Different Metabolic Phenotypes of Obesity and Risk of Coronary Artery Calcium Progression and Incident Cardiovascular Disease Events: The CARDIA Study

Abstract

Background: To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events. Methods: A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000–2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m 2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes. Results: During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369–2.264] to 2.047 [1.380–3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout. Conclusions: Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00005130.

Association of metabolic health and obesity with coronary heart disease in adult cancer survivors

“…Obesity is known to increase the risk for CHD even among metabolically healthy individuals 11 . This may be due to several mechanisms, including increased oxidative stress and vascular calcification resulting from the activation of vascular bone morphogenetic protein 40,41 . In addition, adipose tissues release adipokines that can induce a proinflammatory effect, disrupting vascular homeostasis and promoting atherogenesis.…”

“…vascular calcification resulting the activation of vascular bone morphogenetic protein. 40,41 In addition, adipose tissues release adipokines that can induce a proinflammatory effect, disrupting vascular homeostasis and promoting atherogenesis. Even MHO individuals have been found to have elevated levels of C-reactive protein and circulating proinflammatory monocytes, indicating the presence of inflammation.…”

Diabesity in Elderly Cardiovascular Disease Patients: Mechanisms and Regulators

“…The CARDIA study included patients with several obesity phenotypes (with healthy and unhealthy metabolism). Its analysis has demonstrated the highest risk for coronary artery calcification (CAC) progression in obese subjects with unhealthy metabolism and the lowest risk in non-obese subjects [ 19 ]. Ageing is also considered the major risk factor of CVD.…”

Association between BMI-based metabolic phenotypes and prevalence of intracranial atherosclerotic stenosis: a cross-sectional study

“…Several studies have demonstrated that the presence of metabolic syndrome heightens the risk of stroke and myocardial infarction (10)(11)(12). Some studies have reported on the correlation between different metabolic phenotypes and the risk of cardiovascular disease, but the conclusions have not been consistent (13)(14)(15). This indicates that different metabolic types may have varying risks for cardiovascular diseases.…”