Can we use BMI as a biomarker for heart disease risk?

EAS 2011

- Data from over 71,000 Danish subjects in three large observational studies show a simple cause and effect relationship between body mass index (BMI) and ischaemic heart disease (IHD) risk. Thus, BMI is likely to be preferable to C-reactive protein (CRP) in evaluating cardiovascular disease risk.

C-reactive protein (CRP) is a sensitive biomarker of systemic inflammation.¹ Elevated CRP levels are associated with an increased risk of cardiovascular events. In addition, CRP might be directly involved in mediating local inflammation. This has led some to suggest a causal role for CRP in cardiovascular disease. However, as discussed by Professor Borge Nordestgaard, Copenhagen City Hospital, University of Copenhagen, Denmark the data instead support the view that CRP is an inflammatory marker of IHD. This led him to speculate that other inflammatory biomarkers may be relevant to heart disease risk. He highlighted the possibility that BMI might be of relevance, given that individuals who are obese (BMI >30 kg/m²) have increased levels of inflammatory markers, including CRP.

Indeed, data from a Mendelian randomization study showed a strong, positive association between circulating CRP and BMI.² It is likely that this association is driven by BMI, as CRP is a marker of elevated adiposity.

This was investigated further in a study, reported at the Wednesday Plenary session. Data were obtained from the Copenhagen General Population study, the Copenhagen City Heart study and the Copenhagen Ischaemic Heart Disease study. Using an observational analysis approach, for every 4 kg/m² increase in BMI there was a 26% increase in risk of IHD. The investigators investigated the effect of specific genes known to be associated with obesity (FT0, MC4R, TMEM18), on IHD risk. The greater the frequency of these alleles, the greater the risk of IHD; individuals with 3 or 4 alleles (of 6 in total) had 20-22% increase in IHD risk.

When the data were analysed using an instrumental variable approach, taking into account the effect of these genes, each 4 kg/m² increase in BMI was associated with a 52% increase in IHD risk. Taken together, these data show an independent cause and effect between BMI and IHD. ‘Given that BMI is a simple marker that can be readily measured these data are likely to have implications for public health policy,’ concluded Professor Borge Nordestgaard, Copenhagen City Hospital, University of Copenhagen, Denmark.

Further work is needed to elucidate the mechanism of this effect.

References

1. The Emerging Risk Factors Collaboration: C-reactive protein concentration and risk of coronary heart disease, stroke and mortality: An individual participant meta-analysis. Lancet 2009; DOI: 10.1016/S0140–6736(09)61717–7.

2. Timpson NJ, Nordestgaard BG, Harbord RM, Zacho J, Frayling TM, Tybjærg-Hansen A, Davey Smith G. C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization. International Journal of Obesity 35, 300-308 (February 2011) doi:10.1038/ijo.2010.137.