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 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 ≥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.