Key result
Higher TIMP-1 levels are linked to ~50% increased incidence of hypertension over 4 years.
Why the study?
Biomarkers of extracellular matrix remodeling are associated with prevalent hypertension cross-sectionally, but their relations to longitudinal blood pressure changes and hypertension incidence are unknown.
Do higher plasma concentrations of extracellular matrix remodeling biomarkers predict the incidence of hypertension and blood pressure progression in nonhypertensive adults?
Cohort (n=595)
No
Do higher plasma concentrations of extracellular matrix remodeling biomarkers predict the incidence of hypertension and blood pressure progression in nonhypertensive adults?
Odds Ratio: 1.5 (95% CI 1.08–2.08)
Higher circulating levels of matrix remodeling biomarkers like TIMP-1 and MMP-9 may antedate the onset of hypertension and reflect early vascular remodeling.
Higher TIMP-1 levels were associated with incident hypertension; hypothesis-generating for matrix remodeling in BP progression and should not yet change practice.
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 >or=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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Dhingra et al. (2009) conducted a cohort in Nonhypertensive (n=595). Higher plasma TIMP-1 concentration vs. Lower plasma TIMP-1 concentration was evaluated on Incidence of hypertension (OR 1.50, 95% CI 1.08 to 2.08). A 1-SD increment of log-TIMP-1 was associated with a 50% higher incidence of hypertension and a 21% higher risk of blood pressure progression over 4 years.
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