Cardiovascular and Metabolic Health in Autoimmune Disease

Key Points & Suggestions for Metabolic and Cardiovascular Health

  1. Obesity can both put a person at greater risk for developing an autoimmune disease and worsen the course of an autoimmune disease once developed. Treatments should be utilized to support individuals with autoimmune disease so that they can lose weight in a healthy manner.
  2. Some of the best measures for assessing adiposity and obesity include body anthropometrics including waist to hip ratio and bioelectrical impedance analysis for body fat percentage.
  3. Blood sugar issues such as hyperglycemia and diabetes exist on a spectrum and it often takes many years to progress from suboptimal blood sugar control and hyperglycemia to diabetes via the process of increasing insulin resistance.
  4. Hyperglycemia can be a primary cause for disturbing the intestinal barrier and gut ecosystem and likely plays a role in the development and progression of autoimmune disease.
  5. The best laboratory measures for assessing blood sugar control include hemoglobin a1c, fasting insulin, HOMA-IR and data from a continuous glucose monitor (CGM). While there are additional markers to consider, the use of these four provides great insight into one’s metabolic health for a reasonable cost.
  6. Atherosclerosis is the pathologic process by which the body responds to damage inside of arteries. Over time this process can lead to the development of obstructing and immunogenic plaque that can compromise blood flow and act as a source of immune reactivity.
  7. Cholesterol is an essential fat carried around the body in various lipoproteins. It can be deposited at sites of blood vessel damage as part of the atherosclerosis process, but it and of itself is not the primary problem in the development of cardiovascular disease.
  8. Small and oxidized low density lipoprotein (LDL) particles appear to have higher potential for initiating and potentiating the atherosclerosis process. Laboratory studies that measure lipoprotein size and number may be critical tools for assessing cardiovascular risk in those with autoimmune disease.
  9. Many autoimmune conditions are associated with increased cardiovascular risk including heart attacks and stroke. The mechanisms behind these associations appear to be related to chronic inflammation that directly impacts blood vessel health as well as lipoprotein metabolism that indirectly affects the atherosclerosis process.
  10. Elevated and dysregulated blood sugar is one of the primary causes of atherosclerosis and thus is interrelated with lipoprotein metabolism and the development of cardiovascular disease.

Introduction to Cardiovascular and Metabolic Health in Autoimmune Disease

For those with autoimmune disease, it is quite easy to focus solely on the autoimmune disease itself, monitoring disease activity through both clinical and laboratory measures. While monitoring a specific autoimmune condition is certainly critical and necessary in order to adequately minimize suffering and improve quality of life, it is all too easy to become so narrowly focused on the disease itself that we miss some of the other critical processes that have become out of balance. Two of the most critical overarching systems that require attention in every individual and perhaps even more so in those with autoimmune disease include the cardiovascular and metabolic systems.

Defining Metabolic and Cardiovascular Health

Metabolic health can be considered the health of an individual’s nutrient partitioning and energy utilization systems. We eat foods every day that contain various macro and micronutrients, and our bodies must use the micronutrients to assist in the metabolization of the macronutrients in order to make cellular energy known as ATP.

Click Here To Learn More About Macronutrients and Micronutrients in Your Diet

One metaphor I commonly give my patients in order to think about these metabolic processes is that of an exchange system. Generally speaking, you can think of the food you eat as a foreign currency when compared to your body’s currency. Your body must take the apple, which we will call US Dollars, and convert it through mechanical and chemical processes to ATP or what we will call Euros. You see, your body can only use Euros (ATP) to carry out cellular processes and must continually perform exchanges using the various macronutrients that we eat such as carbohydrates, proteins and fats in order to function.

As you may already be beginning to see, disturbances to the exchange system will not only lead to compromised exchanges, but also compromised downstream processes in additional cellular pathways. We will explore some of these pathways and potential compromises shortly, but first let’s define our other key term, cardiovascular health.

Cardiovascular health can best be described as the health of an individual’s heart and blood vessels. We have two major types of blood vessels: arteries and veins. Arteries generally carry oxygenated blood to tissues so that they can carry out efficient metabolic processes (our exchange systems) and maximize the production of our cellular currency ATP. Veins generally carry deoxygenated blood after the metabolic processes have occurred so that the blood can be restored with oxygen from the lungs. There are also specialized blood vessels called capillaries that connect these two systems. Capillaries are critical to getting blood into and out of all cells in the body. The heart, as you likely already know, acts as a receiving station for venous blood, as a pumping station to the lungs in order to restore blood oxygen levels and as a pumping station to the rest of the body once the blood has returned from the lungs with restored oxygen levels. In concert, our cardiovascular system functions with our metabolic systems without conscious input.

While we do have conscious overrides whereby we can increase and decrease heart rate (to a certain extent), modulate the activity of blood vessels with things like exercise and breath holding and even prepare the metabolic system by simply thinking about or smelling food, these interconnected systems are primarily autonomous, and oftentimes do not present symptoms of imbalance until things have gone horribly wrong. Preventing such problems and being aware of one’s risk for metabolic and cardiovascular issues is precisely what we are talking about today!

With these definitions set, you may be asking a few questions:

  1. How do I know if I have optimal metabolic and cardiovascular health?
  2. What are the most common metabolic and cardiovascular diseases?
  3. Do I have increased risk for metabolic and cardiovascular disease because I have an autoimmune condition?

We will seek to answer all of these today. First, let’s start with the primary metabolic and cardiovascular diseases.

Metabolic Disorders and Autoimmune Disease

When it comes to assessing issues with metabolic health, one cannot begin or end a discussion without talking about obesity and diabetes. Obesity is defined as excessive adiposity or fat mass for a given height and gender. Body mass index (BMI) has been classically used as a marker of adiposity, however it is only a guesstimate based on a rough formula that does not take into account muscle mass or other body abnormalities that could disturb its accuracy. Measurements such as waist to hip ratio and even bioimpedance devices that estimate fat percentage are typically better tools for adequately assessing adiposity in an individual.

Over the years there has been a concept known as “metabolically healthy obesity” that was theorized as a state where certain obese individuals who did not show signs of disturbed blood sugar or diabetes were considered to be as healthy as those without diabetes who were normal weight (1). With further research in larger populations over longer time periods, it appears that the static definition of “metabolically healthy obesity” may provide a false sense of security, as these individuals do appear at higher risk for premature death and cardiovascular disease when compared to healthy normal weight controls (1,2). When we examine one of the main mechanisms for the development of diabetes, we see that the process indeed takes time, and gradually develops in those with greater adiposity given the various dysregulated signals sent from the excess adipose tissue itself. From this lens, medically speaking, I treat obesity very seriously and while we can accept and love ourselves no matter our body form, I as doctor must support my obese patients in efforts of healthy weight loss even if they are not currently showing signs of elevated blood sugar or diabetes.

Connections Between Autoimmunity and Obesity

When we start to look for connections between autoimmune diseases and obesity, a few things stand out. First, almost all autoimmune diseases are more prevalent in obese indivdiuals as compared to lower weight individuals, with obese indivduals at significantly higher risk for developing many autoimmune diseases (3). When examining the literature, it appears that the associations and risk are strongest for Rheumatoid Arthritis (RA), Multiple Sclerosis (MS), Psoriasis and Psoriatic Arthritis (PsA) with additional associations for Inflammatory Bowel Disease (IBD), Autoimmune Thyroid Disease (Graves and Hashimoto’s) and Type 1 Diabetes (3).

While this type of data and these associations may not appear to be helpful for those already diagnosed with an autoimmune disease, there is additional data showing “obesity worsens the course of RA, SLE (lupus), IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA (3). You see, obesity not only places an individual at higher risk for developing an autoimmune condition, but can worsen the disease course for those with an autoimmune disease and make some treatments less likely to work. This is something we cannot ignore.

Defining Diabetes

When we step beyond obesity, the other major metabolic condition to consider is diabetes. There are two forms of diabetes, Type 1 which is an autoimmune condition affecting the production of insulin and Type 2 which is a complex condition typically characterized by elevated, but less effective insulin. For the sake of this article, when I refer to diabetes I will be referring to Type 2 diabetes. In order to understand diabetes, we need to explore a little physiology and biochemistry involving carbohydrates and sugar.

How the Body Makes Energy From Carbohydrates and Controls Blood Sugar

Carbohydrates are one the primary macromolecules that the body must convert (exchange) through many biochemical processes in order to make ATP. Many of the most common foods we consume contain some level of carbohydrate or sugar. The body has designed an elegant signaling system in order to notify cells when sugar is more plentiful and to take it out of the blood so that the cell can carry out the various energy exchange processes. The primary hormone used as the signal for sugar availability is insulin. After consuming a meal containing carbohydrates, the body will release insulin into the bloodstream in order to signal globally that sugar (glucose) is here and we can exchange glucose for ATP! This process happens very quickly as there are downsides to having high levels of glucose in the blood stream and not in the cells. We will talk more about those a little bit later in the cardiovascular disease section. If the insulin signaling system is working properly, the glucose will rise slightly in the bloodstream as it is absorbed from the gut. Over the course of about 30-90 minutes following a meal, the glucose will be moved from the bloodstream into cells such that the blood returns to its previous level of glucose. At rest, most individuals have a blood glucose level of between 75-95 mg/dL. This may rise to between 120-140 mg/dL after a carbohydrate rich meal, but usually returns to a level between 75-95 mg/dL within 90-120 minutes.

What Can Cause Elevated Blood Sugar?

Now you may be asking, what would cause the blood glucose to go higher than 140 mg/dL after a meal or to not stay between 75-95 mg/dL when one hasn’t recently eaten food? One of the primary reasons this can occur is because one eats a meal that is too high in carbohydrates and or calories at one time. You may be asking, what is too high? I was purposefully vague because, for a given individual, this is extremely variable and depends on a number of factors. To make this even more complicated, we are coming to see that even the exact same food can cause very different blood glucose and insulin responses in two different people. In groundbreaking research, a group from Israel published a paper in Nature in 2015 showing the individualized nature of glycemic response to various foods (4). To make the findings even more compelling, the researchers built a predictive model that connected people’s blood sugar responses with the health of the gut microbiome (4). We will talk a little more about the gut and gut microbiome here shortly. Needless to say, I cannot readily know what foods and carbohydrates may cause your blood sugar to increase to higher than desired levels or to stay elevated even when you have not recently eaten. Generally speaking food lower in carbohydrates or more rich in fiber will not cause large spikes in blood sugar, but the specific responses to individual foods is markedly variable. But small spikes in blood sugar are not that bad are they if I come back to a normal level afterwards, right? Well, we are actually not so sure.

How Elevated Blood Sugar Can Alter Genetic Expression

There is emerging data that elevated blood sugar also known as hyperglycemia can alter genetic expression of various metabolic and inflammatory pathways in cells that remains relatively permanent or “memorized” even after one’s blood sugar has returned to normal levels (5,6). There are theories that this is one of the mechanisms for why blood sugar in diabetics can become very challenging to control or why diabetics develop cardiovascular diseases despite making improvements in their blood sugar.

How Elevated Blood Sugar Affects Gut Permeability and Gut Health

Outside of these epigenetic changes that can occur as a result of hyperglycemia, we are also coming to understand how hyperglycemia affects the health of the gut. In various models, researchers have demonstrated how hyperglycemia can itself lead to pathological intestinal permeability whereby various constituents of the gut lumen can get into the bloodstream leading to a host of negative inflammatory responses (7). As was alluded to in the Nature paper, blood sugar responses to certain foods may be better predicted by the current state of someone’s intestinal barrier and gut microbiome than the food or carbohydrate content of this food itself. This is quite astounding. The connection between metabolic diseases such as diabetes and obesity with disturbances in the gut potentially mediated through vicious cycles of hyperglycemia induced barrier dysfunction and later gut dysbiosis is an emerging area of research that is actively shedding more light behind the multiple layers of dysfunction in patients with metabolic disease (8).

Connecting Hyperglycemia, Gut Health and Autoimmune Disease

Bringing this discussion of diabetes and blood sugar dysregulation to the realm of autoimmunity, we are starting to see that hyperglycemia and elevated blood sugar could be a causative element for the development of intestinal permeability, gut dysbiosis and immune activation, one of the main tenets of Dr. Alessio Fasano’s theory about the development of autoimmunity (9). Hyperglycemia, it then appears, even independent of diabetes, is a worrisome finding and should be explored more thoroughly in those with autoimmune disease. You may now be asking, “What is the difference between hyperglycemia and diabetes?” While medically these may be considered two different entities with two different billing codes, they exist on an interrelated continuum. Let’s examine this further.

The Role of Insulin to Control Blood Sugar

As I shared earlier, insulin is charged with the role of signaling to cells when glucose is available. It should be a quick “on and off” signal with the cells “listening” intently to the insulin signal when presented. If the cell starts to experience increased stress such as with increased caloric intake/energy throughput or begins to be damaged by increased reactive oxygen species (the exhaust of the energy exchange process) it may want to stem the flux of glucose until it has stabilized these disturbances within the cellular environment. In these cases, the cell, even in the presence of insulin, may not take up glucose as readily as when it was in a better state of homeostatic energy balance. The body, seeking to mitigate the risks of keeping sugar circulating in the bloodstream, will then start to increase the amount of insulin released as the original insulin was unable to adequately perform its function, essentially appearing to the body as if it wasn’t even released in the first place. Over time, if this process continues to occur and expands to more and more tissues, we will start to see higher and higher levels of insulin, even in states of fasting when there shouldn’t even be a significant signal from insulin. This overall pathological process is what we call insulin resistance or the development of hyperinsulinemia. It is almost always a precursor to the progression to overt diabetes, where even high levels of insulin cannot keep blood sugars within normal ranges.

This begs the question, are most doctors regularly measuring insulin or using measures of insulin resistance in their patients? How about in those that are overwight and obese? The short answer in both of these cases, sadly, is no.

Instead of wasting time trying to explain why fasting insulin is not a regularly performed lab, I will simply state that, in my opinion, fasting insulin and the associated marker of insulin resistance known as HOMA-IR appear to be some of the most critical markers for assessing metabolic health in normal and obese individuals and can be used in conjunction with someone’s fasting blood sugar to determine the presence of any insulin resistance (10). While measuring fasting insulin and HOMA-IR is certainly a step up from a simple fasting or even post meal blood sugar reading, there is another lab test and emerging technology offering even greater promise for those seeking to better understand their metabolic health.

Continuous Glucose Monitors: A New Way to Track Blood Sugar

Known as a continuous glucose monitor (CGM), these tiny sensors are placed on the skin with a hair-like needle probing into the cellular interstitial fluid just beneath the skin’s surface. With the hair-like needle stabilized just under the skin, it continuously measures one’s level of glucose in the interstitial fluid. While the fluid glucose levels are not precisely the same as blood glucose levels, these continuous readings can be calibrated to reveal trends representing one’s blood sugar readings throughout the day. With this one little device, one can suddenly start to see how one’s blood sugar responds to simply waking up with the first boost of cortisol, to food intake and exercise, and to emotional stressors and poor sleep. Sampling without any need for finger sticks or additional interventions, one is given continuous data that can help show an individual precisely how he or she is responding to the many stimuli in the surrounding environment. As you can see, changes in blood sugar can occur because of so many other things outside of just food, and a simple device such as a CGM can provide one with personalized data regarding one’s blood sugar that was once impossible to obtain.

In my practice currently, I have started to implement the use of CGM’s more routinely with my patients. With each sensor worn over a two-week time period, we can extract a month’s worth of helpful data with just two sensors and essentially painless use. While there are a few options for CGM’s, I am currently using products from Abbott (no relation) within their Freestyle Libre series. When paired with a phone app and software from a company called Nutrisense, you can actually use your smartphone to track your blood sugars real time from the applied sensor. I have even used one of these devices myself in conjunction with the Nutrisense software and it has arguably provided some of the most actionable and critical data to inform my dietary and lifestyle choices. (If you are interested in getting your own CGM from Nutrisense, follow this link to learn more).

Key Points & Suggestions for Metabolic Health

  1. Obesity can both put a person at greater risk for developing an autoimmune disease and worsen the course of an autoimmune disease once developed. Treatments should be utilized to support individuals with autoimmune disease so that they can lose weight in a healthy manner.
  2. Some of the best measures for assessing adiposity and obesity include body anthropometrics including weight to hip ratio and bioelectrical impedance analysis for body fat percentage.
  3. Blood sugar issues such as hyperglycemia and diabetes exist on a spectrum and it often takes many years to progress from suboptimal blood sugar control to diabetes.
  4. Hyperglycemia can be a primary cause for disturbing the intestinal barrier and gut ecosystem and likely plays a role in the development and progression of autoimmune disease.
  5. The best laboratory measures for assessing blood sugar control include hemoglobin a1c, fasting insulin, HOMA-IR and data from a CGM.

Defining Cardiovascular Disease and the Process of Atherosclerosis

Moving away from metabolic diseases and potential laboratory measures of metabolic health, let’s step now into the interrelated world of cardiovascular disease. While cardiovascular disease involves a complex set of processes, the primary pathology and process I will be speaking about today is something known as atherosclerosis. Atherosclerosis is the pathologic process by which the body repairs damage to the inside of arteries, our oxygen carrying blood vessels. I say pathologic as while we have intricate processes to repair damage to our arteries, the process over time can lead to the development of obstructing and immunogenic plaque that can compromise blood flow and act as a source of immune reactivity. Essentially, the body has developed an ideal short term solution to repair blood vessels, that unfortunately can have negative long term consequences. When plaques become so severe or unstable, one can experience complete obstruction of arterial blood flow, thus leaving certain tissues without oxygen and other critical nutrients. The two most problematic conditions associated with these obstructions of blood flow are heart attacks (decreased blood supply to heart tissue) and strokes (decreased blood supply to the brain). The process of atherosclerosis as you can imagine, can affect essentially any artery in the body, with the arteries serving the heart and the brain having the most tragic consequences.

What Exactly Is Cholesterol and What Does It Do?

Many of you at this point are likely thinking, I heard cholesterol is involved in this atherosclerosis process, does “high” cholesterol predispose me to developing this progressive disease? While this could be a topic in its own right for an entire article, the short answer to this question is, not exactly. Cholesterol, you see, is itself a critical component, a critical fat for the body. It is a building block for cell membranes, a precursor to vitamin D and other sex steroids such as estrogen and testosterone. Without cholesterol we wouldn’t survive. It is so critical that even though we can consume it from our diet, our body has a redundant pathway to make cholesterol for the previously described purposes. So how does cholesterol get involved in the atherosclerosis process?

The Role of Lipoproteins in Cardiovascular Health and Disease

Cholesterol is a fat and as such requires specialized proteins to carry it around the blood that is mostly water. These transport proteins are aptly called lipoproteins or “fatty” proteins. Three of the most important lipoproteins in the human body are low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein(a) Lp(a). While these proteins carry fats and fat soluble vitamins outside of cholesterol, medicine has primarily focused on their cholesterol carrying capacity. Ever had a lipid test? Did you have your LDL-C measured? This measurement is a measurement of the amount of cholesterol inside of your LDL particles. HDL-C is a measurement of the amount of cholesterol inside of your HDL particles. When added together with the amount of cholesterol in very low density lipoproteins (VLDL) you will essentially get your total cholesterol. In general LDL-C is higher than HDL-C which is higher than VLDL-C. Go back to a previous lipid panel and add those three numbers up and you should get a number close if not identical to your total cholesterol.

So we have different lipoproteins that carry cholesterol, does each lipoprotein have a different function? Yes they do. In general, LDL particles carry cholesterol to tissues of the body such as to the gonads to make sex steroids, to the skin to make vitamin D, and to tissues in general to build/restore cell membranes. HDL particles generally carry cholesterol back to the liver as part of recycling and the repartitioning process. When we start to think about the process of atherosclerosis and repairing damaged arteries, we see that the LDL particles are intimately involved in this complex response. When we look at the literature, we see that naive or unmodified LDL particles carrying cholesterol do not inherently seem to pose a risk to the atherosclerosis process (11). When these LDL particles begin to change shape or undergo chemical modifications such as oxidation, however, things begin to change rather quickly (11). It appears that oxidized LDL particles act as a pro-inflammatory signal that can lead to a cyclical process of fat deposition in a damaged artery and further forms of repair leading to a permanent disturbance of the artery structure (11). Furthermore, it appears that smaller LDL particles, as compared to larger sized LDL particles, pose an even greater risk in this atherosclerosis propagation process (11). You may then be asking, how do I know if I have small LDL particles or oxidized LDL particles? Does the basic lipid panel or LDL-C tell me anything about that? Sadly it does not. But these tests do exist!

How to Measure Lipoproteins

In order to better understand someone’s lipoprotein metabolism, labs have developed specialized tests for determining the precise number and size of various lipoproteins such as HDL and LDL. Going by slightly different names depending on the lab such as NMR Lipoprofile or Quest’s CardioIQ ® Ion Mobility test, these tests are beginning to shed tremendous light on an individual’s lipoprotein metabolism, arguably supplanting basic lipid profiles. When we start to compare the benefit of a lipoprotein lab assessment versus a basic lipid panel, we see that there are a non-trivial number of individuals who appear to have “normal” findings on the basic lipid panel, but actually have a problematic milieu of small or oxidized LDL particles (12,13). It should be clearly stated, however, that simply having a high number of small LDL particles or oxidized LDL particles does not mean you will develop or already have atherosclerosis. It simply points to greater risk that could be further increased or decreased with other modifiable environmental factors.

Are Individuals with Autoimmune Disease at Higher Risk for Cardiovascular Disease?

Turning our attention to the world of autoimmunity, let us try to answer the question, are those with autoimmune diseases at higher risk for developing atherosclerosis and having adverse events such as heart attacks and strokes?

While it would be impossible to group all autoimmune diseases together and make specific recommendations for those with any autoimmune disease, a few general themes stand out. First, those with certain rheumatologic conditions such as rheumatoid arthritis and lupus appear to be at the highest risk for cardiovascular disease (14,15). In addition, those with psoriatic arthritis and psoriasis also appear to have higher risks for developing cardiovascular disease (16). Those with systemic sclerosis (also known as scleroderma) have a more unique set of cardiovascular pathologies to which they are susceptible, and indeed, require specific cardiometabolic assessment and management (17).

When we start to look at hypothyroidism or Hashimoto’s thyroiditis, things get a little more complicated. First off, it appears important to distinguish between those with Hashimoto’s thyroiditis with normal thyroid hormone levels and those with overt hypothyroidism as there does appear to be differences in risk between these two groups. When we broadly look at hypothyroidism and even subclinical hypothyroidism where an individual’s TSH is increased, but thyroid hormone levels remain normal, individuals are more likely to develop various abnormalities in heart function including arterial damage and atherosclerosis (18). Treatment with replacement medication does appear to mitigate most of these risks and has stronger benefits for those of younger age as the process of atherosclerosis begins in our teenage years and requires many years to progress (18).

While I have obviously not listed every autoimmune disease specifically here regarding its association to cardiovascular disease risk, let’s try to step back to the 30,000 foot view to understand the possible mechanisms why those with autoimmune disease may be at greater risk for cardiovascular disease.

The Role of Chronic Inflammation and Cardiovascular Disease

While it seems obvious, it is important to start this discussion by recognizing the chronic immune dysregulation present in autoimmune disease and the potential for chronic cycles of inflammation. When looking at the literature, it appears that this increase in immune reactivity and inflammation itself can propagate the atherosclerosis process (14,15). If the bloodstream is chronically filled with inflammatory mediators and reactive immune cells, an individual will be at higher risk for atherosclerosis and disease progression. Therefore, even if someone has an autoimmune disease for which the population data suggests a higher risk, if that individual is better able to control one’s disease and thus chronic inflammation, they do not necessarily have an elevated risk compared to the healthy population. This is why understanding one’s potential risks from population level research and then personalizing the assessment based on metabolic and cardiovascular specific testing is so important.

Individuals who follow a whole foods based diet such as the Mediterranean diet and even the Paleolthic diet appear to be at lower risk for cardiovascular disease (19, 20, 21). Additional positive lifestyle habits such as engaging in a moderate level of exercise and even obtaining sufficient sleep appear to all support lowering cardiovascular risk (22). Coupled with the well established goals of avoiding smoking and maintaining normal blood pressure, there is much one can do to mitigate any increased risk that may exist from an underlying autoimmune condition.

The Role of Genetics and Cardiovascular Disease

Now some may still be questioning, but what about family history and genetics, do these play even more critical roles for those with autoimmune disease? When we look at obesity and diabetes, while there are indeed some genetic associations with these conditions, they are actually much more strongly related to lifestyle habits such dietary patterns and exercise. Even when we look at conditions of dyslipidemia or dysregulated cholesterol and lipoprotein metabolism, purely genetic causes for disturbed lipoprotein metabolism is the exception rather than the rule.

The one relative exception behind that statement involves the often forgotten lipoprotein known as Lp(a). Lp(a) is a specialised form of LDL whose levels appear to be strongly associated with genetic predispositions rather than diet or lifestyle. Time and time again I will see patients with optimal expanded lipoprotein and blood sugar indices, but elevated Lp(a). Is an elevated Lp(a) in isolation an issue putting one at higher cardiovascular disease risk? The data is not conclusive, and it can be challenging to piece apart confounding variables such as insulin resistance without diabetes, poor dietary intake, etc, but most of the research points to an increased risk for cardiovascular disease with elevated levels of Lp(a) independent of other lipoprotein levels (23).

Research specific to autoimmune disease and Lp(a) additionally reveals strong associations with elevated levels and increased cardiovascular risk for rheumatologic conditions such as RA, lupus and antiphospholipid syndrome (24). As Lp(a) levels are relatively resistant to dietary and lifestyle changes, screening for elevated levels in individuals with autoimmune disease and a family history of early cardiovascular disease, especially when independent of traditional risk factors like smoking, obesity, and classic dyslipidemia is a reasonable choice. In my practice, given the relative low cost of a Lp(a) test, I have even taken a more liberalized approach to screen for elevated levels in almost all of my patients with a heavy focus on those with autoimmune disease.

Addressing Cardiovascular Disease Upstream

Moving forward this discussion regarding the interrelationship of genetics, blood sugar control and lipoproteins, I want to make one final important point. When we start to examine the pathogenesis of high levels of small LDL particles and damaged or oxidized LDL particles, we see that these outcomes are majoritively downstream of dysregulated blood sugar and chronic inflammation, processes that are highly influenced by diet and lifestyle. While traditional medicine focuses tremendously on directly addressing irregularities of blood cholesterol and lipoproteins with drug based therapies, the majority of issues with elevated LDL particle numbers including small LDL particles can actually be addressed by improving blood sugar control, increasing physical movement and reducing chronic stress.

Understanding which problems are actually downstream versus upstream of a particular issue, allows us to improve cardiovascular health and thus decrease cardiovascular risk as a byproduct of addressing issues with blood sugar and physical activity. While there are no magic bullets to address everyone’s problems, one cannot go wrong by first properly assessing one’s blood sugar control and adiposity in conjunction with one’s dietary intake and exercise patterns with the goal of trying to identify early developing issues before one develops full blown diabetes or gains a significant burden of adipose tissue.

Key Points & Suggestions for Cardiovascular Health

  1. Atherosclerosis is the pathologic process by which the body responds to damage inside of arteries. Over time this process can lead to the development of obstructing and immunogenic plaque that can compromise blood flow and act as a source of immune reactivity.
  2. Cholesterol is an essential fat carried around the body in various lipoproteins. It can be deposited at sites of blood vessel damage as part of the atherosclerosis process, but it and of itself is not the primary problem in the development of cardiovascular disease.
  3. Small and oxidized LDL particles appear to have higher potential for initiating and potentiating the atherosclerosis process. Laboratory studies that measure lipoprotein size and number may be critical tools for assessing cardiovascular risk in those with autoimmune disease.
  4. Many autoimmune conditions are associated with increased cardiovascular risk including heart attacks and stroke. The mechanisms behind these associations appear to be related to chronic inflammation that directly impacts blood vessel health as well as lipoprotein metabolism that indirectly affects the atherosclerosis process.
  5. Elevated and dysregulated blood sugar is one of the primary causes of atherosclerosis and thus is interrelated with lipoprotein metabolism and the development of cardiovascular disease.

Final Thoughts

I hope you have enjoyed this exploration of metabolic cardiovascular health in autoimmune disease. Please refer to the selection of Key Points within each section of the article or at the beginning of the article as they serve as a relative table of contents and summary for what is discussed. In addition I have provided a comprehensive list of readily accessible and affordable lab tests within the realms of metabolic and cardiovascular health. Please share a question or let us know what you think of the article in the comments section. As always we wish you continued success on your health journey!

List of Recommended Lab Tests

  1. CBC + Differential
  2. Hemoglobin a1c
  3. Comprehensive Metabolic Panel
  4. Fasting Insulin
  5. Calculate HOMA-IR from Fasting Insulin and Fasting Glucose: Use Calculator
  6. NMR Lipoprofile or Cardiac IQ ® Ion Mobility Lipoprotein Fractionation + Standard Lipid Panel
  7. Apolipoprotein b (ApoB)
  8. Lipoprotein (a) [Lp(a)]
  9. Continuous Glucose Monitor (Explore Nutrisense to obtain sensors and phone based software)

Accessory Tests

  1. Oxidized LDL
  2. Uric Acid
  3. High sensitivity C-reactive protein (hs-CRP)
  4. Homocysteine

Note: This article and these laboratory recommendations are strictly informational in nature and do not constitute or substitute for professional medical advice. For those interested in pursuing a professional medical relationship in order to obtain described testing, you can visit my clinical website. In addition, it is also important to recognize that seeking to obtain or actually obtaining these labs without medical counsel or from a current medical provider that is unfamiliar with the lab reference ranges or each lab’s relevance to metabolic and cardiovascular health may create more stress and burdens for your health, so I strongly encourage you to only pursue such testing in the setting of a trusting and strong medical relationship.

CLICK TO EXPAND // References

References

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  2. Yeh TL, Chen HH, Tsai SY, Lin CY, Liu SJ, Chien KL. The Relationship between Metabolically Healthy Obesity and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis. J Clin Med. 2019;8(8):1228. Published 2019 Aug 15. doi:10.3390/jcm8081228
  3. Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13(9):981-1000. doi:10.1016/j.autrev.2014.07.00
  4. Zeevi D, Korem T, Zmora N, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079-1094. doi:10.1016/j.cell.2015.11.001
  5. Pirola L, Balcerczyk A, Tothill RW, et al. Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells. Genome Res. 2011;21(10):1601-1615. doi:10.1101/gr.116095.110
  6. Vigorelli V, Resta J, Bianchessi V, et al. Abnormal DNA Methylation Induced by Hyperglycemia Reduces CXCR 4 Gene Expression in CD 34+ Stem Cells. J Am Heart Assoc. 2019;8(9):e010012. doi:10.1161/JAHA.118.01001
  7. Thaiss CA, Levy M, Grosheva I, et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science. 2018;359(6382):1376-1383. doi:10.1126/science.aar3318
  8. Chakaroun RM, Massier L, Kovacs P. Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders?. Nutrients. 2020;12(4):1082. Published 2020 Apr 14. doi:10.3390/nu12041082
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About Rob Abbott, M.D.

Rob Abbott, M.D. is Autoimmune Wellness's resident Medical Advisor. He is medical director and the functional physician for Resilient Roots: Functional and Evolutionary Medicine in Charlottesville, Virginia. He completed his family medicine internship with VCU-Shenandoah Valley in Winchester Virginia and is a graduate of the University of Virginia (U.Va.) School of Medicine where he served as a student ambassador for the U.Va. School of Nursing’s Compassionate Care Initiative, promoting resilience, compassion and self-care. He has completed additional training with the Institute for Functional Medicine, is a Kresser Institute ADAPT Level 1 trained clinician, and is an AIP Certified Coach. Rob approaches medicine from an evolutionary and functional perspective and practices what he calls “spiritually focused and evolutionarily informed functional medicine.” In his free time, Rob enjoys creative expression through writing, sharing blogs, poetry and podcasts through his website amedicinalmind.com.

4 comments

  • Jill Goldman says

    What a thorough, well written, helpful article on an important subject! Thank you so much for this. It will help me as I navigate my health journey.

  • Julie says

    I was told I have metabolic disease and that I have reactive hypoglycemia along with a Hashimoto’s and Celiac diagnosis. I asked my doc if using blood test strips would help me track my sugar levels to help me understand when it’s happening since I can’t sense/feel it well. He said that wouldn’t be very effective since my issue is at a cellular level and wouldn’t be reflected accurately in the strip reading. Would the CGM /Nutrisense provide a better reading? Thank you for your help.

    • Thanks for the message. So from you have described, the CGM and Nutrisense software would indeed give you a much better idea of trends around meals and if your levels are indeed dropping low. While you will need to confirm the initial readings from the CGM with finger stick readings- the glucose strips to calibrate, the CGM will give you the trends up and down where you can see how your body reacts to certain things such as food, sleep, stressful situations, etc.

  • Alex says

    Well written article
    I have been trying to get doctors to pay attention to my inflammation.
    It seems They are not equipped to deal with inflammation caused by metabolic disease and PCOS.

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