Association between body size phenotypes and subclinical atherosclerosis

Authors: ROSSELLO, XAVIER - National Center For Cardiovascular Research(CNIC); FUSTER, VALENTIN - National Center For Cardiovascular Research(CNIC); OLIVA, BELEN - National Center For Cardiovascular Research(CNIC); FERNANDEZ-FRIERA, LETICIA - National Center For Cardiovascular Research(CNIC); LOPEZ-MELGAR, BEATRIZ - National Center For Cardiovascular Research(CNIC); MENDIGUREN, JOSE - Banco De Santander; LARA-PEZZI, ENRIQUE - National Center For Cardiovascular Research(CNIC); BUENO, HECTOR - National Center For Cardiovascular Research(CNIC); FERNANDEZ-ORTIZ, ANTONIO - National Center For Cardiovascular Research(CNIC); IBANEZ, BORJA - National Center For Cardiovascular Research(CNIC); ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/31/2020
Publication Date: 9/3/2020
Citation: Rossello, X., Fuster, V., Oliva, B., Fernandez-Friera, L., Lopez-Melgar, B., Mendiguren, J.M., Lara-Pezzi, E., Bueno, H., Fernandez-Ortiz, A., Ibanez, B., Ordovas, J.M. 2020. Association between body size phenotypes and subclinical atherosclerosis. Journal of Clinical Endocrinology and Metabolism. 105(12):3734-3744. https://doi.org/10.1210/clinem/dgaa620.
DOI: https://doi.org/10.1210/clinem/dgaa620

Interpretive Summary: Obesity contributes to reduced life expectancy, impaired quality of life, and disabilities, mainly in those individuals who develop cardiovascular diseases, type 2 diabetes, osteoarthritis, and cancer. However, there is a large variation in the individual risk to developing obesity-associated comorbid diseases that cannot simply be explained by the extent of adiposity. In this context, the relationship between body mass index (BMI), cardiometabolic disorders, and subclinical atherosclerosis is poorly understood. This study aimed to evaluate the association between body size phenotypes and subclinical atherosclerosis, evaluated using state-of-the-art cardiac imaging, in a cohort of middle-aged asymptomatic subjects (n = 3909). Analyses were conducted by investigators in Spain and at the HNRCA in Boston. For metabolically healthy subjects, the presence of subclinical atherosclerosis increased across BMI categories, whereas fewer differences were observed for metabolically unhealthy subjects. In summary, the prevalence of subclinical atherosclerosis varies across body sizes. Pharmacologic and lifestyle interventions might modify their cardiovascular risk by facilitating the transition from one body size to another.

Technical Abstract: CONTEXT: The underlying relationship between body mass index (BMI), cardiometabolic disorders, and subclinical atherosclerosis is poorly understood. OBJECTIVE: To evaluate the association between body size phenotypes and subclinical atherosclerosis. DESIGN: Cross-sectional. SETTING: Cardiovascular disease-free cohort. PARTICIPANTS: Middle-aged asymptomatic subjects (n=3909). A total of 6 cardiometabolic body size phenotypes were defined based on the presence of at least 1 cardiometabolic abnormality (blood pressure, fasting blood glucose, triglycerides, low high-density lipoprotein cholesterol, homeostasis model assessment-insulin resistance index, high-sensitivity C-reactive protein) and based on BMI: normal-weight (NW;BMI<25), overweight (OW;BMI=25.0-29.9) or obese (OB;BMI>30.0). MAIN OUTCOME MEASURES: Subclinical atherosclerosis was evaluated by 2D vascular ultrasonography and non-contrast cardiac computed tomography. RESULTS: For metabolically healthy subjects, the presence of subclinical atherosclerosis increased across BMI categories (49.6%, 58.0%, and 67.7% for NW, OW, and OB, respectively), whereas fewer differences were observed for metabolically unhealthy subjects (61.1%, 69.7%, and 70.5%, respectively). When BMI and cardiometabolic abnormalities were assessed separately, the association of body size phenotypes with the extent of subclinical atherosclerosis was mostly driven by the coexistence of cardiometabolic risk factors: adjusted OR=1.04 (95% confidence interval [CI], 0.90-1.19) for OW and OR=1.07 (95% CI, 0.88-1.30) for OK in comparison with NW, whereas there was an increasing association between the extent of subclinical atherosclerosis and the number of cardiometabolic abnormalities: adjusted PR=1.21 (95% CI, 1.05-1.40), 1.60 (95% CI 1.99-1.93), 1.92 (95% CI, 1.48-2.50), and 2.27 (95% CI, 1.67-3.09) for 1,2,3 and >3, respectively, in comparison with non-cardiometabolic abnormalities. CONCLUSIONS: The prevalence of subclinical atherosclerosis varies across body size phenotypes. Pharmacologic and lifestyle interventions might modify their cardiovascular risk by facilitating the transition from one phenotype to another.