Early exercise interventions used from Duke trial to decrease cardiovascular disease

By Brittany Vekstein

With 2022 underway and we are still living a relentless pandemic, our health continues to be of the upmost importance and physical activity has been shown to not only improve health, but help prevent the onset of many diseases.

In February we celebrate and raise awareness for Heart Month, a time when the national spotlight is on cardiovascular disease.

One cardiologist at Duke focused on heart disease, specifically from a preventative standpoint, is Dr. William E. Kraus.

William E. Kraus, MD, Richard and Pat Johnson University Distinguished Professor at Duke University School of Medicine, a cardiologist, researcher, and affiliated faculty for the Duke Center for Applied Genomics & Precision Medicine (CAGPM), is studying exercise effects in individuals ranging from healthy to those at-risk of disease and those with disease, such as coronary heart disease. For the last 35 years, the Kraus laboratory particularly focuses on increased physical activity as the means by which to prevent premature cardiovascular death. Kraus’ well-known randomized exercise trials – STRRIDE (Studies of a Targeted Risk Reduction Intervention through Defined Exercise) are being used to investigate genetic predictors associated with individuals dropping out from or adherence to an exercise intervention. Postdoc Katherine Collins, PhD, is a research assistant in the Kraus Lab part of this endeavor, through the CAGPM T32 fellowship.

Specifically, Kraus Lab is currently working on a project using data from the STRRIDE trial to undertake the project, “Molecular Predictors of Dropout from and Adherence to Lifestyle Interventions.” The team has identified multiple variants within an array of genes associated with an individual’s ability to adhere to -- or lack of ability to adhere to (i.e. dropout) -- the STRRIDE exercise interventions. During her fellowship, Dr. Collins’ goal is to validate findings Kraus and his team have made to identify genetic variants associated with dropout and adherence to the randomized exercise trials. The team has investigated potential mediators of the genetic association with intervention dropout. During Collins’ time as a T32 fellow, she has been a valuable contributor to the project, bringing biospecimens from a 12-month behavioral weight loss randomized trial and utilizing data from the 2-year caloric restriction dietary intervention – CALERIE™ (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) trial to further investigate Dr. Kraus’ initial findings.

“The CAGPM T32 fellowship has provided me hands-on experience, under the mentorship of Dr. Kraus, in human clinical trials, bio-banking, developing human samples into bio-molecular data, and human translational research as a whole,” said Collins. “This fellowship has helped me establish a foundation for my future research endeavors around precision medicine approaches in exercise and lifestyle interventions.”

These findings will help guide future interventions and help identify those individuals who may be most at-risk or prone to dropout or have poor adherence to exercise. The overarching goal of this investigation is to develop a personalized medicine approach for exercise, giving interventionists the ability to target at-risk individuals early in the invention process, pushing them past the key dropout phase—the initial 2 months—of the exercise intervention.

“We know physical activity is good and anything is better than none and more is better than less,” said Kraus. “However, the responses to physical activity and exercise are individually different, partly mediated by genetic factors. The tendency to engage in and maintain regular physical activity patterns are mediated by a combination of personality and genetic factors.” 

Lack of physical activity is an ongoing public health concern. This is contributing to heart disease, even for people that have no risk factors, while also increasing the rates of obesity, diabetes, high blood pressure, and more.

“Outside of communicable diseases, cardiovascular disease remains the number one cause of premature death in the US and the World,” said Kraus. “The spectrum of cardiometabolic risk factors—hypertension, abnormal blood lipids and diabetes—are, separately and combined, the major non-lifestyle risk factor contributors to cardiovascular risk. Smoking, the lack of physical activity, and poor diets are the major lifestyle-related risk factors which also contribute to worsening hypertension, lipids and diabetes.”

Studies like these ultimately aim to help individuals maintain active lifestyles long-term.

Many of these issues will be addressed during the Genomic & Precision Medicine Forum on February 24, 2022, where Dr. Kraus will be presenting on “Components of Personalized Lifestyle Medicine with a Focus on Physical Activity.” Learn more and register to attend the virtual talk on Zoom.

Learn more about the Molecular Transducers of Physical Activity Consortium here

Learn more about the Center for Applied Genomics & Precision Medicine Post-Doctoral Training Program by viewing the website here

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