In October, the American Heart Association published new guidelines for preventing stroke. This is not surprising. New guidelines for different conditions are released often, and the last guidelines for stroke prevention were released in 2014. The new guidelines are notable for the vast array of at-risk subgroups of the population identified, and for identifying GLP-1 agonists as a possible tool for reducing the risk of stroke. I love that these guidelines are forward-focused — the authors’ intent is to prevent stroke — and that they highlight women and the role of estrogen in stroke.
I also appreciated that these guidelines recognized the role of “social determinants of health” — that is, factors such as education, economic stability, access to care, and experiences of racism. The authors outline a compelling case for further research into these factors in the guidelines. Understanding how these factors affect patient experience is critical but beyond the scope of our conversation today.
Guidelines serve two purposes. First, they draw attention to the condition they address and can help direct funding for further research. Identifying those in the population at particular risk for developing a medical problem can help physicians like me focus our screening efforts and raise alarm bells when we see symptoms in a patient at increased risk. Second, the guidelines provide treatment recommendations.
But guidelines are not rules intended to be slavishly followed in all cases. The best guidelines are based on robust evidence, but the authors must rely on the evidence that is available. And they approach writing guidelines as individuals with past experience and biases. I always approach guidelines with a specific question in mind: should this guidance change my practice? With that in mind, let’s take a look at these new guidelines.
What is a stroke?
A stroke is a sudden blockage or bleeding in an artery that delivers blood to the brain. It interrupts the blood flow to a part of the brain, leading to damage in that area that can be temporary or more permanent. Stroke is the fifth leading cause of death in the U.S., and it is preventable.
Strokes are more common in women — 57% of all strokes occur in women. As a result, it is important to understand why women are at increased risk for stroke and to use the tools we have to reduce that risk.
What is the connection between estrogen and stroke?
The relationship between the brain, the vasculature that circulates to the brain, and estrogen are not fully understood. We do know that very high-estrogen states such as pregnancy predispose women to stroke. This seems to be due to increased risk of blood clots when estrogen levels are high. The authors observe that the risk of stroke is highest during pregnancy in the two weeks following delivery. This correlates with the time when estrogen levels are highest.
High-dose combination birth control pills containing estrogen also increase the risk of stroke via the same mechanism. Multiple randomized trials have demonstrated that the higher the dose of estrogen in birth control pills, the higher the risk of stroke. However, modern birth control pills contain much less estrogen than older birth control pills, and thus the risk with these pills is small. The guidelines quantify this risk by estrogen dose, with the lowest-dose pills increasing stroke risk only modestly.
Additionally, the overall risk of stroke in young women is quite small, so even in pregnancy and among women on birth control pills, the incidence of stroke is very small. But the role estrogen plays in clotting provides us with useful information about the role of estrogen in stroke.
How, then, do we think about the rise in risk for stroke as we age? And why are women with primary ovarian insufficiency and early menopause at increased risk of stroke?
After menopause, estrogen levels fall, so the risk of blood clots decreases. But we also know that estrogen reduces plaque formation in the arteries of premenopausal women. After menopause, when estrogen levels are low, plaques can begin to form in the arteries and ultimately lead to blockage.
The authors of the new guidelines note that hormone therapy with estrogen leads to a slightly increased stroke risk, citing two reviews (here and here). Much of the data in these reviews comes from the Women’s Health Initiative study, which used oral conjugated equine estrogen.
The guidelines provide specific risk levels for different forms of estrogen. In particular, they note that estrogen given through the skin as a patch or gel, in the doses typically given for perimenopausal symptoms, does not increase a woman’s risk of stroke.
How do pregnancy complications affect stroke risk?
In our perimenopausal years, the baseline risk of stroke is small, but after menopause, stroke risk increases for all women and especially those with a history of pregnancy complications such as gestational hypertension, preeclampsia, gestational diabetes, stillbirth, and preterm delivery. According to the new guidelines, the risk of stroke is increased by about 75% in women with a history of complicated pregnancy.
As we have discussed before, we do not think that pregnancy complications cause chronic disease later in life. Rather, the normal physiology of pregnancy reveals changes in women’s bodies that were always present that predispose them to stroke later in life. However, understanding the mechanisms by which pregnancy complications and stroke risk are connected is one key area in need of research that is identified in the guidelines.
What can you do to reduce your risk for stroke?
The first step to reducing your risk for stroke is knowing you are at risk. These guidelines go a long way toward helping women and their doctors recognize their risk factors. Many of the recommendations for reducing risk are not new. Aggressive blood pressure control and reducing cholesterol levels with statins are key steps. For those at high risk, the authors recommend following a Mediterranean diet — the only diet with evidence of health benefits in randomized controlled trials. They do not recommend a low-fat diet due to lack of evidence that it is effective.
What is new in these guidelines regarding risk reduction is the role of GLP-1 agonists like semaglutide (the active ingredient in Ozempic and Wegovy). However, their endorsement is less sweeping than some media reports have suggested. The authors recommend GLP-1 agonists in patients with Type 2 diabetes because they have been shown to lower blood sugar and reduce the risk of stroke in these patients.
GLP-1 agonists have been shown to reduce the risk of cardiovascular disease, including stroke, in patients with obesity or overweight and a history of cardiovascular disease but without diabetes. These guidelines are focused on primary prevention — preventing strokes in those people who do not have diagnosed cardiovascular disease. As a result, the authors do not recommend GLP-1 agonists in patients without diabetes specifically for the prevention of stroke, but patients who are overweight or obese may benefit from GLP-1 agonists for many other reasons. Many of my patients who take GLP-1 agonists have many reasons for doing so. I do not think these guidelines will change my prescribing habits.
Where these guidelines will change my practice, which is about 90% women, is reminding me to identify those women at increased risk for stroke and help them reduce their risk.
The bottom line
- New guidelines for the prevention of stroke specifically address the increased risk of stroke for some women, including those with a history of gestational hypertension, preeclampsia, gestational diabetes, preterm birth, and stillbirth.
- The guidelines outline the evidence regarding high-estrogen states and stroke risk.
- In addition to the typical recommendations for reducing stroke risk, such as lowering blood pressure and cholesterol, the authors recommend treating Type 2 diabetes with GLP-1 agonists because these medications reduce stroke risk. They do not recommend GLP-1 agonists to prevent a first stroke for patients with overweight and obesity but no diabetes.
Log in
I am surprised by the listing of the Mediterranean Diet as the only diet with proven health benefits in clinical trials, and the linked article appears to focus on weight loss. I’ve been working toward the DASH diet to manage my own hypertension, diabetes, and cholesterol risks, and was under the impression there is a wealth of research, including clinical trials. Weight loss is not a goal/need of mine. Hope I’m not on the wrong track!