Improving Cardiovascular Health for Women: The Essentials for Every OB/GYN Practice

Well, thank you so much and I am so excited to be here and get to speak to OB-GYNs all around the country because we are now at the cusp of a very new event, you know, using our skills to help all of our women patients to recognize their cardiovascular risk. And then we can take steps to help potentially avert who knows what kind of adverse event. So this is a first for women OB-GYNs for many have not been screening for cardiovascular risk. So we’re going to look at what particular women are the ones that you should be putting high on your radar to be screening. And then what can you actually do in terms of screening? And then because I am both board certified in OB-GYN and in integrative medicine, I will share some of my personal tools that I use to help my women patients who are in need of help to lower their cardiovascular risk so they can actually optimize their health span that’s living the longest possible healthy life. It turns out that we as OB-GYNs have a unique opportunity to help women patients because many women use us as their sole doctor and come to us more than any other physician for their routine screenings. The Well Woman exam is a well-established type of health care visit for women, and most women will come every single year to their OB-GYN. So we have this unique opportunity now to screen women who actually have significant risk for cardiovascular disease. But we need to recognize which women are the most at risk. That should be highest on our radar. So think about pregnancy, because pregnancy is a unique stress test for women. And when women have pregnancy related complications like gestational diabetes, pre-eclampsia, pregnancy induced hypertension or growth restriction, and even pre-term labor and deliveries, they are all red flags that these women have underlying metabolic issues that are expressing themselves in this stress test environment, this inflammatory state known as pregnancy, a very unique state for women. And those women should be high on our radar to be screening for cardiovascular risk for the rest of their lives, not just later when they’re older, but at every stage, once they have completed a pregnancy with such a complication. Polycystic ovary disease, which we’ll talk about in more detail, is the most common endocrine disorder of women and very associated but very underrecognized as a metabolic risk problem and oral contraceptives, which are now being used by the very vast majority of women. Something like 90% of women will use oral contraceptives during their lifetime. And that’s not really recognized as a potential risk for cardiovascular events. Everyone knows you’re not going to give birth control pills to a woman who’s just had a heart attack or a stroke. Well, we should be aware that they in themselves have some risk associated with them, and just that should be on our radar. And then menopause, the universal event that brings cardiovascular risk to 100% of women. So cardiovascular risk remains a very huge issue in the U.S. and of course, around the world. It’s the number one killer of all women. It beats all cancers combined. So. And this is not just with referring to really elderly women in their late, late eighties and nineties. We’re talking about women who are really in the prime of their lives in their fifties and sixties and seventies. And these women are really experiencing issues that we can help to recognize and even prevent. It turns out that a very high percentage of women, their first sign of cardiovascular disease, is actually death. How terrible is that? And so it’s up to us now as often the prime caregiver of women to help them to recognize the risk and then take steps to avert it. And it turns out that the prime screening tool that most people have been using, which is just an ordinary lipid profile, is going to miss a huge percentage of these women before, in fact, 50% of women who have coronary artery disease have normal LDL levels, levels under 100. And look at the cost. I mean, of course, you can never put a cost on suffering and early loss of life. But in terms of what the U.S. spends, it’s over $300 billion annually. This is not sustainable, of course. So let’s talk about some of the key conditions of women that I want to put on your radar and look at these women as containing high risk of developing cardiovascular disease. So polycystic ovary disease, which we talked about as the number one metabolic and cardiovascular risk of reproductive age women, is often not recognized for the metabolic component. Here we see in this slide that, yes, it’s involved with high rates of infertility and chronic and ovulation period problems, pregnancy problems, and then the associated hyper androgen issues of acne and hirsutism and alopecia, all of which make women incredibly miserable. But as we go to the next slide, we see it’s so much more than that. There are huge metabolic issues that women with PCOS are experiencing. They are intrinsically inflamed. They have high rates of insulin resistance, lipid problems, visceral obesity, which of course is associated with terrible rates of metabolic syndrome and inflammation, which we’ll talk about as the main issue. Hypertension, fatty liver and cardiovascular issues involving the vascular system, endothelial dysfunction. So let’s look a little bit more at this. And of course, the vast majority are overweight and obese and have weight loss resistance. So metabolic issues are pervasive in women suffering from polycystic ovary syndrome. It turns out that we now understand some very fundamental issues that we did not understand just a very few years ago involving PCOS. Women with PCOS have problems with estradiol. They actually make it to at a too lower rate. They have low levels of systemic estradiol. They have poor production from their ovaries and their hormone receptors for estradiol are not functioning properly. So essentially, I want you to think of PCOS as a state of intrinsic estradiol deficiency. And as we look through this, we’ll see that women with PCOS have extremely similar metabolic and cardiovascular manifestations to women in menopause who obviously have low levels of estrogen production because their ovaries are no longer producing estradiol. So there’s a lot in common and this helps to explain and will help you to understand why women with PCOS and women with menopause should all be high on your radar for screening for cardiovascular risk. So this slide says a lot. It shows that women with PCOS typically have elevated LH and low FSH and because of that, they have ovarian dysfunction. They actually have increased androgen production, typically testosterone, but they do not convert testosterone properly into estradiol. So they actually have low levels of FSH which is very key to the the stimulation of the enzyme aromatase, which causes the conversion of testosterone to estradiol. So they have high estradiol. I mean, rather they have high testosterone, low estradiol. And look at what is associated with it. They have abnormal production of insulin. They have high levels of insulin because they have insulin resistance. And this is involving their skeletal muscle, which we now know is incredibly important in glucose metabolism. They have high rates of fatty liver, and when you have fatty liver, you end up with a dysregulated liver, you end up with uncontrolled gluconeogenesis and production of high levels of fat triglycerides. So we end up with high production of fat, we end up with fatty liver, we end up with insulin resistance and we have a problem that is pervasive throughout the body, leading to high rates of metabolic dysfunction and metabolic syndrome. This is how I want you to understand PCOS. This is our new understanding and why all women with PCOS have issues that should be screened for regarding their cardio metabolic state. So now that you understand PCOS as a condition of estrogen deficiency and menopause, of course, as a condition of estrogen deficiency, you can see how all of these different manifestations are linked together and so many issues involving menopause are very involved with women with PCOS and high and highlighted in red are the metabolic disorders, the high rates of insulin resistance and diabetes, cardiovascular risk and of course associated atherosclerosis. So recognize the risk that these women are living with and the sequela of having high amounts of visceral fat, dysregulated hormones, insulin resistance and as well, and we don’t have time to get into it, but it’s a huge new understanding is the role of the gut, the gut microbiome impaired gut barrier function, also known as leaky gut and regulation of our immune system and the production of inflammatory cytokines. All of this links to both menopause and women with PCOS and they have high rates of inflammation, and inflammation is the driving force of much of what is going on in PCOS and also in menopause. As you can see, there’s so much similarity once you have understanding of low levels of estrogen, then you can see how it all links together and everything in the body, in the female body is in some way linked to estrogen. And then there’s this key other issue that I want you to understand, which is nitric oxide, this incredible gas, which is a signaling agent, a redox signaling agent involved in reduction and oxidation. It’s an antioxidant. And women with polycystic ovary syndrome also menopause have low production of nitric oxide. Nitric oxide is very important for arterial health. And we’re going to go over this in more detail. And one of the surrogate markers for nitric oxide is a laboratory test that I use routinely called ADMA. So when you have high levels of ADMA, that is a reflection of low production of nitric oxide in the arteries itself through this enzyme, this key enzyme called endothelial nitric oxide synthase, it’s ENOS, it’s there and that is driven by estrogen estradiol. So as we know, there’s low levels of estradiol in women with menopause, in women with PCOS, and therefore you have low production of nitric oxide in the arteries, which is really important for the health of the lining, the endothelial lining of arteries. And as a side note, just a quick side note, nitric oxide is very important for immune health regulation. Everything in the body, as you hopefully know, is multitasking. Nothing does just one thing. So nitric oxide is also involved in immune regulation and women with PCOS have higher rates of many autoimmune conditions. Women in menopause have higher rates of, for example, rheumatoid arthritis, which is autoimmune. And we now know and this is also new information that women who are the majority of sufferers from autoimmune disease, that autoimmune disease is also associated with increased cardiovascular risk. So I don’t want to get into it. There’s no time for all that. And you may not be the primary caregiver of women with autoimmune disease, but be aware that autoimmune diseases of all sorts have higher rates of cardiovascular risk. And if there’s no other doctor that’s screening them, make sure you’re the one, because you could be the life saver. And here’s bringing in the oral contraceptive issue. It turns out that birth control pills lower the production of nitric oxide. And this is a really important take home message. That’s why we would not give birth control pills to women with serious metabolic or cardio metabolic dysfunction because we know that birth control pills can increase blood pressure, birth control pills can increase insulin resistance. So birth control pills are what they are. They’re incredibly effective at preventing unwanted pregnancies. That’s a big plus for them. But they also are metabolic dysfunction creators. That’s just what they are. We need to understand birth control pills, increase glucose dysregulation. They are pro fibrotic. They increase the production of the elements that create more blood clotting in the body. That’s why we don’t give birth control pills to people who’ve had strokes, heart attacks, blood clots. So when you have women and I’m sure many of you have lots of patients on birth control pills, please be aware that these are not good for cardiometabolic health. We give them to women who are young who can deal with this, but a lot of women are now using them when they’re older. So be aware that birth control pills have elements that affect cardio metabolic health. We need to recognize this. And women who’ve been on birth control pills sometimes for decades now, they have potentially higher rates of cardiovascular issues. Please, let’s be screening them. So nitric oxide is such a key element for cardiovascular health, for the endothelial health of arteries. And the arteries, of course, are the highways delivering oxygen and nutrients throughout the body. We need to have healthy arteries, nitric oxide. Look at all the things that nitric oxide does. It improves dilation of the blood vessels. So it helps prevent hypertension, it reduces blood clotting, reduces inflammation in the artery wall itself, lowers free radical formation, reduces the oxidation of LDL, which we’re going to talk about because LDL itself never killed anyone. We need LDL what we don’t want it to be exposed to free radicals and become inflamed and oxidized. That’s what creates the problems. And of course, we when we have nitric oxide, we maintain the health of the artery wall. These are hugely important issues. And as I mentioned, menopause, polycystic ovary syndrome, birth control pills, lower nitric oxide. We need to keep that in mind so that when you don’t have enough nitric oxide, everything the opposite happens. You end up with all of these problems. So please keep this in mind. These are really important. Take home messages about some of the mechanisms that estrogen puts in play to keep cardiovascular health properly functioning. So here’s a quick slide that I just want to just go over with you so that you understand this really important lab test that I use. It’s very a big, very big part of my toolbox for looking at the cardiovascular health of my women patients. And that is ADMA. So what we see here is that arginine leads to the production of ADMA. Arginine also is the precursor for nitric oxide. Now when ADMA is made, normally there’s an enzyme, DDAH, which breaks it down into its other components. The dimethylamine and L-citrulline and that is great. But when you have an inflammatory state, which we now know menopause is inflammatory, PCOS is inflammatory, birth control pills create inflammation. When you have free radicals and you develop oxidation of your LDL, you have these inflammatory cytokines circulating like tumor necrosis factor alpha. It blocks that enzyme that creates the degradation of ADMA and you have build up of ADMA. What happens is ADMA blocks this critically important enzyme that’s in the arteries called eNOS, endothelial nitric oxide synthase that is critically important for the production of nitric oxide, this amazing gas, this antioxidant gas that keeps our arteries healthy. And when we have all this inflammation, which is intrinsic to aging, to PCOS, to birth control pills, and in women who have autoimmune diseases, that you have the blockage of this enzyme that breaks down ADMA you have increased ADMA, you block this enzyme that makes nitric oxide and you have problems with your arteries because you have reduced production of this critically important gas nitric oxide. Now, estrogen can help overcome and increase the production of nitric oxide by stimulating this enzyme eNOS. The problem is what happens when you don’t have enough estrogen. That is why after menopause, when all these things come into play, or women who are on birth control pills, women who are suffering from PCOS, they don’t have enough estrogen and they cannot overcome the developing inflammation and its consequences. And ADMA will rise. And we can measure that in blood and it will give us an idea of what’s going on. So estrogen is my favorite hormone, I think, ever gynecologist to have as your favorite hormone estrogen. And we should understand it better that estrogen has receptors throughout the entire female body because reproduction and metabolic health are one. It’s a really important take home message. The reproductive functions of women are not separate from their metabolic function. Of course, nature wants a healthy woman to have pregnancies and deliver a healthy baby, so the whole body of a woman is intertwined with estrogen working throughout through all the different organs of the body to keep a woman’s body functioning properly. And I highlighted in red the endothelium of arteries, muscle in heart and muscle in the artery walls themselves that these are key players. But as you see, everything is involved with estrogen. Look at liver, the GI tract. If we look at mitochondria, that the energy powerhouses of cells, bones and joints and muscles, all of which have key metabolic functions, nothing is a single functioning thing in our body. Everything is working in this beautiful interplay. And estrogen is key to keeping it all humming together. And when we don’t have enough estrogen just to drive home this point one more time, you end up with dysfunction. And it could be also from hormone resistance and also not going to have time to go into it, but endocrine disruptors, all those terrible chemicals that we’re bathed in these days, the phthalates, the Bisphenol As, the heavy metals and all of these things that can interfere with proper estrogen functioning as well. And this is another whole subject that hopefully we’ll talk about another day. But whenever you don’t have enough estrogen, you end up with metabolic dysfunction as you can see in this slide. And this slide also just puts it all together. It shows this is when you don’t have enough estrogen, all the organs in the body are linked together in metabolic health or metabolic dysfunction. And in the center there, it shows the fat which is infiltrated with inflammatory cells, the macrophages. And when you have this uncontrolled situation of metabolic dysfunction and you have inflammatory free fat that’s out of control, you don’t have estrogen controlling it, you have chronic inflammation. See how it says in the center, low grade inflammation with increased inflammatory cytokines. And this is what drives all of these cardiovascular issues is this chronic inflammation. So we now have tools, laboratory tests that enable us to recognize what’s going on in the body. We need to access these tools because look at what happens to women, universal issues, menopause. There’s not a woman that can escape it. You can’t meditate your way out of menopause. You can’t eat vegetables to get out of menopause. You may delay it, but you cannot escape it. 100% of women will experience menopause. Menopause intrinsically creates vascular impact. 85% of women in the U.S. by the age of 75 are hypertensive. And this is including women who try to do healthy things because without estrogen, you already know you’re not going to make proper nitric oxide. All these different organs of your body are going to be in this interplay that results in metabolic dysfunction. So hypertension happens to almost 100% of women by age 75. We need to have this on our radar that women in menopause will develop some degree of cardiovascular risk. Now, every woman is different. Some women have, you know, different genes and they have different diets, they have different reserves. But every woman intrinsically will have some increased risk when they lose their peripheral ovarian production of estrogen. And this is also the same for women with PCOS. And so it’s all around loss of estrogen. And we need to be aware that menopause and cardiovascular risk go hand in hand. Estrogen, I just want to mention in terms of lipids, estrogen after loss of estrogen, whether from endocrine disruptors, whether from PCOS, whether from menopause, and of course, universally with menopause, you’re going to have effects on the lipid profile. Estrogen supports HDL. That’s why we know that women before menopause have far lower rates of cardiovascular events than men. It’s not an accident. It’s because we have all that estrogen and it supports higher levels of HDL. I’m sure you all know that. And estrogen moderates LDL because it promotes the production and function of liver LDL receptors. So after menopause, the liver doesn’t function the same way. And the liver, hepatic LDL receptors are not functioning well. So the liver cannot pick up the cholesterol for recycling and elimination as well in women after menopause. So now, you know, women have PCOS. That’s the number one endocrine dysfunction of women. Every woman is going to have menopause. And about 90% of women have been on or using birth control pills. And many women have pregnancy related complications that are predictors of cardiovascular risk for the rest of their lives, recognizing that pregnancy is essentially a stress test of women. So every woman has some issue at some point. So what are we going to do? We are now, to, we are now to recognize that we are tasked with screening our women patients. This is now been dictated to us. And I, I embrace this by the American Heart Association and the American College of OB-GYN that we OB-GYNs should be screening. Well, we know that there are certain risk factors that we cannot change, but we should be aware of them. Right. We can’t change our age or gender or menopausal status or our previous medical history. We cannot change those things or our family history, but we should be aware of them. And then there are things that we actually can change and the things that we can change we should try to affect. That’s what we do as doctors, right? We try to help women to lead the healthiest possible lives possible. So where do we begin? I begin with, of course, the physical, the history. We’ve already kind of dealt with that. And then I do laboratory testing. I love to know where I’m at. I cannot monitor what I never measure. So I love laboratory tests. It tells me so much about what’s going on in a person. It’s all noninvasive. I actually in my office have low cost imaging studies. I can do carotid intima-media thickness testing, echocardiograms, but many of you can’t access that. So but everyone can access laboratory tests as a very practical and very efficient way of trying to understand what’s going on within the bodies of their women patients. So I know and you know, now that inflammation that was the key part of that slide I showed you that showed fat with all its infiltration with the inflammatory macrophages as central to all of these processes that are occurring, involving all of the organs of the body that are involved in cardio metabolic dysfunction. We now know it’s a total body process and inflammation is both a consequence and a driver of many of these problems that women will face with their cardiovascular systems. And we can now measure these inflammatory markers. And that’s what I love doing. And I’ll go through my key ones that I use in all of my women patients when I’m looking for cardiovascular risk. And I never do just a lipid profile. We know I just I told you a few moments ago that half of women have normal LDL levels. That’s not the issue. We want to look at more sophisticated lipid markers and insulin. Insulin is a such a huge issue, metabolic syndrome, insulin resistance. So we definitely want to look at insulin and hemoglobin A1C. I always look at insulin because insulin is a more sensitive marker of early dysfunction involving the glucose regulation systems of the body and oxidized LDL. I mentioned no one dies of LDL. It has to be oxidized. That’s what gets into the plaque and creates problems when you have free radicals and oxidized LDL. And that’s a wonderful test to measure. I look at ferritin, which is often a sign when it’s high of fatty liver and liver dysfunction and inflammation in the liver. I like to look at some of the genetic markers which we don’t have time to deal with today, but they are also very important in terms of risk factor and issues with detoxification and methylation are important. B12 and homocysteine. I like to measure homocysteine is an independent risk marker for cardiovascular disease and is often related to B vitamin deficiency. And and that’s another topic for another day. Vitamin D we now know is sort of a ubiquitous marker for just about everything, and we want to have adequate levels. I like to have a level of about a 50. Omega 3 fatty acids are very anti-inflammatory. We want to have all of the fatty acids. Omega 6 is not evil and omega 3 is not, you know, like it’s wonderful. They’re both important. We want to have adequate amounts of all the fatty acids. And very few people, though, in our country have deficiencies of omega 6. What they have is often deficiencies of omega 3. So I definitely want to see where omega 3 is that because that’s also a key issue in cardiovascular metabolic health. Uric acid, which is underappreciated as a marker of cardiovascular risk, not just about gout, it’s also about lipid and glucose regulation and is an independent cardiovascular risk marker as well. Heavy metals I always like to measure, we now know that most plaque involves some kind of heavy metals and as women, aged women who lived through the heyday of leaded gasoline and that’s your women patients now in their sixties and seventies and older, they often have high levels of lead in their bones. And as their bones start to lose their calcium, they actually free up lead and lead is associated with hypertension. So keep that in mind. And thyroid low thyroid is associated with high lipids. And we definitely want to look at our thyroid function and especially in younger women, but really in all women, we want to look at antibodies because Hashimotos autoimmune thyroid is really at epidemic levels and we really want to know what’s going on with the immune system because the immune system and the cardiovascular systems are completely interrelated. And of course we want to look at hormones. I actually don’t look at it all the time, but pregnenolone, which is an anabolic neurosteroid, is associated with high levels of stress when you have low levels. And so it’s a really interesting marker that you might want to become familiar with. And sometimes I look at other micronutrients because we know that the body can’t work properly if it doesn’t have the right nutritional content. So let’s look at some of the data here. The CANTOS trial, which was published in the New England Journal of Medicine in 2017, was really a landmark study. I have been telling people for ages that just looking at lipids is not where it’s at. You’ve got to look at inflammation because that’s what’s driving all of these issues. It’s both a consequence and a driver. This was the first study that showed that totally independent of cholesterol lowering, that cholesterol was not touched, that by lowering inflammation, you lowered cardiovascular risk. How not amazing is that for people who know about this. But for many people, this was a revelation that you can leave lipids alone and just lower systemic inflammation and cardiovascular risk goes down. Now, no one is recommending that you use an immune modulator on all your patients to lower inflammation. We have wonderful lifestyle ways that we can implement in our women patients to lower their inflammation. We don’t have to use pharmaceuticals like they did in this study. But what the key takeaway is that lowering inflammation lowers cardiovascular risk independent of lowering cholesterol. That is such a huge take home message. And like I said, for me it’s like, of course, but for many people that was a revelation. So if we look at this wonderful picture of an artery and we look at the progression of the internal dysfunction of the artery, of the endothelial lining and the production of plaque and ultimately rupture of plaque, and that can lead, of course, to heart attacks, strokes and death. So that’s what we never want to see our patients have to suffer from. So we want to get on we want to get on the bandwagon early and start recognizing the risk of our patients when we can actually do something. Because we I’m sure you and I, we don’t deal with patients when we’re not first responders for heart attacks and strokes. That’s not what we do as OB-GYNs. But we see our women patients far before those kinds of events need to occur. And we can, by looking at earlier risk markers, not the end stage, but the earlier markers, we can help implement lifestyle changes to help our women patients avert that end stage event. So let’s look at some of these amazing markers that I incorporate in my practice and you can now incorporate in yours. The first one, which is an earlier marker of incipient cardiovascular disease, are the F2-Isoprostanes. You may never have heard of this. It’s a urine test and it’s a wonderful test that shows the state of oxidative stress in the body, the actual gold standard. So what it actually is measuring are called lipid peroxides or the peroxidation of lipids, the oxidation free radical of these fatty acids. Now fatty acids include like arachidonic acid. So it’s looking at that, it’s looking at fatty acid oxidation or what we call lipid peroxides. And this is incipient in terms of its information of what can happen in the body once you start having this state of free radical and inflammation that can lead to the earliest production of plaque in the arteries. And this is often a lifestyle issue. We know that elevated F2-Isoprostanes are present in people who are smokers or people who are exposed to second or third hand smoke and people who eat a lot of processed foods. And now there was just a recent article just came out this week, which was hardly surprising for us who know this sort of thing that the ultra processed foods, the high consumption of ultra processed foods, increase early death and cardiovascular risk. Of course it does. That’s not the food that anyone should be eating, but yet that is what so many people are eating, this highly processed, ultra processed foods. This leads to the production of free radicals and elevated F2-Isoprostanes. And you can measure this on your patients and you can then follow how they’re eating and their lifestyles by measuring this amazing test that measures lipid peroxides. And then I mentioned oxidized LDL. Oxidized LDL is the critical thing about LDL. LDL, That’s oxidized is so dangerous, we definitely have to measure this. And once again, it can be an earlier earlier marker of the incipient development of cardiovascular risk and plaque formation. For once you have oxidation of LDL, it’s no longer recognized by the liver LDL receptors. The liver is not capable of properly extracting oxidized LDL from the blood to get rid of it, but it is recognized as an inflammatory issue and immune cells like macrophages will recognize it as something that needs to be disposed of and will gobble it up phagocytosis and will take it in and create these foam cells. And these can then get into unhealthy artery linings and create plaque. So oxidized LDL is such an important tool, we need to measure it. I measured on all of my patients, and this is such an amazing study, the CARDIA study. Look at this. It shows that elevated oxidized LDL levels pre predicts metabolic syndrome. Metabolic syndrome is what leads to cardiovascular issues, right? When you have hypertension and you have high levels of insulin resistance and so forth that’s what leads to these terrible issues of cardiovascular risk, heart attacks and strokes. If we look at the top part of this graph, we see oxidized LDL when you have high levels like the 5th quintile, when you have high levels of oxidized LDL, you have significantly increased risk of metabolic syndrome. But look at when you look at just straight LDL, look, it doesn’t matter how high it is, it doesn’t correlate with the onset of metabolic syndrome. That’s why just measuring a plain lipid profile with just plain LDL isn’t giving you the information you need. You need to see what the oxidation as the free radical state of LDL. That’s what causes the harm to the arteries, not just having LDL so elevated LDL is a tremendous risk marker for cardio metabolic disease. And as you can see, it can be an early marker for metabolic syndrome. That early development, it’s related very, very much to poor lifestyle choices, which you can impact and help your patients to overcome. Because if you don’t, then this can lead to chronic disease with diabetes, cardiovascular disease, heart attacks and strokes. You can intervene at an early stage to help your women patients to not develop those sequelae. Once again take home message, ADMA and SDMA is a marker for renal function, which we won’t go into today. But ADMA is a surrogate marker for nitric oxide. And this I’ve drilled into your heads. You’ll never forget nitric oxide, you’ll honor it and respect it the way I do because you have high levels. When you have high levels and you have lower levels of ADMA, you have cardiovascular well-being. But when you have high levels of ADMA, which is the reflection of low levels of nitric oxide, you have cardiovascular cardio metabolic risk. Microalbumin another one of my favorite markers. So microalbumin, when you have macroalbumin, when you have a lot of protein coming out in the urine, that’s a sign of nephrotic syndrome or renal disease. But when you have very small amounts of but you know, excessive but small amounts of microalbumin, low levels of this protein leaking through the arteries in the kidney and into the urine, it’s a sign of endothelial dysfunction that the lining, which is so key to the function of the cardiovascular system, the lining of arteries is not functioning properly and it’s integrity is altered. So just as you can have impaired gut barrier function or what we call leaky gut, you can have impaired function of the endothelium and have what I’ve named leaky arteries. And so some of the protein that’s normally in the blood leaks out and you can actually measure it in the urine. So this is an amazing marker for dysfunction of the endothelium of arteries, a test that is not implemented often enough. And from this point on, I hope you will make this part of your standard of care for your women patients to see what the health of their endothelial function is by measuring microalbumin. It’s a simple urine test. Most of you have probably heard of high-sensitivity C or C-reactive protein, and it is associated with heart disease. But the thing about it is that this is a reactive phase, so that means it can go up just because you didn’t get enough sleep the night before or you have a bad cold or you have, you know, a toenail infection or or something. So you have to measure this on a repetitive basis to see if it stays up. So anything that keeps it elevated, which can include autoimmune disease or systemic inflammation from low levels of nitric oxide or gut dysbiosis, where you have a leaky gut and you have the wrong gut microbiome or chronic stress or chronic sleep deficiency, all kinds of things that can be done in a chronic way to keep a chronically elevated hsCRP that is associated with cardiovascular risk. So that should be standard in your toolbox. So CRP has been shown to be a strong predictor of cardiovascular events when it stays up and it is once again more predictive than LDL. I mean, LDL has been glorified as a risk marker and I think we should put it to bed. I mean, it has some role, but let’s be real. Just looking at LDL is not predictive of cardiovascular disease the way these other markers are. So let’s access what actually works and leave behind the 50 year old studies that really are not really applicable in our new, not modern knowledge. So if we look at plaque now, of course, plaque itself doesn’t kill anyone, but ruptured plaque does. So we want to not just know if someone has plaque, but what’s the state of the plaque? Is it at risk for rupture? That’s what these two tests I’m going to tell you about now can give you that information. So these are later tests that you’d want to be looking at for your women patients with more moderate to severe risk. So like the older women or the women who already are showing signs of metabolic dysfunction, like they already have pre-diabetes and such. So myeloperoxidase we’re going to talk about in a moment that looks at the response of our immune system to fissures and erosions and changes in plaque that can show a risk of vulnerable plaque for rupture. And the Lp-PLA2, which is also incredibly useful for looking at the inside of the plaque and the structure and and degree of stability of the covering of the plaque or the cap. So let’s take a look at these in more detail. So Lipoprotein-Associated Phospholipase A2 or Lp-PLA2 Activity. No, anything that ends in the word ace is an enzyme. So now you know, this is an enzyme and it looks at disease activity involving macrophages. And so this is an enzyme produced by the white cells, the macrophages that are located within the atherosclerotic lesions and cells underneath the cap with the collagen cap near the necrotic core of the plaque itself. And when you have high levels of this enzyme, the two which are produced by these macrophages, it is a concern for potential instability of the plaque within the artery itself. So when you have a high level of Lp-PLA2, I want you to recognize that that patient has a significantly increased risk. And and in women, the risk for the next five years is about doubled. So this is not insignificant. So this test is a really red flag thing. Maybe this is a patient you want to refer to a cardiologist or an internist, but you will be the star. You will be the one that’s recognizing this risk in this woman. And MPO, myeloperoxidase, so now you know anything that it’s an ase that is an enzyme. Myelo is white, peroxidase is like peroxide. It’s an enzyme produced by white blood cells designed to kill invaders, invaders like viruses and bacteria. So what the heck is this doing being measured in your blood? Well, it’s the response of these white cells to vascular injury that’s going on in vulnerable plaque. Now, this may or may not be related and this is some very new, interesting potential information here that it may be related to circulating even bacteria that are coming that are seeded from the mouth. That’s why all of your women patients, especially if they have elevated myeloperoxidase, should have a really good visit to their dentist. And looking at gingivitis because it’s now recognized that seeding of bacteria from infections that can even be stealth infections in the mouth may be contributing to unstable plaque and heart attacks and strokes. So MPO is another huge red flag. So when you have an elevated myeloperoxidase, it’s showing that there’s a real active issue going on with the white blood cells that are circulating and that’s measurable in the blood that is indicative of vulnerable plaque. And when you have elevations of both Lp-PLA2 and myeloperoxidase that is a super red flag that these women have potentially very unstable plaque and active inflammation going on in their arteries as well. So please those are patients you want to definitely refer so you can be like I said the superstar of recognizing the potential that these women have for having heart attacks and strokes and getting them into high level care. And when they have one or the two elevated, their risk is less but still substantial. So please, these are very high risk women. Please make sure you recognize and get them proper care. So I’m just going to touch on hormones. No matter what we do after menopause, we can’t replace the ovaries. You know, the ovaries are not just hormones given out in a bolus every day or the same thing every day. The way that hormones are produced by the ovaries is rhythmic. It’s ultradian, it’s circadian, it’s lunar, it’s more complex than we have or we have the ability to do. Conventional does something I mean, in favor of hormones. But I need to just have everyone recognize we can’t replace the ovaries. I hope that there will be way more research involving looking at physiologic restoration of hormones. But right now we do have to be cognizant of what the official recommendations are and then work within our own comfort level in terms of treating women in menopause with hormones. I’m I’m very pro hormone. That is my personal opinion. But I’m not here to discuss hormones in great detail. But I hope we’ll have lots more research and we’ll have more wisdom that will come out in the future because the Women’s Health Initiative did not use physiologic hormones or delivered in a transdermal way. So we just have to keep in mind that the Women’s Health Initiative was not using human hormones or and was using oral hormones. So what can we do? Well, exercise should be part of our toolbox in treating all of our women patients. It increases nitric oxide and the array of benefits from exercise is phenomenal. So every woman should get on an exercise program. And in my office we do exercise prescriptions and exercise evaluations, fitness evaluations. And if you can’t do that in your office, see, well, you can find a really qualified trainer to work with. And of course, nutrition. Diet goes without saying as being critically important. So there’s a lot of data on the Mediterranean diet. I personally, especially initially leave out the dairy. This is my own opinion because it’s really hard to get any quality dairy in the U.S. Most of the cows are pregnant, and even when they’re eating organic, it’s usually organic corn. So I usually find most dairy products to be quite inflammatory. We now know from studies out of the Harvard School of Public Health that the high intake of dairy has not correlated with improved bone, but rather decreased bone health. So don’t think dairy is what it’s been made out to be. It’s not really great for bones, and it’s usually quite inflammatory. And I usually leave out all wheat products that are not organic because it’s quite inflammatory. It’s coated with glyphosate and gluten itself can be irritating to the gut. And what I focus on is healing the gut and trying to get a healthy gut microbiome. Another big complex subject. And I love vegetables, vegetables and fiber. So think of carbohydrates as the friend of women, not the enemy. As long as they’re complex, not not processed. And it’s full of beans and lentils and lots of wonderful variety of vegetables and fruit polyphenol rich foods. I also incorporate not just what you eat, but when you eat. We now know that circadian rhythm is really everything to metabolic health. And so please have your patients stop eating at about by 8:00 at the latest. Not eat all day long, not eat more than three meals, try to have a big breakfast, try to fast for about 13 hours at night, which has been shown to reduce recurrence of breast cancer. Try to do some fasting, another whole subject for another day. But not eating helps the body to reset the circadian rhythm and the gut microbiome. So this idea of eating constantly, or eating and grazing is actually not good for a metabolic health. So I want to do a quick study. This is a typical patient who you can care for as an OB-GYN. She is just a healthy woman who’s 50. She’s gone into menopause. She’s been eating pretty healthy. But over the last couple of years, her sleep has deteriorated. She’s put on weight. Her appetite is dysregulated. She has a lot of GI symptoms, mood swings, hot flashes, low sex drive and foggy brain. We now know these are very typical. This is not a really, really high risk patient, one that you can care for yourself. And when I checked, she was already pre-diabetic. Her hemoglobin A1C was 5.8. She had elevated triglycerides, but yet her her LDL cholesterol was normal. All her markers of inflammation, her ADMA was elevated, her hs-CRP was elevated, um, her myeloperoxidase and Lp-PLA2 was not they were not elevated, but her other markers of inflammation were mildly elevated. She was at the beginning stages. This is exactly the patient that you can care for. I actually did a four point cortisol and found this is not uncommon. Her cortisol levels were high at night when they should be and low in the morning when they should be high. She has a flip circadian rhythm that’s very typical for women in menopause. She was had all the markers for menopause, low estradiol, high FSH and her testosterone, which is separate from menopause, was at the low end of the reference range. I did all the things I told you in terms of lifestyle and I am as an integrative doctor, I use some nutraceuticals. Now, I don’t give all these things as separate products. I have my own protocol and if you’re interested in my actual products or protocols, please feel free to email me. But you don’t have to even access any of these supplements. Just have them eat a lot of cruciferous vegetables, eat probiotic fermented foods, make sure they get enough sleep and have stopped eating all the time. Go to bed at the right time, exercise and not skip breakfast and stop eating by 8:00 at night. You don’t even have to use nutraceuticals, if at all. If you don’t care for it. By 4 weeks, she’d lost weight, was already feeling so much better, but she was still having a lot of hot flashes. And so I did add hormones. I used transdermal and you can use the conventional products, but they are and they are bioidentical. And I did all the same things with my lifestyle. I added some nutraceuticals which help with insulin resistance like berberine and chromium, alphalipoic acid, magnesium. I gave a couple of supplements to help her with her sleep, more magnesium and l-theanine, which is a derivative from green tea and a couple of other nutraceuticals. And at 6 months later she lost a ton of weight, she was sleeping well. Her hot flashes had completely resolve and she’d gotten on to a regular exercise program. Everything was better. This is the kind of patient that you can screen and you can treat. When you have patients who have a more severe disease, you can certainly refer out, but you as an OBGYN can now take over the care of many of your patients and certainly screen all of them. Women are going to go through menopause. Many women have PCOS. Most women use birth control pills. They’re going to have altered estrogen production, they’re going to develop metabolic issues. It’s inevitable, but through proper diet, lifestyle and appropriate supplementation, proper screening, you as an OB-GYN can make a monumental difference in the life , the cardiovascular status of all of your women patients. And I thank you so much for joining me today. Thank you so much, Dr. Gersh. What a great presentation. Operator, If you are there, we’ll have you review the instructions for a live question. Audience If you can hang on with us, we did run a little bit late. I know a lot of you have questions, but hang in there with us and we’ll go if it works for you, Dr. Gersh, about 10 minutes more. Yes, I am here. I am so sorry. There’s just so much to cover. Oh, it was fabulous. All right, operator, if you’re there, if you could just review the instructions, I we’ve got lots of questions, Dr. Gersh. So. Operator. We’ll I’m here. Thank you. We’ll now begin the question and answer session. If you would like to ask a question, please press star followed by the number 1. Please, unmute your phone and record your name clearly once you are prompted. To cancel your request, you may press star 2. One moment please for the first question. While we’re waiting to see if there’s any live questions, we’ll just start with a lot of interest about nitric oxide. They’re asking, should you should you prescribe a nitric oxide supplement? If so, which one should be recommended? Great question. Well, first, I just want to start with the natural ways that you can up your production of nitric oxide. So about half the nitric oxide comes from production in the arteries from the endothelial nitric oxide synthase, but the other half comes from the GI tract from what you eat. So if you eat nitrate containing vegetables and the one that gets the most play or beets, but all green leafy vegetables have nitrates in them, and then it combines with the bacteria in your mouth, that’s why having a healthy mouth microbiome is so important because the bacteria in the mouth make these enzymes called reductases, those that convert nitrates to nitrites. And then in the stomach you need to have stomach acid, B-12, magnesium and zinc. And then and further down as well in the GI tract, the nitrites are converted into nitric oxide. So and then it can diffuse out. So eating lots of green leafy vegetables and beets. So I myself have a drink which I make and I’ll give you my recipe. You take 2 large beets, you peel them, they’re raw, and then you take 2 carrots, you peel the carrots and 1 or 2 stalks of celery and ginger to taste. You put it all in like a Vitamix or a very good blender, and you turn it into juice, drink it slowly, mix it with your saliva, and drink a big glass of that every day. And that will help to raise your own nitric oxide production. In terms of supplements, yes, there are nitric oxide supplements that and but what I want you to know is that the ones that you should use are ones that contain l-citrulline. Now, I know that a lot of people think arginine, which is a precursor of nitric oxide, is a good thing to take, but it actually isn’t. It gets broken down by the enzyme arginates it won’t even get into you and it can actually go down other pathways that are not productive or not good. But l-citrulline is recycled into nitric oxide, so any supplement you take to promote nitric oxide production should have l-citrulline and usually some beet extract as well, and often vitamin C, which is also really helpful. And the products, if I can say the products that I use are neo40 which you can also buy online and nitric oxide Ultra, which is a product by pure encapsulation. So those are the ones that I personally implement in my practice. And but you always want to incorporate the nutritional, you know, aspects as well. Thank you so much. One more question that we we got a lot of regarding total cholesterol and lowering inflammation and lowering total total cholesterol. So this one says if a client has over 225 total cholesterol and over 150 ldl-c, should the focus be on lowering inflammation or also lowering total cholesterol? Another great question. So I always get more than just a plain lipid panel, as I mentioned. So I want to look at remember, the total cholesterol is going to look at all different aspects. And if you get just a cholesterol panel, you’re not going to know what their state of oxidation is like. So remember, it’s oxidized LDL that creates problems, not just plain LDL. So I want to know the status of inflammation. Absolutely. I want to know the status of inflammation of that patient. And so I want to know the oxidized LDL status. I want to know all the other inflammation markers, and I want to know their apolipoprotein A1 and their apolipoprotein B. So Apolipoprotein A1 is also known as reverse cholesterol. So it’s actually the particle. Remember, cholesterol never travels by itself. It has to be in a vehicle. It it needs a lipoprotein carrier. So different lipoproteins have different functions and how they manifest in terms of carrying cholesterol around the body. So apolipoprotein A1 is what I call the cleanup crew or reverse cholesterol. It goes out and it picks up cholesterol and returns it to the liver for recycling or disposal down the chute, you know, down the bile duct and into the into the gut. And so very high levels of apolipoprotein A1, which will also translate into a high total cholesterol, are actually wonderful. You want to have high levels. Now, when you have high levels of apolipoprotein B, that’s a sign that your liver is maybe going overboard and making too much cholesterol. Then you have to think, why is it making too much cholesterol? Because that’s a reflection of something. It can be reflection of low thyroid. So check the thyroid. Low thyroid will give you high cholesterol. It can also be a reflection of inflammation. Low estrogen levels or chronic stress. Chronic stress will cause high cholesterol. So you don’t want to just lower cholesterol. That’s very old fashioned. You want to look at why is their cholesterol high and look at the causes like is there chronic inflammation? Maybe the patient isn’t getting adequate sleep, there’s hormonal imbalances, is endocrine disruptors. You know, that’s, you know, high levels of heavy metals or other, you know, environmental toxins. We can have too much pesticides and herbicides. And all of these things we now know are very instrumental in altering our metabolic state. So we want to look at reasons for why cholesterol is elevated. And and it’s not that I’m not against lowering cholesterol, but just doing that by itself without looking at the underlying etiology. You’re missing the boat in this day and age. And there are nutraceuticals like bergamot, which have actually been compared in studies. Of course, they’re very small studies to statins without some of the impact, the negative impacts on muscle health and strength and, you know, pain levels and also on the co-Q10 levels that you don’t get that with bergamot. But these are small studies. But there are some there is some data that bergamot and also berberine can help lower cholesterol without some of the negatives. And and we know that the first line therapy from both the American Heart Association and and all organizations, the American Diabetes Association, all these organizations say first line therapy is lifestyle. So work on lifestyle first before you start adding in the pharmaceuticals and see what you can do. And it’s amazing what you can do. Just like what I did with my patient in that example to lower the inflammatory components that are happening in a woman and then the cholesterol will go down naturally. And and don’t underestimate the value of giving bioidentical estrogen. You know, it’s a it’s controversial. I never want to tell people to do anything that’s controversial, but I’m just giving you my own opinion because I’m allowed to do that, that I do use a lot of bioidentical hormones in my menopausal women. And I see very good results with their lipids. But once again, that’s my own personal experience. Thank you. Operator. Are there any calls on on queue? Yes, ma’am. We have one question from Patricia Fahy. Ma’am, your line is open. Um, you did speak about estrogen and progesterone, but I’m curious about your opinion on testosterone supplementation, particularly when you mentioned PCOS being a high cardiovascular risk. And of course, they also have high levels of testosterone. Many women are getting testosterone treatments and often are being supplemented to very high levels. So I’m curious, I know there’s not many studies done yet, but I’m curious if you have any opinion to know of any current studies that are looking at testosterone in women and cardiovascular disease? Well, in terms polycystic ovary syndrome. So they’ve shown that lowering the testosterone does not improve the cardiovascular cardiometabolic issues of women with PCOS. So the testosterone is more of a an effect then a cause. But it is of course, it’s always hard to, you know, cherry pick through all of these different things. But testosterone is caused in women with PCOS because they have poor production of estradiol in the ovaries because their aromatase is not working properly and their receptors are not working properly, their estrogen receptors. And that drives the increased production of LH that the ovary is trying to make more estrogen, but it can’t. But it drives up the testosterone because testosterone is always the precursor hormone to estradiol. And then when you have this chronic inflammatory state in women with PCOS that drives up IGF1, insulin-like growth factor one, and it turns out that IGF1 also drives the ovary to make more testerone. So it’s like a wicked cycle that causes more testosterone production in women with PCOS, but that is more the consequence than the actual cause of the metabolic dysfunction of women with PCOS. In terms of women in menopause, we absolutely know that testosterone has a has a role. We know more from the lot of data with men. That testosterone, first of all, in part is converted into estrogen as its main benefit. So we know that most organs make their own estrogen in addition to getting estrogen from the peripheral production of the ovary. And that’s actually what keeps women going in menopause is because and that’s what, of course, has children and men getting a lot of estrogen because many organs make estrogen. They have the enzyme aromatase, but they make it all from, of course, the precursor androgens. And when androgens go down in menopause, then women have less ability to make estrogen on site in the different organs that make estrogen. So it’s sort of a double whammy. They make less from their ovaries, of course, but then they also make less estrogen from their organs that make estrogen. And that’s including many, many organs, of course, the brain being a dramatic one. But the heart makes estrogen. And, of course, breasts and lungs and skin to many, many organs. The gut makes estrogen for many organs. It’s not always recognized are making estrogen. That’s how men get it. And men have plenty of estrogen, but it’s not circulating. It’s made on site in the different organs and from androgen. So giving women some testosterone just to bring it into a middle physiologic range is probably protective. But we have much more data in that in men and even in men, it’s still remaining controversial, which is sort of interesting because the basic science data is all there. What we don’t have as a lot of human studies. So my personal this is once again, my personal opinion is that every woman will have a better functioning body if she has physiologic levels of hormones, because we know what hormones do from a scientific perspective. We know that hormones are very key information delivery systems. So I personally do give women I measure the levels of testosterone and I do replace bioidentical testosterone. And it has to be done through compounding because there is no other accessing of testosterone for women. But I don’t give them high levels. I give them just to be sort of in the mid-range of the physiologic level, because that’s how women’s bodies work best. If we think about when is a woman healthiest that she’s around 25 and she has all her normal hormones, that’s when she’s about healthiest. So we know that we’ve done studies with men that if we give men testosterone to be about the levels of a healthy 20 year old male, and he loses belly fat, he thinks better, he feels better. So we don’t have a lot of studies. You’re absolutely right. We don’t have a lot of studies in women, but we have science. And so for those of us who believe in the science and are willing to go ahead and it’s not, you know, standard of care always. And that’s why I’m telling you, this is always my personal opinion that I believe that having women have somewhat as close as we reasonably can, physiologic levels of hormones will help their bodies working in the most physiologic way. Can I ask you what you consider a mid physiologic level? Sure. of testerone for a....? Yeah for one for a typical like reference range for testosterone? It’s like they’re all these ranges are kind of big. So it could be like 10 or 13 up to about 50. So I’m looking around 30. Okay, So I was talking about testosterone supplementation that’s rampant. Anything So in in our part of our country where they they supplement them to the 2 and 300s on a regular basis. Well, I don’t believe that. I don’t believe in giving women do not have normal levels of testosterone in 2 and 300. So I know there are some people that are doing testosterone pellets with very high levels. I am not for that. I am very I’m very simple in my thinking. I think whatever nature does is best. So the best we can do as doctors is to try to give the body what’s designed to have and not to try to create a new norm. Because women do not have normal testosterone levels in the 2 and 300 levels. Thank you. So I’m not looking for that. I am not I’m not that that maverick at all. I, I think trying to mimic nature with the right food, the right sleep and physiologic levels of hormones is is where it’s at.