US physician practices for diagnosing familial hypercholesterolemia: data from the CASCADE-FH registry

Abstract

Background In the US familial hypercholesterolemia (FH), patients are underidentified, despite an estimated prevalence of 1:200 to 1:500. Criteria to identify FH patients include Simon Broome, Dutch Lipid Clinic Network (DLCN), or Make Early Diagnosis to Prevent Early Deaths (MEDPED). The use of these criteria in US clinical practices remains unclear. Objective To characterize the FH diagnostic criteria applied by US lipid specialists participating in the FH Foundation's CASCADE FH (CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia) patient registry. Methods We performed an observational, cross-sectional analysis of diagnostic criteria chosen for each adult patient, both overall and by baseline patient characteristics, at 15 clinical sites that had contributed data to the registry as of September 8, 2015. A sample of 1867 FH adults was analyzed. The median age at FH diagnosis was 50 years, and the median pretreatment low-density lipoprotein cholesterol (LDL-C) value was 238 mg/dL. The main outcome was the diagnostic criteria chosen. Diagnostic criteria were divided into five nonexclusive categories: “clinical diagnosis,” MEDPED, Simon Broome, DLCN, and other. Results Most adults enrolled in CASCADE FH (55.0%) received a “clinical diagnosis.” The most commonly used formal criteria was Simon–Broome only (21%), followed by multiple diagnostic criteria (16%), MEDPED only (7%), DLCN only (1%), and other (0.5%), P < .0001. Of the patients with only a “clinical diagnosis,” 93% would have met criteria for Simon Broome, DLCN, or MEDPED based on the data available in the registry. Conclusions Our findings demonstrate heterogeneity in the application of FH diagnostic criteria in the United States. A nationwide consensus definition may lead to better identification, earlier treatment, and ultimately CHD prevention.

Detection of familial hypercholesterolemia in patients from a general practice database

“…This means that GPs have a great diagnostic potential [14,15]: the high number of contacts with most of the population assisted by the GP in a few years allows a systematic and effective approach to this problem, simply applying what is already recommended by the guidelines as normal good clinical practice.…”

“…Given the hereditary transmission of the disease, the cascade screening of relatives should follow the identification of an affected person (index patient) [14,20]. In fact, it is important to underline that, in most cases, the GP has to manage an entire family unit, so that effective communication with all family members is a key point to make patients more conscious of their condition, in order to encourage changes in lifestyle and improve adherence to drug treatment.…”

Heterozygous Null LDLR Mutation in a Familial Hypercholesterolemia Patient With an Atypical Presentation Because of Alcohol Abuse

“…In a US registry of FH patients (mostly diagnosed clinically without genetic confirmation), the median (IQR) plasma triglyceride level was 116 mg/dL (82–170, n = 1867). 10 Furthermore, patients with mutation-confirmed FH – like our patient – have slightly lower triglycerides than mutation-negative FH patients: in a Spanish population of FH patients, the median (IQR) triglyceride level was 97 (68–139, n = 459) in those with LDLR or APOB mutations while the median (IQR) triglyceride level was 122 mg/dL (n = 366, range of 86–189 mg/dL) in those without an identifiable mutation. 11 …”

Genetic Testing Preferences and Intentions in U.S. Patients with Clinically Diagnosed Familial Hypercholesterolemia

“…The underlying genetic etiology of FH is well-described, such that an estimated 60-80% of individuals clinically diagnosed with autosomal dominant FH carry a pathogenic variant in LDLR, APOB or PCSK9 4 . There has been low awareness and recognition of FH as a Mendelian cause for high cholesterol in the US 5 . FH remains severely underdiagnosed in the US with only up to approximately 10% of affected individuals identified 4 .…”

“…Nevertheless, in the US, very few patients diagnosed with FH have had genetic testing 5 . The reasons for the low uptake of genetic testing in this population have not been systematically explored.…”