In our cohort with severe obesity, both well-established (hsCRP and total calprotectin) as well as more novel inflammatory proteins (including calprotectin subunit S100A9 and several amyloid isoforms) were significantly higher in serum from patients with low midwall mechanics, a group with comparable BMI and EF, but higher clustering of traditional CV risk factors (including hypertension and diabetes) compared to patients with preserved LV MWS. Here, S100A9 is linked to obesity due to melanocortin 4 receptor deficiency.