~ Hidden Cardiac Risk Factors

By William Faloon

Despite significant advances in heart attack prevention over the past 35 years, cardiac disease remains the leading cause of death in the Western world.1

Conventional medical doctors routinely prescribe drugs that reduce potentially dangerous cholesterol and low-density lipoprotein (LDL) while sometimes boosting beneficial high-density lipoprotein (HDL). Although more people take cardiac drugs than ever before, hundreds of thousands of Americans still perish each year from heart failure while under a doctor's care.

New members often ask us why their coronary arteries continue to narrow even when they have followed all the steps their cardiologist has prescribed. The answer is that atherosclerosis has multiple underlying causes. Unless every one of these risk factors is corrected, aging adults will continue to suffer epidemic levels of vascular diseases, including heart attack and stroke.

Life Extension long ago uncovered cardiac risks that mainstream doctors ignore. Recent scientific studies have validated that atherosclerosis is indeed a multifactorial process,2-5 and that taking aggressive preventive actions can dramatically reduce one�s chances of dying from cardiovascular disease.

Why Excess Fibrinogen Is So Dangerous

Fibrinogen, a protein produced by the liver, plays a role in the development of atherosclerotic plaque. Fibrinogen can also cause acute blood clot formation that may block a coronary artery (causing a heart attack) or a cerebral artery (causing an ischemic stroke).

Back in 1996, Life Extension published data indicating that high blood levels of fibrinogen predisposed people to heart attacks. In 2001, we reported on studies indicating that high levels of fibrinogen are also a significant risk factor for suffering a stroke.6-9

Numerous reports now link elevated fibrinogen to increased heart attack and stroke risk.10 One compelling study measured fibrinogen blood levels at baseline and then carefully tracked a large group of physicians over a period of several years.11 In physicians with fibrinogen levels higher than 343 (milligrams per deciliter of blood), heart attack risk doubled compared to physicians with a fibrinogen reading below this number.

Even after adjusting for other risk factors such as body mass index, diabetes, hypertension, alcohol consumption, and HDL there was an approximately twofold increase in heart attack risk among physicians with the higher fibrinogen levels. In the physician study subjects who were given 325 mg of aspirin every other day, heart attack rates were still twice as high in those with elevated fibrinogen (though aspirin did reduce heart attack incidence across all fibrinogen ranges). Study subjects who did not take aspirin and had higher fibrinogen levels had a startling 3.6-fold increase in heart attack incidence.11

The scientists who conducted this study stated that fibrinogen "appears to be an independent risk factor for cardiovascular disease."11 This means that even if you control all other cardiac risk factors, if your fibrinogen level is over 343 mg/dL, this by itself could cause you to suffer a heart attack.

Elevated fibrinogen is not only a powerful predictor of who will develop coronary artery disease. A brand new study shows that high fibrinogen foretells who is likely to die within 42 months of suffering a heart attack. According to the scientists who conducted this 2006 study, "fibrinogen levels were the only independent predictor of mortality..."12

Despite all of this scientific evidence, few doctors today bother to check their patients' blood levels of fibrinogen. This may start to change.

Fibrinogen Finally Gets Mainstream Respect

The October 28, 2005, issue of the Journal of the American Medical Association contains an evaluation of pooled human data on fibrinogen and various diseases. A total of 154,211 study subjects were analyzed. Based on age and sex alone, the findings show that for each 100-mg/dL increase in fibrinogen over the initial baseline level, there was a 2.4-fold greater likelihood of contracting coronary heart disease.13

After adjusting for other risk factors such as diabetes, blood pressure, body mass index, and LDL, the coronary heart disease risk was 1.8-fold greater for each 100-mg/dL increase in fibrinogen levels.13 These findings corroborate previous studies suggesting that fibrinogen is a significant risk factor for heart attack and stroke!14-21

In those with fibrinogen increases of 100-mg/dL over baseline, deaths from cancers of the digestive tract, smoking-related cancers, and hormone-related cancers were also greater.13

What These Studies Tell Us

In the United States, fibrinogen is typically measured in milligrams per deciliter (mg/dL) of blood. Today's standard laboratory reference range for fibrinogen is 193-423 mg/dL. Thus, according to conventional standards, fibrinogen levels as high as 423 mg/dL are acceptable.

Previous studies have indicated higher risks of heart attack, stroke, and other vascular diseases as fibrinogen levels rise above 300 mg/dL.22-26

The doctors who authored this study published in the American Medical Association's own journal found that regardless of one's fibrinogen level at baseline (levels evaluated at baseline were between 250 and 562 mg/dL), any increase of 100 mg/dL over baseline is associated with a significantly increased risk of heart attack, stroke, other vascular diseases, and cancer.13

Based on data from dozens of published studies, it would appear that aging adults should strive for a fibrinogen level of 200-300 mg/dL.

FOUR WAYS FIBRINOGEN CAUSES HEART DISEASE

Fibrinogen has been shown to be a significant risk factor for cardiovascular disease. While scientists have yet to confirm all of fibrinogen's pathological mechanisms, they have discovered the following:
  1. As a key factor in blood viscosity (thickness), elevated fibrinogen may decrease blood flow, especially through partially blocked arteries.27-29

  2. Through its conversion to fibrin, fibrinogen may promote the formation of abnormal blood clots inside coronary arteries.30-32

  3. Fibrinogen appears to directly contribute to the atherosclerosis process by binding to LDL and stimulating the proliferation of vascular smooth muscle, thereby disrupting the endothelium.33,34

  4. By binding to certain platelet membrane receptor sites, fibrinogen may facilitate platelet aggregation inside blood vessels, thus initiating occlusive arterial blood clots.35
How Fibrinogen Facilitates Cancer

The doctors who conducted this huge study published by the American Medical Association were surprised to see increased rates of cancer in those with higher fibrinogen levels.

Fibrinogen is the precursor to fibrin in the body. Researchers believe that cancer cells use fibrin to coat themselves in order to hinder their recognition by the immune system. In addition, fibrin relays a signal to cancer cells to initiate angiogenesis, which is the growth of new blood vessels into the tumor. Fibrin-associated angiogenesis sets the stage for tumor growth and metastasis.

Cancer patients often demonstrate a hyper-coagulation state, with elevated fibrinogen playing a significant role in the process. The administration of anti-coagulant drugs like low-molecular-weight heparin has been shown to improve survival in those stricken with cancer.36,37 Anti-coagulant drugs break down fibrin in the body. Those with higher fibrinogen levels produce more fibrin. Cancer cells use this fibrin to protect themselves against the body's immune system and facilitate growth. Based on these understandings, taking steps to lower fibrinogen not only reduces heart attack and stroke risk, but also may reduce one's odds of developing cancer.

With the confirmatory findings about the lethal dangers of excess fibrinogen, it is more important than ever to have one's blood checked, to initiate fibrinogen-reducing strategies, and to have follow-up fibrinogen blood tests to assess how your fibrinogen-lowering intervention is working!

Glucose: The Sweet, Silent Killer

Scientists have known for decades that diabetics have far greater incidences of heart attack and stroke. Those with uncontrolled diabetes exhibit chronic and dangerously high levels of blood glucose.

In a startling study released by Johns Hopkins University scientists, even healthy people with higher normal blood glucose levels were shown to have more cardiac events.87

The researchers used a blood test (hemoglobin A1C) that evaluates glucose control over the previous three to four months. This test measures the percentage of sugar reactions (glycation) that have occurred in red blood cells. The "standard reference range" states that hemoglobin A1C up to 5.7% is "normal." However, the Johns Hopkins researchers found that hemoglobin A1C levels above 4.5% (even in non-diabetics) predicted greater heart attack risk.

Those with higher-than-desired blood glucose levels display no symptoms. In too many instances, however, excess glucose silently contributes to atherosclerosis and ensuing heart disease. This is why annual blood testing and proper evaluation of test results are so crucial.

PROTECTING AGAINST FIBRINOGEN'S LETHAL EFFECTS

Many dietary supplements and drugs used today exert some fibrinogen-lowering effect. For example:
  • Fish oil taken in daily doses of 3000 mg or greater has been shown to lower fibrinogen levels.38-41 It may be no coincidence that fish oil has also been shown to reduce heart attack risk.42-44 In addition to reducing triglycerides,45-48 suppressing inflammation,49-51 decreasing platelet stickiness,52,53 and protecting against arrhythmia,54-56 fish oil's ability to lower fibrinogen may be another mechanism responsible for its cardioprotective effects.

  • Olive oil has also been shown to lower fibrinogen in humans with elevated fibrinogen levels.57,58

  • For those able to tolerate its usually harmless but unpleasant side effects, niacin can help lower fibrinogen.59-61

  • High serum vitamin A and beta-carotene levels have been associated with reduced fibrinogen levels in humans.62 Animals fed a vitamin A-deficient diet have an impaired ability to break down fibrinogen. When animals are injected with vitamin A, they produce tissue plasminogen activator (tPA), which breaks down fibrinogen.63-65

  • Excessive homocysteine blocks the natural breakdown of fibrinogen by inhibiting the production of tissue plasminogen activator (tPA).66 Folic acid,67-69 trimethylglycine (TMG),70 vitamin B12,67,71-74 and vitamin B675 reduce elevated homocysteine levels.

  • Vitamin C may help reduce fibrinogen. In one study, heart disease patients were given either 1000 or 2000 mg a day of vitamin C to measure the fibrinogen breakdown effect. At 1000 mg a day, there was no detectable change in fibrinolytic activity or cholesterol. At 2000 mg a day of vitamin C, there was a 27% decrease in the platelet aggregation index, a 12% reduction in total cholesterol, and a 45% increase in fibrinolysis (fibrinogen breakdown) activity.76

  • The fibric acid class of drugs (especially fenofibrate) can lower fibrinogen by 15-40%. This drug's primary side effect is increases in indicators of liver damage in 7.5% of users (compared to only 1.4% in the placebo group). High doses of niacin may also induce increases in indices of liver damage.77

  • Agents that inhibit platelet aggregation may reduce the risk that fibrinogen will cause an abnormal arterial blood clot. Platelet aggregation inhibitors include aspirin,78 green tea,79 ginkgo,80 garlic,81 and vitamin E.82 Drugs such as pentoxifylline and Plavix also inhibit abnormal platelet aggregation and improve blood flow through the capillaries.83-86


For optimal protection against heart attack, it makes sense to try to reduce fibrinogen levels to around 200-300 mg/dL. Some people will find this impossible, but from what we now know, any reduction in fibrinogen may correlate with a reduced risk of heart attack, stroke, and cancer.

A common misconception among supplement users is that if they take nutrients that have been shown to favorably influence a risk factor (such as reducing fibrinogen), then they do not have to worry about that risk factor. Since 30-50% of plasma fibrinogen level is genetically determined, it makes sense to have your blood tested to make sure that you do not have to take additional steps to reduce your fibrinogen.

Deadly Consequences of Flawed Reference Ranges

A blood chemistry test can reveal your glucose level. Regrettably, the medical establishment has misjudged the safe upper limit for fasting glucose. The result is that doctors are failing to warn patients when their glucose levels are too high.

Initially, back in 1979, doctors diagnosed diabetes when fasting glucose levels reached 140 mg/dL on two separate occasions. In 1997, the guidelines were changed, and fasting glucose levels of 126 mg/dL or greater became the new standard for diagnosing diabetes, with concern about impaired glucose metabolism being raised when blood sugar levels were between 110 and 125 mg/dL. The slow-to-respond conventional medical establishment finally advised in 2003 that doctors should be concerned about impaired glucose metabolism when blood sugar levels reach 100 mg/dL.

Conventional medicine's flawed understanding of glucose metabolism has caused tens of millions of needless deaths. As you will soon read, even today's accepted normal glucose ranges can predispose aging adults to startlingly high mortality rates.

Life Extension has always advised members that optimal glucose levels are below 100 mg/dL.

We based our position on published studies showing increased longevity for those in lower glucose ranges.88-91 We also had the advantage of inside information about calorie-restriction experiments that indicated ideal glucose levels to be around 74 mg/dL.

Keep Glucose in Lower Reference Ranges

Several years ago, Life Extension alerted members that those with higher 'normal' blood glucose readings were at increased risk of premature death.92

Our warning was based on a study showing greater cardiovascular disease incidence as blood glucose levels rise past 85 mg/dL.93 Back in those days, doctors did not worry about glucose until it reached far higher levels. Contrary to conventional wisdom, we advised members to try to keep their glucose levels at 85 mg/dL or lower.

Newly published studies have documented the fact that higher glucose readings elevate vascular disease risk.94-99 In heart attack victims admitted to the hospital, those with the highest glucose levels have been shown to be much more likely to suffer severe cardiac outcomes (and death).95,97,98 One study looked at emergency room cardiac patients in 2002 and found that 65% were either diabetic or had impaired glucose control.96 The cumulative findings from these studies mandate that aging humans take aggressive steps to maintain optimal blood glucose levels.

An annual blood chemistry test is the best way to make sure your glucose level is in an optimal range. The hemoglobin A1C test is an even better indicator of your glucose levels, as it measures that amount of glycation that glucose has inflicted on your red blood cells during the previous three to four months.

HEMOGLOBIN A1C AND CARDIAC RISK

The hemoglobin A1C blood test measures the percentage of hemoglobin that has become glycated as a result of glucose-protein reactions. Hemoglobin A1C has long been used to monitor long-term control of diabetes.

The level of hemoglobin A1C is increased in the red blood cells of people with poorly controlled glucose. Since the test evaluates hemoglobin in red blood cells (which normally live about 120 days), the level of hemoglobin A1C reflects the average blood glucose level over the previous three to four months.

Based on recent findings, an ideal reading of hemoglobin A1C is 4.5% or lower.87 Standard laboratory reference ranges, however, erroneously indicate that non-diabetics can have a hemoglobin A1C reading as high as 5.7%. We now know that the greater the level of hemoglobin A1C above 4.5%, the more likely one is to suffer a heart attack.

Diabetics often have hemoglobin A1C levels higher than 7%, which helps explain the multitude of sugar-related complications suffered by those unable to maintain healthy blood glucose levels.

It is commonly recommended that hemoglobin A1C be measured every three to six months in diabetics. The new data show that higher hemoglobin A1C levels in non-diabetics predict heart attack risk. This indicates that the hemoglobin A1C blood test may have a role in alerting those with less-than-optimal glucose control that they should make lifestyle changes. Lowering the level of hemoglobin A1C by any amount improves one's chances of staying healthy.

Whether you use your own doctor, a commercial laboratory, or our blood testing service, I encourage every member to have his or her blood tested at least once a year.

See References Below.


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