on February 24, 2005
Arteriosclerosis, Thrombosis, and Vascular Biology. 2005
Published online before print February 24, 2005, doi: 10.1161/01.ATV.0000160351.95181.d0
Published online before print February 24, 2005, doi: 10.1161/01.ATV.0000160351.95181.d0
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Submitted on October 1, 2004
Accepted on February 10, 2005
Association of C-Reactive Protein With Blood Pressure and Hypertension. Life Course Confounding and Mendelian Randomization Tests of Causality
George Davey Smith *;
From the Department of Social Medicine, University of Bristol; Division of Cardiovascular and Medical Sciences, University of Glasgow; and Human Genetics Division, School of Medicine, University of Southampton School of Medicine, UK.
* To whom correspondence should be addressed. E-mail: zetkin{at}bristol.ac.uk.
Background--C-reactive protein (CRP) has repeatedly been associated with blood pressure and prevalent and incident hypertension, but whether a causal link exists is uncertain.
Methods and Results--We assessed the cross-sectional relations of CRP to systolic blood pressure, pulse pressure, and prevalent hypertension in a representative sample of >3500 British women aged 60 to 79 years. For both outcomes, substantial associations were observed. However, these associations were greatly attenuated by adjustment for a wide range of confounding factors acting over the life course. We further investigated causality using a Mendelian randomization approach by examining the association of the 1059G/C polymorphism in the human CRP gene with CRP and with blood pressure, pulse pressure, and hypertension. The polymorphism was associated with a robust difference in CRP, and the expectation would be for higher blood pressure and pulse pressure and greater prevalence of hypertension among those carrying the genetic variant associated with higher CRP levels. This was not observed, and the predicted causal effects of CRP on blood pressure, pulse pressure, and hypertension using instrumental variables methods were close to 0, although with wide CIs.
Conclusions--CRP levels are associated with blood pressure, pulse pressure, and hypertension, but adjustment for lifetime confounding and a Mendelian randomization approach suggest the elevated CRP levels do not lead to elevated blood pressure.
Key words: C-reactive protein • blood pressure • hypertension • Mendelian randomization • 1059 G/C variant
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