Plasminogen activator inhibitor-1 activity and the 4G/5G polymorphism are prospectively associated with blood pressure and hypertension status

Objectives: Plasminogen activator inhibitor-1 (PAI-1) has consistently shown positive associations with blood pressure (BP). Whether elevations in PAI-1 levels precede or result from raised BP is still under debate and data on prospective studies are limited. Hence, we investigated the prospective associations of PAI-1 and the 4G/5G polymorphism with brachial and central BP and pulse pressure (PP) over a 10-year period. Methods: Black South Africans aged 30 years and older were included. Baseline data collection commenced in 2005 (n = 2010) with follow-up data collection in 2010 (n = 1288) and 2015 (n = 926). Plasma PAI-1 activity (PAI-1act), 4G/5G polymorphism genotyping, waist circumference and BP measurements were performed and analysed using sequential regression and mixed models. Results: In multivariable adjusted analyses, PAI-1act and the 4G/4G (vs. the 5G/5G) genotype increased the odds of developing hypertension in the total group [1.04 (1.01; 1.08) and 1.82 (1.07; 3.12) respectively]. Furthermore, PAI-1act was prospectively associated with brachial SBP (r = 0.0815) and PP (r = 0.0832) in the total group, and with central PP in women (r = 0.1125; all P < 0.05). Addition of waist circumference to the models either decreased or nullified the contribution of PAI-1act to BP and hypertension development. Conclusion: PAI-1act and the 4G/4G (vs. the 5G/5G) genotype increased the odds of developing hypertension. Furthermore, PAI-1act associated prospectively with both brachial and central BP. These associations were mediated in part by central adiposity. The study supports the hypothesis that PAI-1 also contributes to hypertension development rather than solely being a consequence thereof