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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/).

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.

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.

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.

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.

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 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.

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.

Large artery stiffness is an index of vascular aging associated with cardiovascular mortality. Whereas traditional risk factors for arterial stiffness are known, the contribution of socioeconomic factors is 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. In 7803 adults, carotid stiffness was determined by high-precision carotid echo-tracking. Individual deprivation data included education, living alone, occupation, and Evaluation of the Deprivation and Inequalities of Health in Healthcare Centers score. Neighborhood deprivation was determined from commune level data (smallest administrative subdivision) 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. Analyses were conducted separately in males and females. Individual deprivation (lower education and occupation in males and living alone and higher Evaluation of the Deprivation and Inequalities of Health in Healthcare Centers in both populations) was adversely related to carotid stiffness, independently of potential confounders ( P P

BACKGROUND: Arterial stiffness may contribute to late-life depression via cerebral microvascular damage, but evidence is scarce. No longitudinal study has evaluated the association between arterial stiffness and risk of depressive symptoms. Therefore, we investigated the association between carotid artery stiffness and incident depressive symptoms in a large community-based cohort study.METHODS: This longitudinal study included 7013 participants (mean age 59.7 +/- 6.3 years; 35.8% women) free of depressive symptoms at baseline. Carotid artery stiffness (high-resolution echo tracking) was determined at baseline. Presence of depressive symptoms was determined at baseline and at 4 and 6 years of follow-up, and was defined as a score >= 7 on the validated Questionnaire of Depression, Second Version, Abridged and/or new use of antidepressant medication. Logistic regression and generalized estimating equations were used.RESULTS: In total, 6.9% (n = 484) of the participants had incident depressive symptoms. Individuals in the lowest tertile of carotid distensibility coefficient (indicating greater carotid artery stiffness) compared with those in the highest tertile had a higher risk of incident depressive symptoms (odds ratio: 1.43; 95% confidence interval: 1.10-1.87), after adjustment for age, sex, living alone, education, lifestyle, cardiovascular risk factors, and baseline Questionnaire of Depression, Second Version, Abridged scores. Results were qualitatively similar when we used carotid Young's elastic modulus as a measure of carotid stiffness instead of carotid distensibility coefficient, and when we used generalized estimating equations instead of logistic regression.CONCLUSIONS: Greater carotid stiffness is associated with a higher incidence of depressive symptoms. This supports the hypothesis that carotid stiffness may contribute to the development of late-life depression.

Background: Mortality of ST-segment–elevation myocardial infarction (STEMI) decreased drastically, mainly through reduction in inhospital mortality. Prehospital sudden cardiac arrest (SCA) became one of the most feared complications. We assessed the incidence, outcome, and prognosis’ predictors of prehospital SCA occurring after emergency medical services (EMS) arrival. Methods and Results: Data were taken between 2006 and 2014 from the e-MUST study (Evaluation en Médecine d’Urgence des Strategies Thérapeutiques des infarctus du myocarde) that enrolls all STEMI managed by EMS in the Greater Paris Area, including those dead before hospital admission. Among 13 253 STEMI patients analyzed, 749 (5.6%) presented EMS-witnessed prehospital SCA. Younger age, absence of cardiovascular risk factors, symptoms of heart failure, extensive STEMI, and short pain onset-to-call and call-to-EMS arrival delays were independently associated with increased SCA risk. Mortality rate at hospital discharge was 4.0% in the nonSCA group versus 37.7% in the SCA group ( P P Conclusions: More than 1 of 20 STEMI presents prehospital SCA after EMS arrival. SCA occurrence is associated with a 10-fold higher mortality at hospital discharge compared with STEMI without SCA. PCI is the strongest survival predictor, leading to a twice-lower mortality. This highlights the persistently dramatic impact of SCA on STEMI and the major importance of PCI in this setting.

AimsAveraged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.Methods and resultsAn individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration ( n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.ConclusionAveraged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

International audience; Background - Our knowledge of hypertrophic cardiomyopathy (HCM) mainly originates from quarternary centres. The objective is to assess the current management of HCM patients in a large multicentre French register according to the level of expertise. Methods and results - A total of 1431 HCM patients were recruited across 26 (11 expert and 15 non-expert) centres in REMY, a prospective hospital-based register of adult HCM patients. A sarcomeric origin was suspected in 1284 (89.7%) patients [261 (20.3%) with a reported gene mutation, 242 (18.8%) genotype-negative], while 107 (7.5%) had a diagnosis of non-sarcomeric HCM. Patients managed in non-expert centres were older (P

Diabetes mellitus (both type 1 and 2) affects an estimated 425 million people worldwide and if current trends continue, ≈693 million people (10% of the population) will have diabetes mellitus by 2045.1 Patients with type 2 diabetes mellitus (T2D) are at an increased risk of damage to target organs. The causes for these adverse changes are unknown, however, high blood pressure (BP) or hypertension, is likely to play a contributory role. Indeed, T2D and hypertension commonly coexist and may act synergistically to promote clinical events.

Objective: Aim of the study is to investigate the impact of COVID-19 lockdown on trajectories of vascular stiffness among a large population of users of a connected bathroom scale, allowing reliable measurements of pulse wave velocity (PWV) Design and method: Pulse wave velocity (PWV) recordings obtained by Withings Heart Health & Body Composition Wi-Fi Smart Scale users before and during lockdown were analyzed. We compared two demonstrative countries: France who applied strict lockdown rules (n=26,196) and Germany, who applied partial lockdown (n=26,847). Subgroup analysis was conducted in users of activity trackers and home blood pressure monitors (HBPM). Linear growth curve modeling and clustering trajectories analyses were performed Results: During lockdown a signi ficant reduction in PWV, weight, BP and physical activity was observed in the overall population. PWV reduction was signi fi-cantly greater in France than in Germany, corresponding to an improvement of 5.2 months in vascular age In the French population three clusters of PWV trajectories were identi fied: decreasing (21.1%), stable (60.6%) and increasing PWV (18.2%). Decreasing and increasing PWV clusters had both higher PWV and vascular age at baseline compared to stable PWV cluster. Only decreasing PWV cluster showed a signi ficant weight reduction (-400 g), whereas living alone was associated with increasing PWV Conclusions: Total lockdown induced a reduction in vascular stiffness in a signi ficant proportion of French smart scale users. Impact on long term behaviors and cardiovascular health remains to be established.

Background: In-hospital mortality of ST-segment–elevation myocardial infarction (STEMI) has decreased drastically. In contrast, prehospital mortality from sudden cardiac arrest (SCA) remains high and difficult to reduce. Identification of the patients with STEMI at higher risk for prehospital SCA could facilitate rapid triage and intervention in the field. Methods: Using a prospective, population-based study evaluating all patients with STEMI managed by emergency medical services in the greater Paris area (11.7 million inhabitants) between 2006 and 2010, we identified characteristics associated with an increased risk of prehospital SCA and used these variables to build an SCA prediction score, which we validated internally and externally. Results: In the overall STEMI population (n=8112; median age, 60 years; 78% male), SCA occurred in 452 patients (5.6%). In multivariate analysis, younger age, absence of obesity, absence of diabetes mellitus, shortness of breath, and a short delay between pain onset and call to emergency medical services were the main predictors of SCA. A score built from these variables predicted SCA, with the risk increasing 2-fold in patients with a score between 10 and 19, 4-fold in those with a score between 20 and 29, and >18-fold in patients with a score ≥30 compared with those with scores P for trend Conclusions: At the early phase of STEMI, the risk of prehospital SCA can be determined through a simple score of 5 routinely assessed predictors. This score might help optimize the dispatching and management of patients with STEMI by emergency medical services.

Background Obesity prevalence has dramatically increased over recent years and is associated with cardiovascular diseases, but data are lacking on its prognostic impact in out-of-hospital cardiac arrest (OHCA) patients. Methods Data of all consecutive OHCA patients admitted in two cardiac arrest centers from Paris and suburbs between 2005 and 2012 were prospectively collected. Patients treated by therapeutic hypothermia (TH) were included in the analysis. Logistic and Cox regression analyses were used to quantify the association between body mass index (BMI) at hospital admission and day-30 and 1-year mortality respectively. Results 818 patients were included in the study (median age 60.9 [50.8–72.7] year, 70.2% male). Obese patients (BMI>30kgm −2 ) were older, more frequently male and evidenced more frequently cardiovascular risk factors than normally (18.5 −2 ) or overweight patients (25 −2 ). Post-resuscitation shock and therapeutic hypothermia failure were more frequent in obese patients. Overall mortality at day-30 and one-year was 63.8 and 67.2%, respectively. After multivariate adjustment, BMI>30kgm −2 was independently associated with day-30 mortality (Odds ratio [OR] in comparison with normally weight patients 2.45; 95% confidence interval [95%CI: 1.32–4.56; p Conclusion In the present study, obesity was independently associated with day-30 mortality in successfully resuscitated ICU TH OHCA patients. Further studies are needed to understand the mechanisms that underpin this finding.

Objective— We hypothesized that subclinical markers of vascular structure and function, which are independent predictors of cardiovascular disease, would be less frequent in subjects with ideal than poor cardiovascular health (CVH) as defined by the American Heart Association (AHA). Approach and Results— Carotid parameters were measured using high-precision echotracking device in 9155 nonreferred participants attending a health checkup in a large health center in Paris (France) between 2008 and 2012. According to the AHA, participants with 0 to 2, 3 to 4, and 5 to 7 metrics (smoking, physical activity, body mass index, diet, blood glucose and total cholesterol, blood pressure) at the ideal level were categorized as having poor, intermediate, and ideal CVH. Carotid parameters were dichotomized according to their median value, and multivariable logistic regression analysis was performed. Mean age was 59.5 (SD 6.3) years; 39% were females, and ideal CVH was present in 10.11% of the study participants. After adjustment for age, sex, education, and living alone and compared with a poor CVH, an ideal CVH was associated with lower common carotid artery intima–media thickness (odds ratio=1.64; 95% confidence interval 1.40, 1.93), absence of carotid plaques (odds ratio=2.14; 95% confidence interval 1.60, 2.87), lower Young’s elastic modulus (odds ratio=2.43; 95% confidence interval 2.07, 2.84), and higher carotid distensibility coefficient (odds ratio=2.90; 95% confidence interval 2.47, 3.41). Conclusions— In community subjects aged 50 to 75 years, ideal CVH was associated with substantially less arterial stiffness and thickness. These associations might contribute to the lower risk of cardiovascular diseases in subjects with ideal CVH.

Arterial stiffness is increased with chronic inflammatory disorders. The reduction of inflammation by immunomodulatory therapy is associated with a restoration of arterial function. The aims of the study were to perform a meta-analysis to determine whether arterial stiffness is increased in patients with inflammatory bowel disease (IBD) and a meta-regression analysis to correlate arterial stiffness with anti-TNFα therapy.Systematic review registration number: CRD42015017364. A systematic literature search for arterial stiffness in IBD was performed using PubMed, Scopus, and Google Scholar databases (last accessed on 23 September 2015). The search terms were 'arterial stiffness,' 'vascular stiffness,' or 'pulse wave velocity' in combination with 'inflammatory bowel disease,' 'inflammatory bowel diseases,' 'Crohn's disease,' or 'ulcerative colitis.' Inclusion criteria included peer-reviewed publications reporting original data, a minimum of 20 study participants tested, and pulse wave velocity (PWV) measured via validated devices. Publications with titles or abstracts appearing to meet the inclusion criteria were selected and reviewed by two authors according to PRISMA 2009 guidelines.Carotid-femoral PWV (cf-PWV) was measured in nine cross-sectional studies (234 patients with Crohn's disease, 342 with ulcerative colitis, and 435 control study participants). Compared with control patients, cf-PWV was significantly increased in patients with Crohn's disease [mean difference 1.34 z-score; 95% confidence interval (CI) 0.71-1.97 z-score; P 0.0001] and ulcerative colitis (mean difference 1.08 z-score; 95% CI 0.55-1.61 z-score; P 0.0001). In a meta-regression analysis, cf-PWV was reduced in IBD patients treated with anti-TNFα therapy (β -2.6 m/s; 95% CI -4.9 to -0.2 m/s; P = 0.03).cf-PWV is increased in both ulcerative colitis and Crohn's disease patients.

Background/Objectives: The baroreflex is a crucial mechanism acutely modulating vascular tone and heart rate response to maintain blood pressure (BP) in an optimal range. A decrease in baroreflex sensitivity (BRS) is associated with ageing, and pathological conditions such as hypertension and diabetes. Antihypertensive agents are generally known to have beneficial effect on the BRS, however it is still uncertain if the effect is mediated through a more compliant arterial wall or a sympathoinhibitory action. Methods: In the Paris Prospective Study III [1], spontaneous baroreflex, carotid stiffness and pharmacological drugs intake were available in 7967 adults (aged 55–75 years). The neural component of the baroreflex sensitivity (nBRS) was obtained with a cross-spectral analysis of variations in carotid distention rate and R-R intervals. Pharmacological classes were analysed according to the Anatomical Therapeutic Chemical (ATC) classification. Individuals with a BP lowering medication (BP-treated) were paired to non-BP treated individuals with a similar cardiovascular risk (controls) using a propensity score matching procedure (n = 1182 pairs). Results: Amongst pharmacological classes of BP lowering agents, only agents acting on the renin-angiotensin system (ACEi-ARB) were associated with nBRS (β = –0.08, p = 0.045). Compared to their matched controls, ACEi-ARB users had lower nBRS (2.79 ± 0.66 vs. 2.90 ± 0.62, p = 0.03). In multivariate analysis, ACEi-ARB remained significant (stdβ = –0.09, p = 0.025) after adjustment for carotid stiffness (stdβ = 0.25, p < 0.001) and systolic pressure (stdβ = –0.20, p < 0.001). Conclusion: In this epidemiological study, ACEi-ARB were negatively associated with nBRS. This effect is independent of BP and stiffness, which may suggest an inhibition of sympathetic activity by ACEi-ARB.