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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

JAMA. 2003;290:2945-2951.

Context  Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce.

Objective  To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension.

Design, Setting, and Participants  A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected.

Main Outcome Measure  Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg.

Results  During follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP.

Conclusion  C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.

Author Affiliations: Department of Medicine, Center for Cardiovascular Disease Prevention and the Division of Preventive Medicine (Drs Sesso, Buring, Blake, Gaziano, and Ridker), and Department of Medicine, Donald W. Reynolds Center for Cardiovascular Research (Drs Sesso, Buring, and Ridker), Brigham and Women's Hospital and Harvard Medical School; Department of Epidemiology, Harvard School of Public Health (Drs Sesso and Buring); and Department of Laboratory Medicine, Children's Hospital and Harvard Medical School (Dr Rifai), Boston, Mass.

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