Shah Svati H, Bain James R, Muehlbauer Michael J, Stevens Robert D, Crosslin David R, Haynes Carol, Dungan Jennifer, Newby L Kristin, Hauser Elizabeth R, Ginsburg Geoffrey S, Newgard Christopher B, Kraus William E
Department of Medicine, Duke University, Durham, NC, USA.
Circ Cardiovasc Genet. 2010 Apr;3(2):207-14. doi: 10.1161/CIRCGENETICS.109.852814. Epub 2010 Feb 19.
Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events.
We performed mass-spectrometry-based profiling of 69 metabolites in subjects from the CATHGEN biorepository. To evaluate discriminative capabilities of metabolites for CAD, 2 groups were profiled: 174 CAD cases and 174 sex/race-matched controls ("initial"), and 140 CAD cases and 140 controls ("replication"). To evaluate the capability of metabolites to predict cardiovascular events, cases were combined ("event" group); of these, 74 experienced death/myocardial infarction during follow-up. A third independent group was profiled ("event-replication" group; n=63 cases with cardiovascular events, 66 controls). Analysis included principal-components analysis, linear regression, and Cox proportional hazards. Two principal components analysis-derived factors were associated with CAD: 1 comprising branched-chain amino acid metabolites (factor 4, initial P=0.002, replication P=0.01), and 1 comprising urea cycle metabolites (factor 9, initial P=0.0004, replication P=0.01). In multivariable regression, these factors were independently associated with CAD in initial (factor 4, odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74; P=0.02; factor 9, OR, 0.67; 95% CI, 0.52 to 0.87; P=0.003) and replication (factor 4, OR, 1.43; 95% CI, 1.07 to 1.91; P=0.02; factor 9, OR, 0.66; 95% CI, 0.48 to 0.91; P=0.01) groups. A factor composed of dicarboxylacylcarnitines predicted death/myocardial infarction (event group hazard ratio 2.17; 95% CI, 1.23 to 3.84; P=0.007) and was associated with cardiovascular events in the event-replication group (OR, 1.52; 95% CI, 1.08 to 2.14; P=0.01).
Metabolite profiles are associated with CAD and subsequent cardiovascular events.
分子工具可能有助于深入了解心血管疾病风险。我们评估了代谢产物是否能区分冠状动脉疾病（CAD）并预测心血管事件的风险。
我们对CATHGEN生物样本库中的受试者进行了69种代谢产物的质谱分析。为了评估代谢产物对CAD的区分能力，对两组进行了分析：174例CAD患者和174例性别/种族匹配的对照者（“初始组”），以及140例CAD患者和140例对照者（“重复组”）。为了评估代谢产物预测心血管事件的能力，将病例合并（“事件组”）；其中，77474例在随访期间经历了死亡/心肌梗死。对第三个独立组进行了分析（“事件重复组”；n = 63例发生心血管事件的患者，66例对照者）。分析包括主成分分析、线性回归和Cox比例风险分析。两个主成分分析衍生因子与CAD相关：一个由支链氨基酸代谢产物组成（因子4，初始组P = 0.002，重复组P = 0.01），另一个由尿素循环代谢产物组成（因子9，初始组P = 0.0004，重复组P = 0.01）。在多变量回归中，这些因子在初始组（因子4，比值比[OR]，1.36；95%置信区间，1.06至1.74；P = 0.02；因子9，OR，0.67；95%置信区间，0.52至0.87；P = 0.003）和重复组（因子4，OR，1.43；95%置信区间，1.07至1.91；P = 0.02；因子9，OR，0.66；95%置信区间，0.48至0.91；P = 0.01）中均与CAD独立相关。一个由二羧基酰基肉碱组成的因子预测了死亡/心肌梗死（事件组风险比2.17；95%置信区间，1.23至3.84；P = 0.007），并且在事件重复组中与心血管事件相关（OR，1.52；95%置信区间，1.08至2.14；P = 0.01）。
代谢产物谱与CAD及随后的心血管事件相关。
