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Cardiac insulin resistance in subjects with metabolic syndrome traits and early subclinical atherosclerosis

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posted on 2023-09-15, 18:39 authored by Ana Devesa, Valentin Fuster, Ravi Vazirani, Inés García-Lunar, Belén Oliva, Samuel España, Andrea Moreno-Arciniegas, Javier Sanz, Cristina Perez-Herreras, Héctor Bueno, Enrique Lara-Pezzi, Ana García-Alvarez, Vicente Martínez de Vega, Leticia Fernández Friera, Maria G. Trivieri, Antonio Fernández-Ortiz, Xavier Rossello, Javier Sanchez-Gonzalez, Borja Ibanez

Objective:

Experimental evidence suggests that metabolic syndrome (MetS) is associated with changes in cardiac metabolism. Whether this association occurs in humans is unknown.

Research Design and Methods:

821 asymptomatic individuals from the PESA study (50.6[46.9-53.6] years, 83.7% male) underwent two whole-body 18F-FDG PET-MR 4.80.6 years apart. Presence of myocardial 18F-FDG uptake was evaluated qualitatively and quantitatively. No myocardial uptake was grade as 0, while positive uptake was classified in grades 1-3 according to target-to-background ratio tertiles.

Results:

156 participants (19.0%) showed no myocardial 18F-FDG uptake, and this was significantly associated with higher prevalence of MetS (29.0% vs 13.9%, p<0.001), hypertension (29.0% vs 18.0%, p=0.002), and diabetes (11.0% vs 3.2%, p<0.001), and with higher insulin-resistance index (HOMA-IR, 1.64% vs 1.23 %, p<0.001). Absence of myocardial uptake was associated with higher prevalence of early atherosclerosis (i.e. arterial 18F-FDG uptake, p=0.004).

On follow-up, the associations between myocardial 18F-FDG uptake and risk factors were replicated, and MetS was more frequent in the group without myocardial uptake. The increase in HOMA-IR was associated with a progressive decrease in myocardial uptake (p<0.001). In 82% of subjects, the categorization according to presence/absence of myocardial 18F-FDG uptake did not change between baseline and follow-up. MetS regression on follow-up was associated with a significant (p<0.001) increase in myocardial uptake.

Conclusions:

Apparently healthy individuals without cardiac 18F-FDG uptake have higher HOMA-IR and higher prevalence of MetS traits, cardiovascular risk factors, and early atherosclerosis. An improvement in cardiometabolic profile is associated with the recovery of myocardial 18F-FDG uptake at follow-up.

Funding

The PESA study is funded by the CNIC and Santander Bank. B.I. is supported by the European Commission (ERC-CoG 819775, and H2020-HEALTH 945118), by the Spanish Ministry of Science and Innovation (PID2019‐110369RB‐I00), and by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). A.D. is an Alfonso Martin Escudero fellow and is scientifically supported by La Caixa Foundation. The CNIC is supported by the ISCIII, the Ministry of Science and Innovation, and the Pro CNIC Foundation. CNIC is a Severo Ochoa Center of Excellence (CEX2020-001041-S).

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