Impact of Obesity on Cardiovascular Disease
Obesity is associated with increased risk of cardiovascular disease (CVD), heart failure, diabetes, cancer, and ultimately all-cause mortality. Obesity is causally related to dyslipidemia, hypertension, and diabetes, all strong CVD risk factors, and so causally related to CVD risk. In fact, a substantial part of the risk imparted by obesity on CVD outcomes operates via traditional risk factors. Obese men are almost twice as likely and women almost two and half times as likely to develop hypertension. Obese individuals are around 50% more likely to have a stroke and have around 6–12 times higher risks of developing type 2 diabetes compared to those with a normal BMI.
Obesity is also linked to greater risk for development of heart failure. Yet, there appears to be an obesity paradox in established heart failure such that the risk of death is lower in overweight and mildly obese individuals than in those with normal weight. Such observations are likely partially driven by reverse causality whereby disease-specific issues drive weight loss rather than higher weight per se being protective.
While obesity is most commonly defined by BMI, the importance of body fat distribution and markers such as waist circumference, waist: hip ratio, visceral and ectopic fat volumes are becoming better appreciated. The concept of harmful fat distribution is therefore topical and recent evidence suggest those who can store more fat subcutaneously (and so delay their ectopic depot expansions until much heavier) have lesser diabetes and cardiovascular risks. This paradigm may also largely explain men’s greater risks for both chronic conditions at similar BMI’s to women.
Trials of weight loss add strong support for causal links between adiposity and CVD; for example, the best evidence suggests that losing around 1 kg reduces SBP by around 1 mmHg. Weight loss also improves lipid profiles with reduced total cholesterol, LDL-cholesterol, and in particular triglyceride levels. Weight loss of around 5 kg reduces the risk of obese individuals progressing to impaired glucose tolerance and type 2 diabetes. In those with type 2 diabetes, 5 to <10% intentional weight loss is associated with 3.5 times increased odds of obtaining a 0.5% reduction in HbA1c. Not surprisingly, substantial weight loss has been associated with significantly lower mortality from several causes.
This chapter will show how the best epidemiological evidence, using methods to lessen the impact of reverse causality, supports strong graded links between adiposity and CVD. It will also examine and explain the apparent obesity paradox of heart failure. The chapter will then describe the effect on CVD outcomes of robust lifestyle and surgical intervention studies and trials. Finally, we will also explain how genetics data have helped support causal associations between increasing BMI and CVD, including understanding better the causal links between regional adiposity and CVD.
In conclusion, several lines of evidence, including observational, trial, and genetic, collectively support causal links between obesity, cardiovascular morbidity and mortality, and all-cause mortality.
KeywordsObesity Cardiovascular disease Heart failure Obesity paradox Weight reduction Bariatric surgery Regional adiposity Ectopic fat
- Britton KA, Fox CS. Ectopic fat depots and cardiovascular disease. Circulation. 2011;124(24):e837–41. Available at: http://circ.ahajournals.org/cgi/doi/10.1161/CIRCULATIONAHA.111.077602. Accessed 19 Mar 2017.
- Collaboration, N.R.F. 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. Lancet. 2016;387(10026):1377–96. Available at: http://linkinghub.elsevier.com/retrieve/pii/S014067361630054X. Accessed 14 Feb 2017.
- Coutinho T, et al. Central obesity and survival in subjects with coronary artery disease. J Am Coll Cardiol. 2011;57(19):1877–86. Available at: http://linkinghub.elsevier.com/retrieve/pii/S0735109711007327. Accessed 21 Mar 2017.PubMedCrossRefGoogle Scholar
- Després J-P. Excess visceral adipose tissue/ectopic fat the missing link in the obesity paradox? J Am Coll Cardiol. 2011;57(19):1887–9. Available at: http://www.onlinejacc.org/content/accj/57/19/1887.full.pdf. Accessed 7 May 2017.PubMedCrossRefGoogle Scholar
- Emerging Risk Factors Collaboration, et al. Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet. 2011;(9771):377, 1085–1395. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21397319. Accessed 7 May 2017.
- Foster MC, et al. Fatty kidney, hypertension, and chronic kidney disease. Hypertension. 2011;58(5):784–90. Available at: http://hyper.ahajournals.org/content/58/5/784.short. Accessed 8 May 2017.PubMedPubMedCentralCrossRefGoogle Scholar
- Holmes MV, et al. Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis. Am J Hum Genet. 2014;94(2):198–208. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928659/pdf/main.pdf. Accessed 7 May 2017.PubMedPubMedCentralCrossRefGoogle Scholar
- International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. 2006.Google Scholar
- Jensen MD, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults. Circulation. 2014;129(25 suppl 2):S102–38. Available at: http://circ.ahajournals.org/lookup/doi/10.1161/01.cir.0000437739.71477.ee. Accessed 13 Mar 2017.PubMedCrossRefGoogle Scholar
- Kwok CS, et al. Bariatric surgery and its impact on cardiovascular disease and mortality: a systematic review and meta-analysis. Int J Cardiol. 2014;173(1):20–8. Available at: http://linkinghub.elsevier.com/retrieve/pii/S0167527314003799. Accessed 13 Mar 2017.PubMedCrossRefGoogle Scholar
- Lim EL, et al. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011;54(10):2506–14. Available at: http://link.springer.com/10.1007/s00125-011-2204-7. Accessed 16 Sept 2016.PubMedPubMedCentralCrossRefGoogle Scholar
- National Institute for Health and Care Excellence (NICE). Weight management: lifestyle services for overweight or obese adults. 2014.Google Scholar
- National Institute for Health and Clinical Excellence (NICE). Obesity: the prevention, identification, assessment and management of overweight and obesity in adults and children. 2006. Available at: https://www.nice.org.uk/guidance/cg43/evidence
- National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults – the evidence report. Obes Res. 1998;6(suppl 2):51–209S.Google Scholar
- Neter JE, et al. Influence of weight reduction on blood pressure. Hypertension. 2003;42(5):878–84. Available at: http://hyper.ahajournals.org/content/42/5/878.long. Accessed 7 May 2017.PubMedCrossRefGoogle Scholar
- Nordestgaard BG, et al. The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach. Minelli C, editor. PLoS Med. 2012;9(5):e1001212. Available at: http://dx.plos.org/10.1371/journal.pmed.1001212. Accessed 7 May 2017.
- Nordström A, et al. The higher prevalence of type 2 diabetes in men than in women is associated with differences in visceral fat mass. J Clin Endocrinol Metab. 2016;101(10):3740–6. Available at: http://press.endocrine.org/doi/10.1210/jc.2016-1915. Accessed 4 Sept 2016.PubMedCrossRefGoogle Scholar
- Poobalan A, et al. Effects of weight loss in overweight/obese individuals and long-term lipid outcomes – a systematic review. Obes Rev. 2004;5(1):43–50. Available at: http://doi.wiley.com/10.1111/j.1467-789X.2004.00127.x. Accessed 7 May 2017.PubMedCrossRefGoogle Scholar
- Scottish Intercollegiate Guidelines Network. Scottish Intercollegiate Guidelines Network SIGN management of obesity. 2010. Available at: http://www.sign.ac.uk/pdf/sign115.pdf. Accessed 7 May 2017.
- Sjöström L, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1):56. Available at: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2011.1914. Accessed 16 Dec 2016.PubMedCrossRefGoogle Scholar
- Stefan N, Kantartzis K, Häring H-U. Causes and metabolic consequences of fatty liver. Endocr Rev. 2008;29(7):939–60. Available at: http://press.endocrine.org/doi/abs/10.1210/er.2008-0009. Accessed 16 Sept 2016.PubMedCrossRefGoogle Scholar
- The Global BMI Mortality Collaboration. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388(10046):776–86. Available at: http://linkinghub.elsevier.com/retrieve/pii/S0140673616301751. Accessed 27 Dec 2016.
- The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration. Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1·8 million participants. Lancet. 2014;383(9921):970–83. Available at: http://linkinghub.elsevier.com/retrieve/pii/S014067361361836X. Accessed 28 Dec 2016.
- The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145–54. Available at: http://www.nejm.org/doi/10.1056/NEJMoa1212914. Accessed 7 May 2017.
- Wing RR, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes care. 2011;34(7):1481–6. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21593294. Accessed 13 Mar 2017PubMedPubMedCentralCrossRefGoogle Scholar
- World Health Organisation. Global status report on noncommunicable diseases 2010. 2011. Available at: http://apps.who.int/iris/bitstream/10665/44579/1/9789240686458_eng.pdf. Accessed 7 May 2017.
- World Health Organisation. WHO | Obesity and overweight. World Health Organization. 2016. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 7 May 2017.
- World Health Organization. WHO | Obesity: preventing and managing the global epidemic. WHO. 2000. Available at: http://www.who.int/nutrition/publications/obesity/WHO_TRS_894/en/. Accessed 7 May 2017.
- Yaghootkar H, et al. Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension, and heart disease. Diabetes. 2016;65(8):2448–60. Available at: http://diabetes.diabetesjournals.org/content/65/8/2448.long. Accessed 4 May 2017.