Abstract
Background and aimsLow cardiorespiratory fitness is a strong and independent risk factor for cardiovascular disease (CVD). Serum profiling of healthy individuals with large differences in cardiorespiratory fitness may therefore reveal early biomarkers of CVD development. Thus, we aimed to identify circulating lipoprotein subfractions differentially expressed between groups of individuals with large differences in cardiorespiratory fitness, measured as maximal oxygen uptake (VO2max). MethodsHealthy subjects (40–59 years) were selected from the third wave of the Trøndelag health study (HUNT3) based on having an age-dependent high VO2max (47.1 ± 7.7 mL kg−1·min−1, n = 103) or low VO2max (31.4 ± 4.9 mL kg−1·min−1, n = 108). The individuals were matched on gender, age, physical activity level and fasting status. Results99 lipoprotein subfractions were quantified in serum samples using nuclear magnetic resonance (NMR) lipidomics. Standard clinical analyses showed similar levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol between the groups, and slightly higher levels of triglycerides in participants with low VO2max. Thirteen lipoprotein subfractions were increased in the low VO2max group compared to the high VO2max group (p < 0.005), including mainly large very low-density lipoprotein (VLDL) subfractions. In addition, triglyceride levels in small-sized HDL and LDL particles were increased in participants with low VO2max. Correlation analyses between VO2max and lipoproteins subfractions displayed a negative correlation between VO2max and the levels of cholesterol and phospholipids in the small HDL particles. The lipoprotein profile of individuals with low VO2max is similar to the profile of insulin resistant individuals. ConclusionsLow VO2max was associated with enrichment of large VLDL particles, as well as an increased triglycerides content in the small and dense HDL and LDL particles. This unfavorable lipid profile is likely to be involved in the strong associations between VO2max and CVD.
Highlights
Cardiorespiratory fitness, measured as maximal oxygen uptake (VO2max), is a strong marker of cardiac health
Low VO2max was associated with enrichment of large VLDL particles, as well as an increased triglycerides content in the small and dense High-density lipoprotein (HDL) and LDL particles
Journal Pre-proof Based on this, lipoprotein signatures of healthy individuals with low VO2max may provide information on processes associated with the initial phases of cardiovascular disease (CVD) development, as well as new biomarkers of atherosclerosis
Summary
Cardiorespiratory fitness, measured as maximal oxygen uptake (VO2max), is a strong marker of cardiac health. Large-scale epidemiological studies have shown that low VO2max is the single best predictor of future cardiovascular disease (CVD) mortality both in healthy individuals and in patients with CVD.[1,2,3,4,5,6] there is an inverse relationship between VO2max and the presence of metabolic risk factors for CVD, such as atherogenic lipoproteins and levels of inflammation markers.[7,8] profiles of serum lipoprotein subfraction associated with low VO2max are still undetermined.[9]. We aimed to identify circulating lipoprotein subfractions differentially expressed between groups of individuals with large differences in cardiorespiratory fitness, measured as maximal oxygen uptake (VO2max). The individuals were matched on gender, age, physical activity level and fasting status
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