Kario K, Matsuo T, Kobayashi H, Matsuo M, Sakata T, Miyata T, Shimada K
Department of Internal Medicine, Awaji-Hokudan Public Clinic, Hyogo, Japan.
Arterioscler Thromb Vasc Biol. 1996 Mar;16(3):455-61. doi: 10.1161/01.atv.16.3.455.
We studied the relationship among albuminuria, factor VII (FVII) hyperactivity, and endothelial cell damage in 6 elderly hypertensive subjects. The plasma levels of activated FVII (FVIIa), FVII coagulant activity, FVII antigen (FVIIag), von Willebrand factor (vWF), and thrombomodulin were measured to assess FVII hyperactivity and endothelial cell damage, and urinary albumin excretion rate (UAE) was calculated using 12-hour nighttime (7 pm to 7 am) urine collection (mean for 2 consecutive nights). We performed 24-hour ambulatory blood pressure monitoring in all 61 hypertensive patients and classified them into a white-coat hypertension group (n=12) and a sustained hypertension group (n=49). For the levels of FVII, vWF, and thrombomodulin, there were no differences between the white-coat hypertension group and normotensive control subjects (n=25). In the sustained hypertensive group, only the microalbuminuric subgroup (UAE, 15 to 300 microgram/min: n=30) showed significant elevation compared with the normotensive group for the level of FVIIa (mean [95% confidence interval]: 4.0 [3.6 to 4.4] versus 3.0 [2.6 to 3.3] ng/mL, P<.001), the FVIIa/FVIIag ratio (an indicator of activation of FVII zymogen to FVIIa) (1.33 [1.19 to 1.50] versus 1.04 [0.92 to 1.19], P<.01), the level of vWF (188 [165 to 214] % versus 144 [129 to 160] %, P<.01), and thrombomodulin (11.7 [10.3 to 13.3] versus 9.3 [8.5 to 10.3] ng/mL, P<.01). In contrast, none of these levels in the normoalbuminuric hypertensive group (UAE <15 microgram/min, n=19) differed from that in the normotensive control group. These results suggest that among elderly hypertensives, only those with microalbuminuria show enhancement of FVII activation and endothelial cell damage, while patients with white-coat hypertension and normoalbuminuric hypertensives do not show these accompanying abnormalities. Thus, increased levels of FVII activity and markers of endothelial cell damage might account for the higher risk of cardiovascular events in essential hypertension with microalbuminuria.
我们研究了6名老年高血压患者蛋白尿、凝血因子VII（FVII）活性亢进与内皮细胞损伤之间的关系。检测血浆中活化FVII（FVIIa）、FVII凝血活性、FVII抗原（FVIIag）、血管性血友病因子（vWF）和血栓调节蛋白的水平，以评估FVII活性亢进和内皮细胞损伤，并通过收集12小时夜间（晚上7点至早上7点）尿液（连续两晚的平均值）计算尿白蛋白排泄率（UAE）。我们对所有61名高血压患者进行了24小时动态血压监测，并将他们分为白大衣高血压组（n = 12）和持续性高血压组（n = 49）。对于FVII、vWF和血栓调节蛋白的水平，白大衣高血压组与血压正常的对照组（n = 25）之间没有差异。在持续性高血压组中，只有微量白蛋白尿亚组（UAE为15至300微克/分钟：n = 30）的FVIIa水平（平均值[95%置信区间]：4.0[3.6至4.4]与3.0[2.6至3.3]纳克/毫升，P <.001）、FVIIa/FVIIag比值（FVII酶原激活为FVIIa的指标）（1.33[1.19至1.50]与1.04[0.92至1.19]，P <.01）、vWF水平（188[165至214]%与144[129至160]%，P <.01）和血栓调节蛋白（11.7[10.3至13.3]与9.3[8.5至10.3]纳克/毫升，P <.01）与血压正常组相比有显著升高。相比之下，正常白蛋白尿高血压组（UAE <15微克/分钟，n = 19）的这些水平与血压正常对照组没有差异。这些结果表明，在老年高血压患者中，只有微量白蛋白尿患者表现出FVII激活增强和内皮细胞损伤，而白大衣高血压患者和正常白蛋白尿高血压患者没有这些伴随的异常。因此，FVII活性升高和内皮细胞损伤标志物可能是微量白蛋白尿原发性高血压患者心血管事件风险较高的原因。
