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C-reactive protein: associations with haematological variables, cardiovascular risk factors and prevalent
Mark Woodward1, Ann Rumley, Gordon D O Lowe
1Institute for International Health, University of Sydney, Australia. mwoodward@iih.usyd.edu.au
Insights
C-reactive protein (CRP) correlates with cardiovascular disease risk factors. While CRP is linked to prevalent cardiovascular disease, this association is largely explained by other risk factors, particularly fibrinogen, except for a residual effect in women.
Area of Science:
- Biochemistry
- Epidemiology
- Cardiovascular Medicine
Background:
- C-reactive protein (CRP) is a proposed cardiovascular disease (CVD) risk factor.
- Its association with CVD is confounded by classical and hematological risk factors.
Purpose of the Study:
- To investigate the correlation of high-sensitivity CRP with CVD risk factors.
- To determine the association between CRP and prevalent CVD, considering confounders.
Main Methods:
- High-sensitivity CRP assay on stored plasma samples from 414 men and 515 women (North Glasgow MONICA survey).
- Correlations assessed with hematological variables, classical CVD risk factors, and prevalent CVD.
- Statistical adjustment for classical risk factors and fibrinogen.
Main Results:
- CRP correlated with age, oral contraceptive use, menopause, and most classical risk factors (excluding blood pressure).
- CRP also correlated with interleukin-6, hematocrit, viscosity, red cell aggregation, white cell count, and coagulation factors (fibrinogen, FVII, FVIII, FIX).
- CRP was associated with prevalent CVD in men and women, but this became non-significant after adjusting for classical risk factors and fibrinogen, with a residual independent effect noted in women.
Conclusions:
- Correlations with classical and hematological risk factors explain a significant part of the CRP-CVD association.
- A residual, independent effect of CRP on prevalent cardiovascular disease may exist in women.
Abstract:
C-reactive protein (CRP) has been proposed as a risk factor for cardiovascular disease; however, this association is confounded by mutual relationships with both classical and haematological cardiovascular risk factors. We, therefore, measured CRP with a high-sensitivity assay in stored plasma samples from 414 men and 515 women in the north Glasgow MONICA (MONItoring trends in CArdiovascular diseases) survey, to study its correlation with haematological variables, classical risk factors and prevalent cardiovascular disease. CRP correlated with age, oral contraceptive use, menopause and most classical cardiovascular risk factors (except blood pressure). CRP also correlated with plasma levels of the pro-inflammatory cytokine interleukin 6, and haematocrit, viscosity, red cell aggregation, white cell count, and coagulation factors [fibrinogen, factor (F) VII in women, FVIII, FIX] and inhibitors (antithrombin and protein C in women; protein S) but not coagulation activation markers. CRP was significantly associated with prevalent cardiovascular disease in both men (P = 0.03) and women (P = 0.009), however, the association became non-significant after adjustment for firstly classical risk factors, then fibrinogen. We conclude that correlations with classical and haematological risk factors account for a substantial component of the association of CRP with prevalent cardiovascular disease, but there is evidence of a residual, independent effect among women.
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