FIND FH, Starting at Stanford

In years gone by there was Where’s Waldo? Then there was Finding Nemo. Today, on a more serious note but important even to small children, there is FIND FH.

FH, or familial hypercholesterolemia, is a genetic predisposition to very high levels of LDL cholesterol (the bad cholesterol) that may first manifest itself as a fatal heart attack at a premature age. There are therapies, statin-based, that reliably improve outcomes for patients with FH. But there is a big problem: 90 out of 100 patients who have FH do not know they have it or perhaps even what it is. Many physicians are equally in the dark about the disease and therefore do not screen patients for it. FIND FH hopes to change all that.

In an ambitious tripartite campaign, an academic center (Stanford Medicine), a nonprofit advocacy group (the FH Foundation), and a pharmaceutical company (Amgen) seek to FIND (Flag, Identify, Network, Deliver) FH using computer-based algorithms to troll through large databases including electronic medical records and locate patients who likely have the disease. At Stanford, FIND FH is being led by Joshua W. Knowles, MD, PhD (assistant professor, cardiovascular medicine), Kenneth Mahaffey, MD (professor, cardiovascular medicine), and Nigam H. Shah, MBBS, PhD (assistant professor, biomedical informatics).

According to Knowles, “Our overall goal is to turn the tide on FH by increasing the diagnosis of this underappreciated, underdiagnosed, and undertreated condition, thereby preventing heart attacks and saving lives.”

FIND FH is financed by Amgen and by the American Heart Association through a National Innovative Research Award. The AHA describes the award’s objective as supporting “highly innovative, high-risk, high-reward research that could ultimately lead to critical discoveries or major advancements that will accelerate the field of cardiovascular and stroke research.”

There are estimated to be somewhere between 600,000 and 1,200,000 cases of FH in the United States alone; the worldwide number could be as high as 34,000,000. The goal of the FIND FH project is not only to identify patients with FH but also to engage them, educate them, and ultimately save them from premature death from an overabundance of cholesterol in their bodies.

The goals of the researchers involved in FIND FH are lofty. Starting with Stanford patients who have been diagnosed with FH, they will teach computers to find patterns in those patients’ medical records. For this part of the research, they will use medical informatics methods designed by Shah. “We will be using machine learning approaches to build a patient classifier to phenotype patients,” says Shah. “As an analogy, think of sorting email into spam or not spam: no one does it using rules any more; it's done using models built via machine learning.” 

The next step will be to let those computers loose on the medical records of current Stanford patients without a diagnosis of FH. Here the hope is that the algorithms the computers use will be accurate, thereby “flagging” undiagnosed but potential FH patients.  Then, through the patients’ designated healthcare provider, those patients will be contacted and evaluated for the most appropriate screening and therapy. Ultimately, the hope is that this will lead to screening of other potentially affected family members as each child of a parent with FH has a 50% chance of inheriting it as well.

Knowles, who in addition to his Stanford responsibilities also serves as chief medical advisor of the Familial Hypercholesterolemia Foundation, is also a principal architect of CASCADE FH, a national patient registry of FH patients designed to follow patients longitudinally with data entered both by physicians who treat patients with the disease and by the patients themselves.