Overweight Increases CHD Risk Independent of BP and Cholesterol

The adverse effects of overweight on BP and cholesterol levels could account for about 45% of the increased risk for CHD. Even moderately overweight individuals have an increased risk of coronary heart disease (CHD) that is independent of the effects of their weight on blood pressure and cholesterol levels, a new meta-analysis in more than 300,000 people shows.
Dr Rik P Bogers (National Institute for Public Health and the Environment, Bilthoven, the Netherlands) and colleagues tell us se that it was already known that obese individuals have an increased risk of CHD independent of blood pressure and cholesterol, but this is one of the first studies to show a similar finding with regard to moderate overweight. The results are important, he says, because they indicate that even when overweight people are optimally treated for hypertension and hypercholesterolemia, they will still retain an elevated risk of CHD.

"This indicates that overweight or obesity should be included in commonly used risk-stratification schemes, such as Framingham," Bogers states. Such models have not traditionally incorporated body mass index (BMI) or other measures of body weight — such as waist-to-hip ratio — although some newer models being assessed do include BMI, such as the recently proposed Q-RISK score in the UK.

Bogers and colleagues included 21 studies in their meta-analysis, including a total of 302,296 participants and 18,000 CHD events in predominantly white populations from around the world. They found that a five-unit increment in BMI was associated with a 29% increased risk of CHD and, after additional adjustment for blood pressure and cholesterol levels, with a 16% increased risk.

"The present study indicates that adverse effects of overweight on blood pressure and cholesterol levels could account for about 45% of the increased risk of CHD and that there is still a significantly increased risk of CHD that is independent of these effects," the researchers note.

Relative risks of CHD for moderate overweight and obesity compared with normal weight, with and without adjustments for BP and cholesterol

Study group adjustments	RR for moderate overweight	p value for heterogeneitya	RR for obesity	p value for heterogeneitya
All studies, adjusted for age, sex, physical activity, and smoking	1.32	0.007	1.81	< 0.001
All studies, additionally adjusted for blood pressure and cholesterol	1.17b	0.15	1.49b	< 0.001

a. p value for heterogeneity in RR between studies
b. p < 0.001 for difference in RR with and without adjustment for BP and cholesterol level
Bogers et al say that several mechanisms could underlie an effect of overweight on CHD independent of traditional risk factors, including a state of low-grade inflammation, endothelial dysfunction, and hemostatic imbalance favoring coagulation, among others.

In the US National Cholesterol Education Program Adult Treatment Panel III, obesity is not listed as a risk factor because it is said to operate through diabetes and other risk factors, Bogers et al note. So including data on diabetes and glucose intolerance — which were not available — in this meta-analysis "would have further attenuated the RR of CHD associated with overweight," they admit.

However, while he believes diabetes does also contribute to the increase in CHD associated with overweight, he doesn’t think it can account for all of the risk remaining after adjustment for blood pressure and cholesterol.
The bottom line, says Bogers, is that "the worldwide increase in moderate overweight may drive the incidence of CHD upward."

Bogers RP, Bemelmans WJ, Hoogenveen RT, et al. Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels. A meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med 2007;167(16):1720-1728.