Study suggests that inflammation may play a role in developing high blood pressure

December 09, 2003

High levels of C-reactive protein are associated with an increased risk of developing high blood pressure, according to an article in the December 10 issue of The Journal of the American Medical Association (JAMA).

Increased levels of C-reactive protein are associated with chronic activation of the immune system, otherwise known as an inflammatory response, according to background information in the article. High C-reactive protein levels have also been linked to an increase risk of heart attack and stroke. Because of this association, some researchers believe that hypertension (high blood pressure) may be in part an inflammatory disorder.

Howard D. Sesso, Sc.D., M.P.H., of Brigham and Women's Hospital and Harvard Medical School, Boston, and colleagues examined whether C-reactive protein levels were associated with hypertension.

The researchers studied 20,525 women who participated in the Women's Health Study, which started in 1992. Women participating in this study were 45 years or older at the beginning of the study, and had normal blood pressures (systolic blood pressure less than 140 mm Hg; diastolic blood pressure less than 90 mm Hg). Blood samples collected at the beginning of the study were used to measure C-reactive protein levels. Women were followed up for a median of 7.8 years (half the women were followed up longer than 7.8 years, half were followed up less than 7.8 years) for the development of hypertension.

Over the follow-up period, 5,365 women developed high blood pressure. The researchers found that "Overall, there was a positive association between increasing levels of C-reactive protein and risk of developing hypertension," the authors write. Participants with the highest levels of C-reactive protein measured at the beginning of the study were about twice as likely to develop hypertension.

"This study provides evidence that baseline levels of C-reactive protein are modestly but independently associated with an increased risk of incident hypertension, even among those with very low initial [blood pressures]," the authors write. "This finding for C-reactive protein was independent of baseline levels of [blood pressure]. Similar effects were observed among those participants without baseline coronary risk factors and in analyses where C-reactive protein was considered a continuous variable. These data suggest that inflammation may have a potentially important role in the development of hypertension," the authors conclude. (JAMA. 2003;290:2945-2951. Available post-embargo at jama.com)

Editor's Note: This study was supported by research grants from the National Institutes of Health (Bethesda, Md.), a Scientist Development grant from the American Heart Association (Dallas), with additional support from Pharmacia Inc., the Doris Duke Foundation (New York, N.Y.), the Donald W. Reynolds Foundation (Las Vegas), and the Leducq Foundation (Paris). Co-author Paul M. Ridker, M.D., M.P.H., is named as a co-inventor on patents filed by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and is a Donald W. Reynolds Investigator and receives additional support from the Doris Duke Charitable Foundation and the Leducq Foundation.

EDITORIAL: INFLAMMATION, HYPERTENSION, AND THE METABOLIC SYNDROME

In an accompanying editorial, Scott M. Grundy, M.D., Ph.D., of the University of Texas Southwestern Medical Center, Dallas, discusses the link found by Sesso et al between inflammation (as evidenced by high levels of C-reactive protein) and hypertension, and notes a similar association between low-grade inflammation and metabolic syndrome. "[Metabolic syndrome] consists of a clustering of several metabolic components in one individual," writes Dr. Grundy, including obesity, and dyslipidemia (disorders of lipoprotein metabolism, which includes high cholesterol levels).

Dr. Grundy writes that "Sesso et al did not specifically address the question of what proportion of individuals with high-normal levels of C-reactive protein actually met criteria for the metabolic syndrome," but "nonetheless, the present demonstration of an apparent connection between low-grade inflammation and hypertension supports the concept that elevated blood pressure should be listed as one of the components of the metabolic syndrome."

Dr. Grundy also notes that more research is needed to explain the relationship between inflammatory markers like C-reactive protein, the metabolic syndrome and cardiovascular and arterial disease. (JAMA. 2003;290:3000-3002. Available post-embargo at jama.com)
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