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Article ; Online: Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome.

Tardif, Jean-Claude / Pfeffer, Marc A / Dubé, Marie-Pierre

2022

Language	English
Publishing date	2022-11-15
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehac644
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Zs.A 1563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 640: Show issues

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Article ; Online: Childhood Maltreatment and Leukocyte Telomere Length: Cardiac Vagal Activity Influences the Relation in Older Adults.

Connor, Alexandra / Deschamps, Alain / Busque, Lambert / Tardif, Jean-Claude / Bourgoin, Vincent / Dubé, Marie-Pierre / Busseuil, David / D'Antono, Bianca

Psychosomatic medicine

2024 Volume 86, Issue 3, Page(s) 146–156

Abstract: Objective: Childhood maltreatment is associated with shorter leukocyte telomere length (LTL). However, the influence of cardiac vagal control on this relation is unknown. We examined whether cardiac vagal control at rest and in response to stress ... ...

Abstract	Objective: Childhood maltreatment is associated with shorter leukocyte telomere length (LTL). However, the influence of cardiac vagal control on this relation is unknown. We examined whether cardiac vagal control at rest and in response to stress moderates or cross-sectionally mediates the relationship between childhood maltreatment and LTL. Methods: Participants were 1179 men and women (aged 65 [7.2] years) suffering from coronary artery disease or non-cardiovascular chronic disease. They completed a childhood maltreatment questionnaire and underwent a stress protocol while electrocardiogram was monitored. High-frequency heart rate variability (HF-HRV) measures were obtained at rest, during stress, and after stress in absolute and normalized units (nu). LTL was measured using quantitative polymerase chain reaction. Mediation and moderation analyses were performed. Result: HF-HRV and HF-HRV in normalized units (HFnu) measures did not mediate the childhood maltreatment-LTL relation. However, baseline HFnu ( p = .027) and HFnu reactivity ( p = .051) moderated the relation. Specifically, maltreatment was associated with significantly lower LTL among those with baseline HFnu at ( b = -0.059, p = .003) or below the mean ( b = -0.103, p < .001), but not among those with higher baseline HFnu. It was also associated with significantly lower LTL among participants who showed either blunted ( b = -0.058, p = .004) or increased HFnu ( b = -0.099, p = .001) responses to stress but not in those with large decreases in HFnu. Conclusions: Childhood maltreatment was associated with lower LTL in those who showed a distinct cardiac vagal profile at baseline and in response to stress. The mechanisms and implications remain to be determined.
MeSH term(s)	Male ; Humans ; Female ; Aged ; Child ; Coronary Artery Disease ; Anxiety ; Leukocytes ; Telomere ; Child Abuse
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	3469-1
ISSN	1534-7796 ; 0033-3174
ISSN (online)	1534-7796
ISSN	0033-3174
DOI	10.1097/PSY.0000000000001290
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Ui I Zs.181: Show issues

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Article ; Online: Predictive risk factors for hospitalization and response to colchicine in patients with COVID-19.

Tardif, Jean-Claude / Cossette, Mariève / Guertin, Marie-Claude / Bouabdallaoui, Nadia / Dubé, Marie-Pierre / Boivin, Guy

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2022 Volume 116, Page(s) 387–390

Abstract: Objective: A predictive model for hospitalization due to COVID-19 or death was developed in the placebo group (N=2,084) from a large clinical trial of colchicine in COVID-19 patients (N = 4,159).: Results: The 7 variables retained in the predictive ... ...

Abstract	Objective: A predictive model for hospitalization due to COVID-19 or death was developed in the placebo group (N=2,084) from a large clinical trial of colchicine in COVID-19 patients (N = 4,159). Results: The 7 variables retained in the predictive model were age, gender, body-mass index, history of respiratory disease, use of diabetes drugs, use of anticoagulants, and use of oral steroids at the time of randomization. An optimal threshold value identified from the predictive model was used to classify high-risk patients (those with a predicted probability above the optimal threshold) and low-risk patients (those with a predicted probability below the optimal threshold). The number needed to treat to prevent 1 hospitalization or death with colchicine treatment decreased from 71 in the whole study population (N = 4,159) to 29 in the high-risk subgroup (N=1,692). Conclusion: This model could serve to identify high-risk subjects who will particularly benefit from early colchicine therapy.
MeSH term(s)	COVID-19/drug therapy ; Colchicine/adverse effects ; Colchicine/therapeutic use ; Hospitalization ; Humans ; Risk Factors ; SARS-CoV-2 ; Treatment Outcome
Chemical Substances	Colchicine (SML2Y3J35T)
Language	English
Publishing date	2022-01-14
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2022.01.020
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Zs.A 4516: Show issues

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Article ; Online: ExPheWas: a platform for cis-Mendelian randomization and gene-based association scans.

Legault, Marc-André / Perreault, Louis-Philippe Lemieux / Tardif, Jean-Claude / Dubé, Marie-Pierre

Nucleic acids research

2022 Volume 50, Issue W1, Page(s) W305–W311

Abstract: Establishing the relationship between protein-coding genes and phenotypes has the potential to inform on the molecular etiology of diseases. Here, we describe ExPheWas (exphewas.ca), a gene-based phenome-wide association study browser and platform that ... ...

Abstract	Establishing the relationship between protein-coding genes and phenotypes has the potential to inform on the molecular etiology of diseases. Here, we describe ExPheWas (exphewas.ca), a gene-based phenome-wide association study browser and platform that enables the conduct of gene-based Mendelian randomization. The ExPheWas data repository includes sex-stratified and sex-combined gene-based association results from 26 616 genes with 1746 phenotypes measured in up to 413 133 individuals from the UK Biobank. Interactive visualizations are provided through a browser to facilitate data exploration supported by false discovery rate control, and it includes tools for enrichment analysis. The interactive Mendelian randomization module in ExPheWas allows the estimation of causal effects of a genetically predicted exposure on an outcome by using genetic variation in a single gene as the instrumental variable.
MeSH term(s)	Mendelian Randomization Analysis/methods ; Phenotype ; Genetic Association Studies ; Causality ; Phenomics ; Genome-Wide Association Study/methods ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2022-04-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac289
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Zs.A 1067: Show issues

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Article ; Online: A dataset of proteomic changes during human heat stress and heat acclimation.

Gagnon, Daniel / Barry, Hadiatou / Barhdadi, Amina / Oussaid, Essaid / Mongrain, Ian / Lemieux Perreault, Louis-Philippe / Dubé, Marie-Pierre

Scientific data

2023 Volume 10, Issue 1, Page(s) 877

Abstract: Hotter climates have important impacts on human health and performance. Yet, the cellular and molecular responses involved in human heat stress and acclimation remain understudied. This dataset includes physiological measurements and the plasma ... ...

Abstract	Hotter climates have important impacts on human health and performance. Yet, the cellular and molecular responses involved in human heat stress and acclimation remain understudied. This dataset includes physiological measurements and the plasma concentration of 2,938 proteins collected from 10 healthy adults, before and during passive heat stress that was performed both prior to and after a 7-day heat acclimation protocol. Physiological measurements included body temperatures, sweat rate, cutaneous vascular conductance, blood pressure, and skin sympathetic nerve activity. The proteomic dataset was generated using the Olink Explore 3072 assay, enabling a high-multiplex antibody-based assessment of protein changes based on proximity extension assay technology. The data need to be interpreted in the context of the moderate level of body hyperthermia attained and the specific demographic of young, healthy adults. We have made this dataset publicly available to facilitate research into the cellular and molecular mechanisms involved in human heat stress and acclimation, crucial for addressing the health and performance challenges posed by rising temperatures.
MeSH term(s)	Adult ; Humans ; Acclimatization ; Heat-Shock Response ; Proteomics ; Heat Stress Disorders/genetics
Language	English
Publishing date	2023-12-07
Publishing country	England
Document type	Dataset ; Journal Article
ZDB-ID	2775191-0
ISSN	2052-4463 ; 2052-4463
ISSN (online)	2052-4463
ISSN	2052-4463
DOI	10.1038/s41597-023-02809-5
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Article ; Online: Interplay between hereditary and acquired factors determines the neutrophil counts in older individuals.

Gagnon, Marie-France / Provost, Sylvie / Sun, Maxine / Ayachi, Sami / Buscarlet, Manuel / Mollica, Luigina / Szuber, Natasha / Dubé, Marie-Pierre / Busque, Lambert

Blood advances

2023 Volume 7, Issue 13, Page(s) 3232–3243

Abstract: Blood cell production is a complex process, partly genetically determined and influenced by acquired factors. However, there is a paucity of data on how these factors interplay in the context of aging, which is associated with a myeloid proliferation ... ...

Abstract	Blood cell production is a complex process, partly genetically determined and influenced by acquired factors. However, there is a paucity of data on how these factors interplay in the context of aging, which is associated with a myeloid proliferation bias, clonal hematopoiesis (CH), and an increased incidence of myeloid cancers. We investigated hereditary and acquired factors underlying blood cell trait variability in a cohort of 2996 related and unrelated women from Quebec aged from 55 to 101 years. We performed a genome-wide association study, evaluated the impact of chronic diseases, and performed targeted deep sequencing of CH driver genes and X-chromosome inactivation (XCI)-based clonality analyses. Multivariable analyses were conducted using generalized linear mixed models. We document that aging is associated with increasing neutrophil and monocyte counts and decreasing lymphocyte counts. Neutrophil counts were influenced by the variants in the region of GSDMA and PSMD3-CSF3, but this association decreased with age; in parallel, older individuals with cardiometabolic comorbidities exhibited significantly higher neutrophil counts (4.1 × 109/L vs 3.83 × 109/L; P < .001) than younger individuals. These age-related diseases were also associated with an increase in other myeloid-derived cells. Neither CH nor XCI clonality correlated with neutrophil counts. In conclusion, we show that neutrophil counts are genetically influenced, but as individuals age, this contribution decreases in favor of acquired factors. Aging is associated with a myeloid proliferation bias which is greater in the presence of cardiometabolic comorbidities but not of CH. These findings support that cell-extrinsic factors may contribute to the myeloid shift possibly through low-grade inflammation.
MeSH term(s)	Humans ; Female ; Aged ; Neutrophils ; Genome-Wide Association Study ; Leukocyte Count ; Aging/genetics ; Cardiovascular Diseases ; Pore Forming Cytotoxic Proteins
Chemical Substances	GSDMA protein, human ; Pore Forming Cytotoxic Proteins
Language	English
Publishing date	2023-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008793
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Zs.A 7153: Show issues

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Article ; Online: Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors.

Sun, Maxine / Cyr, Marie-Christyne / Sandoval, Johanna / Lemieux Perreault, Louis-Philippe / Busque, Lambert / Tardif, Jean-Claude / Dubé, Marie-Pierre

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2023 Volume 32, Issue 6, Page(s) 776–783

Abstract: Background: Cancer survivors are at an increased risk of cardiovascular disease (CVD) compared with the general population. We sought to evaluate the impact of mosaic chromosomal alterations (mCA) on death of CVD causes, coronary artery disease (CAD) ... ...

Abstract	Background: Cancer survivors are at an increased risk of cardiovascular disease (CVD) compared with the general population. We sought to evaluate the impact of mosaic chromosomal alterations (mCA) on death of CVD causes, coronary artery disease (CAD) causes, and of any cause in patients with a cancer diagnosis. Methods: The study was a prospective cohort analysis of 48,919 UK Biobank participants with a cancer diagnosis. mCAs were characterized using DNA genotyping array intensity data and long-range chromosomal phase inference. Multivariable Cox regression models were used to ascertain the associations of mCAs. Exploratory endpoints included various incident cardiovascular phenotypes. Results: Overall, 10,070 individuals (20.6%) carried ≥ 1 mCA clone. In adjusted analyses, mCA was associated with an increased risk of death of CAD causes [HR, 1.37; 95% confidence interval (CI), 1.09-1.71; P = 0.006]. In sub-analyses, we found that carriers of mCAs diagnosed with kidney cancer had an increased risk of death of CVD causes (HR, 2.03; 95% CI, 1.11-3.72; P = 0.022) and CAD causes (HR, 3.57; 95% CI, 1.44-8.84; P = 0.006). Women diagnosed with breast cancer who carried a mCA also had a higher risk of death of CAD causes (HR, 2.46; 95% CI, 1.23-4.92; P = 0.011). Conclusions: Among cancer survivors, carriers of any mCA are at an increased risk of CAD death compared with noncarriers. Mechanistic studies should be considered to better ascertain the biological mechanisms underneath the observed associations between mCAs and cardiovascular events for specific cancer types. Impact: There may be clinical relevance in considering mCAs in patients diagnosed with cancer and undergoing treatment.
MeSH term(s)	Female ; Humans ; Cancer Survivors ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/genetics ; Cohort Studies ; Neoplasms/complications ; Neoplasms/epidemiology ; Neoplasms/genetics ; Prospective Studies ; Risk Factors ; Mosaicism ; Chromosomes, Human, Y
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-22-1290
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Zs.A 3693: Show issues

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Article ; Online: The relationship between perceived parenting practices and anxiety in adults with congenital heart disease.

Houchi, Cylia / Marcil, Marie-Joëlle / Nadarajah, Kishani / Mageau, Geneviève A / Khairy, Paul / Marin, Marie-France / Cossette, Mariève / Dubé, Marie-Pierre / Chaix, Marie-A / Mongeon, François-Pierre / Dore, Annie / Mondésert, Blandine / Ibrahim, Reda / Brouillette, Judith

The Canadian journal of cardiology

2024

Abstract: Background: Patients with congenital heart disease (CHD) and their parents face challenges throughout their lives that can lead to anxiety lasting into adulthood. We aim to assess the association between perceived parenting practices and anxiety beyond ... ...

Abstract	Background: Patients with congenital heart disease (CHD) and their parents face challenges throughout their lives that can lead to anxiety lasting into adulthood. We aim to assess the association between perceived parenting practices and anxiety beyond pediatric medical-surgical histories in adults with CHD. Methods: A cross-sectional study of adults with CHD was conducted at the Montreal Heart Institute (MHI). Perception of parental practices during childhood was retrospectively assessed using validated self-report questionnaires, while anxiety in adulthood was assessed with the Hospital Anxiety and Depression Scale (HADS). Sociodemographic and medical information were collected from a questionnaire and medical records. Hierarchical multiple linear regression was conducted. Results: Of the 223 participants, 59% were female, and the mean age was 46 ± 14 years. Perceived parenting practices explained more variance (11%) in the anxiety score than pediatric medical-surgical history (2%). In our final model, anxiety was significantly associated with age, parental history of anxiety, and positive parenting practices, but not with overprotection. Conclusions: Parenting practices are associated with anxiety in adults with CHD beyond pediatric medical-surgical history and sociodemographic. Positive parenting practices may be protective against anxiety in adulthood. Longitudinal studies are needed to determine causality.
Language	English
Publishing date	2024-05-03
Publishing country	England
Document type	Journal Article
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2024.04.022
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Zs.A 2150: Show issues

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Article ; Online: Randomized Clinical Trial Needed to Confirm Whether Dalcetrapib Improves Outcomes for Specific ADCY9 Genotype.

Pfeffer, Marc A / Dubé, Marie-Pierre / Tardif, Jean-Claude

JAMA cardiology

2018 Volume 3, Issue 9, Page(s) 897

MeSH term(s)	Benzodiazepines ; Case-Control Studies ; Genotype ; Humans ; Sulfhydryl Compounds ; Vascular Diseases
Chemical Substances	Sulfhydryl Compounds ; Benzodiazepines (12794-10-4) ; dalcetrapib (3D050LIQ3H) ; evacetrapib (51XWV9K850)
Language	English
Publishing date	2018-08-08
Publishing country	United States
Document type	Letter ; Comment
ISSN	2380-6591
ISSN (online)	2380-6591
DOI	10.1001/jamacardio.2018.2379
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Article ; Online: Pharmacogenomics of blood lipid regulation.

Legault, Marc-André / Tardif, Jean-Claude / Dubé, Marie-Pierre

Pharmacogenomics

2018 Volume 19, Issue 7, Page(s) 651–665

Abstract: Blood lipids are important modifiable risk factors for coronary heart disease and various drugs have been developed to target lipid fractions. Considerable efforts have been made to identify genetic variants that modulate responses to drugs in the hope ... ...

Abstract	Blood lipids are important modifiable risk factors for coronary heart disease and various drugs have been developed to target lipid fractions. Considerable efforts have been made to identify genetic variants that modulate responses to drugs in the hope of optimizing their use. Pharmacogenomics and new biotechnologies now allow for meaningful integration of human genetic findings and therapeutic development for increased efficiency and precision of lipid-lowering drugs. Polygenic predictors of disease risk are also changing how patient populations can be stratified, enabling targeted therapeutic interventions to patients more likely to derive the highest benefit, marking a shift from single variant to genomic approaches in pharmacogenomics.
MeSH term(s)	Cholesterol, HDL/blood ; Cholesterol, HDL/genetics ; Cholesterol, LDL/blood ; Cholesterol, LDL/genetics ; Coronary Disease/blood ; Coronary Disease/drug therapy ; Coronary Disease/genetics ; Gene Expression Regulation ; Humans ; Hypolipidemic Agents/adverse effects ; Hypolipidemic Agents/pharmacokinetics ; Hypolipidemic Agents/therapeutic use ; Membrane Transport Proteins/genetics ; Pharmacogenetics ; Polymorphism, Single Nucleotide ; Triglycerides/blood ; Triglycerides/genetics
Chemical Substances	Cholesterol, HDL ; Cholesterol, LDL ; Hypolipidemic Agents ; Membrane Transport Proteins ; Triglycerides
Language	English
Publishing date	2018-04-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2019513-8
ISSN	1744-8042 ; 1462-2416
ISSN (online)	1744-8042
ISSN	1462-2416
DOI	10.2217/pgs-2018-0007
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