C-Reactive Protein and Other Markers of Cardiovascular Risk

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

In 1996, age-adjusted death rates per 100,000 for cardiovascular disease were estimated at 134.6. A great decline in the rate of cardiovascular deaths, historically accounting for over 40 percent of all deaths in the United States from about 1950 to 1986, was attributed largely to complementary approaches in public health. A decline in cigarette smoking, changes in the public diet, with a decrease in consumption of saturated fat (meat and dairy) and transfats (margarines and shortening), and a dramatic improvement in medical care, with improved diagnostics, coronary-care units, emergency medical services, and drugs resulted in a greatly lowered risk for cardiovascular disease. Despite this progress, death from cardiovascular disease continues to be the second leading cause of death behind iatrogenic death (normal health care practice), and the rate for cardiovascular mortality has risen dramatically from 1996 to 2007. By 2015, the greatest cause of death from disease in the U.S. was still heart disease, for both men and women, accounting for about a fourth of all deaths, and 11.3 percent of adults were diagnosed with a heart disease. Finding accurate markers for the disease to determine early risk and then taking the necessary steps to prevent serious heart disease by improving cardiovascular health is very important for all of us.

The Centers for Disease Control and Prevention (CDC) stated at the beginning of the 21st century that, despite medication, over 70 percent of persons with high blood pressure do not have the blood pressure controlled, and death rates for stroke have not declined in the last decade or so. The CDC stated that increased measures of prevention in public health are needed, including environmental strategies, improved public diet, and addressing new or emerging risk factors, such as total homocysteine, fibrinogen and high C-reactive protein, as well as contributing infectious agents such as Helicobacter pylori overgrowth, herpes retrovirus, and Chlamydia pneumoniae (found in over half of the population by age 20 in a 2007 Swedish study). The complex contributors to cardiovascular disease such as bacterial heat shock proteins, endotoxins, and advanced glycation endproducts (AGEs) are also attracting increased attention in public health. While public health experts are loathe to implicate common pharmacological treatments in cardiovascular pathology, this subject has been the focus of much concern as well, after the data surfaced concerning the large number of cardiovascular deaths attributed to Phen-fen weight loss medications, Cox-2 inhibiting non-steroidal anti-inflammatory drugs, and now the cardiovascular risks linked to newer diabetic medications and the complete arena of synthetic hormonal treatments and contraception. Physicians can no longer ignore the cardiovascular risks in treatment, citing the need to keep silent to insure the benefits of overall treatment. A more nuanced approach is increasingly demanded by a public with greater access to information, and integrating Complementary Medicine is finally becoming accepted in standard medicine. There is no simple and single focus in preventing cardiovascular disease, and a more holistic approach is sorely needed.

In the last few decades we have grown somewhat complacent about cardiovascular disease, believing that drugs to control blood pressure and cholesterol will stop cardiovascular disease. These allopathic medications do not stop the underlying array of health problems and dysfunctions that lead to cardiovascular disease and death, though. As new cardiovascular markers, such as C-reactive protein (hs-CRP), high homocysteine, high-sensitivity cardiac troponin T (hs-cTnT), and fibrinogen are recognized, the patient and physician population has looked to an overly simplistic answer, namely, how do I block these dangerous chemicals in the body. Unfortunately, like cholesterol, C-reactive protein, homocysteine, troponin, and fibrinogen are not the villains that we make them out to be, but instead are normal molecules in the body that are essential to health. The excesses of these chemicals are due to the homeostasis of the body being stressed, and simply blocking these chemicals with drugs will not correct the actual underlying problems. What we need to learn how to do is to correct the causes of high cholesterol, lipid imbalance, high blood pressure, high C-reactive protein (CRP), high homocysteine level, high troponin T, and excess fibrinogen. This requires a more comprehensive approach, and the need to intelligently integrate Complementary Medicine and TCM to achieve the goals. In 2007, the age-adjusted death rate from cardiovascular disease was 190.9 per 100,000, a significant increase from 1996, and the public, as well as the medical community, needs to address this health concern. In 2011, the U.S. CDC reported that deaths from heart disease and stroke had dropped to 168 per 100,000, still much higher than in 1996, mainly due to increased drops in cigarette smoking and improvements in the public diet in recent years, but much more can be achieved if we pay attention to what these new markers for cardiovascular disease tell us about the underlying health problems we face. A continued focus on failed pharmaceutical strategies with blood pressure and cholesterol control will not achieve the goal of reduction of our greatest health risk, cardiovascular disease.

Cardiovascular risk refers to the many factors that increase your risk of having a stroke, heart attack, congestive heart failure, sudden cardiac death or other life threatening problem with the heart and blood vessel integrity. Since cardiovascular disease is the leading cause of death in the United States, after iatrogenic cause and motor vehicle accidents, this is a big concern for everyone. Family history, diabetes, obesity and aging are the most important risk factors, but atherosclerotic plaques and poorly maintained health of the blood vessels have been a big focus in modern holistic medicine. More detailed research has found that this accumulation of plaque on the artery walls has more to do with inflammation and scarring than it has to do with simple levels of total cholesterol in the blood. While cholesterol and lipids are part of the accumulation in plaque, inflammatory and clotting chemicals are a more important part of the mechanism of plaque buildup, as is the accumulation of calcium, or calcification, and CRP is an important marker of this chronic inflammatory stress. Advanced glycation endproducts (AGEs) are also now known to be integral to the formation of atherosclerotic plaques. These unhealthy sugar protein and fat complexes are primarily a result of the modern diet and commercial foods, but are also formed in our bodies due to modern physiological stresses and environmental toxins. C-reactive protein is an important marker of excess inflammatory dysfunction, and along with the advanced glycation endproduct A1C, the protein enzyme troponin, and homocysteine levels, we are now able to assess cardiovascular risk more intelligently. The problem with this improved cardiovascular risk assessment is what to do to decrease this risk.

Since about 1985, modern medicine has focused on decreasing cardiovascular risk primarily by lowering cholesterol and blood pressure. While these factors were important in the early understanding of cardiovascular risk, our knowledge of this subject now far exceeds these early findings. Simple levels of total cholesterol bound to our circulating lipids, and chronic elevated blood pressure, are now known to be less important to avoidance of stroke and heart attack than inflammatory and metabolic stress. The problem is that the pharmaceutical industry has devoted so much money to products to decrease cholesterol and blood pressure, and these products are now the biggest money makers in the the industry, that profit has once again defeated logic, and public health considerations, in the field of implementing scientific advances on the subject of actually decreasing cardiovascular risk. Cholesterol is just one of the materials that accumulate in atherosclerotic plaque, and mild hypertension will not cause a stroke or heart attack unless the arteries themselves are unhealthy. The sensible modern patient and physician will focus on healthy arteries and reduction of the mechanisms that cause atherosclerotic plaque as the most important health concerns in preventing future stroke and heart attack. For example, high homocysteine levels have been decidedly linked to higher cardiovascular risk, and various cardiovascular diseases, for decades, but indicate that this high homocysteine is a marker for impaired endothelial function in blood vessel membranes, oxidation of low density lipids (LDL), inflammatory processes on the blood vessel membranes, poor lipid metabolism, thrombotic tendency and poor platelet health. These issues are not addressed by taking the current array of cardiovascular medications. They also will not be addressed by too simplistic of a strategy with nutritional supplements. A more professional holistic approach is needed in cardiovascular disease prevention, and Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) has to be a part of this new strategy.

To demonstrate how effective these newer biomarkers of cardiovascular risk are, a February 8, 2011 article the Journal of the American Medical Association (JAMA) reported that a long-term study at Mount Sinai Cardiovascular Institute in New York found that elevated levels of cardiac enzymes creatine kinase or troponin, measured in the first 24 hours after coronary artery bypass surgery, was a clear indicator of early, intermediate, and long-term risk of cardiovascular death. This data was collected from about 19,000 patients in 7 randomized studies, with follow-up varying from 3 to 5 years, and clearly identifies risk factors other than high cholesterol that determine the most significant underlying health problems. To better understand the implications of these findings, read further in this article so see how Complementary and Integrative Medicine (CIM/TCM) can improve the underlying health problems that are most important in cardiovascular disease. While the subject of inflammatory and metabolic dysfunction, and healthy maintenance of blood vessel epithelium can be daunting to the patient, some knowledge of our physiology and anatomy can be life-saving.

Since 2003, a number of scientific discoveries have elucidated the subject of cardiovascular risk. Just when the majority of Americans became comfortable with the notion that high cholesterol, sustained high blood pressure, aging and weight gain were the only things to worry about, studies showed that there were more accurate test indicators for risk. The trouble now for patients is to understand just what these markers mean to their own individual health and what to do about it. The first step is to demand that these more accurate markers for cardiovascular risk are assessed in laboratory blood tests. Troponin, CRP, A1C, homocysteine, IL-6, PAI, P-selectin, E-selectin, LMWF factor 7, and antibody to oxidized LDL may all be assessed for a complete analysis, but at least CRP, A1C, homocysteine and troponin should be tested, and an honest evaluation of the results discussed with your physicians. While the MD may suggest drug prescription within his scope of knowledge, the Complementary Medicine physicians, such as the Licensed Acupuncturist and herbalist (L.Ac.), may suggest specific herbal and nutrient medicines that would apply to these risk factors, as part of an individualized and synergistic treatment protocol that addresses the underlying health problems which create these markers of cardiovascular disease. These strategies should be integrated intelligently. As current science progresses, so does the quality of care in evidence-based Complementary and Integrative Medicine. The first step in this process is for the patient to become educated to these various risk factors and understand the implications. Consulting with a knowledgeable Licensed Acupuncturist and herbalist, or a Naturopathic Physician, will help dramatically to achieve this pro-active goal in preventing future cardiovascular disease and mortality.

For many Americans, the healthy choice for decreasing cardiovascular risk has been to try safe conservative methods first, and then, if necessary, resort to long term use of drugs. Drugs to reduce high blood pressure, lipid cholesterol imbalance, and metabolic syndrome may also be used for a shorter period of time if the proper steps are taken to improve underlying health, thus reducing long-term adverse health effects, or side effects, or these medications. Integration of professional guidance and holistic treatment is essential.

Many patients are deciding to try to do the things to regain a healthy metabolism and then try going off of these statins and beta-adrenergic inhibitors, etc. that are now so routinely prescribed to reduce cardiovascular risk. The risks and side effects of long term use of drugs themselves are alarming to many, and often times even to the prescribing medical doctors in recent years. Complementary Medicine offers the patient much help to intelligently and effectively improve the underlying health and regain a healthy metabolic homeostasis. Chronic inflammatory stress is another chief concern, and one which can be dealt with in a systematic manner. Decreasing lipid cholesterols and high blood pressure a little has not reduced cardiovascular deaths in the United States appreciably, yet we now hold a widespread belief that this is all we need to do to accomplish the task. The actual benefits of these common drugs for patients with mildly elevated, or fluctuating, lipid cholesterols and blood pressure, are very small. The search for a better understanding of the real mechanisms of cardiovascular risk has come up with such interesting findings as C-reactive protein (CRP). Along with this indicator, or marker protein, are other important markers, such as protein BNP (brain natriuretic peptide), and high homocysteine, which have been found to perhaps be better indicators of cardiovascular risk than cholesterol counts because they point to the real culprits. Advanced glycation endproducts (AGEs), such as A1C, are also becoming important markers of atherosclerotic risk and cardiovascular disease, and are now routinely tested to diagnose type 2 diabetes or Metabolic Syndrome. It has been shown that chronic use of statin drugs both advances Metabolic Syndrome to a state of diabetes and artificially raises the A1C index. How to respond to these new findings of cardiovascular risk when they occur, with healthy choices of diet, lifestyle, nutrient supplements, herbs and Complementary Medicine, is now a new and confusing subject for many individuals, as well as their M.D, and consulting a professional CIM/TCM physician is needed. The array of new information is dizzying, even for those professionals that deal with this subject every day at work. Choosing the knowledgeable medical specialists and integrating care with a knowledgeable Complementary Medicine physician, such as a Licensed Acupuncturist and herbalist, is the ticket for success.

The list of markers for cardiovascular inflammation include not only C-reactive protein (CRP) and advanced glycation endproducts (A1C), but interleukin (IL-6), fibrinogen (LMWF factor VII), fibrinolytic factors (PAI) endothelial platelet activators (P-selectin, von Willebrand factor), and antibody to oxidized low density lipoprotein. All of these inflammatory markers are potential indicators of excess cardiovascular inflammatory and atherosclerotic risk. The days of believing that simple control of blood pressure and total cholesterol will insure prevention of stroke and heart attack are over. A complete and holistic regimen to restore the whole health picture and decrease chronic inflammation and oxidative stress is necessary. The way to achieve this is not with a magic pill, but with a sensible holistic health regimen, utilizing Complementary Medicine and professional holistic health care. Some of these markers of cardiovascular disease are emerging as markers for other common health problems as well. For instance, CRP and IL-6 are now highly associated with a high percentage of patients diagnosed with depression, and the link between innate immunological dysfunctions and a variety of common disease mechanisms is emerging.

In 2009, a meta-review of scientific study of a low-glycemic diet by the University of Toronto found that such a diet, with a predominance of whole foods and grains and natural sweeteners, and avoidance of processed foods and sugars, were found to dramatically reduce CRP (C-reactive protein), aid in weight control, promote healthy HDL-C (high density lipoprotein cholesterol), and decrease cardiovascular risk. A study of 80 patients with a high BMI (body mass index, or ratio of fat to muscle) who were given a low-glycemic diet for just 28 days, then switched to a high-glycemic diet for 28 days acquired a significantly higher CRP marker, which was lowered significantly when they ate a low-glycemic diet. Dietary regimens are proven to be more important than drug regimens to prevent cardiovascular disease. Integrating dietary and lifestyle changes with short courses of professional guidance, acupuncture and an individualized herbal and nutrient protocol will achieve the success we need to finally decrease cardiovascular disease and mortality considerably.

This article will help to explain how a holistic approach to your health, and a number of key nutrients, may address the subject of cardiovascular risk. The nutrients studied include Vitamins B2, B6, B12, folic acid, Vitamins E, C, Taurine, CoQ10, SAMe, and omega-3 essential fatty acids EPA and DHA, as well as AGE reducing P5P, B1 thiamine, L-Carnosine, N-acetyl cysteine, and ALA (alpha lipoic acid). A separate article on this website deals with the subject of advanced glycation endproducts (AGEs) and the maintenance of healthy AGE receptors (RAGE). Which of these nutrient supplements to incorporate into treatment protocol, when and for how long, are questions best left to the Complementary Medicine physician, such as a Licensed Acupuncturist, who is also able to integrate herbal medicine and acupuncture to synergistically achieve better effects. Much research supports a wide variety of herbs to achieve a variety of goals in cardiovascular protection. Understanding is the first step to a healthy protocol and better quality of life and disease prevention. This article is one small contribution to this understanding.

Markers of cardiovascular disease and underlying health problems

Testing for cardiovascular risk is now much easier and cheaper than in the past. With the development of saliva and veinous blood stick testing by such esteemed labs as ZRT (Zava Research Technologies) in Portland, Oregon, samples can be collected by the patient and sent to the lab for analysis. ZRT conducts a cardiometabolic assessment utilizing hs-CRP, A1C, fasting insulin, fasting triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, and VLDL cholesterol, and provides an expert individualized analysis of the cardiometabolic profile that guides integrative protocol in treatment. Such testing has become a great tool for the Complementary Medicine physician, such as the Licensed Acupuncturist and herbalist, or Naturopathic physician. Instead of the standard blood tests, this panel will reveal how the body is utilizing these important markers, and the overall holistic assessment of these factors will suggest the direction of therapeutic protocol, with more focused use of herbal and nutrient formulas, individual herbs and nutrient chemicals, and even acupuncture, as well as dietary changes.

  • CRP, or C-reactive protein: this protein is produced mainly in the liver in response to acute or chronic inflammatory stress, and chemical signals from fat cells and immune macrophages stimulate increased production. CRP is not a pathological protein, but is part of the complex complement immune response to pathogens and excessive inflammatory stress. A wide range of conditions will stimulate increased CRP, and CRP alone does not diagnose a disease, but chronically elevated CRP is a strong marker for cardiovascular risk, atherosclerosis, and insulin resistant metabolic syndrome. High CRP levels are also seen in a majority of patients diagnosed with a depressive mood disorder. CRP mainly binds to unhealthy membrane cells to stimulate an immune complement response guided by antibodies to clear old dysfunctional and dead cells so that new healthy cells may grow and replace them. A number of herbs have been shown to be associated with reduction of CRP levels, such as Rehmannia glutinosa (Sheng di huang), and more research is underway to provide proof of the positive cardio-protective effects of herbs. The combination of American ginseng (Xi yang shen), wild rhubarb root (Da huang), and Trichosanthes kirilowii (Gua lou ren) has also been shown to reduce CRP significantly in animal studies, and such research will aid the formulation of cardioprotective Chinese herbal formulas in the future.
  • A1C, or glycosylated/glycated hemoglobin: this advanced glycation or glycosylation endproduct (AGE) is conjugated with hemoglobin, the iron-containing metalloprotein in our red blood cells, and is formed by exposure of hemoglobin to excess glycation, the bonding of a protein or lipid with a sugar. Glycation occurs without an enzyme controlling the process, while glycosylation occurs with enzymatic control. Fructose, and especially high fructose corn syrup, now the most common of industrial sugars, are highly associated with glycation endproducts. Fructose and galactose (milk sugar) have ten times the glycation activity of glucose. While A1C is a marker for high blood sugar, or glucose, it is also an indicator that excess of unhealthy AGEs are present, and is an accurate indicator of cardiovascular risk and atherosclerosis.
  • Troponin: both troponin and creatine kinase are accurate markers for cardiovascular disease, but unlike CRP and the selectins, these are markers of ill health of the tissues with calcification and the heart muscles. Troponin is the protein that calcium binds to to regulate the contractability of both heart and skeletal muscles. When calcification, or accumulation of calcium molecules, occurs, or when cardiac muscle cells are unhealthy or die, higher levels of troponin are seen in blood circulation.
  • P-selectin and E-selectin: P-selectin is a protein that functions as a cell-adhesion molecule on activated endothelial cells that line the inner membrane of blood vessels, as well as activated platelets. P-selectin plays an essential role in recruiting white blood cells (leukocytes) to areas of inflammation on these arterial walls, especially when histamine or thrombin activate the cells, as in atherosclerosis. E-selectin, or endothelial-leukocyte adhesion molecule, is similar to P-selectin, but is activated by immune cytokines, such as IL-6. E-selectin is associated with lectins, and a number of plant sterols, sometimes called phytoestrogens, such as genistein, daidzein and formononetin (red clover isoflavone), have been found to reduce E-selectin. Herbal and nutrient formulas that aid clearing of excess lectins, or provide phytosterols, are thus able to benefit the patient with chronic overexpression of E-selectin. P-selectin, unlike E-selectin, is stored in the cardiovascular membrane cells, and plays a major role in stimulating increased E-selectin responses. Both of these chemicals are also linked to cancer metastasis. Certain cytokines that are highly associated with chronic inflammatory disease, such as tumor necrosing factor-alpha (TNF-alpha), and IL-1 (interleukin-1) are known to stimulate increased E-selectin expression as well.
  • Fibrinogen: fibrinogen is a blood plasma glycoprotein that is synthesized as needed in the liver and converted by thrombin to fibrin during the blood coagulation, or clotting process. Fibrin is a good marker for cardiovascular disease and can be measured in venous blood, with just simple veinous blood stick and blotter samples, making this a potentially useful tool in assessing cardiovascular risk in the future. Excess fibrins may be cleared with select proteolytic enzymes, such as nattokinase and serratopeptidase.

Patient Knowledge is the Key to a Pro-Active Approach, and CRP and BNP Must be Understood for the Patient to Make the Right Choices

CRP, or C-reactive protein is a protein produced in the liver in response to inflammation or injury, and is an indicator of what we might call 'blood heat', which indicates inflammatory responses that are associated with the atherosclerotic changes and chronic injury and scarring of the arterial walls. CRP itself is not a negative health problem, but points to a developing problem that should be taken care of. CRP is also called hs-CRP, or highly sensitive C-reactive protein, because it is a sensitive indicator of possible arterial inflammation in response to unhealthy arterial walls.

Physiologically, CRP binds to the surface of old or dying cells on our membranes, especially blood vessel membranes, or epithelium, and activates the complement immune responses to clear these unhealthy cells and prompt regrowth of new healthy cells. CRP mainly works by prompting antibodies such as IgG and IgM to regulate the pro-inflammatory processes to destroy these unhealthy cells more efficiently, via the complement C1Q complex. C1Q is a complex protein regulator that resembles collagen fibrins. While CRP was first identified as an acute phase inflammatory regulator, we now know that the liver produces chronically elevated levels of CRP when the blood vessel walls become unhealthy. Chronically elevated CRP is a sign that we need to work harder to help our bodies clear unhealthy vascular epithelium and replace it with healthy cells and tissues. Elevated CRP is a clear sign that the patient is at increased risk of not only cardiovascular disease, but also diabetes and hypertension. While we might assume that this inflammatory marker should indicate other inflammatory diseases, CRP is seldom elevated in many chronic inflammatory autoimmune diseases, such as dermatomyositis, scleroderma and polymyositis. It appears the chronically elevated CRP is most related to the gradual development of atherosclerotic plaques on arterial walls.

Many factors may be involved in irritations of the arterial walls. Arterial plaques accumulate at these inflamed or scarred areas to try to repair this damage and to make the arterial wall thick so that it won't burst and cause a stroke or heart attack. Unfortunately, this process often isn't helped by our lifestyle and diet, and instead of a healthy repair, we acquire a thickening that can lead to a thrombus, or circulating blood clot, or narrowing, called stenosis. When this thrombus is large and breaks off into our circulation it can stop critical blood flow, in the brain (stroke or TIA), heart (heart attack) or lung (pulmonary embolism). Even a person that is trying to be healthy may not have a totally healthy immune inflammatory response. Reducing cholesterol may not have the protective result that we need. What we need to do is to correct the repair mechanism of our tissues, which is the inflammatory system, and to stop whatever we are doing that is causing the irritation of the blood vessel walls.

A large study by the Harvard School of Public Health, of over 700 nurses, showed that those nurses in the highest quartile of trans fat consumption had blood levels of CRP that were 73 percent higher than those in the lower quartile (Lopez-Garcia et al; Journal of Nutrition 135(3):562-6). A follow-up study at Harvard showed that women with a deficiency of magnesium in the diet generally had higher levels of circulating CRP and E-selectin, a cell adhesion molecule activated by inflammatory immune cytokines that is expressed only on endothelial cells such as arterial membranes in response to chronic inflammation. Such studies show how improved dietary habits, such as avoidance of fast foods, processed foods, and margarine, and incorporation of healthy sources of magnesium, such as sea salt, beans, steel-cut oats, flax seed, and poppy seeds, are important to maintain cardiovascular health. A complete array of such healthy choices should be incorporated into the patient diet and lifestyle. More importantly, a short course of treatment from a Complementary Medicine physician, such as a Licensed Acupuncturist and herbalist, or a Naturopathic physician should be utilized to acutely correct the problem when these cardiovascular markers show that health problems exist.

High C-reactive protein (CRP) levels indicate that we should take a more comprehensive look at our healthy choices, and perhaps seek some professional help in Complementary Medicine to understand and achieve our goals. CRP is associated with insulin resistance, obesity, cardiovascular disease, hypertension, high triglycerides, tissue plasminogen activator, and cellular fibronectin (Yudkin, Stehouwer, Coppack 1998), and even thin patients may be experiencing insulin resistance. Reducing CRP in excess, and the associated health problems is important. Clearing irritants from the blood and improving our inflammatory regulation is the key to this process. While cigarette smoke is a known source of blood irritants linked to cardiovascular inflammation, many chemicals in our environment and food may get into the blood to cause vessel scarring as well. Our liver tries to detoxify the blood before they circulate and cause damage. Unfortunately, if our gastrointestinal health is a problem, these toxins may enter the bloodstream instead of going, via the portal system, straight to the liver. This is called Leaky Gut Syndrome, and often happens if the stomach and small intestine function is not completely healthy, such as with acid regurgitation, IBS, etc. Addressing issues of gastrointestinal dysfunction and liver health, improving the glutathione metabolism, gastric hypofunction, and celiac disease, for instance, may play an important role in cardiovascular health maintenance. Overgrowth of Helicobacter pylori (H. pylori), a symbiotic bacteria in the stomach, is often associated with gastric dysfunction and IBS syndromes, and is associated with increased cardiovascular risk as well.

While most of us are now aware that scientific study has found strong links between obesity, Metabolic Syndrome, and cardiovascular disease, we may not be aware of the reasons for these comorbidities. C-reactive protein has been linked to obesity and Metabolic Syndrome directly. An article published in Nature Medicine in 2006 (cited below in information resources) revealed that scientists found that induction of leptin resistance, a key aspect of Metabolic Syndrome and obesity, may occur through direct interaction of high C-reactive protein (CRP) with leptin. Leptin and resistin are hormones secreted by our fat cells that act as inflammatory mediators, and leptin levels are highly linked to insulin resistance at fat cell receptors. A variety of leptin-interacting regulatory proteins in circulation have now been identified, but one of the most important of these proteins is CRP. These studies also found that concentration of leptin can stimulate increased expression of CRP in the liver. When increased fatty liver, adiposity, and Metabolic Syndrome, or insulin resistance, is evident, dietary changes, improvement in liver health, and resolution of leptin resistance and excess circulating leptin levels is thus important not only to weight loss, diabetes, and obesity, but also to decrease in cardiovascular risk. A number of herbal chemicals and patented herbal and nutrient formulas have been heavily researched at University Medical Colleges, such as Leptin X, to reduce circulating leptin levels. Leptin X utilizes high viscosity polysaccharides from the herb acacia with esterified fatty acids. Of course, with such complex physiological imbalances, a holistic protocol may be needed to address the whole cycle of dysfunction. To understand more about leptin, insulin, adiponectin, and resistin, hormonal and inflammatory mediating chemicals secreted by our cells, go to the article on this website entitled Insulin resistance.

Allergies may also be a problem. If too many allergens from food or air circulate in our blood, allergic reactions may result in inflammatory scarring. While allergic medications may quiet symptoms, they will not adequately prevent this allergic mechanism. Excessive microbes, such as bacteria or fungi, or yeast and viruses, may get into our circulation too often to also cause inflammatory reactions. Systemic infections such as candidiasis are carried in our blood vessels and can have a negative effect on cardiovascular health and maintenance. Hypersensitivity reactions and chronic inflammation then occur, which puts much stress on our cardiovascular maintenance as well.

If the liver is not functioning optimally, the ability to clear toxins, microbes, allergens etc. from the blood may not be strong enough to protect us. Liver function is stressed by too much work or insufficient nutrients. Excess use of medications that must be processed by the liver, excess alcohol consumption, nervous stress, chronic muscle tissue inflammation, hormonal deficiencies, etc. are reasons that the liver is working too hard. Since the liver is mainly responsible for converting fats and proteins to sugars and vice versa, metabolic syndromes may be causing too much work for the liver. Nutrients such as essential fatty acids, antioxidants, bioflavonoids etc. may be deficient, hindering the liver processes. The word essential means that we must get these nutrients in our diet. Our liver and other tissues can't manufacture enough of them. Since essential fatty acids are key components in the making of inflammatory regulating chemicals, this is an important subject.

Essential Fatty Acids and Other Nutrients Key to Inflammatory Healing of Arterial Walls, Reduction of Atherosclerotic Plaques, and a Healthy Heart

Studies in Europe have shown that the increased intake of healthy essential fatty acids both prevented cardiovascular disease and resulted in much longer survivability for patients after a heart attack. Since beneficial essential fatty acids are highly associated with inflammatory regulation, this is a key ingredient to take when high CRP levels are noted. High levels of inflammatory leukotrienes, platelet activating factor and reactive oxidants in blood leukocytes of patients with high cholesterol suggest that these inflammatory mechanisms explain why atherosclerotic plaque forms more easily in patients with high cholesterol. On the other hand, a 2006 Angioplasty study by the National Heart Lung and Blood Institute found that angioplasty 3-28 days after a heart attack did not benefit the patients and instead had a risk of harm. Understanding how real changes in the diet, incorporating an array of healthy fats, such as fresh nuts and seeds, unprocessed oils such as olive, walnut and coconut, avocados, yoghurt, legumes, beans and whole grains, may benefit cardiovascular health and your metabolism, is important. What is overlooked in healthy essential fatty acid metabolism is that we need a balance of the main types of essential fatty acids, commonly called omega-3, omega-6 and omega-9. While research has shown that the typical modern American diet rich in red meat, simple carbohydrates and processed foods produces a deficiency in the omega-3 types, we cannot treat all individuals with a one-size-fits-all approach. This is not realistic or true.

Fatty acids are the components of fat that define their melting points, texture and flavor. Saturated fats have a higher melting point, keep solid easier, and don't oxidize or go rancid as quickly. The food industry uses these fats to lengthen shelf-life of commercial foods, and has created trans-fats, or converted unsaturated fats, to act like saturated fats in this regard. Trans fat is neither an essential fatty acid, nor is it at all healthy, and is directly associated with increased CRP and E-selectin, markers of cardiovascular inflammation. It is now used in most commercial products. Examples of trans fat include margarine, shortening, partially hydrogenated vegetable oils, and stearic acid in animal fat, such as lard. Avoidance of trans fats is thus very important.

Saturated fat comes mainly from red meat and dairy but also from some commercial fats, such as coconut, palm and cottonseed oils. Saturated fats are linked to atherosclerosis and heart disease in a number of studies. The World Health Organization has determined that there is convincing evidence of certain saturated fatty acids increasing risk or probability of cardiovascular disease. These are palmitic, myristic and lauric acids, found predominantly in beef, dark chocolate, salmon, butter, eggs, processed coconut, palm and soy oils. Merely adding more farmed salmon to the diet is not enough to improve the balance of essential fatty acids. Adopting a plant-based diet with healthy oils, whole grains and beans, and an array of fresh vegetables, is most important.

The bottom line is that fresh whole food is necessary to get beneficial essential fatty acids from the diet and whole grains, beans, legumes, nut and seed oils, fish and vegetables are the principal sources. To supplement, algaes such as spirulina, chlorella and blue-green algae, found in health superfood drinks, and nutritional supplements such as krill oil and black currant seed oil, also supply significant doses of essential omega 3 and 6 fatty acids.

Everyone has heard of omega-3 and omega-6 fatty acids by now, but who really has a basic understanding of this subject? Here are a few key points. The modern American diet has changed and with it a drastic increase in cardiovascular deaths have occured, linked to a decrease in consumption of healthy essential fatty acids. Various essential fatty acids are needed to produce hormone-like substances in our bodies called prostaglandins (PG) that play an important role in regulation of cellular processes of all kinds, but especially in regulating inflammatory processes. Two types of essential fatty acid are often deficient in our bodies in relation to arachidonic acid: linolenic and linoleic acids, which produce PGE3 and PGE1. Omega-3 and Omega-6 fatty acids are names for linolenic and linoleic acids respectively, as well as other fatty acids, such as EPA and DHA (omega 3). Arachidonic acid, also an omega-6, produces PGE2, and is primarily derived from red or fatty meats. Linolenic and linoleic acids (omega 3 and 6) are primarily obtained from whole grains, nuts, seeds, fish and vegetables.

"Omega-3 essential fatty acids are proven to both produce the needed inflammatory mediators but also to help reduce the effects of harmful fat and cholesterol accumulations. Besides a diet rich in fresh whole grains, beans, legumes, nuts, seeds, fish and vegetables, a supplement of Omega-3 may be recommended. The most concentrated supplement, which also contains a natural preservative to prevent oxidation and rancidity, is krill oil, very high in EPA and DHA, which the body may not be able to synthesize sufficiently in certain circumstances."

Other nutrients that reduce the cholesterol and fat accumulations in the arteries are lecithin (found in most legumes, and soy), niacin, choline and Vitamins E and C. Studies have shown that simple increases in Vitamins E and C resulted in about 30% reduction of CRP levels, the same results seen with studies of Crestor (Free Radical Medicine and Biology Oct. 10, 2008; American Journal Clinical Nutrition 86:1392:2007). Whole grain and vegetable fiber helps to reduce blood lipids, and bitter grains, such as rye, quinoa, amaranth and oats (steel cut) are most helpful in cleansing arteries. Paul Pritchford, the author of Healing with Whole Foods is a reliable source of this type of information. L-arginine and B6 are also proven helpful to reduce risk of atherosclerosis and heart disease. L-arginine is the substrate for nitric oxide production, which plays a significant role in vasoreactivity, along with niacin. Enothelium, or artery lining dysfunctions are thought to be a reason for L-arginine deficiency or inhibition. Vitamin B6 helps with the utilization of L-arginine. Aged garlic and pomegranate extract have also been studied and positive findings of reduced atherosclerotic plaque associated.

Cholesterol is produced in the body and is a plentiful and useful hormone. Of course, animal bodies have a lot of cholesterol in them, and so meat is a big dietary source, but this cholesterol from dead animals may not be as useful as the cholesterols your own body produces. When cholesterol molecules begin to break down, the body must eliminate them in the bile. Cholesterol is a steroid hormone and circulates attached to proteins of various densities. Of course, we know that these good complexes are high density, and that excess low density lipoproteins (LDL), when excessive, are associated with atherosclerotic plaque. HDL and LDL do not signify good and bad cholesterol. The same cholesterol is complexed in both of these lipoproteins. Good cholesterol may be that which is produced by a healthy liver, or the adrenals, skin, intestine, testes and aorta, rather than eaten. Yes, even our main arteries produce cholesterol, and this may have a relationship to atherosclerotic plaque (read further). High meat cholesterol intake suppresses the synthesis of healthy cholesterol in the liver, but not the other tissues. Healthy cholesterols may reduce the risk of atherosclerosis as well as increase the possiblity of healthier steroid hormones, which are made from cholesterol. Our main source of Vitamin D is derived from a cholesterol metabolite in our skin, activated by short exposure to sunlight. We see that consuming less meat may have a number of healthy implications, along with encouraging a healthier cholesterol metabolism, as long as the vegetarian portion of your diet contains healthy essential fatty acids.

The oils and foods highest in Omega-3 and healthy Omega-6 essential fatty acids (EFAs) are: toasted walnut and hazelnut oils, pumpkin seed oil, flax oil, fresh fish oil, krill oil, fermented soy products, dark leafy greens, fresh nuts, seeds, legumes, vegetables, spirulina, salmon, sardine, tuna, lake trout, anchovy, and butterfish. While olive oil is a healthy oil, it is not a high source of these essential fatty acids, and other oils should be added to the diet. Always use oils that are unrefined and preferrably as fresh as possible and stored correctly. Oxidized oils may have the beneficial essential fatty oils broken down and harmful metabolites occuring. The best sources of supplemental essential fatty acids EPA and DHA are found in krill oil and spirulina. A balance between Omega-3 and Omega-6 essential fatty acids is most important, and linolenic and linoleic acids should not be overlooked. Studies have shown that taking both Omega-3 and Omega-6 supplements improve benefits for osteoporosis and various diseases, although a diet rich in all of these essential fatty acids is most important. One type of Omega-6 EFA, arachidonic acid, derived mainly from meat, has predominated, and caused an imbalance that is pro-inflammatory, leading to the generalization that using Omega-3 supplements is a one-size-fits-all solution. Each individual needs to assess their diet and make the right choices, though, as we are not all alike, and do not all eat the 'typical' diet.

Coenzyme Q10

This nutrient, often deficient in patients switching to a vegan diet, but also in the population at large, is found to be a commonly depleted nutrient for patients with cardiovascular problems. CoQ10 is also commonly depleted with use of medications such as hypertension beta-blockers, cholesterol lowering statins, cholesterol lowering fibric acid derivatives, and tricyclic antidepressants. For this reason, key subsets of patients at risk should seriously consider periodic supplementation. CoQ10 is a ubiquitous antioxidant found in most cells in our body, and deficiency has been linked to cardiovascular disease. European studies have demonstrated the proven benefits of CoQ10 in prevention of stroke recurrence and this supplement has become standard protocol for many medical doctors in Europe and Japan prescribed to patients after a stroke, TIA or heart attack. The benefits of CoQ10 are many, though, although the supplement is still relatively expensive, and it may be wise to take it periodically, not continuously, and take the CoQ10-H2 form of the supplement, which is proven to deliver much more to the cells.

High Homocysteine levels

Excess Homocysteine as an independent risk factor for cerebrovascular disease, coronary artery disease, peripheral vascular disease, thrombophilia such as DVT and PE, carotid atherosclerosis and aortic atheroma has been documented since the 1960s. High homocysteine induces oxidative stress and modification of methylation processes linked to atherosclerosis and cardiovascular risk. Patients with low folate levels are shown to have consistently high homocysteine levels, and some population studies have found the over 70 percent of target populations are deficient in folates, or folic acid. More recently, high homocysteine levels are linked to osteoporotic bone fractures and Alzheimer's disease. The key to understanding how high homocysteine levels are linked to these health risks is to understand the homocysteine metabolism and use a restorative medicine to regain a healthy homeostatic balance. An allopathic approach of just blocking homocysteine will do no good.

Research has proven that a set of nutrient molecules can help restore healthy homocysteine metabolism. The combination of Vitamin B6, B2 and folic acid has been shown to reduce homocysteine levels, while B complex has not shown to be effective. The most active forms of these nutrient molecules are P5P (B6), riboflavin (combined with B3 inositol hexacotinate in sustained release form, as ATP Cofactors), and 5MTHF (active folate), and taking these molecules may insure that they are not just excreted, but actually do their job. Taurine has also been shown to be effective in reducing excess homocysteine levels, and research at the University of California Davies showed that an enhanced taurine supplement combined with grape seed extracts could significantly lower systolic blood pressure and aid both the heart and blood vessels in human clinical trials (IBP from Health Concerns). Grape seed extract is rich in the essential fatty acid GLA, as well as proanthycyanidins, pycnogenol, OPCs, and other beneficial nutrient chemicals. Vitamin B12, which is difficult to absorb for many patients due to lack of intrinsic factor in the stomach lining, is also proven helpful to reduce high homocysteine levels and is a supplement often taken with folic acid. To insure B12 absorption, take a quality sublingual product at a high dose, by crushing the tablets between two spoons and letting it absorb into the bloodstream directly through the membranes under the tongue, or take B12 methocobalamine in liquid form. B12 injections are also effective. N-acetyl cysteine, another amino acid metabolite now used to enhance intestinal membrane health and aid thyroid metabolism, is now also proven effective to reduce high homocysteine levels, as is the nutrient betaine, found in steel cut oats, barley and dried barleygrass powder, the herbs Urtica doica (nettle), Althea officianalis root (Marshmallow), Gou qi zi (Lycium or Wolfberry), Wu tong (Firmiana simplex), and Huang qi (Astragalus).

The combination of P5P, 5MTHF, B12, IBP, N-acetyl cysteine, and ATP Cofactors provides a complete synergistic prescription for reduction of high homocysteine by encouraging the glutathione metabolism and membrane maintenance with methionine and cysteine. Of course, one need not take these nutrient medicines constantly, but periodic supplementation with the combination may insure effect, while improved diet will supply the body with its needs on the whole. With such a complete protocol, regaining a healthy homocysteine metabolism is probable. While some studies have shown limited benefit for a simple constant taking of B12, folic acid and B6 for patients with vascular disease, this points to a need to adopt more complete and holistic treatment regimens in Complementary Medicine, and not look for a simple magic pill. It also points to the need to take the best type and quality of these nutrient medicines, and the right dosage. Individualized treatment protocols using acupuncture, herbal and nutrient medicine, dietary advice, and improved lifestyle habits, as well as attention to overall health and contributing health factors provides a sound preventive strategy. The HOPE-2 and NORVIT trials with a simplistic high dose regimen of B6, B12 and folic acid to reduce homocysteine were not successful because using a high dose of B6 is not healthy, and was shown to actually increase cardiovascular risk in a subset of the subjects. This indicates that we need to take a more holistic and realistic approach to this subject, and actually utilize professional individualized treatment to correct the underlying health problems, not just a simplistic high dose regimen of a few nutritional supplements.

Understanding of this metabolism in a basic sense is important to utilization of nutrient medicine to dramatically decrease cardiovascular risk. As with all markers for cardiovascular risk, we must ask ourselves why excess homocysteine is linked to cardiovascular risk. Studies have shown that high homocysteine levels may cause cardiovascular damage by creating accumulation of S-adenosyl-L-homocysteine, which inhibits an enzyme that mediates methylation metabolism of various catecholamines (epinephrine/adrenaline for example) and catechol estrogens, which act as neurotransmitters and neurohormonal regulators of the autonomic nervous system. When the cardiovascular tissues fail to break down and clear these catecholamines and catechol estrogens, overstimulation of the sympathetic nervous system creates excess oxidative products, or free radicals, in the blood vessel walls. This oxidative damage leads to atherosclerotic plaque, and nervous overstimulation leads to excess stress on the cardiovascular system and high blood pressure. Antioxidants such as ALA (alpha lipoic acid) are thus useful as well. Insuring a better homocysteine metabolism may be especially important for women, who experience a high risk for heart attacks, especially stress-induced heart attacks related to a poor homocysteine metabolism.

This metabolic scenario is very revealing. We find that patients with high levels of nervous stress, nutritional deficiencies, and oxidative stress incur damage to the blood vessel walls that leads to atherosclerosis, high blood pressure, and increased risk of strokes and heart attacks. High homocysteine levels have also been implicated in increased risk for Parkinson's and Alzheimer's neurodegenerative disease, and estrogen-induced breast cancers, making this metabolic disturbance more alarming than our levels of low density lipoproteins. Studies have also connected high homocysteine levels to metabolic syndrome, which is commonly called diabetes type 2. Addressing the homeostatic imbalances that lead to high circulating homocysteine is thus very important to reducing cardiovascular risk in a number of important ways, and may improve overall health and quality of life as well.

Research has shown that these nutritional deficiencies mentioned above, rare genetic defects, some chronic diseases, and certain pharmaceutical drugs may be linked to the cause of high homocysteine levels. Ironically, some drugs used to treat high cholesterol, such as fibrates and nicotinic acid can raise homocysteine levels by as much as 30 percent. Examples of fibrate drugs include Lopid (gemfirbozil) and Tricor (fenofibrate), as well as Lipocin (clinofibrate), Modalim (ciprofibrate), and Bezalip (bezafibrate), and are commonly prescribed with statin drugs. Nicotinic acid drugs include Niacor, Slo-Niacin, and Niaspan. It appears that these drugs developed to lower cholesterol to prevent cardiovascular disease actually increased the risk. Methotrexate (immune suppressant anti-rheumatic) and acid inhibiting drugs (Nexium, Prilosec and Prevacid) were also found to cause excess homocysteine levels by depleting or blocking absorption of folates and B vitamins. High alcohol and coffee intake, and cigarette smoking have been linked to higher homocysteine levels as well. Each individual should assess their underlying health factors to improve the health of their cardiovascular system and reduce inflammatory and oxidant stress. These findings of adverse effects of medication may have prompted the resistance to acknowledging excess homocysteine as a health threat for decades, and now designing studies to discount it.

While the subject of high homocysteine levels has been the subject of much debate because of the complexity of the metabolic mechanism and indirect nature of the problem to cardiovascular damage, what we know is very revealing to a healthy approach with Complementary and Integrative Medicine. Studies have shown that women are more likely to have a high homocysteine level linked to cardiovascular pathology, and that emotional problems with repressed anger and hostility are often found in study patients with high homocysteine levels. This is explained by the metabolic mechanism mentioned above, with failure to clear catechol estrogen accumulation, which may be more pronounced in women. Metabolic disturbance also stimulates increased emotional problems. In the texts of Traditional Chinese Medicine, ancient medical doctors wrote that repressed or constrained emotions are a significant cause of internal disease, and that there was a pattern of types of emotional disturbance linked to the various organ systems. Repressed anger and hostility was linked to the liver system. Today, even standard medicine is addressing these mind-body mechanisms, as much research is proving that physicians from two thousand years ago were right.

Homocysteine is a product of normal breakdown of the amino acid methionine in the liver system. Excess methionine may occur with poor liver function, either with dysfunction in breaking down proteins or transforming amino acids, or with processing of fats, since methionine is also a lipotropic compound that helps the liver process fats (lipids). The nutrient medicine betaine has been found to improve homocysteine and mehtionine metabolism in the liver, and is commonly used in TCM formulas to treat inflammation and promote tissue repair. A diet of excess fat and protein could also lead to excess methionine and thus excess homocysteine levels. The most important factor in high homocysteine metabolism may be the lack of folic acid, though. Homocysteine and methionine freely transform one into the other as needed in our metabolism, but homocysteine is transformed back into methionine only when there is sufficient methylated folate, or betaine derived from choline. Since high homocysteine levels may indirectly inhibit methylation, a vicious metabolic cycle may arise, contributing to deficiency in folate conversion of homocysteine back into methionine. Women with cardiovascular risk may have a deficiency of folic acid, choline, and perhaps even acquire a deficiency of methionine in this scenario, and neurohormonal imbalances would also contribute. Poor diet and stress of the liver function would also contribute. We see in this presentation the explanation why so many patients find success with reducing blood pressure and lipoprotein levels when they improve their diets and reduce stress, along with taking some of these nutritional supplements for awhile.

Studies in the last 15 years have also shown that there may be a synergistic association of high homocysteine levels and resistance to activated protein C in the onset of thrombotic disease (not related to C-reactive protein), or atherosclerosis. Studies indicate that elevated homocysteine may affect both the vascular wall structure and the blood coagulation system. Activated protein C (APC) is a Vitamin K dependent blood plasma protein whose deficiency, or acquired resistance, has long been linked to risk for venous thromboses, and blood clots, or atheroma, in general. Activated protein C is important in the regulation of thrombin generation, and is thus cardioprotective, and is also important in maintaining permeability of blood vessels, and reacting to chronic inflammation, and modulating programmed cell death (apoptosis). Activated protein C is mainly found near blood vessel walls (epithelium), and resistance at the APC receptors on the blood vessel walls thus increases cardiovascular risk in a number of ways.

Pathologically, we see that sustained high homocysteine levels are due to impairment of one homocysteine metabolic pathway leading to an impairment of a second homocysteine pathway, and too simplistic of a treatment protocol will not have enough effect on this impaired homeostasis, or metabolic balance. Two key metabolic pathways, remethylation and transsulfuration, are involved. Both the regulation of the methionine to homocysteine, perhaps regulated by SAMe, and the regulation of conversion of cystathionine to homocysteine are important, and the variety of factors that could upset this metabolism and catabolism, including oxidant stress and poor glutathione metabolism, need to be addressed to normalize homocysteine levels. Research has revealed that patients with excess homocysteine levels tend to have excess methionine levels, but deficient S-adenosylmethionine, and while we have understood the roles of SAMe, betaine stimulated conversion of homocysteine to methionine, the role of B12 and active folate, and N-acetyl cysteine in this feedback cycle, the correction, or restoration of the cycle still eludes us, because this restoration involves a more holistic normalization of metabolic homeostasis. A more thorough and complete package of care is obviously needed to achieve the broad goals in reducing cardiovascular risk, and such holistic protocol continues to be challenged by standard medicine, still seeking a simplistic one-size-fits-all scheme.

SAMe and the potential benefits to aid cardiovascular health

S-adenosyl methionine, or SAMe, is a popular, but somewhat expensive supplement. SAMe is an essential methionine in our metabolism, contributing methyl groups to a wide range of processes, including formation of DNA, protein metabolism and phospholipid metabolism. Formation of SAMe in the body may be hindered when there exists a problem with methionine metabolism, or when the enzymes that regulate this transformation are adversely affected by hormonal imbalances or nutritional deficencies. Also, with increased liver stress, and excess methionine in the diet, from a meat or protein oriented diet, conversion of methionine to SAMe can be deficent. Taking of SAMe supplement rarely produces immediate dramatic effects, and so it is not a popular supplement, but in this subset of patients, could greatly benefit metabolism, help clear nutritional abnormalities, and reduce cardiovascular risk.

Adrenal stress and abnormal cortisol metabolism as prime causes of the metabolic disturbances leading to high homocysteine levels

Study of hormonal disorders associated with high homocysteine levels includes study of adrenal disorders such as Cushing's Syndrome, which is also associated with increased cardiovascular risk. A study to determine relationships found that patient's with Cushing's Syndrome, involving excess cortisl levels, often resulting in inexplicable weight gain, hypertension, osteoporosis, decreased liver metabolism, agitation and mental disturbance, and sometimes amenorrhea, all had high homocysteine levels and low taurine levels. Insulin and glucose levels were also higher in patients with active disease, and serum B12 levels were deficient. The researchers concluded that these metabolic abnormalities were likely directly or indirectly caused by abnormal cortisol levels, and were completely normalized when cortisol levels and diurnal rhythm were also normalized. The study is presented below in additional information.

Such studies as these demonstrate the multifactorial and holistic nature of cardiovascular risk. A number of factors lead to increased adrenal stress syndrome, and abnormality of diurnal cortisol levels. While Cushing's Syndrome is often an extreme presentation of this problem, caused by tumor, or by the taking of synthetic steroid medications, many patients are presenting with subclinical adrenal stress syndromes in practice today. Neurohormonal imbalances are becoming frequently diagnosed and treated. Patients often find this combination of symptoms slowly worsening, and are frustrated by a lack of diagnosis that would explain all of the problems mentioned above. Treatment of this adrenal stress and metabolic disorder with a holistic approach often gives amazing results, and decreases the risk of cardiovascular disease very much.

Resveratrol and the potential and proven beneifts to aid cardiovascular health

Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenol, is a compund that is now much studied, and in fact much research in development has been devoted by pharmaceutical companies to achieve an effective synthetic resveratrol due to its proven efficacy regarding a variety of diseases. While the pharmaceutical industry continues to state that resveratrol is derived from grapes and wine, the fact is that the resveratrol supplements, first developed by the Chinese, come from the herb Polygonum cuspidatum (Hu zhang), and that an enormous amount of grape skin or wine would be needed to achieve a single therapeutic dose. In 2010, experts at the University of Kansas Medical Center published a report that resveratrol possesses significant anti-angiogenic properties and is cardioprotective. They sought to identify the exact mechanisms by which this herbal extract worked, and found that modulation of inflammatory enzymes AKT and MEK kinase inhibited FOXOsa phosphorylation to stabilize capillaries and endothelial tissues. These experts, stated that "in conclusion, regulation of FOXO transcription factors by resveratrol may play an important role in angiogenesis which is critical for cancer, diabetic retinopathy, rheumatoid arthritis, psoriasis, and cardiovascular disorders" (PMID: 20012470). What they didn't reveal is that the herbal chemical played a modulatory role in these mechanisms, supporting healthy homeostatic mechanism. Resveratrol quickly metabolizes to other helpful chemicals in the body, including quercetin and pterostylbene, which are sometimes combined with resveratrol in supplements. Resveratrol is a strong antioxidant and inflammatory modulator as well, inhibiting inducible nitric oxide, NF-Kb, AP-1 and MMP, and stimulates endotheilial nitric oxide synthase activity. Thus, the potential benefits for cardiovascular care are substantial.

Acupuncture and Cardioprotective Effects Studied and Proven

By 2013, a number of studies in China found that specific acupuncture and electroacupuncture treatments could both prevent future heart attacks and greatly aid recovery from them. Studies in Shanghai showed that animals induced with ischemia-reperfusion (IR) injury (damage to heart tissues when blood supply returns after a period of ischemia, or no blood flow, or lack of oxygen) recovered much faster than controls when electroacupuncture at the point P6 was performed. IR injury involves oxidant stress, inflammatory complement stress, leukocyte endothelial cell adhesion, platelet-leukocyte aggregation, increased microvascular permeability, and decreased endothelium-dependent relaxation. All of these tissue changes may become permanent and result in a compromised heart. Treatment with anti-inflammatory drugs is problematic, as this could disrupt inflammatory processes that are necessary, or result in immunosuppression. Treatment with Complementary Medicine offers the patient safe and practical methods to achieve faster resolution of IR injury and modulation of homeostatic inflammatory mechanisms that are cardioprotective.

To find the mechanisms by which acupuncture stimulation could improve post-ischemic recovery, experts at the University of Toronto, Division of Cardiology, in Canada, used the same markers that demonstrated success with remote preconditioning of the heart in prior studies. They found that animals with induced IR injury subjected to 60 minutes of electroacupuncture stimulation at P6 point, Neiguan, showed significant reduction in infarct size and improved functional recovery over controls. The degree of cardioprotection and recovery after heart attack to heart tissues was equal to that of remote preconditioning therapy (PMID: 23529221). In 2012, at the Fourth Military Medical University, in Xi'an, China, 70 children with congenital heart defects scheduled for cardiac surgical repair were randomized in a controlled trial of just transcutaneous electrical stimulation (TENS) at the point P6, since children are historically treated successfully by surface stimulation at acupuncture points, and there were significant benefits in recovery after surgery in the acupuncture TENS group, measured by levels of the markers CRP (C-reactive protein) and cTnl (cardiac troponin I) reductions (PMID: 22380768). This study followed a randomized controlled human clinical trial in 2010, using elecroacupuncture bilaterally at the points P6, LU7 and LU2 for 30 minutes daily for 5 days before cardiopulmonary bypass surgery. The results showed a significant reduction in cardiac Troponin I for the acupuncture group compared to controls, showing that this simple treatment greatly benefited cardiac recovery from the surgery (PMID: 20172127). Similarly, in 2014, at the Shanghai 6th People's Hospital, experts at the Department of Cardiology found in laboratory studies that pre-treatment with the herb Salvia miltirorrhiza (Dan shen) before induced heart attack with Ischemia-Reperfusion injury in laboratory animals improved a number of makers of cardiac health over controls significantly, including decreased ST-segment, myocardium MDA, CK-MB, and increased antioxidant enzyme levels, as well as upregulating inflammatory chemokines p-JAK-2 and p-STAT3 that were associated with decreased myocardial TNF-alpha and IL-6 (PMID: 24831834). Such studies demonstrate the significant benefits from integrating Complementary Medicine in the form of Traditional Chinese Medicine into cardiac care and prevention.

Information Resources: Additonial Information and Links to Scientific Studies

  1. An overview of recent long-term clinical studies on cholesterol-lowering is presented at Our Bodies Ourselves, a health resource center in Boston: http://www.ourbodiesourselves.org/book/menoexcerpt.asp?id=65
  2. A 2013 meta-review of all scientific literature published in BioMed Central found that the blood marker hemoglobin A1C, an advanced glycation endproduct (AGE), was associated with increased risk or prevalence of cardiovascular disease and chronic kidney disease even if the patients were not diagnosed with diabetes, which standard medicine utilizes this marker for exclusively: http://www.ncbi.nlm.nih.gov/pubmed/23865389
  3. A 2007 review of all scientific literature by the Center for Cardiovascular Disease Prevention of Harvard Medical School, Boston, Massachusetts, U.S.A. reports that there is consensus that hsCRP is an accurate predictor of cardiovascular risk despite the controversies regarding the acceptance of the inflammatory hypothesis of the etiopathology of atherosclerosis, which diminishes the importance of statin drugs as the first line of prevention: http://www.ncbi.nlm.nih.gov/pubmed/17531663
  4. A 2005 study by the Harvard School of Public Health showed that in a large study of nurses, those in the upper quarter of chronic consumption of trans fats had a 73 percent higher average of circulating CRP than those who consumed the least trans fats: http://www.ncbi.nlm.nih.gov/pubmed/15735094
  5. A 2013 analysis of the TRUTH study published in the Journal of Atherosclerosis and Thrombosis, the official publication of the Japan Atherosclerosis Society, found that CRP was a more useful predictor of cardiovascular events than arterial plaque changes with statin therapy: http://www.ncbi.nlm.nih.gov/pubmed/23748166
  6. A 2011 review of biomarkers for cardiovascular risk, by experts at the University Medical Center Utrecht, The Netherlands, shows that classical markers, such as high cholesterol, are unreliable, as half of patients with cardiovascular disease do not have a threatening level of high cholesterol, and merely lowering the cholesterol threshold is a cynical approach to prevention. Newer markers for disease must address the vulnerable plaque on arterial membranes, not overall plaque, which is caused by inflammation and calcification. Some reliable markers are also non-specific, though, such as hsCRP, and need more specific biomarkers to make firm conclusions. One promising biomarker is excess osteopontin (OPN), which was shown to be associated with a 4-fold risk of more cardiovascular events after carotid endarterectomy. Such study also reveals that merely inhibiting expression of biomarkers with new drugs is problematic, as it does not reduce the drivers of these biomarkers. The answer to this conundrum is obviously a more holistic approach using a number of protocols researched to reduce the underlying factors associated with these biomarkers, such as OPN and E-selectin. More and more research is showing the potential for herbal and nutrient medicine to achieve this goal: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131712/
  7. A 2015 review of the cardiovascular association with obstructive sleep apnea, by experts at the University of Crete School of Medicine, in Herakion, Crete, Greece, notes that CRP is consistently elevated in both cardiovascular disease and sleep apnea, indicating that chronic inflammation is one of the key factors in these diseases: http://www.ncbi.nlm.nih.gov/pubmed/25992322
  8. A 2012 study at Maastricht University Medical Center, The Netherlands, found that the now widely used marker for cardiac disease in Europe, high-sensitivity cardiac troponin T (hs-cTnT), is a useful prognostic biomarker in patients with chest discomfort suspected for coronary heart disease, and an independent predictor for cardiac risk: http://www.ncbi.nlm.nih.gov/pubmed/22558116
  9. A 2008 study at Leiden University Medical Centre, Leiden, Zuid Holland, the Netherlands, found that the widely accepted marker for cardiomyopathy, and accurate predictor of outcomes with cardiac arrest, or heart attack, high-sensitivity cardiac troponin T (hs-cTnT), proved to be a very accurate predictor of hospital mortality in the emergency room for patients with heart attack and suspected infection: http://www.ncbi.nlm.nih.gov/pubmed/23965276
  10. A 2008 study at the National University of Singapore showed that a common Chinese medicinal herb, Rehmannia glutinosa (Sheng di huang), reduced CRP levels, indicating potent anti-inflammatory effect: http://www.ncbi.nlm.nih.gov/pubmed/19051338
  11. A 2013 study at the Peking University Health Science Center, in Beijing, China, found that the Chinese herb Astragalus membranaceous (Huang qi), one of the most commonly used herbs in formulas in Traditional Chinese Medicine, exhibited significant cardioprotective effects, decreasing cardiac troponin and other markers of cardiovascular risk, and dramatically improving cardiac function in laboratory animals with induced myocardial ischemia and arterial occlusion (atherosclerotic stenosis). In addition, the herbal extract reduced oxidative stress markers, such as malondialdehyde (MDA), and improved superoxide dismutase (SOD), as well as blocking calcium channel overload: http://www.ncbi.nlm.nih.gov/pubmed/23968862
  12. A 2013 study at the Fourth Military Medical University, Xi'an, China, found that a chemical in the Chinese herb Salvia miltiorrhiza (Dan shen), magnesium lithospermate B, exerted significant cardioprotective effects in vivo and in vitro, via antioxidant pathways, increasing superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), decreasing malandialdehyde (MDA) toxicity, and significantly limiting infarct size in laboratory animals with induced heart attack, preventing leakage of creatine kinase MB (CK-MB): http://www.ncbi.nlm.nih.gov/pubmed/23596818
  13. A 2002 study by the University of South Carolina reveals the mechanism of cardiovascular damage from high homocysteine levels: http://www.ncbi.nlm.nih.gov/pubmed/12371153/
  14. A study published by the NIH PubMed shows that taurine is effective in lowering homocysteine levels, which might be effective to reduce atherosclerosis: http://www.ncbi.nlm.nih.gov/pubmed/19239173
  15. An overview of high homocysteine scientific data is presented at the health website of the University of Michigan Health System: http://health.med.umich.edu/healthcontent.
  16. An article in the American Journal of Nutrition reveals many aspects of the homocysteine metabolism in relation to liver function: http://jn.nutrition.org/cgi/content/full/136/6/1701S
  17. An article in the American Journal of Medical Sciences from 1998 links excess homocysteine levels to arteriosclerotic disease and stroke, Vitamin B6, B12, and folate deficiency, resistance to activate protein C, and blood coagulation disorders: http://www.amjmedsci.com/pt/re/ajms
  18. A 1992 paper by Joshua William Miller of Rutgers, State University of New Jersey, outlines what was then known of the pathology of high sustained homocysteine, and unfortunately, we do not seem to have solved the holistic puzzle of this pathological homeostatic imbalance in the 23 years since: http://www.researchgate.net/profile/Joshua_Miller4/publication/21426599_The_pathogenesis_of_homocysteinemia_interruption_of_the_coordinate_regulation_by_S-adenosylmethionine_of_the_remethylation_and_transsulfuration_of_homocysteine/links/00b7d513f511605a6e000000.pdf
  19. A 2005 study showing a relationship between adrenal stress and high cortisol and cardiovascular disease with all of the common metabolic markers such as high homocysteine levels is presented here by researchers at the Federico II University in Naples, Italy, and published in the Journal of Clinical Endocrinology and Metabolism: http://jcem.endojournals.org/cgi/content/full/90/12/6616
  20. A 2006 study published in Nature Medicine revealed that C-reactive protein (CRP) is perhaps the most important of the regulatory proteins that interact with leptin in circulation. Not only is leptin resistance induced by excess CRP, but high concentration of leptin is also found to stimulate increased expression of CRP in the liver, producing a vicious cycle of metabolic imbalance. Since high CRP levels are an important cardiovascular marker, these findings have great implications and suggest a more holistic approach may be needed to reduce cardiovascular risk: http://www.nature.com/nm/journal/v12/n4/full/nm1372.html
  21. A 2001 study published in the Journal of the American Medical Association (JAMA) showed that C-reactive protein (CRP) and interleukin-6 (IL-6) are highly associated with chronic inflammation, cardiovascular disease and Metabolic Syndrome (type 2 diabetes), with an emphasis on these as firm markers of risk for Metabolic Syndrome. Other causes for these elevations of CRP and IL-6, noted in this study, included use of synthetic hormones, excess alcohol consumption, high BMI (excess weight), cigarette smoking, and lack of daily exercise: http://jama.ama-assn.org/content/286/3/327.short
  22. A comprehensive analysis of the physiological significance of glycemic index was performed utilizing the available research in 2009, by the University of Toronto, Ontario, Canada, Department of Nutritional Sciences, and published in the Journal of the American College of Nutrition. Research findings showed that foods with a low glycemic index are associated with improvement in serum lipids, reductions of the key marker for inflammatory disease and cardiovascular risk, C-reactive protein, aid in weight control, improve levels of high density lipoprotein cholesterol (HDL-C), decrease risk of developing diabetes, cardiovascualar disease, and various cancers, including breast, colon, and prostate: http://www.jacn.org/content/28/4_Supplement_1/439S...
  23. A 2007 study at the Harvard School of Public health found that women with the lowest nutritional intake of magnesium generally had higher markers of cardiovascular risk, such as CRP and E-selectin, and a modest association between magnesium deiciency and chronic inflammatory stress was established: http://www.ncbi.nlm.nih.gov/pubmed/17413107
  24. A 2008 review of scientific study of C-reactive protein (CRP) and cardiovascular pathology by East Tennessee State University, in Johnson City, Tennessee, U.S.A., found that while CRP is highly correlated with cardiovascular risk, the exact mechanism of this association is unclear, as CRP both increases in circulation and binds to inflamed and damaged cells, but in normal levels is shown to exert an array of effects on almost any type of cell in the body, with many of these mechanisms associated with atherosclerotic plague formation, CRP binding to aggregated low-density lipoproteins. Some of the CRP is found to be bound to bacterial endotoxins, and CRP is shown to stimulate the immune complement responses in vascular infarction as well, but in most studies of highly sensitive CRP (hsCRP) the normal level of CRP is shown to be atheroprotective. It thus appears that CRP acts in a more complex manner with other chemicals in the body to achieve various biochemical goals, depending upon the array, or quantum, of complementing chemicals, such as immune cytokines, metabolic hormones, etc. Because of this, the hope of finding a simple allopathic drug to affect CRP to treat or prevent disease appears to be nearly impossible. Instead, holistic therapy that helps the body to achieve healthy homeostatic levels of CRP appears to be the best way to utilize this metabolic pathway to prevent or treat cardiovascular disease: http://www.ncbi.nlm.nih.gov/pubmed/18293141
  25. A 2013 study at Chiba University in Japan found that not only C-reactive protein (CRP) and IL-6 increases were markers in silent brain infarction, but that the aldehyde acrolein was a significant marker. The study showed in laboratory animals that the tissues at the area of thrombotic stroke, or infarction, acrolein produced in these damaged cells stimulated excess expression of the inflammatory cytokine IL-6, which stimulated increased CRP, and that this process is seen in human cells as well. Acrolein is produced by the alkylation of glutathione in cells, and this transfer of an alkyl may be in the form of free radical reactive oxygen species, or oxidants, indicating that oxidative stress in a stroke with infarction may be the cause of high levels of acrolein, IL-6, and CRP. http://www.ncbi.nlm.nih.gov/pubmed/23763486
  26. A 2012 study at Michigan State University showed that anthocyanins reduce the secretion of IL-6, an inflammatory cytokine that is known to activate C-reactive protein in cardiovascular disease. Here the anthocyanins (flavonoid pigments) were derived from tart cherry, but medicinal extracts more commonly used include pomegranate extract, bilberry extract, schisandra berry, acerola and grape seed extract, as well as Phytolacca americana (Pokeweed). Anthocyanins are soluble in both water and alcohol, and are proven to exert antioxidant and anti-cancer effects, and inhibit growth of heliobacter pylori. The addition of such anthocyanin flavonoids in the overall cardiovascular treatment protocol could thus be a valuable addition in both treatment and prevention: http://www.ncbi.nlm.nih.gov/pubmed/22703874
  27. A 2002 summary of research into infectious agents linked to cardiovascular disease, by the University of Oulu, Finland, and the National Public Health Institute of Finland, revealed that at that time, evidence of clear association between several chronic low-grade infections and cardiovascular diseases is apparent. The only persistent infectious agents identified at that time in atherosclerotic plague were Chlamydia pneumoniae and various herpes retroviruses, but even in 2002, bacterial heat shock proteins and other indirect agents were evident contributors as well: http://www.sciencedirect.com/science/article/pii/S1473309901001682
  28. A 2016 study of atherosclerotic plaque, by the Texas Tech University School of Medicine, showed in tissue studies from legs amputated as a complication of diabetic disease that bacterial biofilm structures in arterial atherosclerotic plaques are prevalent and suggest that chronic inflammation and low-grade infection is a key factor in progression of atherosclerosis: http://www.ncbi.nlm.nih.gov/pubmed/26878370
  29. A 2015 study at the Baskent University School of Medicine, in Ankara, Turkey, showed that Milk Thistle, or Silymarin, shows much potential in reducing bacterial and microbial biofilms, especially in gram-positive bacterial strains:http://www.ncbi.nlm.nih.gov/pubmed/25937395
  30. A 2009 study at the Shanghai Jiao Tong University School of Medicine showed that the Chinese herbal chemical Berberine significantly inhibited bacterial biofilm formation in tissue cultures. Berberine, from Coptis Chinensis, or Huang Lian, is now much studied and proven to both decrease bacterial and viral infection and inflammation, but to benefit cardiovascular health in a variety of ways: http://www.ncbi.nlm.nih.gov/pubmed/19157797
  31. A 2013 study at the Sri Ramachandra University School of Medicine, in Chennai, India, showed that Berberine, Curcumin, chitosan and eugenol, all herbal chemicals, significantly inhibited bacterial biofilm formation, here studied with Klebsellia pneumoniae, but applicable to a variety of microbes that form difficult biofilms that resist the immune system: http://www.ncbi.nlm.nih.gov/pubmed/24377137