P2.03 THE PLASMINOGEN ACTIVATOR INHIBITOR-1 (4G/5G) POLYMORPHISM AFFECTS CENTRAL ARTERIAL BLOOD PRESSURE IN WOMEN

Abstract

Plasminogen activator inhibitor (PAI-1) is the key inhibitor of the fibrinolytic system, modulating cellular responses associated with vascular remodeling. Elevated plasma PAI-1 has been positively correlated to systolic- and diastolic blood pressure, measured in the brachial artery, and is increased in hypertensive patients. The (4G/5G) polymorphism in the PAI-1 promoter influences plasma concentrations, 4G/4G subjects having higher plasma PAI-1 levels than 5G carriers. The effect of the (4G/5G) polymorphism on central arterial pressures is unknown. Hence, the aim of this study was to test whether the PAI-1 4G/5G polymorphism affects central arterial blood pressure. 400 subjects, 212 men and 188 women (70–88 years) were studied. Central pressures and waveforms were calculated from radial artery pressure waveforms by the use of the SphygmoCor device, using a generalized transfer function. The PAI-1 (4G/5G) genotype was determined. Central aortic blood pressures were higher in female carriers of the 4G/4G genotype than female subjects carrying the 4G/5G and 5G/5G genotypes, (P=0.014, P=0.004 and P=0.003 for central systolic-, diastolic- and mean arterial pressure, respectively). Adjustment for variables related to hypertension (age, BMI, DM, smoking, LDL-cholesterol, fasting glucose) had no effect on the associations. No association was found between PAI-1 genotype and brachial blood pressure in either men or women. Our findings show that the PAI-1 (4G/5G) polymorphism is associated with central arterial blood pressure in women. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central arterial hypertension.