Obesity: A Growing Multifaceted Problem

Keywords
Obesity / complications; Overweight / physiopathology; Hypertension; Dyslipidemias; Public Health

Overweight and obesity are defined as body mass index (BMI) of 25-29.9 kg/m² and ≥ 30 kg/m², respectively. It is an alarming public health problem worldwide. Brazilian data show that 52.5% of Brazilians are overweight, and 17.9%, obese¹. In the USA, 35% of the adults are obese².

One major problem of obesity is its common association with arterial hypertension, dyslipidemia, insulin resistance and diabetes in the metabolic syndrome context^3,4. The adipose tissue plays a relevant role in the secretion of inflammatory and humoral mediators, which can favor the increase in blood pressure and insulin resistance⁵. This area has witnessed several advances, mainly related to epigenetic changes. Obese individuals, for example, show DNA hypermethylation in a specific region that encodes adiponectin, favoring lower secretion of that compound and exacerbating metabolic disease⁶.

Obesity, either independently or not, is recognized as an important risk factor for cardiovascular disease and heart failure^7,8. However, not all aspects of that association have been clarified. For example, a Brazilian national case series of 4050 asymptomatic patients undergoing exercise stress echocardiography has shown a greater prevalence of hypertension, diabetes, dyslipidemia, family history and sedentary lifestyle among obese individuals. However, on multivariate analysis adjusted for confounding factors, obesity has not associated with myocardial ischemia⁹. On the other hand, in patients with acute coronary syndrome, the abdominal circumference measure has associated with recurring angina, but not with other complications during hospitalization¹⁰.

Regarding the association of obesity and heart failure, in a case series with participants of the Framinghan study, an elevation of 1 kg/m² has increased by 5% the risk of developing heart failure^7,11. In fact, cardiac remodeling, clinically detected as left ventricular hypertrophy and left atrial enlargement, is observed in obese individuals^12,13. There are several hypotheses relating obesity to cardiac remodeling, and consequently to myocardial dysfunction. Experimental studies have suggested the participation of insulin resistance, altering the energetic metabolism and favoring the intracardiac accumulation of lipids, a phenomenon described as lipotoxicity¹². In addition, changes in calcium transport, in collagen and in epicardial fat have been reported as potential mechanisms responsible for obesity-induced cardiac remodeling, associated with myocardial dysfunction^12,14,15. It is worth noting that genetic changes, such as ALK7 gene polymorphism, which encodes the TGF-beta receptor, can be related to ventricular remodeling in patients with metabolic syndrome¹⁶. On the other hand, experimental studies have not identified the participation of the glycolytic pathway¹⁷ or imbalance between phosphorylated and total phospholamban¹⁸, but have reported a reduction in the expression of type-I collagen in high-fat diet-induced obese rats¹⁹. Another important, although less studied, aspect is the possibility of right ventricular remodeling, caused by pulmonary hypertension, resulting from the restriction imposed by obesity or coexistence of obstructive sleep apnea syndrome^12,20. Thus, the precise pathophysiological mechanisms associated with remodeling in obesity remain to be elucidated.

However, in some clinical situations, patients with overweight and mild obesity have had fewer hospitalizations and lower mortality as compared to those with lower BMI^7,21-23. The same apply to the triceps skinfold, whose values greater than 20 mm have been associated with lower mortality²⁴. This has been known as the paradox of obesity, and, although the mechanisms involved are unknown, the following hypotheses have been proposed: the U-shaped behavior, in which the extremes have higher risks; obese patients would be on more optimized treatments; and obese individuals could have a higher metabolic reserve to offset the catabolic changes of a chronic disease, such as heart failure⁷.

Another point that has been gaining attention recently is the overweight of children and adolescents. A Brazilian study, assessing 4609 children between 6 and 11 years of age, has shown that 24.5% of them are overweight²⁵. In addition, overweight children and adolescents have a higher prevalence of arterial hypertension and dyslipidemia^13,25,26. This context promotes the early increase of the cardiovascular risk, suggested by the correlation of BMI and insulin resistance, left ventricular mass index and intimal layer thickness of the common carotid artery¹³.

Finally yet importantly, the management of the obese patient poses another challenge. Weight regain induced by complex interactions between the hormonal and neuronal pathways, which regulate food intake, lifestyle, food pattern and genetic characteristics, hinders the continuous therapeutic approach of the obese patient²⁷. Thus, medications or bariatric surgeries are accepted as useful to reduce BMI²⁷. However, it is worth noting that the ultimate objective of the treatment is change in lifestyle and use of strategies to keep the patient motivated to loose weight^28,29.

Regarding obesity and its association with cardiovascular disease, there are still many gaps to be filled. Likewise, obesity remains a priority for future studies, both clinical and experimental, in an attempt to better understand its pathophysiological mechanisms and its clinical repercussions.

References

• ¹
  Ministério da Saúde. Vigitel Brasil 2014 - Vigilância de fatores de risco e proteção para doenças crônicas por inquérito telefônico [Internet]. [Acesso em 2015 jan 10]. Disponível em: portalsaude.saude.gov.br/images/pdf/2015/abril/15/PPT-Vigitel-2014-.pdf.
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• ²
  Centers for disease control and prevention. Adult overweight and obesity [internet]. Division of nutrition, physical activity, and obesity, national center for chronic disease prevention and health promotion. [Cited in 2015 Jan 10]. Available from: http://www.cdc.gov/obesity/adult/index.html
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  Kim AY, Park YJ, Pan X, Shin KC, Kwak SH, Bassas AF, et al. Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance. Nat Commun. 2015;6:7585.
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  Chase PJ, Davis PG, Bensimhon DR. The obesity paradox in chronic heart failure: what does it mean? Curr Heart Fail Rep. 2014;11(1):111-7.
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  Martins F, Campos DH, Pagan LU, Martinez PF, Okoshi K, Okoshi MP, et al. High-fat diet promotes cardiac remodeling in an experimental model of obesity. Arq Bras Cardiol. 2015 Aug 18. [Epub ahead of print].
• ¹⁶
  Zhang W, Wang H, Zhang W, Lv R, Wang Z, Shang Y, et al. ALK7 gene polymorphism is associated with metabolic syndrome risk and cardiovascular remodeling. Arq Bras Cardiol. 2013;101(2):134-40.
• ¹⁷
  Campos DH, Leopoldo AS, Lima-Leopoldo AP, Nascimento AF, Oliveira-Junior SA, Silva DC, et al. Obesity preserves myocardial function during blockade of the glycolytic pathway. Arq Bras Cardiol. 2014;103(4):330-7.
• ¹⁸
  Freire PP, Alves CA, Deus AF, Leopoldo AP, Leopoldo AS, Silva DC, et al. Obesity does not lead to imbalance between myocardial phospholamban phosphorylation and dephosphorylation. Arq Bras Cardiol. 2014;103(1):41-50.
• ¹⁹
  Silva DC, Lima-Leopoldo AP, Leopoldo AS, Campos DH, Nascimento AF, Oliveira Junior SA, et al. Influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Arq Bras Cardiol. 2014;102(2):157-63.
• ²⁰
  Sokmen A, Sokmen G, Acar G, Akcay A, Koroglu S, Koleoglu M, et al. The impact of isolated obesity on right ventricular function in young adults. Arq Bras Cardiol. 2013;101(2):160-8.
• ²¹
  Zuchinali P, Souza GC, Alves FD, d'Almeida KS, Goldraich LA, Clausell NO, et al. Triceps skinfold as a prognostic predictor in outpatient heart failure. Arq Bras Cardiol. 2013;101(5):434-41.
• ²²
  Kenchaiah S, Pocock SJ, Wang D, Finn PV, Zornoff LA, Skali H, et al; CHARM Investigators. Body mass index and prognosis in patients with chronic heart failure: insights from the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) program. Circulation. 2007;116(6):627-36. Erratum in: Circulation. 2007;116(6):e136.
• ²³
  Lavie CJ, De Schutter A, Alpert MA, Mehra MR, Milani RV, Ventura HO. Obesity paradox, cachexia, frailty, and heart failure. Heart Fail Clin. 2014;10(2):319-26.
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  Rosaneli CF, Baena CP, Auler F, Nakashima AT, Netto-Oliveira ER, Oliveira AB, et al. Elevated blood pressure and obesity in childhood: a cross-sectional evaluation of 4,609 schoolchildren. Arq Bras Cardiol. 2014;103(3):238-44.
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  Soares TS, Piovesan CH, Gustavo Ada S, Macagnan FE, Bodanese LC, Feoli AM. Alimentary habits, physical activity, and framingham global risk score in metabolic syndrome. Arq Bras Cardiol. 2014;102(4):374-82.
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  Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; Obesity Society. 2013 AHA/ACC/TOS Guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023.

Publication Dates

• Publication in this collection
  Nov 2015