FAQ Episode 57: Between Head and Heart: how vascular factors identify disease risk, and what to do about it.

Inflammatory Markers, Endothelial Reactivity and Migraine

Nov 20, 2024

Migraine and Cardiovascular Disease: What's the Link and Who's Most at Risk? — Migraine Again

A good part of why managing migraine is difficult is because so many body parts either contribute to or interact with its expression. For this post, we will concentrate more on the vascular, or blood flow compartment of this matrix along with some practical tips on evaluation and therapy options.

Some parts of this post get complex, so those of you who want to “get to the bottom line” may want to skim through and look for the Action Considerations section at the end.

Vascular disease and migraine have an intertwined relationship. Smooth muscle constriction in blood vessels limits downstream oxygen delivery which, when severe enough, is the source of an aura preceding a migraine. In severe enough cases it can even include transient hemiplegia (stroke like symptoms.)

The next step in most migraines is a rebound vasodilation which stretches and provokes surrounding soft tissue to promote the severe pain many experience with a migraine episode. Anything that raises the baseline inflammation of the inner, or endothelial lining of the affected vessels can be part of this root cause factor for recurring migraines.

Both migraine and cardiovascular disease (CVD) are common problems with a similar vascular component for women. Around 20% of women will experience migraine at some point, and CVD is the leading cause of death for women in the US, with some form of it affecting over 40% of the female population-some 60 million women. Measures taken to improve blood flow for migraine can also reap long term benefits for any organ system that likes to run on oxygen.

Can we predict vascular disease?

A recent study published August 2024 in the New England Journal of Medicine1 asked how we could identify long term risk for vascular inflammation by following almost 28,000 women for a 30 year time frame. This article looked at three lab biomarkers for vascular inflammation: a) highly sensitive c-reactive protein (hs-CRP), b) LDL cholesterol and c) Lipoprotein a (also known as Lp(a) ) levels. Each correlates with blood vessel disease, and all three together were an even more potent predictor of long term risk. Let’s do a brief review of each:

Highly sensitivity-CRP
CRP is a liver protein which is produced in response to inflammation in the body. It can be an useful indicator of inflammation, especially in blood vessels. Unfortunately, an elevated level doesn’t pinpoint the underlying source. It could reflect an acute injury or infection vs a chronic condition. During the “COVID years,” as I refer to 2020-2022, I saw CRPs in acutely ill COVID patients that were 10-20 times higher than I’d seen before. This correlated with the immune mediated inflammation that caused the related lung and vascular damage of this infection. Dental infections, a recent bout of ‘flu,’ autoimmune disorders, poorly controlled diabetes, recent trauma, smoking and even a sedentary lifestyle can raise this level. Typical lab values are 0-3, with less than 0.7 being the preferable range.
LDL cholesterol
While cholesterol is often blamed for vascular disease, it is more of a marker than a root cause. Cholesterol is essential for various bodily functions, including hormone production and cell membrane integrity.Subfractions like LDL or Lipoprotein (a) become a potential problems when they are oxidized due to inflammation. Lowering LDL with statin drugs, without managing the factors that lead to inflammation is incomplete therapy. I’ll outline some management strategies later in this post.
Lipoprotein (a)
This is a subtype of the cholestrol family which: 1) makes your blood clot more easily 2) makes it harder for blood clots to break down and 3) promotes inflammation that can make a plaque break open, allowing even more local clotting, and thus potential obstruction. Optimal Lp(a) level is considered to be below 30 mg/dL. Because its hard to change, its not very helpful to test it frequently. But if you’re aware that its elevated, you know to work the other risk factors with a little greater motivation. While there is currently no drug therapy for elevated Lp(a), there are some other avenues that may budge this risk factor some, which will review below.

All three of these tests are easy to get and as one of the study’s authors put it: “We can't treat what we don't measure." Now, we in medicine do that more than we admit…as with hormone support for women, but that’s a topic for another day’s discussion.

What the markers tell us

When all three biomarkers were combined, we find that when compared to women with the lowest levels, women at the highest levels had:

more than a 1.5-times increased associated risk for stroke
more than a three-times increased associated risk for CAD (the cause of heart attacks)

Of the three markers, the highly sensitivity CRP carried the most predictive weight. One reason for this is that the lipoproteins are made far more atherogenic, or “sticky” when they are inflammed, or chemically speaking, when they are oxidized. Elevated hs-CRP is also associated with migraine, especially migraine with aura2 , which is not surprising, as inflammation is one of the foundational root cause factors for migraine headaches.

Elevated Lp(a) is also associated specifically with migraine.3 Lp(a) often has a strong family history of genetic inheritance. Because of this, many doctors won’t order it unless you have a family history of heart attack or stroke, especially at a younger than typical age. You may need to ask for it specifically.

Bottom line: elevated levels of any or all of these tests tell you that you have what was a previously unknown or undefined root cause factor potentially promoting your migraines. Sorry about that. But better to light one candle than curse the darkness, right?

Who should get a check on these blood tests?

For the purpose of this post, there are two groups who should consider getting the three tests mentioned above:

if you have a personal history of migraine, especially with an associated aura. Even more so if you also have known or suspected heart disease.
if you have a family history of migraine, especially if also positive for a family history of heart attack and/or stroke. Even more so if the involved family member was less than age 60 years at the time. You may be carrying risk factors that have not yet been defined, or may not have developed clinical symptoms as of yet.
although this post is focused on women with vascular risk factors, other studies have shown that the correlation is equally applicable to men.

What to do if the markers we’ve discussed are elevated?

Although I’ll also review non-drugs supplements that assist in lowering these markers, the most effective measures are lifestyle modifications that reduce the body’s inflammatory response. Many of these measures are also discussed in my FAQ posts and in greated detail in the Natural Migraine Relief course.

If these changes were so easy to make, we would all be doing them. You can best achieve success with small steps forward over time. I’ve found that the New Year’s Resolution bulletpoint plan for quick success routinely fails to get long term results. Consider the following measures that can reduce the effects of inflammation, and most likely in the process, your migraines as well:

Dietary: your diet can contribute heavily to the inflammatory process. You can reduce this by:
-managing blood sugar and insulin response by avoiding added sugar and refined carbs by avoiding highly processed food. Whole food fruits and vegetables are better choice and can actually reduce the L(a) level some.
-minimize seed oils, which are also common in processed foods. See more details on this in section 6. Lowering LDL cholesterol
Avoid environmental toxins: our food chain is the source of many of these, including:
-antibiotics and steroid hormones in meats
-glyphosate, mycotoxins and heavy metals in grains
Eat fresh, local and organic as often as possible.
Exercise: For most adults, it is impossible to improve your metabolic efficiency and promote weight loss by diet alone. Some level of combined cardio + whole body strength/resistance training are essential for everyone. Physical activity can also help to lower Lipoprotein (a).
Weight loss: the visceral fat you carry (in and around your abdomen) has a chronic low grade inflammatory effect that is above and beyond the obesity associated risks of insulin resistance and progressive glucose intolerence. Losing even 10-15 lbs can make a measureable difference. Do your best to preserve your muscle mass. Those who use the GLP-1 drugs (ozempic, etc.) may find that they lose as much muscle as fat. If you take this route, heed the advice of “start low and go slow.” I know you want results “now,” or at least before that destination wedding this spring. Gradual loss with the strength training to preserve and tone muscle will serve best to lose weight and reduce whole body inflammation.
Stop smoking: Pretty self-explainatory. Its not hard to envision that 400+ oxidized chemicals have a pro-inflammatory effect on the lining of your blood vessels.
Lowering LDL cholesterol: The standard medical approach to anyone with an LDL level of over 100 mg/dL is to promote the use of a statin drug to block the liver’s manufacture of cholesterol, as you can see the following schematic (from a lecture by Dr. Duane Graveline, who has documented concerns about statin side effects):
As you can see, there are five other downstream products, down past the point where statins intervene, in this pathway beside cholesterol Each of these products are critical for specific and beneficial chemistry in healthy cells. Not every person has clinically significant side effects from statin drug use, but many have cumulative deficits that erode quality of life and then basic health function over time. If you want to take a deep dive on concerns about statin drug use, take a look at the article: “The Great Cholesterol Scam and The Dangers of Statins: Exploring the Actual Causes and Treatments of Heart Disease.” If you do use a statin drug, always ask the prescriber for the lowest dose possible, and take CoQ10 200 mg along with it.
A non-drug approach to elevated LDL is to ask if there are specific and treatable reasons for LDL to run high:
1. LDL can act as an antioxidant, and its rise can indicate that is attempting to manage the inflammation induced by an excess of polyunsaturated fatty acids (PUFAs), like linoleic acid. Most of us ingest too many PUFAs from seed oils, and one of the first things to do if your LDL is too high is to identify and reduce the intake of these oils. Common sources include sunflower, grapeseed, peanut, sesame, soybean, canola and corn oils. See the following chart. We want to choose seed oils that have the lowest linoleic acid content.
2. You will also find then in restaurant cooked or fried foods and in many processed snack foods. Since foods using these oils are typically also high in processed grains and sugar, there are multiple reasons to drastically reduce them in your diet. In doing this you can address two of the three markers we have been discussing: cholesterol as LDL, and also the inflammation that drives up the CRP marker.
1. All adrenal hormones have the cholesterol molecule as their base building block. Unfortunately, when adrenal hormone levels are low, the body may respond by increasing the cholesterol level in an effort to force the production of the downstream hormones! Supporting adrenal building blocks like pregnenolone and DHEA, if they are low, can relieve this feedback pressure on cholesterol and LDL levels. You can readily get blood levels for these hormones. Be aware that the typical “normal levels” for these are short of the optimal levels. For instance:
  Typical DHEA-sulphate level = 30-240
  Optimal DHEA-sulphate level = 250-350
  Typical Pregnenolone level = 22-230
  Optimal Pregnenelone level = 200-220
When you have a clinical problem like excess LDL, insufficient adrenal
output, heart disease or migraines, you may need to achieve optimal
levels to clear disease and limit symptoms.
You most likely would benefit from consulting a physician familiar with
this situation to achieve a balance. You can find more details for either
Lesson 17: Hormone Root Cause factors in Migraine: The Adrenal gland
or Lesson 24: Getting another opinion: finding an integrative or
functional medicine minded practitioner by becoming a paid subscriber
for this blog, which includes the entire Natural Migraine Relief for
Women course.
7. Spend healthy time in the sun: Sun exposure stimulates the production of nitric oxide (NO) through the skin. Elevated nitric oxide levels:
-dilate your blood vessels and lowers blood pressure.
-protects the endothelial layers where cumulative damage can occur.
-increases mitochondrial melatonin which improves cellular energy.
This is especially important if you have migraines
Mid morning or afternoon sun is safer, but 15-20 minutes of mid-day sun is okay without sunblock. Be aware that if you have a diet high in seed oils (see the discussion under “6) Lowering LDL cholesterol,” above) that you may more easily experience sun damage. You may need weeks or months of reducing seed oils in the diet to reduce your sun sensitivity.
Optimize your gut health — Poor gut health can lead to systemic inflammation, a risk factor for both vascular disease and migraines. One variant of this is known as leaky gut syndrome, a condition where the epithelial lining of your digestive tract becomes excessively permeable.
This can allow unwanted substances like endotoxins and food antigens to enter your bloodstream, triggering pro-inflammatory immune responses. To address this:
-consider getting a blood test for IgG Food Allergies. If you have definable food antigens getting past the gut barrier, the immune system registers the insult with the level if IgG antibodies it produces. If you don’t limit reactive foods it will make it more difficult to heal any gut barrier disruptions. And if you don’t what to avoid it, its hard to alter your diet effectively. You can get testing done direct-to-consumer with kits like everlywell.com, or done through the office of most integrative minded physicians.
-to bring your gut microbiome back on track and reduce inflammation, incorporate fermented foods, such as grass fed yogurt, sauerkraut, kimchi or kefir into your diet.
-consider taking a high-quality probiotic. Maintaining a diverse and balanced gut microbiome can strengthen intestinal defenses and your overall health.
Beneficial nutrients and supplements to consider:

Curcumin: one of my favorite natural anti-inflammatory therapies. Take 500 mg once or twice a day. Look for a product with “95% curcuminoids” on the ingredients label.
Bromelain: also useful for inflammation, at 500 mg once or twice day, taken apart from meals. If you also have soft tissue inflammation (joints and tendons) this can provide a dual benefit.
French maritime bark extract: also known as brand name “Pycnogenol,” has been shown to positively impact endothelial function by improving blood flow and reducing oxidative stress. When vascular inflammation is a player in heart disease or migraine, improving function in the inner “endothelial layer” is key. Daily dose is 100 mg.
Beet root extract: enhances production of nitric oxide, for relaxation of blood vessels. Caution: this has been know to WORSEN migraines for some people, possibly by initiating the dilation phase of the headache.
Coenzyme Q10 — CoQ10 is a powerful antioxidant essential for cellular energy production, making it particularly beneficial for the cardiac muscles, which have over 5,000 mitochondria per cell (vs 1,000 per most cells.)A study published in the journal Antioxidants (Basel)²⁰ says that CoQ10 helps reduce oxidative stress, lowers the risk of death from cardiovascular causes and improves outcomes in patients undergoing coronary artery bypass surgery.4 It also helps prevent the buildup of oxLDL in arteries, reduce vascular stiffness and high blood pressure, improve endothelial function by cutting down on reactive oxygen species (ROS) and boost NO levels. If you have migraines, or take statin drugs, you should aim for a dose no lower than 200 mg/day.
Magnesium levels: although I have extolled the benefit of magnesium for migraines and heart health for years, I was amazed the first time I learned that there are more than 3,750 magnesium-binding sites on human proteins and more than 500 enzymes in your body that rely on magnesium for optimal function. Unfortunately, it is estimated that ~60%+ of Americans are magnesium depleted. Healthy levels are critical for for normal vasomotor tone, nerve impulse conduction, muscle contraction and reducing inflammation. Several studies, including one in the European Journal of Clinical Nutrition5 found that there is an inverse relationship between levels of magnesium in the body of participants and the level of c-reactive proteins. It concluded that the beneficial effect of magnesium intake on chronic diseases could potentially be explained by the effect the mineral has on inhibiting inflammation. This would include migraine headaches, which is why it is part of the “Basic Four” nutrients that I want everyone with migraine to give a trial. I’ve posted part of my paid course Lesson 6: Integrative Therapy for Migraines for you to give some background and details on “The Basic Four.” Click the Lesson 6 link just above and after reading the first~10 paragraphs you will see the dosing details for those four key nutrients.
If you have either vascular disease or migraine, taking daily magnesium citrate, glycinate or in a chelated form in the 400-600 mg/day dosage range would be a reasonable measure.

Action Considerations:

Consider getting the three tests mentioned initially: a) highly sensitive c-reactive protein, b) LDL cholesterol and c) Lipoprotein (a)
Look through the eight factors (listed above) that can minimize your vascular and migraine risk, and list the ones that apply best to you. Your best bet is several small lifestyle changes consistently applied. Yes, we want results “right away,” but if you have migraines, we are also looking for longer term solutions that have staying power.
Consider which, if any of the nutritional supplements listed in this post may apply to your situation and test results. I would advise starting with just one or two to keep things simple. If you have migraines, I would include the “Basic Four” as mentioned above (see Lesson 6: Integrative Therapy for Migraines.)
Remember that any one provocative element for migraine is almost always a part of a larger matrix of contributing factors as to why you have migraine headaches. You may find that the Natural Migraine Relief course can assist you at finding the most specific non-drug options that best address your individual needs.

Always remember that although I am a physician writing this post, I am not your primary care physician. Please seek advice for your specific medical concerns with your personal physician, and do not quit or change your current medication plans without consulting the prescribing physician.

My hope is that you become an educated custodian of your health, making informed decisions that promote your well-being, in partnership with your trusted medical advisors.

Natural Migraine Relief