Correspondence

Serum Cholesterol in Young Men and Cardiovascular Disease

N Engl J Med 1993; 329:138July 8, 1993

Article

To the Editor:

Klag et al. (Feb. 4 issue)1 report a strong correlation between the serum cholesterol level measured early in adult life in men and the incidence of cardiovascular disease in midlife. In contrast to other investigators,2-4 they did not find a “J-shaped” relation between total mortality and the serum cholesterol level. Such a relation has been attributed to an excess of deaths from noncardiovascular causes among patients with low levels of serum cholesterol -- for example, from cancer, accidents, or suicide. From the authors' Table 2, we calculated death from noncardiovascular causes. This was consistent with a positive relation between the serum cholesterol level and mortality from noncardiovascular causes, in contrast to studies that have found an inverse relation between serum cholesterol and mortality from noncardiovascular causes. Could the authors comment on their findings in the context of the other studies?

B. Corvilain, M.D.
J. Matte, M.D.
C. Litvine, M.D.
Erasme Hospital, Free University of Brussels, B-1070 Brussels, Belgium

4 References

1. 1

   Klag MJ, Ford DE, Mead LA, et al. Serum cholesterol in young men and subsequent cardiovascular disease. N Engl J Med 1993;328:313-318
   Full Text | Web of Science | Medline

2. 2

   Neaton JD, Blackburn H, Jacobs D, et al. Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Arch Intern Med 1992;152:1490-1500
   CrossRef | Web of Science | Medline

3. 3

   Stemmermann GN, Chyou PH, Kagan A, Nomura AMY, Yano K. Serum cholesterol and mortality among Japanese-American men. Arch Intern Med 1991;151:969-972
   CrossRef | Web of Science | Medline

4. 4

   Jacobs D, Blackburn H, Higgins M, et al. Report of the Conference on Low Blood Cholesterol: mortality associations. Circulation 1992;86:1046-1060
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The J-shaped relation between serum cholesterol and total mortality seen in midlife studies is due in part to lower serum cholesterol levels in people with subclinical cancer and other chronic diseases. Our study differed in that the men were enrolled at a relatively young average age (22 years) and, because of the entrance requirements for medical school, were likely to be healthy. Such a bias is therefore unlikely because our population was young and healthy at the time of serum cholesterol determination.

The incidence rates in Table 2 of our paper were calculated with Kaplan-Meier analysis. This takes into account withdrawals from the study. Because withdrawal times may vary for different end points, the subtraction of one cumulative incidence rate from another may not yield accurate estimates. In our data, there was no relation between serum cholesterol and mortality from noncardiovascular causes (P = 0.6). We are currently investigating the relation between serum cholesterol and cause-specific mortality in this cohort.

Michael J. Klag, M.D., M.P.H.
Lucy A. Mead, Sc.M.
David M. Levine, M.D., M.P.H. Sc.D., M.D., M.P.H. Sc.D.
Johns Hopkins University School of Medicine, Baltimore, MD 21205