An understanding of mechanisms underlying the development of
essential hypertension is critical for designing prevention and treatment strategies. Selected
biomarkers may be elevated before the onset of
hypertension, but previous studies are limited by cross-sectional designs or a focus on single
biomarkers. We prospectively studied 1456 nonhypertensive individuals who had baseline measurement of 9
biomarkers:
C-reactive protein (
inflammation);
fibrinogen (
inflammation and
thrombosis);
plasminogen activator inhibitor-1 (fibrinolytic potential);
aldosterone,
renin,
B-type natriuretic peptide, and
N-terminal proatrial natriuretic peptide (neurohormonal activity);
homocysteine (renal function and
oxidant stress); and urinary
albumin/
creatinine ratio (glomerular endothelial function). Incident
hypertension, defined as blood pressure > or =140/90 mm Hg or
antihypertensive therapy, developed in 232 participants over a mean follow-up of 3 years. After adjustment for clinical risk factors, the
biomarker panel was significantly associated with incident
hypertension (P=0.002). Three (of 9)
biomarkers were significantly related to incident
hypertension on backward elimination (multivariable-adjusted odds ratios, per SD increment in
biomarker):
C-reactive protein (1.26; 95% CI: 1.05 to 1.51),
plasminogen activator inhibitor-1 (1.28; 95% CI: 1.05 to 1.57), and urinary
albumin/
creatinine ratio (1.21; 95% CI: 1.02 to 1.43). The incidence of
hypertension was 4.5, 6.4, and 9.9 per 100 person years for participants with 0, 1, and > or=2 elevated
biomarkers, respectively (elevation defined as > or =1 SD above the mean). The threshold of > or =2 elevated
biomarkers for predicting
hypertension was associated with high specificity (0.92) but low sensitivity (0.15).
Biomarkers of
inflammation, reduced fibrinolytic potential, and low-grade
albuminuria are jointly associated with the incidence of
hypertension. These data support the premise that abnormalities in multiple
biological pathways antedate the onset of overt
hypertension.