Heart health for women changes after 40 due to aging and hormonal shifts. Discover why heart disease looks different for women than men, and what is really going on behind the scenes.
Every day countless midlife women are blindsided by seemingly overnight changes to their heart health.
“I knew women’s heart disease risk rose after menopause, but honestly, as an athlete I allowed myself to be blissfully ignorant…until I hit late perimenopause myself,” writes Selene Yeager, creator of Fiesty Menopause. “It was jarring to see my LDL cholesterol skyrocket into the red on my InsideTracker graph over the transition.”
How could this be? We’ve all been sold this idea that if we have a “healthy lifestyle,” we’re guaranteed rockstar metabolic health forever. But this just isn’t the case, and it’s time women understand what is really going on.
As I’ve done my research for my book for midlife women, I’ve made some important discoveries. And I’m revealing a missing piece to the heart-health puzzle I don’t think midlife women know about.
But before we get into all the details, you need to understand the why behind our protective sex hormones.
Why Estrogen and Progesterone are heart protective
You’ve probably heard that declining levels of estrogen increase the risk of heart disease. It’s true that estrogen has both an antioxidant and anti-inflammatory effect, and women’s risk for heart disease rises after menopause.
After learning this, I was determined to find out what exactly our sex hormones do to help our heart and vascular system.
One of the key functions of both estrogen and progesterone, and their receptors, is they help stimulate nitric oxide (NO) production in the vascular endothelium. This is the layer of cells that line blood vessels, which are critical to vascular health and function.
This is summarized in this 2018 review in Heart and Circulatory Physiology:
Generally, E2 [estradiol] exposure in women increases vascular relaxation and endothelial-dependent vasodilation, increasing blood flow in numerous vascular beds. NO bioavailability can also be impacted by oxidative stress, and it is well known that estrogens have antioxidant capabilities.
In short, having a healthy endothelium plays a central role in vascular tone, blood flow, and blood pressure regulation. This is important because you need a healthy endothelium to keep plaque from forming on the vessel wall.
The importance of Nitric Oxide
Starting as early as 1876, nitroglycerin has been used to treat heart patients, which is basically nitric oxide at work. But it wasn’t until a century later that scientists discovered nitric oxide.
Nitric oxide is a gas in the body that has a multitude of functions. For this post, we’ll focus on its important function of dilating blood vessels and increasing blood flow to and from the heart. Nitric oxide has a very short half-life, so your body is constantly making it.
I detail more about nitric oxide before in this post.
Studies show that as we get older, the enzyme that helps make nitric oxide, nitric oxide synthase (NOS) released from endothelial cells, stops working as well. When menopause hits, nitric oxide levels decline even further, making matters worse.
Endothelial Dysfunction: a silent pre-disease state
Without as much nitric oxide, the endothelium suffers, also called “endothelial dysfunction,” and arteries slowly narrow.
Endothelial dysfunction is the silent, initial step in the development of atherosclerosis. It goes unnoticed because clinical signs aren’t apparent yet.
According to a 2021 review in International Journal of Molecular Sciences:
Endothelial dysfunction is generated when there is an imbalance in the production or bioavailability of endothelium-derived nitric oxide (NO), generating a decreased vasodilator response and a prothrombotic and proinflammatory endothelium
This is where things get complicated. There is no agreed upon screening tool for endothelial dysfunction, even though identifying it early is crucial. There is also no test to measure a person’s nitric oxide levels.
Studies most often use a measure called flow-mediated dilation (FMD) of the brachial or femoral artery, an NO dependent process. You can see from the bar chart, how FMD decreases with menopause stage.
So, if midlife women are going to prevent or stop endothelial dysfunction in its tracks, they need to do some investigative work.
Check these underlying conditions first
An optimal functioning thyroid supports heart health, and after 40, thyroid dysfunction in women peaks.
But it’s not just overt hyper or hypothyroidism that can cause problems, but more subtle changes. In one study, women in the lower most quartile for Thyroid Stimulating Hormone (TSH, 0.3–1.44 mIU/L), were less likely to have metabolic syndrome than those in the upper quartile (TSH, 2.48–4.00 mIU/L).
(FYI – most consider subclinical hypothyroidism >4 and overt hypothyroidism >10)
In another study with postmenopausal women, higher TSH was linked to a higher risk of cardiovascular disease than in women with TSH in the normal range.
Estrogen also affects the thyroid’s ability to produce T3 and T4, so during the menopause transition, the pituitary gland releases more TSH to stimulate the thyroid. And a higher TSH, reduces the endothelium’s ability to make nitric oxide.
Another condition is high homocycteine, referred to as hyperhomocysteinemia. After menopause homocysteine increases, which has been linked to impaired nitric oxide availability and endothelial dysfunction. This is why I recommend a multivitamin with B vitamins as outlined in this post.
Another biomarker to check is uric acid, which also can increase post menopause. High uric acid is linked to gout and joint pain, and you guessed it, decreased availability of nitric oxide.
Work with the appropriate healthcare provider to resolve these issues if they come up.
More subtle signs of Endothelial Dysfunction
Indirect measures of endothelial function include current cardiovascular screening tools such as blood pressure, LDL cholesterol, triglycerides and ApoB.
Insulin resistance and endothelial dysfunction are often related so you could see higher fasting blood glucose and insulin. A quick ratio of HDL/triglycerides can help you determine risk for insulin resistance. In one study, >3 increased increased the risk of insulin resistance in women 40-60 years old.
In my FREE biomarker guide, I mention a test called ADMA which is also an indicator but rarely done. CRP, a marker of inflammation, is also associated with endothelial function.
But there are physical symptoms as well. In a 2017 study in Menopause, 272 women aged 40-60 free of cardiovascular disease had their hot flashes monitored and had FMD done. Women age 40-53 with more frequent hot flashes had lower FMD, indicating poorer endothelial health.
In these women, hot flashes were a stronger indicator than other risk factors and even estrogen levels. We already know that severe hot flashes are linked to higher cardiovascular disease risk and women should not just brush them off.
From Endothelial Dysfunction to Coronary Microvascular Disease
In her late fifties, for two years Barbara Fleeman tried to get answers to her symptoms of chronic cough, exhaustion and shortness of breath. After running “typical” tests, doctors told her there was nothing wrong with her heart.
“No one would listen to me or think the problem was my heart,” she said in this article on Cedars-Sinai.org. “I needed someone to believe me when I would tell them my heart hurts.”
She went to the Barbra Streisand Women’s Heart Center where, after ordering a cardiac magnetic resonance imaging scan (MRI), she was diagnosed with coronary microvascular disease (CMD). Further testing revealed she had endothelial dysfunction.
Coronary microvascular dysfunction (CMD) also referred to as “small vessel disease,” is dysfunction of the small arteries, arterioles, venules, and capillaries. And the majority of people with CMD- 60-75%- are women.
That’s why heart attack symptoms different for women than men. In fact, half of women with chest pain, like Barbara, have no blockages in the main arteries and are told they are fine.
Women, may or may not have chest pain, but also experience extreme fatigue and tiredness, dizziness, indigestion, shortness of breath, chronic cough, and pain or pressure in the lower chest or upper abdomen. It can be mistaken for the flu.
Men tend to have squeezing chest pressure or pain, jaw, neck or back pain and nausea or vomiting.
What makes matters worse, is that CMD may be a breeding ground for other diseases found more frequently in women such as heart failure with preserved ejection fraction, Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension (PAH), endothelial dysfunction in diabetes, diabetic cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis.
And, as stated in this 2020 review in the Journal of Women’s Health, “…an imbalance between the endothelium-derived vasodilator nitric oxide (NO) and the vasoconstrictor endothelin-1 (ET-1) is a proposed mechanism for CMD.
The good news is we can boost nitric oxide levels
In my research I’ve found many ways women over 40 can boost nitric oxide to help prevent endothelial dysfunction. Of course, menopausal hormone therapy, especially when taken close to menopause, can help increase nitric oxide. But there are plenty of other ways too.
Half of the nitric oxide we get actually comes from our diet and the other half from our endothelial cells.
Women benefit from adding nitrate-rich foods, including leafy greens, beets, and celery. Supplements are also available, like HumanN Superbeets. Bacteria in our mouth reduces nitrates to nitrites, which get turned into nitric oxide with help from stomach acid.
But we need to ditch mouthwash and antacids that block the body’s ability to make nitric oxide from food. See this post for more details.
Lowering LDL cholesterol and Apo-B can help increase the bioavailability of nitric oxide. I am a big fan of the portfolio diet, which includes adding foods proven to lower cholesterol as much as statins including nuts, sticky fiber like oats and beans, soy foods, and plant-sterol margarine.
Anything that decreases oxidative stress in the body will help increase nitric oxide, including a diet rich in antioxidants, not smoking, good sleep, lower stress, exercise, and moderate to no alcohol.
Another exciting way to increase nitric oxide is breathing through your nose, deep breathing, and strengthening breathing muscles. Our sinuses are lined with nitric oxide so when we take in air this way, we also take in nitric oxide.
The menopause transition also negatively affects lung function. And this can cause intermittent hypoxia, or periodic low levels of oxygen, which decreases nitric oxide. Luckily, women can strengthen their breathing muscles using inspiratory muscle strength training that I dish about in this Instagram Reel.
Of course, in my book and newsletter, I will include many more ways to boost nitric oxide as I continually make discoveries about the unique needs of midlife women.
Heart disease research for women is lacking
I didn’t complete this article in one day, but rather, spent four plus years accumulating these golden nuggets of information. I have to do this because, unfortunately, the research is not as far along as it should be.
According to the American Heart Association’s Go Red for Women, 1 in 3 women die of heart disease or stroke compared to 1 in 31 dying of breast cancer. Yet the research in women’s heart disease is much less. And less research means poor awareness in our medical system.
Although it’s unlikely younger midlife women have heart disease, it’s very possible the silent form of endothelial dysfunction has taken root. And menopause undoubtedly accelerates this risk.
I suspect that of many of the symptoms of menopause are at least partly due to this decline in nitric oxide. Studies hint at this as a key mechanism and one randomized control trial found that women who wore nitroglycerin patches had a large reduction in hot flashes.
Are you getting riled up yet that women’s health is so behind the times?
Midlife women need to be proactive
Wherever you are in your journey, just know that heart health after 40 comes down to this: we midlife women need to be pro-active in taking care of our endothelial function, so we don’t move onto the next stage of heart disease.
And if you or a loved one have symptoms mentioned in this post, you need to push for more testing by printing this handout and giving it your doctor.
Send this post to family or a friend or share it on social media. We can’t wait around. Too many of women’s lives depend on it.