In this community-based prospective study, we found that the MUN in young adulthood was significantly related to worse LV function but not LV hypertrophy compared to the MHN. Furthermore, we found that obesity in young adulthood was significantly associated with LV hypertrophy and worse LV function irrespective of metabolic status. These findings suggested that young adults should not only maintain metabolic health, but also, and more importantly, normal weight.
Obesity And Metabolically Healthy Obesity In Young Adults
Obesity, a burden of epidemic proportions, continues unabated in the United States, and it is estimated that the prevalence of obesity will reach 48.9% by 2030 [19]. Current guidelines consider people with obesity to be in stage A of HF [8]. A prospective study demonstrated that greater BMI in early adulthood is associated with impaired LV function and LV hypertrophy [20], which may be driven by obesity-related risk factors, such as hyperglycemia, hypertension, or dyslipidemia [21]. Young adults gain weight faster than other age groups but have not yet reached the stage of life that metabolic syndrome typically emerges [22], The current guideline defines obesity without metabolic risk factors as MHO [23]. The prevalence of MHO ranged from 6%-60% in obese adults [24, 25], and was higher in young adults than older adults [26–28]. However, data on the association of MHO in young adulthood with cardiac remodeling and dysfunction are still lacking. Therefore, our study, evaluating the effects of metabolic phenotypes of young adulthood on cardiac structure and function, provided further evidence that obesity is associated with unfavorable alteration in LV structure and function regardless of metabolic status.
Comparison With Previous Studies
In recent years, MHO has attracted increasing interest. Several studies have investigated associations of metabolic phenotypes in middle-aged and older populations with cardiac structure and function [9–12]. Two prior cross-sectional studies reported that MUO was associated with preclinical impaired LV systolic and diastolic function [9, 12]. However, the relationship between MHO and impaired diastolic function, as reflected by the E/e′ ratio, was not significant. Furthermore, in a small study (n = 67) that investigated the effect of BMI and metabolic health on myocardial function, impaired myocardial function was associated with poor metabolic health rather than obesity [10]. In addition, a relatively large cross-sectional study involving 789 Korean individuals showed that poor metabolic health was related to more significant adverse effects on LV structure and function than obesity [11]. Findings from these cross-sectional studies suggested that poor metabolic health in middle-aged and older individuals was more closely associated with LV hypertrophy and dysfunction, and implied that we should pay more attention to maintaining metabolic health rather than normal weight. However, a prospective longitudinal study emphasized the adverse effects of obesity in young adulthood on cardiac structure and function [20]. Of note, this study did not consider the effects of different obesity phenotypes. Our findings bridge a gap in the literature by providing evidence that MHO in young adulthood is associated with LV hypertrophy and incipient dysfunction in midlife and that the association is stronger in individuals with MUO, which emphasizes the need for young adults to maintain a healthy weight.
Implications
Findings from our study link obesity in young adulthood with LV hypertrophy and incipient dysfunction in midlife regardless of metabolic status, which may make young adults more aware of the adverse effects of obesity. That is particularly concerning the marked growth of prevalence of overweight and obesity in adolescents and young adults. For example, the prevalence of overweight and obesity was over 40% among African-Americans [29]. Previous studies indicated poor metabolic health was more significantly related to LV remodeling and dysfunction in middle-aged and older adults [9, 10]. However, young adults have not yet reached the stage of life that metabolic syndrome typically emerges, and the prevalence of MHO in young adulthood was higher than that of older adults.[26–28] Furthermore, individuals with MHO may not receive early and more aggressive treatment for weight loss. Therefore, our study focused on MHO in young adulthood and proved that obesity is associated with LV hypertrophy and incipient dysfunction irrespective of metabolic status, consistent with current guideline [8]. Emphasizing obesity-related cardiac damage may motivate young adults to more aggressively control weight.
MHO is not stable and more than one-third of individuals with MHO develop MUO [30]. In our study, the relationship between obesity and LV hypertrophy and dysfunction was more evident in participants with poor metabolic health. Previous studies demonstrated that individuals who maintained MHO have a lower risk of cardiovascular disease and all-mortality than individuals with MHO converted to MUO [7, 30]. Fortunately, MHO is not irreversible and could return to MHN after treatment. A large nationwide population-based study including 7,148,763 Korean individuals demonstrated that the transition from MHO to MHN protected against hospitalization for HF [31]. Moreover, moderately 3–10% weight loss can bring significant improvement of metabolic health [32, 33]. Therefore, obese young adults should give adequate attention to lose weight irrespective of metabolic status, which may contribute to minimizing the burden of HF.
Strengths And Limitations
The strengths of our study included using data from a standardized echocardiographic assessment in a large, community-based sample with a long-term follow-up of 25 years and the ability to account for confounding factors. In addition, to our knowledge, this may be the first study to comprehensively investigate the association of different metabolic phenotypes in young adulthood with cardiac structure and function.
However, our study also had several limitations. First, because the CARDIA trial was an observational study and our study did not analyze the change in echocardiographic indices at follow-up, our results could not determine causal inferences or reverse causation. We attempted to adjust for common confounding factors, but the effects of residual confounding factors may still have been present. Second, we could not assess the association of obesity or metabolic health with HF because there were limited HF cases in the CARDIA cohort. Third, there is no unified consensus on the definition of MHO [5]. To overcome this limitation, we used the most common definition, which defines MHO as obesity without metabolic syndrome [6, 34, 35]. Fourth, since our study was only performed in young adults who were white or black, the relationship between metabolic phenotypes and cardiac remodeling in other racial groups and at other ages warrants future investigation.