If running 15 miles a week is heart healthy, running 45 miles a week gives you a cardiovascular system three times as clean and strong, right?

A new study sounds a serious alarm about such thinking, adding to a growing body of research on the topic of excessive endurance exercise.

You’ve heard of the runner’s high. Researchers now want you to hear about runner’s plaque — coronary artery plaque.

In short: Running super-long distances for many years might backfire on you.

“Years of extreme exercise efforts appear to erase some benefits you get from moderate exercise, so that your risk of heart disease, of dying of coronary disease, is the same as a sedentary person,” said James O’Keefe, preventive cardiologist at St. Luke’s Hospital in Kansas City, Mo.

O’Keefe said the study found that men who were marathon runners for 25 years had 62 percent more plaque buildup in their coronary arteries than men who were sedentary but were similar to the runners in other respects, including age.

And the increased quantity of plaque in the marathoners’ arteries included both hard, or calcified, plaque and the more dangerous soft, fatty plaque. The latter is the kind that can be predisposed to rupture and cause a heart attack.

O’Keefe is co-author of the paper in the latest issue of Missouri Medicine, the journal of the Missouri State Medical Association. The study was conducted by Robert Schwartz and colleagues at the Minneapolis Heart Institute Foundation.

An unwavering advocate of exercise and its benefits, O’Keefe said the study adds weight to the idea that the potent benefits of exercise are “dose dependent.”

That is, the right amount matters. Being sedentary is unhealthy. Regular, moderate exercise bestows long-term benefits.

While logging huge numbers of miles and running marathons can keep you thinner, lower your risk for type 2 diabetes and offer other benefits, it appears the subsequent wear and tear on the heart is a potential drawback, O’Keefe said.

The study’s marathoners, who had run at least one 26.2-mile race a year for 25 years, had a lower weight, resting heart rate and body mass index than the non-runners. The average age of both groups was in the 50s.

That works out well for the 3-milers — keep doing that, O’Keefe said — but it’s cautionary news for marathoners and ultramarathoners, at least those who have been at it for years.

Like John C. Hagan III, a Kansas City area ophthalmologist and editor of Missouri Medicine.

“I started running in 1967, and those were the days when the police would stop you and ask you what you were running from,” said Hagan, who wrote a personal article to accompany the plaque study.

A lifelong dedicated runner, Hagan participated in more than 25 half marathons, four marathons and two half Ironman Triathlons. He typically ran 30 to 40 miles a week.

So he was surprised when at age 61 he was diagnosed with atrial fibrillation, a heart rhythm problem. After learning more about runners with heart problems, he finally decided to get a heart scan for his coronary artery calcium score, an indicator of heart artery plaque.

He still felt confident his running had provided protection. A calcium score of 100 or less is considered mild calcification, and 400 is considered extensive. His score was 1,606.

“As a physician and a runner, I felt betrayed,” he said. “I thought I was out there exhausting myself, building an absolutely indestructible heart.”

Hagan is 70 now and no longer runs, but he walks 30 minutes nearly every day and regularly swims and lifts weights.

“Do a marathon if it’s on your bucket list, when you’re young,” he said, “then cut way back.”

Two years ago, in a report published in the journal Mayo Clinic Proceedings, O’Keefe and fellow authors cited evidence that extreme endurance training may cause structural damage to the heart, making it stiff and enlarged. That paper showed moderate running distances two to five times a week at moderate speeds offered the best health benefits and even 15 minutes a day of physical activity was helpful.

Eladio Valdez, coach of the Runner’s Edge training group in the Kansas City area, said he is aware of recent research about the potential ill effects of years of long-distance running, and last year he held a clinic for his clients on the topic.

“I told my runners, ‘We can’t ignore this research,’” he said.

While such studies don’t offer definitive answers yet, Valdez said, the research is “sobering,” and he encourages his long-distance runners to see their cardiologist and to consider a scan.

Running fewer miles also reduces overuse injuries, and he has seen clients gravitate to more moderate regimens.

A runner for more than 30 years, Valdez has cut back his miles from about 40 a week to 20 to 25. He plans on running one more marathon this fall — the 25th anniversary of his first marathon — and then no more.