Three cases first:
A young woman I met recently (outside the hospital) told me her Dad died suddenly a couple of years ago. He was fine, then he was stone cold dead. The wife went outside for a minute and came back to find her husband dead in the chair. There were no warnings. No chest pains, no breathing problems, and no real diseases, except well-controlled high blood pressure.
A middle-aged man came to see me in the office because his brother died suddenly while jogging. The patient wanted to know his risk of heart disease and what he could do to prevent premature death. Both my patient and his dead brother were in decent shape.
Finally, a well-educated patient, who did not have heart disease, asked me about the decision to take statins. His primary care doctor recommended the drug based on his cholesterol level plus his age. This man had read the studies showing only modest benefits for statins in primary prevention.
*****
Gene Risk Scores
My most recent column over at theHeart.org | Medscape Cardiology delves into the use of genetic data to help predict heart disease.
I know; writing and reading about genetics is akin to eating broccoli instead of pizza. Give me leeway for a minute or so, this is nifty stuff. I learned bunches.
First some background: We now know there are many gene locations on our chromosomes that associate with coronary artery disease. At these areas are many single nucleotide changes, called SNPs, or single nucleotide polymorphisms, that may individually or together influence the risk of getting heart disease. SNPs sound tricky but really they are just a single substitutions of say an A for T or G for a C in the DNA.
In recent years, researchers have been able to cull these many SNPs into a composite score, called a GRS, or gene risk score. Companies like 23andMe used to report gene risk scores for heart disease but the FDA asked them to stop. (That’s probably coming back soon.)
My point is that these gene scores are not pie-in-the-sky stuff.
Now to the compelling evidence. In the Medscape Cardiology column (you need to give your email to read), I review the numerous studies of using gene risk scores to predict heart disease. It can be summarized into five main points:
- Gene risk scores are not just a fancy family history. The score predicted heart disease independently of self-reported family history. The obvious weakness of a self-reported family history is that people live different lives from their parents.
- Gene risk scores can predict different trajectories of heart disease risk. If you plot survival curves of low genetic risk versus high genetic risk people, the people with high risk scores get heart disease at a younger age.
- Genetics may help pinpoint those individuals who may benefit most from statins. I cited multiple studies showing that individuals with high genetic risk garnered much greater risk reduction from statins than did those with low genetic risk. This is really cool. The researchers actually used blood from patients in the randomized controlled trials for statins to show these gradients of benefits.
- Gene risk scores may influence people to change behavior. I also cited studies showing that people with high genetic risk who pursue healthy behaviors can reduce the chance of a future event.
- Gene risk scores have advantages over imaging tests such as coronary artery calcium. For one, CAC depends on age. Gene scores can identify young people at risk. Another advantage is that gene scores are a simple blood test rather than a scan.
I hope you read my column on theheart.org | Medscape Cardiology: Who Needs a Statin? DNA Beats Current Risk Calculators. The reference list of studies is there.
In the column, I cite work that Dr. Eric Topol and colleagues from Scripps are doing. They are in beta-development of a free-mobile app that takes a person’s 23andMe data and churns out a risk score on your phone. It’s called MyGeneRank.
Your doctor can’t easily order gene risk scores now. Insurance doesn’t cover them. But the tests are not too expensive. My prediction is that soon enough, knowing your gene risk scores will be like knowing your LDL–only the gene data will be far more useful.
JMM
P.S. I needed a lot of help to learn this stuff. Dr Pradeep Natarajan of Harvard deserves a shout out for taking the time to explain much of this to me. You can follow him and his mentor Dr. Sek Kathiresan on Twitter.
Dr. Eric Topol, who is editor-in-chief of Medscape, a famous cardiologist and now genomics researcher also helped me learn this material.