Department of Epidemiology, College of Public Health & Health Professions and College of Medicine, University of Florida, 2004 Mowry Rd, Gainesville, FL, 32610, USA.
Center for Genetic Epidemiology and Bioinformatics, University of Florida, Gainesville, FL, USA.
Geroscience. 2023 Aug;45(4):2669-2687. doi: 10.1007/s11357-023-00793-7. Epub 2023 Apr 13.
Dyslipidemia is an independent and modifiable risk factor for aging and age-related disorders. Routine lipid panel cannot capture all individual lipid species in blood (i.e., blood lipidome). To date, a comprehensive assessment of the blood lipidome associated with mortality is lacking in large-scale community-dwelling individuals, especially in a longitudinal setting. Using liquid chromatograph-mass spectrometry, we repeatedly measured individual lipid species in 3,821 plasma samples collected at two visits (~ 5.5 years apart) from 1,930 unique American Indians in the Strong Heart Family Study. We first identified baseline lipids associated with risks for all-cause mortality and CVD mortality (mean follow-up period: 17.8 years) in American Indians, followed by replication of top hits in European Caucasians in the Malmö Diet and Cancer-Cardiovascular Cohort (n = 3,943, mean follow-up period: 23.7 years). The model adjusted age, sex, BMI, smoking, hypertension, diabetes, and LDL-c at baseline. We then examined the associations between changes in lipid species and risk of mortality. Multiple testing was controlled by false discovery rate (FDR). We found that baseline levels and longitudinal changes of multiple lipid species, e.g., cholesterol esters, glycerophospholipids, sphingomyelins, and triacylglycerols, were significantly associated with risks of all-cause or CVD mortality. Many lipids identified in American Indians could be replicated in European Caucasians. Network analysis identified differential lipid networks associated with risk of mortality. Our findings provide novel insight into the role of dyslipidemia in disease mortality and offer potential biomarkers for early prediction and risk reduction in American Indians and other ethnic groups.
血脂异常是衰老和与年龄相关疾病的独立且可改变的危险因素。常规血脂谱无法捕捉血液中的所有个体脂质种类（即血脂组学）。迄今为止，在大规模社区居住人群中，特别是在纵向研究中，缺乏对与死亡率相关的全血脂组学的综合评估。本研究使用液相色谱-质谱法，在来自美国印第安人 1930 个个体的 3821 个血浆样本中，在两次访视（约 5.5 年）时重复测量了个体脂质种类。我们首先确定了与全因死亡率和 CVD 死亡率相关的基线血脂（美国印第安人的平均随访期：17.8 年），随后在欧洲白种人（n=3943，平均随访期：23.7 年）的马尔默饮食与癌症心血管队列中对前 5 位的命中进行了复制。该模型调整了基线时的年龄、性别、BMI、吸烟、高血压、糖尿病和 LDL-c。然后，我们研究了脂质种类变化与死亡率风险之间的关系。通过错误发现率（FDR）对多重检验进行控制。我们发现，多种脂质种类的基线水平和纵向变化，例如胆固醇酯、甘油磷脂、神经鞘磷脂和三酰基甘油，与全因或 CVD 死亡率风险显著相关。在美洲印第安人中发现的许多脂质可以在欧洲白种人中复制。网络分析确定了与死亡率风险相关的差异脂质网络。我们的研究结果为血脂异常在疾病死亡率中的作用提供了新的见解，并为美洲印第安人和其他种族群体的早期预测和风险降低提供了潜在的生物标志物。
