Publications by authors named "Jacques Genest"

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. Despite the devastating effect of this disease on atherosclerotic cardiovascular health, the disease phenotype and severity are more heterogeneous than previously thought. The predictors of atherosclerotic cardiovascular disease (ASCVD) in HoFH patients have never been systematically studied.

View Article and Find Full Text PDF

Background: In Canada, 2 guidelines provide guidance for the management of dyslipidemia. The Patients, Experience, Evidence, Research simplified lipid guidelines, intended for primary care practitioners, and the Canadian Cardiovascular Society guidelines, intended for all practitioners, are based on differing methodologies with distinct priorities and preferences. The disparate approaches may contribute to confusion among family practitioners and their co-managed patients, with the potential for compromised care, differing standards for training in the fundamentals of lipidology, and differing criteria that might be used in practice audits to evaluate quality of care.

View Article and Find Full Text PDF

Background And Aims: Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297).

View Article and Find Full Text PDF
Article Synopsis
  • Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder that raises LDL cholesterol levels and increases the risk of coronary artery disease, affecting about 1 in 300 people, but the severity varies widely among patients.
  • * Researchers studied 1,123 clinically diagnosed FH patients and 723 genetically identified FH patients, analyzing genetic data to create polygenic risk scores (PRSs) for cardiometabolic traits.
  • * Findings revealed that clinically diagnosed FH patients had higher LDL levels and a greater incidence of cardiovascular disease, and their higher PRSs for CAD and others indicated that genetic factors influence the severity of FH symptoms.*
View Article and Find Full Text PDF

Introduction: The progression of coronary atherosclerosis is an active and regulated process. The Wnt signaling pathway is thought to play an active role in the pathogenesis of several cardiovascular diseases; however, a better understanding of this system in atherosclerosis is yet to be unraveled.

Methods: In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting were used to quantify the expression of Wnt3a, Wnt5a, and Wnt5b in the human coronary plaque, and immunohistochemistry was used to identify sites of local expression.

View Article and Find Full Text PDF

Background: Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD).

Methods: We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD.

View Article and Find Full Text PDF
Article Synopsis
  • Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder leading to very high LDL cholesterol levels and early heart disease, and this study aimed to explore how treatment and outcomes differ between men and women with HoFH.
  • The research included 48 patients, finding that while the median age at diagnosis and LDL cholesterol levels were slightly different between sexes, the overall treatment approaches and major cardiovascular events (like heart attacks and strokes) were comparable.
  • The findings suggest that even though women generally have a lower cardiovascular risk, HoFH significantly impacts this, and further research is needed to better understand sex differences in larger groups of patients.
View Article and Find Full Text PDF

Background: Familial hypercholesterolemia (FH) is a genetic condition causing premature atherosclerotic cardiovascular disease (ASCVD). It is well established that patients with FH should be treated with statin therapy. However, there exists discordance concerning low-density lipoprotein cholesterol-lowering goals in the management of these patients between different guidelines worldwide.

View Article and Find Full Text PDF

Background: Familial hypercholesterolemia (FH), a common genetic condition, is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease (ASCVD). Recent data indicate an undertreatment of females with FH.

Objective: To characterize the role of sex in the perception of FH, its associated ASCVD risk and treatment.

View Article and Find Full Text PDF
Article Synopsis
  • Familial hypercholesterolemia (FH) is linked to early heart disease caused by high LDL-C levels, and this study compared the effectiveness of a full next-generation sequencing (NGS) genetic panel to a partial one currently used in Quebec.
  • The research analyzed data from patients diagnosed with severe hypercholesterolemia at McGill University Health Centre, using advanced genetic testing techniques to detect FH variants.
  • Results showed that about 73.8% of genetically tested patients had pathogenic variants; the full NGS panel identified significantly more variants than the MSSS panel, leading to a notable reclassification of 39.3% of patients from probable to definite FH.
View Article and Find Full Text PDF

Background: Hypercholesterolemia is a common condition characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of atherosclerotic cardiovascular disease (ASCVD). Indigenous populations experience disproportionate rates of ASCVD, however, the extent to which hypercholesterolemia contributes to this burden is unknown.

Objectives: This study aimed to estimate the prevalence of hypercholesterolemia, severe hypercholesterolemia, and familial hypercholesterolemia (FH) in Indigenous populations in Canada, the United States, Australia, and New Zealand.

View Article and Find Full Text PDF

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Untreated patients present with extensive xanthomas and premature atherosclerosis. Lipid-lowering therapy is highly efficacious and has dramatically increased life expectancy of patients with HoFH.

View Article and Find Full Text PDF

Background: The association between familial hypercholesterolemia (FH) and premature atherosclerotic cardiovascular disease (ASCVD) is well established. Several risk factors other than the cumulative low-density lipoprotein cholesterol (LDL-C) have been shown to modulate the severity of the phenotype in these patients. However, the effect of the metabolic syndrome (MetS) on ASCVD risk in FH remains to be determined.

View Article and Find Full Text PDF

The recent identification of the cell-surface protein DSC1 (desmocollin 1) as a negative regulator of HDL (high-density lipoprotein) biogenesis has attracted us to revisit the old HDL biogenesis hypothesis: HDL biogenesis reduces atherosclerosis. The location and function of DSC1 suggest that DSC1 is a druggable target for the promotion of HDL biogenesis, and the discovery of docetaxel as a potent inhibitor of the DSC1 sequestration of apolipoprotein A-I has provided us with new opportunities to test this hypothesis. The FDA-approved chemotherapy drug docetaxel promotes HDL biogenesis at low-nanomolar concentrations that are far lower than used in chemotherapy.

View Article and Find Full Text PDF

ATP-binding cassette transporter A1 (ABCA1) has been identified as the molecular defect in Tangier disease. It is biochemically characterized by absence of high-density lipoprotein cholesterol (HDL-C) in the circulation, resulting in the accumulation of cholesterol in lymphoid tissues. Accumulation of cholesterol in arteries is an underlying cause of atherosclerosis, and HDL-C levels are inversely associated with the presence of atherosclerotic cardiovascular disease (ASCVD).

View Article and Find Full Text PDF

Background: Malignant tumours of the aortic valve apparatus are extremely rare and difficult to diagnose. Their proximity to the coronary ostium may cause an acute coronary syndrome (ACS) either by infiltration or by embolization.

Case Summary: We report a case of primary aortic valve undifferentiated sarcoma causing recurrent episodes of ACS, and we provide a literature review for primary cardiac valve tumours.

View Article and Find Full Text PDF

Background: A simplified Canadian definition was recently developed to enable identification of individuals with familial hypercholesterolemia (FH) and severe hypercholesterolemia in the general population. Our objective was to use a modified version of this new definition to assess contemporary disease prevalence, treatment patterns, and low-density lipoprotein cholesterol (LDL-C) control in Ontario, Canada.

Methods: We identified individuals aged 66 to 105 years who were alive as of January 1, 2011, using the rdiovascular alth in mbulatory Care esearch eam (CANHEART) database, which was created by linking 19 population-based health databases in Ontario.

View Article and Find Full Text PDF
Article Synopsis
  • Patients with familial hypercholesterolemia (FH) have high LDL cholesterol levels, increasing their risk of cardiovascular disease (CVD), and the study aimed to analyze how different LDL receptor (LDLR) mutations influence major adverse cardiovascular events (MACEs).
  • The multinational cohort study included 2,131 heterozygous FH patients aged 18-65, revealing that those with a null mutation had a significantly higher incidence of MACEs (12%) compared to those with a defective mutation (6%), and also showed higher baseline LDL cholesterol levels.
  • Results showed that carriers of the null mutation had about a 2-fold higher risk of experiencing MACEs despite adjusting for traditional risk factors, emphasizing
View Article and Find Full Text PDF
Article Synopsis
  • Decades of research demonstrate a strong link between high-density lipoprotein cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), consistent across different populations.
  • Animal studies indicate that boosting HDL particles could help prevent atherosclerosis, suggesting a potential target for therapy.
  • However, recent data challenges the idea that HDL-C is directly causal in ASCVD, and drugs aimed at increasing HDL-C have mostly been ineffective in preventing or treating the disease.
View Article and Find Full Text PDF

Aims: Homozygous familial hypercholesterolaemia (HoFH) is an orphan disease defined by extreme elevations in low-density lipoprotein cholesterol, cutaneous xanthomas, and pre-mature atherosclerotic cardiovascular disease. Survival has more than doubled over the past three decades. Aortic stenosis (AS) [supravalvular aortic stenosis (SVAS) or valvular aortic stenosis (VAS)] is commonly encountered.

View Article and Find Full Text PDF

Atherosclerosis is a chronic inflammatory condition in which macrophages play a major role. Janus kinase 2 (JAK2) is a pivotal molecule in inflammatory and metabolic signaling, and Jak2 activating mutation has recently been implicated with enhancing clonal hematopoiesis and atherosclerosis. To determine the essential in vivo role of macrophage (M)-Jak2 in atherosclerosis, we generate atherosclerosis-prone ApoE-null mice deficient in M-Jak2.

View Article and Find Full Text PDF

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by extreme elevations of low-density lipoprotein cholesterol (LDL-C) and extremely premature atherosclerotic cardiovascular disease. To date, impacts of HoFH and its treatment on the psychosocial wellbeing of patients have been poorly characterized.

Objectives: We performed a systematic review of the association between HoFH and health-related quality of life (HRQL).

View Article and Find Full Text PDF

The capacity of macrophages to dispose of cholesterol deposited in the atherosclerotic plaque depends on their ability to activate cholesterol efflux pathways. To develop athero-protective therapies aimed at promoting macrophage cholesterol efflux, cholesterol metabolism in THP-1 monocyte-derived macrophages has been extensively studied, but the intrinsic sensitivity of monocytes and the lack of a standardized procedure to differentiate THP-1 monocytes into macrophages have made it difficult to utilize THP-1 macrophages in the same or similar degree of differentiation across studies. The variability has resulted in lack of understanding of how the differentiation affects cholesterol metabolism, and here we review and investigate the effects of THP-1 differentiation on cholesterol efflux.

View Article and Find Full Text PDF