high (HR 0.62; 95% CI 0.45, 0.86), and moderate-low (HR 0.74; 95% CI 0.56, 0.98). Results were similar for IFG, but the effect sizes were smaller. CONCLUSIONS Compared with stable low CVH, other patterns of change in CVH were associated with lower risk of T2D and IFG.

OBJECTIVE Increased carotid stiffness and remodelling is reported in patients with moderate and advanced chronic kidney disease (CKD) and is associated with cardiovascular events. Here, we tested the hypothesis that carotid artery alterations start earlier, during mild CKD. METHODS Within the Paris Prospective Study 3, a large prospective observational survey of nonreferred people aged 50-75 who received an extensive health check-up, there were 294 participants with glomerular filtration rate (GFR) of at least 45 and less than 60 ml/min per 1.73 m (Stage 3A CKD), 840 participants with GFR 60-89 ml/min per 1.73 m with proteinuria (Stage 2 CKD), 4666 participants with GFR 60-89 ml/min per 1.73 m without proteinuria and 3317 individuals with GFR at least 90 ml/min per 1.73 m at study recruitment. Carotid artery measurements were performed using a high-resolution echotracking device. RESULTS Compared with patients with GFR at least 90 ml/min per 1.73 m, the carotid distensibility and strain progressively decreased (P for trend

IMPORTANCE The association of positive airway pressure (PAP) with reduced mortality in patients with obstructive sleep apnea (OSA) remains uncertain.OBJECTIVE To investigate the association between PAP prescription and mortality.DESIGN, SETTING, AND PARTICIPANTS This multicenter, population-based cohort study evaluated data from the Sleep Heart Health Study (SHHS), a long-term observational cohort study that included participants between 1995 and 1998, with a mean follow-up of 11.1 years. Analyses were performed in September 2018. Within the SHHS, we compared patients with obesity and severe OSA with (n=81) and without (n=311) prescription of PAP therapy, after matching patients from each group by age, sex, and apnea-hypopnea index.EXPOSURES Self-reported use of PAP.MAIN OUTCOMES AND MEASURES All-cause mortality.RESULTS Of 392 study participants, 316 (80.6%) were men, and mean (SD) age was 63.1 (11.0) years. Ninety-six deaths occurred; 12 among the prescribed-PAP group and 84 among the nonprescribed-PAP group, yielding crude incidence rates of 12.8 vs 24.7 deaths per 1000 person-years. In Cox multivariate analysis, the hazard ratio (HR) of all-cause mortality for prescribed PAP therapy was 0.38 (95% CI, 0.18-0.81). After propensity matching, the HR of all-cause mortality for prescribed PAP therapy was 0.58 (95% CI, 0.35-0.96). According to survival curves, the difference in mortality appears 6 to 7 years after initiation of PAP therapy.CONCLUSIONS AND RELEVANCE Positive airway pressure prescription is associated with reduced all-cause mortality, and this association appears several years after PAP initiation. If replicated, these findings may have strong clinical implications.

ObjectiveWe aimed to investigate the association between cardiovascular health (CVH), as defined by the American Heart Association, and several sleep disturbances.MethodsTwo community-based cohorts, the Paris Prospective Study 3 (PPS3, France, n=6441) and the CoLaus study (Switzerland, n=2989) were analysed. CVH includes 7 metrics which all can be classified as poor, intermediate and ideal. Global CVH score was categorised into poor (0–2 ideal metrics), intermediate (3–4 ideal metrics) and ideal (≥5 ideal metrics). Associations between global CVH and self-reported sleep disturbances (proxy of sleep-disordered breathing [SDB], excessive daytime sleepiness, insomnia symptoms and short/long sleep duration) and SDB severity measured by polysomnography (PSG) were investigated. Adjusted OR/relative risk ratio (RRR) and 95% CIs were estimated. Subjects with previous cardiovascular disease were excluded.ResultsCompared with poor CVH, subjects with intermediate and ideal global CVH had lower odds of self-reported SDB in both cohorts (ORs 0.55; 95% CI 0.44 to 0.68 and 0.35; 95% CI 0.22 to 0.53, respectively) and had lower SDB severity measured by PSG (RRR 0.07; 95% CI 0.02 to 0.20) in CoLaus. Subjects with intermediate and ideal global CVH had lower odds of excessive daytime sleepiness in PPS3 (ORs 0.82; 0.72 to 0.95 and 0.80; 0.82 to 1.02, respectively). No consistent associations were found between CVH and sleep duration or insomnia symptoms.ConclusionsHigher levels of CVH are associated with lower odds of SDB and excessive daytime sleepiness. However, causal interpretation cannot be made and associations might be bidirectional.

Background: \ud Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.\ud \ud Objectives: \ud This study sought to test the association between the rs9349379 genotype and SCAD.\ud \ud Methods: \ud Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.\ud \ud Results: \ud The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.\ud \ud Conclusions: \ud The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Objective: The mechanisms underlying the association between low number of masticatory units and cardiovascular disease remain unclear. Under a nutritional framework, we hypothesized that poor masticatory capacity could represent an early sign of elevated cardiovascular disease risk as evaluated by circulating markers of systemic inflammation and cardiomyocyte stress or damage. Approach and Results: In this cross-sectional analysis of the Paris Prospective Study III, a community-based observational study, 4837 adults aged 50 to 75 without cardiovascular disease history underwent a full-mouth clinical examination and plasma NTproBNP (N-terminal natriuretic propeptide), hs-CRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6), hs-TNI (high-sensitivity troponin I) were measured using highly sensitive technics. Poor masticatory capacity was defined as P =0.045). The significant association between poor masticatory capacity and higher IL-6 in multivariable analysis was confounded by body mass index. There was no association between functional masticatory units and hs-TNI even in unadjusted analysis. Conclusions: The present findings support a nutritional pathway whereby diet alterations and the resulting abdominal obesity associated with poor masticatory capacity may contribute to the higher level of IL-6 and to the lower level of NTproBNP, respectively.

Aims Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene. Conclusion This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.

Introduction Several anthropometric measurements are variably recommended to assess adiposity in routine practice, with less agreement on their comparative performance. We assessed and compared the relationship of seven anthropometric measures of adiposity—waist circumference (WC), waist‐to‐height ratio (WHtR), Body Mass Index (BMI), Ponderal Index (PI), Conicity Index (C index), A Body Shape Index (ABSI), and Body Roundness Index (BRI)—with blood pressure (BP) levels and prevalent hypertension in adult Cameroonians. Methods Data were collected as Cameroon's contribution to the global May Measurement Month 2017(MMM17) survey. Participants were nonpregnant adults, who had no BP measurement in the past year and with no prior hypertension diagnosis. Hypertension was defined as systolic BP ≥140 mm Hg and/or diastolic ≥90 mm Hg. Odds ratios (ORs) for the presence of hypertension per 1 SD increase in each adiposity metrics were estimated in separate logistic regression models. Assessment and comparison of discrimination used the area under the receiver operating characteristics curve (AUC) and nonparametric methods. Results We included 14 424 participants (8210 [58.25%] female; 39.84 ± 14.33 years). There was a graded association between measures of adiposity and prevalent screen‐detected (newly diagnosed) hypertension, with effect sizes being mostly within the same range across measures of adiposity. AUC for hypertension prediction ranged from 0.709 with PI to 0.721 with BRI for single measures, and from 0.736 to 0.739 with combinations of measures of adiposity. Conclusion WC, WHtR, and BRI were strongly associated with BP and better predicted prevalent hypertension, with effects enhanced with the inclusion of BMI.

International audience; Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.