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Corresponding author. Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec − Université Laval, 2725, chemin Sainte-Foy, A-2029, Québec, QC, G1V 4G5, Canada.
The epidemic proportions reached by obesity all over the world remains a constant topic of discussion in both the medical/scientific literature and in the media. Figures published by the NCD Risk Factor Collaboration network are far from being encouraging. For instance, it has been estimated that by 2025 the global prevalence of obesity will have reached 18% in men and exceed 21% in women [
NCD Risk Factor Collaboration Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants.
]. Population-based cohorts have all shown that there is a progressive increase in the risk of morbidity and mortality as a function of increasing body mass index (BMI) values, the BMI being the most commonly used anthropometric index to crudely classify individuals into normal weight, overweight and obesity categories [
]. Despite such overwhelming evidence that a higher body weight (standardized for height) is associated with an increased risk of cardiovascular outcomes, obesity has failed to be identified as an independent risk factor for CVD once intermediate risk factors (blood pressure, lipids, diabetes) are taken into account [
Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies.
]. Thus, although excess adiposity crudely assessed by an elevated BMI drives intermediate risk factors, we still do not have evidence that losing weight through lifestyle modification programs reduces CVD outcomes. It is also very important to point out that the dramatic rise in obesity is not only limited to adults. The number of overweight and obese children and adolescents is high and on the rise in several regions of the world [
NCD Risk Factor Collaboration Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults.
]. This phenomenon is a major source of concern not only because of its related short-term cardiometabolic complications such as dyslipidemia, hypertension, and type 2 diabetes [
]. Indeed, the seminal work of Henry McGill has has documented that the atherosclerosis process starts at a young age, and that the number of young individuals developing atherosclerosis is on the rise, especially when risk factors are present [
]. For instance, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study has documented the natural history of atherosclerosis in approximately 3000 young subjects aged 15–34 years old who died accidently [
]. Several measurements were performed on post-mortem arteries along with the lipoprotein-lipid profile as well as other cardiometabolic risk variables including the thickness of the panniculus adiposus and the BMI as indicators of adiposity. In young men, obesity was associated with more extensive fatty streaks and raised lesions in the right coronary artery [
]. Several additional analyses from the PDAY study reported significant associations between obesity and accelerated coronary atherosclerosis, particularly in young men [
]. Whether this phenomenon was associated with a greater risk of developing coronary heart disease was also investigated, yielding at times mixed results. An increased body weight in adolescence or early adulthood has been associated with an increased risk of coronary heart disease in some studies [
Association of body mass index measured in childhood, adolescence, and young adulthood with risk of ischemic heart disease and stroke: findings from 3 historical cohort studies.
In order to further explore the issue of the impact of excess body weight while being a young adult as well as of the magnitude of weight changes over decades on coronary atherosclerosis, investigators of the Swedish CArdioPulmonary bioImage Study (SCAPIS) used noninvasive imaging technologies to quantify the extent of atherosclerosis in the coronary and carotid arteries of their participants along with information obtained by proteomics/metabolomics/genomics technologies, with the ultimate goal of improving prediction of CVD risk. In this issue of Atherosclerosis, Bergström et al. [
] document the risk of midlife coronary atherosclerosis as a function of body weight at 20 years of age (reported by participants), of body weight measured at midlife and of body weight changes over that period. The SCAPIS sample included 25,181 female (51%) and male participants without previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass graft, with a mean age of 57 years. Coronary atherosclerosis was assessed by coronary computed tomography angiography and total coronary atherosclerotic burden was calculated using the segment involvement score (SIS) which provides a measure of the total number of coronary segments with atherosclerosis irrespective the degree of stenosis.
A higher body weight at age 20 was associated with an increased probability of having coronary atherosclerosis in both men and women after adjusting for site, age, height, LDL-cholesterol, smoking, alcohol intake, education status and level of physical activity. Body weight at midlife (50–64 years) was also associated with a higher probability of having a SIS>0. Further adjustments for systolic blood pressure, type 2 diabetes and treatment for dyslipidemia and hypertension did not substantially alter these associations. When Duke or coronary artery calcification scores were used instead of SIS, essentially similar conclusions were reached. However, when weight changes from body weight at age 20 were examined, the magnitude of associations were lower and were only found in men having a higher weight at age 20. No relationship was found with weight changes in women.
The SCAPIS investigators should be commended for having conducted such a large cardiometabolic imaging study with imaged coronary arteries obtained in more than 25,000 men and women. Firstly, results confirm that a high body weight at the start of our adult lives is predictive of more coronary atherosclerosis at midlife (irrespective of the method or score used), a finding which emphasizes the importance of primordial prevention [
Life’s Essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association.
]. Unfortunately, with the rapidly growing epidemic of obesity in the pediatric population resulting, among others, from sedentary behaviors and a lack of physical activity, a somber future can be foreseen [
Sedentary behaviors in today's youth: approaches to the prevention and management of childhood obesity: a scientific statement from the American Heart Association.
]. Promotion of healthy lifestyle at school and development of environments permissive to healthy eating habits and physically active lifestyle for all should therefore be a top priority.
Secondly, midlife body weight was also found to be associated with coronary atherosclerosis, an expected finding considering the abundant literature on the topic [
Waist circumference as a marker of obesity is more predictive of coronary artery calcification than body mass index in apparently healthy Korean adults: the Kangbuk Samsung Health Study.
]. However, the lack of robust association between weight changes since early adult years and midlife coronary atherosclerosis, may appear, at first glance as a counterintuitive finding. However, several factors could explain these results. For instance, the use of body weight as an anthropometric variable to assess overweight and obesity is likely to have misclassified a substantial number of individuals regarding their changes in body composition and body fat distribution [
]. Although some weight gain is expected with healthy aging, the question that should have been addressed is the composition and location of such weight gain. For example, a physically active individual may increase his/her muscle mass with some limited changes in body fat mass whereas a sedentary person may lose some muscle mass while gaining some adipose tissue, particularly in the abdominal visceral region [
]. Such individual differences in body composition and adipose tissue distribution changes will likely have a major impact on the rate of progression of coronary atherosclerosis. Thus, the investigators have the opportunity to further explore these issues in their formidable database. What happened to female and male participants matched for weight gain but who differed in their level of physical activity or visceral adiposity?
Furthermore, as the authors have imaging data, it would be interesting to examine the contribution of ectopic fat depots on coronary atherosclerosis beyond weight changes. Individual differences in visceral adiposity, epicardial adiposity, liver fat and skeletal muscle fat are all factors that could explain why a given weight gain may be associated with considerable individual variation in coronary atherosclerosis assessed at midlife (Fig. 1). Moreover, menopause has been associated with an acceleration in the accumulation of visceral adipose tissue [
]. Considering that approximately 75% of women in SCAPIS were above 54 years of age, it is likely that a significant subgroup of female participants were in the post-menopausal stage at the time of examination. This phenomenon has not been taken into account in the analyses and should deserve further investigation. Use of hormonal replacement therapy known to affect body fat distribution would also be another issue to explore.
Fig. 1Schematic representation of the rate of progression (slow or accelerated) of coronary atherosclerosis as it relates to healthy or unhealthy lifestyle habits and ectopic fat deposition.
Again, the SCAPIS investigators should be congratulated for conducting such a remarkable cardiometabolic imaging study. Study findings (association between current coronary atherosclerosis assessed at midlife and reported body weight at age 20) emphasize the need to intervene early, both in clinical practice and through population-based initiatives. The study findings are consistent with the notion that weight changes over decades is too crude as a phenotype to be helpful in the discrimination of individuals at high risk of coronary atherosclerosis. Monitoring weight changes over decades of our adult lives is like only looking at the tip of a potentially deadly iceberg. However, with the richness of SCAPIS, we should expect many additional findings in months/years to come to document the importance of paying attention to key behaviors (such as level of moderate to vigorous physical activity directly measured by accelerometry) as well indices of body fat distribution (such as visceral and ectopic adiposity and of simple clinical tools such as waist circumference).
Meanwhile, results of the present study underline the need to intervene early by filling the gap between clinical- and population-based approaches if we want to produce future generations of citizens not entering their adult lives with premature coronary atherosclerosis. The current obesity epidemic is rather a lifestyle epidemic resulting from the fact that we have designed a socioeconomic model most often not permissive to healthy behaviors. Premature atherosclerosis resulting from high-risk forms of overweight and obesity will require more than medical solutions.
Financial support
J.P.D. is the Scientific Director of the International Chair on Cardiometabolic Risk supported by the Fondation de l’Université Laval and is the co-chair holder of the Chaire de recherche en santé durable funded by Fonds de recherche du Québec – Santé. Research from J.P.D. is currently supported by the Canadian Institutes of Health Research (Foundation grant FDN-167278).
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
NCD Risk Factor Collaboration
Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants.
Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies.
Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults.
Association of body mass index measured in childhood, adolescence, and young adulthood with risk of ischemic heart disease and stroke: findings from 3 historical cohort studies.
Life’s Essential 8: updating and enhancing the American Heart Association’s construct of cardiovascular health: a presidential advisory from the American Heart Association.
Sedentary behaviors in today's youth: approaches to the prevention and management of childhood obesity: a scientific statement from the American Heart Association.
Waist circumference as a marker of obesity is more predictive of coronary artery calcification than body mass index in apparently healthy Korean adults: the Kangbuk Samsung Health Study.
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