(Don't) Be Still, My Beating Heart - Part 2

Heart Disease and why DNA matters

Genes involved in the function of our cardiovascular system differ, ranging from those involved in the structure of the heart, the shape and density of the muscle cells and connective tissues, and even the function of the cells involved in sending electrical signals to tell the heart to pump. Genes can even influence how much cholesterol our bodies create. (You read that right! Not all cholesterol comes from our food!).

Genetic research is helping us understand these cardiovascular genes better, but we still don’t know fully how every gene works or how every variant in a gene affects the way it functions.

Caveats pushed aside, DNA testing can help many people understand their risk of developing heart or blood vessel disease better. Or even understand what the underlying cause might be for a condition they have already developed. One example is DNA testing for the genes that are known to be involved in Familial Hypercholesterolemia (FH), a common and under-diagnosed cause of high cholesterol.

DNA testing can also help in understanding which medications might work better for one person over another. Pharmacogenomic testing for certain heart drugs called statins is becoming more commonly used to help prescribing doctors understand who might over- or under-react to certain medications.

Are these genes isolated to one person or is everyone in a family at risk?

Here’s where things get tricky! Some genes have a much stronger role and can act in isolation. Other genes have only mild effects on risk for cardiovascular issues.

Sometimes it matters which combination of genes you inherit, so your risk may differ from your mother, your father, and even your siblings and children.

On the other hand, some genes (and to be more specific, certain well-known changes in certain genes) can be seen to affect multiple people in a family in the same way. There are both new and established methods being used in assessing risk for heart disease, such as calculating polygenic risk scores for individuals based on testing a number of genes and single-variant cascade testing in a family where one strong genetic factor has already been found.

It’s hard to know what type of risk you are facing without knowing if there is one or multiple genetic factors you are dealing with and what type of environmental influences might also be at play. This is where I often call on my cardiovascular specialized friends in the world of genetic counseling to offer insight! More on that in part 3.

What to do with a third-party health report

I hear from many people who have taken a DIY approach to trying to figure out their risk for heart disease. Some have used third party tools like sequencing.com or Promethease. What I’ve found is that as a whole, the third party analysis tools that can dig deeper into a consumer DNA raw data file do not distinguish between the high risk, moderate risk, and low risk genes very well. Neither do they clearly explain these nuances.

This failure to distinguish between different levels of risk makes consumer reports less helpful in nearly all situations than a medical grade test report would be. You may see a finding on your report and read too much into it if it fits what you already believe about your risk for a heart condition. On the flip side, if you don’t see any concerning heart findings at the top of the report you may feel somewhat relieved, when it’s possible you have a high-risk gene variation that was not looked at by the consumer test.

The next step after you’ve found a possibly-concerning finding is to have it repeat-tested in a medical grade lab.

This is called confirmatory testing, and a genetic counselor like someone at Genome Medical is your friend in navigating the DNA testing system to have this done.

How family history helps

We try to include family history whenever possible in considering someone’s health risks. Many heart diseases are hereditary – meaning the risk to develop a heart or vascular issue has been passed down from parents to offspring.

We see some families have a very strong pattern of heart disease, matching a type of inheritance referred to as autosomal dominant in the world of medical genetics.

This means that both women and men can inherit the disorder and that only one copy (the dominant form) of a gene variant is necessary to cause disease rather than two (as seen in recessive disease). Only one gene is thought to be involved in these situations, rather than a collection of them.

Specialized testing has been developed for types of autosomal dominant cardiomyopathy (heart muscle disease) and sudden arrhythmia (irregular heart beat). This testing has been a major game-changer and has helped identify people who don’t yet show symptoms but are at high risk.

To test, or not to test, that is the question

Having a strong family history of heart attacks and other cardiovascular issues can be worrisome, as can not having any knowledge of your family history at all. But knowledge is power, and DNA testing has progressed to the point that it can help in many different situations. The results of DNA testing have helped prevent poor outcomes for some people at risk for cardiovascular issues by investigating and catching a problem BEFORE it has a chance to cause sudden death or cause problems that can’t be reversed. By understanding your risk of contracting heart disease as best you can, it may be possible to take preventative measures (such as heart monitoring or starting medication) to lower this risk.

It can be tough to decide on your own which test is best.

Some DNA tests cover both pharmacogenomic findings and cardiovascular disease risks, while others test for only one or the other. Getting a polygenic risk score requires a different testing approach than doing a single-gene or single-variant test. There are different offerings on the consumer testing market than there are on the medical DNA testing market.

The third and final post in this series will help you understand who genetic counselors are and how working with one is the best way to make sure you have the right test for your particular situation and that your understanding of what the results mean is accurate.

The third and final post in this series (coming soon!) will dive into more about genetic counselors - including how you can find one and how they can help!