Meyer Friedman, MD, died at the University of California Medical Center in San Francisco on Friday, April 27, 2001⇓. He was 90 years of age.
After earning his undergraduate degree at Yale University (New Haven, Conn) in 1931, he obtained his doctorate in medicine at the Johns Hopkins University (Baltimore, Md) in 1935. During a research career that spanned 62 years, he served first as director of the Harold Brunn Institute for Cardiovascular Research in San Francisco (1939 to 1984), then as director of the Meyer Friedman Institute (San Francisco), which was founded in his honor in 1984. He published 542 articles in peer-reviewed journals, as well as 5 books.
Friedman was the first to show that cholesterol was absorbed by the lymphatic vessels of the distal ileum. He discovered further that the liver esterifies this cholesterol, providing it with an envelope composed of a protein, a phosphatide, and triglycerides, and that in the absence of dietary cholesterol, the liver is able to synthesize it. He also showed that the liver is the chief source of cholesterol not derived from food. He was the first to perform coronary angiograms in dogs (Circulation. 1950;1:1182). For medical and legal reasons, he was reluctant to try the procedure on humans. In 1958, however, Dr Mason Sones of the Cleveland Clinic in Ohio informed Friedman that he had accidentally injected contrast material into the right coronary artery of a 26-year-old patient suffering from rheumatic valve disease. There were no ill effects, and Sones asked if Friedman had seen any in his dogs. Friedman replied in the negative. Sones then told him he would try the procedure in humans, and he did so. Coronary angiography is now standard worldwide.
Friedman was among the first to show that myocardial infarctions usually were caused by rupture of a soft, subintimal atheromatous “abscess” with superimposed thrombosis. In addition, his research indicated that the negative emotions and behavior associated with stress, especially hostility, time urgency, and insecurity, contributed to the onset of atherosclerosis and myocardial infarctions. He coined the term “hurry sickness,” which will appear in the forthcoming edition of the Oxford English Dictionary.
Friedman initially decided to study the effects of stress on the heart after an upholsterer pointed out to him that the fronts of the seats and arms of the chairs in his waiting room were wearing out much too rapidly. Patients were tense and sitting on the edges of their seats. Friedman and Dr Ray Rosenman measured the cholesterol levels of 40 accountants throughout the year, finding that those levels rose precipitously during tax time.
Friedman and Rosenman then applied for a grant to study the effects of the emotions and behavior associated with stress on the heart and were told that only psychologists and psychiatrists could apply. The grantor told the two that they could overcome this problem if they named the clinical, visible signs of stress “type A behavior.” This they did, and grants were forthcoming.
Friedman and Rosenman established discriminant criteria, a number of physical signs that could be detected during a videotaped clinical examination (VCE) and scored, which meant the results would be reproducible. In an 8.5-year prospective study (the Western Collaborative Group Study) involving 3154 healthy men (age, 39 to 59), they demonstrated that men with type A behavior were significantly more prone to develop myocardial infarctions (P=0.003 for younger men; P=0.019 for older men).
After this initial study, Friedman and colleagues refined their discriminant and positivity criteria, yielding better results. They undertook another randomized study (the Recurrent Coronary Prevention Study), this time of 862 men and women who had had myocardial infarctions. They demonstrated that, with appropriate behavior modification, the recurrence rate in the treatment group after 4.5 years was 44% lower than in the control group that did not get behavior modification therapy (P=0.005). Friedman and colleagues wanted to continue the study, but the National Institutes of Health, which funded the study, believed that the interim results were so convincing that it would be unethical not to treat the control group.
The results of these 2 large studies were confirmed in 5 of 6 subsequent studies that used the VCE; the only negative study allowed the interviewers to speak for only 5 minutes instead of the customary 20 minutes. Since then, however, 5 other studies using the Cook-Medley hostility scale found no association between hostility and coronary artery disease. Intrigued by this schism, Friedman gave 21 ambulatory postinfarction patients the Cook-Medley questionnaires in addition to the VCE. Of the 21 patients given the questionnaires, 12 reported themselves as nonhostile; 20 of the 21 examined by the VCE were found to be severely hostile.
Meyer Friedman was involved in another 10-year study of type A behavior right up to the time of his death.