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A New, Independent Risk Factor for Heart Disease

August 2004

By William Faloon

William Faloon

Conventional doctors have long recognized obesity, cigarette smoking, high blood pressure, elevated cholesterol, and diabetes as major risk factors for a heart attack. A startling report reveals a new, independent risk factor that markedly affects the severity of coronary artery disease.

As most Life Extension members know, angina and heart attacks often manifest when the major coronary arteries become occluded with unstable atherosclerotic plaque. In a newly published study, doctors measured the degree of coronary artery disease using angiographies and then carefully evaluated all of the known risk factors that could explain the blocked coronary arteries.

The surprising finding from this new study is that blood pressure, cholesterol, diabetes, smoking, and body mass index may not be the major predictors of degree of coronary artery blockage. Instead, the three independent risk factors that predicted the severity of coronary artery occlusion were age, high-density lipoprotein (HDL), and free testosterone. In this instance, “independent risk factor” means that if you did everything else recommended to protect your heart, you would still be at greater risk for serious coronary artery blockage if you had low testosterone and low HDL.

In this study, aged men with low free testosterone and low HDL showed more severe coronary blockage, leading the doctors to conclude:

“These findings, together with the findings of previous studies from other laboratories, raise the possibility that in men selected for coronary arteriography, age, HDL, and free testosterone may be stronger predictors of degree of coronary artery disease than are blood pressure, cholesterol, diabetes, smoking, and body mass index (BMI).”1

What These Findings Mean to You
The aging arterial system, along with low levels of beneficial HDL, has long been associated with coronary artery disease. The unexpected finding in this study was that low free testosterone is also an independent predictor of the degree of coronary artery disease in men.

Life Extension members take many steps to protect their arterial systems against the deleterious effects of aging. They keep homocysteine, low-density lipoprotein (LDL), glucose, C-reactive protein, and other atherosclerosis-inducing factors at the lowest possible levels.

Artery-protecting HDL can be increased by taking high doses of niacin and chromium, and/or one glass of red wine per day.2-6 Increasing free testosterone is relatively simple to do in any man who does not have prostate cancer.

Over the past year, a remarkable number of studies have confirmed that low testosterone adversely affects cardiovascular health. We will discuss these reports and also update members on the latest studies about testosterone and prostate cancer risk.

Testosterone and Stroke Risk
One way to evaluate one’s risk for a stroke is to undergo a sonogram to measure carotid artery thickness. When excess occlusion is detected, a risky surgical procedure (carotid endarterectomy) is performed to restore blood flow to the brain.

In a study published by the American Heart Association in April 2004, sonograms were used to measure the carotid intima-media thickness in 195 independently living elderly men in 1996 and again in 2000. The researchers also measured blood levels of free testosterone in these men.

The results showed that men with low testosterone had a 3.57 times greater progression of carotid intima-media thickening than those with higher testosterone levels. These associations were independent of body mass index, waist-to-hip ratio, hypertension, diabetes, smoking, and serum cholesterol levels. The doctors concluded:

“Low free testosterone levels were related to intima-media thickening of the common carotid artery in elderly men independently of cardiovascular risk factors.”7

Testosterone for Chronic Heart Failure
Chronic heart failure is a disabling condition characterized by exercise intolerance and shortness of breath. The disease arises from prolonged inflammatory cytokine activation that also causes severe muscle wasting. Testosterone in-creases anabolic function, improves arterial dilation, augments cardiac output, and is known to have anti-inflammatory activities. Low testosterone is a common characteristic in men suffering from heart failure.

In a report published this year, 20 men with an average age of 62 took part in a randomized study in which testosterone or placebo was injected every two weeks for 12 weeks. Compared to the placebo group, men receiving testosterone could walk 3.5 times farther. Mean symptom scores and a critical blood measurement of heart function (brain natriuretic peptide) improved in men receiving testosterone, but not in the placebo group. A trend toward improved mood scores was noted in the testosterone group, which is important because men with chronic heart failure have high rates of depression. The doctors concluded that 12 weeks of testosterone treatment led to significant improvements in physical capacity and symptoms.8

Testosterone and Glycation
The best way to measure long-term blood sugar levels is the hemoglobin A1c test. A higher percentage of hemoglobin A1c is correlated with increased cardiovascular mortality. Elevated hemoglobin A1c percentage may also be an indicator of how much age-accelerating glycation is occurring throughout the body.

A study published in February 2004 measured blood levels of testosterone in 1,419 men and compared them to the percent-ages of hemoglobin A1c.9 The findings showed that men with elevated hemoglobin A1c (and diabetes) had lower levels of testosterone and that these associations were independent of obesity and body fat distribution.

Life Extension has published extensively about the lethal dangers of glycation, whereby sugar molecules bind with amino acids to form nonfunctioning structures in the body called advanced glycation end products. As large amounts of proteins become glycated, tissues throughout the body become nonfunctional. The proteins of diabetics are highly prone to glycation because of poor glucose control.10-12

The arterial system is a major casualty of the glycation process. This new study reveals how low testosterone may increase the glycation process, and helps explain why testosterone deficiency has been associated with increased risk of cardiovascular disease and atherosclerosis in men.

Most Life Extension members take carnosine to help slow the glycation process, which is a normal (albeit pathological) aspect of aging.9 This latest study indicates that overweight and diabetic men should seek to maintain high-normal testosterone levels.

Testosterone and Ejection Fraction
One way to measure the heart’s pumping capacity is to measure how much blood it pumps after each beat compared to the amount of blood remaining in the heart. This measurement is called the ejection fraction. Healthy people have an ejection fraction of 56-78%, while those with congestive heart failure are often well below 30%.

In a study published in August 2003, 96 men underwent ejection-fraction testing and coronary artery angiograms to measure the degree of coronary occlusion. The ejection fraction was substantially lower in men with low testosterone levels. Men with the lower ejection fractions averaged only 28% of the free testosterone level of men with the higher ejection fractions. The findings also showed that men with proven coronary artery disease had about 50% less total and free testosterone than healthy controls. This is the first study in a clinical setting to show that low levels of free testosterone are characteristic of patients with low ejection fraction.13

In a related study, 12 men with stable chronic heart failure were enrolled in a crossover trial in which they received either testosterone or placebo and were monitored over six hours. The subjects were then switched the next day, receiving the second treatment and repeated cardiac output monitoring. Compared with placebo, testosterone treatment resulted in a relative increase in cardiac output. This was accompanied by a reduction in systemic vascular resistance compared to baseline. These maximal changes coincided with peak elevation in serum bioavailable testosterone. The doctors concluded that administration of testosterone increases cardiac output acutely, apparently via reduction of left ventricular after-load.9

These two studies corroborate the previously discussed findings indicating that testosterone replacement could be of enormous benefit to men with heart disease.