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

Major efforts have been made to reduce the burden of sports-related sudden cardiac arrest (SrSCA). The extent to which the incidence, management, and outcomes changed over time has not been investigated.The purpose of this study was to assess temporal trends in SrSCA incidence, management, and survival.Using data from the French National Institute of Health and Medical Research, we evaluated the evolution of incidence, prehospital management, and survival at hospital discharge of SrSCA among subjects aged 18 to 75 years, over 6 successive 2-year periods between 2005 and 2018.Among the 377 SrSCA, 20 occurred in young competitive athletes (5.3%), whereas 94.7% occurred in middle-aged recreational sports participants. Comparing the last 2-year to the first 2-year period, SrSCA incidence remained stable (6.24 vs 7.00 per million inhabitants/y; P = 0.51), with no significant differences in patients' mean age (46.6 ± 13.8 years vs 51.0 ± 16.4 years; P = 0.42), sex (men 94.7% vs 95.2%; P = 0.99), and history of heart disease (12.5% vs 15.9%; P = 0.85). However, frequency of bystander cardiopulmonary resuscitation and public automated external defibrillator use increased significantly (34.9% vs 94.7%; P 0.001 and 1.6% vs 28.8%; P = 0.006, respectively). Survival to hospital discharge improved steadily, reaching 66.7% in the last study period compared with 23.8% in the first (P 0.001).Incidence of SrSCA remained relatively stable over time, suggesting a need for improvement in screening strategies. However, major improvements in on-field resuscitation led to a 3-fold increase in survival, underlining the value of public education in basic life support that should serve as an example for SCA in general.

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

Extracellular vesicles (EV) are increasingly recognized as a therapeutic option in heart failure. They are usually administered by direct intramyocardial injections with the caveat of a rapid wash-out from the myocardium which might weaken their therapeutic efficacy. To improve their delivery in the failing myocardium, we designed a system consisting of loading EV into a clinical-grade hyaluronic acid (HA) biomaterial. EV were isolated from umbilical cord-derived mesenchymal stromal cells. The suitability of HA as a delivery platform was then assessed in vitro. Rheology studies demonstrated the viscoelastic and shear thinning behaviors of the selected HA allowing its easy injection. Moreover, the release of HA-embedded EV was sustained over more than 10 days, and EV bioactivity was not altered by the biomaterial. In a rat model of myocardial ischemia reperfusion, we showed that HA-embedded EV preserved cardiac function (echocardiography), improved angiogenesis and decreased both apoptosis and fibrosis (histology and transcriptomics) when compared to intramyocardial administration of EV alone. These data thus strengthen the concept that inclusion of EV into a clinically useable biomaterial might optimize their beneficial effects on post-ischemic cardiac repair.

Background: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. Methods: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. Results: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5–11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P =0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19–10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 ( P =0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96–40.95]). Conclusions: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03837574.

International audience; Background: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far.Objectives: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs).Methods: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee.Results: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication.Conclusions: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574)

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

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

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.

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.

Background: Extracellular vesicles (EV) mediate the therapeutic effects of stem cells but it is unclear whether this involves cardiac regeneration mediated by endogenous cardiomyocyte proliferation. Methods: Bi-transgenic MerCreMer/ZEG (n = 15/group) and Mosaic Analysis With Double Markers (MADM; n = 6/group) mouse models underwent permanent coronary artery ligation and received, 3 weeks later, 10 billion EV (from human iPS-derived cardiovascular progenitor cells [CPC]), or saline, injected percutaneously under echo guidance in the peri-infarcted myocardium. Endogenous cardiomyocyte proliferation was tracked by EdU labeling and biphoton microscopy. Other end points, including cardiac function (echocardiography and MRI), histology and transcriptomics were blindly assessed 4-6 weeks after injections. Results: There was no proliferation of cardiomyocytes in either transgenic mouse strains. Nevertheless, EV improved cardiac function in both models. In MerCreMer/ZEG mice, LVEF increased by 18.3 ± 0.2% between baseline and the end-study time point in EV-treated hearts which contrasted with a decrease by 2.3 ± 0.2% in the PBS group; MADM mice featured a similar pattern as intra-myocardial administration of EV improved LVEF by 13.3 ± 0.16% from baseline whereas it decreased by 14.4 ± 0.16% in the control PBS-injected group. This functional improvement was confirmed by MRI and associated with a reduction in infarct size, the decreased expression of several pro-fibrotic genes and an overexpression of the anti-fibrotic miRNA 133-a1 compared to controls. Experiments with an anti-miR133-a demonstrated that the cardio-reparative effects of EV were partly abrogated. Conclusions: EV-CPC do not trigger cardiomyocyte proliferation but still improve cardiac function by other mechanisms which may include the regulation of fibrosis.

International audience; Objectives: This study aimed to assess the impact of pulmonary valve replacement (PVR) on ventricular arrhythmias burden in a population of tetralogy of Fallot (TOF) patients with continuous cardiac monitoring by implantable cardioverter-defibrillators (ICDs).Background: Sudden cardiac death is a major cause of death in TOF, and right ventricular overload is commonly considered to be a potential trigger for ventricular arrhythmias.Methods: Data were analyzed from a nationwide French ongoing study (DAI-T4F) including all TOF patients with an ICD since 2000. Survival data with recurrent events were used to compare the burden of appropriate ICD therapies before and after PVR in patients who underwent PVR over the study period.Results: A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% male) were included from 40 centers. Over a median follow-up period of 6.8 (interquartile range: 2.5 to 11.4) years, 26 patients (15.8%) underwent PVR. Among those patients, 18 (69.2%) experienced at least 1 appropriate ICD therapy. When considering all ICD therapies delivered before (n = 62) and after (n = 16) PVR, the burden of appropriate ICD therapies was significantly lower after PVR (HR: 0.21; 95% confidence interval [CI]: 0.08 to 0.56; p = 0.002). Respective appropriate ICD therapies rates per 100 person-years were 44.0 (95% CI: 35.7 to 52.5) before and 13.2 (95% CI: 7.7 to 20.5) after PVR (p < 0.001). In the overall cohort, PVR before ICD implantation was also independently associated with a lower risk of appropriate ICD therapy in primary prevention patients (HR: 0.29 [95% CI: 0.10 to 0.89]; p = 0.031).Conclusions: In this cohort of high-risk TOF patients implanted with an ICD, the burden of appropriate ICD therapies was significantly reduced after PVR. While optimal indications and timing for PVR are debated, these findings suggest the importance of considering ventricular arrhythmias in the overall decision-making process. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

Introduction Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. Objective We aimed to describe long-term follow-up of TOF patients implanted with ICD through a nationwide French registry. Methods Nationwide French Registry including all TOF patients with an ICD initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event endpoint was the time from ICD implantation to first appropriate ICD therapy. Clinical events were centrally adjudicated by a blinded committee. Results A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (IQR) follow-up of 6.8 (2.5–11.4) years, 78 (47.3%) patients received at least one appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively, P = 0.03). Overall, 71 (43.0%) patients presented with at least one ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) primary prevention patients, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with respectively no, one, two, or ≥ three guideline-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (HR 3.47, 95% CI 1.19–10.11), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P = 0.006) ( Fig. 1 ). Conclusions Patients with TOF and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification.

ObjectivesThe incidence of cardiovascular diseases is increasing and there is a growing need to provide access to quality cardio drugs in Africa. In the SEVEN study, we analysed 1530 cardiovascular drug samples randomly collected from 10 African countries. By that time, of the seven drugs products analysed, only those containing amlodipine and captopril had very low assay values with active substance contents that could be less than 75% of those expected. In this article we investigate complementary aspects of the amlodipine and captopril samples so to explain the previously observed low assays for these two drugs.DesignPost hoc analysis of the captopril and amlodipine drugs samples and their packages collected in the context of the SEVEN study.Setting10 countries were concerned: Benin, Burkina Faso, Congo, Democratic Republic of the Congo, Guinea, Côte d’Ivoire, Mauritania, Niger, Senegal and Togo.ParticipantsLocal scientists and hospital practitioners collected the drug samples in the 10 African countries.Outcome measuresThe drug amount and the relative amounts of drug impurities, as well as the main compounds of the drugs packaging, were analysed.ResultsIdentification of the blister packaging of the samples led to separate both amlodipine and captopril drug samples in two groups. Mann Whitney’s bilateral test showed a significant difference (pConclusionBased on these results, particular attention should be paid to the materials and types of packaging used in order to minimise the lack of control over the exposures and drug circuits present in these different countries.

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.

International audience

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.

[EN] OBJECTIVES: Prevention of postischaemic ventricular dilatation progressing towards pathological remodelling is necessary to decrease ventricular wall deterioration. Myocardial tissue engineering may play a therapeutic role due to its capacity to replace the extracellular matrix, thereby creating niches for cell homing. In this experimental animal study, a biomimetic cardiopatch was created with elastomeric scaffolds and nanotechnologies. METHODS: In an experimental animal study in 18 sheep, a cardiopatch was created with adipose tissue-derived progenitor cells seeded into an engineered bioimplant consisting of 3-dimensional bioabsorbable polycaprolactone scaffolds filled with a peptide hydrogel (PuraMatrix (TM)). This patch was then transplanted to cover infarcted myocardium. Non-absorbable poly(ethyl) acrylate polymer scaffolds were used as controls. RESULTS: Fifteen sheep were followed with ultrasound scans at 6 months, including echocardiography scans, tissue Doppler and spectral flow analysis and speckle-tracking imaging, which showed a reduction in longitudinal left ventricular deformation in the cardiopatch-treated group. Magnetic resonance imaging (late gadolinium enhancement) showed reduction of infarct size relative to left ventricular mass in the cardiopatch group versus the controls. Histopathological analysis at 6 months showed that the cardiopatch was fully anchored and integrated to the infarct area with minimal fibrosis interface, thereby promoting angiogenesis and migration of adipose tissue-derived progenitor cells to surrounding tissues. CONCLUSIONS: This study shows the feasibility and effectiveness of a cardiopatch grafted onto myocardial infarction scars in an experimental animal model. This treatment decreased fibrosis, limited infarct scar expansion and reduced postischaemic ventricular deformity. A capillary network developed between our scaffold and the heart. The elastomeric cardiopatch seems to have a positive impact on ventricular remodelling and performance in patients with heart failure., The RECATABI Project (Regeneration of Cardiac Tissue Assisted by Bioactive Implants) was financially supported by the 7th Framework Programme (FP7) of the European Commission. Project ID: 229239. Funded under FP7-NMP and the European Regional Development Fund (FEDER Spain).

International audience; Background: According to guidelines, implantable cardioverter defibrillator (ICD) candidates must have a "reasonable expectation of survival with a good functional status >1 year". Identifying risk for early mortality in ICD candidates could be challenging. We aimed to identify factors associated with a =1-year survival among patients implanted with ICDs.Methods: The DAI-PP program was a multicenter, observational French study that included all patients who received a primary prevention ICD in the 2002-2012 period. Characteristics of patients who survived = III), and atrial fibrillation were significantly associatedwith

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.

Sudden cardiac death (SCD) is a devastating event for families, who have to deal with both the pain of the loss and the uncertainty regarding risk for other family members ([1][1],[2][2]). The need for psychological support and cascade screening of first-degree relatives to assess their risk have

Aims We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P

Background Public Access Defibrillation (PAD) programs have emerged since mid-1990s with the aim of improving survival from Out-of-Hospital Cardiac Arrest (OHCA). The extent to which their implementation in the community differs among different areas has not been evaluated. Methods We carried out a 5-year prospective national evaluation of PAD programs in 51 French districts (29.3 million inhabitants), through the cumulative density of Automated External Defibrillator (AEDs) and the proportion of persons educated in Basic Life Support (BLS). Results Major regional discrepancies were observed with AED density from 5 to 3399 per 100,000 inhabitants per 1000 km 2 , and BLS-educated inhabitants varying from 6955 to 36,636 per 100,000 inhabitants. Only 18 districts (35.3%) achieved both AED density and educational rate above median (>13,988 and >22, respectively). Extrapolating the data from the French national registry on sports OHCA, mean survival rate was two-folds higher with AED density above the median (7.9% vs. 17.8%, P 0.001) and four-fold higher with BLS-education above the median (5.0% vs. 20.9%, P 0.001). In the group with both AED density and BLS-education level above the median, the survival rate reached up to 22.5%. Only the rate of population BLS education remained independently associated with survival (OR 1.64, 95% Confidence Interval 1.17–2.31; P = 0.0045). Conclusions Major heterogeneities in PAD programs exist, with significant room for better coordination in implementation. Population education in BLS provides an important benefit, regardless of the density of AEDs deployed, which should be taken into account in planning public health policies for improving OHCA survival.

Temporal Trends Over a Decade of Defibrillator TherapyBackground Technology and clinical practice surrounding the use of the primary prevention implantable cardioverter defibrillator (ICD) are in a state of constant evolution. The purpose of the study was to test the hypothesis of significant temporal trends in characteristics and outcomes over a decade of ICD therapy. Methods Between 2002 and 2012, 5,539 consecutive patients (age 62.5 ± 11 years, 84.9% male), with ischemic or nonischemic cardiomyopathy, implanted with a primary prevention ICD from 12 centers in France were included. Information on characteristics and outcomes (including causes of death) were evaluated over a median follow-up of 994 days (466-1,667). Results In addition to a shift in the type of devices implanted with a significant increase in cardiac resynchronization therapy-defibrillator (CRT-D) over time (43.6 to 60.4%, P = 0.0001), an increase in mean age (from 61.5 ± 11.6 to 63.2 ± 10.9 years, P = 0.0016), proportion of nonischemic cardiomyopathy (31.0 to 44.7%, P 30 days after implant) complications significantly increased (4.6 to 7.6%, P = 0.003). Conclusion Our findings demonstrate significant changes in patterns of use and outcomes in primary prevention ICD over the last decade with reductions in mortality and appropriate therapies, counterbalanced by an increase in complications.

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.

Introduction Extracellular Vesicles (EV) seem to mediate the benefits of cell therapy for ischemic heart failure. Although their mechanism of action remains poorly understood, one hypothesis is that they might trigger the generation of new cardiomyocytes. The doubly transgenic fate-mapping MerCreMer/ZEG mice model was thus used to distinguish whether these putative new cardiomyocytes originated from the division of preexisting ones (GFP+, Troponin T [TnT+], EdU+) or differentiated from endogenous progenitors, in which case they would stain positive for TnT+/EdU+ but negative for GFP. Methods Myocardial infarction was induced in 35 MerCreMer/ZEG mice by permanent occlusion of the left anterior descending coronary artery. Three weeks later, the surviving mice (n=18) with a left ventricular ejection fraction (LVEF) ≤45% received transcutaneous echo-guided injections in the peri-infarct myocardium of either EV (from 1.4 million human iPS-derived cardiovascular progenitor cells; 10 billion particles, n=9) or PBS (n=9); osmotic pumps were implanted to deliver EdU for 7 days in order to track the proliferation of new and native cardiomyocytes. Four-6 weeks after treatment all mice were evaluated by echocardiography (n=9 per group) and MRI (7 in each group), and then sacrificed for histological assessment, blindly. Results Based on echocardiography (MRI data pending), EV improved LVEF by 16% relative to baseline while a decrease of 4% was observed in the PBS group (p=0.46). The number of new cardiomyocytes (TnT+/EdU+/GFP+) did not significantly differ between the EV-treated hearts and the controls, and averaged 0.54% of the total heart cell content in infarct, peri-infarct and remote areas. However, EV treatment better preserved preexisting GFP+/WGA+/TnT+ cardiomyocytes in the peri-infarct area as their number was greater by 5.15% compared to PBS (32 sections analyzed for each mouse). Compared to the PBS control group, EV delivery was also associated with a 2.5% decrease in fibrosis, a reduction of infarct size by 14.9%, and an increase in angiogenesis in the peri-infarct area (with a between-group absolute difference of 71 capillaries, on the basis of isolectin staining). Conclusions EV secreted by iPS-derived cardiovascular progenitors improve the function of chronically infarcted hearts. Preservation of the existing cardiomyocyte pool and limitation of adverse remodeling and scarred tissue, likely favored by increased neoangiogenesis, are the main mechanisms mediated by the EV, while fate mapping allowed to exclude the generation of new cardiomyocytes.

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 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.

This review summarizes the main findings of the French multicentre DAI-PP pilot programme, and discusses the related clinical and research perspectives. This project included retrospectively (2002–2012 period) more than 5000 subjects with structural heart disease who received an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death, and were followed for a mean period of 3 years. The pilot phase of the DAI-PP programme has provided valuable information on several practical and clinically relevant aspects of primary prevention ICD implantation in the real-world population, which are summarized in this review. This pilot has led to a prospective evaluation that started in May 2018, assessing ICD therapy in primary and secondary prevention in patients with structural and electrical heart diseases, with remote monitoring follow-up using a dedicated platform. This should further enhance our understanding of sudden cardiac death, to eventually optimize the field of preventative actions. © 2019 Elsevier Masson SAS; Cet article résume les principaux résultats de la phase pilote du programme DAI-PP et discute ses perspectives scientifiques. Ce projet a inclus plus de 5000 sujets (pendant la période 2002–2012) ayant une cardiopathie et implantés d’un défibrillateur automatique implantable (DAI) en prévention primaire de la mort subite avec un suivi moyen de 3 ans. Cette évaluation pilote du programme de recherche DAI-PP, mené dans la vraie vie, a permis d'identifier des messages importants concernant la prévention primaire de la mort subite de patients porteurs de cardiomyopathies dilatées ou cardiopathies ischémiques, résumés dans cet article. Cette phase préliminaire a également permis l'initiation d'une évaluation prospective, débutée en mai 2018, avec pour ambition d'évaluer la prévention primaire et secondaire quelque soit le phénotype sous jacent (structurel ou électrique), en utilisant une nouvelle plateforme de télésurveillance. DAI-PP devrait permettre de mieux comprendre différents aspects de la mort subite cardiaque, pour au final en améliorer la prévention.

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

Aims Current guidelines do not propose any age cut-off for the primary prevention implantable cardioverter-defibrillator (ICD). However, the risk/benefit balance in the very elderly population has not been well studied. Methods and results In a multicentre French study assessing patients implanted with an ICD for primary prevention, outcomes among patients aged ≥80 years were compared with Conclusion Primary prevention ICD recipients ≥80 years in the real world had relatively low associated comorbidity. Rates of appropriate therapies and device-related complications were similar, compared with younger subjects. Nevertheless, the inherent limitations in interpreting observational data on this particular competing risk situation call for randomized controlled trials to provide definitive answers. Meanwhile, a careful multidisciplinary evaluation is needed to guide patient selection for ICD implantation in the elderly population.

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.

Background Cell-based therapies are being explored as a therapeutic option for patients with chronic heart failure following myocardial infarction. Extracellular vesicles (EV), including exosomes and microparticles, secreted by transplanted cells may orchestrate their paracrine therapeutic effects. We assessed whether post-infarction administration of EV released by human embryonic stem cell–derived cardiovascular progenitors (hESC-Pg) can provide equivalent benefits to administered hESC-Pg and whether hESC-Pg and EV treatments activate similar endogenous pathways. Methods Mice underwent surgical occlusion of their left coronary arteries. After 2–3 weeks, 95 mice included in the study were treated with hESC-Pg, EV, or Minimal Essential Medium Alpha Medium (alpha-MEM; vehicle control) delivered by percutaneous injections under echocardiographic guidance into the peri-infarct myocardium. functional and histologic end-points were blindly assessed 6 weeks later, and hearts were processed for gene profiling. Genes differentially expressed between control hearts and hESC-Pg–treated and EV-treated hearts were clustered into functionally relevant pathways. Results At 6 weeks after hESC-Pg administration, treated mice had significantly reduced left ventricular end-systolic (−4.20 ± 0.96 µl or −7.5%, p = 0.0007) and end-diastolic (−4.48 ± 1.47 µl or −4.4%, p = 0.009) volumes compared with baseline values despite the absence of any transplanted hESC-Pg or human embryonic stem cell–derived cardiomyocytes in the treated mouse hearts. Equal benefits were seen with the injection of hESC-Pg–derived EV, whereas animals injected with alpha-MEM (vehicle control) did not improve significantly. Histologic examination suggested a slight reduction in infarct size in hESC-Pg–treated animals and EV-treated animals compared with alpha-MEM–treated control animals. In the hESC-Pg–treated and EV-treated groups, heart gene profiling identified 927 genes that were similarly upregulated compared with the control group. Among the 49 enriched pathways associated with these up-regulated genes that could be related to cardiac function or regeneration, 78% were predicted to improve cardiac function through increased cell survival and/or proliferation or DNA repair as well as pathways related to decreased fibrosis and heart failure. Conclusions In this post-infarct heart failure model, either hESC-Pg or their secreted EV enhance recovery of cardiac function and similarly affect cardiac gene expression patterns that could be related to this recovery. Although the mechanisms by which EV improve cardiac function remain to be determined, these results support the idea that a paracrine mechanism is sufficient to effect functional recovery in cell-based therapies for post-infarction–related chronic heart failure.

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.

Objective: To assess the incidence of cardiovascular diseases (CVD) and type-2-diabetes in patients with psychiatric disorders. Methods: A population-based study was conducted using the Swedish national health registries. Patients were identified from the Electronic Medical Records (EMR) in 20 primary care centers and were categorized in four diagnosis cohorts according to their first psychiatric diagnosis: bipolar disorder, schizophrenia, major depressive disorder, or other mood disorder. A control cohort of patients with no psychiatric disorders followed in the same primary care centers was also identified. Incident CVD and type-2-diabetes were defined as the presence of a diagnosis of CVD or diabetes during the follow-up period in patients without prior event. Results: The age and sex standardized incidence rate of CVD was 13.5 per 1000 patient-year in the patients with any psychiatric disorder versus 6.3 per 1000 patient-year in the controls. A similar trend was observed for incident diabetes (5.7 versus 3.4 per 1000 patient-year, respectively). The bipolar disorder and the schizophrenia cohorts showed the highest standardized incidence rates. Conclusion: Incidence of CVD and to a lesser extent type-2-diabetes was particularly high in patients with psychiatric disorders. This carries strong clinical implications for the prevention of CVD and type-2-diabetes in these patients.

The frequency, characteristics and outcomes of primary prevention implantable cardioverter defibrillator (ICD) recipients who eventually undergo heart transplantation (HT) during follow-up have not been well described.In a cohort of patients with heart failure implanted with an ICD for primary prevention of sudden cardiac death, to identify those at high risk of subsequent HT and evaluate ICD usefulness.Between 2002 and 2012, 5539 patients received a primary prevention ICD across 12 centers, and were enrolled in the DAI-PP programme, including 5427 with full HT information available.During a median follow-up of 1024 days (interquartile range 484-1702 days), 176 (3.2%) patients underwent HT. Median duration between ICD implantation and HT was 484 days (IQR 169-1117 days). Among those aged≤65 years (theoretical age limit for HT registration in France), the overall incidence per 1000 person-years was 18.03 (95% confidence interval [CI]: 15.32-20.74). Left ventricular ejection fraction25% (hazard ratio [HR]: 3.43, 95% CI: 2.34-5.04; P0.0001), younger age (HR: 0.95, 95% CI: 0.93-0.96; P0.0001), New York Heart Association (NYHA) class III-IV (HR: 2.67, 95% CI: 1.79-4.00; P0.0001) and no cardiac resynchronization therapy (HR: 2.09, 95% CI: 1.39-3.14; P=0.0004) were independently associated with HT. Patients with these three characteristics (excluding age) had a 1-year HT rate of 15.2%. Incidence of appropriate ICD therapies was 92.7 per 1000 person-years for patients who underwent HT versus 76.1 for those who did not (P=0.64).The overall incidence of HT in this primary prevention population was relatively high, especially among young patients with a very low ejection fraction, an advanced NYHA class and were unsuitable for cardiac resynchronization therapy (up to 15% annually). Patients awaiting HT experienced a significant rate of appropriate ICD therapies, reinforcing the importance of specific cardiac rhythm management in these patients.

Background: Physical activity (PA) is beneficial for baroreflex sensitivity (BRS), but it is unclear whether the type of PA has similar effects on the neural (nBRS) or vascular (carotid stiffness) components of BRS. We sought to determine this in healthy adults from a community- based study via assessment of occupational (OPA), sport (SPA), leisure (LPA) and total PA (TPA). Methods: In 8649 adults aged 50 to 75 years, resting nBRS (estimated by low frequency gain, from carotid distension rate and heart rate) and carotid stiffness were measured by high-precision carotid echotracking. PA was self-reported using the Baecke questionnaire, which distinguishes OPA, SPA, LPA and TPA. The associations between PA and nBRS and carotid stiffness were quantified using multivariate linear regression analysis. Analyses were conducted separately in the working and non- working population. Results: In working adults (n = 5039), OPA was associated with lower nBRS function (p = 0.026) and borderline higher carotid stiffness (p = 0.08). When stratified by education, this association remained only in those with less than tertiary education. SPA was associated with higher nBRS (p = 0.0005) and borderline lower carotid stiffness (p = 0.052). Neither LPA nor TPA was associated with nBRS or carotid stiffness. In non-working adults (n = 3610), SPA and TPA were both associated with lower carotid stiffness (p = 0.012 and p = 0.020), but not nBRS. LPA was not associated with either parameter. Conclusion: Occupation-related PA is associated with lower nBRS function and higher carotid stiffness, especially in those with lower education. Higher amounts of sport-related PA are associated with higher nBRS and lower carotid stiffness.

IMPORTANCE There is consistent evidence of the association between ideal cardiovascular health and lower incident cardiovascular disease (CVD); however, most studies used a single measure of cardiovascular health.OBJECTIVE To examine how cardiovascular health changes over time and whether these changes are associated with incident CVD.DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study in a UK general community (Whitehall II), with examinations of cardiovascular health from 1985/1988 (baseline) and every 5 years thereafter until 2015/2016 and follow-up for incident CVD until March 2017.EXPOSURES Using the 7 metrics of the American Heart Association (nonsmoking; and ideal levels of body mass index, physical activity, diet, blood pressure, fasting blood glucose, and total cholesterol), participants with 0 to 2, 3 to 4, and 5 to 7 ideal metrics were categorized as having low, moderate, and high cardiovascular health. Change in cardiovascular health over 10 years between 1985/1988 and 1997/1999 was considered.MAIN OUTCOME AND MEASURE Incident CVD (coronary heart disease and stroke).RESULTS The study population included 9256 participants without prior CVD (mean [SD] age at baseline, 44.8 [6.0] years; 2941 [32%] women), of whom 6326 had data about cardiovascular health change. Over a median follow-up of 18.9 years after 1997/1999, 1114 incident CVD events occurred. In multivariable analysis and compared with individuals with persistently low cardiovascular health (consistently low group, 13.5% of participants; CVD incident rate per 1000 person-years, 9.6 [95% CI, 8.4-10.9]), there was no significant association with CVD risk in the low to moderate group (6.8% of participants; absolute rate difference per 1000 person-years, -1.9 [95% CI, -3.9 to 0.1]; HR, 0.84 [95% CI, 0.66-1.08]), the low to high group, (0.3% of participants; absolute rate difference per 1000 person-years, -7.7 [95% CI, -11.5 to -3.9]; HR, 0.19 [95% CI, 0.03-1.35]), and the moderate to low group (18.0% of participants; absolute rate difference per 1000 person-years, -1.3 [95% CI, -3.0 to 0.3]; HR, 0.96 [95% CI, 0.80-1.15]). A lower CVD risk was observed in the consistently moderate group (38.9% of participants; absolute rate difference per 1000 person-years, -4.2 [95% CI, -5.5 to -2.8]; HR, 0.62 [95% CI, 0.53-0.74]), the moderate to high group (5.8% of participants; absolute rate difference per 1000 person-years, -6.4 [95% CI, -8.0 to -4.7]; HR, 0.39 [95% CI, 0.27-0.56]), the high to low group (1.9% of participants; absolute rate difference per 1000 person-years, -5.3 [95% CI, -7.8 to -2.8]; HR, 0.49 [95% CI, 0.29-0.83]), the high to moderate group (9.3% of participants; absolute rate difference per 1000 person-years, -4.5 [95% CI, -6.2 to -2.9]; HR, 0.66 [95% CI, 0.51-0.85]), and the consistently high group (5.5% of participants; absolute rate difference per 1000 person-years, -5.6 [95% CI, -7.4 to -3.9]; HR, 0.57 [95% CI, 0.40-0.80]).CONCLUSIONS AND RELEVANCE Among a group of participants without CVD who received follow-up over a median 18.9 years, there was no consistent relationship between direction of change in category of a composite metric of cardiovascular health and risk of CVD.

Background: Physical activity (PA) is beneficial for baroreflex sensitivity (BRS), but it is unclear whether the type of PA has similar effects on the neural (nBRS) or vascular (carotid stiffness) components of BRS. We sought to determine this in healthy adults from a community- based study via assessment of occupational (OPA), sport (SPA), leisure (LPA) and total PA (TPA). Methods: In 8649 adults aged 50 to 75 years, resting nBRS (estimated by low frequency gain, from carotid distension rate and heart rate) and carotid stiffness were measured by high-precision carotid echotracking. PA was self-reported using the Baecke questionnaire, which distinguishes OPA, SPA, LPA and TPA. The associations between PA and nBRS and carotid stiffness were quantified using multivariate linear regression analysis. Analyses were conducted separately in the working and non- working population. Results: In working adults (n=5039), OPA was associated with lower nBRS function (p=0.026) and borderline higher carotid stiffness (p=0.08). The associations between OPA and nBRS remained independent after additionally adjusting for SPA (p=0.03) and exaggerated exercise blood pressure (p=0.005), a predictor of future hypertension and cardiovascular events. When examining the type of OPA separately (i.e. lifting heavy loads, standing or walking at work) lifting heavy loads only was associated with impaired nBRS (p=0.048). When stratified by education, this association remained only in those with less than tertiary education. SPA was associated with higher nBRS (p=0.0005) and borderline lower carotid stiffness (p=0.052). Neither LPA nor TPA was associated with nBRS or carotid stiffness. In non-working adults (n=3610), SPA and TPA were both associated with lower carotid stiffness (p=0.012 and p=0.020), but not nBRS. LPA was not associated with either parameter. Conclusion: Occupation-related PA, in particular lifting heavy loads, is associated with lower nBRS function, especially in those with lower education. Higher amounts of sport-related PA are associated with higher nBRS and lower carotid stiffness.

Introduction: Systemic hypertension is a rapidly growing epidemic in Sub-Saharan Africa. Adequacy of blood pressure(BP) control and the factors influencing it, especially the role of socio-economic status(SES) have not been well studied in this part of the world. Hypothesis: We therefore aimed to quantify the association of SES both at the individual and at the country level with BP control in Sub-Saharan Africa. Methods: We conducted a cross-sectional survey in urban clinics of twelve countries, both low-income and middle-income, in Sub-Saharan 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: A total of 2198 hypertensive patients (58.4±11.8years; 39.9% male) were included, of whom 1017(46.3%) were from low-income and 1181(53.7%) from middle-income countries. Individual wealth level was low, mid and high in 376(17.6%), 1053(49.2%) and 713(33.3%) patients respectively. Uncontrolled hypertension was present in 1692 patients(77.4%) including 1044(47.7%) with ≥grade 2 hypertension. The proportion of uncontrolled hypertension progressively increased with decreasing level of patient individual wealth, respectively 72.8%, 79.3% and 81.8%(p for trend Conclusions: Low individual wealth was significantly associated with poor hypertension control, especially in low-income countries. Strategies for hypertension control in Sub-Saharan Africa should especially focus on people in the lowest individual wealth groups who also reside in low-income countries.