Management of Hypertension in Pregnancy and Postpartum

Podcast Transcript

Announcer:

Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic.

Deirdre Mattina, MD:

Well, I'm very delighted to be here with all of you today. So I'm going to move right ahead and dive into hypertension and pregnancy. And first, I think it's really important for us to recognize how prevalent maternal mortality is in the US and the healthcare disparities that it has created in treating women. We can see that over the last few years we can see that black women are three to four times more likely to die in childbirth than other ethnic groups. And when we look at developed nations, the levels of maternal mortality and according to the CDC maternal mortality is really limited to those first six weeks postpartum. But if we extend that to the one year that's pregnancy-related deaths, about 84% of those deaths are preventable. And many of these things have common care paths that are easily treatable, like hypertension in pregnancy, hemorrhage and infection. And that's why I think it's so important that we talk about this topic today.

So first, getting to the definition of hypertensive disorders in pregnancy. Just like in any time of our clinical phases, we're defining hypertension as a blood pressure greater than 140 over 90 on at least two occasions. We have a severe range of high blood pressure that can be a systolic greater than one 60 or a diastolic greater than 110 that's sustained for at least 15 minutes. And these hypertensive disorders of pregnancy affect about five to 10% of pregnancies. And previously, it can affect long-term cardiovascular disease risk. When we further break down what these hypertensive disorders are, we're really talking about chronic hypertension, which may be pre-existing hypertension prior to pregnancy or occurring less than 20 weeks of gestation. And importantly, it lasts longer than three months postpartum. Gestational hypertension in contrast happens later in pregnancy after 20 weeks of gestation, and it's really isolated to the pregnancy and resolves by three months postpartum.

And then we move into our more severe forms of hypertensive disorders, which are preeclampsia, chronic hypertension with superimposed preeclampsia, eclampsia and the HELLP syndrome. So it's important if we have a woman that is contemplating pregnancy and has pre-existing hypertension to really talk and think about this as preconception counseling, we're going to search for any existing end-organ damage like renal failure because we know that women with chronic hypertension getting pregnant, about one in four of them are going to develop preeclampsia through in their pregnancy. So searching for any kidney disease, which can also increase risk of preeclampsia. Also, many of these women are young, so we want to make sure that we have done a thorough workup into the cause and the etiology of their hypertension to exclude any other secondary causes like thyroid dysfunction, renal artery stenosis, etc. And then we're really going to work hard at looking at modifiable risk factors.

So obviously lifestyle, things like salt intake, exercise, other things that we can work on to sort of get the blood pressure and other risk factors in check before they get pregnant. And then we're also going to talk about transitioning to preferred agents. For anyone that's contemplating conception, we want to sort of move away from any teratogenic agents and get them on meds that are safe to use in pregnancy and lactation and really educating women on what the maternal and fetal risks are because I think there is a misconception that hypertension is kind of a benign even I hate that ICD code that is benign hypertension because really I don't see any hypertension as benign.

So when we talk about our preferred drugs in pregnancy, we're really talking about the heavy players being labetalol and nifedipine as our first-line agents, and that can be spaced off through multiple times a day. There is some information about alpha-methadone. In practice, I have never used that drug myself. And then we're looking at second and third-line agents. We're talking about hydralazine, maybe diuretics that can be used additionally without causing dehydration. And clonidine can also be used. Just to note that we're really trying to avoid the teratogenic medications like ACE inhibitors, ARBs, MRAs and even ARNIs, which are popular for use for many other conditions. Now those have not been studied in pregnancy yet. And then in the acute setting, if we have severe sustained hypertension, we can use IV labetalol, IV hydralazine or short-acting nifedipine as well.

So when we're talking about chronic hypertension in pregnancy, especially as I alluded to, this has a very high risk of preeclampsia, which can pretend future cardiovascular disease. These numbers are on the rise in recent decades, about 67% increase of women with chronic hypertension in pregnancy. And again, we can see this healthcare disparity because about the largest increase that we've seen in chronic hypertension in pregnancy comes within African-American women. And we believe that these numbers are increasing because of the obesity epidemic and advancing maternal age in pregnancy. So the trial published a couple years ago was really important because traditionally, ACOG and others have really sort of been reticent to treat hypertension in pregnancy unless it was in the severe range.

So the trial really was a nice trial that had an active treatment arm, treating even mild hypertension to a target less than 140 over 90. And the control group was sort of a standard therapy only treating severe hypertension, which in this trial was defined as a blood pressure greater than 160 or diastolic greater than 105. And so in those two treatment arms, we looked at the outcomes, primary outcomes of preeclampsia, preterm birth, placental abruption and fetal or neonatal death. And actually, there was a statistically significant decrease in events in those that were treated to the target of less than 140 over 90. When we look at other outcomes of small for gestational age, which had been the concern for treating blood pressure in pregnancy, there was no difference in the two groups between gestational age or low birth weights. And there was also no difference in adverse maternal or fetal outcomes in the two groups. So there was no signal of harm for getting to that target blood pressure of less than 140 over 90. And there was benefit in terms of reducing preeclampsia and preterm deliveries. So this has kind of changed the game on how we think about hypertension. And when we're defining hypertension in pregnancy, we don't yet know what level is too low in pregnancy, but we know that we're targeting that top number of less than 140 over 90.

And what we're looking at preeclampsia, I think many of us are probably familiar with how we diagnose preeclampsia. Again, the standard high blood pressure essentially after 20 weeks of gestation is pretty rare to see preeclampsia early on in pregnancy. Classically, this is accompanied by proteinuria, but you can still diagnose preeclampsia with other severe features like thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or other CNS findings like headache or vision changes as well. And while we were looking at, I know this is going back to older data from studies in the eighties and early two hundreds that we can see really a link between preeclampsia and chronic hypertension. And I think this is really important because we have seen preeclampsia in the past kind of been parlayed into this isolated incidence of pregnancy and not really thought of how it can affect long-term outcomes. But we're really seeing that even in preeclampsia, this may have resolved very quickly after pregnancy, but there is almost a fourfold increase in developing chronic hypertension. This is important because worldwide, chronic hypertension is one of the main causes of cardiovascular mortality and heart failure. And if we think about women developing high blood pressure in the 10 to 15 years postpartum, that really would be premature onset and we're exposing them to a longer time for end organ damage.

Preeclampsia also associated with a twofold increase in ischemic heart disease and also all-cause mortality has a slight increase with preeclampsia. So these are not benign findings, and I think it's important that we educate women in the postpartum phase about what these future risks are, because many times they forget these diagnoses because it has not really been emphasized or it's not asked in many of their clinical follow-up visits. In my postpartum heart program when I'm educating women that have had hypertensive disorders in pregnancy, including preeclampsia, and we can look in the non-pregnant state when we have the uterus, when we're non-pregnant, there's not much that we have to do in terms of blood flow. These spiral arteries invade, they sort of dilate, provide nitric oxide and blood flow that's needed. Obviously, in the pregnant state, these spiral arteries invade and cause this sheer stress, which up-regulates these upstream arteries, releases a lot more nitric oxide. It can triple, quadruple the uterine blood flow. The baby is happy, placenta is happy, and we have a nice normal delivery.

However, in preeclampsia there is this microvascular dysfunction. The spiral arteries do not dilate enough. They're not creating enough upstream stress to release this nitric oxide. Blood flow is decreased. The placenta itself can be smaller and hypoxic and even have [inaudible infarcts. Baby then releases stress hormones, and then this begets the preeclampsia. If we look closer at what these pathways are, again, what we're really trying to do is increase uterine blood flow, and we can do that in two ways, but we're trying to reduce vasoconstriction and increase vasodilation. So generally in pregnancy, we upregulate estrogen levels and this sort of helps in this pathway and the eNOS pathway to upregulate nitric oxide and also hydrogen sulfide. This results in sort of different pathways through cyclic GMP that can increase uterine artery dilation and decrease uterine artery constriction.

In the preeclampsic state, we have shown that there are lower levels of estrogen. That can be for several reasons. We can see these lower synthesis of esterase in people that have gestational diabetes and also in obesity. There is some association with higher leptin levels and reduced estrogen. And so these pathways are not upregulated as they naturally would in the pregnant state. So we have less nitric oxide, less hydrogen sulfide, and then that in turn creates that combination of vasoconstriction instead of vasodilation. This is what we consider as a failed stress test for women when they have these adverse pregnancy outcomes of hypertension and preeclampsia. This is really sort of the signal or the first sign that maybe they have microvascular dysfunction starting at a very early age and why this may be linked to future heart disease.

So far, screening for preeclampsia in low-risk women has not been associated with a very high predictive value. So it's not yet prime time to sort of look for all of these pathways, look for uterine blood flow indices. We haven't really found what is the treatment option that best sort of works even when we do find some dysfunction. And there's limited evidence that this accurate prediction really reduces early-onset preeclampsia. But what we have seen promises in the role of aspirin, so we really look for what are the risk factors for preeclampsia so we can identify those at moderate and high risk that may benefit for some intervention. The highest risk features are going to be any chronic medical conditions like diabetes, hypertension, lupus, renal disease and moderate risk factors are going to be things like obesity, family history, advanced maternal age, or other risk factors that could be associated like personal history of low birth weight in the past. And so the reason why aspirin is thought to be important is because obviously, it can increase vascular relaxation through the nitric oxide pathway, but we're really looking at thromboxane A2 levels and decreased platelet aggregation to increase blood flow through the uterine artery.

So the NICE guidelines and the USPSTF guidelines are pretty congruent in their recommendations if there is one or more moderate risk factor. It advocates for aspirin, for preeclampsia prophylaxis beginning at 12 weeks. And if there is one high-risk factor, then that also advocates for the use of aspirin for preeclampsia prophylaxis after 12 weeks. The caveat being here is that the strongest meta-analysis has really shown the most efficient dose is greater than a hundred milligrams of aspirin. And that meta-analysis also shows that it's best when used before 16 weeks. So yes, the guidelines have it right on the timing. I think 12 weeks is a good time. I think the dose is still to be debated. I think most commonly we're using 81 milligrams in the US, but you may see sometimes what I will recommend the use of 162 milligrams because the data is strongest with 100 milligrams.

Also down the pike are statins. These are good for preeclampsia because as we looked at studies of human carotid plaques, we can see that statins can decrease plaque inflammation. They stabilize plaque through metalloproteinases. Also, when we look at statin therapies, they reduce platelet reactivity and inflammatory cells. Also, they can upregulate that eNOS pathway, which we've already shown can help improve uterine blood flow. So this is how it may be used in preeclampsia prophylaxis, can decrease high sensitivity CRP levels very rapidly when used even in short periods of times, and it can inhibit T-cell activation. So again, this seems like the perfect drug for the pathophysiology that we're talking about of microvascular dysfunction and preeclampsia. And we can see how this plays out in this pathway specifically in trophoblastic invasion, improving placental perfusion, working on these angiogenic pro factors that increase vasodilation and reduce vasoconstriction, reducing oxidative stress. And when we look more closely at the cellular levels, really these are impacts at the trophoblast level, platelets, macrophages, the endothelial cells and vascular smooth muscle cells, really just working on those effects of reducing inflammation, decreasing thrombosis and improving vascular formation.

So the FDA, maybe about two or three years ago now has removed the black box warning for use of statins in pregnancy. So it still seems uneasy for people to recommend statins in pregnancy. And I want to be clear that this is not yet ready for primetime. It still is being studied in human trials, but I do think this is going to be the next frontier for pregnancy management for preeclampsia reduction.

As we now shift to the postpartum phase, really I think one of the major obstacles to postpartum care is the lack of Medicaid coverage and why this is important because about half of pregnancies in the US are covered by Medicaid. So when we're talking about geographical areas that may have limited access to Medicaid, we're really placing a burden on women in childbearing years. The existing coverage for those that don't have expanded Medicaid is really 60 to 90 days postpartum. So when we're talking about pregnancy-related deaths, many women that may need care or ongoing care for adverse pregnancy outcomes may have no coverage to be able to see doctors at that time. And this can further create disparities because we're looking at those that have Medicaid as their primary insurance coverage tend to be younger under the age of 30, and they also tend to be black and brown. So we can see lots of Native Americans, American Indians and black women predominantly are using Medicaid for their maternal insurance.

So when we look now, this postpartum vote has newly been termed the fourth period, having limited to no prenatal care and late entry into the antepartum care are correlated with patients being less likely to follow up postpartum, which is unfortunate. So it's important for us as caregivers to realize what those barriers are. Cost, transportation, language, child care, and limited health literacy. We're also working towards key post management goals, and these are the sort of buckets that I look for when I'm managing in my Postpartum Heart Clinic. The ACOG guidelines currently say that anyone with a hypertensive disorder in pregnancy should have a blood pressure check within 72 hours of delivery. There are many ways that can happen. They can have an ambulatory blood pressure and send text messages, do virtual visits come into the clinic afterwards. We're also going to educate women on signs and symptoms of preeclampsia and peripartum cardiomyopathy, and also have pathways which can sort of check for those things if they present to the emergency room.

And again, in talking about ambulatory blood pressure monitoring, these blood pressure cuffs are not necessarily covered by Medicaid, and so it can be difficult to try to get the funding for women to do this to make it easier. So I think this is one area where we work on as a public health initiative. We also want to educate patients on their future pregnancy risk.

If they're thinking about having other pregnancies and had preeclampsia, what that's going to mean in terms of aspirin, pregnancy planning, do they need to see maternal-fetal medicine and educate them on the future risk of cardiovascular disease as well? And of course, I'm always talking to them about lifestyle counseling and referring them to a primary care. There is this sort of care gap when you're in your twenties and thirties, you may only be seeing your OB or GYNs to have babies or have gynecologic care, not necessarily seeing a family practice or primary care physician to measure lipids, blood pressure, talk about weight and lifestyle counseling. So we refer all of these to establish primary care so they can be seen within the year of their delivery as well.

Here at Cleveland Clinic, we've used a unique model of the shared medical appointment to sort of capture all of these adverse pregnancy outcomes. I work very closely with my team of a nurse practitioner and a medical assistant, and we see multiple patients up to 10 patients a day. And we're counseling them on those buckets of postpartum care as we talked about, so that we can sort of minimize this risk and educate them on their future risks going forward. As we're talking about blood pressure management, the postpartum, we can become more liberal in some of the medications we use. We still are using nifedipine and labetalol primarily, and we will down titrate them as they need to postpartum if they're able to. We can use ACE inhibitors in lactation. However, I still sort of shy away from these medications unless there is an indication for heart failure, mostly because unless they're decided that they're not having any future pregnancies, that in which case you would have to switch them off and on again. I usually will stick to beta blockers and calcium channel blockers plus minus diuretics until needed. And why it's important to discuss lifestyle measures. This is a very interesting study, a very young patients 20 to 44 looking at their baseline cardiovascular health before they got pregnant. This is loosely based on the American Heart Association Simple 7 at the time. So we're looking at diet patterns, activities, smoking, weight, blood pressure, cholesterol and sugars.

So of these young women getting pregnant, we were saying that they're in ideal cardiovascular health if they're meeting four to five of those Simple 7 measures. And only 5% of young American women are in ideal cardiovascular health when they get pregnant. About two-thirds of women are intermediate cardiovascular health, meeting two to three of those components. And 35% of women are in poor cardiovascular health when they get pregnant. So this obviously plays a fact in why we have worse outcomes in America because we're starting at a baseline respect that's higher than most. We can use diet and lifestyle measures to counsel these women as well. There is a lot of emerging data about Mediterranean diet, not only for heart disease prevention, but specifically for maternal and fetal outcomes.

In some of these smaller randomized controlled trials and randomized controlled trials plus cohorts, we're really seeing a dramatic reduction, primarily in gestational diabetes, also in preeclampsia and preterm delivery and small for gestational age. So we counsel them all. We actually calculate a Mediterranean diet score in our Postpartum Clinic, and we give them resources about plant-based eating as well.

And then the most important thing we talk about in a postpartum phase is really what is the contraception or the pregnancy risk going forward? And just as a reminder to those of you out there who don't do this very often, there are certain conditions where pregnancy is not recommended, right? These are the very high-risk patients. These might not be the ones you see that are coming in for hypertensive disorders, but anyone with pulmonary artery hypertension, severe systolic dysfunction with an EF less than 30%, severe valvular heart disease or left-sided valvular heart disease that is uncorrected, these are the patients that we really want to get them in and counsel them about avoiding pregnancy.

And when we're looking at the types of contraception, anyone with high blood pressure that's ongoing or requiring blood pressure medications, we really want to avoid combined contraceptive pills with estrogen because those can elevate blood pressure as well. So we're talking about either IUDs, which are copper or progesterone-only, implant on or progesterone-only pills.

So again, I leave you with these key postpartum management goals, which are several different buckets where we're looking at really encompass blood pressure, lifestyle, and future cardiovascular risk. And I thank you so much for your time.

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