Boston - A research team from the Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH) has found that elevated cholesterol levels appear to be a risk factor for preeclampsia, a condition of pregnancy that can have dangerous consequences for both the mother and child. The report analyzed data from the Nurses' Health Study II, which is based at the Harvard School of Public Health and BWH, and appears in the October issue of Obstetrics and Gynecology.
"This may prove to be one of the few controllable risk factors for preeclampsia, a disorder for which we have no treatment and one that affects thousands of women every year," says Ravi Thadhani, MD, MPH, of the MGH Renal Unit and the Channing Laboratory at BWH, the study's first author. "We need to learn more about exactly which lipids are involved in this observation, but it's a first step toward developing effective prevention techniques."
Much is still unknown about the ultimate cause of preeclampsia or toxemia, a condition in which a pregnant woman develops high blood pressure and other metabolic abnormalities. If not appropriately managed, a woman with preeclampsia can proceed to eclampsia - characterized by seizures - or liver or kidney failure. Any of these complications can prove fatal.
Preeclampsia also increases the risk of premature delivery or may make it necessary to perform an emergency cesarean, since delivery is the only real cure for the condition. In such instances, the baby faces the numerous risks associated with prematurity. It is estimated that preeclampsia occurs in 5 percent of pregnancies and is more common in women having their first pregnancy. While preexisting diabetes and high blood pressure have been identified as risk factors, standard treatments for those conditions have not been effective in reducing the risk.
"We wanted to look at factors that could be modified before pregnancy or early on and may play an important role in the disorder," says Thadhani, "Other studies have shown that obese women have two or three times the risk of developing hypertensive disorders of pregnancy - a category that includes preeclampsia and a less serious condition called gestational hypertension. Since obesity can be associated with a number of metabolic changes, including increases in blood lipids [fatty substances like cholesterol and triglycerides], we examined more closely the role of obesity and elevated lipids in both preeclampsia and gestational hypertension."
The research team identified almost 16,000 women participating in the Nurses' Health Study II who reported at least one pregnancy between 1991 and 1995, excluding those who had chronic hypertension before pregnancy. Women who had reported either gestational hypertension or preeclampsia in the study's regular surveys taken in 1993 and 1995 were sent a questionnaire to confirm their earlier report and request permission to review their medical records. Permission was received and adequate medical records acquired more than 600 women, and of those, 216 had confirmed gestational hypertension and 86 had confirmed preeclampsia. Information on those two groups was compared with survey-reported data on the almost 15,000 women in the original sample not reporting any hypertensive disorder of pregnancy.
The researchers found that increased weight was associated with gestational hypertension but not generally with preeclampsia. (The exception was that the risk of preeclampsia was increased in the most overweight group - women with a body mass index of 30 or more.) However, they found a strong association between elevated cholesterol and preeclampsia. Of the 86 women surveyed who had preeclampsia, 22 percent reported having elevated cholesterol levels before pregnancy, compared with only 11 percent of those with gestational hypertension or in the control group.
Dr. Thadhani notes that this result supports and is supported by a British study that appeared in the Sept. 4 issue of The Lancet. "That article suggested that Vitamins C and E may reduce the risk of preeclampsia in women at high risk for the disorder, probably because those vitamins are antioxidants. That meshes nicely with our result associating elevated cholesterol with preeclampsia, because cholesterol contributes to oxidative stress - damage to blood vessels caused when lipids are oxidized and release harmful molecules called free radicals."
More knowledge is needed, however, to devise treatments to reduce this cholesterol-associated risk, Thadhani explains. "The information in Nurses' Health Study II only indicates elevated overall cholesterol, it doesn't break it down into components like LDL ["bad cholesterol"] and triglycerides. Future studies need to confirm our findings and better define what specific lipids are involved, which will give us targets for prevention. Until then, we can say that pregnant women who have elevated cholesterol before their pregnancies and who have other risk factors - like first pregnancy, diabetes, and preexisting hypertension - should be followed more closely by their obstetrician.
"At the moment," he continues, "there is a debate among physicians as to the usefulness of checking cholesterol levels in young women. This study certainly suggests a possible reason for doing so, but more work is needed before guidelines should be changed."
The study was supported by grants from the American Kidney Fund and the National Institutes of Health. The report's co-authors are Meir Stampfer, MD, DrPH, David Hunter, MBBS, ScD, Joann Manson, MD, DrPH, and Caren Soloman, MD, MPH, of the division of Preventive Medicine at BWH; and Gary Curhan, MD, ScD, the study's senior author, of the MGH Renal Unit and BWH.
The Nurses' Health Study II was initiated in 1989 in connection with the established Nurses' Health study that began in 1976 at BWH and is the longest major women's health study ever undertaken. The NHS and NHS II have resulted in hundreds of journal articles, many groundbreaking findings on how to prevent some of the major causes of disease and death in women.
The Massachusetts General Hospital and Brigham and Women's Hospital are founding members of Partners HealthCare Sytem, an integrated health care delivery network founded in 1994 to serve eastern Massachusetts. Both are teaching hospitals of Harvard Medical School, are among the top hospital recipients of research grants from the National Institutes of Health, and have consistently been recognized as top-ten hospitals in the annual rankings published by U.S. News and World Report. The institutions share a commitment to leadership and excellence in all aspects of patient care, education and research.
Journal
Obstetrics and Gynecology