Multiple biomarkers and the risk of incident hypertension
Multiple biomarkers and the risk of incident hypertension
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DOI：
10.1161/01.hyp.0000256956.61872.aa
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发表时间：
2007-03-01
期刊：
影响因子：
8.3
通讯作者：
Vasan, Ramachandran S.
中科院分区：
文献类型：
--
作者：
Wang, Thomas J.;Gona, Philimon;Vasan, Ramachandran S.
了解原发性高血压发生的机制对于制定预防和治疗策略至关重要。选定的生物标志物可能在高血压发病前升高，但以前的研究受到横断面设计或专注于单一生物标志物的限制。我们前瞻性研究了1456名非高血压患者，他们基线测量了9种生物标志物：C反应蛋白（炎症）;纤维蛋白原（炎症和血栓形成）;纤溶酶原激活物抑制剂-1（纤溶潜能）;醛固酮、肾素、B型利钠肽和N-末端前心钠肽（神经激素活性）;同型半胱氨酸（肾功能和氧化应激）;和尿白蛋白/肌酐比值（肾小球内皮功能）。在平均3年的随访中，232名参与者发生了高血压事件，定义为血压>= 140/90 mm Hg或接受抗高血压治疗。校正临床危险因素后，生物标志物组与高血压事件显著相关（P = 0.002）。在后向排除法中，3个（共9个）生物标志物与高血压事件显著相关（多变量校正的比值比，生物标志物每SD增量）：C反应蛋白（1.26; 95% CI：1.05 - 1.51），纤溶酶原激活物抑制剂-1（1.28; 95% CI：1.05 - 1.57）和尿白蛋白/肌酐比值（1.21; 95% CI：1.02 - 1.43）。高血压的发病率分别为4.5、6.4和9.9/100人年，分别为0、1和>= 2个升高的生物标志物（升高定义为高于平均值>= 1 SD）。预测高血压的阈值≥ 2个升高的生物标志物与高特异性（0.92）但低敏感性（0.15）相关。炎症生物标志物、纤溶潜能降低和低度白蛋白尿与高血压发病率相关。这些数据支持了多个生物学通路的异常先于显性高血压发病的前提。
An understanding of mechanisms underlying the development of essential hypertension is critical for designing prevention and treatment strategies. Selected biomarkers may be elevated before the onset of hypertension, but previous studies are limited by cross-sectional designs or a focus on single biomarkers. We prospectively studied 1456 nonhypertensive individuals who had baseline measurement of 9 biomarkers: C-reactive protein (inflammation); fibrinogen (inflammation and thrombosis); plasminogen activator inhibitor-1 (fibrinolytic potential); aldosterone, renin, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide (neurohormonal activity); homocysteine (renal function and oxidant stress); and urinary albumin/creatinine ratio (glomerular endothelial function). Incident hypertension, defined as blood pressure >= 140/90 mm Hg or antihypertensive therapy, developed in 232 participants over a mean follow-up of 3 years. After adjustment for clinical risk factors, the biomarker panel was significantly associated with incident hypertension (P = 0.002). Three (of 9) biomarkers were significantly related to incident hypertension on backward elimination (multivariable-adjusted odds ratios, per SD increment in biomarker): C-reactive protein (1.26; 95% CI: 1.05 to 1.51), plasminogen activator inhibitor-1 (1.28; 95% CI: 1.05 to 1.57), and urinary albumin/creatinine ratio (1.21; 95% CI: 1.02 to 1.43). The incidence of hypertension was 4.5, 6.4, and 9.9 per 100 person years for participants with 0, 1, and >= 2 elevated biomarkers, respectively (elevation defined as >= 1 SD above the mean). The threshold of >= 2 elevated biomarkers for predicting hypertension was associated with high specificity (0.92) but low sensitivity (0.15). Biomarkers of inflammation, reduced fibrinolytic potential, and low-grade albuminuria are jointly associated with the incidence of hypertension. These data support the premise that abnormalities in multiple biological pathways antedate the onset of overt hypertension.