Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort

Q Medicine
M. Lacruz, A. Kluttig, D. Tiller, D. Medenwald, I. Giegling, D. Rujescu, C. Prehn, J. Adamski, S. Frantz, K. Greiser, R. Emeny, G. Kastenmüller, J. Haerting
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引用次数: 29

Abstract

Background—The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown. We aim to investigate the association of these risk factors with metabolites and their changes during 4 years. Methods and Results—One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was used for the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI, alcohol consumption, and smoking were associated with lipid metabolism (reduced lyso- and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines, and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. Conclusions—This study showed sex-specific effects of lifestyle risks factors on human metabolism and highlighted their long-term metabolic consequences.
心血管危险因素与血液代谢物浓度相关及其在4年期间的变化
生活方式风险因素对人体代谢的总体影响迄今尚不清楚。我们的目的是研究这些危险因素与代谢物的关系及其在4年内的变化。方法和结果:采用靶向代谢组学方法,使用AbsoluteIDQ试剂盒p150 (Biocrates)在1030名基线年龄为45至83岁的人群中检测血清样本中的163种代谢物。我们评估了代谢物浓度(28种酰基肉碱、14种氨基酸、9种溶血胆碱、72种磷酸胆碱、10种鞘磷脂和己糖总量)与5种生活方式危险因素(体重指数、饮酒、吸烟、饮食和运动)之间的关系。采用校正相关协变量的多水平或简单线性回归模型分别评估横截面或纵向关联;多重测试修正基于错误发现率。BMI、饮酒和吸烟与脂质代谢相关(溶酶和酰基烷基磷脂酰胆碱降低,二酰基磷脂酰胆碱浓度升高)。吸烟与酰基肉碱呈正相关,BMI与非必需氨基酸呈负相关。较少的代谢物显示出与基线危险因素相关的相对变化:5种不同酰基-烷基磷脂酰胆碱的增加与较低的饮酒量和BMI以及更健康的饮食有关。酪氨酸水平升高与BMI有关。吸烟和身体质量指数的性别特异性影响被发现与酰基肉碱代谢特别相关:女性身体质量指数越高,男性年龄越长与酰基肉碱的增加有关。结论:本研究显示了生活方式风险因素对人体代谢的性别特异性影响,并强调了其长期代谢后果。
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来源期刊
Circulation-Cardiovascular Genetics
Circulation-Cardiovascular Genetics CARDIAC & CARDIOVASCULAR SYSTEMS-GENETICS & HEREDITY
CiteScore
3.95
自引率
0.00%
发文量
0
期刊介绍: Circulation: Genomic and Precision Medicine considers all types of original research articles, including studies conducted in human subjects, laboratory animals, in vitro, and in silico. Articles may include investigations of: clinical genetics as applied to the diagnosis and management of monogenic or oligogenic cardiovascular disorders; the molecular basis of complex cardiovascular disorders, including genome-wide association studies, exome and genome sequencing-based association studies, coding variant association studies, genetic linkage studies, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics; integration of electronic health record data or patient-generated data with any of the aforementioned approaches, including phenome-wide association studies, or with environmental or lifestyle factors; pharmacogenomics; regulation of gene expression; gene therapy and therapeutic genomic editing; systems biology approaches to the diagnosis and management of cardiovascular disorders; novel methods to perform any of the aforementioned studies; and novel applications of precision medicine. Above all, we seek studies with relevance to human cardiovascular biology and disease. Manuscripts are examined by the editorial staff and usually evaluated by expert reviewers assigned by the editors. Both clinical and basic articles will also be subject to statistical review, when appropriate. Provisional or final acceptance is based on originality, scientific content, and topical balance of the journal. Decisions are communicated by email, generally within six weeks. The editors will not discuss a decision about a manuscript over the phone. All rebuttals must be submitted in writing to the editorial office.
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