摘要
Individuals with a high degree of salt sensitivity(SS)have a greater risk of cardiovascular disease(CVD),but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear.This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs,based on the MetaSalt study,which was a dietary salt-intervention trial conducted at four centers in China in 2019.A total of 528 participants were recruited and underwent 3 days of baseline observations,a 10-day low-salt intervention,and a 10-day highsalt intervention.Plasma untargeted metabolomics,lipidomics,and BP measurements were scheduled at each stage.Participants were grouped into extreme SS,moderate SS,and salt-resistant(SR)individuals according to their BP responses to salt.Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness.Mendelian randomization(MR)analyses were applied to establish the causal pathways among the SS-related metabolites,BP,and CVDs.Among the 713 metabolites,467 were significantly changed after the high-salt intervention.Among them,the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups.Of the remaining nonsalt-related metabolites,the baseline levels of 11 metabolites were related to SS.These 41 metabolites explained 23%of the variance in SS.Moreover,SS and its metabolomics signature were positively correlated with arterial stiffness.MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP,indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause.Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs.This study provides insight into understanding the biology and targets of SS and its role in CVDs.
