Obesity and ischemic heart disease: defining the link.

Abstract

Obesity is a complex metabolic disorder that afflicts 35% of the adult population in the United States. As an important risk factor for ischemic heart disease (IHD) and its metabolic precedents, it has become one of the most serious health problems in many parts of the world. Nordestgaard et al1 have previously reported that an allelic score for obesity based on 3 single nucleotide polymorphisms (SNPs) associates with IHD and in accord with other findings2,3 supports a causal relationship. As reported in this issue,4 they have sought to define the intermediates underlying the increased risk. Article, see p 665 Their approach represents a novel application of Mendelian randomization principles to mediation analysis directed at exploring potential causal mechanisms that may link adiposity to cardiovascular disease focusing on lipoproteins, blood pressure (BP), glucose, and C-reactive protein (CRP). Using SNPs that contribute significantly to each of body mass index (BMI), and intermediary variables affecting IHD risk, including nonfasting remnant cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic and diastolic BPs, glucose, and CRP, they sought to clarify to what extent these variables contribute to increased IHD risk with increasing adiposity (Figure). One strength of this study is the large study population consisting of 3 large Danish cohorts, encompassing ≈90 000 individuals and ≈14 000 IHD outcomes. Figure. On the basis of the tenets of Mendelian randomization, …