Certain combinations of complications during pregnancy raise the mother’s risk of premature cardiovascular disease–related death decades later by as much as sevenfold, according to a report published online Sept. 21 in Circulation.
These findings from a large observational cohort study with 50 years of follow-up indicate that the body’s extreme response to the challenges of pregnancy either expose or initiate an underlying vulnerability to CVD, researchers said.
©American Heart Association
Previously, a few individual complications of pregnancy have been linked to premature CVD death in the mother, but this is the first study to identify two unsuspected complications – glycosuria and an abnormal decline in hemoglobin – and to identify particular combinations of complications that are especially high risk. Now that this link is established, clinicians can identify patients who develop these complications in current pregnancies or experienced them in past pregnancies and target them for early CVD prevention, said Piera M. Cirillo, staff scientist, and Barbara A. Cohn, Ph.D., director of Child Health and Development Studies, Public Health Institute, Berkeley, Calif.
Given the substantial challenge pregnancy presents to a woman’s cardiovascular system – demanding a doubling of blood volume, increased cardiac output, marked elevation of coagulation factors, changes in blood pressure, temporary hyperlipidemia, increased insulin resistance, and the temporary accumulation of visceral fat – “pregnancy is really a stress test for the cardiovascular system,” Dr. Cohn said in a statement accompanying the report.
Dr. Cohn and Ms. Cirillo analyzed the records of 14,062 healthy women (67% white, 23% black, 3% Latina, 4% Asian, and 3% other races) enrolled in a study of prenatal health when they were pregnant in 1959-1967, following them up for CVD death in 2011. These study participants were a median of 26 years old at enrollment and a median of 66 years at follow-up. The complications of interest were early preeclampsia, late preeclampsia, preexisting hypertension, gestational hypertension, glycosuria (a surrogate for gestational diabetes, which wasn’t routinely assessed at the time of the original study), abnormal hemoglobin changes during pregnancy, hemorrhage, delivery of a small-for-gestational-age (SGA) baby, and irregular menses preceding pregnancy (a surrogate for polycystic ovarian syndrome).
A total of 9,059 mothers (64%) had none of these complications, 4,293 (31%) had a single complication, and 710 (5%) had at least two complications. There were 368 CVD deaths, which occurred at a median age of 66 years, the investigators said (Circulation. 2015 Sep 21. doi: 10.1161/circulationaha.113.003901).
The presence of one or more complications raised the risk of premature CVD death by roughly twofold to as high as sevenfold, depending on the complication. Preeclampsia, and particularly early-onset preeclampsia, was the strongest predictor of CVD death before age 60 years, followed by preexisting hypertension and the presence of glycosuria. Preterm and SGA delivery and abnormal decline in hemoglobin were less strong but still significant predictors. Hemorrhage and irregular menses showed no association with premature CVD death.
These risk factors were specific to CVD death and showed no association with all-cause mortality or cancer-related mortality, the investigators noted. Mothers who had both preexisting hypertension and a preterm delivery were at 7-fold-higher risk of premature CVD death, those who had preexisting hypertension plus preeclampsia were at 5.6-fold higher risk, those with preexisting hypertension plus an SGA baby were at 4.8-fold higher risk, and those with gestational hypertension plus preterm delivery were at fivefold higher risk.
The investigators discovered that an abnormal decline in hemoglobin during pregnancy also predicted premature CVD death. Most mothers show a steady decline in hemoglobin, beginning in early pregnancy and continuing through week 32. At 32-36 weeks hemoglobin increases, then it declines again until week 38, when it stabilizes until delivery at a level slightly below that seen in early pregnancy. The abnormal decline was clearly distinct from this established pattern, with higher-than-normal hemoglobin early in the second trimester and lower-than-normal levels in the third.
Early high hemoglobin is known to be a marker for poor fetal growth, placental infarction, and high blood viscosity, while later low hemoglobin “may indicate a failure to produce red cells in sufficient volume to ‘catch up’ to plasma volume increases, or could indicate a defect that results in late increases in blood volume. Thus, abnormal hemoglobin decline may be an early indicator of the lack of an adaptive response that ultimately results in increased CVD in these women,” Ms. Cirillo and Dr. Cohn said.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the study. Ms. Cirillo and Dr. Cohn reported having no relevant financial disclosures.