Coronary Heart Disease in Young Adults. A Multidisciplinary Study

Background/Questions

The influence of Paul White’s exposure to the noted British investigators James Mackenzie and Thomas Lewis is manifest in this pioneer study. The natural history of coronary disease in young adults who had a myocardial infarction before age 40 was studied by White at the Massachusetts General Hospital, beginning in 1946, where he scrambled for a year or so to recruit patients among his Boston colleagues. Matters were regularized when a small staff supported by White and the Commonwealth Fund was engaged and when Menard Gertler joined to recruit for and direct the study full-time. The search was broadened when Stanley Garn, a young Harvard anthropologist, joined the study (Gertler and White 1954).

Garn, in an interview 50 years later, was as enthusiastic (and unrevealing of details!) as he had been the day he was drafted at the beginning of time. Belying his profound scholarship, all he would say when asked about the study’s a priori hypotheses, important questions, and methods, was: “We just went and did it. Everything was unknown. Everything was important. Everybody was welcoming.” To the young anthropologue, everything about the Young Coronary Study was “fun,” was “being at the right place at the right time.” And, he claims grandly, it “led to everything that followed!”(Garn 2003) The basic assumption was “the belief that the individual who had coronary occlusion at an early age would show predisposing characteristics.” (Gertler and White 1954. pg 2)

Method/Design

The study used both closely pair-matched and unmatched controls as the investigators learned-while-doing the case-control study method, Eventually it was transformed into a prospective study followed 25 years.

In their search for the perfect study, they over-excluded and over-matched the 100 young coronary cases recruited from 250 referrals, but proceeded to hospitalize them for a sophisticated battery of tests of “morphological, genetic, athletic, occupational, physiological, psychological, clinical, dietary, hormonal, and biochemical aspects”(ibid. pg 2).

Results

The study found a profound sex difference, not entirely a matter of selection bias, in that 97 of the 100 young coronaries were male, but they were surprised to find few other significant cross-sectional differences. In the young patients there was some excess of one ethnicity (Jewish), of mesomorphic and male build and associated athletism, yet more feminine psychological scores, and there were elevated serum lipoproteins, uric acid, and salivary redox potentials, but no difference in dietary lipids or in blood pressure.

Conclusions/Discussion

The authors conclude: “. . .it may be suggested that the coronary individual studied in this group is a male with a high component of physical masculinity as probably due to inherited characteristics, but his mental attitudes are tempered either by illness or by the acculturation to which he is exposed by virtue of his driving psychological make-up.” (ibid. pg 78)

Their early book is a treasure for references to the first systematic studies in coronary disease and for presenting questions about causes that were in the minds of investigators at mid-century. The Young Coronary Study, thoroughgoing and using all available methods and measurements of the time, demonstrated the difficulty of post hoc analysis in separating the effects of disease from its causes. This led Paul White to his position everafter to recommend prospective studies of coronary disease and strongly support Framingham and Seven Countries study, which he did before all audiences that would listen.

Follow-up

Gertler published a 25-year follow-up of the cases and controls of the 1940s study, publishing it three years after Paul White’s death in 1973 (Gertler and White 1976). In it he reviewed all then-current U.S. prospective studies and undertook extensive multivariable analysis of his prospective data with the Cornfield method newly on the scene. The main questions for the follow-up study were: “Is obesity a prime etiological factor in this disorder? Is there a coronary physique type?” (ibid. pg 71).

He did not answer these questions definitively, but found predictive a tendency toward less linearity of build. The follow-up confirmed prediction using lipoprotein fractions and suggested the importance of coagulation factors. The second volume of 1976 provides a scholarly summary of the seven then-current U.S. cohort studies in CHD risk and their contributions up until the mid-70s. It gave appropriate credit to each and suggesting that the difference in prime variables studied “elucidates one of the reasons for the ofttimes, inconsistent findings reported” (ibid. pg 31).

Gertler seemed pleased in the end that the 1950s concern of Gertler, Garn, and White for the potential of coronary disease prevention had become an official NIH program in the form of multifactor preventive trials (Gertler, Garn, and White 1951). (HB)