Inflammation plays a crucial role in all stages of atherosclerosis, and various inflammatory markers have been studied to date. C-reactive protein (CRP) is the most well-studied, says Dr. Kullo, due to its ease of measurement and stability in stored samples. Elevated high-sensitivity CRP levels have been linked to future cardiovascular events in several cohort studies around the world.

Arterial stiffness is a manifestation of arteriosclerosis, and measures of arterial stiffness include pulse wave velocity (PWV), pulse pressure, and augmentation index (AIX) which is a measure of arterial stiffness and wave reflection. In terms of cardiovascular risk, for example, aortic PWV has been shown to predict cardiovascular events in apparently healthy subjects (1). AIX has been shown to predict cardiovascular mortality in patients with end-stage renal disease (2) and to be associated with coronary artery disease in men under the age of 60 (3).

Is CRP, a marker of systemic inflammation associated with measures of arterial stiffness? In a study of 214 asymptomatic subjects from the community reported by Dr. Kullo's group, CRP values were measured with a high-sensitivity assay and log transformed. Log CRP was significantly correlated with aortic AIX, aortic PWV and pulse pressure (4). Acute systemic inflammation has been shown to increase arterial stiffness and decrease wave reflections (5) and there is data to show that arterial stiffness is increased in individuals with chronic inflammation (6). Finally there is also data relating CRP levels to prevalent hypertension (7) and incident hypertension (8). Dr. Kullo discusses some possible underlying mechanisms for these associations and ends with a summary.

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After viewing this presentation the participant will be able to discuss:

- CRP as a marker of inflammation
- Measures of arterial stiffness
- The association of inflammatory markers and measures of arterial stiffness
- Associations of acute and chronic inflammation to measures of arterial stiffness
- The relationship of inflammatory markers to hypertension
- Some of the mechanisms that may underly these associations

1. Francesco U.S. Mattace-Raso, MD, PhD; Tischa J.M. van der Cammen, MD, PhD; Albert Hofman, MD, PhD; Nicole M. van Popele, MD, PhD; Michiel L. Bos, MSc; Maarten A.D.H. Schalekamp, MD, PhD; Roland Asmar, MD, PhD; Robert S. Reneman, MD, PhD; Arnold P.G. Hoeks, PhD; Monique M.B. Breteler, MD, PhD; Jacqueline C.M. Witteman, PhDArterial Stiffness and Risk of Coronary Heart Disease and Stroke: The Rotterdam Study Circulation. 2006;113:657-663.

2. Gérard M. London; Jacques Blacher; Bruno Pannier; Alain P. Guérin; Sylvain J. Marchais; Michel E. SafarArterial Wave Reflections and Survival in End-Stage Renal Failure Hypertension. 2001;38:434.

3. Thomas Weber, MD; Johann Auer, MD; Michael F. O’Rourke, MD; Erich Kvas, ScD; Elisabeth Lassnig, MD; Robert Berent, MD; Bernd Eber, MDArterial Stiffness, Wave Reflections, and the Risk of Coronary Artery Disease Circulation. 2004;109:184-189.

4. Iftikhar J. Kullo, James B. Seward, Kent R. Bailey, Lawrence F. Bielak, Brandon R. Grossardt, Patrick F. Sheedy II, Patricia A. Peyser and Stephen T. TurnerC-Reactive Protein Is Related to Arterial Wave Reflection and Stiffness in Asymptomatic Subjects From the Community American Journal of Hypertension. Volume 18, Issue 8 , August 2005, Pages 1123-1129.Hypertension. 2001;38:434.

5. Charalambos Vlachopoulos, MD; Ioanna Dima, MD; Konstantinos Aznaouridis, MD; Carmen Vasiliadou, MD; Nikolaos Ioakeimidis, MD; Constadina Aggeli, MD; Marina Toutouza, MD; Christodoulos Stefanadis, MDAcute Systemic Inflammation Increases Arterial Stiffness and Decreases Wave Reflections in Healthy Individuals Circulation. 2005;112:2193-2200.

6. Mary J. Roman; Richard B. Devereux; Joseph E. Schwartz; Michael D. Lockshin; Stephen A. Paget; Adrienne Davis; Mary K. Crow; Lisa Sammaritano; Daniel M. Levine; Beth-Ann Shankar; Elfi Moeller; Jane E. SalmonArterial Stiffness in Chronic Inflammatory Diseases Hypertension. 2005;46:194.

7. Lakoski SG, Cushman M, Palmas W, Blumenthal R, D'Agostino RB Jr, Herrington DM.The relationship between blood pressure and C-reactive protein in the Multi-Ethnic Study of Atherosclerosis (MESA) J Am Coll Cardiol. 2005 Nov 15;46(10):1869-74.

8. Howard D. Sesso, ScD, MPH; Julie E. Buring, ScD; Nader Rifai, PhD; Gavin J. Blake, MD, MPH; J. Michael Gaziano, MD, MPH; Paul M. Ridker, MD, MPH C-Reactive Protein and the Risk of Developing Hypertension JAMA. 2003;290:2945-2951.