Plasma tissue inhibitor of matrix metalloproteinase-1 level is increased in normotensive non-dippers in association with impaired glucose metabolism.

Non-dipping (nocturnal blood pressure [BP] decrease<10%) is related to accelerated urinary salt excretion (u-NaCl), and increased risk of left ventricular hypertrophy (LVH) and cardiovascular events. We evaluated whether non-dippers exhibit an advanced extracellular matrix fibrosis, in relation to increased u-NaCl, among normotensive subjects. We measured plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), a marker of collagen fibrosis in extracellular matrix, to evaluate the relationship between non-dipping and u-NaCl in 73 normotensive subjects (no antihypertensive medications, clinic BP<140/90 mmHg and/or 24-h ambulatory BP<125/80 mmHg). Non-dippers had a significantly higher percentage of subjects with impaired fasting glucose (IFG) or diabetes mellitus (DM), and had a greater left ventricular mass index (LVMI), plasma TIMP-1 level and u-NaCl than dippers (IFG or DM: 24.0 vs. 6.3%, p=0.029; LVMI: 118+/-31 vs. 103+/-26 g/m(2), p=0.039; TIMP-1: 168+/-35 vs. 151+/-30 pg/mL, p=0.035; u-NaCl: 5.1+/-1.7 vs. 3.9+/-1.7 g/12 h, p=0.005). In logistic regression analysis, non-dipping was independently associated with u-NaCl and TIMP-1. u-NaCl was correlated with non-dipping (r=0.35, p=0.003) and serum glucose level (r=0.26, p=0.027). On the other hand, TIMP-1 level was significantly correlated with the presence of IFG or DM (r=0.23, p=0.046), but not with u-NaCl. In conclusion, plasma TIMP-1 level, a measure of cardiovascular fibrosis in extracellular matrix, is greater in normotensive non-dippers than in dippers; however, the increased TIMP-1 level may be related to impaired glucose metabolism, and non-dipping may be related to increased u-NaCl associated with high serum glucose levels in normotensive subjects. (Hypertens Res 2008; 31: 2045-2051).