Outrunning Your Genes: Exercise Offsets CVD Events Among High-Risk Subjects

Once again, another large study is boosting the benefits of being active, fit, and strong, with investigators reporting that higher physical activity levels, cardiorespiratory fitness, and grip strength are associated with lower risks of incident cardiovascular disease and all-cause mortality.

This latest study, however, goes one step further: using genetic risk scores, the researchers showed that the higher an individual’s physical activity level, cardiorespiratory fitness, and grip strength, the lower their likelihood of coronary heart disease and atrial fibrillation among those at the highest risk for future events.

“We see that even if you’re at high genetic risk, there is a benefit to being physically active, having better fitness, and having more strength. That’s an important message,” senior investigator Erik Ingelsson, MD, PhD (Stanford University School of Medicine, CA), told TCTMD. “You can partly try to combat the risk you’re born with by being physically active.”

The new study, which was published online April 9, 2018, in Circulation, is an analysis of 502,635 individuals participating in the longitudinal UK Biobank study. To TCTMD, Ingelsson said the study is unique given its size; this allowed the researchers to assess not only the association between physical activity, fitness, and strength with cardiovascular disease but also specific endpoints such as coronary heart disease (CHD), stroke, atrial fibrillation, and heart failure.

Additionally, physical activity levels were assessed using objective measures, specifically a wrist-worn accelerometer that measured activity over 7 days in more than 103,000 subjects, as well as with subjective self-reporting. Grip strength and cardiorespiratory fitness were also assessed using objective measures, including submaximal exercise testing. The median follow-up was 6.1 years.

‘Very Robust and Strong Associations’

Each standard deviation (SD) increase in grip strength was associated with an approximate 12% to 13% reduction in CHD, atrial fibrillation, and cardiovascular disease events. Each SD increase in fitness was associated with a 25% reduction in CHD, a 39% reduction in atrial fibrillation, and a 32% reduction in cardiovascular disease. Greater grip strength and higher cardiorespiratory fitness were also associated with lower risks of ischemic stroke and heart failure, while grip strength was inversely linked with risk of hemorrhagic stroke. 

Physical activity levels were also inversely associated with cardiovascular disease events and heart failure, although the association was weaker compared with grip strength. Ingelsson said the association between cardiovascular events and self-reported physical activity was “notably more modest” when compared with the inverse association between accelerometer-measured physical activity levels and clinical outcomes.   

Overall, greater grip strength, higher physical activity (self-reported and accelerometer-documented), and greater cardiorespiratory fitness was associated with lower risks of all-cause mortality. Each SD increase in physical activity levels among those who wore the accelerometer was associated with a 44% reduction in the risk of all-cause mortality, for example. Each SD increase in fitness and grip strength was associated with a 24% and 22% lower risk of death, respectively.

“In the general population, if you disregard genetics, we see a very robust and strong association between all of these measures of physical activity, strength, and fitness with [future] disease,” said Ingelsson. “The more physical activity [you do], the more fit you are, the stronger you are, the lower the risk of disease in the next 6 years, for all types of cardiovascular disease.”  

The researchers also evaluated the risk-modifying associations of fitness and physical activity in individuals with different genetic risks for CHD and atrial fibrillation. A genetic risk score, which was based on markers identified in genome-wide association studies, was calculated to identify individuals at low, moderate, or high risk for CHD and atrial fibrillation.

The data showed, “regardless of genetic risk, there is a benefit to being physically active and fit,” said Ingelsson. Greater grip strength and higher cardiorespiratory fitness were associated with a lower risk of incident CHD and atrial fibrillation in each genetic risk-score group (P < 0.001 in each genetic risk category).

Those at high risk for events who were most physically fit had a 49% lower risk for CHD and a 60% lower risk for atrial fibrillation when compared with individuals at high risk for events but who had low cardiorespiratory fitness. Similarly, those with high genetic risk who had high grip strength had a 31% lower risk for CHD and a 39% lower risk for atrial fibrillation compared with those who had low muscular strength. Physical activity levels showed a similar inverse relationship with CHD and atrial fibrillation across the genetic risk scores, but the relationship was more modest, say investigators. 

Biggest Bang Amongst High-Risk Subjects

Carl “Chip” Lavie, MD (John Ochsner Heart and Vascular Institute, New Orleans, LA), who was not involved in the analysis, highlighted the large sample size as one of the study’s strengths. He said that, as in many studies, the higher-risk patients stand to gain the most benefit from high levels of physical activity, better cardiorespiratory fitness, and greater muscular strength.

“In current clinical practice, we do not know this detail of genetic risk, other than the simple family history of early heart disease or stroke,” he told TCTMD in an email. “Certainly, one cannot choose their parents, or at least at present change their genes. However, the worse the genetic risk is, the more need there is for physical activity, including aerobic exercise to increase cardiorespiratory fitness, and resistance exercise to increase muscular strength.”