Does elevated C-reactive protein cause human atherothrombosis? Novel insights from genetics, intervention trials, and elsewhere

Research output: Contribution to journalJournal articleResearchpeer-review

PURPOSE OF REVIEW: To evaluate evidence from human epidemiology, mechanistic studies, animal studies, human genetics, and human intervention trials to address whether elevated C-reactive protein (CRP) causes human atherothrombotic cardiovascular disease. RECENT FINDINGS: Human epidemiology demonstrates that elevated CRP levels are associated with increased risk of atherothrombosis. Mechanistic and animal studies provide evidence both for and against a causal relationship of CRP with atherothrombosis. Human genetics demonstrate that genetic variation in the CRP gene is associated with lifelong increased CRP levels, but not with increased risk of atherothrombosis. A human intervention trial in healthy people with low LDL cholesterol and elevated CRP demonstrated that aggressive statin treatment caused reductions of 50% in LDL cholesterol, 37% in CRP, 50% in atherothrombotic cardiovascular events, 20% in total mortality, and 45% in venothrombotic events. Importantly, the maximal atherothrombotic treatment benefits were obtained in those who achieved the lowest levels of both LDL cholesterol and CRP. SUMMARY: Given the data available in mid-2009, elevated CRP per se does not seem to cause atherothrombotic cardiovascular disease, which questions whether CRP-reducing agents will prevent these diseases. However, inflammation per se possibly contributes to atherothrombotic and venothrombotic disease, and CRP measurement may be used in risk assessment and treatment monitoring in atherothrombotic cardiovascular disease.
Original languageEnglish
JournalCurrent Opinion in Lipidology
Issue number5
Pages (from-to)393-401
Number of pages9
Publication statusPublished - 2009

Bibliographical note

Keywords: Animals; Arteries; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials as Topic; Estrogens; Humans; Thrombosis

ID: 20569865