Preeclampsia and Long-Term Heart Risk Explained

A pregnant woman's blood plasma expands by half in about seven months. No diet, no training program, no drug produces that kind of cardiovascular load on purpose. For some women with underlying heart or lung disease, that expansion alone is dangerous enough that doctors will say a pregnancy cannot safely continue (14:54). For almost everyone else, the body simply absorbs it, along with a cascade of other demands: a new organ growing hormones out of nothing, a metabolism that deliberately turns insulin-resistant, a cervix that must dissolve and reopen on a schedule nobody fully understands. Kathryn Gray, a maternal-fetal medicine specialist and division chief at the University of Washington School of Medicine, spends her career inside this process, and in conversation with Peter Attia she keeps returning to one idea: pregnancy does not just grow a baby. It tests a woman's organs so thoroughly that the results are diagnostic.

Gray puts it plainly early on.

"It is a cardiovascular stress test... and it is a metabolic stress test because there's increased insulin resistance." — Kathryn Gray [08:35]

The cardiovascular side shows up first as numbers: plasma volume climbs steadily from early pregnancy, accelerates in the second trimester, and plateaus around a 50% increase by 28 weeks (14:32). Red blood cell mass doesn't keep pace, so a mild, expected anemia follows. The metabolic side is subtler. By the second half of pregnancy, a woman's tissues become less responsive to insulin, on purpose, so that glucose stays in the bloodstream longer and more of it reaches the placenta and the fetus. For most women this is simply adaptive. For some, the body overshoots: glucose stays too high, and the diagnosis becomes gestational diabetes.

That diagnosis used to be made by risk factors alone, catching only about half of actual cases, which is why universal screening between 24 and 28 weeks became standard (29:36). The test itself is unglamorous: a sugary drink, a blood draw an hour later, and if that one-hour value is too high, a longer fasting test to confirm. Once a diagnosis is made, the treatment targets are specific, a fasting glucose under 95 mg/dL or a one-hour postprandial reading under 140 mg/dL (33:28). Treatment starts with diet and monitoring, but the clock is short. There's no three-month trial period when the baby arrives in three months anyway, so Gray's team typically gives a woman one to two weeks before escalating (34:14). When medication becomes necessary, insulin is first-line, not metformin or other oral drugs, because the safety data for insulin is strongest and it most reliably improves outcomes for the newborn (33:57). For the baby, the stakes of poorly controlled glucose are real: excess growth, higher odds of a difficult delivery, and a kind of improvised hyperinsulinemia that can leave the newborn with dangerously low blood sugar once it is cut off from the mother's glucose supply (28:35).

What happens after delivery is where this condition becomes more than an obstetric footnote. Gestational diabetes usually resolves within days of birth. But the risk it reveals does not disappear. Gray says about fifty percent of women who develop gestational diabetes will eventually develop type 2 diabetes (57:50), which is why she pushes hard on follow-up screening and lifestyle changes long after the pregnancy ends.

A placenta that turns against its host

Preeclampsia is the more dramatic version of this same idea: a pregnancy complication that is really a stress test with teeth. Gray defines it as new-onset high blood pressure after 20 weeks of gestation, usually with protein showing up in the urine, sometimes with headaches, vision changes, or pain under the right ribs (37:10). The diagnostic threshold is a systolic pressure of 140 mmHg or a diastolic pressure of 105 to 110 mmHg (38:02). It affects somewhere between 5% and 7% of pregnancies in the United States (39:56), and it is unlike the slow-building hypertension of a sixty-year-old with a decade of arterial damage behind it. This version can go from normal to seizures, stroke, and organ failure within weeks, sometimes before term (44:32).

The mechanism, worked out largely through research by nephrologist Ananth Karumanchi at Beth Israel in Boston, one of Gray's early mentors, starts in the placenta itself. Normally, placental cells called trophoblasts invade the mother's uterine arteries and widen them into low-pressure vessels that can feed the placenta adequately. When that invasion falls short, the placenta becomes oxygen-starved, and in response it releases a protein called sFlt into the mother's bloodstream.

"That molecule soaks up the VEGF, an important growth factor for maintaining vessel endothelial cell function, and that affects both the endothelial cells of the maternal vessels and the endothelial cells in the glomerulus of the kidney." — Kathryn Gray [42:17]

VEGF, short for vascular endothelial growth factor, keeps the cells lining blood vessels functioning normally. Starve them of it, and vessels throughout the mother's body, including the glomerulus, the filtering unit of the kidney, start to fail. That single mechanism explains both halves of the diagnosis: the hypertension and the protein leaking into urine.

There is no cure for preeclampsia short of delivering the baby and the placenta. Doctors can buy time with antihypertensive drugs like nifedipine and labetalol (52:33), medications barely used outside pregnancy because they aren't especially good blood pressure drugs otherwise. ACE inhibitors and ARBs, which would be first-line for a non-pregnant hypertensive patient, are known to be unsafe for the fetus and are avoided entirely during pregnancy (52:54). Once the placenta is delivered, the underlying process usually resolves, though not always quickly. Some women's blood pressure normalizes within days; others need antihypertensive medication for six to twelve weeks, and some develop hypertension that never fully resolves (53:38).

That lingering effect is the part of the conversation that seems to matter most going forward. Cohort studies, Gray says, have shown for some time that hypertension during pregnancy, even when it resolves after delivery, predicts a woman's future risk of atherosclerotic cardiovascular disease (55:23). Part of the explanation is genetic overlap: the first large genome-wide association study of preeclampsia found that its strongest genetic signals were also among the strongest signals for essential hypertension generally (56:31). Pregnancy, in other words, may simply unmask a predisposition that was always there. But Gray is careful to note this has been known inside obstetrics for a long time without making its way into primary care, where a woman's history of preeclampsia or gestational diabetes rarely shows up on a cardiovascular risk questionnaire (55:41).

Delivery, and what gets left unfunded

The back half of the conversation turns to delivery itself, where the data are more mundane but still surprising. Cesarean section rates have roughly tripled over the past fifty years, from around 10% to about 30% at many academic medical centers today (63:55). Roughly 20% of deliveries that start out expected to be vaginal convert to cesarean along the way (103:06), for reasons ranging from a non-reassuring fetal heart tracing to labor that simply fails to progress. The choice of incision matters for the future: a low transverse incision, cut low and sideways across the uterus, carries less than a 1% risk of rupture in a later labor, while a classical incision, cut vertically through thicker uterine muscle (typically necessary for very preterm deliveries), carries roughly a 10% rupture risk, high enough that Gray says women with that incision are advised not to labor again (66:08, 67:04).

Stillbirth, defined as any fetal death after 20 weeks, occurs in about one in 160 pregnancies in the United States (70:31), a number Gray calls startling even to her. Despite full workups, including placental pathology, fetal autopsy, and genetic testing, around half of these cases remain unexplained (72:48).

The conversation ends on funding, not biology. Gray points out that the NIH institute that funds the most pregnancy-related research, the National Institute of Child Health and Human Development, does not have the word pregnancy anywhere in its name.

"We still lack interventions and treatments because of lack of investment in research in this area." — Kathryn Gray [113:30]

It is a small, telling detail: an entire field named for the child it eventually produces, not for the body that does the work. Gray's larger point, threaded through the whole conversation, is that pregnancy offers a uniquely early and uniquely legible readout of a woman's long-term health, hypertension, metabolism, kidney reserve, laid bare years or decades before those systems would otherwise show strain. The information is already being collected, in blood pressure cuffs and glucose tests, at every prenatal visit. What's missing, she argues, is the institutional memory to carry it forward.