Do pro football players have a higher risk of dying earlier?

The study, published Thursday in the medical journal JAMA, is the latest research to highlight the potential health impacts associated with football.

Much of the focus on player health has been on concussions and chronic traumatic encephalopathy, or CTE, a neurodegenerative disease. CTE causes Alzheimer's-like symptoms, including memory loss, confusion, aggression, rage and, at times, suicidal behavior. It is believed to result from repeated trauma to the head, causing a buildup of the abnormal protein tau, which clumps in the brain. There is no treatment, and diagnosis is confirmed only through examination of the brain on autopsy.

On Monday, former Green Bay Packers quarterback Brett Favre told CNN's Christiane Amanpour that the only way to make the game safer is to not play, although he admits the NFL isn't going to go away.

"Concussions will continue to be a serious issue. There's only so much that helmets can do. So we'll look at it from a treatment standpoint. And the only other option is not to play," he said.

Apples-to-apples comparison

Authors of the new study on increased risk of death caution that the increase may not be as significant as it sounds. "It's suggestive but not definitive," said Dr. Atheendar Venkataramani, an associate professor of medical ethics and health policy at the University of Pennsylvania. In fact, the mortality rate difference was statistically insignificant but still raises key questions.

Still, Venkataramani believes he and his colleagues have done the first apples-to-apples comparison to really understand the toll football takes on professional players.

Previous research has found that professional football players have lower overall death rates as well as lower rates of cancer and heart disease than men of similar age and ethnicity who do not play pro football.

But Venkataramani said it's hard to make any determinations from those comparisons. "It struck us that it's hard to draw definitive conclusions from them because NFL athletes are different from the general population," he said. Elite athletes in general tend to have healthier lifestyles than the rest of us.

Isolating the impact of football

In an effort to isolate just what the impact of professional football was, Venkataramani and his colleagues did a retrospective study comparing the life expectancies of professional NFL players who debuted in the league between 1982 and 1992 and compared them to a group of "replacement players" who filled the NFL rosters for three games when players were on strike in 1987.

The researchers found the players' data through Pro Football Reference, an online sports reference database, and tracked their health through December 31, 2016. Because of the nature of the online database, the researchers acknowledged that some of the information used could have been misrepresented or incorrect.

When comparing the 2,933 career NFL players to the 879 "replacement players," the study authors found 144 deaths among the career players, or 4.9% of that group. There were 37 deaths among the replacement players, which represented just 4.2% of that group. Because the number of players being evaluated was so small, Venkataramani said it was hard to determine the significance of the differences.

The researchers also analyzed the deaths and found that while heart disease was the No. 1 cause of death in both groups, as it is around the world. However, car accidents, drug overdoses and neurological diseases were more common reasons for death among career players than among "replacement players." Previous studies have found that professional football players are more likely to develop neurodegenerative diseases like amyotropic lateral sclerosis and Alzheimer's.

Venkataramani also noted that the players' age by the cutoff date was probably a factor in the study. At the end of the study, on average, the men were just 52 years old. "These people were pretty young. There's not a lot of death. We anticipate as these cohorts age, there will be more events," he said.

Venkataramani and his colleagues have discussed continuing to follow this group of players, and they welcome other researchers to build on their work and learn more about the differences between the two groups. "I think anyone who's interested in following them should," he said.

An editorial published alongside the study by researchers not involved in the report said that "Although the life expectancy of professional football players was not significantly reduced based on the current evidence, the health of professional athletes should remain a focus of future research."

The editorial also noted that because of the higher incidence of neurological disease in the career players, it continues to be vital to focus on the connection between repeated head trauma and neurological disease.

Hard to draw any definitive conclusions

Dr. Ken Mautner, an assistant professor of orthopedics at Emory University's School of Medicine, was hesitant to read too much into the findings because of the many factors football players deal with.

"There are so many variables in looking at this topic of former professional athletes, when it comes to substance abuse and healthy behaviors and risky behaviors, head injuries. So these are all negative things. And on the other side, you have super healthy specimens," he said.

Mautner, the head team physician for the NBA's Atlanta Hawks and team physician for the MLB's Atlanta Braves, was not involved with the new study.

"I commend what (the researchers) were trying to do. And even showing not much of a difference is saying something else. It may lend to the fact that football players aren't really dying at an earlier age. There is something to take from all of that," Mautner said.

Ultimately, though, "it's hard to draw any definitive conclusions from this study," and he wouldn't let it dissuade anyone from playing professional football.

"It's been really elusive to figure out if playing in the NFL causes certain health conditions, and we're just trying to provide a way to answer that question more reliably," Venkataramani said. He hopes this study will pave the way for future analysis of what the impact of football is.

The NFL said that "this new study seems to support other previous studies that have not shown an increase in mortality among NFL players when compared to similar cohorts. ... As with all new research on this topic, we will look at it closely to see what we can learn to better enhance the well being of our current and former players."

Venkataramani and his colleagues acknowledge the shortcomings of the study but believe it is an important stepping stone toward further understanding of the impact of the game on professional players. "None of it is truly definitive, but it's just sort of pointing us on better studies," he said.

Mautner agreed: "It's interesting information ... and will hopefully open the door for other studies."