• DOI:10.1001/JAMA.294.14.1799
• Corpus ID: 6128916

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

@article{Danesh2005PlasmaFL,
  title={Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.},
  author={John Danesh and Sarah Lewington and Simon G Thompson and Gordon D. O. Lowe and Rory Collins and John B. Kostis and A. C. Wilson and Aaron R. Folsom and K. K. Wu and Michal Benderly and Uri Goldbourt and Johann Willeit and Stefan Kiechl and John W. G. Yarnell and Peter M. Sweetnam and Peter C. Elwood and Mary Cushman and Bruce M. Psaty and Russell P. Tracy and Anne Tybjaerg-hansen and Frits Haverkate and Moniek P. M. de Maat and Francis Gerry R Fowkes and A. J. Lee and Felicity B Smith and Veikko V Salomaa and Kennet Harald and Renata Rasi and Elina M. Vahtera and Pekka Jousilahti and Juha Pekkanen and Ralph B. D'Agostino and William B. Kannel and Peter W. F. Wilson and Geoffrey H Tofler and Carmen Luisa Arocha-Pi{\~n}ango and A. Rodriguez-Larralde and Elena Nagy and Mercedes Elena Mijares and Ra{\'u}l A Espinosa and E Rodriquez-Roa and Elena Ryder and Mar{\'i}a Diez‐Ewald and Gilberto Campos and Virginia Fern{\'a}ndez and Enrique Torres and Roberto Marchioli and Franco Valagussa and Annika Rosengren and Lars W. Wilhelmsen and Georgios Lappas and Henry Eriksson and Peter Cremer and Dorothea Nagel and J. David Curb and Beatriz L. Rodr{\'i}guez and Katsuhiko Yano and Jukka T. Salonen and Kristiina Nyyssönen and Tomi-Pekka Tuomainen and Bo Hedblad and Peter Lind and Hannelore Loewel and Wolfgang Koenig and Tom W. Meade and Jackie A. Cooper and Bianca L. De Stavola and C. Knottenbelt and George J. Miller and Kenneth A. Bauer and Robert D. Rosenberg and S. Sato and Akihiko Kitamura and Yoshihiko Naito and Timo Palosuo and Pierre Ducimetiere and Philippe Amouyel and Dominique Arveiler and Alun E. Evans and Jean Ferri{\`e}res and I Juhan-vague and Annie Bingham and Helmut Schulte and Gerd Assmann and Bernard Cantin and Beno{\^i}t Lamarche and Jean-Pierre Despr{\'e}s and Gilles R. Dagenais and Hugh Tunstall-Pedoe and Mark Woodward and Yoav Ben-Shlomo and George Davey Smith and V. Palmieri and Jeunliang Yeh and Alicja Regina Rudnicka and Paul M. Ridker and Francesco Rodeghiero and Alberto Tosetto and James Shepherd and Ian Ford and Michele Robertson and Eric J. Brunner and M J Shipley and Edith J. M. Feskens and Daan Kromhout and Alfred Dickinson and Belinda K Ireland and Kelsey Juzwishin and Stephen Kaptoge and Sarah Lewington and Anis Memon and Nadeem Sarwar and Matthew Walker and Jeremy G. Wheeler and Ian R. White and Angela M. Wood},
  journal={JAMA},
  year={2005},
  volume={294 14},
  pages={
          1799-809
        }
}

• J. Danesh, S. Lewington, +113 authors A. Wood
• Published 12 October 2005
• Medicine
• JAMA

CONTEXT
Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke.

OBJECTIVE
To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data.

DATA SOURCES
Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators.

STUDY SELECTION
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.

DATA EXTRACTION
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.

DATA SYNTHESIS
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.

CONCLUSIONS
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.