Women With Heterozygous FH Less Likely to Receive Treatment

Liam Davenport

October 19, 2020

There are gender differences among patients with heterozygous familial hypercholesterolemia (HeFH) in terms of when the disease is diagnosed, how it is treated, and the levels of low-density lipoprotein (LDL) cholesterol attained, suggest data from a large multinational registry.

Moreover, less than 40% of children with HeFH are receiving lipid-lowering medication, and those who are typically have LDL cholesterol levels similar to untreated children.

The research was presented at the European Atherosclerosis Society 2020 Virtual Congress on October 6, held online this year due to the COVID-19 pandemic.

For the first analysis, researchers looked at data from the European Atherosclerosis Society (EAS) Familial Hypercholesterolemia Studies Collaboration (FHSC) Global Registry, which includes almost 17,000 men and 20,000 women with probable or confirmed HeFH.

Lead author Antonio J. Vallejo-Vaz, PhD, EAS FHSC Coordinating Centre, Imperial College London, England, said that the data show "there are differences in FH characteristics and management by gender."

"Despite being an inherited condition, FH is identified late, with women being identified slightly later than men, and presenting with slightly higher LDL cholesterol."

He noted that there are also gender differences in the prevalence of cardiovascular (CV) risk factors and disease, with women having approximately half the prevalence of coronary artery disease (CAD) than that of men.

"LDL cholesterol goal attainment is low at the time of registry entry in both genders, with women less frequently on goal and on intensification of therapy," Vallejo-Vaz added.

He therefore called for "greater attention on the early identification and management of FH," and that addresses the differences between men and women.

In a separate analysis, Kanika Dharmayat, MPH, also from the EAS FHSC Coordinating Centre, and colleagues looked at data on almost 8000 children with HeFH, finding that less than 40% were being treated with lipid-lowering medications, and only around 10% were receiving statins.

She also noted that "untreated LDL cholesterol levels in children are lower on average than adults, and this could have implications for LDL cholesterol levels that trigger an FH clinical diagnosis and/or subsequent genetic testing."

Dharmayat highlighted that, even when treated, there was no change in LDL cholesterol levels among children aged less than 9 years, which "could be due to under treatment, as suggested by the limited proportion of children receiving lipid-lowering medications and...the small proportion receiving statins."

Mary P. McGowan, MD, chief medical officer at the The FH Foundation, Pasadena, California, told theheart.org | Medscape Cardiology that the gender differences seen in adults are "very consistent" with the data they have published from their US database.

She said that "women are less aggressively treated" than men, but on the other hand "women do have fewer risk factors, so there's a lot to tease out. Are they less aggressively treated because they're viewed as being somewhat less at risk?"

McGowan noted, however, that "the treatment is not great for either men or women, or children, and it just shows that FH needs to be recognized more commonly and needs to be treated more aggressively."

Turning to the data in children, she pointed out that "in Europe in general, FH is diagnosed more genetically than it is clinically, and I think that's certainly well documented in the United States [that] we don't do as many genetic tests."

She added that it is "interesting and disappointing that kids are not readily treated with statins. The guidelines in both Europe and in the United States are very clear that statins should be initiated...not that people are following them."

McGowan believes that it is clear from the data that physicians "are looking at pediatric lipids through the lens of adult dyslipidemia, and we should be thinking about FH in children with LDL cholesterol levels greater than 160 md/dL versus with adults greater than 190 mg/dL."

Lifelong LDL Elevation

Vallejo-Vaz began his presentation by noting that FH affects approximately 1-in-3000 individuals and causes in lifelong elevation of LDL cholesterol levels that result in premature atherosclerotic CV disease.

While there is a need to address the condition on a worldwide basis to improve diagnosis, treatment, family screening, and education, he noted that a lack of integrated approach has limited the impact of the various initiatives undertaken so far.

The EAS FHSC Global Registry was established to harmonize and pool global knowledge by bringing together regional and national data from cohorts, registries, and databases containing individuals with FH.

The researchers included patients with a clinical and/or genetic diagnosis of heterozygous or homozygous FH and the non-FH relatives of index cases. From a network of investigators in 68 countries, they had received, by September 2020, data on more than 62,500 individuals from 63 countries.

The aim of the current analysis was to examine disparities between men and women in terms of FH detection and management, and the impact of LDL cholesterol on CV risk reduction.

The team selected 36,835 adults with a probable or definite diagnosis of HeFH, which included 16,890 (45.8%) men and 19,945 (54.2%) women.

They found that women were older on average at baseline, at 48.1 years vs 45.2 years for men (P < .01), and had an older age at HeFH diagnosis, at 46.0 years vs 43.5 years (P < .01).

While the prevalence of diabetes, stroke, and peripheral artery disease was similar between women and men, women were more likely to have hypertension, at 19.1% vs 17.2% for men (P < .001).

They were, however, less likely to have CAD, at 12.4% vs 21.5% for men (P < .001), and premature CAD, at 7.0% vs 14.6% for men (P < .001).

Women were also less likely to smoke than men (20.4% vs 28.4%; P < .001), and were less likely to have a body mass index of at least 25 kg/m2 (46.2% vs 56.9%; P < .001).

Women were less likely than men to be taking lipid-lowering medication at baseline, at 58.4% vs 61.1% (P < .01), and less likely to be on combination therapy, at 19.9% vs 22.7% (P < .01).

Statins were used to a similar extent in both men and women. However, ezetimibe (Nustendi) was less frequently used by women, at 23.4% vs 25.9% among men (P < .01).

Perhaps unsurprisingly, women were less likely to achieve an LDL cholesterol level < 100 mg/dL than men, at 12.7% vs 14.6% (P < .01).

Vallejo-Vaz also presented data on index vs non-index cases of CV disease, showing that, in both genders, the prevalence of CAD, premature CAD, and peripheral artery disease was markedly lower in non-index cases.

He said that this underlines "the need for earlier screening" for HeFH, "and this is consistent for both genders."

Lipid Lowering in Children With FH

For the second study, Dharmayat presented data on 7982 children from the EAS FHSC Global Registry, including 4235 aged over 9 years.

She said that the diagnosis was made using the Dutch Lipid Clinic Network (DLCN) criteria in 80% of cases, and over 90% had a genetic test, which revealed a variant in the LDL receptor gene.

Among children aged 9 years or younger, 38.9% were receiving lipid-lowering medications, with 5.6% taking statins, while 35.9% of older children were taking such medications, with 12.4% receiving statins.

LDL cholesterol levels were, overall, similar between children aged up to 9 years and older children, at a median of 176.7 mg/dL (95% CI, 143.1 - 218.1) and 174.0 mg/dL (95% CI, 137.0 - 215.0).

Among children aged up to 9 years, there was almost no difference in LDL cholesterol levels between those receiving lipid-lowering medications and those not.

A small difference emerged among older children, however, with use of the medications associated with lower lipid levels.

Another notable aspect of the EAS FHSC Global Registry is that approximately 90% of the children were from Europe.

Dharmayat said that there is "a lack of data from other regions, despite FH affecting all regions and ethnicities," which "suggests an unmet need."

No funding was declared. Vallejo-Vaz disclosed honoraria from Amgen, Mylan, Akcea; consultancy fees from Bayer;  and research grants (inst.) from Pfizer, Amgen, MSD, Sanofi, Regeneron, Daiichi-Sankyo.

European Atherosclerosis Society 2020 Virtual Congress: Characteristics of Adults with Heterozygous Familial Hypercholesterolaemia stratified by gender, presented October 6, 2020; Abstract P1110, presented October 5, 2020.

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