Circulating ectoenzyme CD38 is associated with diastolic dysfunction in subjects with metabolic syndrome: a population-based cross-sectional study
S Ministrini, A Tirandi, S Bengs, Y M Puspitasari, N Verheyen, A Kuenzli, S C Conace, T F Luescher, M Abdellatif, G G CamiciAbstract
Introduction
Myocardial stiffening and diastolic dysfunction (DD) are predominant features of myocardial ageing and metabolic cardiomyopathy [1,2]. CD38 is a nicotinamide adenine dinucleotide (NAD+)-dependent ectoenzyme expressed in cardiomyocytes [3]. Its expression progressively increases during aging, causing intracellular NAD+ depletion and mitochondrial dysfunction [4]. Previous studies showed that NAD-depletion plays a pivotal role in DD [5]. However, the role of soluble circulating CD38 in DD is still unclear.
Methods
CD38 was measured by enzyme-linked immunosorbent assay in 954 subjects enrolled in the Biomarkers of Personalised Medicine study (BioPersMed) [6], a single-centre prospective observational cohort study base in Graz (AT). Subjects had at least one traditional cardiovascular risk factor or type 2 diabetes mellitus. Diastolic function was assessed by echocardiography. Diastolic dysfunction was defined by an e’ velocity <6.5 cm/s associated with any of the following criteria: E/e’ >14, E/A <0.8 or >2, and left atrial diameter >51 mm for women or >55 mm for men [7,8]. Metabolic syndrome was defined according to the recommendations of the Adult Treatment Program III of the National Cholesterol Education Program [9].
Results
Circulating CD38 was inversely associated to e’ velocity at univariate linear regression analysis (p< 0.001, Figure 1). This association was confirmed after correction for potential confounders, namely age, and metabolic syndrome (β= -0.07; p< 0.001). Subjects with a clinical diagnosis of DD displayed significantly higher levels of CD38 after correction for the above-mentioned confounding factors (OR for doubling of CD38= 3.5, p= 0.029). Interestingly, a sensitivity analysis showed a significant association between CD38 and DD only in subjects with metabolic syndrome (OR for doubling of CD38= 2.6, p= 0.036; Figure 2)
Conclusions
CD38 inversely associates with e’ velocity and, therefore, with DD in subjects with metabolic syndrome. Although the causal relationship between circulating CD38 and DD requires additional investigations, it represents an addressable molecular target for the treatment of metabolic cardiomyopathy.Figure 2Figure 1