Frequency of adding salt to foods, metabolic signature, and the risk of extracoronary atherosclerotic vascular disease progression

Wei Cheng, Chenghui Cao, Wen Gong, B Q Yu, Liang Tang, Z W Zhu, S H E N G H Zhou

Background The frequency of adding salt to foods reflects an individual’s long-term salt preference, and excessive salt intake may increase cardiovascular risk. However, the association between this behavioral indicator and extracoronary atherosclerotic vascular disease, along with its underlying metabolic signature, remains inadequately characterized. Methods We included 495,291 participants from the UK Biobank and assessed the frequency of adding salt to foods. Cox proportional hazards regressions modeled the associations of salt-adding frequency with incident peripheral arterial disease (PAD) and incident carotid artery stenosis (CAS), and related events, respectively. Results During a median of 13.9 years of follow-up, 7,461 incident cases of PAD and 8,067 cases of CAS were identified. When fully adjusted for confounders, participants who sometimes, usually, or always added salt to foods showed an increased risk of developing PAD of 8%, 16%, and 35%, respectively, compared to those who never/rarely did. A comparable pattern of risk increase was also evident for CAS, with 26% higher risk in participants who always added salt to foods. In addition, consistent associations were observed for vascular-related events. Genetic analyses further revealed that the association between salt-adding frequency and PAD was independent of genetic predisposition. Finally, a metabolic signature for salt-adding frequency was constructed using 26 metabolites, which mediated 36.4% and 19.9% of the increased risks for PAD and CAS, respectively. Conclusion Our study shows that frequently adding salt to foods is associated with an increased risk of extracoronary atherosclerotic vascular disease and related events, with circulating metabolites playing a partial mediating role.