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NEW YORK (Reuters Health) – Globally, familial hypercholesterolemia (FH) is diagnosed late, and control of LDL cholesterol in patients is far below recommendations, acetazolamide for open angle glaucoma a new analysis shows.

“Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy,” Dr. Antonio J. Vallejo-Vaz of Imperial College London and colleagues in the European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC), write in The Lancet.

“Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier,” they add. “Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia.”

The researchers performed a cross-sectional analysis of registry data from more than 42,000 adults from 56 countries who were diagnosed with probable or definitive heterozygous FH.

Three-quarters were diagnosed with the Dutch Lipid Clinic Network criteria, 84% were in the Europe World Health Organization (WHO) region. At diagnosis, the median age was 44 years, and at entry into the registry, 46.

The prevalence of cardiovascular risk factors increased with age and varied by WHO region. The prevalence of coronary disease was 17% (2% stroke and 5% peripheral artery disease). It increased with concentrations of untreated LDL cholesterol and was roughly two times lower in women than in men.

Among patients receiving lipid-lowering medications, 16,803 (81%) received statins and 3,691 (21%) received combination therapy. In general, men were prescribed more-potent lipid-lowering medication than were women.

In patients not taking lipid-lowering medications, median LDL cholesterol was 5.43 mmol/L, compared to 4.23 mmol/L among those taking the medications. Only 2.7% of patients taking lipid-lowering medications had LDL-cholesterol levels of less than 1.8 mmol/L, the target recommended by most guidelines.

Receiving combination therapy, especially with three drugs and with PCSK9 inhibitors, was linked with significantly greater odds of having LDL cholesterol of less than 1.8 mmol/L.

Compared with index patients (that is, the first documented FH case in a family), non-index patients (relatives identified through screening) were younger. They also had lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all P<0.001).

Excluding the Netherlands, Europe showed higher prevalence of hypertension, and the Eastern Mediterranean region had higher prevalence of diabetes and higher BMI. In comparison, the Dutch cohort showed lower prevalence of these cardiovascular risk factors.

“It was important to do this study to understand the current state of affairs in familial hypercholesterolemia identification and treatment, and to create a collaborative platform to enable future progress,” said Dr. Seth S. Martin, an associate professor of medicine and the director of the Advanced Lipid Disorders Program at Johns Hopkins Medicine in Baltimore, Maryland.

“A major strength of this study is its global nature, with participation of 56 countries,” Dr. Martin, who was not involved in the study, told Reuters Health by email. “This allowed for a unique view of familial hypercholesterolemia detection and care around the world and the ability to better understand differences between countries.”

The authors of a linked editorial write, “Additional research is needed to assess the burden of familial hypercholesterolaemia in countries by income status, to better characterise and resolve care disparities for women and under-represented communities, and to test strategies towards a more personalised and universally accessible treatment.”

“Nevertheless, this initial FHSC report is a clear call for more effective implementation of WHO recommendations,” add Dr. Marina Cuchel of the Perelman School of Medicine of the University of Pennsylvania, in Philadelphia, and Dr. Mary P. McGowan of the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.

Dr. Vallejo-Vaz did not respond to requests for comment.

Pfizer, Amgen, Merck Sharp and Dohme, Sanofi-Aventis, Daiichi Sankyo and Regeneron funded the study.

SOURCES: https://bit.ly/3lZqUIt and https://bit.ly/3ERDW3r The Lancet, online September 7, 2021.

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