Obesity and cardiovascular health: the size of the problem

Abstract

. One strength of the umbrella review is that it assesses multiple biases for relevant outcomes as well as the stratification of findings into distinct levels of evidence. A multitude of umbrella reviews have been carried out over the last few years covering widely varying clinical disorders; however, none so far on obesity and multiple cardiovascular outcomes. In their study published in this issue of the European Heart Journal, Kim et al. conducted an umbrella review of 12 systematic reviews, where they identified 53 results from metaanalyses from altogether 501 cohorts, and 12 Mendelian randomization (MR) studies. Observational epidemiological studies suffer from many potential biases, including confounding and reverse causation. This limits their ability to identify causal associations. Because data from long-term randomized controlled trials of interventions against overweight and obesity are rare or non-existent, and only available in selected populations, causality between elevated indices of body weight and outcomes is difficult to establish. As a novel feature of this study, the authors incorporated MR studies into the body of evidence from observational studies. MR refers to the use of genetic variants as a proxy for environmentally modifiable exposures and can be implemented within observational epidemiological studies. The method can be considered as analogous to randomized controlled trials. In this instance, genetically predicted higher BMI and central adiposity can be regarded as randomly distributed with potential confounders equally distributed, and therefore there will be no need to consider reverse causation, which is particularly relevant with respect to obesity. For example, a Jshaped or U-shaped relationship between adiposity and outcomes is common, particularly in older and sicker populations, reflecting the influence of ageing and disease on body weight, and not that a higher weight in itself is protective. This is the first umbrella review on the topic of obesity and several types of fatal and incident cardiovascular outcomes, in this case hypertension, stroke, atrial fibrillation, venous thrombo-embolism, heart failure, valvular disease, and coronary heart disease. The authors performed a search for systematic reviews and metaanalyses of observational and MR studies that were published up to January 2021; the former in order to estimate the size of the effect and the latter to determine evidence of causality. About half of the associations were supported by high-level evidence. Associations were consistent between sexes and across global regions. The evidence level was assessed through MR studies, and graded at four levels (very low, low, moderate, and high). The net results are shown in a graphical abstract. The effect size in risk for every 5 kg/m increase in incidence varied from 10% increase for haemorrhagic stroke (low evidence) to 49% for hypertension (high evidence). The corresponding effect sizes for heart failure and coronary heart disease (CHD) were 41% and 15%, respectively (both high evidence). Similarly, among conditions with supported moderate or high level causality for obesity (BMI between 30 and 35 kg/m) were pulmonary embolism, venous thromboembolism, atrial fibrillation, as well as CVD and CHD mortality. In the MR studies, the effect size per 1 kg/m was 12% for heart failure and 7% for CHD, both with high evidence for causality. Among disorders with low or very low evidence levels for associations and/or weak evidence of causality were all-cause and haemorrhagic stroke, stroke and heart failure mortality, and sudden cardiac death. Accordingly, with respect to heart disease, collective evidence suggests that rising BMI is a risk factor for both CHD and heart failure, although the evidence concerning the link between categories (overweight, obese, and severely obese) and heart failure was weak. The authors note specifically that these heterogeneous results across adiposity categories complicate the interpretation of the association. Still, many studies will not have included a very large number of severely obese, which is the fastest growing category. Also, only adults were studied; we know from studies of very large populations of adolescents undergoing medical evaluation before military service that the increase in risk for several outcomes associated with rising BMI is much steeper than that usually seen for adults. The massive work undertaken in the study by Kim et al. is of particular interest for our understanding of current trends in heart disease incidence, and potentially also of what to expect in the future when increasing numbers of overweight, obese, and severely obese people who are now young or adolescent become middle aged and Editorial 3405