The results of this prospective population-based study indicate that the risk of ischemic heart disease associated with a high BMI depended entirely on whether features of insulin resistance syndrome were simultaneously present. Thus, although obese men were more susceptible to developing features of the syndrome, their risk of ischemic heart disease was elevated only when more than 4 of the 7 features were present. Interestingly, the risk of ischemic heart disease among normal-weight men was also increased in the subgroup displaying more than 4 of the 7 syndrome features.
Increased body weight and BMI have been associated with an increased risk of ischemic heart disease in several populations, but this has not been a consistent finding. The authors of the Framingham Offspring Study reported an approximate 2-fold increase in the 10-year risk of coronary artery disease in subjects with a BMI of 30 kg/m2
or more compared with those with a BMI less than 21 kg/m2
after adjustment for age.14
On the other hand, the results of the Prospective Cardiovascular Munster Study indicated that BMI did not independently contribute to cardiovascular risk in multiple logistic regression analysis.15
Stevens and associates suggested that, among men aged 30–74 years, higher body weight increased the risk of death from cardiovascular disease over a 12-year period among subjects aged 44 years or less but not among men older than 65 years.16
Because our cohort included only men 6–76 years of age, the high-risk age group (30–44 years) in the study by Stevens and associates was absent from our study, which may explain why the association between increased BMI was not significantly associated with an increased risk of ischemic heart disease in our study. The National Cholesterol Education Program Adult Treatment Panel III (NCEP III) has recently recognized the metabolic syndrome as an important risk factor for ischemic heart disease among both men and women.17
It has been estimated, on the basis of results of the Third National Health and Nutrition Examination Survey, that more than 1 in 5 adults in the United States have the metabolic syndrome,17
with almost a doubling of this prevalence (43%) among people older than 60 years.17
Our study results show that the risk of ischemic heart disease increased as a function of the cumulative number of insulin resistance syndrome features, with 3 or more metabolic features resulting in a 2–4-fold increase in the risk of ischemic heart disease. These results are consistent with data from previous studies that suggested that the prevalence of unstable angina pectoris and history of myocardial infarction were highest among patients with 5 insulin resistance syndrome features as defined by the NCEP III.18
The results of our study suggest that the risk attributable to obesity largely depends on the concomitant presence of features of insulin resistance syndrome. Thus, among obese men, who would generally be considered to be at high risk of ischemic heart disease, those who accumulated fewer than 5 features of the syndrome were not at increased risk. This subgroup represented 71.9% of all obese men. Conversely, normal-weight men with 5 or more features of insulin resistance syndrome had a risk of ischemic heart disease 3.01 times higher than of those presenting with fewer than 3 features. About 6% of all normal-weight men had 5 or more features of insulin resistance syndrome. These results confirm that insulin resistance syndrome is more prevalent among obese men. Yet, BMI appears to be a poor atherogenic index for characterizing the risk of ischemic heart disease associated with insulin resistance syndrome. We therefore believe that clinicians should not use BMI to assess the long-term risk of ischemic heart disease attributable to obesity. Other measures of adiposity, such as waist circumference, which reflects total adiposity by regional deposition of fat as well, may be a more useful and adequate clinical tool for predicting risk of ischemic heart disease. In that regard, Janssen and associates have demonstrated that, after adjustment for waist circumference as a continuous variable, the likelihood of insulin resistance syndrome was similar in all BMI groups.19
Future studies will have to demonstrate that a combination of risk factors, and more particularly a combination of insulin resistance syndrome features and indices of obesity such as waist girth, has a greater clinical utility.
There were a number of limitations to our study. Unfortunately, we could not use the NCEP III definition of the metabolic syndrome in our cohort because data on waist girth and fasting plasma glucose levels were not collected in the study cohort in 1985. Our intent was not to propose a new definition of the metabolic syndrome but, rather, to examine how specific features of this syndrome modify the risk of ischemic heart disease attributable to variations in BMI. Physical activity was not assessed as thoroughly in 1985, and thus the extent to which adjustment for physical activity would have modified the interrelation between BMI, features of insulin resistance syndrome and risk of ischemic heart disease could not be analyzed. Our 1985 data on diet are also fragmentary, and thus they were not added to the multivariate. Finally, it must be stressed that much of the medical history (e.g., diabetes, medication use) was by self-report and was not further validated.
Our results indicate that the risk of ischemic heart disease associated with an elevated BMI was significantly modulated by features of insulin resistance syndrome. These data challenge the concept that the clinical definition of obesity, based on weight and height, is adequate as a clinical tool for the primary prevention of ischemic heart disease. Alternative measures such as waist circumference should be considered and thoroughly investigated.
β See related article page 1315