Publications by authors named "Jean-Philippe Empana"

152 Publications

Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23.

Eur Heart J 2021 Mar 3. Epub 2021 Mar 3.

Sorbonne Université, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris 75013, France.

Aims : Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure.

Methods And Results : We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10-11 and 7.7 × 10-4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10-8 and 1.4 × 10-3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 27% increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene.

Conclusion : This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.
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http://dx.doi.org/10.1093/eurheartj/ehab030DOI Listing
March 2021

COVID-19-related medical research: a meta-research and critical appraisal.

BMC Med Res Methodol 2021 01 4;21(1). Epub 2021 Jan 4.

Paris Translational Research Epidemiology and Biostatistics Department, Hôpital Necker, 149 rue de Sèvres, 75015, Paris, France.

Background: Since the start of the COVID-19 outbreak, a large number of COVID-19-related papers have been published. However, concerns about the risk of expedited science have been raised. We aimed at reviewing and categorizing COVID-19-related medical research and to critically appraise peer-reviewed original articles.

Methods: The data sources were Pubmed, Cochrane COVID-19 register study, arXiv, medRxiv and bioRxiv, from 01/11/2019 to 01/05/2020. Peer-reviewed and preprints publications related to COVID-19 were included, written in English or Chinese. No limitations were placed on study design. Reviewers screened and categorized studies according to i) publication type, ii) country of publication, and iii) topics covered. Original articles were critically appraised using validated quality assessment tools.

Results: Among the 11,452 publications identified, 10,516 met the inclusion criteria, among which 7468 (71.0%) were peer-reviewed articles. Among these, 4190 publications (56.1%) did not include any data or analytics (comprising expert opinion pieces). Overall, the most represented topics were infectious disease (n = 2326, 22.1%), epidemiology (n = 1802, 17.1%), and global health (n = 1602, 15.2%). The top five publishing countries were China (25.8%), United States (22.3%), United Kingdom (8.8%), Italy (8.1%) and India (3.4%). The dynamic of publication showed that the exponential growth of COVID-19 peer-reviewed articles was mainly driven by publications without original data (mean 261.5 articles ± 51.1 per week) as compared with original articles (mean of 69.3 ± 22.3 articles per week). Original articles including patient data accounted for 713 (9.5%) of peer-reviewed studies. A total of 576 original articles (80.8%) showed intermediate to high risk of bias. Last, except for simulation studies that mainly used large-scale open data, the median number of patients enrolled was of 102 (IQR = 37-337).

Conclusions: Since the beginning of the COVID-19 pandemic, the majority of research is composed by publications without original data. Peer-reviewed original articles with data showed a high risk of bias and included a limited number of patients. Together, these findings underscore the urgent need to strike a balance between the velocity and quality of research, and to cautiously consider medical information and clinical applicability in a pressing, pandemic context. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/5zjyx/.
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http://dx.doi.org/10.1186/s12874-020-01190-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780085PMC
January 2021

Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes.

J Am Soc Nephrol 2021 Feb 15;32(2):397-409. Epub 2020 Dec 15.

Université de Paris, Institut National de la Santé et de la Recherche Médicale U970, Paris Translational Research Centre for Organ Transplantation, Paris, France

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.
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http://dx.doi.org/10.1681/ASN.2020040464DOI Listing
February 2021

Depressive symptoms and non-adherence to treatable cardiovascular risk factors' medications in the CONSTANCES cohort.

Eur Heart J Cardiovasc Pharmacother 2020 Oct 28. Epub 2020 Oct 28.

Université de Paris, Faculty of Health, School of Medicine, Paris, France.

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.
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http://dx.doi.org/10.1093/ehjcvp/pvaa124DOI Listing
October 2020

Early and Supernormal Vascular Aging: Clinical Characteristics and Association With Incident Cardiovascular Events.

Hypertension 2020 Nov 8;76(5):1616-1624. Epub 2020 Sep 8.

From the INSERM, U970, Paris Cardiovascular Research Center-PARCC, France (R.M.B., J.-P.E., P.B., S.L.).

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-age<-5.7 years), normal (Δ-age -5.7 to 6.8 years) and supernormal vascular aging (Δ-age>6.8 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 (<0.01) and inversely associated with cardiovascular events. Compared with normal vascular aging, supernormal vascular aging had lower risk (hazard ratio, 0.59 [95% CI, 0.41-0.85]), whereas early vascular aging had higher risk (hazard ratio, 2.70 [95% CI, 1.55-4.70]) of cardiovascular events, in particular coronary events. There was no significant association with all-cause mortality. This study represents the first validation of the clinical significance of the supernormal vascular aging concept, based on prospective data. Its further characterization may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14971DOI Listing
November 2020

Trajectories of glomerular filtration rate and progression to end stage kidney disease after kidney transplantation.

Kidney Int 2021 01 8;99(1):186-197. Epub 2020 Aug 8.

Université de Paris, INSERM, PARCC, Paris Translational Research Centre for Organ Transplantation, Paris, France; Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.kint.2020.07.025DOI Listing
January 2021

Health Literacy and Primordial Prevention in Childhood-An Opportunity to Reduce the Burden of Cardiovascular Disease.

JAMA Cardiol 2020 Jul 29. Epub 2020 Jul 29.

Université de Paris, INSERM U970, Paris Cardiovascular Research Centre, Integrative Epidemiology of Cardiovascular Disease, Paris, France.

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http://dx.doi.org/10.1001/jamacardio.2020.2864DOI Listing
July 2020

The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale.

Gerontology 2020 1;66(5):447-459. Epub 2020 Jul 1.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria,

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.
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http://dx.doi.org/10.1159/000508498DOI Listing
July 2020

Poor adherence to medication and salt restriction as a barrier to reaching blood pressure control in patients with hypertension: Cross-sectional study from 12 sub-Saharan countries.

Arch Cardiovasc Dis 2020 Jun - Jul;113(6-7):433-442. Epub 2020 May 17.

Sorbonne Université, AP-HP, Sorbonne Université, Hôpital Saint Antoine, Service de Pharmacie, 75012 Paris, France; Université de Paris, INSERM U970, Paris Cardiovascular Research Centre, Integrative Epidemiology of cardiovascular disease, Paris, France.

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.
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http://dx.doi.org/10.1016/j.acvd.2019.11.009DOI Listing
September 2020

Identification and Characterization of Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation: A Population-Based Study.

Circulation 2020 Jun 4;141(24):1954-1967. Epub 2020 May 4.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (R.L., J.K.P., J.K.).

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 (<0.001), donor male sex (<0.001), donor tobacco consumption (=0.001), recipient dyslipidemia (=0.009), class II anti-human leukocyte antigen donor-specific antibodies (=0.004), and acute cellular rejection ≥2R (=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 (<0.001).

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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044924DOI Listing
June 2020

Sleep apnoea is associated with hearing impairment: The Paris prospective study 3.

Clin Otolaryngol 2020 09 22;45(5):681-686. Epub 2020 May 22.

Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, Paris, France.

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.
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http://dx.doi.org/10.1111/coa.13557DOI Listing
September 2020

Type 2 Diabetes Mellitus Is Independently Associated With Decreased Neural Baroreflex Sensitivity: The Paris Prospective Study III.

Arterioscler Thromb Vasc Biol 2020 05 19;40(5):1420-1428. Epub 2020 Mar 19.

Université de Paris, INSERM U970, Paris Cardiovascular Research Centre (PARCC), Integrative Epidemiology of Cardiovascular Disease team, Paris, France (R.E.C., L.O., C.G., N.D., X.J., P.B., J.-P.E.).

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 BRS (nBRS) and mechanical component of the BRS is altered in those with high metabolic risk (HMR, impaired fasting glucose and 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 [time elapsed between two successive R waves] intervals) and mechanical BRS were measured by high-precision carotid echotracking. The associations between overt T2D or HMR as compared with subjects with normal glucose metabolism and nBRS or mechanical BRS 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 normal glucose metabolism (59±6 years, 57% male). Compared with normal glucose metabolism, nBRS was significantly lower in HMR subjects (β=-0.07 [95% CI, -0.12 to -0.01]; =0.029) and in subjects with T2D (β=-0.18 [95% CI, -0.29 to -0.07]; =0.002) after adjustment for confounding and mediating factors. Subgroup analysis suggests significant and independent alteration in mechanical BRS 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 normal glucose metabolism subjects.
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http://dx.doi.org/10.1161/ATVBAHA.120.314102DOI Listing
May 2020

Depression, antidepressants and low hemoglobin level in the Paris Prospective Study III: A cross-sectional analysis.

Prev Med 2020 06 8;135:106050. Epub 2020 Mar 8.

Université de Paris, Paris Descartes Faculty of Medicine, Paris, France; Inserm, UMR-S970, Paris Cardiovascular Research Center, Team 4 Integrative Epidemiology of Cardiovascular disease, Paris, France.

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 antidepressant intake were independently associated with lower hemoglobin level (β = -0.074; p = .05 and β = -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 (β = -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.
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http://dx.doi.org/10.1016/j.ypmed.2020.106050DOI Listing
June 2020

Hostility, depression and incident cardiac events in the GAZEL cohort.

J Affect Disord 2020 04 28;266:381-386. Epub 2020 Jan 28.

Université de Paris, Faculty of Medicine, Paris, France; AP-HP.Centre-Université de Paris, Hôpital européen Georges-Pompidou, Service de psychiatrie et d'addictologie de l'adulte et du sujet âgé, Paris, France; Université de Paris, INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, Paris.

Background: Psychological factors such as hostility and depression have been associated with cardiovascular disease. However, their role in predicting incident cardiac events independently one of another is not clear.

Methods: Among 10,304 GAZEL middle-aged workers free of cardiovascular diseases in 1993, 581 incident cardiac events were validated from 1994-2014. Hostile traits (cognitive hostility, behavioral hostility, irritability and negativism) were assessed with the Buss and Durkee Hostility Inventory at baseline. Depressive symptoms were assessed at baseline and every three years with the Center for Epidemiological Studies Depression scale. We used Cox proportional hazards models to calculate hazard ratios (HR) of hostile traits for incident cardiac events adjusting for baseline self-reported socio-demographics and family history of coronary heart diseases (model 1), then additionally for time-dependent depressive symptoms (either as a binary or continuous variable) (model 2) and for yearly self-reported modifiable cardiovascular risk factors (physical activity, smoking, body mass index, diabetes, dyslipidemia and hypertension) (model 3).

Results: In Model 1, the only hostile trait associated with incident cardiac events was irritability (HR for one interquartile range: 1.16, 95% confidence interval: 1.02-1.32). This association was no longer statistically significant when further adjusting for depressive symptoms. Depressive symptoms, in turn, remained significant predictors of cardiac events with HRs ranging from 1.40-1.49 (binary).

Limitations: Hostility traits were measured only once.

Conclusions: Depressive symptoms might explain the association between irritability and cardiac events and should therefore be prioritized in interventions aiming to prevent cardiovascular disease. Further research is needed to identify the mechanisms underlying this association.
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http://dx.doi.org/10.1016/j.jad.2020.01.164DOI Listing
April 2020

Association Between Occupational, Sport, and Leisure Related Physical Activity and Baroreflex Sensitivity: The Paris Prospective Study III.

Hypertension 2019 12 4;74(6):1476-1483. Epub 2019 Nov 4.

From the University de Paris, INSERM, U970, Paris Cardiovascular Research Centre (PARCC), Integrative Epidemiology of Cardiovascular Disease Team, France (R.E.C., M.-C.P., L.O., C.G., T.T.v.S., X.J., J.-P.E.).

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]; =0.022) whereas sport PA was associated with better nBRS (β=0.04; [95% CI, 0.02-0.07]; =0.003) and mBRS (β=-0.05; [95% CI, -0.09 to -0.00001]; =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]; =0.012 and β=-0.05; [95% CI, -0.10 to 0.009]; =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.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13461DOI Listing
December 2019

Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium.

Eur J Prev Cardiol 2020 02 16;27(3):234-243. Epub 2019 Oct 16.

Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, UK.

Aims: Averaged 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 Results: An 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 ( = 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.

Conclusion: Averaged 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.
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http://dx.doi.org/10.1177/2047487319877078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008553PMC
February 2020

Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study.

BMJ 2019 09 17;366:l4923. Epub 2019 Sep 17.

Université de Paris, INSERM, Paris Translational Research Centre for Organ Transplantation, Paris, France.

Objective: To develop and validate an integrative system to predict long term kidney allograft failure.

Design: International cohort study.

Setting: Three cohorts including kidney transplant recipients from 10 academic medical centres from Europe and the United States.

Participants: Derivation cohort: 4000 consecutive kidney recipients prospectively recruited in four French centres between 2005 and 2014. Validation cohorts: 2129 kidney recipients from three centres in Europe and 1428 from three centres in North America, recruited between 2002 and 2014. Additional validation in three randomised controlled trials (NCT01079143, EudraCT 2007-003213-13, and NCT01873157).

Main Outcome Measure: Allograft failure (return to dialysis or pre-emptive retransplantation). 32 candidate prognostic factors for kidney allograft survival were assessed.

Results: Among the 7557 kidney transplant recipients included, 1067 (14.1%) allografts failed after a median post-transplant follow-up time of 7.12 (interquartile range 3.51-8.77) years. In the derivation cohort, eight functional, histological, and immunological prognostic factors were independently associated with allograft failure and were then combined into a risk prediction score (iBox). This score showed accurate calibration and discrimination (C index 0.81, 95% confidence interval 0.79 to 0.83). The performance of the iBox was also confirmed in the validation cohorts from Europe (C index 0.81, 0.78 to 0.84) and the US (0.80, 0.76 to 0.84). The iBox system showed accuracy when assessed at different times of evaluation post-transplant, was validated in different clinical scenarios including type of immunosuppressive regimen used and response to rejection therapy, and outperformed previous risk prediction scores as well as a risk score based solely on functional parameters including estimated glomerular filtration rate and proteinuria. Finally, the accuracy of the iBox risk score in predicting long term allograft loss was confirmed in the three randomised controlled trials.

Conclusion: An integrative, accurate, and readily implementable risk prediction score for kidney allograft failure has been developed, which shows generalisability across centres worldwide and common clinical scenarios. The iBox risk prediction score may help to guide monitoring of patients and further improve the design and development of a valid and early surrogate endpoint for clinical trials.

Trial Registration: Clinicaltrials.gov NCT03474003.
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http://dx.doi.org/10.1136/bmj.l4923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746192PMC
September 2019

Change in Cardiovascular Health and Incident Type 2 Diabetes and Impaired Fasting Glucose: The Whitehall II Study.

Diabetes Care 2019 10 15;42(10):1981-1987. Epub 2019 Aug 15.

Université de Paris, INSERM U970, Paris Cardiovascular Research Centre (PARCC), Integrative Epidemiology of Cardiovascular Disease Team, Paris, France.

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.
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http://dx.doi.org/10.2337/dc19-0379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364667PMC
October 2019

Defining Exposure and Non-exposure in Observational Studies of Sleep Apnea Treatment-Reply.

JAMA Otolaryngol Head Neck Surg 2019 Aug 8. Epub 2019 Aug 8.

Paris Descartes University, Paris, France.

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http://dx.doi.org/10.1001/jamaoto.2019.1883DOI Listing
August 2019

Association of ideal cardiovascular health at age 50 with incidence of dementia: 25 year follow-up of Whitehall II cohort study.

BMJ 2019 08 7;366:l4414. Epub 2019 Aug 7.

Inserm U1153, Epidemiology of Ageing and Neurodegenerative diseases, Université de Paris, 75010 Paris, France.

Objectives: To examine the association between the Life Simple 7 cardiovascular health score at age 50 and incidence of dementia.

Design: Prospective cohort study.

Setting: Civil service departments in London (Whitehall II study; study inception 1985-88).

Participants: 7899 participants with data on the cardiovascular health score at age 50.

Exposures: The 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 Measure: Incident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017.

Results: 347 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).

Conclusion: Adherence to the Life Simple 7 ideal cardiovascular health recommendations in midlife was associated with a lower risk of dementia later in life.
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http://dx.doi.org/10.1136/bmj.l4414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664261PMC
August 2019

Factors associated with poor adherence to medication among hypertensive patients in twelve low and middle income Sub-Saharan countries.

PLoS One 2019 10;14(7):e0219266. Epub 2019 Jul 10.

Department of Pharmacy, Saint Antoine hospital, HUEP, AP-HP, Paris, France.

Introduction: Over the past few decades, the prevalence of hypertension has dramatically increased in Sub-Saharan Africa. Poor adherence has been identified as a major cause of failure to control hypertension. Scarce data are available in Africa.

Aims: We assessed adherence to medication and identified socioeconomics, clinical and treatment factors associated with low adherence among hypertensive patients in 12 sub-Saharan African countries.

Method: We conducted a cross-sectional survey in urban clinics of both low and middle income countries. Data were collected by physicians on demographics, treatment and clinical data among hypertensive patients attending the clinics. Adherence was assessed by questionnaires completed by the patients. Factors associated with low adherence were investigated using logistic regression with a random effect on countries.

Results: There were 2198 individuals from 12 countries enrolled in the study. Overall, 678 (30.8%), 738 (33.6%), 782 (35.6%) participants had respectively low, medium and high adherence to antihypertensive medication. Multivariate analysis showed that the use of traditional medicine (OR: 2.28, 95%CI [1.79-2.90]) and individual wealth index (low vs. high wealth: OR: 1.86, 95%CI [1.35-2.56] and middle vs. high wealth: OR: 1.42, 95%CI [1.11-1.81]) were significantly and independently associated with poor adherence to medication. In stratified analysis, these differences in adherence to medication according to individual wealth index were observed in low-income countries (p<0.001) but not in middle-income countries (p = 0.17). In addition, 26.5% of the patients admitted having stopped their treatment due to financial reasons and this proportion was 4 fold higher in the lowest than highest wealth group (47.8% vs 11.4%) (p<0.001).

Conclusion: This study revealed the high frequency of poor adherence in African patients and the associated factors. These findings should be useful for tailoring future programs to tackle hypertension in low income countries that are better adapted to patients, with a potential associated enhancement of their effectiveness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219266PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619761PMC
February 2020

Chewing capacity and ideal cardiovascular health in adulthood: A cross-sectional analysis of a population-based cohort study.

Clin Nutr 2020 May 13;39(5):1440-1446. Epub 2019 Jun 13.

INSERM U970, Paris Cardiovascular Research Centre (PARCC), University of Paris, 56 rue Leblanc, 75015 Paris, France; INSERM U970, Paris Cardiovascular Research Centre (PARCC), Integrative Epidemiology of Cardiovascular Disease (Team 4), 56 rue Leblanc, 75015 Paris, France.

Background And Aims: To study the association between chewing capacity-a prerequisite for eating- and the level of cardiovascular health (CVH).

Methods: 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).

Results: 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.

Conclusion: This is the first study suggesting that adults with a preserved chewing capacity have an increased likelihood to be at an ideal behavioural CVH.
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http://dx.doi.org/10.1016/j.clnu.2019.05.029DOI Listing
May 2020

Response by Climie et al to Letter Regarding Article "Individual and Neighborhood Deprivation and Carotid Stiffness: The Paris Prospective Study III".

Hypertension 2019 08 24;74(2):e30. Epub 2019 Jun 24.

INSERM, U970, Department of Epidemiology, Paris Descartes University, Paris, France.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13392DOI Listing
August 2019

Individual and Neighborhood Deprivation and Carotid Stiffness.

Hypertension 2019 06;73(6):1185-1194

From the INSERM, U970, Department of Epidemiology (R.E.C., MC.P., C.G., T.T.v.S., X.J., JP.E.).

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<0.05). Neighborhood deprivation was adversely related to carotid stiffness in males ( P<0.05), but not in females. Socioeconomic deprivation, both at 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.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.12186DOI Listing
June 2019

Association of Positive Airway Pressure Prescription With Mortality in Patients With Obesity and Severe Obstructive Sleep Apnea: The Sleep Heart Health Study.

JAMA Otolaryngol Head Neck Surg 2019 06;145(6):509-515

Paris Descartes University, Faculty of Medicine, Paris, France.

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.
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http://dx.doi.org/10.1001/jamaoto.2019.0281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583022PMC
June 2019

Cardiovascular health and sleep disturbances in two population-based cohort studies.

Heart 2019 10 8;105(19):1500-1506. Epub 2019 Apr 8.

Universite Paris Descartes, Paris, France.

Objective: We aimed to investigate the association between cardiovascular health (CVH), as defined by the American Heart Association, and several sleep disturbances.

Methods: Two 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.

Results: Compared 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.

Conclusions: Higher 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.
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http://dx.doi.org/10.1136/heartjnl-2018-314485DOI Listing
October 2019

A large-scale exome array analysis of venous thromboembolism.

Genet Epidemiol 2019 06 19;43(4):449-457. Epub 2019 Jan 19.

Department of Emergency Medicine, Center for Vascular Emergencies, Massachusetts General Hospital, Boston, Massachusetts.

Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] ~0.08%). We confirmed associations with previously identified VTE loci, including ABO, F5, F11, and FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene-based analysis. Given our sample size, we had greater than 80% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low-frequency and rare variants associated with VTE risk.
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http://dx.doi.org/10.1002/gepi.22187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520188PMC
June 2019