In a recent study published in The Lancet, researchers attempted to evaluate the clinical and genetic characteristics, as well as the global impact, of current practice on health outcomes of the rare, inherited disorder known as HoFH. According to results, researchers indicated that HoFH is often undertreated—especially in lower income countries—and is sometimes diagnosed after atherosclerosis or aortic stenosis is already present.

To obtain a better understanding of the characteristics of HoFH, as well as its clinical diagnosis and outcomes, researchers utilized the HoFH International Clinical Collaborators registry to identify 751 patients from 38 countries with HoFH. Within this cohort, 75% had biallelic pathogenic variants of HoFH. The researchers collected data on patients with either a clinical, genetic, or a clinical and genetic diagnosis of HoFH.

The researchers found that 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. Of the 751 patients, the average age of diagnosis was 12 years (interquartile range [IQR] 5.5-27.0 years), 389 (52%) were female, and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were Caucasian, 121 (23%) were Asian, and 68 (13%) were African American or mixed race.

The major manifestations of atherosclerotic cardiovascular disease (ASCVD) or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol (LDL-C)levels were 14.7 mmol/L (IQR 11.6-18.4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 patients received ezetimibe, and 243 (39%) of 621 patients received lipoprotein apheresis. On-treatment LDL-C levels were lower in high-income countries (3.93 mmol/L, IQR 2.6-5.8) versus lower income countries (9.3 mmol/L, 6.7-12.7), with greater use of three or more lipid-lowering therapies ([LLT]; 66% vs. 24%, respectively), and consequently more patients reaching guideline-recommended LDL-C goals (21% vs. 3%, respectively). A first major adverse cardiovascular event occurred a decade earlier in lower income countries, at an average age of 24.5 years (IQR 17.0-34.5) versus 37.0 years (29.0-49.0) in high-income countries (adjusted hazard ratio 1.64, 95% CI 1.13-2.38).

The authors concluded that globally, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. They also noted that greater usage of multi-LLT regimens is correlated with lower LDL-C levels and better outcomes, observing that significant global disparities exist in treatment regimens, control of LDL-C levels, and cardiovascular event-free survival, which warrants a critical reassessment of global health policy to diminish inequalities and enhance outcomes for all patients with HoFH.

In a statement on the Healio News website, Marina Cuchel, MD, PhD, research associate professor of medicine at the University of Pennsylvania Perelman School of Medicine, stated, "I hope that this study will help increase the awareness of this condition in both physicians and policymakers, so that country-specific strategies can be widely and systematically implemented for the early identifications of these patients and for appropriate and equitable access to effective medications when needed."

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