Excess weight Independently Increases Risk of Heart Disease

BILTHOVEN, The Netherlands, Sept. 10 -- Pounds weigh heavily on the risk of developing coronary heart disease, independent of traditional risk factors, according to a meta-analysis.

Excess weight alone increases the risk of coronary heart disease by 17% to 49%, depending on weight, Rik P. Bogers, Ph.D., of the National Institute for Public Health and the Environment here, and colleagues reported in the Sept. 10 issue of Archives of Internal Medicine.

The extent to which moderate overweight (BMI 15.0-29.9) and obesity (? 30.0) are associated with an increased risk of coronary heart disease through adverse effects on blood pressure and cholesterol levels is unclear, as is the risk that remains after these mediating effects are considered, the researchers wrote.

Dr. Bogers and his team analyzed the worldwide combined data from 21 studies of overweight and heart disease that included 302,296 healthy, mainly white persons. Studies came from a regular check of PubMed and Medline databases as far back as the 1960s with additional studies from Medline from 1996 to 2005.

Relative risks (RRs) of coronary heart disease associated with moderate overweight and obesity with and without adjustment for blood pressure and cholesterol concentrations were calculated by members of the worldwide collaboration of prospective cohort studies

A total of 18,000 cardiac events or deaths occurred during follow-up. After adjustment for age, sex, physical activity, and smoking, moderately overweight individuals had a 32% increased risk of coronary heart disease compared with normal-weight individuals (adjusted RR 1.32, 95% confidence intervals 1.24-1.40), the researchers reported.

Obese individuals had an 81% increased risk compared with normal weight individuals (RR 1.81, 1.56 - 2.10).

After additional adjustment for blood pressure and cholesterol levels, the excess risk associated with being moderately overweight still remained, although it was reduced nearly in half to 17% (RR 1.17, 1.11-1.23).

After additional adjustment for blood pressure and cholesterol levels, the excess risk associated with being obese was cut to a 49% excess risk (RR, 1.49, 1.32-1.67).

The relative risk associated with a five-unit increase in BMI was 29% (RR 1.29, 1.22- 1.35) before adjusting for blood pressure and cholesterol levels. After adjustment, the five-unit increase amounted to a 16% increased risk (RR 1.16, 1.11-1.21).

Several mechanisms could underlie the independent effect of overweight on coronary heart disease, the researchers said.

These include, low-grade inflammation, endothelial dysfunction, hemostatic imbalance favoring coagulation, impaired endothelial vasodilatory responses, left ventricular hypertrophy, and reduced heart rate variability. Furthermore, they said, overweight is associated with an increased risk of diabetes.

The present study has two important implications, Dr. Bogers said. First, even being moderately overweight is associated with an increased risk of coronary heart disease.

Second, the fact that the relative risks remained statistically significant after adjustment for blood pressure and cholesterol levels, adds to the evidence that overweight itself increases coronary heart disease risks independent of traditional risk factors.

This implies, the researchers said, that, even under the theoretical scenario that optimal treatment would be available for hypertension and hypercholesterolemia in overweight persons, they still would have an elevated risk of coronary heart disease.

Some alternative explanations for the findings should be noted, the researchers said.

For example, they did not control for diet, which has been shown to be related to coronary heart disease, because detailed data were not included in the studies they reviewed. However, they noted, in the Nurses' Health Study, the largest study included, adjustment for diet had virtually no effects on the association between BMI and heart disease.

Another limitation was the fact that the findings applied to predominantly white, healthy persons.

Commenting on their findings, the researchers noted that the worldwide increase in numbers of people who are moderately overweight may drive the incidence of coronary heart disease upward.

Although the effects of confounders, such as specific dietary factors, cannot be completely ruled out, the researchers said, negative effects are exerted both through adverse influences on blood pressure and cholesterol levels but also through other pathways, the researchers said.