INTRODUCTION

Obesity is a major global public health concern strongly linked to chronic diseases, including cardiovascular disease, type 2 diabetes, and certain cancers [1]. Traditionally, obesity has been defined solely by body mass index (BMI); however, this approach has significant limitations in accurately reflecting an individual's metabolic health. In January 2025, The Lancet Diabetes & Endocrinology Commission proposed a novel clinical redefinition of obesity, introducing two classifications: “clinical obesity” and “preclinical obesity” [2]. This review discusses the implications of this refined understanding of obesity, particularly from the perspective of cardiovascular disease prevention.

DEFINITIONS OF CLINICAL AND PRECLINICAL OBESITY

Clinical obesity is defined as "a chronic, systemic illness characterized by functional alterations in tissues, organs, or overall individual health due to excess adiposity" [2]. This definition extends beyond fat accumulation, emphasizing measurable functional impairments and clinical abnormalities resulting from excessive adipose tissue. Conversely, preclinical obesity is defined as "a state of excess adiposity with preserved tissue and organ function" [2]. Although functional impairments are currently absent, preclinical obesity is associated with a heightened risk of progression to clinical obesity and related diseases. This stage represents a critical opportunity for early intervention to prevent adverse health outcomes.

DIAGNOSTIC CRITERIA FOR CLINICAL AND PRECLINICAL OBESITY

The diagnosis of clinical obesity is based on two main criteria (Fig. 1) [2]. The first criterion involves anthropometric evidence of excess adiposity, confirmed either directly through body fat measurements (when available) or indirectly through additional anthropometric indices (e.g., waist circumference, waist to hip ratio, or waist to height ratio) combined with BMI. For individuals with a BMI exceeding 40 kg/m², excess adiposity can be pragmatically presumed without further verification. The second criterion involves clinical evidence of obesity-related functional impairment, indicated by observable reductions in tissue or organ function (e.g., clinical signs, symptoms, or diagnostic test results) or significant, age-adjusted limitations in activities of daily living (e.g., bathing, dressing, toileting, continence, eating). Functional impairments can manifest across multiple organ systems, including cardiovascular (e.g., reduced left ventricular systolic function, chronic/recurrent atrial fibrillation, pulmonary arterial hypertension, heart failure, elevated arterial blood pressure), metabolic (e.g., cluster of hyperglycemia, elevated triglycerides, low high-density lipoprotein cholesterol), respiratory (e.g., sleep apnea/hypopnea from increased upper airway resistance), musculoskeletal (e.g., chronic severe knee or hip pain), and other systems (e.g., central nervous system, liver, kidney, reproductive organs).

The diagnosis of preclinical obesity utilizes the same anthropometric criteria as clinical obesity for confirming excess adiposity but is differentiated by the absence of functional organ impairments, daily activity limitations, or objective signs of obesity-related dysfunction. Essentially, preclinical obesity represents confirmed excess adiposity without clinical manifestations, signifying a stage before symptom onset and thus an increased future risk of progression to clinical obesity or obesity-related diseases. Clearly distinguishing clinical from preclinical obesity is critical for risk stratification and guiding appropriate preventive or therapeutic strategies.

BEYOND BMI: IMPLICATIONS FOR CARDIOVASCULAR RISK

One of the most significant shifts in the newly proposed diagnostic criteria for obesity is moving beyond BMI alone, emphasizing diverse anthropometric indicators to assess excess fat accumulation [2]. This change has substantial implications for cardiovascular disease risk assessment and prevention.

Detection of hidden risk in normal weight individuals

BMI alone is inadequate for detecting “normal weight obesity” or “metabolically unhealthy normal weight” conditions [3]. These phenotypes, characterized by excess visceral or ectopic fat accumulation despite a normal BMI, are associated with increased cardiovascular risk. Traditional BMI-based approaches struggle to identify these at-risk groups. A large-scale US study highlighted considerable discrepancies between obesity defined by BMI and body fat percentage, with pronounced differences especially in individuals within intermediate BMI ranges. Furthermore, those identified as obese by body fat percentage but not by BMI demonstrated more metabolic abnormalities and cardiovascular risk factors [4].

Importance of body fat distribution

Body fat distribution, beyond total fat mass, critically influences cardiovascular risk. Central obesity and visceral fat accumulation independently predict adverse cardiovascular outcomes [5]. An international consensus statement emphasized that even within identical BMI categories, cardiovascular risk escalates with increased waist circumference [6]. A meta-analysis revealed visceral fat accumulation is independently associated with heightened cardiovascular events and mortality risk, regardless of BMI [7]. Additionally, a Mendelian randomization study provided causal evidence linking body fat distribution to cardiovascular disease independent of BMI [8].

Links to cardiovascular risk profiles and ethnic considerations

Expanded anthropometric measurements strongly correlate with cardiometabolic risk profiles. Individuals with higher visceral fat frequently exhibit insulin resistance, dyslipidemia, and hypertension [9]. Obesity-related dyslipidemia, characterized by elevated triglycerides, decreased high-density lipoprotein cholesterol, and increased small, dense low-density lipoprotein particles, is closely associated with heightened atherosclerosis risk [10]. These metabolic profiles serve as important early indicators of cardiovascular disease risk, underscoring the importance of comprehensive anthropometric assessments.

Previous research has identified notable ethnic and racial variations in body fat distribution patterns and their associations with cardiovascular risk. A cross-sectional study revealed that Asian populations exhibit higher visceral and ectopic fat accumulation at lower BMI values compared to Europeans [11]. This observation has led to recognition of the "metabolically obese normal weight (MONW)" phenotype, indicating health risks at lower BMIs and relatively higher body fat among Asians than other populations [12]. A Korean study similarly demonstrated that individuals with normal BMI but elevated visceral fat had cardiometabolic risk profiles comparable to overt obesity [13]. These consistent findings align with the World Health Organization's recommendation of lower BMI thresholds for defining overweight (≥23 kg/m²) and obesity (≥25 kg/m²) in Asian populations [14]. Advanced body composition analysis using dual-energy x-ray absorptiometry indicates that Asians typically have 3% to 5% higher body fat percentages than Caucasians at equivalent BMIs [15]. These ethnic differences in body composition and metabolic risk highlight the limitations of universal BMI cutoffs, emphasizing the new diagnostic paradigm’s incorporation of broader anthropometric measures for more accurate cardiovascular risk assessment, particularly within Asian populations.

Implications for cardiovascular disease prevention

Deeper understanding of the relationship between obesity and cardiovascular disease

Obesity contributes to atherosclerotic cardiovascular disease development through interconnected pathways involving hypertension, dyslipidemia, insulin resistance, and chronic inflammation [16]. Epidemiological and pathophysiological studies, including Mendelian randomization analyses, support a causal association between adiposity and cardiovascular disease [17]. Notably, extensive cohort data suggest that obesity is more strongly linked to heart failure than to atherosclerotic cardiovascular events [18]. A US-based cohort study further demonstrated a significant association between BMI and increased cardiovascular risk, particularly heart failure, across all obesity classifications [19].

Clear criteria for early intervention

Differentiating between clinical and preclinical obesity provides explicit criteria for early intervention, facilitating differentiation between healthy and diseased states, and enabling personalized intervention strategies based on individual health risk profiles [2]. This distinction allows clinicians to identify individuals at subclinical risk who may benefit substantially from timely lifestyle modifications. Individuals with preclinical obesity have preserved organ function, making targeted lifestyle interventions particularly beneficial in preventing progression to clinical disease. Additionally, this stratification aids the strategic allocation of healthcare resources, directing more intensive interventions toward individuals identified as having a higher cardiovascular risk [20].

Enhanced cardiovascular risk prediction

The relationship between obesity and cardiovascular disease is intricate, and BMI alone is insufficient for accurately evaluating cardiovascular risk at an individual level [21]. Incorporating cardiovascular abnormalities—such as hypertension, heart failure, and atrial fibrillation—into clinical obesity diagnostic criteria allows for more precise identification of individuals already at heightened cardiovascular risk [2]. Obesity contributes to heart failure through mechanisms including hemodynamic overload, metabolic dysfunction, inflammation, and mechanical effects [22]. These mechanisms are particularly significant in heart failure with preserved ejection fraction (HFpEF), where obesity plays a specific pathophysiological role [22]. For example, data from the Framingham Heart Study revealed that a 1-unit increase in BMI elevates heart failure risk by 5% in men and 7% in women [23]. A retrospective US cohort study reported that over 80% of HFpEF patients were overweight or obese, highlighting the strong association between adiposity and HFpEF [24]. Epicardial fat also contributes to cardiovascular pathology through both physical proximity and proinflammatory signaling, as cytokines produced by epicardial adipose tissue negatively impact myocardial function and induce structural remodeling, particularly relevant in HFpEF [25].

Evidence for cardiovascular effects of weight loss

Therapeutic interventions targeting obesity, particularly with glucagon-like peptide-1 (GLP-1) receptor agonists, have shown promising cardiovascular benefits. Clinical trials such as STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) showed that weight reduction with semaglutide significantly improved symptoms and quality of life in patients with HFpEF and obesity [26]. Additional studies confirmed that caloric restriction and exercise training similarly enhance cardiovascular fitness in this patient population [27]. Beyond HFpEF, several large-scale cardiovascular outcome trials have validated significant cardiovascular advantages associated with GLP-1 receptor agonists. The PIONEER 6 (Peptide Innovation for Early Diabetes Treatment 6) trial with oral semaglutide [28] and the SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects With Type 2 Diabetes) trial with injectable semaglutide [29] established cardiovascular safety, with trends toward reduction in major adverse cardiovascular events (MACE). More recent landmark research in the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial demonstrated that semaglutide significantly reduced the risk of MACE by 20% in patients with established cardiovascular disease and overweight or obesity without diabetes [30]. Similarly, the REWIND (Researching Cardiovascular Events with a Weekly Incretin in Diabetes) trial using dulaglutide reported a 12% reduction in MACE among a broad participant group, many of whom lacked established cardiovascular disease [31]. These cardiovascular benefits likely result from multiple mechanisms, including reduced adiposity, improved endothelial function, anti-inflammatory effects, and direct cardiovascular actions [32]. Collectively, this accumulating evidence underscores that addressing clinical obesity pharmacologically, particularly with GLP-1 receptor agonists, can offer substantial cardiovascular protection, representing a paradigm shift in cardiovascular risk reduction strategies in obese patients.

Optimization of treatment strategies

From a treatment perspective, clearly distinguishing between clinical and preclinical obesity helps inform and tailor management goals. Clinical obesity requires active intervention aimed at reversing organ dysfunction and enhancing clinical outcomes, whereas preclinical obesity necessitates preventive strategies to halt or slow disease progression [2]. This clear differentiation enables more efficient resource allocation and targeted interventions for cardiovascular disease prevention.

Managing clinical obesity effectively, especially when cardiovascular manifestations are involved, typically necessitates a multidisciplinary approach incorporating primary care physicians, cardiologists, endocrinologists, dietitians, exercise specialists, and behavioral health professionals. Such a team-based model addresses both physiological and behavioral aspects of obesity, facilitating comprehensive treatment of the multifaceted mechanisms through which obesity influences cardiovascular health.

Redefinition of treatment goals beyond weight loss

Traditionally, obesity treatments have predominantly used weight loss as the primary indicator of success. However, the new paradigm emphasizes improvement in organ function and remission of clinical obesity as essential treatment goals [2]. This shift directly prioritizes enhancing cardiovascular health rather than focusing exclusively on weight reduction. Remission of clinical obesity is defined as partial or complete resolution of tissue or organ dysfunction abnormalities evident in clinical and laboratory evaluations. Given that treatment responses may differ based on the specific systems affected (e.g., cardiovascular, metabolic, musculoskeletal), individualized treatment plans are crucial for effectively addressing each patient's unique health profile [2].

CLINICAL APPLICATIONS AND RESEARCH CHALLENGES

For effective clinical implementation, standardizing diagnostic tools to evaluate obesity-related organ dysfunction is essential. Current guidelines lack explicit recommendations for assessing functional impairments across various organ systems. Future clinical protocols should incorporate these new obesity classifications into cardiovascular risk stratification and care planning [33,34]. Specifically, patients with clinical obesity and heightened cardiovascular risk might benefit substantially from more intensive, multimodal intervention strategies.

Additionally, longitudinal studies are needed to explore how clinical and preclinical obesity influence cardiovascular event occurrence and prognosis [2]. Presently, the prevalence of clinical obesity and progression rates from preclinical to clinical obesity remain unclear. Developing biomarkers to improve the diagnosis and prognostic evaluation of clinical obesity is necessary, as these biomarkers could significantly enhance early identification and intervention strategies for patients with obesity and elevated cardiovascular risk.

CONCLUSIONS

The redefinition of obesity into clinical and preclinical categories represents a paradigm shift in obesity diagnosis and management. By transitioning beyond BMI to consider organ dysfunction and adiposity distribution, this approach establishes a more precise and clinically relevant framework. From a cardiovascular disease prevention perspective, this novel concept offers numerous advantages: it facilitates personalized interventions tailored to individual risk levels, refines cardiovascular risk assessment, promotes efficient resource allocation, and redefines treatment goals towards functional improvements beyond weight loss alone. This paradigm shift will likely influence clinical practice guidelines and reimbursement policies by providing a scientific foundation for obesity treatment coverage based on functional impairments rather than arbitrary BMI thresholds or associated comorbidities. Healthcare systems may need to develop standardized protocols for evaluating obesity-related organ dysfunction and update documentation systems accordingly. While further research on practical clinical application and long-term outcomes is warranted, this innovative proposal holds significant potential to transform obesity management and markedly reduce the global cardiovascular disease burden.

ARTICLE INFORMATION

Conflicts of interest

The author has no conflicts of interest to declare.

Funding

This study was supported by a Korea University Grant.

Fig. 1.

Diagnostic criteria for clinical and preclinical obesity in adults as redefined by the Lancet Diabetes & Endocrinology Commission [2]. ADL, activities of daily living; BMI, body mass index; CNS, central nervous system; DVT, deep vein thrombosis; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; NAFLD, nonalcoholic fatty liver disease; PCOS, polycystic ovary syndrome.

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References

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