When assistant professor Joshua Knowles, MD, PhD (cardiovascular medicine), identifies a patient with familial hypercholesterolemia, that discovery marks the beginning of a hunt. Even as the new patient undergoes treatment to reduce levels of low-density lipoprotein cholesterol (LDL-C) and stave off early atherosclerotic cardiovascular disease, a search gets underway for family members who might unknowingly be harboring the same disorder. First in this family-based cascade screening are the proband’s closest relatives – parents, siblings, children – followed by screening of the closest relatives of any in that group who are positively identified and then by screening of the closest relatives of any in that group who have the disease.  

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease that occurs in approximately 1 in 250 persons. Those who have FH exhibit very high levels of LDL-C even as children and have a very high (2.5 to 10 times increased) risk of cardiovascular disease. The existence of new therapies that promise to control LDL-C and reduce its attendant risks by about 80 percent increases the urgency to identify patients who are unaware that they have FH.

In a recent publication in the Journal of the American Medical Association (2017;318:381-2), Knowles and his colleagues describe how they trace the disease throughout a family once they have identified a case. Finding new patients in a family requires cholesterol testing or genetic testing or both.

Electronic health records (EHR) are another means of identifying FH patients by searching for a specific ICD-10 code and a family history of FH. Researchers anticipate that they will soon be able to apply algorithms to EHR, laboratory, and billing code data or large-scale DNA sequencing to identify patients as well.

The authors note that the techniques they employ to identify new cases of FH are not without limitations beyond the medical condition. Concerns include the privacy of patients, their ability to purchase life or disability insurance, as well as the current high cost of genetic testing.

Medical journals have recently begun reporting a measurement of the “buzz” surrounding the articles they publish. For the FH article by Knowles et al., that measurement, the Attention Score, achieved a level of 129, which puts it “in the top 5% of all research outputs ever tracked by Altmetric”; it indicates how frequently readers shared, cited, reported in the media, and tweeted about it. As a vehicle for raising awareness about a serious medical condition among physicians who might not encounter a case very often, if ever, the article was a winner. For the estimated 90 percent of US patients with FH who are unaware that they have the disease, the odds that they may yet be diagnosed just improved.

Knowles’s coauthors were Daniel J. Rader, MD, of the University of Pennsylvania, and Muin J. Khoury, MD, PhD, of the Centers for Disease Control and Prevention.