發生多次子癲前症會增加懷孕後的高血壓風險

作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　根據7月份高血壓(Hypertension)期刊中一篇以登記資料為基礎的世代研究結果，有兩次懷孕子癲前症的婦女，懷孕後的高血壓風險增加，與之後的第2型糖尿病風險無關。
　　
　　丹麥哥本哈根Rigshospitalet的Jacob A. Lykke醫師等人寫道，有關高血壓懷孕異常和各種後續心血管疾病的關聯、以及第2型糖尿病影響的資料很少。我們使用丹麥國家登記資料設計一個研究，探討以下狀況之間的關聯：(1)初次懷孕時的高血壓懷孕異常與之後的心血管發病率和第2型糖尿病；(2)發生(輕微和嚴重)子癲前症、早產、初次懷孕時胎兒小於妊娠年齡(small for gestational age，SGA)與之後的心血管發病率和第2型糖尿病；(3)第2次懷孕時是否有初發或復發的子癲前症(輕微和嚴重)，與之後的心血管發病率和第2型糖尿病；(4)第2型糖尿病對前述狀況的影響。
　　
　　此研究世代包括於1978至2007年間在丹麥初次產下單胞胎的782,287名婦女，以及536,419名連續兩胎單胞胎的婦女。相關的狀況有妊娠高血壓以及輕微和嚴重的子癲前症，研究結果為後續的高血壓、缺血性心臟病、鬱血性心衰竭、栓塞事件、中風、第2型糖尿病。在第一個模式中，研究者校正早產、胎兒小於妊娠年齡、胎盤早剝、死產，第二個模式中，他們也校正發生第2型糖尿病。
　　
　　妊娠高血壓之後，後續的高血壓風險增加5.31倍(範圍：4.90 - 5.75)，輕微子癲前症之後增加3.61倍(範圍：3.43 - 3.80)，嚴重子癲前症之後增加6.07倍(範圍：5.45 - 6.77)。妊娠高血壓之後，後續的第2型糖尿病增加3.12倍(範圍：2.63 - 3.70)，嚴重子癲前症之後增加3.68倍(範圍：3.04 - 4.46)。
　　
　　對於兩次懷孕都有子癲前症的婦女，後續的高血壓風險增加6.00倍(範圍：5.40 - 6.67)，只有第一次懷孕有子癲前症的婦女則增加2.70倍(範圍：2.51 - 2.90)，只有第二次懷孕有子癲前症的婦女則增加4.34倍(範圍： 3.98 - 4.74) 。妊娠高血壓之後，後續的血栓事件風險增加1.03倍(範圍：0.73 - 1.45)，輕微子癲前症之後增加1.53倍(範圍：1.32 - 1.77) ，嚴重子癲前症之後增加1.91倍(範圍：1.35 - 2.70) 。
　　
　　研究作者寫道，高血壓懷孕異常與後續的第2型糖尿病和高血壓有強烈關聯，而高血壓與後續的第2型糖尿病無關。這些高血壓異常的嚴重度、順序以及復發，增加了後續的心血管事件風險。醫師以及其他健康照護專業人士在估計心血管疾病風險時，應將婦女的懷孕結果納入。
　　
　　研究限制包括，高血壓診斷的低敏感度；終點的準確度可能偏低；可能無法報告血脂異常以及其他代謝症狀因素；無法控制身體質量指數、抽菸或社會經濟狀態等。
　　
　　研究作者結論表示，因為高血壓懷孕異常與後續的心血管發病率有強烈關聯，特別是高血壓和第2型糖尿病，兩者都是重要的代謝症狀，這些異常之間可能存在有直接的關聯。而且，高血壓異常的嚴重度似乎傾向與血栓事件有關；這在處方口服避孕藥給這些婦女時也應謹慎考量。及早確認這些婦女將有助於促進介入，包括調整其他心血管風險因素為主、或者以藥物預防為輔。
　　
　　研究作者之一曾經擔任回顧與子癲前症相關醫療紀錄的專家證人，也曾擔任Ortho Clinical Diagnostics和Beckman Coulter兩家公司的諮詢委員。其他研究作者宣告沒有相關財務關係。


Multiple Preeclampsia Incidents May Increase Risk for Hypertension After Pregnancy

By Laurie Barclay, MD
Medscape Medical News

July 28, 2009 — Women who have 2 pregnancies complicated by preeclampsia are at a higher risk for hypertension after pregnancy, which is independent of the risk for subsequent type 2 diabetes mellitus, according to the results of a registry-based cohort study reported in the June issue of Hypertension.

"Minimal data exist concerning the relationship between hypertensive pregnancy disorders and various subsequent cardiovascular events and the effect of type 2 diabetes mellitus on these," write Jacob A. Lykke, MD, from Rigshospitalet in Copenhagen, Denmark, and colleagues. "We have designed a study using the Danish National Registries investigating the association among the following: (1) hypertensive pregnancy disorders in a first pregnancy and later cardiovascular morbidity and type 2 diabetes mellitus; (2) combinations of (mild and severe) preeclampsia, preterm delivery, and small for gestational age (SGA) offspring in a first pregnancy and later cardiovascular morbidity and type 2 diabetes mellitus; (3) the parity and recurrence of preeclampsia (mild and severe) in the second pregnancy and later cardiovascular morbidity and type 2 diabetes mellitus; and (4) the contribution of type 2 diabetes mellitus to the above associations."

The study cohort consisted of 782,287 women delivering in Denmark from 1978 to 2007 with a first singleton pregnancy and 536,419 women with 2 first consecutive singleton deliveries. Relevant exposures were gestational hypertension and mild and severe preeclampsia, and the study outcomes were subsequent hypertension, ischemic heart disease, congestive heart failure, thromboembolic event, stroke, and type 2 diabetes mellitus. In 1 model, the investigators adjusted for preterm delivery, small for gestational age, placental abruption, and stillbirth, and in a second model, they also adjusted for the development of type 2 diabetes mellitus.

After gestational hypertension, the risk for subsequent hypertension was increased 5.31-fold (range, 4.90 - 5.75) vs 3.61-fold (range, 3.43 - 3.80) after mild preeclampsia and 6.07-fold (range, 5.45 - 6.77) after severe preeclampsia. Increased risks for subsequent type 2 diabetes mellitus were 3.12-fold (range, 2.63 - 3.70) after gestational hypertension and 3.68-fold (range, 3.04 - 4.46) after severe preeclampsia.

For women having 2 pregnancies with preeclampsia, the risk for subsequent hypertension was increased 6.00-fold (range, 5.40 - 6.67) vs 2.70-fold (range, 2.51 - 2.90) for preeclampsia in the first pregnancy only and 4.34-fold (range, 3.98 - 4.74) for preeclampsia in the second pregnancy only. After gestational hypertension, the risk for subsequent thromboembolism was 1.03-fold (range, 0.73 - 1.45) vs 1.53-fold (range, 1.32 - 1.77) for mild preeclampsia and 1.91-fold (range, 1.35 - 2.70) for severe preeclampsia.

"Hypertensive pregnancy disorders are strongly associated with subsequent type 2 diabetes mellitus and hypertension, the latter independent of subsequent type 2 diabetes mellitus," the study authors write. "The severity, parity, and recurrence of these hypertensive pregnancy disorders increase the risk of subsequent cardiovascular events....Physicians and other health care professionals should be encouraged to include the history of a woman's pregnancy outcomes when estimating the risk of cardiovascular disease."

Limitations of this study include low sensitivities for hypertensive diagnoses; potentially low accuracy of the endpoints; possible failure to report dyslipidemia and other factors of a metabolic syndrome; and inability to control for body mass index, smoking, or socioeconomic status.

"Because hypertensive pregnancy disorders are strongly linked with subsequent cardiovascular morbidity, especially hypertension and type 2 diabetes mellitus, both being essential components of the metabolic syndrome, a possible direct link may exist between these disorders," the study authors conclude. "Also, the severity of the hypertensive disorders seems to predispose to thromboembolic events; this also merits caution when prescribing oral contraceptives for these women. Identifying these women early will allow for prompt intervention, either primarily as modification of other classical cardiovascular risk factors or secondarily as medical prophylaxis."

One of the study authors has been an expert witness to review medical records related to preeclampsia and has served on the advisory boards of Ortho Clinical Diagnostics and Beckman Coulter. The other study authors have disclosed no relevant financial relationships.