Skip to content

A conversation about using genetics to advance cardiovascular medicine


In recognition of American Heart Month, Stanford Health Care is hosting a heart fair on Saturday. The free community event includes a number of talks ranging in topic from the latest developments in treating atrial fibrillation to specific issues related to women's heart health.

During the session on heart-disease prevention, Joshua Knowles, MD, PhD, will deliver a talk titled "How We Can (and Will) Use Genetics to Improve Cardiac Health." Knowles' research focuses on familial hypercholesterolemia, a genetic disease that causes a deadly buildup of cholesterol in the arteries. He and colleagues recently launched a project that uses a big-data approach to search electronic medical records and identify patients who may have the potentially fatal heart condition.

To kick off the conversation about preventing heart disease, I contacted Knowles to learn more about how the genomics revolution is changing the cardiovascular medicine landscape and what you can do to determine if you have a genetic heart disorder. Below he explains why heart disease is a "complex interplay between genetics and environment" and what the future may hold with respect to personalized treatments and pharmacogenetics.

Let's start by talking about your work on familial hypercholesterolemia (FH). How has the understanding of the genetic basis of FH evolved over the last few years, and what key questions remain unanswered?

For FH, there has been a revolution in our understanding. FH causes very elevated cholesterol levels and risk of early onset heart disease. We used to think that it affected 1 in 500 individuals, but recent studies have pointed out that this is probably an underestimate and it may affect as many as 1 in 200 people. This means that there may be as many as 1 million people in the United States who are affected. We have also identified new genes that cause FH, and the identification of some of these genes has directly translated into the development of a new class of drugs (so called PCSK9 inhibitors) to treat this condition.

What steps can patients take to determine if they are at risk of, or may have, a genetic cardiovascular disorder like FH?

The easiest way is to know about your family history of medical conditions- to know what illnesses affected parents, grandparents, uncles, aunts and other relatives. Of course, genes aren't the only things that are passed in families. Good and bad habits, such as exercise patterns, smoking and diet, are also passed down through the generations. But a family history of heart disease or certain forms of cancer is certainly a risk factor.

Past research suggests that patients with a genetic predisposition to heart disease can significantly reduce their chances of having a heart attack or stroke by making changes to their lifestyle, such as eating a diet rich in fruits and vegetables. Can lifestyle changes overcome genetics?

Heart disease is a result of the complex interplay between genetics and environment - lifestyle, for instance. For some people with specific genetic conditions, such as familial hypercholesterolemia or hypertrophic cardiomyopathy, the effect of genetics tends to dominate the effect of environment because the genetic effect is so large.

For the vast majority of people without these "Mendelian" forms of heart disease, which follow the laws of inheritance were derived by nineteenth-century Austrian monk Gregor Mendel, it's difficult to determine at an individual level how much of the risk is due to genes and how much is due to environment (this is for things like high blood pressure, high cholesterol, coronary disease). One clue is certainly family history. However, for most of these diseases the genes are not "deterministic" - that is, people are not destined to have these diseases. Some are more at risk than others, but there are certainly ways to mitigate genetic risk through lifestyle choices. Choosing not to smoke and exercising regularly are two examples of ways you can help to greatly minimize genetic risk.

Switching gears to talk more generally about the field of cardiovascular medicine: What has the field gained from the Human Genome Project?

The Human Genome Project provided a "roadmap," or the foundation, for all studies that have come since then. Before the human genome effort researchers and physicians didn't have a very good understanding of how genes can influence health, we didn't even know the total number of genes. In fact, there was a huge competition to estimate the number of genes. Most thought there would be close to 100,000 human genes. But it turns out that there are more like 19,000. We also didn't know how the genes were organized in the genome. We knew that there would be a lot of genetic variation between individuals, but to find and understand that genetic variation across populations first requires the basic roadmap.

Pharmacogenomics is another thing we've been hearing a lot about. It has proven useful in cancer treatments, but is it making its way into cardiovascular medicine? 

Pharmacogenetics is certainly a promising field and is beginning to make inroads into cardiovascular medicine. There are recommendations for changing treatment strategies for several medicines including statins (like simvastatin or Zocor), warfarin (Coumadin), clopidogrel (Plavix).

In terms of the future, there are large efforts underway, including many at Stanford, to translate the promise of genetics into the care of individual patients. For most disease management (and other applications like risk prediction) we haven't yet shown that the incorporation of this information can dramatically affect outcomes. However, as we accumulate more data and do larger studies, this is likely to change. Certainly, we are starting to see an increase in the number of new drugs that are emerging from the genetic discovery studies that were started five to ten years ago. That may be the most immediate benefit of the genetic revolution. Again, PCSK9 inhibitors are the poster child for this kind of translation.

Previously: Big data used to help identify patients at risk of deadly high-cholesterol disorder, A ssathi (partner) to thwart heart disease in South Asians, Lack of exercise shown to have largest impact on heart disease risk for women over 30Born with high cholesterol and A moose no longer: How I faced down my fears of heart disease
Photo by le vent le cri

Popular posts