FAU’s Charles Hennekens, the researcher whose report in the Physician’s Health Study, published 24 years ago in the New England Journal of Medicine, explained to the world that aspirin prevented a first heart attack.
When did aspirin first come across your radar as a potential preventative measure for cardiovascular disease?
Aspirin is as old as medicine itself. Hippocrates found that an extract produced from the bark of a white willow tree, which had an aspirin-like compound, would relieve pain in patients—especially women in labor. One of my friends at NIH jokes that aspirin is even older than medicine because when Moses came down from the mountain, he was told by God to take two tablets. ...
Felix Hoffmann, working in the laboratories of Bayer, synthesized aspirin more than 100 years ago. Aspirin went on to become the most widely used drug in the world in the 20th century. But its effect on cardiovascular disease was not known to anyone—including Bayer. I have an old advertisement from Bayer, and at the bottom it says, “Does not affect the heart.” Little did they know.
In 1971, John Vane did this landmark research that basically finds that aspirin inhibits the ability of blood platelets to stick together. [Vane would share the Nobel Prize in Physiology or Medicine in 1982.]
So I’m at Harvard, working on my dissertation, and I’m interested in aspirin. And sure enough, in a case control study for my thesis, it looks like the men who took aspirin had a slightly lower risk of dying from heart disease. ... I met Doll and Richard Peto [professor of medical statistics and epidemiology at the University of Oxford], and they were interested—and from that stemmed my application to do the Physicians Health Study through NIH.
At the time, there wasn’t that much enthusiasm in the heart, lung and blood institute. Their belief, and it wasn’t unrealistic given the basic science of aspirin [and the inhibition of clotting], was that it was a little far out for clinical cardiovascular disease.
When I reapplied, I had reviewed some research involving beta-carotene—the vegetable part of vitamin A found in green leafy vegetables—might prevent cancer and heart disease. That got it funded. So it was a trial funded by the heart and cancer institute.
So now, it’s all these years later, and it looks like beta-carotene has nothing to do with heart disease or cancer—but it looks like aspirin does.
I got the funding, and then the study was supposed to go on. But the data monitoring board said that the heart attack risk is reduced so big that it’s unethical to keep this from people. So they stopped the study early, and it was published that aspirin prevented a heart attack.
Working with Doll and Richard Peto, we also found that aspirin was beneficial in people who’ve already had heart attacks and strokes. [Another study would find that aspirin given during a heart attack reduced the death rate by 20 percent.]
I’ve had the good fortune to be involved in primary prevention, secondary prevention and then during an acute heart attack.
I’m pleased to report that colleagues at Dartmouth have done randomized trials that show that aspirin not only prevents colon polyps, but if you have colon polyps, it prevents their development into cancer. So colon cancer has randomized evidence on aspirin; I’m hoping there are studies out there that can look at other cancers.
I recently said that aspirin was the wonder drug of the 20th century—and if this keeps up, it may be the wonder drug of the 21st century as well.
Was there skepticism after the initial release?
There was some on a worldwide basis. But my original concern was that they were willing to put it in the water supply. To this day, I don’t believe that you should take aspirin in primary prevention—unless you have a risk that exceeds the side-effects risk of taking aspirin. I don’t want to see a society where we see a woman in her 30s taking aspirin when there is no benefit until she’s in her 60s.
If your residual risk of [cardiovascular disease] is 10 percent or more, aspirin will be a huge benefit. It will reduce your risk of a heart attack by one-third.
It’s an over-the-counter pill, and there’s a lot of misinformation. You can’t just give out aspirin willy-nilly.
Has there been a study in which you were involved where the results took you by surprise?
In the lab, beta-carotene is a molecule that dazzles you. It has anti-carcinogenic effects in both initiation and promotion. And there were studies [that indicated] it may lower the risk of heart disease and cancer.
But it didn’t pan out. In 13 years of treatment and follow-up of 22,000 dedicated physicians who took their pills every day, beta-carotene had absolutely no impact on cancer or cardiovascular disease. Neutral. No benefit, no harm.
Since those findings, others have claimed that there’s harm with beta-carotene. I don’t think that’s right.
As an advocate of preventive medicine, what scares you?
My big concern today is that we have the longest life expectancy in the history of our society. But we’re not healthy. In many ways, it’s better living through chemistry. These drug therapies, which should only be adjunct to healthy lifestyles, are the ones that are keeping people alive.
Another concern as someone who’s been a preventive medicine person: The same tobacco companies that are settling lawsuits in the U.S. are flooding the Third World with tobacco. Then there’s the fast-food stores ... there are 3,700 Kentucky Fried Chickens in China. I was in Beijing after Mao died; everyone was thin, fit and riding bicycles. Now, the BMI in Beijing, the weight adjusted for height, is the way it was in the U.S. in 1990.
Tobacco and obesity are driving a pandemic of cardiovascular disease. Malnutrition and infection are no longer the leading killers in the world. It’s cardiovascular disease. You can see the changing pattern in Japan, which has the longest life expectancy in the history of the world, as it Westernizes. Heart attacks, colon cancer, which has the same risk factor pattern as cardiovascular disease—way on the rise. That was virtually unheard of in Japan before.
Most of middle-age America is not suffering from smoking, but they are suffering from obesity and its correlates. Up to this year, we’ve been the fattest society in the history of the world. If you have morbid obesity, you take off seven to 10 years of your life.