Paternal inheritance predicts earlier cardiovascular event onset in patients with familial hypercholesterolemia

Paquette, Martine; Fantino, Manon; Bernard, Sophie; Baass, Alexis

doi:10.1016/j.atherosclerosis.2021.06.006

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…Unlike the Spanish study, only patients with an identified FH genetic mutation were included in our study. Another study conducted by a Canadian group 9 showed that ASCVD occurred 2 years earlier in the case of PaI of FH gene mutation. Several hypotheses might explain why their results differ from our study: (1) the Canadian study included half the number of patients; (2) the study design was different since they studied event-free survival; (3) no data on subclinical coronary atherosclerosis evaluated by CAC score was collected.…”

Section: Discussionmentioning

confidence: 99%

“…7 In this study, Vermissen et al showed that maternal inheritance of the LDLR mutation was associated with a 2.2-fold higher relative risk of mortality compared to paternal inheritance, supporting the fetal origin of adulthood disease. More recently, 2 studies in FH have provided contradictory results: (1) in a large cohort of Spanish HeFH patients, Marco-Benedí et al 8 found no difference in the prevalence of ASCVD events between 1231 HeFH-mothers/offspring and 1174 HeFH-fathers/offspring; (2) Paquette et al 9 showed that paternal inheritance of the HeFH mutation in 725 genetically-confirmed patients was associated with a paradoxical 1.5-fold increased risk for ASCVD events as compared to maternal inheritance. The great number of environmental factors involved in the prevalence of ASCVD may explain these heterogeneous results.…”

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confidence: 99%

“…(2) Paquette et al 9 showed that paternal inheritance of the HeFH mutation in 725 genetically-confirmed patients was associated with a paradoxical 1.5-fold increased risk for ASCVD events as compared to maternal inheritance. The great number of environmental factors involved in the prevalence of ASCVD may explain these heterogeneous results.…”

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confidence: 99%

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Maternal Inheritance of Familial Hypercholesterolemia Gene Mutation Predisposes to Coronary Atherosclerosis as Assessed by Calcium Score in Adulthood

Mourre

Giorgi

Boccara

et al. 2023

ATVB

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Background: Animal studies have demonstrated that fetal exposure to high maternal cholesterol levels during pregnancy predisposes to aortic atheroma in the offspring. In humans, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease later in life. We wanted to assess whether maternal/paternal inheritance of familial hypercholesterolemia (FH) gene mutation could be associated with subclinical coronary atherosclerosis. Methods: We retrospectively included 1350 patients, followed in the French registry of FH, with a documented genetic diagnosis. We selected 556 age- and sex-matched pair of patients based on the sex of the parents who transmitted the FH gene mutation, free of coronary cardiovascular event, and with a subclinical coronary atherosclerosis evaluation assessed using coronary artery calcium (CAC) score. We performed univariate and multivariate analysis to assess the individual effect of parental inheritance of the FH gene mutation on the CAC score. Results: In the whole population, patients with maternal inheritance of FH gene mutation (n=639) less frequently had a family history of premature cardiovascular events (27.7% versus 45%, P <0.0001) and were 2 years older (46.9±16.8 versus 44.7±15.9 years old, P =0.02) than those with paternal inheritance (n=711). There was no difference in the prevalence of cardiovascular events between the two groups. In the matched subgroup, maternal inheritance was significantly associated with an increase in CAC score value by 86% (95% CI, 23%–170%; P =0.003), a 1.81-fold risk of having a CAC score ≥100 Agatston units (95% CI, 1.06–3.11; P =0.03), and a 2.72-fold risk of having a CAC score ≥400 Agatston units (95% CI, 1.39–5.51; P =0.004) when compared with paternal inheritance in multivariate analysis. Conclusions: Maternal inheritance of FH gene mutation was associated with more severe subclinical coronary atherosclerosis assessed by CAC score and may be considered as a potential cardiovascular risk factor.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Maternal Inheritance of Familial Hypercholesterolemia Gene Mutation Predisposes to Coronary Atherosclerosis as Assessed by Calcium Score in Adulthood

Mourre

Giorgi

Boccara

et al. 2023

ATVB

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“…On the other hand, a significant association between maternal inheritance and increased coronary artery calcium scores was observed in 1350 French patients, but no difference in prevalence of cardiovascular events [ 48 ▪ ]. Surprisingly, a Canadian study found a younger age at first event and a 1.5-fold increased risk of ASCVD adjusted for confounders with paternal inheritance compared to maternal inheritance [ 49 ]. More studies in FH are needed to elucidate the contradictory findings regarding inheritance pattern and lipid levels and cardiovascular outcomes.…”

Section: Dyslipidemia During Pregnancy: Consequences For the Offspringmentioning

confidence: 99%

Lipid metabolism during pregnancy: consequences for mother and child

Mulder,

Kusters,

Roeters van Lennep

et al. 2024

Current Opinion in Lipidology

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Purpose of review Accommodating fetal growth and development, women undergo multiple physiological changes during pregnancy. In recent years, several studies contributed to the accumulating evidence about the impact of gestational hyperlipidemia on cardiovascular risk for mother and child. This review aims to provide a comprehensive overview of the current research on lipid profile alterations during pregnancy and its associated (cardiovascular) outcomes for mother and child from a clinical perspective. Recent findings In a normal pregnancy, total and LDL-cholesterol levels increase by approximately 30–50%, HDL-cholesterol by 20–40%, and triglycerides by 50–100%. In some women, for example, with familial hypercholesterolemia (FH), a more atherogenic lipid profile is observed. Dyslipidemia during pregnancy is found to be associated with adverse (cardiovascular) outcomes for the mother (e.g. preeclampsia, gestational diabetes, metabolic syndrome, unfavorable lipid profile) and for the child (e.g. preterm birth, large for gestational age, preatherosclerotic lesions, unfavorable lipid profile). Summary The lipid profile of women during pregnancy provides a unique window of opportunity into the potential future cardiovascular risk for mother and child. Better knowledge about adverse outcomes and specific risk groups could lead to better risk assessment and earlier cardiovascular prevention. Future research should investigate implementation of gestational screening possibilities. Graphical_abstract http://links.lww.com/COL/A29

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“…Indeed, some studies have reported that CVD risk depends on the sex of the hypercholesterolemic parent. Surprisingly, a recent study suggested that, in genetically confirmed ADH kindreds, paternal inheritance of the ADH-causing mutation ( n = 321) decreases the time onset of a cardiovascular event compared with maternal inheritance ( n = 268) [ 151 ]. However, not all studies have found this association.…”

Section: Other Causes Of High Plasma Ldl Cholesterol Levelsmentioning

confidence: 99%

Genetic Determinants of Plasma Low-Density Lipoprotein Cholesterol Levels: Monogenicity, Polygenicity, and “Missing” Heritability

Martín‐Campos

2021

Biomedicines

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Changes in plasma low-density lipoprotein cholesterol (LDL-c) levels relate to a high risk of developing some common and complex diseases. LDL-c, as a quantitative trait, is multifactorial and depends on both genetic and environmental factors. In the pregenomic age, targeted genes were used to detect genetic factors in both hyper- and hypolipidemias, but this approach only explained extreme cases in the population distribution. Subsequently, the genetic basis of the less severe and most common dyslipidemias remained unknown. In the genomic age, performing whole-exome sequencing in families with extreme plasma LDL-c values identified some new candidate genes, but it is unlikely that such genes can explain the majority of inexplicable cases. Genome-wide association studies (GWASs) have identified several single-nucleotide variants (SNVs) associated with plasma LDL-c, introducing the idea of a polygenic origin. Polygenic risk scores (PRSs), including LDL-c-raising alleles, were developed to measure the contribution of the accumulation of small-effect variants to plasma LDL-c. This paper discusses other possibilities for unexplained dyslipidemias associated with LDL-c, such as mosaicism, maternal effect, and induced epigenetic changes. Future studies should consider gene–gene and gene–environment interactions and the development of integrated information about disease-driving networks, including phenotypes, genotypes, transcription, proteins, metabolites, and epigenetics.

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Paternal inheritance predicts earlier cardiovascular event onset in patients with familial hypercholesterolemia

Cited by 9 publications

References 24 publications

Maternal Inheritance of Familial Hypercholesterolemia Gene Mutation Predisposes to Coronary Atherosclerosis as Assessed by Calcium Score in Adulthood

Maternal Inheritance of Familial Hypercholesterolemia Gene Mutation Predisposes to Coronary Atherosclerosis as Assessed by Calcium Score in Adulthood

Lipid metabolism during pregnancy: consequences for mother and child

Genetic Determinants of Plasma Low-Density Lipoprotein Cholesterol Levels: Monogenicity, Polygenicity, and “Missing” Heritability

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