Cardiovascular Recommended Products:
L-ARGININE................................................ ARTICHOKE LEAF EXTRACT
BETA CAROTENE ....................................................................BROMELAIN
CALCIUM CITRATE ..............................................................L-CARNITINE
CDP CHOLINE ...................................................CHONDROITIN SULFATE
CHROMIUM .......................................................................CHRONOFORTE
CONJUGATED LINOLEIC ACID (CLA) .............................................DHEA
FIBER FOOD ..................................................................FOLIC ACID + B12
GAMMA E TOCOPHEROL/TOCOTRIENOL ........................GASTRO PRO
GRAPE SEED EXTRACT .....................................................BABY ASPIRIN
HERBAL CARDIOVASCULAR FORMULA .............................VITAMIN E
KYOLIC GARLIC .................................................. LIFE EXTENSION MIX
SUPER BOOSTER ...............................LIQUID EMULSIFIED VITAMIN A
MAGNESIUM ..............................................................NO FLUSH NIACIN
OLIVE LEAF EXTRACT............................................................ OPTI ZINC
PECTA SOL MODIFIED CITRUS PECTIN.......................POLICOSANOL
PURE GAR W/EDTA .........................................................................SAM-E
ALPHA LIPOIC ACID W/BIOTIN..................SUPER CARNOSINE CAPS
COENZYME Q10 (COQ10) ...........................CURCUMIN W/BIOPERINE
GREEN TEA EXTRACT................................GINKGO BILOBA EXTRACT
SUPER GLA / DHA ..................................................SELENIUM DROPPER
TAURINE ..............................................................................................TMG
TOCOTRIENOL FROM RICE BRAN ....................................VITAMIN B1
VITAMIN B12 ..........................................................VITAMIN B3 NIACIN
VITAMIN B6 .............................................................................VITAMIN C

The Hazards of Hyperhomocysteinemia
Experiments show that if homocysteine accumulates in the cell, all methylation reactions are inhibited. Because methylation is used for so many body processes (apart from homocysteine metabolism), if this system becomes dysfunctional, essential pathways are foiled. For example, methylation is fundamental to maintaining healthy DNA, lessening the possibility of mutations and strand breaks. Since DNA strand breaks have been detected in the biopsies of diseased cardiac tissue, it is suspected that strand breaks fuel the progression of heart disease. In addition, DNA strand breaks are associated with accelerated aging and a greater cancer risk (Domagala et al. 1998; Seki et al. 1998).

If homocysteine is not detoxified and begins to accumulate, plaque builds up in the endothelial cells lining the arteries through various mechanisms. For example, homocysteine speeds the oxidation of cholesterol, which then becomes bound to small, dense LDL particles. Macrophages then take up the particles to become foam cells in plaque. The earliest detectable lesion of atherosclerosis is the fatty streak (consisting of lipid-laden foam cells that are macrophages that have migrated as monocytes from the circulation into the subendothelial layer of the intima) that later become fibrous plaque (Naruszewicz et al. 1994; Cranton et al. 2001). Dr. Kilmer McCully, a crusader for the homocysteine theory of heart disease, says that homocysteine plays a key role in every pathophysiological process that leads to arteriosclerotic plaque (McCully 1996).

A heart attack or stroke is more likely to occur as homocysteine promotes coagulation factors, favoring clot formation (Magott 1998). The European Journal of Clinical Investigation reported that 40% of all stroke victims have elevated homocysteine levels compared to only 6% of controls (Brattstrom et al. 1992). Other studies chronicled similar findings: the elevations in homocysteine in 16 of 38 patients with cerebrovascular disease (42%), seven of 25 with peripheral vascular disease (28%), and 18 of 60 with coronary vascular disease (30%) but in none of the 27 normal subjects (Clarke et al. 1991).

In addition to causing cardiovascular disease by increasing the incidence of blood clots, hyperhomocysteinemia triggers atherosclerosis by encouraging smooth muscle cell proliferation, intimal-medial wall thickness, thromboxane A2 activity, lipid abnormalities, and the binding of Lp(a) to fibrin (Magott 1998; Sandrick 2000).

Vascular integrity is compromised as homocysteine blocks production of nitric oxide in the cells of blood vessel walls, causing vessels to become less pliable and even more susceptible to plaque buildup (Boger et al. 2000; Holton 2001). Scientists explain that vessels lose their expansion capacities as homocysteine reduces nitric oxide's availability (Tawakol et al. 2002). Homocysteine significantly hampers coronary microvascular circulation by impairing dilation functions.

Drs. Allen Miller and Gregory Kelly explain that homocysteine facilitates the generation of hydrogen peroxide. By creating oxidative damage to LDL cholesterol and endothelial cell membranes, hydrogen peroxide can then promote injury to vascular endothelium (Starkebaum et al. 1986; Stamler et al. 1993; Miller et al. 1997). Nitric oxide (also known as endothelium-derived relaxing factor) normally protects endothelial cells from damage by reacting with homocystine, forming S-nitrosohomocysteine, which inhibits hydrogen peroxide formation. However, as homocysteine levels increase, this protective mechanism can become overloaded, allowing damage to the endothelial cells to occur (Stamler et al. 1992, 1993, 1996).

Genes are also involved in homocysteine attack. This has a significant impact upon the cardiovascular system, as homocysteine activates genes in blood vessels, encouraging the coagulation process and the proliferation of smooth muscles (Outinen et al. 1999).

Since homocysteine wields such a powerful cardiovascular blow from so many different directions, it is estimated that a 3-unit increase in homocysteine equates to a 35% increase in heart attack risk (Verhoef et al. 1996). The risk becomes even greater if hyperhomocysteinemia occurs with other risk factors. For example, a hypertensive woman with elevated homocysteine levels has a 25-fold increased risk of vascular disease.

Other homocysteine/disease associations are:

High concentrations of homocysteine and low levels of folate and vitamin B6 are associated with an increased risk of extracranial carotid-artery stenosis, particularly in the elderly (Selhub et al. 1995).
Higher levels of homocysteine predispose deep venous thrombosis (den Heijer et al. 1996).
The link between hyperhomocysteinemia-hypercholesterolemia and hypothyroidism is clearly drawn in the section devoted to Thyroid Disease appearing in this protocol.
Plasma homocysteine levels predictably increase with elevations in creatinine. As chronic renal failure occurs, hyperhomocysteinemia is frequently observed (Wilcken et al. 1979; Chauveau et al. 1993).
Homocysteine metabolism is impaired in patients with Type II diabetes. Intramuscular injections of 1000 mcg of methylcobalamin (a homocysteine-lowering nutrient) once a day for 3 weeks reduced elevations of plasma homocysteine in diabetic test subjects (Araki et al. 1993).
While the focus of this protocol is upon cardiovascular disease, it should be noted that individuals suffering with Alzheimer's disease, depression, eye problems, liver damage, Crohn's disease, ulcerative colitis, irritable bowel disease, pernicious anemia, and Parkinson's disease often present with elevated homocysteine levels (Refsum et al. 1991; Savage et al. 1994; Mayer et al. 1996; Cattaneo et al. 1998; Clarke et al. 1998; Romagnuolo et al. 2001; Duan et al. 2002).
A large-scale prospective study of 4700 Norwegian men and women (65-67 years of age) showed that for each 5-millimol/L increase in plasma homocysteine levels, the number of deaths from all causes jumped 49%. This included a 50% increase in cardiovascular deaths, a 26% increase in cancer mortality, and a 104% increase in noncancer and noncardiovascular fatalities (Vollset et al. 2001).
Chronically high levels of homocysteine normally affect 30-40% of healthy elderly people. But in older individuals with severe illnesses, the prevalence of hyperhomocysteinemia may almost double. Based on a random testing of 600 hospitalized elderly patients (ages 65-102 years), researchers found evidence of hyperhomocysteinemia in over 60% of those with serious chronic conditions): 70% presented with vascular disease and 63% presented with cognitive impairment (Ventura et al. 2001). Impaired kidney function, the use of drugs (particularly diuretics), and malnutrition were suspected as causes of age-related hyperhomocysteinemia. Of the senior population in the United States, 67% have one or more vitamin levels within 15% of the lower recommended range, suggesting the need for review of reference values in elderly people.

While cholesterol does not normally pose a cardiac risk until levels exceed 240 mg/dL, some researchers consider homocysteine so capricious that even so-called normal levels may contribute to heart disease. Homocysteine levels should be kept as low as possible, below 7 micromol/L of blood plasma. Laboratories usually regard levels up to 15 micromol/L as normal, but epidemiological data reveal that homocysteine levels above 6.3 reflect a steep, progressive increase in the risk of a heart attack (Robinson et al. 1995). Although the incidence of hypertension, thrombotic stroke, peripheral vascular disease (gangrene), blood vessel toxicity, and the risk of heart attack escalate as homocysteine levels increase, homocysteine levels are not routinely evaluated in a cardiovascular work-up.

The Therapeutic section and the sections Homocysteine Lowering Nutrients and Elimination Pathways detail a program to assist in managing hyperhomocysteinemia. Note: Because of homocysteine's role in the metabolism of sulfur and methyl groups, elevated levels of homocysteine would be expected to negatively impact the biosynthesis of SAMe, carnitine, chondroitin sulfate, coenzyme Q10, creatine, cysteine, dimethylglycine, glucosamine sulfate, glutathione, melatonin, pantethine, phosphatidylcholine, and taurine. Many of these substances are profiled in the Therapeutic section for their cardioprotection and restorative qualities. The short supply of these agents could severely disable cardiac performance (Miller 1997).

Syndrome X
For the past 20 years, eclectic physicians have judged Syndrome X to be a powerful indicator of an eventual heart attack. For clarity, let it be understood that a syndrome represents clusters of symptoms. In Syndrome X, the symptoms are an inability to fully metabolize carbohydrates; hypertriglyceridemia; reduced HDL levels; smaller, denser LDL particles; increased blood pressure; visceral adiposity; disrupted coagulation factors; insulin resistance; hyperinsulinemia; and, often, increased levels of uric acid. Note: For years, high uric acid levels have been associated with cardiovascular disease, but the relationship was poorly understood. Dr. Gerald Reaven unraveled the link when he determined that elevations in uric acid are often prompted by Syndrome X, a forerunner to heart disease (Fang et al. 2000).

Until hyperinsulinemia is diagnosed and a therapeutic course is charted, the arteries are under severe attack and the risk of a blood clot increases. Lesions, or wounds and injuries, damage the arteries; the attempts at vascular repair corrode the vasculature with atheromatous material, blockading and closing off vital circulatory routes. The population of sticky platelets increases along with the production of free radicals. Lipogenesis (the production and accumulation of fat in arterial tissue) encourages smooth muscles in the vasculature to proliferate. Along with excessive amounts of fibrinogen (a plasma protein that encourages the clotting of blood), PAI-1 is induced, further increasing the likelihood of a blood clot. HMG-CoA reductase, the rate-limiting enzyme involved in hepatic cholesterol production, appears to be simulated in both diabetic and nondiabetic animal studies amidst high levels of insulin (Dietschy et al. 1974).

Syndrome X interferes with glucose delivery, a consequence initiated by insulin's nonresponsiveness at the receptor site on the cell. Normally, ordinary levels of insulin will escort glucose into the cell, leaving a bloodstream favoring neither hyper- or hypoglycemia. In Syndrome X, the receptor turns a cold shoulder to the hormone, and insulin is no longer able to deposit its cargo; as a result, glucose loads up in the bloodstream. The pancreas is aware of the problem and attempts to resolve it by discharging more and more insulin. The logic appears to be that since normal levels of insulin cannot get the job done, perhaps greater and greater amounts of circulating insulin will be able to drive glucose, the principal metabolic fuel, into our 100 trillion cells.

In most cases of Type II diabetes, the problem is insulin resistance and inadequate compensatory insulin; in Syndrome X, insulin resistance and excessive amounts of insulin are the hallmarks. The vast difference between the two conditions is that in Syndrome X, the pancreas does not falter in its effort to pump out insulin (Reaven 2000). It sounds as if the host has won, but the following reasons discredit this logic.

The pancreas can tire in its endless effort to supply compensatory insulin, and insulin-dependent diabetes will result.
Hormones are powerful substances with an equally meaningful purpose. When insulin is not used for its intended functions, insulin builds up in the bloodstream, and from various perspectives, the risk of heart disease increases.
For example, the Quebec Cardiovascular Study found that individuals with elevated levels of triglycerides and LDL cholesterol, plus low HDL cholesterol, had 4.4 times the risk of heart disease compared to men with none of the risk factors. But the risk soars to 20-fold for men with a triad of elevated fasting insulin, apolipoprotein B, and small, dense LDL particles. According to Dr. Benoit Lamarche (Laval University), hyperinsulinemia should not be overlooked as an independent risk factor for ischemic heart disease. His case-controlled study of 91 patients and 105 controls found fasting insulin levels 18% higher in cases than controls. For each 30% increase in insulin concentration, there was a 70% increase in the risk of ischemic heart disease over 5 years (Despres et al. 1996; Physician's Weekly 1998b).

Insulin growth factor-1 (IGF-1), a hormone that increases the body's sensitivity to insulin and promotes clearance of glucose and toxic metabolites, appears critical to surviving the crisis and aftermath of a heart attack (Conti et al. 2001). Lower levels of IGF-1 during the early phase of a myocardial infarction are associated with poorer clinical outcomes, arrhythmias, ischemia, and death.

Italian researchers measured IGF-1 levels in the blood of patients within 24 hours of the onset of heart attack symptoms. IGF-1 (a hormone that enhances the elasticity of blood vessels, strengthens heartbeat, and increases blood flow) was about 5 times lower compared to healthy controls (47 ng/mL versus 189 ng/mL). The transient reduction of IGF-1 during the early phase of infarction appears to cause an acute worsening of insulin resistance.

A decline in IGF-1 is also linked to poorer prognosis following a heart attack. Of the 23 patients evaluated regarding IGF-1 levels (postinfarction), 12 experienced adverse clinical events in the 90-day follow-up period. The two individuals with the lowest IGF-1 levels died from the heart attack or its complications. Negative end results were attributed to reduced insulin sensitivity, glucose clearance, fat metabolism, and cardiac function. Interestingly, infusing IGF-1 into rats (programmed to develop metabolic syndrome) alleviated hyperphagia (overeating), obesity, hyperinsulinemia, hyperleptinemia (excesses of a hormone frequently found in the bloodstream of overweight, cardiac-prone individuals), and hypertension (Vickers et al. 2001).

The IGF-1 system is regulated by various stimuli, including hormones, growth factors, and nutritional status (Fu et al. 2001). For example, IGF-1 increased when protein foods were emphasized in the diet, in combination with adequate levels of vitamin D and calcium (Rizzoli et al. 2001).

Unfortunately, many physicians fail to consider insulin resistance as a forerunner to Type II diabetes and cardiovascular disease. A fasting blood glucose level above 115 mg/dL, triglycerides above 160 mg/dL, low HDL cholesterol, blood pressure persistently over 140/90 mmHg, total cholesterol above 240 mg/dL, and 10-15 pounds of extra weight are important evaluations regarding the likelihood of insulin resistance (Challem et al. 2000). A normal 2-hour postprandial glucose is generally between 70-139 mg/dL. If fasting or 2-hour postprandial insulin levels are measured, a normal range is 6-35 mcIU/mL. The Life Extension Foundation believes that fasting insulin levels over 5 mcIU/mL may be a cause for concern, and respected physicians and scientists are aligning with this projection.

Even if these tests are run, physicians often err in properly assessing the cumulative values of multiple irregularities. The signs are all there, but a failure to connect the dots can lead to a treatment that never addresses the source of the ill health. Syndrome X is largely a nutritional disease that is manageable with dietary corrections, reducing carbohydrates such as sweets, pastas, and breads and instating good fats in carbohydrates' place (consult the section entitled Essential Fatty Acids in this protocol for a discussion regarding good and bad fats).

The Harvard University School of Public Health announced that women between the ages of 38-63 increased their risk of heart attack by about 40% if their diet contained quantities of carbohydrates, particularly refined carbohydrates (Liu et al. 2000). It has been determined that the type of food selected and the quantity consumed determine how much insulin must be supplied.

Dr. Gerald Reaven believes an appropriate breakdown of the food groups should be about 45% of calories from carbohydrates, 40% from fat, and 15% from protein. Substituting appropriate fats for carbohydrates quiets an insulin release from the pancreas, and a primary step in Syndrome X has been averted. Dr. Reaven cautions that current dietary recommendations, that is, replacing fats with carbohydrates, may be fine for some individuals, but it is a grievous, even fatal, suggestion for those who are insulin resistant (Reaven et al. 2000). Note: Nutritionists reviewing the concept of macronutrient fractions stress the importance of selecting healthy foods to supply requirements. Eating ad libitum from unwise food choices, but within acceptable percentages, could still render the diet unhealthy from many perspectives.

To read more about Syndrome X, consult the sections entitled Hypertension, Obesity, Sedentary Lifestyle, Fibrinolytic Activity, and Beta-Blockers. Also, the Therapeutic section has supplemental recommendations to assist in controlling Syndrome X, including alpha-lipoic acid, conjugated linoleic acid, DHEA, essential fatty acids, magnesium, vitamin A, and vitamin C.

C-Reactive Protein (CRP)
CRP is a marker for systemic inflammation that rises several hundredfold in response to acute tissue injury but stays relatively stable in the absence of inflammation. CRP appears in the serum before the erythrocyte sedimentation rate begins to rise, often within 24-48 hours of the onset of inflammation. Elevated CRP levels can indicate the presence of chronic low-grade inflammation, with linkage to blood vessel damage and vascular disease (Pasceri et al. 2000). High levels of CRP appear to alert inflammatory processes that have the potential to disrupt fatty plaque buildup inside blood vessels, causing a critical rupture; the end result is a blood clot.

When CRP levels are factored in as a cardiovascular risk, along with hypertension, diabetes, elevated cholesterol, family history, and BMI, there is significant improvement in predicting cardiac health compared with models that exclude CRP testing. Ten prospective studies (six in the United States and four in Europe) have consistently shown that hs-CRP is a powerful predictor of a future first coronary event in apparently healthy men and women. ("hs" refers to high sensitivity testing, the only method able to discriminate the subtle differences in CRP in a range that accurately predicts coronary risk.)

As new as CRP is to many as a risk factor in coronary artery disease, Rudolf Virchow, a German pathologist (1821-1902), hypothesized that inflammation was the causative factor in the atherogenic process. Decades later, scientists confirmed that increased monocytes (white blood cells critical in early plaque development) and macrophages (mononuclear phagocytic cells capable of scavenging and ingesting dead tissue and degenerated cells) are present, particularly at points of plaque rupture. It appears that CRP and several other inflammatory markers may be elevated many years prior to a coronary event.

However, data from the University of Texas Health Sciences Center indicate that CRP is more than a measurable antecedent preceding a cardiac problem. CRP, along with the cooperative efforts of an unidentified serum factor, acts directly upon the blood vessels to activate adhesion molecules in endothelial cells: the intercellular adhesion molecule (ICAM-1) and the vascular cell adhesion molecule (VCAM-1). VCAM-1 appears to be an early molecular marker of lesion-prone areas as a response to experimental hypercholesterolemia. In humans, ICAM-1 and VCAM-I expression is increased in the endothelium of atherosclerotic plaque. Researchers concluded that CRP appears intricately involved in the inflammatory process, thus proving to be a potential target for the treatment of atherosclerosis (Pasceri et al. 2000; Biomedical Science 2001; Alvaro et al. 2002).

The journal Circulation reports that CRP appears able to affect the activity of LDL cholesterol (increasing atherogenesis). The cycle begins as stranded LDL is taken up by macrophages; macrophages, gorged with fats contained in blood, become bloated and develop into foam cells. When foam cells have reached their maximum load, they explode, discharging their fatty contents into the blood vessel wall at the site of injury. The presence of added fat signals the need for more macrophages to clean up the mess. They stuff themselves, explode, and the cycle starts anew. Since native LDL does not induce foam cell formation, CRP appears to ready LDL for uptake by the macrophages, initiating the sequence (Braley 1985; Zwaka et al. 2001).

In the Physicians' Health Study, middle-aged men deemed healthy at baseline were evaluated over an 8-year period in regard to CRP levels and a cardiovascular event. This study showed that those in the highest quartile of hs-CRP had a twofold higher risk of (future) stroke, a threefold higher risk of (future) heart attack, and a fourfold higher risk of (future) peripheral vascular disease (Rifai et al. 2001a, 2001b). Stroke patients with the highest CRP levels were nearly 2.4 times more likely to die within the next year compared to patients with the lowest levels (DiNapoli et al. 2001). Another of hs-CRP's strengths is its ability to detect at-risk patients with normal cholesterol levels.

The risk of stroke, according to data reported in the New England Journal of Medicine, decreased among those using statin drugs (White et al. 2000). The Cholesterol and Recurrent Events Trial concluded that pravastatin (administered long term) appears to be doing more than reducing cholesterol, perhaps acting as an anti-inflammatory. Another study (also published in the New England Journal of Medicine) reported that pravastatin reduced CRP levels after both 12- and 24-weeks' administration, independent of LDL cholesterol levels. It appears statin therapy may prevent coronary events among individuals with relatively low lipid levels but with elevated levels of CRP (Ridker et al. 2001). Conversely, some drugs, including hormone replacement therapy, actually increase CRP levels and the inflammatory response.

Researchers hypothesized in the Journal of the American College of Cardiology that the cytomegalovirus (CMV) (herpes-type viruses) may stimulate an inflammatory response, reflected by elevated CRP levels. The journal Circulation reported that older people who have IgG antibodies to the herpes simplex-I virus experienced a twofold increase in the risk of a myocardial infarction or coronary heart disease death. Since the relationship between CMV and coronary heart disease is not observed in all people, researchers consider the ability of individuals to control CMV inflammatory activities, the variable in the progression to a myocardial infarction (Zhu et al. 1999; Siscovick et al. 2000).

The infectious process in heart disease is chronicled in numerous studies, but the microorganisms involved remain of interest. Subsequently, a group of researchers from Johannes Gutenberg University (in Mainz, Germany) evaluated 572 heart patients. They tested for antibodies in the bloodstream that would show that the immune system had at some stage been exposed to a variety of different viruses and bacteria. These included herpes simplex-1 and -2, which cause cold sores and genital herpes; Epstein-Barr virus, which causes mononucleosis, chlamydia, and flu virus; and Helicobacteria pylori, which causes stomach ulcers. Then they looked at the patients again 3 years later to see how many had survived. The death rate was 3.1% in patients who tested positive for only a few of the viruses or bacteria, 9.8% for those with four or five, and 15% in those positive for six to eight. Among those who had the most advanced artery hardening, 20% of those exposed to between six and eight infections had died, compared to 7% of those with three or fewer (BBC 2002b).

Japanese researchers concentrated upon finding a method to distinguish between bacterial and viral infection by measuring inflammatory markers, among them C-reactive protein (CRP). They found that during the acute stage of bacterial infections, CRP levels were moderately or highly increased, whereas in viral infections, CRP levels were normal or slightly increased. The researchers propose that the measurement of CRP (among various inflammatory markers) during the acute phase of illness, that is, within 5 days of onset, is of value to determine whether the infection is caused by a bacteria or virus (Sasaki et al. 2002). For an opposing view regarding the association between viruses and CRP levels, please consult the section entitled Link Between Infections and Inflammation in Heart Disease in this protocol.

Figure 4 shows the risk factors associated with CRP (data extracted from publications authored by Dr. Paul Ridker). It is important to note that risk factors vary according to individual publications and may change with future publications.

Risk Factors Associated with CRP
RELATIVE RISK FOR:1
MEN CRP (mg/L) .....Future MI (heart attack) ..............Future Stroke
>2.11............................................ 2.9 .................................1.9
1.15-2.10 ......................................2.6 .................................1.9
0.56-1.14 ......................................1.7 .................................1.7
<0.55 ............................................1.0 .................................1.0

RELATIVE RISK FOR:
WOMEN CRP (mg/L) ....Future MI (heart attack) ..........Future Stroke
>7.3 .............................................5.5 ....................................5.5
3.8-7.3 .........................................3.5 ....................................3.5
1.5-3.7 .........................................2.7 ....................................2.7
<1.5 .............................................1.0 ....................................1.0
1Relative risk is the ratio of the chance of a disease developing among members of a population exposed to a factor compared to a similar population not exposed to the factor.
Ridker et. al. (1998); Ridker et. al. (1997).

Current research indicates that persistent CRP elevation, lasting longer than 96 hours following a successful coronary stent implantation, is predictive of prolonged inflammation leading to re-stenosis (Gottsauner-Wolf et al. 2000). Patients who developed restenosis within the first 6 months had increases in CRP levels for up to 96 hours following the procedure, although their baseline CRP had been normal. Patients without restenosis displayed an increased CRP level that was sustained for no longer than 48 hours and subsequently decreased. Higher CRP levels appear predictive of less satisfactory end results, following angioplasty and stent procedures.

Although many of the newer risk factors are not yet standardized, some laboratories are using a CRP reference range of 0.24-1.69 mg/L. Recent medical events resulting in tissue injury, infections, or inflammation may increase CRP levels and, if not factored into clinical interpretations, can distort results.

To read more about factors affecting CRP levels, consult the sections referring to Smoking, Obesity, Sedentary Lifestyle, Gender, Gum Disease, and The Link Between Infections and Inflammation in Heart Disease. Improved glycemic control and normalizing blood pressure may also assist in reducing inflammation and (subsequently) CRP levels.

CRP appears responsive to aspirin, DHEA, fish oil, pravastatin, vitamin C, vitamin E, and vitamin K supplementation (consult the Therapeutic Section to learn more about natural products). As research continues, it may be found that many other nutrients and herbs known for their anti-inflammatory properties are equally valuable in maintaining healthy CRP levels. Note: CRP appears to reduce levels of vitamins A, C, and E, as well as carotenoids, zinc, and selenium. Individuals with elevations in CRP may wish to emphasize these nutrients for their contribution to cardiac health.

THE LINK BETWEEN INFECTIONS AND INFLAMMATION IN HEART DISEASE

Infections are of particular interest because of the increasing attention paid to the role of inflammation in heart disease, according to David S. Siscovick, M.D., professor of medicine and epidemiology at the University of Washington. The data incriminate the infectious process in various phases known to contribute to heart disease. For example, current research suggests that infection may be an important determinant of fibrinogen levels, offering one possible explanation for the association between chronic or acute infection and vascular events (Woodhouse et al. 1997). Many researchers class inflammation as worse than cholesterol at triggering heart attacks. Note: Men with hypercholesterolemia and inflammation have a significantly higher risk of cardiovascular death (2.4) compared to those with only high cholesterol levels (1.4) (Engstrom et al. 2002).

Dr. Paul Ridker (Boston's Brigham and Women's Hospital) recently explained that everyone reaching middle age has some degree of fat buildup, that is, plaque in the vasculature. New evidence suggests the plaque becomes threatening if weakened by inflammation, which makes the buildup squishy and fragile. Even a small lump can burst, promoting the formation of a clot that in turn chokes off blood flow and causes a heart attack. Thus, reducing the inflammatory process is of equal importance to lipid monitoring in controlling the dangers of plaque (Associated Press 2002).

Researchers observed that mortality from ischemic heart disease markedly increases during the flu season, particularly among the elderly. One reason for this appears to be that patients with influenza A, a flu virus, tend to have much higher levels of CRP. Researchers at Rochester General Hospital and Rochester School of Medicine and Dentistry showed that CRP increased 370% during infection and that old age magnified the increase (Falsey et al. 2001; Horan et al. 2001).

A higher white blood cell count, common when the body is fighting off infection, is associated with an increased coronary risk by diminishing blood flow to the heart muscle and encouraging blood clot formation. The higher the white blood cell count, the greater the patient's risk of death from a heart attack or of developing congestive heart failure (Barron et al. 2000).

In fact, angina pectoris appears less a prognosticator of a forthcoming heart attack than a febrile (flu-like, feverish) infection prior to the attack. Peter Ammann, M.D. (Switzerland), stated that he has observed significantly higher numbers of myocardial infarctions among patients with febrile conditions, mainly of the upper airways, within 2 weeks prior to infarction (Ammann et al. 2000; Healthlink 2000).

Bacteria appear to gain entry into the heart via immune cells, most likely activated in the process of clearing infections from the respiratory passages. The bacteria most suspected of initiating coronary problems are Chlamydia pneumoniae, Pasteurella aerogenes, Enterococcus endocarditis, Staphylococcus aureus, Enterococcus faecalis, Candida albicans, and Viridan streptococcus. (Some researchers add H. pylori, a bacteria associated with duodenal ulcers, peptic ulcers, and chronic gastritis, to the list.)

Tissue specimens from patients who had undergone a carotid endarterectomy showed high levels of C. pneumoniae in 11 of 17 cases (64%). The American Heart Association also reported that C. pneumoniae was found in the infected arteries of autopsied cardiac patients. Dr. Tatu Juvonen (Oulu University Hospital in Finland) explains that C. pneumoniae is a specific microbial antigen that causes inflammation and atherosclerotic cells to proliferate (Juvonen 2000; Mosorin et al. 2000; Vink et al. 2001).

An alternative to this dismal situation may be antibiotic therapy, controlling the inflammatory process attacking the vessel wall. An American study of more than 16,000 British patients showed that people treated with two types of antibiotics had a significantly reduced risk of heart attack. Those treated with tetracyclines were at 30% less risk than patients not given antibiotics, while those who took quinolones (antimicrobials) had a 55% reduced risk. It appears antibiotics may act in the same fashion as anti-inflammatory drugs, reducing inflammation in the arteries (BBC News 1999, 2002a).

Inflammation appears to be an independent risk factor that may explain cardiovascular disease in the presence of normal cholesterol, blood pressure, and coronary arteries. MINC patients, individuals experiencing a myocardial infarction with normal coronary arteries, should be at lower risk for a cardiac event because they most often have normal electrocardiograms, higher HDL levels, and no significant impairment in LDL cholesterol. Dr. Ammann believes the trigger may be systemic inflammation or specific infective agents, advancing a benign complaint to a life-threatening condition. Interestingly, migraine headaches have also been observed as forerunners to a heart attack in otherwise healthy individuals (Ammann et al. 2000; HealthLink 2000).

IS ATRIAL FIBRILLATION PREDICTIVE OF CARDIAC MORTALITY?

Atrial fibrillation, a condition shared by over 2 million Americans, occurs when the atria, the upper chambers of the heart, beat faster than the lower two chambers, the ventricles. Many problems can cause atrial fibrillation, including a leaky heart valve, hypertension, obesity, stimulants (including caffeine and alcohol), medications (such as sumatriptan, a headache drug), and thyroid disorders. Dr. Robert Atkins, M.D., adds that patients should be evaluated for heavy metal intoxication and mycoplasmal infections, factors also capable of provoking atrial fibrillation.

Although not immediately life-threatening, atrial fibrillation may cause up to a 30% reduction in cardiac output, resulting in shortness of breath, fatigue, and reduced exercise capacity. In fact, the American Heart Association no longer regards atrial fibrillation as a benign disorder. About 75,000 strokes related to atrial fibrillation occur each year in the United States. Up to 23% of such patients die, and 44% experience significant neurologic deficits. (The mortality rate from other causes of stroke is about 8%.) Nonetheless, Dr. H.J. Crijns (University Hospital Gröningen, the Netherlands), declares that even patients with heart failure should not be in greater danger because of atrial fibrillation if the condition is well managed (Kennedy 1999; Alpert 2000; Crijns et al. 2000).

Blood thinners are often prescribed for atrial fibrillation, but a program based in natural medicine is also helpful. While full correction of the chaotic rhythm associated with atrial fibrillation is often difficult to achieve, nutritional supplements can lessen the risk of a blood clot. Dr. William Campbell Douglass, M.D., states that vitamin E (800 IU daily), cod liver oil capsules (4 daily), olive oil (1 tbsp daily), and bromelain (about 750 mg 3 times a day on an empty stomach) have similar action to Coumadin and aspirin, thinning the blood and reducing the risk of a thrombotic event (Douglass 1996). Other heart nutrients such as CoQ10, hawthorn, carnitine, taurine, magnesium, and ginkgo biloba are also important. To read more about the supplements recommended for atrial fibrillation, please consult the Therapeutic section of this protocol. Also refer to the Thrombosis Prevention protocol in this book.

Cardiovascular Disease Protocol Pg (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14)

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease