Plasma Inflammatory Markers and the Risk of Developing Hypertension in Men

BACKGROUND: Several cross-sectional, but few prospective, studies suggest that inflammation may be involved in the development of hypertension. We examined markers of inflammation—high-sensitivity C-reactive protein, interleukin-6, and soluble intercellular adhesion molecule-1—and a marker of fibrinolysis, D-dimer, for their associations with incident hypertension in the Physicians’ Health Study. METHODS AND RESULTS: Baseline blood values and information on hypertension-related risk factors were collected in 1982. Incident hypertension was defined as self-reported initiation of antihypertensive treatment, systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg during follow-up. With use of a nested case-control design, 396 cases of incident hypertension and controls free of hypertension were matched 1:1 on age (mean 47.4 years) and follow-up time. In crude matched-pair analyses, the conditional relative risks of hypertension in the second through fourth versus the lowest quartiles for plasma high-sensitivity C-reactive protein were 1.27, 1.73, and 1.81 (P(trend)=0.01); for interleukin-6, 1.22, 1.02, and 1.51 (P(trend)=0.06); for soluble intercellular adhesion molecule-1, 1.00, 0.80, and 1.26 (P(trend)=0.37); and for D-dimer, 1.61, 1.81, and 1.52 (P(trend)=0.46). Multivariable adjustment attenuated the estimates. The multivariable relative risks of hypertension in the second through fourth compared to the lowest quartiles of high-sensitivity C-reactive protein were 1.24, 1.60, and 1.47 (P(trend)=0.20); for interleukin-6, 1.08, 0.92, and 1.36 (P(trend)=0.16); for soluble intercellular adhesion molecule-1, 0.89, 0.79, and 1.18 (P(trend)=0.55); and for D-dimer, 1.48, 1.68, and 1.38 (P(trend)=0.63). CONCLUSIONS: Elevated plasma inflammatory markers and D-dimer were nonsignificantly associated with a higher risk of hypertension among initially healthy men.