Metabolically healthy obesity often a ‘transient state’ on slide to CVD
Metabolically healthy obesity (MHO) is not a stable state—rather, it's a slippery slope toward metabolic syndrome and increased risk of cardiovascular disease (CVD), suggests a long-term study published April 23 in the Journal of the American College of Cardiology.
An analysis of more than 5,000 participants from the Multi-Ethnic Study of Atherosclerosis cohort found 48 percent of those with MHO at baseline developed metabolic syndrome over 12 years of follow-up. These people showed 60 percent increased odds of incident CVD compared to those who were of healthy weight or remained MHO, with evidence of a cumulative effect. Participants were seen for follow-up visits every two years, and people who had metabolic syndrome on multiple visits showed an increasingly high risk of CVD.
Associations for coronary heart disease, stroke and heart failure were similar to the trends observed for CVD overall. The researchers estimated metabolic syndrome mediated about 62 percent of the relationship between obesity and CVD during the follow-up period.
“Obesity has been repeatedly shown to be one of the strongest risk factors for the development of MetS (metabolic syndrome) and its CVD risk factor components,” wrote lead author Morgana Mongraw-Chaffin, PhD, with the department of epidemiology and prevention at Wake Forest School of Medicine, and colleagues.
“In this respect, MetS may be a marker of the threshold of cumulative obesity exposure that translates to measurable CVD risk. … In contrast to the conclusion that obesity is less important for the development of CVD, multiple mediation analyses, including this one, indicate that obesity is likely a major primary cause of both MetS and the resulting CVD risk.”
Metabolic syndrome is a clustering of risk factors that often lead to diabetes or CVD. For this study, the researchers defined metabolic syndrome as meeting at least three of the following criteria: high triglycerides, low HDL cholesterol, hypertension, high fasting glucose and large waist circumference. Obesity was defined as BMI above 30.
Past studies have been inconclusive regarding the true risk of CVD in individuals who are obese but without metabolic syndrome.
“The level of risk remains contentious, especially for mortality, with MHO seen as either a marker of true resilience or as a transient state on the pathway to risk,” Mongraw-Chaffin and coauthors pointed out.
But earlier studies showing MHO individuals were relatively safe from harmful events may have been limited by short follow-up periods, the authors noted. Their 12-year study led to different conclusions.
“Both transition to MetS and longer duration of MetS were associated with CVD, indicating that those with MHO may experience a lag in risk while they progress to MetS and develop the resultant cardiometabolic risk,” Mongraw-Chaffin et al. wrote. “Similarly, it may be that MHO estimates for mortality are not increased because the lag time is longer for mortality than for CVD and therefore cannot be observed during the follow-up of most studies.”
The authors said their study should serve as a warning to patients with MHO and their clinicians. It could be the last chance to engage in primary prevention before the slide to metabolic syndrome and full-blown CVD risk factors.
“MHO signals an opportunity for weight reduction, and prevention and management of existing MetS components should be prioritized,” they wrote. “Clinical trials of weight loss in patients with metabolically healthy obesity are needed to confirm the benefit of earlier intervention to prevent ischemic events.”
In an accompanying editorial, Prakash Deedwania, MD, and Carl J. Lavie, MD, agreed with Mongraw-Chaffin et al. that weight loss and prevention of obesity in the first place is the best solution. However, they said the study would have been more complete if it had better data on physical activity and cardiorespiratory fitness (CRF), which they believe at least as important as metabolic syndrome in gauging CVD risk among obese individuals.
“Many studies have indicated that CRF may be more important than weight for predicting long-term prognosis,” Deedwania and Lavie wrote. “Additionally, 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.”
With this in mind, they added, people with borderline or mild obesity should be encouraged to maintain or increase their CRF through exercise, as it may be their best option to fight heart disease.
Daniel joined TriMed’s Chicago editorial team in 2017 as a Cardiovascular Business writer. He previously worked as a writer for daily newspapers in North Dakota and Indiana.