Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study.

Background: Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes. Methods: A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes. Results: Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20–6.22). Conclusions: Elevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes. Highlights: Why did we undertake this study? Diabetes is associated with a higher risk of all-cause and cardiovascular disease (CVD) deaths after control of blood pressure, glucose, and lipid. Circulating palmitoyl sphingomyelin (PSM) level is associated with an increased risk of CVD in Chinese patients with diabetes. What is the specific question we wanted to answer? Is PSM a practical predictor for CVD death? What did we find? Circulating PSM levels steadily predicted a 10-year increased risk of CVD death after adjusted for SBP, HbA1c, LDL-c, creatinine, prevalent CVD, and the use of alcohol and statins but not non-CVD death, in individuals with diabetes. What are the implications of our findings? PSM determination may be useful for predicting the long-term risk of CVD death. [ABSTRACT FROM AUTHOR]