麻豆传媒

Persons with obesity can be metabolically healthy or unhealthy, but how does metabolic status impact outcomes when older individuals with obesity undergo an in-hospital cardiovascular procedure?

That question is partially answered in a retrospective observational study of percutaneous intervention (PCI) for acute coronary syndrome. As Rupak Desai, MBBS, an independent researcher in Atlanta, and Aobo Li, MD, of Inspira Health Network in Vineland, New Jersey, and colleagues reported in , the results showed that contrary to conventional belief, metabolically healthy obesity (MHO) did not confer protective effects in this context.

Included in the study were obese persons age 65 and older. The final cohort for analysis consisted of 2,995 patients with metabolically unhealthy obesity (MUHO) matched with 2,995 with MHO. Participants were identified through the National Inpatient Sample Database, 2016–2020, and ICD-10 codes.

The investigators assessed and contrasted patients' initial attributes, concurrent conditions, and results pertaining to the following outcomes: all-cause mortality, cardiogenic shock, length of hospital stay, and hospitalization costs.

Desai elaborated on the findings in the following interview.

What was the impetus for the study?

Desai: The study was motivated by the well-established obesity paradox in patients with coronary artery disease, with some evidence suggesting that obesity could confer protective effects, particularly after PCIs. However, the role of metabolic health as a whole, especially in older adults with obesity, was not well studied, so we aimed to explore the impact of this status in older patients with obesity undergoing PCIs for acute coronary syndrome in a nationally representative sample.

Could you explain the conventional obesity paradox?

Desai: This refers to the observation that, contrary to general assumptions, individuals with obesity sometimes experience better survival rates after cardiovascular events, including heart attacks or surgical interventions, compared with individuals of normal weight. This paradox is observed particularly in short-term in-hospital outcomes, in which patients with a higher body mass index (BMI) often show better outcomes despite the known cardiovascular risks associated with obesity. It challenges the traditional view that obesity always negatively impacts cardiovascular outcomes.

How is metabolically healthy obesity defined?

Desai: This refers to individuals who are classified as obese based on BMI but who do not exhibit concomitant metabolic disorders typically associated with obesity, such as insulin resistance, hyperlipidemia, or hypertension.

These individuals, despite their elevated BMI, are considered to have a relatively healthier metabolic profile. The paper discusses some of the specific mechanisms for this status, including reduced ectopic fat and maintenance of insulin sensitivity.

For our study, we excluded in-patient participants with concomitant hypertension, diabetes mellitus, and hyperlipidemia in order to obtain MUHO and MHO groups based on obesity status.

What were the main findings?

Desai: The study revealed, surprisingly and contrary to the conventional obesity paradox, that patients with MHO, particularly those over age 65 undergoing PCI for ACS, had worse in-hospital outcomes compared with those with MUHO.

Although MUHO and MHO cohorts showed comparable demographic characteristics as to age, sex, race, and payer status, the MHO group demonstrated significantly higher rates of all-cause mortality – 12.4% versus 2.8% – cardiogenic shock, and mechanical circulatory support use. That contradicted our initial hypothesis. However, when we adjusted confounding factors in multivariable analysis, in-hospital deaths were comparable between the two groups.

How do the results add nuance to the obesity paradox -- and what is meant by the paradox within a paradox?

Desai: This study adds nuance by demonstrating that the protective effects of obesity may not apply universally, particularly when metabolic health is taken into account. The concept of the "paradox within a paradox" emerges because despite the belief that being metabolically healthy offers protection, MHO patients exhibited outcomes worse than or comparable to those of MUHO patients.

Thus, even within the framework of the obesity paradox, there are further complexities related to metabolic health status.

What is the next research step needed?

Desai: Ours was a retrospective database study of in-hospital patients and may have been subject to sampling bias. It also lacked laboratory and medication information as well as longitudinal data on long-term outcomes. So the next step is to conduct larger-scale, prospective studies that can better account for confounding variables and provide long-term data on the impact of metabolic health on outcomes in this patient population.

Future research should also include more diverse populations and explore the transition from metabolically healthy to unhealthy states over time. Moreover, since recent reports have questioned the traditional ways of defining obesity based solely on BMI, which may not capture true obesity and cardiovascular risk status in general, more modern tools are required to define obesity based on overall metabolic health and cardiorespiratory fitness.

What is the key takeaway message for clinicians?

Desai: For clinicians, the takeaway is that metabolic health status, rather than obesity alone, plays a crucial role in predicting outcomes after cardiovascular procedures like PCI. In older patients with obesity, those classified as metabolically healthy may still face significant risks. Thus, focusing solely on BMI may be misleading, and a more comprehensive assessment of metabolic health is essential when managing patients with obesity.

Tailoring treatment plans based on both metabolic and obesity status in addition to cardiorespiratory fitness, rather than weight alone, will lead to better patient outcomes.

Read the study here.