Low leptin plasma levels are associated with progression of coronary atherosclerosis in patients with stable coronary artery disease from the SMARTool Study

Background Leptin is an adipokine involved in energy homeostasis and has been related with established vascular risk factors. However, studies on the association of leptin plasma levels with coronary artery disease (CAD) have yielded conflicting results. Purpose Aim of the present study was to evaluate the association between leptin plasma levels and presence, severity and progression of coronary atherosclerosis in patients with suspected stable CAD. Methods In a cohort of 257 patients with symptoms of stable CAD enrolled in the SMARTool study, coronary computed tomography angiography (CTA), plasma leptin levels and clinical and bio-humoral CAD risk profile (including glucose, lipid and inflammation variables) were obtained at enrolment and after 6±1yrs of follow-up. Sixty-four patients were revascularized and the remaining 193 represent the population for the present study. CTA findings were categorised as no-minimal CAD (<30% stenosis), non-obstructive CAD (30%-50% stenosis) and obstructive CAD (>=50% stenosis in at least one major coronary vessel). A CTA risk score (based on plaque extent, severity, composition, and location) was calculated at baseline and at follow-up to assess coronary atherosclerotic burden and its progression (? CTA score>=5). Results CTA findings showed obstructive CAD in 11% of patients at baseline and in 15% at follow-up (p<0.0001). CTA risk score, was 8.03±7.80 at baseline and increased to 10.33±8.17 at follow-up (p<0.0001) with CAD progression in 20% of patients. Leptin plasma levels were inversely related with CTA findings both at baseline and follow-up (Figure). In a Cox model, baseline plasma leptin was an independent predictor of CAD progression, after adjustment for clinical risk factors, biomarkers, and treatment (HR 0.572, 95% CI 0.393-0.834, P=0.0037). Conclusion Plasma leptin is inversely associated with coronary atherosclerotic burden and disease progression in patients with stable CAD. This association is independent of known factors affecting leptin levels. These results could prompt further investigations on the pathophysiological mechanisms of this association. Acknowledgement/Funding EU H2020 research and innovation program under grant agreement No 689068