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November 2003

A Comprehensive Guide to Preventative Blood Testing
By Penny Baron

In non-pregnant women, estradiol is the most commonly measured type of estrogen; levels vary throughout the menstrual cycle, and are reduced to low but constant levels after menopause. Increased levels of estradiol in woman indicate an increased risk of breast or endometrial (lining of the uterus) cancer. In men, estradiol is produced in amounts far lower than in women, and indicates hypothalamic and pituitary function. Increased levels of estradiol along with decreased levels of testosterone may indicate decreased sex drive and ability to urinate. In men, estradiol and testosterone levels should be tested together.

Elevated levels of the amino acid homocysteine have been shown to be an independent risk factor for development of coronary artery disease and thrombosis (stroke). Data also indicate that homocysteine levels may be elevated in patients with depression; if folic acid (which normally helps to break down homocysteine) levels are depressed, homocysteine levels increase

C-Reactive Protein (CRP) and the Cardio CRP Test
Inflammation is a key pathogenic mechanism for development and progression of atherosclerosis and heart disease. Atherosclerosis is essentially an inflammatory response to an injury, such as hypertension, cigarette smoking, a diet rich in low-density lipoproteins (LDL, the so-called “bad” cholesterol), and hyperglycemia, among others. These stimuli elicit secretion of molecules that, along with uptake of cholesterol lipoproteins, most likely form the basis for the atherosclerotic “fatty streak” along arterial walls.

While still present, these risk factors continue to facilitate the attraction and accumulation of inflammatory cells—macrophages, mast cells, and activated T-lymphocytes—within the atherosclerotic plaque. Disruption of this plaque, caused by chronic inflammation, may cause a heart attack as oxygen-deprived blood vessels become clogged with pieces of dislodged plaque material.

C-reactive protein is a very sensitive marker of systemic inflammation, and has emerged as a powerful predictor of coronary heart disease21 and other cardiovascular diseases.

The highly sensitive cardio CRP test is able to measure the presence of C-reactive protein in the blood, even at very early stages of vascular disease, allowing for appropriate intervention with diet, supplements, or anti-inflammatory therapy.

Elevated levels of C-reactive protein have also been found to be associated with risk of developing diabetes Type II,22 loss of cognitive ability in seemingly healthy people,23 Alzheimer’s disease, and depression in the elderly. Furthermore, risk factors for atherosclerosis and heart disease, such as smoking and high blood pressure, elevate blood levels of C-reactive protein that can be detected by the cardio CRP test.24

PSA (prostate specific antigen); free and complexed
Offered as part of the male testing panel, PSA is a very sensitive marker that may suggest prostate cancer. It may also be used to monitor efficacy of therapeutic regimens associated with the prostate.

PSA is normally found at million-fold lower concentrations in the serum than in the seminal fluid. In seminal fluid, PSA predominantly exists in the “free” (uncomplexed) state; in serum, it is generally found bound to inhibitors. Risk of prostate cancer may be assessed by determining absolute amounts of total PSA or by calculating the percent of free PSA compared to total PSA (complexed plus uncomplexed). A study in the New England Journal of Medicine found that 25% of patients with normal digital rectal exams (DRE) and total PSA levels of 4.0–10.0 ng/ml had prostate cancer.25 In the same study group, researchers calculated that risk of prostate cancer increased with decreases in the percentage of free PSA in the serum. In other words, as the ratio of complexed to free PSA increased (concomitant with total increased levels of PSA), risk of prostate cancer increased dramatically.

It should be noted that elevated levels of PSA may not necessarily signal prostate cancer, and prostate cancer may not always be accompanied by expression of PSA. Levels may be elevated in the presence of a urinary tract infection and an inflamed prostate.

In another study recently published in the New England Journal of Medicine, investigators recommended lowering the PSA cutoff from 4.1 ng/ml (the threshold at which biopsy is currently recommended). At the current threshold, it was determined that “82 percent of cancers in younger men and 65 percent of cancers in older men would be missed.”26 But levels below the currently recognized cutoff of 4.1 ng/ml may not distinguish between prostate cancer and benign prostate disease. New tests looking at PSA precursor (proPSA) alongside PSA may aid in improving diagnosis. Clinical trials are currently under way.27

Progesterone levels, included in the female testing panel, may track menstrual/ovulation cycles (levels are highest during mid-cycle, the time of ovulation) and may be used as a marker for ovarian and adrenal tumors, and for leuteal ovarian cysts (increased levels). Decreased levels are associated with amenorrhea (lack of menstruation), fetal death, and toxemia in pregnancy. Adelaide’s Exercise Physiology Laboratory in Australia recently reported that women who exercised during times when progesterone and estrogen levels were at their highest (mid-month) had increased rates of fat metabolism as well as lower perceived exertion levels, suggesting more benefit from exercise during times of peak hormone levels.28

Systemic inflammation and tests for proinflammatory cytokines TNF-a, IL-6, IL-1b and IL-8
While the presence of C-reactive protein indicates inflammation, tests for specific proinflammatory cytokines (which regulate C-reactive protein) may identify the underlying cause of inflammation.

Cytokines are cellular growth factors that are synthesized by nearly every cell of the body and are generally produced only in response to “stress.” Secreted primarily from leukocytes (white blood cells), cytokines regulate the hosts’ response to infection, immune responses, inflammation, and trauma. Cytokines may be either proinflammatory (worsen disease) or anti-inflammatory (reduce inflammation and promote healing). Some studies suggest that susceptibility to disease may result from an imbalance between pro- and anti-inflammatory cytokines.29

There is also mounting evidence that depression may directly stimulate the production of proinflammatory (primarily IL-6) cytokines or indirectly stimulate production by down-regulating the cellular immune response (i.e., prolonged infection and delayed healing fuel sustained cytokine release).30

The pro-inflammatory cytokine panel detects abnormally high levels of the most dangerous inflammatory cytokines in the blood: tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 beta (IL-1b), and interleukin-8 (IL-8).