“If It Isn’t Fun.” – A Physical Activity Pilot Trial
Much of the fun had gone out of the Seven Countries Study surveys by the mid-60s, at least for those not directly involved with the analyses, which was everyone, in fact, but Keys himself. The second five-year survey round was completed. My busy (and fun) developments of survey methods were either done or in publication. My remaining function, to systematically review ECGs, clinical events, and deaths, had become repetitious, routine. And, for reasons outlined elsewhere, my relationship with my boss, Ancel Keys, was estranged. This career crisis was largely resolved in two directions: preoccupation with collaborative trials on the one hand, Diet-Heart, UGDP, and CDP, and on the other, with laboratory studies of physical activity under the guiding impetus of Henry Taylor.
Taylor, Balke, Buskirk, Stamler, and Remington had laid down plans for a Physical Activity Intervention Pilot Study. They saw clearly that intervention with exercise to prevent heart attacks could hardly be undertaken without detailed knowledge of risk, recruitment, adherence and drop-out rates, and training effects on risk factor levels. The mechanics of this pilot study were to occupy my major energies for many months to come, testing the participants in a graded fitness test to 3 mph, at 1 percent grade increments, and evaluating the computer-averaged ST segment.
In line with my methodological bent and responsibility for monitoring dozens of subjects weekly on the famous old treadmills of the stadium laboratory, I initiated a series of studies on optimal ECG lead placements and stress test regimens. These gave me hands-on experience and insights into exercise physiology, which, combined with improved techniques of electrocardiology, provided an interesting and productive field that I tilled for several years. There were also spin-offs into rehabilitation medicine in a Heart Association Unit in Minnesota and in WHO efforts in research.
Finally, I headed a USPHS Heart Disease Control Program Subcommittee that effectively addressed issues of standardization of exercise testing that was needed for the burgeoning field and which, incidentally, sounded the death knell for Arthur Master’s famous two-step test. The non-standard stress of the Master’s three-minute, two-step test imposed different degrees of circulatory challenge depending on body mass. The good doctor of Manhattan, in those lean days, it was said, would take in $250 a test, and had a dozen or so scheduled each morning. What a sweet deal!
These collaborative efforts led to other useful results: we answered questions about recruitment and participation (50 to 60 percent), about musculoskeletal injuries (25 percent), about differences among responders and non-responders (mainly in smoking habit), about training effects, and about attendance over the 19-month study (50 percent of exercise sessions), and drop-outs (15 percent). The concept of a “faint-of-heart” period was devised, that is, intervention for a period before randomization to reduce eventual drop-outs.
The group of investigators concluded from the pilot, however, that a trial of primary prevention of CHD with exercise as the sole intervention was not feasible.
Attention turned promptly to “Jumbo,” the first formal application for a multiple-risk-factor intervention trial, which included a modest component of unsupervised physical activity as well as simultaneous lowering of the big-three risk factors. The elegantly designed application of Taylor, Stamler, and Remington, to which many of us contributed heavily, was visited by an oversized NIH review panel of 21 narrow experts, virtually assuring a normal distribution of their priority scores and therefore a non-fundable mean score. Jumbo died in the womb.
But the Jumbo concept, and the application itself, would soon serve as foundation for the Institute-initiated Multiple Risk Factor Intervention Trial, MRFIT, which would occupy all our futures for a decade. This was the first example of many in which NHLBI, by one or another mechanism, took over the design, support, and management of collaborative studies in CVD prevention, a controlling policy that goes on today — with ponderous programs and forced partnerships and mixed results.