Additional impact of morning haemostatic risk factors and morning blood pressure surge on stroke risk in older Japanese hypertensive patients

Aims Stroke events occur most frequently in the morning hours. Impaired haemostatic activity and morning blood pressure (BP) surge, defined as the morning BP increase from sleep, have individually been associated with stroke risk in general or hypertensive populations. However, their combined impact on the risk of a stroke remains unknown. Methods and results A total of 514 hypertensive patients aged >50 years (mean 72.3 years; 37men) underwent 24 h BP monitoring, measurement of haemostatic risk factors [plasma fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and prothrombin fragment 12(F12)], and brain MRI at baseline. The incidence of stroke was prospectively ascertained. During an average of 41 months (1751 person-years), there were 43 stroke events (ischaemic, 30; haemorrhagic, 5; undefined, 8). On multivariable analysis adjusted for confounding factors, the hazard ratio [HR (95 confidence interval (CI)] for stroke in the highest vs. lower quartiles of PAI-1 was 2.5 (1.34.6), that for F12 was 2.6 (1.45.0), and that for the morning BP surge was 1.2 (1.11.4; all P< 0.01). In particular, the ratio was substantially higher in cases with the highest quartile of both PAI-1 and F12 levels compared with those with the lower quartiles of both parameters (HR: 8.2; 95 CI: 3.718.2; P< 0.001). Among the patients with the highest quartile of the morning BP surge (n=128), the multivariable HR (95 CI) for the highest vs. lower quartiles of PAI-1 was 3.4 (1.39.1) and that for F12 was 3.3 (1.38.7) (both P< 0.05). Conclusion High levels of plasma PAI-1 and F12, as well as an excessive morning BP surge, are independently and additively associated with an increased risk of stroke in older hypertensive patients.