Association Between Sphingolipids and Cardiopulmonary Fitness in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation

Abstract

The long-term benefits conferred by cardiac rehabilitation (CR) in those with coronary artery disease (CAD) are strongly linked with an improvement in cardiopulmonary fitness. This study aimed to determine the association between peripheral sphingolipids and cardiopulmonary fitness in CAD subjects undertaking CR. Patients with CAD (n = 100, mean age = 64 ± 6 years, 85% male, mean years of education = 17 ± 3 years) underwent 6 months of CR with blood collected at baseline, 3 and 6 months. Cardiopulmonary fitness was assessed by measuring peak oxygen uptake (VO2peak) at all time points. High performance liquid chromatography coupled electrospray ionization tandem mass spectrometry was used to quantify plasma sphingolipid concentrations. Cross-sectional and longitudinal associations between sphingolipids and VO2peak were assessed using linear regressions and mixed models, respectively. Higher concentrations of sphingomyelin C18:1 (β = −0.26, p = .01), ceramides C16:0 (β = −0.24, p = .02), C18:0 (β = −0.29, p = .002), C20:0 (β = −0.24, p = .02) and C24:1 (β = −0.24, p = .01) and monohexylceramide C18:0 (β = −0.23, p = .02) were associated with poorer VO2peak at baseline. An improvement in VO2peak was associated with a decrease in sphingomyelin C18:1 (b = −10.09, p = .006), ceramides C16:0 (b = −9.25, p = .0003), C18:0 (b = −5.44, p = .0003) and C24:1 (b = −2.46, p = .006) and monohexylceramide C18:0 (b = −5.37, p = .005). Specific long chain sphingolipids may be useful markers of fitness and response to exercise in CAD.

Sex-Specific Relationship between the Cardiorespiratory Fitness and Plasma Metabolite Patterns in Healthy Humans—Results of the KarMeN Study

“…In particular, SMs with saturated acyl chains (C18:0 to C24:0) were closely correlated with parameters of obesity or insulin resistance [ 46 ]. As is consistent with our results, previous studies reported negative correlations between CRF and blood SM C18:0 [ 22 , 47 ] or SM C18:1 [ 20 , 47 ] in young [ 22 ] and middle-aged [ 20 ] adults or patients with coronary artery disease [ 47 ]. Despite sex-related differences, our findings indicate that even in healthy individuals and across a broad age range, higher CRF tends to be associated with lower values of potential novel blood biomarkers of the pathophysiological processes underlying cardiometabolic diseases.…”

The Complex Tail of Circulating Sphingolipids in Atherosclerosis and Cardiovascular Disease

“…Thus, specific plasma ceramides, namely d18:1/C16:0-, d18:1/C18:0- and d18:1/C24:1-ceramide, appear to be indicative of plaque instability and CVD fatality. 8 104 105 106 These ceramide species predict cardiovascular events in asymptomatic individuals 78 . Calculation of the ratio of d18:1/C16:0-ceramide to d18:1/C24:0-ceramide significantly improved CAD prediction.…”

How Ceramides Orchestrate Cardiometabolic Health—An Ode to Physically Active Living

“…Thus, the American Heart Association even recommends assessing CRF as a vital sign in clinical practice [97]. Strikingly, several ceramide species were reported to be negatively associated with CRF: Cer (18:0;2/22:1) [103], Cer (18:0;2/24:1) [103], Cer (18:1;2/14:0) [103], Cer (18:1;2/16:0) [103][104][105], Cer (18:1;2/18:0) [105,106], Cer (18:1;2/20:0) [105,106], Cer (18:1;2/22:1) [103] and Cer (18:1;2/24:1) [105]. The three cardiometabolically deleterious ceramide species clinically used in the ceramide-phospholipid score (Cer (18:1;2/16:0), Cer (18:1;2/18:0) and Cer (18:1;2/24:1)) were notably reported to be negatively associated with CRF [12,79].…”