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(Circulation. 2009;119:1101-1107.)
© 2009 American Heart Association, Inc.

Epidemiology

Relations of Matrix Remodeling Biomarkers to Blood Pressure Progression and Incidence of Hypertension in the Community

Ravi Dhingra, MD; Michael J. Pencina, PhD; Peter Schrader, BA; Thomas J. Wang, MD; Daniel Levy, MD; Karol Pencina, MS; Deborah A. Siwik, PhD; Wilson S. Colucci, MD; Emelia J. Benjamin, MD, ScM; Ramachandran S. Vasan, MD

From the National Heart, Lung, and Blood Institute’s Framingham Heart Study (R.D., M.J.P., T.J.W., D.L., E.J.B., R.S.V.), Framingham, Mass; Division of Aging (R.D.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Department of Medicine (R.D.), Alice Peck Day Memorial Hospital, Lebanon, NH; Department of Mathematics and Statistics (M.J.P., P.S., K.P.), Boston University, Boston, Mass; Division of Cardiology (T.J.W.), Massachusetts General Hospital, Boston, Mass; Center for Population Studies (D.L.), National Heart, Lung, and Blood Institute, Bethesda, Md; and the Myocardial Biology Unit (D.A.S., W.S.C.), Cardiology Section (W.S.C., E.J.B., R.S.V.), and Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), Boston University School of Medicine, Boston, Mass.

Correspondence to Ramachandran S. Vasan, MD, Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA 01702-5803. E-mail vasan{at}bu.edu

Received July 27, 2008; accepted December 15, 2008.

Background— Biomarkers of extracellular matrix remodeling are associated with prevalent hypertension in cross-sectional studies, but their relations to longitudinal changes in blood pressure (BP) and hypertension incidence are unknown.

Methods and Results— We evaluated 595 nonhypertensive Framingham Offspring Study participants (mean age 55 years; 360 women) without prior heart failure or myocardial infarction who underwent routine measurements of plasma tissue inhibitor of metalloproteinase-1 (TIMP-1), metalloproteinase-9 (MMP-9), and procollagen III N-terminal peptide. We related plasma TIMP-1, procollagen III N-terminal peptide, and MMP-9 to the incidence of hypertension and progression of BP by 1 category (defined on the basis of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). On follow-up (4 years), 81 participants (51 women) developed hypertension, and 198 (114 women) progressed to a higher BP category. In multivariable models, a 1-SD increment of log-TIMP-1 was associated with a 50% higher incidence of hypertension (95% CI 1.08 to 2.08) and a 21% (95% CI 1.00 to 1.47) higher risk of BP progression. Individuals in the top TIMP-1 tertile had a 2.15-fold increased risk of hypertension (95% CI 0.99 to 4.68) and 1.68-fold (95% CI 1.05 to 2.70) increased risk of BP progression relative to the lowest tertile. Individuals with detectable MMP-9 had a 1.97-fold higher risk of BP progression (95% CI 1.06 to 3.64) than those with undetectable levels. Plasma procollagen III N-terminal peptide was not associated with hypertension incidence or BP progression.

Conclusions— In the present community-based sample, higher TIMP-1 and MMP-9 concentrations were associated with BP progression on follow-up. Additional studies are warranted to confirm our findings.

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Circulation 2009 119: 1067-1068. [Extract] [Full Text]