Wolf Myles, Sandler Laura, Jimenez-Kimble Ricardo, Shah Anand, Ecker Jeffrey L, Thadhani Ravi
Renal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass 02114, USA.
Hypertension. 2002 Dec;40(6):886-91. doi: 10.1161/01.hyp.0000042085.65467.9f.
Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of pregnancy-associated morbidity. Although insulin resistance and inflammation contribute to preeclampsia, prospective data regarding mechanisms of gestational hypertension are sparse. We conducted a prospective, nested case-control study to test the hypotheses that insulin resistance, marked by reduced sex hormone-binding globulin (SHBG) levels, and inflammation, marked by increased C-reactive protein levels, are similarly associated with gestational hypertension. We measured first-trimester C-reactive protein and SHBG levels in 51 women who subsequently developed gestational hypertension and 102 randomly selected normotensive pregnant controls. Compared with controls, first-trimester SHBG levels were significantly reduced among women who later developed gestational hypertension (176+/-73 versus 203+/-79 nmol/L; P=0.03), but there was no difference in C-reactive protein levels. There was statistically significant interaction among nulliparity, first-trimester SHBG levels, and risk of gestational hypertension, such that increasing SHBG levels were associated with significantly reduced risk of gestational hypertension among nulliparous women (odds ratio, 0.64 per 50-nmol/L increase; 95% confidence interval, 0.46, 0.90; P<0.01) but not among multiparous women. This association remained significant after adjusting for potential confounders (odds ratio, 0.55; 95% confidence interval, 0.31, 0.98; P=0.04). We conclude that insulin resistance, but not inflammation, is an independent risk factor for gestational hypertension among nulliparous women. Furthermore, important mechanistic differences exist in the pathogenesis of gestational hypertension comparing nulliparous and multiparous women.
妊娠高血压疾病，包括妊娠期高血压和子痫前期，是妊娠相关发病的主要原因。尽管胰岛素抵抗和炎症与子痫前期有关，但关于妊娠期高血压发病机制的前瞻性数据却很少。我们进行了一项前瞻性巢式病例对照研究，以检验以下假设：以性激素结合球蛋白（SHBG）水平降低为标志的胰岛素抵抗和以C反应蛋白水平升高为标志的炎症与妊娠期高血压同样相关。我们测量了51名随后发生妊娠期高血压的女性和102名随机选择的血压正常的孕妇对照组在孕早期的C反应蛋白和SHBG水平。与对照组相比，后来发生妊娠期高血压的女性孕早期SHBG水平显著降低（176±73对203±79 nmol/L；P=0.03），但C反应蛋白水平没有差异。初产、孕早期SHBG水平和妊娠期高血压风险之间存在统计学上的显著交互作用，即SHBG水平升高与初产妇妊娠期高血压风险显著降低相关（优势比，每增加50 nmol/L为0.64；95%置信区间，0.46，0.90；P<0.01），而经产妇则不然。在调整潜在混杂因素后，这种关联仍然显著（优势比，0.55；95%置信区间，0.31，0.98；P=0.04）。我们得出结论，胰岛素抵抗而非炎症是初产妇妊娠期高血压的独立危险因素。此外，初产妇和经产妇在妊娠期高血压发病机制上存在重要的机制差异。
