To study the relation between diurnal blood pressure variations and silent cerebrovascular damage, we performed both 24-hour ambulatory blood pressure monitoring and brain magnetic resonance imaging in 131 elderly asymptomatic hypertensive patients. Silent cerebrovascular damage was identified by the magnetic resonance imaging findings of lacunae (low intensity in T1-weighted images and high intensity in T2-weighted images) and advanced periventricular hyperintense lesions (on T2-weighted images). The frequency of silent cerebrovascular damage in the 100 patients with sustained hypertension was greater than that in the 31 patients with white coat hypertension. We further classified the former group into nondippers (nocturnal reduction of systolic pressure by < 10% of awake systolic pressure; n = 46), dippers (reduction by > or = 10% to < 20%; n = 38), and extreme dippers (reduction by > or = 20%; n = 16). The extent of silent cerebrovascular damage was least severe in the dipper group (P < .05). This J-shaped relation was not found either with the cardiac hypertrophy detected by electrocardiography or with the renal damage assessed by urinary albumin excretion. More than half of the extreme dippers were patients with isolated systolic hypertension, and this prevalence was significantly greater than that in dippers or in nondippers (21% and 30%, respectively). Extreme dippers also had greater variability of pressure (standard deviation of awake systolic pressure) than dippers. Our results indicate that in addition to nondipping, extreme dipping (marked nocturnal fall of blood pressure) should be considered a type of abnormal diurnal blood pressure variation in elderly patients with hypertension who are likely to have advanced silent cerebrovascular damage.

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We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

"Silent" lacunar stroke, often found in the elderly, has been proposed as a predisposing condition for clinically overt stroke. However, the risk factors related to this condition have not been studied thoroughly. We conducted brain magnetic resonance imaging and measured the levels of fibrinogen, molecular markers of coagulation activation [prothrombin fragment 1 + 2 (F1 + 2)] and endothelial cell damage [von Willebrand factor (vWF) and thrombomodulin], and lipid profiles including lipoprotein (a) [Lp(a)] in 178 asymptomatic, high-risk, Japanese subjects aged 44 to 93 years. We also studied 32 symptomatic patients with lacunar stroke (symptomatic lacunar group). The prevalence of silent lacunar stroke increased with age up to 85 years but decreased with age in those 85 years old and older. Of the 160 elderly subjects ( > or = 60 years) 84 (53%) had > or = 1 lacunar infarcts (silent lacunar group) and the remaining 76 were considered as the nonlacunar group. Fibrinogen and F1 + 2 levels in the silent lacunar group were significantly higher than those in the nonlacunar group (P < .01). Mean Lp(a) levels and the prevalence of subjects with an Lp(a) level > 30 mg/dL were significantly higher in the symptomatic lacunar group than the nonlacunar group (P < .05), whereas these levels in the silent lacunar group were intermediate to those of the other two groups. When we further classified the silent lacunar group into three subgroups based on the number of lacunes (few lacunes, 1 or 2; moderate number of lacunes, 3 or 4; and numerous lacunes, > or = 5), levels of Lp(a), F1 + 2, vWF, and thrombomodulin were significantly higher and Lp(a) levels > 30 mg/dL more common in the numerous-lacune than in the few-lacune subgroup. We conclude that silent lacunar stroke is often found in asymptomatic, high-risk, elderly Japanese patients and that silent multiple lacunar stroke is associated with hypercoagulability, endothelial cell damage, and high Lp(a) levels.

SummaryWe investigated tissue factor pathway inhibitor (TFPI) levels in 44 non-dialysis uremic patients and 36 chronic dialysis patients, as well as the changes of TFPI levels during hemodialysis sessions using heparin (n = 14), low molecular weight heparin (n = 7), nafamostat mesilate (n = 5), and argatroban (n = 2). In non-dialysis uremic patients, TFPI levels increased (mean ± SD: 178 ± 37% of control pooled plasma) along with the impairment of renal function. In chronic hemodialysis patients, TFPI levels were even higher (265 ± 72%) before dialysis, but did not depend on the etiology of renal failure (diabetic or non-diabetic), the interval between dialysis sessions (twice or three times a week), and the duration of hemodialysis. During hemodialysis sessions using heparin, TFPI levels increased 1.2-to 3.5-fold compared with the level before hemodialysis and the degree of increase in TFPI was correlated with the heparin concentration (r = 0.648, p = 0.0001, n = 29). During dialysis sessions using low molecular weight heparin, TFPI levels also increased, but the change was less marked than during dialysis with heparin. TFPI levels did not change during dialysis sessions using nafamostat mesilate or argatroban. In conclusion, TFPI levels were increased by renal failure and by long-term repeated injection of heparin, but the hemodialysis procedure itself did not alter the TFPI level.