Elevated high-sensitivity C-reactive protein (hs-CRP) levels have been found to be significantly related to an increased risk of coronary heart disease in both men and women (1), but how does low-grade inflammation reflected as elevated hs-CRP relate to hypertension, a major cardiovascular risk factor? In this presentation Prof. Niskanen discusses findings from the Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study on the relationship between hs-CRP levels and the risk of future development of hypertension and metabolic syndrome, and evidence for a proatherogenic role of CRP.

Recent studies suggest that hypertension is in part an inflammatory disorder. In 2001 Chae and colleagues reported significant linear relationships between blood pressure measures and levels of the inflammatory markers IL-6 and sICAM-1 in apparently healthy men (2). Subsequent data from the prospective Women's Health Study showed that CRP and blood pressure were independent determinants of cardiovascular risk, and that their predictive value was additive (3). Further, hs-CRP levels were found to be associated with the future development of hypertension (4).

The prospective KIHD study was conducted in a random, age-stratified sample of Finnish men, and men with hypertension or diabetes at baseline were excluded from the incident hypertension analyses of the study. Extending the findings from the Women's Health Study, 11-year follow-up data from the KIHD study showed that men with hs-CRP levels >/= 3.0mg/L were 2.8 times more likely to develop hypertension than those with hs-CRP below 1.0 mg/L after adjusting for features of the metabolic syndrome, lifestyle factors, and their changes (5). It had been previously reported also from the KIHD study that men with hs-CRP >/= 3.0mg/L were at increased risk of developing metabolic syndrome and diabetes compared to those with hs-CRP below 1.0mg/L (6).

Apart from being a risk marker for future cardiovascular events, there is evidence to suggest that human CRP is an active participant in lesion formation (7,8). Prof. Niskanen makes some concluding remarks and discusses future directions for research.

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

- Data from the WHS and KIHD studies on hs-CRP and the risk of future incidence of hypertension
- Data from the KIHD study on hs-CRP and the risk of developing metabolic syndrome or diabetes
- Evidence for direct proatherogenic effects of CRP
- Conclusions and future directions for research

1. Jennifer K. Pai, M.H.S., Tobias Pischon, M.D., M.P.H., Jing Ma, M.D., Ph.D., JoAnn E. Manson, M.D., Dr.P.H., Susan E. Hankinson, Sc.D., Kaumudi Joshipura, B.D.S., Sc.D., Gary C. Curhan, M.D., Sc.D., Nader Rifai, Ph.D., Carolyn C. Cannuscio, Sc.D., Meir J. Stampfer, M.D., Dr.P.H., and Eric B. Rimm, Sc.D.Inflammatory Markers and the Risk of Coronary Heart Disease in Men and Women NEJM. 2004;351:2599-2610.

2. Claudia U. Chae; Richard T. Lee; Nader Rifai; Paul M. Ridker. Blood Pressure and Inflammation in Apparently Healthy Men Hypertension. 2001;38:399.

3. Gavin J. Blake, MD, MPH, MRCPI; Nader Rifai, PhD; Julie E. Buring, ScD; Paul M Ridker, MD, MPH. Blood Pressure, C-Reactive Protein, and Risk of Future Cardiovascular Events Circulation. 2003;108:2993.

4. 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.

5. Leo Niskanen; David E. Laaksonen; Kristiina Nyyssönen; Kari Punnonen; Veli-Pekka Valkonen; Ricardo Fuentes; Tomi-Pekka Tuomainen; Riitta Salonen; Jukka T. Salonen. Inflammation, Abdominal Obesity, and Smoking as Predictors of Hypertension Hypertension. 2004;44:859.

6. D. E. Laaksonen, L. Niskanen, K. Nyyssönen, K. Punnonen, T.-P. Tuomainen, V.-P. Valkonen, R. Salonen and J. T. Salonen. C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men Diabetologia. 2004;47(8):1403 - 1410.

7. Subodh Verma and Edward T. H. Yeh. C-reactive protein and atherothrombosis—Beyond a biomarker: an actual partaker of lesion formation Am J Physiol Regul Integr Comp Physiol 285: R1253-R1256, 2003.

8. Chao-Hung Wang, MD; Shu-Hong Li, MSc; Richard D. Weisel, MD; Paul W.M. Fedak, MD; Aaron S. Dumont, MD; Paul Szmitko, BSc; Ren-Ke Li, MD, PhD; Donald A.G. Mickle, MD; Subodh Verma, MD, PhD. C-Reactive Protein Upregulates Angiotensin Type 1 Receptors in Vascular Smooth Muscle Circulation. 2003;107:1783.