Danesh John, Lewington Sarah, Thompson Simon G, Lowe Gordon D O, Collins Rory, Kostis J B, Wilson A C, Folsom A R, Wu K, Benderly M, Goldbourt U, Willeit J, Kiechl S, Yarnell J W G, Sweetnam P M, Elwood P C, Cushman M, Psaty B M, Tracy R P, Tybjaerg-Hansen A, Haverkate F, de Maat M P M, Fowkes F G R, Lee A J, Smith F B, Salomaa V, Harald K, Rasi R, Vahtera E, Jousilahti P, Pekkanen J, D'Agostino R, Kannel W B, Wilson P W F, Tofler G, Arocha-Piñango C L, Rodriguez-Larralde A, Nagy E, Mijares M, Espinosa R, Rodriquez-Roa E, Ryder E, Diez-Ewald M P, Campos G, Fernandez V, Torres E, Marchioli R, Valagussa F, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Cremer P, Nagel D, Curb J D, Rodriguez B, Yano K, Salonen J T, Nyyssönen K, Tuomainen T-P, Hedblad B, Lind P, Loewel H, Koenig W, Meade T W, Cooper J A, De Stavola B, Knottenbelt C, Miller G J, Cooper J A, Bauer K A, Rosenberg R D, Sato S, Kitamura A, Naito Y, Palosuo T, Ducimetiere P, Amouyel P, Arveiler D, Evans A E, Ferrieres J, Juhan-Vague I, Bingham A, Schulte H, Assmann G, Cantin B, Lamarche B, Després J-P, Dagenais G R, Tunstall-Pedoe H, Woodward M, Ben-Shlomo Y, Davey Smith G, Palmieri V, Yeh J L, Rudnicka A, Ridker P, Rodeghiero F, Tosetto A, Shepherd J, Ford I, Robertson M, Brunner E, Shipley M, Feskens E J M, Kromhout D, Dickinson A, Ireland B, Juzwishin K, Kaptoge S, Lewington S, Memon A, Sarwar N, Walker M, Wheeler J, White I, Wood A
Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.
JAMA. 2005 Oct 12;294(14):1799-809. doi: 10.1001/jama.294.14.1799.
Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke.
To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data.
Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators.
All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded.
Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias.
Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design.
In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
血浆纤维蛋白原水平可能与冠心病（CHD）和中风风险相关。
基于个体参与者数据评估纤维蛋白原水平与主要血管疾病风险以及非血管结局风险之间的关系。
通过计算机辅助检索、手动检索参考文献列表以及与相关研究者的个人交流来识别相关研究。
所有识别出的前瞻性研究均被纳入，这些研究需提供基线纤维蛋白原水平信息以及至少1年随访期间后续主要血管疾病发病率和/或特定病因死亡率的详细信息。如果研究是基于参与者有心血管疾病既往史进行招募的，则被排除；已知患有冠心病或中风的参与者也被排除。
在31项前瞻性研究中的154,211名参与者的个体记录均被提供。在138万人年的随访期间，有6944例首次非致命性心肌梗死或中风事件以及13,210例死亡。特定病因死亡率一般可得。分析采用比例风险模型，对已知心血管危险因素的混杂因素以及回归稀释偏倚进行了调整。
在每个考虑的年龄组（40 - 59岁、60 - 69岁以及≥70岁）中，对于任何冠心病、任何中风、其他血管疾病（如非冠心病、非中风）死亡率以及非血管疾病死亡率的风险，与通常的纤维蛋白原水平存在近似对数线性关联。在所研究的通常纤维蛋白原水平范围内，在任何年龄均未发现阈值证据。对于冠心病，通常纤维蛋白原水平每升高1 g/L，年龄和性别调整后的风险比为2.42（95%置信区间[CI]，2.24 - 2.60）；中风为2.06（95% CI，1.83 - 2.33）；其他血管疾病死亡率为2.76（95% CI，2.28 - 3.35）；非血管疾病死亡率为2.03（95% CI，1.90 - 2.18）。在进一步对几个已确定的血管危险因素测量值进行调整后，冠心病和中风的风险比降至约1.8。在7011名有C反应蛋白值的参与者子集中，在对C反应蛋白进行额外调整后，冠心病的研究结果基本未变。纤维蛋白原水平与冠心病或中风的关联在性别、吸烟、血压、血脂水平或研究设计的几个特征方面没有显著差异。
在这项大型个体参与者荟萃分析中，发现在健康中年成年人的广泛情况下，通常的血浆纤维蛋白原水平与冠心病、中风、其他血管疾病死亡率和非血管疾病死亡率风险之间存在中度强关联。评估纤维蛋白原水平升高与疾病的任何因果相关性需要进一步研究。
