OBESITY AND CARDIOVASCULAR SYSTEM, ANOTHER LOOK.
Our evolving understanding of the interaction of obesity and cardiac risks continues to augment and new data seem confounding. We have come a long way from the simple statement that obesity is a risk factor to the notion that distribution of weight seems to be the primordial factor. However, what about the concept of cardiac protection offered by obesity?
Around the turn of this century, the idea of the obesity paradox came into being when Fleischmann et al published data about mortality and hospital stay among hemodialysis patients1. The findings were the following, “Compared with the normal weight (BMI between 20 and 27.5), the one-year survival rate was significantly higher in the overweight patients and lower in the underweight patients. With a one-unit increase in BMI over 27.5, the relative risk for dying was reduced by 30% (P < 0.04), and with a one-unit decrease in BMI below 20, the relative risk was increased by 1.6-fold (P < 0.01).” Just in case one were to consider this finding a fluke, similar trends were noted for a growing list, cardiovascular risk, COPD and now pulmonary embolism2. On one hand obesity increases the risk of developing the complication but at the same time seems to protect against poor outcome3,4. An explanation offered for obesity paradox is the so-called collider stratification bias3,4, an abstruse theory beyond my grasp. Quoting directly from one author, “…in which conditioning on a variable (e.g., pulmonary embolism) affected by exposure (e.g., obesity) and outcome (pulmonary embolism is a known predictor of mortality) can introduce a spurious association between exposure (obesity is also a known predictor of mortality) and outcome and can even reverse the direction of association, making a harmful exposure appear protective3.” This sounds like a sophisticated way of saying this is a statistical glitch. One can only wonder if this theory is really what’s at play. We are certainly accustomed to the fact that members of a particular class of mediators can have opposite actions. Prostaglandins are a good example. Disentangling the paradox of obesity may have to start with the original sin of conflating it as a homogenous group. What appears to be heterodox observation in survival among members with elevated BMI may be a bit more subtle than at first look. However, one can’t downplay the fact that data show an adverse effect of obesity on cancer risk and survival5,6.
Certainly, we can all observe that at every age group, different body habitus exist. Obese people do live a long life like their lean counterparts, notwithstanding the fact that more of them will be found among patients suffering from cancer, pulmonary embolism, weight-bearing joint pathology, heart disease, diabetes and so on. The classification of obesity based on BMI is a convenient, simple formula but not a comprehensive surrogate marker and more appropriately distribution of fat seems to be a more relevant factor.
The adipocyte so far maligned and renown for its cytokines and their nefarious metabolic consequences is undergoing a reevaluation. In the abdomen and the viscera, such adipocyte lives up to its billing. We assumed that its presence in the buttock and elsewhere was innocuous since it didn’t represent a health risk. But a protective effect? Well, new data in young people show adipocyte as being constantly biologically active but in opposite directions, depending on its location7. Visceral/abdominal fat increases, while leg fat decreases cardiovascular risks. Fat from the arm seems to be neutral or increases risk slightly as the BMI increases. (See table below). The authors provide no theory to explain the difference but cite evidentiary data to support the different biologic activities. Basically, as alluded to above, tumor necrosis factor and plasminogen activator inhibitor are produced by visceral/abdominal fat. Free fatty acids storage is enhanced by leg adipocyte but visceral fat increases its level8
What does all this mean? It’s hard to say. The fact that the adipocyte may have some cardioprotective effect is a pleasant surprise. That it occurs in the leg is problematic since its accumulation at that location is not exactly sought for esthetic reason.
1. Fleischmann, Erwin et al. Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients. Kidney International, 1999, Volume 55, Issue 4, 1560 – 1567.
2. Keller, K., Survival Benefit of Obese Patients with Pulmonary Embolism. Mayo Clinic Proceedings, 2019, Volume 94, Issue 10, 1960-1973.
- Bauer, Philippe R. Obesity Paradox in Pulmonary Embolism: Myth or Reality? Mayo Clinic Proceedings, 2019, Volume 94, Issue 10, 1925 – 1927.
- Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. New England Journal of Medicine 2003; 348(17):1625-1638.
- Schmitz KH, Neuhouser ML, Agurs-Collins T, et al. Impact of obesity on cancer survivorship and the potential relevance of race and ethnicity. Journal of the National Cancer Institute 2013; 105(18):1344-1354.
4. Hailey R. Banack, Jay S. Kaufman. The obesity paradox: Understanding the effect of obesity on mortality among individuals with cardiovascular disease. Preventive Medicine, Volume 62, 2014, 96-102.
7. Yan, YinkunMi, Jie et al. Regional Adipose Compartments Confer Different Cardiometabolic Risk in Children and Adolescents: Mayo Clinic Proceedings, 2019, Volume 94, Issue 10, 1974 – 1982
8. Mauriège P, et al. Regional variation in adipose tissue metabolism of severely obese premenopausal women. J Lipid Res. 1995 Apr;36(4):672-84.