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Cardiologists play key role in helping patients mitigate high genetic CVD risk
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CVD is the leading cause of death in the United States, with about 610,000 related deaths each year, according to the CDC. Genetics play an important role in determining who is most at risk for CVD. However, long-held assumptions about genetic CV risk have proven not to be true, and many cardiologists are beginning to take a more active role in managing risk for these patients.
At one point, genetics were considered insurmountable: Many people assumed that a patient at high genetic risk for CAD would eventually have a cardiac event, possibly fatal, and nothing could derail their fate.
“There have been 50 different spots across the genome that have been correlated with risk [for MI],” Sekar Kathiresan, MD, director of the Center for Genomic Medicine at Massachusetts General Hospital, told Cardiology Today.
Photo by: Gretchen Ertl; printed with permission.
Valentin Fuster, MD, PhD, Kathiresan and colleagues in November 2016 published research in The New England Journal of Medicine demonstrating that a healthy lifestyle could significantly reduce risk for CV events in patients at high genetic CV risk.
“The major take-home is that ... DNA is not destiny,” Kathiresan, also the Ofer and Shelley Nemirovsky MGH Research Scholar, director of the Cardiovascular Disease Initiative at the Broad Institute and associate professor of medicine at Harvard Medical School, said in an interview. “In general, people assume that if you have a high inherited risk for [MI], that means you’re fated to have a problem. What our [recent NEJM] study shows is that despite the fact that you might have a high genetic risk, you actually still have a considerable amount of control over your own health.”
Experts interviewed by Cardiology Today noted that cardiologists can help patients even at the highest levels of genetic CV risk adopt a healthy lifestyle that involves not smoking, maintaining a healthy weight, recommended physical activity and consuming a healthy diet, which could make a major impact on reducing their CVD risk.
While methods to precisely assess genetic CV risk are not yet regularly incorporated into everyday clinical practice, there are steps cardiologists can take to encourage patients believed to have high genetic CV risk to adopt favorable lifestyle habits, experts said.
Substantially lower risk
The NEJM study included 55,685 patients from four cohorts: the prospective Atherosclerosis Risk in Communities (ARIC) study, the Women’s Genomic Health Study, the Malmö Diet and Cancer Study, and the cross-sectional BioImage Study. The researchers stratified patients into five quintiles based on genetic risk, which was determined by the prevalence of 55 genetic variants known to increase CAD risk.
The take-home message from the study is, “If you have a high risk for the genetics that lead to [CAD], even changing the lifestyle into a normal lifestyle can decrease the number of events ... of coronary disease by half,” said Fuster, physician-in-chief at The Mount Sinai Hospital and director of Mount Sinai Heart Institute. “This is very important because many people think ‘Well, if it is a genetic disease, there’s no need for me to take care of anything.’”
Adherence to a healthy lifestyle was determined by a four-factor scoring system: no smoking, no obesity, regular physical activity and a healthy diet.
Patients with high genetic risk had a 91% greater risk for incident coronary events, defined as fatal or nonfatal MI or coronary revascularization, compared with those at low genetic risk (HR = 1.91; 95% CI, 1.75-2.09).
A favorable lifestyle, defined as following at least three of the four healthy lifestyle factors, substantially lowered CAD risk compared with an unfavorable lifestyle. An unfavorable lifestyle meant patients followed only one or none of the healthy factors. For patients in the quintile with the highest genetic risk, a healthy lifestyle was associated with a 46% lower relative risk for coronary events vs. an unfavorable lifestyle (HR = 0.54; 95% CI, 0.47-0.63; see table for more data on the next page).
The study “underlines the need to think beyond just medical therapies in patients that have increased [CV] risk whether they are genetically related or based on acquired behavioral risk,” Sidney C. Smith Jr., MD, FACC, FAHA, FESC, professor of medicine at the Heart and Vascular Center of the University of North Carolina at Chapel Hill and past president of the American Heart Association and World Heart Federation, told Cardiology Today.
The findings have implications for prevention strategies, according to Robert Roberts, MD, FRSC, FRCPC, MACC, LLD (Hon.), chair of the International Society for Cardiovascular Translational Research at University of Arizona.
“Genetic risk should transform primary prevention of heart disease since it remains the same and can be determined anytime from birth to death,” Roberts, a member of the Cardiology Today Editorial Board, said in an interview. “Determining the genetic risk in pre-menopause females and treating accordingly would markedly reduce the disease in the postmenopausal woman.”
Awareness of risk
The genetic test used in the NEJM study is currently not available for routine clinical practice. Many individuals are unaware of their true genetic CV risk.
As a result, cardiologists must rely on family history to determine CVD risk, but first must ensure that their patients are clear on what family history means.
“Many patients will tell me that they have a family history of heart disease, then they’ll say their uncle or their brother has high BP. That is not a family history of heart disease,” Rita F. Redberg, MD, MSc, FACC, professor of medicine at the University of California at San Francisco and Cardiology Today Editorial Board member, said in an interview.
A true family history of CVD is a having a first-degree male relative aged younger than 55 years or a first-degree female relative younger than 65 years who had a sudden cardiac death or event, according to Kathiresan.
“If you have a family history of premature CVD, you [have] about a threefold increase for having heart disease compared to those who don’t have a family history. This is the main way that patients come to our attention regarding genetic risk,” he said. “Family history is one way to get at genetic risk but family history actually captures more than just DNA risk because families share more than just DNA. For example, they share lifestyle habits as well.”
The extent to which the knowledge of increased CVD risk influences lifestyle choices varies, according to the experts interviewed by Cardiology Today.
“Most patients are aware that family history and passed genes have something to do with heart disease risk, but I don’t think most patients are aware of exactly what it means to have a family history,” Redberg said. “For some people it does [influence choices] and some people it doesn’t.”
In his preventive cardiology program, Kathiresan said he sees many patients for whom knowledge of a strong family history is enough to spur a lifestyle change.
“The patients that I see are those who are in their 40s and 50s who have a strong family history [of heart disease],” he said. “They’re worried about their own health, and they come looking for options regarding how to manage their risk.”
The role of cardiologists
Cardiologists are crucial to helping patients manage their high risk for CVD. “It is very important for the cardiologist to understand that they have a role to play in lifestyle modification,” Smith said. “They have a responsibility.”
One of the first steps is to assess the risk factors that can be modified by lifestyle — smoking status, dietary quality, sedentary behavior and excess body weight — as well as the unchangeable risk factors such as age and sex, Robert H. Eckel, MD, professor of medicine in the division of endocrinology, metabolism and diabetes and the division of cardiology, professor of physiology and biophysics, and the Charles A. Boettcher II Chair in Atherosclerosis at University of Colorado Denver Anschutz Medical Campus, told Cardiology Today. Next, he said, turn to risk factors that can be modified with lifestyle and then with medications based on the evidence.
“BP, you can lower. LDL, you can lower. You can help people eat a more heart-healthy diet and to become more physically active. If they have impaired glucose tolerance, you can prevent diabetes by weight reduction,” Eckel, a past president of the AHA, said.
Alcohol is a somewhat questionable risk factor, according to Eckel.
“People who drink modestly tend to have less coronary disease and events than people who don’t drink at all,” he said. “But then, above a certain amount of alcohol intake, then you’re looking at other downsides of alcohol ingestion.”
Smith said that to assess risk in his patients, he uses the ASCVD Risk Estimator developed by the AHA and the American College of Cardiology, and has found that demonstrating the substantial decrease in risk scores that are possible with lifestyle changes “has a significant effect on those patients.”
Education crucial
Educating patients about their CV risk is critical, according to Fuster.
“People don’t know the facts and they don’t know the realities [of heart disease]. People know smoking is bad for your health and obesity is bad, but they don’t know the numbers. What we have to do is educate,” he said.
To achieve better patient education, Fuster and the Fundación Pro CNIC in Spain have collaborated on a free mobile app called The Circle of Health. Available in English and Spanish, the app assesses patients with regard to six CV risk factors: high cholesterol, diabetes, obesity, high BP, smoking and a lack of exercise. The app uses multimedia and an interactive, circular format to evaluate patient risk, provide tips on managing that risk and lead patients to a healthier lifestyle. There are also apps, including ASCVD Risk Estimator and Cardiac Risk Assist, enabling doctors and patients to calculate a CV risk score.
Smith said he works closely with his patients to devise appropriate lifestyle changes. To encourage weight loss, he recommends that patients track their food intake and weigh themselves often.
Healthy lifestyle benefits
In addition, Smith said he generally recommends a Mediterranean-style diet, which encourages the consumption of fresh fruits, vegetables, fish, some nuts and limited intake of wine. However, given the many cultures in the United States, diets must be modified in a culturally sensitive manner, he said.
Diet alone will not reduce CVD risk, so patients must also be encouraged to move their bodies. “The key point about this is to be physically active on a daily basis,” Smith said, noting that ACC/AHA guidelines recommend 30 minutes of physical activity per day. “I like my patients to think that this is something like brushing their teeth. It should occur on a daily basis.”
In Kathiresan’s practice, cardiologists assess risk according to four broad categories: self-reported risk factors, blood test, imaging (ie, CT scan) and the genetic test. This risk assessment provides a quantitative estimate of MI risk over the ensuing 10 years. The cardiologist reviews lifestyle changes, medicines or a combination of the two that may best reduce that risk, according to Kathiresan.
At this point, there is no firm way of determining which patients can rely solely on lifestyle changes to reduce their risk and which patients will require medical intervention. The message that can be conveyed is that “everyone benefits from optimal lifestyle ... whether you’re at high genetic risk, medium genetic risk or low genetic risk,” Kathiresan said.
The guidelines are clearer on who requires the two main medicines that help reduce the risk for a first MI, according to Kathiresan. Any patients whose 10-year risk for MI is greater than 7.5% should consider statin therapy to reduce that risk, he said. There are similar risk calculations for aspirin: low-dose aspirin should be considered in adults aged 50 to 59 years who have a 10% or greater 10-year risk.
Redberg cautioned against relying too much on statins, however. “I don’t know of any magic pills that would preempt heart disease,” she said.
Smith uses long-term risk assessment to motivate his low- to moderate-risk patients to maintain a healthy lifestyle. “I point out that things look good right now ... but [suggest we] take a look at their lifestyle,” he said.
Future research
Future research should focus on three separate populations, experts told Cardiology Today.
“There are three different populations in which the approach is completely different,” Fuster, who also is editor-in-chief of JACC and past president of the AHA and World Heart Federation, told Cardiology Today. “One is the elderly, one is middle age and the other is children.”
In the elderly, not controlling the CV risk factors affects the small blood vessels in the brain and leads to degenerative brain disease; and for people in middle age, it is critical to identify which individuals have evidence of subclinical disease so they can modify their lifestyle accordingly, according to Fuster. In his research, Fuster uses noninvasive 3D ultrasound to spot narrowing in the carotid artery.
Also key to prevention efforts is education of preschoolers, according to Fuster.
“Children between ages 3 to 5 is the time that you can teach all these issues,” Fuster said. Fuster’s research, which now includes about 50,000 children worldwide, involves a program of 70 hours of health education, spread over 6 months.
Kathiresan said he hopes future research will examine how the knowledge of genetic CV risk will influence patients’ adherence to a favorable lifestyle.
“Will that make them ‘get religion’ and do better or does it push people in the other direction?” he asked. “You would assume that giving this information ... is automatically going to be helpful, but we don’t know for sure how people are going to react to those kinds of information. That is an important area of research that needs to be done.” – by Colleen Owens
- References:
- CDC. Heart Disease Facts. www.cdc.gov/heartdisease/facts.htm. Accessed Feb. 11, 2017.
- Khera AV, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1605086.
- Whitman IR, et al. J Am Coll Cardiol. 2017;doi:10.1016/j.jacc.2016.10.048.
- For more information:
- Robert H. Eckel, MD, can be reached at the University of Colorado Denver Anschutz Medical Campus, 12605 E. 16th Ave., Aurora, CO 80045; email: robert.eckel@ucdenver.edu.
- Valentin Fuster, MD, PhD, can be reached at Mount Sinai Hospital, Cardiovascular Medicine Associates, 1190 Fifth Ave., Floor 1, New York, NY 10029; email: valentin.fuster@mountsinai.org.
- Sekar Kathiresan, MD, can be reached at the Kathiresan Lab, 185 Cambridge St., 5th Floor, Boston, MA 02114; email: skathiresan@partners.org.
- Rita F. Redberg, MD, MSc, FACC, can be reached at the University of California San Francisco Division of Cardiology, 505 Parnassus Ave, Suite M-1180, San Francisco, CA 94143; email: rita.redberg@ucsf.edu.
- Robert Roberts, MD, FRSC, FRCPC, MACC, LLD (Hon.), can be reached at University of Arizona College of Medicine–Phoenix, 550 E. Van Buren St, Phoenix, AZ 85004; email: bobrobertsx2@gmail.com.
- Sidney C. Smith Jr., MD, FACC, FAHA, FESC, can be reached at the University of North Carolina Division of Cardiology, 160 Dental Circle, Campus box 7075, Chapel Hill, NC 27599; email: scs@med.unc.edu.
Disclosures: Eckel, Fuster, Kathiresan, Redberg, Roberts and Smith report no relevant financial disclosures.