Life Extension Magazine November 2003
|A Comprehensive Guide to Preventative Blood Testing |
By Penny Baron
Tissue necrosis factor-a
Elevated levels of TNF-a have also been found in people with high blood pressure,31 and together with IL-6 may be associated with risk of heart disease.32 In a study by Verdeccia et al, levels of TNF-a were measured in persons with or without high blood pressure to ascertain if arterial flow-mediated dilation was affected by hypertension and chronic inflammation. Investigators found that regardless of whether blood pressure was controlled with antihypertensive medication, arterial flow-mediated dilation was significantly impaired in the hypertensive group. This group also showed higher levels of TNF-a, indicating persistent inflammation despite controlling blood pressure. This study showed that even when blood pressure is under control, hypertensives still suffer from continuous damage (endothelial dysfunction) to the inner lining of the arterial wall caused by a chronic inflammatory insult. These findings indicate that hypertensives should have their blood tested for TNF-a to assess how much inner wall (endothelial) arterial damage is occurring. If the level of TNF-a is high, aggressive therapies to suppress the inflammatory cascade should be considered.
A study by Lappe et al showed that increased concentration of IL-1b significantly and independently (of cardio CRP) predicted a step-wise increase in the risk of death or myocardial infarction.33
IL-1b is one of the key mediators of immunobiological responses to physical stress. A study by Brambilla et al showed that IL-1b concentrations were significantly higher in patients with panic disorder both before and after alprazolam (Xanax™) pharmacotherapy, suggesting that IL-1b levels may be a marker of panic disorder that is not related to current levels of symptomology.34
Elevated IL-6 is associated with an increased risk for heart attack and stroke. A 1999 study found that individuals with high levels of both IL-6 and CRP were 2.6 times more likely to die during the nearly five-year study period than those with low levels of both measurements of inflammation.37
Elevated IL-6, along with C-reactive protein, may be predictive of development of diabetes Type II.21 Pradhan et al followed 27,628 healthy (free of diagnosed diabetes Type II, cardiovascular disease and cancer) women for four years to determine whether elevated blood levels of IL-6 and CRP were associated with development of diabetes Type II. Investigators found that IL-6 was significantly higher among women who subsequently developed diabetes, and that the highest levels of IL-6 increased risk for diabetes 7.5 times (women in the highest CRP ranges were 15.7 times more likely to develop diabetes Type II). After adjusting for other risk factors—body mass index, family history, smoking, alcohol, exercise, and hormone replacement therapy—women with the highest levels of IL-6 were 2.3 times more likely to become diabetic (4.2 times for the highest CRP blood levels). Investigators concluded that their data supported a possible role for inflammation in the diabetes.
Elevated IL-6 levels have also been found to predict risk of death from all causes, independent of other mortality risk factors.37 Harris et al followed 1,293 healthy, elderly people for 4.6 years to determine the association between IL-6, CRP, and mortality. The study found that increased levels of IL-6 were associated with a twofold greater risk of death (and, to a lesser extent, CRP), and that risk increased to 2.6 times when levels of both IL-6 and CRP were elevated.
Studies have shown a link between IL-6 and insulin-like growth factor I (IGF-I), which normally declines with age. Cappola et al found that the combination of elevated IL-6 and decreased IGF-I synergistically confers a high risk for progressive disability and death in older women.38 Ferrucci et al found that elderly persons with the highest circulating levels of IL-6 were 1.76 times more likely to develop mobility-disability and 1.62 times more likely to develop mobility plus ADL (activities of daily living)-disability compared with persons with the lowest levels of IL-6.39
Fibrinogen is also an acute-phase protein reactant, meaning that it increases in response to disease processes involving tissue inflammation or damage. As discussed in the C-reactive protein section, development of atherosclerosis and heart disease are products of inflammatory processes. As such, fibrinogen, which is a measure of inflammation, can help predict risk of heart disease and stroke, and can complement tests for serum cholesterol, cholesterol lipoproteins, lipids, C-reactive protein, and inflammatory cytokines.
High fibrinogen levels may indicate a risk of heart disease. Levels are also increased in other inflammatory disorders, in pregnancy, and in women taking oral contraceptives. Decreased levels are seen in patients with hereditary afibrinogenemia, intravascular coagulation, primary and secondary fibrinolysis, and liver disease. An increase in dietary fish oils may result in decreased fibrinogen levels,40 which has important implications for patients at risk for heart disease and stroke.