The Obesity Paradox in Cardiovascular Diseases: Rebuttal: Obesity Paradox Does Not Translate to the Promotion of Obesity!

The relationship between obesity and cardiovascular diseases (CVDs) has been the object of numerous investigations in the last 2 decades. The presence of excess fat mass that impairs health defines obesity, which can increase the risk to develop several CVDs and CVD risk factors, such as hypertension, glucose metabolism abnormalities, and dyslipidemia. This needs to be clearly stated to understand what we mean when describing the obesity paradox in patients with established CVD. With these premises, we highlighted that the presence of an obesity paradox reported in several studies and in a number of CVD does not certainly suggest that we promote weight gain, at least not in those who have a normal weight, overweight, or obesity. To the contrary: in those who are underweight, weight gain may perhaps be beneficial, particularly when resulting in lean mass (LM) gain to achieve a normal body weight status. This may also be the case in some with low “normal” weight and low LM.

In our article in the Journal (1), we have discussed that, in patients with established CVD, particularly coronary heart disease (CHD), heart failure (HF), atrial fibrillation, and pulmonary arterial hypertension, obesity has been associated with improved prognosis, at least at the epidemiologic level. We have proposed that such benefits could be partially driven by the excess LM present in individuals with obesity, typically associated with improved cardiorespiratory fitness (CRF), which is, in turn, strongly associated with improved survival.

Based on these principles, we would like to reinforce the message that, if individuals with the above listed CVD did not develop obesity, they could have potentially reduced their likelihood to develop such CVD in the first place, particularly in the absence of concomitant major CVD/CHD risk factors. This is highlighted by our recent articles strongly promoting the preservation of a healthy body weight in those who present body weight and body composition compartments within normal ranges, and avoiding additional weight gain in those who have already developed overweight or obesity (2,3). Promotion of obesity should not be attributed to our work by any means. In a perfect world, all individuals would remain lean during the course of their lifespan, from childhood and adolescence to adulthood, as well as physically active and following a healthy diet (2,4,5). However, this is hardly the case, considering that the prevalence of obesity in the United States has reached epidemic proportion, with 39.6% of adults meeting the body mass index (BMI) criteria for obesity (≥30 kg · m⁻²), 7.7% for severe or morbid obesity (≥40 kg · m⁻²), and over three-fourths either overweight (≥25 and <30 kg · m⁻²) or obese (6).

Because of the high prevalence of overweight and obesity, facing excess adiposity and obesity-related comorbidities has become of crucial importance and an indispensable skill for clinicians and researchers. This approach has clearly changed in the last decades. Generally, if we were sitting with 2 postmyocardial infarction (MI) patients or with a diagnosis of HF 2 to 3 decades ago, one with a BMI in the low 30s kg · m⁻² and one with normal weight with a BMI in the low 20s kg · m⁻², we would have expected that the one with the lower BMI would have presented a more favorable prognosis (7), but we would have been “dead wrong.” Quite the contrary, data that cannot be disregarded have repeatedly demonstrated the opposite, that on average, the post-MI or HF patient with higher weight generally has a better short-and medium-term prognosis. The causes of MI and HF could have certainly been different in those 2 patients, and perhaps the individual with obesity could have prevented those conditions if adiposity was not accumulated in the first place (2,3,7). In this regard, however, there is also evidence that pre-HF obesity is associated with protection years later after HF develops (8).

As we have clearly stated in our article in the Journal (1), we strongly believe that intentional weight loss can improve several CVD risk factors, as well as quality of life and CRF (9–11), but stating that weight loss would result in improved CVD or all-cause mortality would not be supported by the current data, as that remains uncertain and unproven. On the other hand, recent evidence suggests that maintaining or increasing physical activity (PA) and CRF can improve prognosis to a greater degree, independent of BMI and changes in body weight (12–14). Similarly, improved quality of diet has also been associated with reduced risk for major CVD events (15–19), even in subjects with obesity, and independent of BMI and body weight changes. Finally, intensive weight loss has not clearly shown beneficial effects on major CVD events, CVD, or all-cause mortality (20), at least not when the degree of weight loss is <10% (21,22).

We also stated that unintentional weight loss should be avoided and, in fact, investigated, even in patients with obesity and severe obesity. Unintentional weight loss is typically associated with a significant reduction in LM, which is, in turn, associated with the development of sarcopenia, sarcopenic obesity, and cachexia, all conditions associated with reduced CRF and worse prognosis, especially in HF (23–27). The author of the counterargument also proposes that those in favor of the obesity paradox may see the presence of obesity in patients with CVD as “good news.” As stated above, we believe that this should not be the case; however, we should also recognize that, particularly in patients with evidence of wasting presenting with sarcopenia, sarcopenic obesity, or cachexia, promoting further weight loss, especially when not associated with intensive PA/exercise training to prevent LM loss or its further reduction, may not represent an appropriate proven therapeutic strategy. In a patient with concomitant obesity and HF, particularly when HF is advanced and associated with extremely limited functional capacity, further limiting the ability of the individual to increase the levels of PA, the recommendation of losing weight through either caloric restriction or pharmacologic therapeutics should be evaluated at length by the clinicians, as it could result in worsening that patient's condition even further, by losing additional LM and promoting the deterioration of the already impaired CRF.

We would like to conclude by stating that we understand bias well, and therefore, we believe that the author of the counterargument has a strong bias against the obesity paradox; but like this author, we also support the argument that preventing obesity in the first place, preventing additional weight gain in the overweight and obese, and probably purposeful weight loss, especially if associated with increased PA, exercise, and CRF, while preserving LM and muscular strength, would be good strategies in both primary and secondary prevention.