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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.

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/).

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.

This study aimed to investigate the role of cardiovascular health (CVH) and vascular events as potential contributors to socioeconomic inequalities in dementia using causal mediation analyses. We used data from the Three-City Cohort, a French population-based study with 12 years of follow-up, with active search of dementia cases and validated diagnosis. Individual socioeconomic status was assessed using education, occupation and income. A CVH score as defined by the American Heart Association and incident vascular events were considered separately as mediators. We performed multi-level Cox proportional and Aalen additive hazard regression models to estimate the total effects of socioeconomic status on dementia risk. To estimate natural direct and indirect effects through CVH and vascular events, we applied two distinct weighting methods to quantify the role of CVH and vascular events: Inverse Odds Ratio Weighting (IORW) and Marginal Structural Models (MSM) respectively. Among 5581 participants, the risk of dementia was higher among participants with primary education (HR 1.60, 95%CI 1.44–1.78), blue-collar workers (HR 1.62, 95%CI 1.43–1.84) and with lower income (HR 1.23, 95%CI 1.09–1.29). Using additive models, 571 (95% CI 288–782) and 634 (95% CI 246–1020) additional cases of dementia per 100 000 person and year were estimated for primary education and blue-collar occupation, respectively. Using IORW, the CVH score mediate the relationship between education or income, and dementia (proportion mediated 17% and 26%, respectively). Yet, considering vascular events as mediator, MSM generated indirect effects that were smaller and more imprecise. Socioeconomic inequalities in dementia risk were observed but marginally explained by CVH or vascular events mediators. Supplementary Information The online version contains supplementary material available at 10.1007/s10654-021-00788-8.

Background Many kidneys donated for transplant in the United States are discarded because of abnormal histology. Whether histology adds incremental value beyond usual donor attributes in assessing allograft quality is unknown. Methods This population-based study included patients who received a deceased donor kidney that had been biopsied before implantation according to a prespecified protocol in France and Belgium, where preimplantation biopsy findings are generally not used for decision making in the allocation process. We also studied kidneys that had been acquired from deceased United States donors for transplantation that were biopsied during allocation and discarded because of low organ quality. Using donor and recipient characteristics, we fit multivariable Cox models for death-censored graft failure and examined whether predictive accuracy (C index) improved after adding donor histology. We matched the discarded United States kidneys to similar kidneys transplanted in Europe and calculated predicted allograft survival. Results In the development cohort of 1629 kidney recipients at two French centers, adding donor histology to the model did not significantly improve prediction of long-term allograft failure. Analyses using an external validation cohort from two Belgian centers confirmed the lack of improved accuracy from adding histology. About 45% of 1103 United States kidneys discarded because of histologic findings could be accurately matched to very similar kidneys that had been transplanted in France; these discarded kidneys would be expected to have allograft survival of 93.1% at 1 year, 80.7% at 5 years, and 68.9% at 10 years. Conclusions In this multicenter study, donor kidney histology assessment during allocation did not provide substantial incremental value in ascertaining organ quality. Many kidneys discarded on the basis of biopsy findings would likely benefit United States patients who are wait listed.

Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, little is known about CAV trajectories at a population level. Purpose We aimed to identify the different profiles of CAV trajectories. Methods Heart transplant recipients receiving care at 4 academic centers (2004 to 2016) were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was the CAV trajectories, identified with unsupervised latent class mixed models. Results Overall, 1,301 patients were included (609 in France, 206 in Belgium and 486 in the US). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). In the French development cohort, we identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i) Patients without CAV at baseline and non-progression (n=317, 52.1%), ii) patients without CAV at baseline and late onset CAV progression (n=52, 8.5%), iii) patients with mild baseline CAV and mild progression (n=151, 24.8%), iv) patients with mild baseline CAV and accelerated CAV progression (n=89, 14.6%, discrimination 0.92). The 4 CAV trajectories were independently validated in the external validation cohorts from Belgium (discrimination=0.92) and the US (discrimination=0.97). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified and validated 4 distinct CAV trajectories corresponding to specific initial CAV grades and subsequent evolutions. Our results provide the basis for a trajectory-based assessment for risk stratification at early-stage post heart transplantation. Figure 1. Cardiac allograft vasculopathy trajectories in France (n=609), in Belgium (n=206), in USA (n=486). Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. Funding Acknowledgement Type of funding source: None

Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. Little is known about determinants of CAV trajectories at a population level. Purpose We aimed to identify the respective contribution of immune and non-immune factors in the different evolutive profiles of CAV. Methods Heart transplant recipients receiving care at 2 academic centers (2004 to 2016) were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The outcome was CAV trajectories, identified with unsupervised latent class mixed models. The independent, predictive factors of CAV trajectories were investigated with multinomial regressions (NCT04117152). Results Overall, 815 patients were included. The median follow-up post-transplant was 7.7 years (IQR=5.14) with 2,742 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i) Patients without CAV at baseline and non-progression (n=459, 56.3%), ii) patients without CAV at baseline and late onset CAV progression (n=62, 7.6%), iii) patients with mild baseline CAV and mild progression (n=188 23.1%), iv) patients with mild baseline CAV and accelerated CAV progression (n=106, 13.0%, discrimination 0.92). Six early independent predictors of CAV trajectories were identified: donor age (p Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories and their respective immune and non-immune determinants. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring. Factors associated CAV trajectories in multivariate analyses in the derivation cohort. This table shows the association of clinical, immunological, functional and structural parameters associated with CAV trajectories in multivariate multinomial regression analysis. The trajectory of reference was trajectory #1, including patients with no CAV at baseline and stable CAV grade over time. Funding Acknowledgement Type of funding source: None

Background Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, the associations between CAV trajectories and mortality remains poorly described. Purpose We aimed to identify the different evolutive profiles of CAV and to determine the respective association with all-cause mortality. Methods Heart transplant recipients receiving care at 4 academic centers were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was a prediction for CAV trajectories using unsupervised latent class mixed models. We then identified their association with all-cause mortality (NCT04117152). Results Overall, 1,301 patients were included (815 and 486 in the development and validation cohorts, respectively). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i)Patients without CAV at baseline and non-progression (n=823, 63.3%), ii) patients without CAV at baseline and late onset CAV progression (n=79, 6.1%), iii) patients with mild baseline CAV and mild progression (n=261, 20.1), iv) patients with mild baseline CAV and accelerated CAV progression (n=138, 10.6%, discrimination 0.95). The 4 CAV trajectories showed gradient for all-cause mortality (p Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories. These different profiles were associated with distinct prognosis. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring. Figure 1. Overall 10-year survival probability according to the CAV trajectory in the overall cohort (n=1,301). The left part represents the main profiles CAV grades identified with latent class mixed models. Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. The right part represent the Kaplan Meier curves of the different trajectories. Funding Acknowledgement Type of funding source: None

Aims Depression is associated with increased risk of cardiovascular disease (CVD) and the role of poor medical adherence is mostly unknown. We studied the association between depressive symptoms and non-adherence to medications targeting treatable cardiovascular risk factors in the CONSTANCES population-based French cohort. Methods and results We used CONSTANCES data linked to the French national healthcare database to study the prospective association between depressive symptoms (assessed at inclusion with the Center for Epidemiological Studies Depression scale) and non-adherence to medications (less than 80% of trimesters with at least one drug dispensed) treating type 2 diabetes, hypertension, and dyslipidaemia over 36 months of follow-up. Binary logistic regression models were adjusted for socio-demographics, body mass index, and personal history of CVD at inclusion. Among 4998 individuals with hypertension, 793 with diabetes, and 3692 with dyslipidaemia at baseline, respectively 13.1% vs. 11.5%, 10.5% vs. 5.8%, and 29.0% vs. 27.1% of those depressed vs. those non-depressed were non-adherent over the first 18 months of follow-up (15.9% vs. 13.6%, 11.1% vs. 7.4%, and 34.8% vs. 36.6% between 19 and 36 months). Adjusting for all covariates, depressive symptoms were neither associated with non-adherence to medications for hypertension, diabetes, and dyslipidaemia over the first 18 months of follow-up, nor afterwards. Depressive symptoms were only associated with non-adherence to anti-diabetic medications between the first 3–6 months of follow-up. Conclusion Non-adherence to medications targeting treatable cardiovascular risk factors is unlikely to explain much of the association between depressive symptoms and CVD at a population level. Clinicians are urged to search for and treat depression in individuals with diabetes to foster medications adherence.

Objectives Hearing impairment (HI) is a leading impairment worldwide, and identifying modifiable risk factors of HI may have major public health implications. The aim of this study was to investigate the association between obstructive sleep apnoea (OSA) and HI.Design Observational longitudinal study (the Paris Prospective Study 3).Setting Population-based.Participants Volunteers aged 50-75 years and consulting at a preventive medical centre were included between 2008 and 2012. 6797 participants were included in the present analysis.Main outcome measures Audiometry testing was performed in both ears in all participants, and HI was defined by a pure-tone average (PTA) >25 decibels (dB) hearing level in the better ear.Results Obstructive sleep apnoea (estimated by the Berlin questionnaire) was present in 18.6% (n = 1267) and HI in 13.9% (n = 947) of the participants. Mean age was 59.5 years (SD 6.2) and 63.5% were male (n = 4317). In multiple logistic regression modelling, OSA was significantly associated with a 1.21-increased odds of HI (95% confidence interval 1.01-1.44). Several sensitivity analyses supported this finding.Conclusion Obstructive sleep apnoea is associated with a 21% increased odds of HI. These results support active screening of HI in subjects with OSA, and future studies should evaluate whether the treatment of OSA can delay the onset of HI.

Summary Background Sub-Saharan Africa is experiencing a rising burden of hypertension. Antihypertensive medications and diet are the cornerstone of effective hypertension control. Aims To assess adherence to medication and salt restriction in 12 sub-Saharan countries, and to study the relationship between adherence and blood pressure control in patients with hypertension. Methods We conducted a cross-sectional survey in urban clinics in twelve sub-Saharan countries. Data were collected on demographics, treatment and adequacy of blood pressure control in patients with hypertension attending the clinics. Adherence was assessed by questionnaires completed by the patients. Hypertension grades were defined according to European Society of Cardiology guidelines. Association between adherence and blood pressure control was investigated using multilevel logistic regression analysis, adjusting for age, sex and country. Results Among the 2198 patients, 77.4% had uncontrolled blood pressure, 34.0% were poorly adherent to salt restriction, 64.4% were poorly adherent to medication and 24.6% were poorly adherent to both. Poor adherence to salt restriction (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.03–1.72), medication (OR 1.56, 95% CI 1.25–1.93) or both (OR 1.91 1.39–2.66) was related to uncontrolled blood pressure. Moreover, poor adherence to both medication and salt restriction was related to a 1.52-fold (95% CI 1.04–2.22), 1.8-fold (95% CI 1.22–2.65) and 3.08-fold (95% CI 2.02–4.69) increased likelihood of hypertension grade 1, 2 and 3, respectively. Conclusions High levels of poor adherence to salt restriction and medication were noted in this urban sub-Saharan study; both were significantly associated with uncontrolled blood pressure, representing major opportunities for intervention to improve hypertension control in sub-Saharan Africa.

Anemia is known to be associated with depression both in community and clinical populations. However, it is still unknown if this association depends or not on antidepressant intake. We investigated the respective association of depression and antidepressant intake with low hemoglobin level in a large community-based cohort. In 8640 volunteers aged 50 to 75 recruited between June 2008 and June 2012 in Paris (France), we assessed hemoglobin levels (g/dl), depressive symptoms and antidepressant intake. We examined the association of both depression and antidepressant intake with hemoglobin level, adjusting for numerous socio-demographic and health variables. We also assessed the association with specific antidepressant classes. Depression and anti-depressant intake were independently associated with lower hemoglobin level (beta = -0.074; p = .05 and beta = -0.100; p = .02 respectively in the fully-adjusted model). Regarding antidepressant classes, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) intake were associated with lower hemoglobin level (beta = -0.11; p = .01). To conclude, both depression and antidepressant intake were associated with lower hemoglobin level. In particular, as SSRI or SNRIs intake was also related to lower hemoglobin level, these classes should be used with caution in depressed individuals at risk for anemia.

To study the association between chewing capacity-a prerequisite for eating- and the level of cardiovascular health (CVH).This is a cross-sectional analysis conducted on 5430 study participants from the Paris Prospective Study 3 that were subjected to an oral examination by trained dentists at study recruitment between 2008 and 2012. Chewing capacity was determined by the number of functional tooth units (FTUs), and ≥ 5FTUs defined adequate chewing capacity. Subjects were categorized into poor, intermediate, or ideal CVH for the 4 behavioural (smoking status, body mass index, physical activity, diet) and the 3 biological (total cholesterol, fasting glycemia, and blood pressure) factors according to the American Heart Association Life's Simple 7. Multinomial logistic regression was used to explore the association between the number of FTUs (exposure) and ideal or intermediate vs. poor CVH (main outcome).10.31% of the study participants had an ideal CVH and 7% presented an impaired chewing capacity (5 FTUs). Subjects with at least 5 FTUs (OR = 2.37; 95% CI: 1.37-4.12) were more likely to have an ideal global CVH, after adjustment for age, sex, marital status, education, deprivation, depressive status, and dental plaque. This association existed for the behavioural but not the biological CVH, with the strongest association being observed with the diet metric.This is the first study suggesting that adults with a preserved chewing capacity have an increased likelihood to be at an ideal behavioural CVH.

SummaryWe present the results of the largest genome wide association study (GWAS) performed so far in dilated cardiomyopathy (DCM), a leading cause of systolic heart failure and cardiovascular death, with 2,719 cases and 4,440 controls in the discovery population. We identified and replicated two new DCM-associated loci, one on chromosome 3p25.1 (lead SNP rs62232870, p = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication step, respectively) and the second on chromosome 22q11.23 (lead SNP rs7284877, p = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication step, respectively) while confirming two previously identified DCM loci on chromosome 10 and 1, BAG3 and HSPB7. The genetic risk score constructed from the number of lead risk-alleles at these four DCM loci revealed that individuals with 8 risk-alleles were at a 27% increased risk of DCM compared to individuals with 5 risk alleles (median of the referral population). We estimated the genome wide heritability at 31% ± 8%.In silico annotation and functional 4C-sequencing analysis on iPSC-derived cardiomyocytes strongly suggest SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine and beta-alanine transporter whose involvement in myocardial dysfunction and DCM is supported by recent observations in humans and mice. Although less easy to discriminate the better candidate at the 22q11.23 locus, SMARCB1 appears as the strongest one.This study provides both a better understanding of the genetic architecture of DCM and new knowledge on novel biological pathways underlying heart failure, with the potential for a therapeutic perspective.

Background: Large artery stiffness is an index of vascular ageing associated with cardiovascular mortality. While traditional risk factors for arterial stiffness are known, the contribution of socioeconomic factors are less reported. We sought to determine the relationship between arterial stiffness and socioeconomic deprivation (at the individual and neighborhood levels) in healthy males and females. Methods: In 7803 adults, carotid stiffness was determined by high-precision carotid echotracking. Individual deprivation data included education, living alone, occupation and Evaluation of the Deprivation and Inequalities of Health in Healthcare Centers (EPICES) score. Neighborhood deprivation was determined from commune level data (smallest administrative sub-division) available from French National Institute of statistics and Economic Studies (2011) using principal component analysis. The separate and combined associations between individual and neighborhood deprivation (main exposures) and carotid stiffness (outcome) were quantified using linear and multilevel model adjusted for traditional risk factors including age, mean blood pressure, body mass index, fasting glucose, high density lipoprotein, triglycerides, heart rate, history of cardiovascular disease, smoking, alcohol, and physical activity. Analyses were conducted separately in males and females. Results: Individual deprivation (lower education and occupation in males, and living alone and higher EPICES in both populations) was adversely related to carotid stiffness, independently of potential confounders (p < 0.05). Neighborhood deprivation was adversely related to carotid stiffness in males (p < 0.05) but not in females. Conclusion: Socioeconomic deprivation, both at the individual and, to a lesser extent, neighborhood level are associated with carotid stiffness in males. Only individual deprivation is associated with carotid stiffness in females.

Inflammation is a physiological response to aggression of pathogenic agents aimed at eliminating the aggressor agent and promoting healing. Excessive inflammation, however, may contribute to tissue damage and an alteration of arterial structure and function. Increased arterial stiffness is a well-recognized cardiovascular risk factor independent of blood pressure levels and an intermediate endpoint for cardiovascular events. In the present review we discuss immune mediated mechanisms by which inflammation can influence arterial physiology and lead to vascular dysfunction such as atherosclerosis and arterial stiffening. We also show that acute inflammation predisposes the vasculature to arterial dysfunction and stiffening, and alteration of endothelial function and that chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis are accompanied by profound arterial dysfunction which is proportional to the severity of inflammation. Current findings suggest that treatment of inflammation by targeted drugs leads to regression of arterial dysfunction. There is hope that these treatments will improve outcomes for patients. CONDENSED ABSTRACT: Inflammation is a physiological response to aggression of pathogenic agents aimed at eliminating the aggressor agent and promoting healing. Excessive inflammation, however, may contribute to tissue damage and an alteration of arterial structure and function. Increased arterial stiffness is a well-recognized cardiovascular risk factor independent of blood pressure levels. In the present review we discuss (i) mechanisms by which inflammation can influence arterial physiology and lead to vascular dysfunction such as atherosclerosis and arterial stiffening, (ii) clinical models of vascular inflammation, and (iii) current evidence on anti-inflammatory therapy and regression of arterial dysfunction.

Vascular aging is a major contributor to cardiovascular disease and can be quantified by higher carotid stiffness, intima-media thickness and diameter, and hypertension. Weight gain across the lifetime may be an important, modifiable determinant of vascular aging. We therefore aimed to assess lifetime body silhouette trajectories (a marker of weight change across the lifespan) in relation to vascular aging in late adulthood. We used cross-sectional data from a community-based cohort study (n=8243; age, 59.4; 38.7% women). A linear mixed model was used to assess trajectories of recalled body silhouettes from age 8 to 45 years. We assessed carotid artery properties (ultrasonography), resting hypertension (blood pressure ≥140/90 mm Hg or use of antihypertensives), and exaggerated exercise blood pressure, a marker of masked hypertension (systolic blood pressure ≥150 mm Hg during submaximal exercise) at study recruitment when the participants were 50 to 75 years of age. We identified 5 distinct body silhouette trajectories: lean stable (32.0%), lean increase (11.1%), moderate stable (32.5%), lean-marked increase (16.3%), and heavy stable (8.1%). Compared with individuals in the lean-stable trajectory, those in the moderate-stable, lean-marked increase, and heavy-stable trajectories had higher carotid stiffness, intima-media thickness and diameter (odds ratios between 1.23 and 2.10 for highest quartile versus lowest quartile of manifestations of vascular aging; P P

International audience; BACKGROUND - Recent evidence suggests that the association of psychological variables with the risk of coronary heart disease (CHD) might depend upon socioeconomic status (SES). However, it is unclear whether the association between depressive symptoms and CHD risk might differ according to three SES indicators (education, occupational status and household monthly income). METHODS - Among 34,836 working participants of the French CONSTANCES cohort (16,221 men, mean age [SD]: 44.0 [10.4] years) without history of cardiovascular disease, depressive symptoms were assessed with the Center of Epidemiologic Studies Depression scale (CES-D). The Framingham risk equation calibrated to the French population estimated the participant's 10-year risk of CHD. Associations between depressive symptoms and CHD risk were estimated using linear regression models in SES strata. RESULTS - The estimated 10-year risk of CHD was 16.9% in men and 1.8% in women. In men, the increased CHD risk in those with (versus without) depressive symptoms was more pronounced as occupational status decreased, being 0.65% (−0.57; 1.88), 1.58% (0.50; 2.66) and 3.19% (1.30; 5.07) higher in individuals of high, medium and low occupational status, respectively (p for interaction: 0.01). In contrast, effect modification by education or household income was less evident, despite similar trends. In women, no effect modification was found whatever the SES indicator. CONCLUSIONS - Depressive symptoms and 10-year estimated CHD risk were more tightly linked in individuals of lower SES, at least in men. Occupational status was the SES indicator that displays the most obvious effect modification on this association.

Aims: The ESCAPE-NET project (“European Sudden Cardiac Arrest network– towards Prevention, Education and New Effective Treatments”) aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies for survival after SCA on a European scale. Methods: This is an Horizon2020 funded program of the European Union, performed by a European publicprivate consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival after SCA, and 5 deep-phenotyped observational prospective population cohorts for the study of risk factors for occurrence of SCA. Personalized risk scores for predicting SCA onset and for predicting survival after SCA will be derived and validated. Results: The 11 clinical studies with SCA cases comprise 85,790 SCA cases; the 5 observational prospective population cohorts include 53,060 subjects. A total of 15,000 SCA samples will be genotyped for common and rare variants at the Helmholtz Zentrum München (Germany) using the Illumina Global Screening Array which contains > 770,000 SNPs, and after imputation, a database of an estimated > 9 million variants will be available for genome wide association studies. Standardization of risk factors definition and outcomes is ongoing. An Executive Committee has been created along with a Collaboration Policy document. Conclusion: ESCAPE-NET will complement ongoing efforts on SCA outside Europe and within Europe including the EuReCa project.

Objective Hypertension results in more deaths than any other risk factor and has been on the rise in sub-Saharan Africa over the past few decades. Generic drugs have helped improve accessibility and affordability of antihypertensive therapy in developing countries. However, assessment of quality standards of these products is important. We performed a quality assessment of five commonly used antihypertensive generic drugs in 10 sub-Saharan African countries and studied the impact of price on quality. Methods Drug samples were prospectively collected using standardized methods between 2012 and 2014. We developed a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the active ingredient in a certified public laboratory. Quality was defined based on the percentage ratio of measured to expected dosage of active ingredient. Results A total of 1185 samples were assessed, of which 70.0% were generic (n = 830). Among the generic drugs, the percentage of poor-quality drugs was 24.3% (n = 202/830). The percentage ratio of measured to expected dosage of active ingredient ranged from 49.2 to 111.3%; the majority (81.7%) of the poor-quality samples had insufficient quantity of the active ingredient. Moreover, poor quality was not associated with purchase price of the drug. Conclusion In this study from 10 sub-Saharan African countries, nearly one-quarter of the available generic antihypertensive drugs were found to be of poor quality. Concerted measures to improve the quality of antihypertensive drugs could lead to major improvements in hypertension control with attendant reduction of its deleterious consequences in low-income and middle-income countries.

Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers. The histomolecular rejection phenotype associated with complement-activating DSA was characterized by complement deposition and accumulation of natural killer cells and monocytes/macrophages in capillaries and increased expression of five biologically relevant genes (CXCL11, CCL4, MS4A7, MS4A6A, and FCGR3A) indicative of endothelial activation, IFNγ response, CD16-mediated natural killer cell activation, and monocyte/macrophage activation. Compared with standard of care, eculizumab specifically abrogated this histomolecular rejection phenotype and associated with a decreased 3-month rejection incidence rate in patients with complement-activating DSAs (56%; 95% confidence interval [95% CI], 38% to 74% versus 19%; 95% CI, 8% to 35%; P=0.001) but not in those with noncomplement-activating DSAs (9%; 95% CI, 2% to 25% versus 13%; 95% CI, 2% to 40%; P=0.65). In conclusion, circulating complement-activating anti-HLA DSAs are associated with a specific histomolecular kidney allograft rejection phenotype that can be abrogated by complement inhibition.

The impact of time of occurrence has been extensively evaluated for in-hospital cardiac arrests but less for Out-of-Hospital Cardiac Arrests (OHCA). We assessed the impact of the time of occurrence on the characteristics and prognosis of OHCA.Using data from the Paris Sudden Cardiac Death Expertise Center prospective study that includes all OHCA in the Paris Area, we compared characteristics and outcomes of off-hours OHCA (nights and days off) to regular-hours OHCA between 2011 and 2014.Among a total of 9834 OHCA (70.0±17years old, 62.1% males), off-hours OHCA accounted for 63.4%. Although bystanders were more often present (74.4 vs. 72.1%, P=0.01), rates of bystander CPR (46.7 vs. 50.6%, P=0.001) and AED use (1.0 vs. 1.9%, P=0.01) were lower during off-hours. While EMS arrival delays were similar, patients were less often in shockable rhythm (16.3 vs. 19.1%, P0.0001), and return of spontaneous circulation was less frequent (27.5 vs. 31.1%, P0.0001). There was no difference in rates of targeted temperature control (54.8 vs. 54.7%, P=0.75), coronary angiography (57.3 vs. 58.2%, P=0.68) and angioplasty use (32.2 vs. 35.6%, P=0.22). Survival at hospital discharge was lower (4.7 vs. 6.5%, P0.0001) during off-hours. After adjusting for potential confounders, time of occurrence was not associated with worse outcome (OR 0.85, 95% CI 0.69-1.06, P=0.15), and bystander-initiated CPR, shockable initial rhythm and AED use were the main survival predictors (P0.0001).Off-hours OHCA have a 30% lower survival rate, mainly due to differences in initial management (bystander CPR and AED use), illustrating the need to improve bystanders' responsiveness in all circumstances.

Resume But de l’etude Le poids et la taille tels qu’ils etaient a differents âges de la vie sont difficiles a obtenir. Afin d’ameliorer la connaissance de l’historique du poids, Sorensen et al. en 1983, ont developpe un outil a partir de silhouettes permettant d’evaluer la corpulence a differents âges de la vie. Les etudes de validite ont montre que le poids et la taille mesures etaient correles a 80 % a la silhouette rapportee. D’autres etudes ont montre que l’evaluation des silhouettes est un bon moyen de retracer l’historique du poids d’un individu. Tres peu d’etudes epidemiologiques ont utilise cet outil. Une etude francaise a permis de mettre en evidence une diminution du risque de cancer du sein chez les fillettes qui etaient obeses entre l’âge de 8 ans et l’adolescence. Une autre etude a montre qu’un faible poids de naissance ou une silhouette mince avant l’âge adulte sont associees a une augmentation du risque de diabete. A partir de ces constatations, il nous a semble interessant d’evaluer la relation entre la silhouette a 20 ans et le risque d’hypertension a l’âge de 60 ans. Resultats On a observe que la prevalence de l’hypertension a l’âge de 60 etait plus elevee chez les sujets obeses a 20 ans que chez les sujets minces (45,3 % vs 36,7 % ; p Conclusion Cet outil permet une classification pertinente entre minceur et obesite. L’historique de la corpulence est un element important a considerer dans les determinants d’une pathologie, en particulier dans celle de l’hypertension arterielle.

International audience; Background and aimIt was hypothesized that the pattern of coronary occlusion (thrombus composition) might contribute to the onset of ventricular arrhythmia and sudden cardiac death (SCD) in myocardial infarction (MI).MethodsThe TIDE (Thrombus and Inflammation in sudden DEath) study included patients with angiographically-proven acute coronary occlusion as the cause of a ST elevation MI (STEMI) complicated by Sudden Cardiac Death (SCD group) or not (STEMI group). Thrombi were obtained by thrombo-aspiration before primary percutaneous coronary stenting and analyzed with a quantitative method using scanning electron microscopy. We compared the composition of the thrombi responsible for the coronary occlusion between the two groups and evaluated factors influencing its composition.ResultsWe included 121 patients and found that thrombus composition was not different between the SCD group (n = 23) and the STEMI group (n = 98) regarding content of fibrin fibers (60.3 ± 18.4% vs. 62.4 ± 18.4% respectively, p = 0.68), platelets (16.3 ± 19.2% vs. 15.616.7 ±%, p = 0.76), erythrocytes (14.6 ± 12.5% vs. 13 ± 12.1%, p = 0.73) and leukocytes (0.6 ± 0.9% vs. 0.8 ± 1.5%, p = 0.93). Thrombus composition did not differ between patients receiving upstream-use of glycoprotein IIb/IIIa platelet receptor inhibitors (GPI) and patients free of GPI. The only factor found to influence thrombus composition was the ischemic time from symptom onset to primary PCI, with a decreased content in fibrin fibers (57.8 ± 18.5% vs. 71.9 ± 10.1%, p = 0.0008) and a higher platelet content (19.2 ± 19.1% vs. 7.9 ± 5.7% p = 0.014) in early presenters (6 h of ischemic time).ConclusionComposition of intracoronary thrombi in STEMI patients does not differ between those presenting with and without SCD. Time from symptom onset to coronary reperfusion seems to be the strongest factor influencing thrombus composition in M

Background Even if a large majority of out-of-hospital cardiac arrest (OHCA) survivors appear to have a good neurological recovery with no important sequellae, whether health-related quality of life (HRQOL) is altered is less explored. Patients and methods HRQOL was evaluated by telephone interview using SF-36 questionnaire. Each OHCA case was age and gender-matched with 4 controls from the French general population. Association between current condition of the survivors with the 8 dimensions of the SF-36 questionnaire was investigated using MANCOVA. Cluster analysis was performed to identify patterns of HRQOL among CPC1 survivors. Results 255 patients discharged alive from our referral centre between 2000 and 2013 (median age of 55y [45,64], 73.7% males) were interviewed. Global physical and mental components did not differ between CPC 1 survivors and controls (47.0 vs. 47.1, p=0.88 and 46.4 vs. 46.9, p=0.45) but substantially differed between CPC2, CPC3 and the corresponding controls. Younger age, male gender, good neurological recovery and daily-life autonomy at telephone interview were significantly associated with better scores in each SF-36 dimensions. Cluster analysis individualized 4 distinct subgroups of CPC1 patients characterised by progressively increased score of SF-36. Return to work and daily-life autonomy were differently distributed across these 4 groups while pre-hospital Utstein variables were not. Conclusion HRQOL of CPC1 OHCA survivors appeared similar to that of the general population, but patients with CPC2 or 3 had altered HRQOL. Younger age, male gender, good neurological recovery and daily-life autonomy were independently associated with a better HRQOL.

International audience

Physical activity (PA) is a preventative behavior for noncommunicable disease. However, little consideration is given as to whether different domains of PA have differing associations with health outcomes. We sought to determine the association between occupational, sport, leisure, and total PA with baroreflex sensitivity (BRS), distinguishing between neural (nBRS) and mechanical (mBRS) BRS. In a cross-sectional analysis of 8649 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and heart rate) and mBRS (carotid stiffness) were measured by high-precision carotid echo-tracking. PA was self-reported using the validated Baecke questionnaire. The associations between PA and nBRS and mBRS were quantified using multivariate linear regression analysis, separately in the working and nonworking population. In working adults (n=5039), occupational PA was associated with worse nBRS (unstandardized β=−0.02; [95% CI, −0.04 to −0.003]; P =0.022) whereas sport PA was associated with better nBRS (β=0.04; [95% CI, 0.02–0.07]; P =0.003) and mBRS (β=−0.05; [95% CI, −0.09 to −0.00001]; P =0.049). Neither leisure PA nor total PA was associated with nBRS or mBRS. In nonworking adults (n=3610), sport PA and total PA were associated with better mBRS (β=−0.08; [95% CI, −0.15 to 0.02]; P =0.012 and β=−0.05; [95% CI, −0.10 to 0.009]; P =0.018) but not nBRS. These findings suggest differential associations between domains of PA and BRS and may provide insights into the mechanisms underlying the association between occupational PA and cardiovascular disease.

Background Cardiovascular diseases are rapidly growing epidemic in Sub-Saharan Africa. Unlike other regions of the world, death rates due to hypertension are greater for women than men in Africa. Scarce data were available on factors associated with gender in cardiovascular risk factors and complications in Sub-Saharan Africa. Purpose To assess gender differences in cardiovascular risk factors pattern in patients with hypertension in 12 Sub-Saharan countries. Methods We conducted a cross-sectional survey in urban clinics of twelve countries in Africa. Data were collected on demographics, treatment and standardized BP measures were made among the hypertensive patients attending the clinics. BP control was defined as BP Results The EIGHT study enrolled 2198 patients with hypertension in 12 sub-Saharan countries between January 2014 and November 2015. The proportion of women (60,2%) was higher than men and varied significantly according to countries (p Compared to men, women had a higher rate of family cardiovascular background (79% vs 70%, for women and men respectively) (p However, African women had less cardiovascular complications than men (39% vs 52.4%) (p Conclusions Our study highlighted gender differences in cardiovascular risk factors pattern in Sub-Saharan hypertensive patients. Tailoring medical (public health) programs to improve cardiovascular disease prevention that take into women characteristics may enhance their effectiveness.

Background Epidemiological transition in the developing world has resulted in a shift from infectious to non-communicable diseases as leading causes of morbidity and mortality, cardiovascular (CV) disease (CVD) is the first cause of death in Africa. However, data regarding the characteristic of patients with CVD are scarce, especially in Sub-Saharan Africa. Purpose We built an observatory recording the characteristics of all patients admitted to hospital in CV departments and hospital care components in Sub-Saharan Africa (FEBRUARY Study). Methods We conducted a transversal and longitudinal study in CV departments of 29 hospitals from 14 African countries. FEBRUARY study was designed by a multidisciplinary collaborative team of epidemiologists, pharmacists and cardiologists from Africa and France. This ongoing observatory included all patients admitted in hospitalization during the month of February every year since 2016 and will continue every year. Data including socio-demographic and clinical characteristics, causes of admission, clinical, biological, complementary examinations, treatments, length of stay and discharge diagnosis were collected by the investigating physicians. Results Overall 2680 patients were admitted to hospital in February 2016 (n=736), 2017 (n=967), and 2018 (n=987) in CV departments from 14 countries: Benin, Burkina Faso, Burundi, Cameroon, Congo, Côte d'Ivoire, Gabon, Guinea, Mali, Niger, Dem. Rep of The Congo, Senegal, Togo and Sudan (figure). Men represented 58,8%. Mean age of age was 54 years and Women 52 years. The mean length of stay was 9 days, and death rate 10,1%. The main cause of admission was cardiac failure (40,3%) followed by acute coronary syndrome (10.1%) and stroke (9,3%). Among CV risk factors, high blood pressure, sedentary behavior, diabetes, active tobacco consumption and dyslipidemia were present in 46%, 19%, 13%, 11% and 6% of patients, respectively. In a longitudinal analysis, hospital admission due coronary syndrome increased from 7% in 2016 to 10.5% in 2018 (p for trend = 0.03). Length of hospital stay and rate of hospital death remain stable. Hospitalizations by country (FEBRUARY) Conclusion The FEBRUARY observatory is an important tool to describe cardiovascular characteristics of patients in transversal analysis, but also the longitudinal evolution over the coming years in Sub-Saharan Africa.

Background Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) used a single measure of CVH and none investigated the association with incident prediabetes. This study aimed to examine whether changes in CVH are associated with incident T2D and prediabetes. Methods Within the prospective Whitehall II study, CVH was examined serially 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 (non-smoking, and ideal levels of body mass index, physical activity, diet, blood pressure, and total cholesterol, fasting glycaemia was not considered),were categorized as having low, moderate or high CVH. Results There were 6234 participants without prior cardiovascular disease and T2D (mean age 49.8±6.0 years, 70% male) including 5015 who were additionally free of prediabetes (49.6±6.0 years, 67% male) at baseline. Over a median follow-up of 24.8 (IQR 24.0 to 25.2) years, 895 and 1703 incident cases of T2D and prediabetes occurred respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4470 participants without CVD and T2D in the interval, and among 2798 participants additionally free of prediabetes. In multivariate analysis, compared to those with stable low CVH, risk of T2D was lower in those with initially high CVH (HR=0.23; 0.09, 0.56), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR=0.42; 0.33, 0.54), low-moderate/high (HR=0.50; 0.36, 0.69) and moderate-low (HR=0.63; 0.48, 0.83). Results were similar for prediabetes, but effect sizes were smaller. Conclusions Among participants without previous CVD, T2D or prediabetes, change in CVH was related to the risk of incident T2D and prediabetes.

Background/Introduction Increased pulse wave velocity (PWV), is a reliable marker of early vascular aging (EVA). However, the identification of individuals whose arteries are abnormally healthy in comparison to their age and cardiovascular (CV) risk profile might be of interest, to discover novel pathways of cardioprotection and provide preventive strategies for successful vascular aging. Purpose 1) to provide a novel calculation for vascular age and examine his determinants; 2) to test the hypothesis that individuals with the largest difference between chronological and vascular age (C-V age) show a lower rate of CV events than their counterparts, and may thus be defined as the supernormal vascular aging group (SUPERNOVA). Methods Vascular age was defined as predicted age based on classical CV risk factors and PWV. The best fitting model for vascular age was investigated in the multicenter, European, cross-sectional Reference Values for Arterial stiffness Collaboration Database (n=11406). Continuous variables were modelled as smoothing splines. Thereafter, the risk of fatal and non-fatal CV events associated with C-V age was examined in the longitudinal cohort of the Malmo Diet and Cancer Study (n=2663) using Cox proprotional hazard regression models. C-V age was examined as a continuous variable (natural splines) and as a 3 levels categorical variables based on the best grouping of the deciles of C-V age and corresponding to the EVA (8.8 years) respectively. Results In the Reference Values Cohort (age range 17–85 years, 52.4% men, 38.1% hypertensives, 3.9% diabetics, average PWV 7.8 m/s), the most significant predictor of vascular age (full model r2 0.598) was PWV. In the Malmo Diet and Cancer Study Cohort (age 61–89 years, 63.6% men, 64.0% hypertensives, 12.9% diabetics, PWV 11.5 m/s), during follow-up (6.6 years on average), 286 individuals developed a first cardiovascular event. In the Cox survival analysis, C-V age was significantly and inversely associated with CV events. Compare to normal vascular aging, participants with SUPERNOVA had lower risk for CV events [HR 0.51 (0.34–0.76)] whereas those with EVA had a higher risk [HR 2.71 (1.80–4.09)]. Instead, there was no significant association with all-cause mortality. Conclusions The use of PWV and CV risk factors may be useful to define early and supernormal vascular aging in particular, and to assess its clinical relevance towards the risk of cardiovascular disease and death.

ObjectivesTo examine the association between the Life Simple 7 cardiovascular health score at age 50 and incidence of dementia.DesignProspective cohort study.SettingCivil service departments in London (Whitehall II study; study inception 1985-88).Participants7899 participants with data on the cardiovascular health score at age 50.ExposuresThe cardiovascular health score included four behavioural (smoking, diet, physical activity, body mass index) and three biological (fasting glucose, blood cholesterol, blood pressure) metrics, coded on a three point scale (0, 1, 2). The cardiovascular health score was the sum of seven metrics (score range 0-14) and was categorised into poor (scores 0-6), intermediate (7-11), and optimal (12-14) cardiovascular health.Main outcome measureIncident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017.Results347 incident cases of dementia were recorded over a median follow-up of 24.7 years. Compared with an incidence rate of dementia of 3.2 (95% confidence interval 2.5 to 4.0) per 1000 person years among the group with poor cardiovascular health, the absolute rate differences per 1000 person years were −1.5 (95% confidence interval −2.3 to −0.7) for the group with intermediate cardiovascular health and −1.9 (−2.8 to −1.1) for the group with optimal cardiovascular health. Higher cardiovascular health score was associated with a lower risk of dementia (hazard ratio 0.89 (0.85 to 0.95) per 1 point increment in the cardiovascular health score). Similar associations with dementia were observed for the behavioural and biological subscales (hazard ratios per 1 point increment in the subscores 0.87 (0.81 to 0.93) and 0.91 (0.83 to 1.00), respectively). The association between cardiovascular health at age 50 and dementia was also seen in people who remained free of cardiovascular disease over the follow-up (hazard ratio 0.89 (0.84 to 0.95) per 1 point increment in the cardiovascular health score).ConclusionAdherence to the Life Simple 7 ideal cardiovascular health recommendations in midlife was associated with a lower risk of dementia later in life.