Metabolically Healthy Obesity Will Likely Become Unhealthy: MESA

April 25, 2018

People who are obese but without cardiometabolic risk factors, who have so-called metabolically healthy obesity (MHO), may appear to be at low risk for cardiovascular (CV) events. But many, perhaps most, aren't off the hook.

There's a good chance that they will later develop hypertension, glucose intolerance, dyslipidemia, or other elements of the metabolic syndrome (MetS) that in turn raise their risk for coronary heart disease (CHD) and perhaps death. 

That's one message from a new Multi-Ethnic Study of Atherosclerosis (MESA) cohort analysis, say researchers, in which the 12-year risk for CHD events wasn't elevated for those with MHO at baseline overall. But it went up a significant 60% in the subgroup who acquired a high-risk cardiometabolic profile during follow-up.

Moreover, the risk for CHD events among the obese went up over time proportionally with duration of exposure to the cardiometabolic risk factors. Not surprisingly, those who were obese and had some of those risk factors at baseline showed the highest risk for CHD events.

Those findings, along with a MESA analysis from 2016 documenting the cohort's high rate of transition from MHO to obesity accompanied by features of MetS, "I think are fairly intuitive, but maybe very disappointing. We'd love for there to be this group of people who are resilient to obesity," Morgana Mongraw-Chaffin, PhD, Wake Forest School of Medicine, Winston-Salem, North Carolina, told | Medscape Cardiology.

But people with MHO ultimately tend to develop those cardiometabolic risk factors that put them at increased CHD risk, she observed. "It's just taking them a bit longer."

The current MESA analyses, published April 24 in the Journal of the American College of Cardiology with Mongraw-Chaffin as lead author, may therefore help explain earlier studies suggesting that MHO is associated with CV risk only with longer follow-up.

Indeed, it is consistent with those analyses and other research questioning the prognostic usefulness of the MHO classification, including the British Whitehall II study, the European EPIC observational study, the THIN database with almost 3.5 million persons, and other studies. And all of them question earlier observational studies and other research suggesting that MHO may be a prognostically useful classification.

The current study suggests that, for improving cardiovascular risk, "prevention of obesity in the first place is most prudent" and that "prevention of progressive weight gain over time among the overweight and mildly obese is also of high importance," according to an accompanying editorial.

It also "emphasizes the importance of the prevention of the development of the MetS and adequate treatment of MetS if it develops," write Prakash Deedwania, MD, University of California San Francisco, Fresno, and Carl J Lavie, MD, Ochsner Clinical School-University of Queensland School of Medicine, New Orleans, Louisiana.

But the current analysis and most earlier related ones, they write, are limited by inadequate information about the physical-activity levels and cardiorespiratory fitness (CRF) of their participants.

"When assessing subsequent risk in MHO, it is imperative to assess CRF because substantial available evidence supports that obese people, especially those with MHO, with relatively preserved CRF have an excellent prognosis.

"We suspect, therefore, that only those with MHO and low levels of CRF may have significantly increased risk of CHD and most CVD, except for possibly HF [heart failure] with preserved ejection fraction, which is probably increased universally in obesity," they write.

Nearly half of those initially with MHO in the current analysis developed MetS features over time, "so even if they are more fit, it may only be prolonging the process," Mongraw-Chaffin said.

However, Deedwania and Lavie  "do a good job of explaining one of the gaps that we have to fill." The current analysis adjusted for self-reported physical activity levels, but that's admittedly not a great reflection of CRF, which is ideally quantified by measures of oxygen consumption, she noted.

Still, in the current analysis, "There's still some suggestion that obesity itself may be driving that transition to metabolic syndrome and risk."

From the entire MESA cohort, the study excluded any with a CV history and persons who were nonobese (body mass index < 30 kg/m2) with MetS features at baseline or developing during the follow-up.

That left 5005 participants, including 2751 who were nonobese without MetS and 2254 who were obese at baseline. The latter group consisted of 550 with MHO throughout ("stable MHO"), 501 initially with MHO who later acquired MetS features ("unstable MHO"), and 1203 who were obese with MetS features ("metabolically unhealthy obesity" or MUO).

Table. Odds Ratios for CV Events by Obesity and MetS Status Compared With Metabolically Normal Nonobese

Endpoints Odds Ratio (95% Confidence Interval)
Stable MHO 1.03 (0.69 - 1.52)
Unstable MHO 1.60 (1.14 - 2.25)
MUO 2.67 (2.12 - 3.37)


"So in some ways, the results of this study don't say the guidelines and recommendations should be changed at all. If an individual comes in with obesity, a doctor should be looking at the risk factors they already have, and try to work with them to avoid the risk factors that we know they are at risk for in the future," Mongraw-Chaffin said.

"Even if someone is metabolically healthy at the time, if they have obesity they really need those prevention and treatment resources, or in a matter of time they'll be back, and we'll be looking at secondary prevention instead of primary prevention."

Mongraw-Chaffin and her coauthors and both Deedwania and Lavie report that they have no relevant disclosures.

J Am Coll Cardiol. 2018;71:1857-1865. Article, Editorial

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