HealthDay News — Body mass index (BMI) has been causally linked with ischemic heart disease (IHD), recent study results indicate.

Ischemic heart disease risk rose 52% with each 4 kg/m2 in BMI when factoring in genetics (95% CI 1.12 to 2.05), Nicholas J. Timpson, PhD, of the University of Bristol, in England, and colleagues reported online in PLoS Medicine.

“These data add evidence to support a causal link between increased BMI and IHD risk, though the mechanism may ultimately be through intermediate factors like hypertension, dyslipidemia and type 2 diabetes,” they wrote.

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Although previous prospective and retrospective observational studies have linked higher BMI to increased heart disease risks across different populations, none have convincingly demonstrated causality due to confounding, reverse causation and bias, the researchers explained.

So they analyzed IHD incidence among 75,627 study participants, measured BMI and looked at three specific genotypes known to influence BMI: FTO (rs9939609), MC4R (rs17782313), and TMEM18 (rs6548238).

All participants were white and Danish and were pooled from three studies: the population-based Copenhagen General Population and Copenhagen City Heart studies and the case-control Copenhagen Ischemic Heart Disease Study.

Using the genotypes as a combined allele score, the allele score-BMI and allele score-IHD associations were calculated and used in instrumental variable analyses to estimate the causal odds ratio (OR) between BMI and IHD, which was then compared with observational analyses.

A meta-analysis of the three studies revealed that the odds of IHD increased 26% with every 4 kg/m2 increase in BMI (95% CI: 1.19-1.34). A one-unit allele score increase correlated with an 0.28 kg/m² increase in BMI (95% CI 0.22 to 0.34), and an OR for IHD of 1.03 (95% CI: 1.01 to 1.05). 

For those carrying all six alleles, the average increase in BMI was 1.68 kg/m² and the odds for IHD increased by 18%. For a 4 kg/m² increase in BMI, the causal OR for IHD was 1.52 in instrumental variable analysis. 

These “estimates suggest that the same increase in BMI is causally related to an increased risk of ischemic heart disease consistent with observational estimates, if not greater,” the researchers concluded.

Nordestgaard BG et al. PLoS Med. 2012; doi: 10.1371/journal.pmed.1001212.