The Association Between C24:0/C16:0 Ceramide Ratio and Cardiorespiratory Fitness is Robust to Effect Modifications by Age and Sex

Ceramides and cardiorespiratory (CR) fitness are both related to cardiovascular diseases. The associations of three blood plasma ceramides (C16:0, C22:0, and C24:0) with CR fitness in the population-based Study of Health in Pomerania (SHIP-START-1; n = 1,102; mean age 50.3 years, 51.5% women) are investigated. In addition, subgroup analysis according to age (= 54 years) and sex (female/male) is performed. Ceramides are quantified by liquid chromatography/mass spectrometry (LC/MS). CR fitness is assessed by a cardiopulmonary exercise test. Sex and age independent associations are found for higher levels of C24:0 and C24:0/C16:0 ratio with higher maximal oxygen consumption (VO2peak) kg-1 and oxygen consumption at the anaerobic threshold (VO2@AT1) as well as for the relation of C24:0/C16:0 with maximum workload (Wattmax kg-1). In contrast, age/sex subgroup specific inverse associations with Wattmax kg-1 are found in women <54 years for C22:0, while a positive association in men >= 54 years. Higher levels of C24:0 are associated with higher Wattmax kg-1, except for women <54 years, where no significant association can be found. The findings suggest that the use of single ceramides as cardiovascular biomarkers may be inferior, compared to ceramide ratio C24:0/C16:0. Therefore C24:0/C16:0 ratio may be a more suitable and robust cardiovascular biomarker and should be preferred over single ceramides. The present study illustrates associations between blood ceramide levels and cardiorespiratory (CR) fitness parameters. Those associations may be prone to effect modifications by age and sex for single ceramides, while the positive association between ceramide ratio C24:0/C16:0 and CR fitness parameters is robust against those effect modifications, highlighting its potential as biomarker for cardiovascular disease risk prediction. image