Life Can be Less Risky!

Abstract & Commentary

Synopsis: Eighty-seven percent or more of patients with fatal or nonfatal myocardial infarction (MI) have major risk factors prior to the event.

Source: Greenland P, et al. JAMA. 2003;290:891-897.

It has been frequently stated that coronary heart disease (CHD) occurs in the absence of major risk factors in as many as 50% of patients. The purpose of this paper was to determine the frequency of exposure to major risk factors in patients with fatal or nonfatal myocardial infarction.

Three prospective cohort studies were included: the Chicago Heart Association Detection Project in Industry, with a population of 35,642 men and women aged 18-59 years; screens for the Multiple Risk Factor Intervention Trial, including 347,978 men aged 35-57 years; and a population-based sample of 3295 men and women aged 34-59 years from the Framingham Heart Study (FHS). Follow-up lasted 21-30 years.

Fatal CHD in all cohorts and nonfatal MI in the FHS, compared by exposure to major CHD risk factors, defined as total cholesterol of at least 240 mg/dL, systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, cigarette smoking, and diabetes. Participants were stratified by age and sex (18-39 vs 40-59 years). For fatal CHD (n = 20,995), exposure to at least 1 major risk factor ranged from 87% to 100%. Among those ages 40-59 years at baseline with fatal CHD (n =19263), exposure to at least 1 major risk factor ranged from 87% to 94%. For nonfatal MI, prior exposure was documented in 92% (n = 167) of men 40-59 years at baseline and in 87% of women in this age group.

It was concluded that antecedent CHD major risk factor exposures were very common among those who developed CHD, emphasizing the importance of considering all major risk factors in CHD risk estimation and in attempting to prevent clinical CHD. The results challenge claims that CHD events commonly occur in persons without at least 1 major risk factor.

Comment by Ralph R. Hall, MD, FACP

Greenland and colleagues carried out a secondary analysis by changing the cholesterol levels to > 200 mg/dL and the blood pressure criteria to 120/80 mm Hg. The prevalence of risk factors remained at 87% or higher. If this study involving 386,915 subjects doesn’t convince us about the risk factor prevalence in CHD, an additional article in the same issue of JAMA by Khot et al, evaluating the same 4 risk factors in 14 international randomized clinical trials with 122,458 subjects, reached the same conclusions.1

A large number of subjects who had risk factors did not have MI. The reasons for this are probably varied. Some may have been protected by high levels of high density lipoproteins or life style interventions or died with stroke or cancer.

Khot et al note that "much attention has recently focused on the identification of genetic factors that play a role in the development of CHD. Although genetic differences may explain an individual’s propensity to develop CHD in the setting of conventional risk factors, it is doubtful that the population-wide prevalence of CHD is explained by genetic factors. Epidemiological studies have shown that the risk of CHD in populations is largely dependent on the prevalence of conventional risk factors and other environmental factors such as diet.2,3 Furthermore, the prevalence can vary as the environmental conditions change over short periods, as seen in Japanese migration studies."4

The implications for these studies are immense. The authors of these papers note that 2 studies have shown that lack of hypertension, hyperlipidemia, and cigarette smoking was associated with a 77% to 90% reduction in cardiovascular mortality.5,6 There have been numerous trials demonstrating the decreased morbidity and mortality following treatment of elevated cholesterol levels.

The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)4 of high-risk hypertensive subjects without evidence of CHD demonstrated a 36% reduction in death and MI in only 3.3 years. Hackam and Anand in the same issue of JAMA evaluate other risk factors that are associated with CHD. They conclude that the optimal use of C-reactive protein, homocysteine, lipoprotein (a), and fibrinogen in routine screening remains to be determined.7

The message is clear. Treating the 4 major risk factors will dramatically reduce morbidity, mortality and the huge monetary drain on the health care budget.

Dr. Hall, Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.


1. Khot UN, et al. JAMA. 2003;290:898-904.

2. Verchuren WM, et al. JAMA. 1995;274:131-136.

3. Hertog MG, et al. Arch Intern Med. 1995;155:381-386.

4. Worth RM, et al. Am J Epidemiol. 1975;102:481-490.

5. Stamler J, et al. JAMA. 1999;282:2012-2018.

6. Magnus P, Beaglehole R. Arch Intern Med. 2001;161:2657-2660.

7. Hackam DG, Anand SS. JAMA. 2003;290:932-940.