Relations of serum MMP-9 and TIMP-1 levels to left ventricular measures and cardiovascular risk factors: a population-based study.
BACKGROUND
Extracellular matrix remodeling is a hallmark of pathological left ventricular (LV) hypertrophy and heart failure. This process is tightly controlled by the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). We hypothesized that circulating MMP-9 and TIMP-1 levels are altered already in persons with the signs of LV remodeling that forego clinical heart failure.


METHODS
Cross-sectional study in the Prospective Investigation of the Vasculature in Uppsala Seniors, a community-based cohort of 891 70-year-old men and women free from valvular disease, heart failure, and myocardial infarction.


METHODS
We examined relations of serum MMP-9 and TIMP-1 to echocardiographic LV geometry and function. All models were adjusted for sex, height, intra-arterial systolic and diastolic blood pressures, antihypertensive medication use, and serum freezer time.


RESULTS
Serum TIMP-1 was positively related to LV mass and wall thickness (r=0.15, P<0.0001 and r=0.16, P<0.0001, respectively), with a 32 g higher LV mass and 2.2 mm thicker walls in the fourth compared with the first quartile of serum TIMP-1. Serum TIMP-1 was also inversely related to LV ejection fraction (r=-0.10, P=0.009), but not to LV dimension or diastolic function indices. Serum MMP-9 was only weakly related to LV wall thickness and isovolumic relaxation time (r=0.08, P=0.04 and r=-0.08, P=0.04).


CONCLUSIONS
In this large population-based sample, serum TIMP-1 levels were related to LV mass, wall thickness, and inversely to systolic function. This may imply that extracellular matrix remodeling is involved already in the earliest stages of the process leading to heart failure.
Hansson
Jonas
J
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Lind
Lars
L
Hulthe
Johannes
J
Sundström
Johan
J
D000368:Aged; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015150:Echocardiography, Doppler; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D013548:Sweden; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D020257:Ventricular Remodeling
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9