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.
Design: 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).
Conclusion: 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.