Sex differences in cholesterol levels from birth to 19 years of age may lead to increased cholesterol burden in females with FH

Holven, Kirsten B.; Narverud, Ingunn; Lennep, Jeanine Roeters van; Versmissen, Jorie; Øyri, Linn Kristin Lie; Galema‐Boers, Annette M.H.; Langslet, Gisle; Ulven, Stine Marie; Veierød, Marit B.; Retterstøl, Kjetil; Bogsrud, Martin P.

doi:10.1016/j.jacl.2018.02.021

Cited by 25 publications

(14 citation statements)

References 31 publications

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“…Other sex differences may also contribute. For example, across childhood and adolescence, untreated girls with FH demonstrate consistently higher LDL-C levels than untreated boys, 11 and adult women with FH may be undertreated compared with men. 12 We observed patterns in MVP consistent with these prior findings, but additional studies are needed to better understand sex differences while accounting for several potential confounders.…”

Section: Discussionmentioning

confidence: 99%

Coronary Artery Disease Risk of Familial Hypercholesterolemia Genetic Variants Independent of Clinically Observed Longitudinal Cholesterol Exposure

Clarke

Tcheandjieu

Hilliard

et al. 2022

Circ: Genomic and Precision Medicine

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Background: Familial hypercholesterolemia (FH) genetic variants confer risk for coronary artery disease independent of LDL-C (low-density lipoprotein cholesterol) when considering a single measurement. In real clinical settings, longitudinal LDL-C data are often available through the electronic health record. It is unknown whether genetic testing for FH variants provides additional risk-stratifying information once longitudinal LDL-C is considered. Methods: We used the extensive electronic health record data available through the Million Veteran Program to conduct a nested case-control study. The primary outcome was coronary artery disease, derived from electronic health record codes for acute myocardial infarction and coronary revascularization. Incidence density sampling was used to match case/control exposure windows, defined by the date of the first LDL-C measurement to the date of the first coronary artery disease code of the index case. Adjustments for the first, maximum, or mean LDL-C were analyzed. FH variants in LDLR , APOB , and PCSK9 were assessed by custom genotype array. Results: In a cohort of 23 091 predominantly prevalent cases at enrollment and 230 910 matched controls, FH variant carriers had an increased risk for coronary artery disease (odds ratio [OR], 1.53 [95% CI, 1.24–1.89]). Adjusting for mean LDL-C led to the greatest attenuation of the risk estimate, but significant risk remained (odds ratio, 1.33 [95% CI, 1.08–1.64]). The degree of attenuation was not affected by the number and the spread of LDL-C measures available. Conclusions: The risk associated with carrying an FH variant cannot be fully captured by the LDL-C data available in the electronic health record, even when considering multiple LDL-C measurements spanning more than a decade.

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Section: Discussionmentioning

confidence: 99%

Coronary Artery Disease Risk of Familial Hypercholesterolemia Genetic Variants Independent of Clinically Observed Longitudinal Cholesterol Exposure

Clarke

Tcheandjieu

Hilliard

et al. 2022

Circ: Genomic and Precision Medicine

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“…While women typically develop CVD at a later age than men, the risk of CVD is often underestimated in women due to the misperception that females are ‘protected’ against CVD before the menopause [ 18 ]. While premenopausal women have a less pro-atherogenic plasma lipid profile than men, specifically greater high-density lipoprotein (HDL) and lower LDL-cholesterol than men of the same age [ 19 ], a study of children and adolescents with untreated FH suggests that the cholesterol burden with untreated FH is significantly higher in girls than boys [ 20 ]. These factors are likely to contribute to the greater excess CVD burden in women with FH compared to women without FH.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in cardiovascular morbidity associated with familial hypercholesterolaemia: A retrospective cohort study of the UK Simon Broome register linked to national hospital records

et al. 2020

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Background and aims: The UK Simon Broome (SB) familial hypercholesterolaemia (FH) register previously reported 3-fold higher standardised mortality ratio for cardiovascular disease (CVD) in women compared to men from 2009 to 2015. Here we examined sex differences in CVD morbidity in FH by national linkage of the SB register with Hospital Episode Statistics (HES). Methods: Of 3553 FH individuals in the SB register (aged 20-79 years at registration), 2988 (52.5% women) had linked HES records. Standardised Morbidity Ratios (SMbR) compared to an age and sex-matched UK general practice population were calculated [95% confidence intervals] for first CVD hospitalisation in HES (a composite of coronary heart disease (CHD), myocardial infarction (MI), stable or unstable angina, stroke, TIA, peripheral vascular disease (PVD), heart failure, coronary revascularisation interventions). Results: At registration, men had significantly (p < 0.001) higher prevalence of previous CHD (24.8% vs 17.6%), previous MI (13.2% vs 6.3%), and were commenced on lipid-lowering treatment at a younger age than women (37.5 years vs 42.3 years). The SMbR for composite CVD was 6.83 (6.33-7.37) in men and 7.55 (6.99-8.15) in women. In individuals aged 30-50 years, SMbR in women was 50% higher than in men (15.

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“…39 In line with other cross-sectional studies, we show that lipid distributions change with age. 17,18,40,41 When studying adolescents around 11-16 year of age with a pronounced fall in cholesterol levels (see Fig. 1), the use of a fixed LDL-c level for a diagnosis of FH can easily result in a misdiagnosis.…”

Section: Importance Of Lipid Reference Values In Clinical Practicementioning

confidence: 99%

Pediatric lipid reference values in the general population: The Dutch lifelines cohort study

Balder

Lansberg

Hof

et al. 2018

Journal of Clinical Lipidology

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Sex differences in cholesterol levels from birth to 19 years of age may lead to increased cholesterol burden in females with FH

Abstract: FH girls have higher levels of TC, LDL-C, and non-HDL-C levels than boys from birth up to 19 years of age. This may contribute significantly to the total lifelong cholesterol burden in FH women.

Cited by 25 publications

References 31 publications

Coronary Artery Disease Risk of Familial Hypercholesterolemia Genetic Variants Independent of Clinically Observed Longitudinal Cholesterol Exposure

Coronary Artery Disease Risk of Familial Hypercholesterolemia Genetic Variants Independent of Clinically Observed Longitudinal Cholesterol Exposure

Sex differences in cardiovascular morbidity associated with familial hypercholesterolaemia: A retrospective cohort study of the UK Simon Broome register linked to national hospital records

Pediatric lipid reference values in the general population: The Dutch lifelines cohort study

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