Peng Hao, Yeh Fawn, de Simone Giovanni, Best Lyle G, Lee Elisa T, Howard Barbara V, Zhao Jinying
aDepartment of Epidemiology, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, Florida bCenter for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA cDepartment of Clinical and Experimental Medicine, Federico II University, Naples, Italy dEagle Butte Industries Research Inc, Timber Lake, South Dakota eMedStar Health Research Institute, Hyattsville, Maryland, USA.
J Hypertens. 2017 Sep;35(9):1787-1793. doi: 10.1097/HJH.0000000000001375.
Deficient plasminogen activator inhibitor-1 (PAI-1) prevented hypertension in mice. Plasma PAI-1 was associated with hypertension in cross-sectional analyses, but the prospective association of PAI-1 with incident hypertension in large epidemiological studies is scarce.
Leveraging two longitudinal cohorts of American Indians in the Strong Heart Study (SHS, N = 1019) and the Strong Heart Family Study (SHFS, N = 1502), we examined the prospective association of plasma PAI-1 with incident hypertension by multivariate logistic regression, adjusting for age, sex, study site, smoking, drinking, dietary sodium, obesity, lipids, fasting glucose, kidney function, inflammation, and follow-up years. Family relatedness in the SHFS was accounted for using the GLIMMIX procedure. Plasma PAI-1 level at baseline was measured by immunoassay. All participants were free of hypertension, cardiovascular diseases, and chronic kidney disease at baseline.
A total of 305 and 258 participants, respectively, from the SHS (57 ± 7 years) and the SHFS (33 ± 13 years) developed incident hypertension during follow-up. In the SHS, higher level of log-transformed PAI-1 was associated with 1.35-fold increased risk of hypertension [odds ratio (OR) (95% confidence interval): 1.35 (1.06-1.72)]. Analysis using categorical PAI-1 (in tertiles) showed that participants in the highest tertile (≥58 ng/ml) had 63% increased risk for hypertension [OR = 1.63 (1.12-2.37)] compared with those in the lowest tertile (<33 ng/ml). This association was confirmed in the SHFS with similar effect sizes [OR = 1.41 (1.11-1.81) for log-transformed PAI-1; OR = 1.64 (1.08-2.50) for categorical PAI-1: ≥58 vs. <33 ng/ml].
A higher level of plasma PAI-1 is significantly associated with hypertension in American Indians, independent of established risk factors. The potential causality warrants further investigation.
纤溶酶原激活物抑制剂-1（PAI-1）缺乏可预防小鼠患高血压。在横断面分析中，血浆PAI-1与高血压相关，但在大型流行病学研究中，PAI-1与新发高血压的前瞻性关联尚少。
利用强心脏研究（SHS，N = 1019）和强心脏家族研究（SHFS，N = 1502）中两个美国印第安人的纵向队列，我们通过多变量逻辑回归分析了血浆PAI-1与新发高血压的前瞻性关联，并对年龄、性别、研究地点、吸烟、饮酒、饮食钠、肥胖、血脂、空腹血糖、肾功能、炎症和随访年限进行了调整。在SHFS中，使用GLIMMIX程序考虑了家族相关性。通过免疫测定法测量基线时的血浆PAI-1水平。所有参与者在基线时均无高血压、心血管疾病和慢性肾病。
在随访期间，SHS（57±7岁）和SHFS（33±13岁）分别有305名和258名参与者患新发高血压。在SHS中，PAI-1经对数转换后的水平较高与高血压风险增加1.35倍相关[比值比（OR）（95%置信区间）：1.35（1.06-1.72）]。使用分类PAI-1（三分位数）进行的分析表明，与最低三分位数（<33 ng/ml）的参与者相比，最高三分位数（≥58 ng/ml）的参与者患高血压的风险增加63%[OR = 1.63（1.12-2.37）]。在SHFS中也证实了这种关联，效应大小相似[经对数转换的PAI-1的OR = 1.41（1.11-1.81）；分类PAI-1的OR = 1.64（1.08-2.50）：≥58 ng/ml与<33 ng/ml]。
在美国印第安人中，较高水平的血浆PAI-1与高血压显著相关，独立于既定的风险因素。潜在的因果关系值得进一步研究。
