I “I’m 31. How on earth did this happen?” My older brother Bryan sat up; his eyes were dazed after a restless night in the hospital. As Bryan lifted his arm to scratch his head, I could see the bruising on his wrist from the cardiac catheter. “I feel so much better,” he said. He showed me the path the balloon catheter took to a pair of coronary arteries that were 99 and 100 percent blocked, respectively. His cheerful disposition was slightly feigned. He was scared and confused. Until the previous day, no one knew — not even his primary care physician — that my brother had been making his way to a heart attack. A previously healthy 31-year-old with symptoms of an impending heart attack was unexpected. The typical risk factors for coronary artery disease, more common in people over age 65, weren’t there. However, there was one crucial risk factor that would help explain how this happened — our family history.Nearly 20 years before Bryan’s stents were placed, our grandfather died relatively young from complications during open-heart surgery. I still remember the sadness and confusion in our family after his sudden death. A few uncles spent their early 40s and 50s dealing with multiple heart attacks, coronary stents, and bypass surgeries. Even before I started a career in genetic counseling, these familial patterns were striking and unnerving. As a college freshman, I learned that my cholesterol level was three times above normal, exacerbating my fears about familial patterns.My own research at that time led me to adopt a vegetarian diet and to learn about an inherited disease called familial hypercholesterolemia (FH). During my professional training, I learned that coronary artery disease was a complex trait with many genetic and environmental contributors. Our family history could be explained by multiple factors, which provided some relief. But without an affected first-degree relative, like a parent or sibling, I couldn’t diagnose myself with FH. Nevertheless, the possibility would linger for years.Despite knowing our family history, my personal risk felt somewhat distant and ambiguous. This changed when Bryan informed me of his angiogram results and severely elevated cholesterol levels. While flying on the red-eye to be with him, I kept thinking, “There is my affected first-degree relative. This has to be FH. We need genetic testing. I need to be on statins. The other siblings need to be screened.”
Despite knowing our family history, my personal risk felt somewhat distant and ambiguous. This changed when Bryan informed me of his angiogram results and severely elevated cholesterol levels.
During Bryan’s recovery I scheduled an appointment with a preventive cardiologist in a clinic dedicated to FH. We reviewed results of previous lipid panels, clearly showing that nine years of a vegetarian diet and decent physical activity had had little effect on my LDL, or “bad cholesterol.” It continued to be more than double what it should be.My colleagues and I analyzed my five-generation pedigree. We discussed the probable FH diagnosis; I started statin therapy. I had a blood sample drawn for genetic testing, analyzing four genes currently known to be associated with FH: LDLR, APOB, PCSK9, and LDLRAP1.FH is a common, under-recognized genetic disease, affecting as many as one in 250 people worldwide. It is caused by mutations in genes that regulate cholesterol metabolism. The most commonly affected gene is LDLR, which encodes the receptor that snags circulating LDL cholesterol from the blood for disposal via the liver. Mutations in these genes cause a reduced ability to adequately clear LDL cholesterol from the blood, leading to abnormally high levels of this “bad cholesterol.”This lifelong exposure to high LDL significantly increases the risk of coronary artery disease, heart attacks, and strokes at much younger ages. Untreated males with FH have a 50 percent chance of having a heart attack by age 50; women have a 30 percent chance of having a heart attack by age 60. And it is not unusual for FH to present even earlier in adulthood. If they inherit two mutations in these genes — the very rare recessive form of FH — even children and adolescents can be struck by dangerous cardiovascular events. Unfortunately for those of us with FH, diet and exercise have minimal impact on our LDL levels. We need pharmacologic therapy. Given FH’s severity and the possibility of preventing deadly heart problems, identifying people with FH is critical; this is why we need better public awareness of the disease.My genetic testing identified a mutation in the LDLR gene, confirming the FH diagnosis. Bryan was later found to have the same mutation. Over the past several months, my brother and I have discussed absolution, powerlessness, liberation, and empowerment — feelings that are not mutually exclusive in the face of life-threatening genetic disorders and life-altering diagnoses. It is liberating to know that lifestyle changes are expected to have little effect; our LDL levels were not the result of a lack of effort. Our empowerment grows as we become advocates for FH and face our “genetic destinies” together — as a family.I still fear for my heart health and future, but I know FH can be managed. Becoming a patient wasn’t expected, but it has invigorated me. It has changed the way I approach my work. It has made me an advocate. It has made genetics deeply personal. By Benjamin Helm