Functional Blood Chemistry & CBC Analysis Session 10 Inflammation Markers The 19 Deadly Sins of Heart Disease 1. Excess LDL 2. Excess Total cholesterol 3. Low HDL 4. Excess Triglycerides 5. Oxidized LDL 6. High Glucose 7. Elevated HgB A1C 8. Excess Insulin 9. Elevated HS CRP 10. Excess Homocysteine 11. Excess Fibrinogen 12. Low vitamin D 13. Low Vitamin K 14. Low blood EPA/DHA 15. Low Free Testosterone 16. Increased estrogen 17. Increased ferritin 18. Increased BMI 19. Hypertension Cardiovascular Disease and Inflammation High Sensitivity C Reactive Protein (Hs CRP) 1
High Sensitivity C Reactive protein Hs CRP C Reactive Protein Reference Ranges Normal reference range: Men: 0 3 mg/l Women: 0 3 mg/l Optimal reference range: Men: <0.55 mg/l Women <1.5 mg/l SPECIAL NOTE ABOUT CRP TESTING General CRP: reportable range 0.3 to 20 mg/dl or 3 to 200 mg/l. THIS IS NOT THE CORRECT TEST TO USE. High Sensitivity CRP: usually reported on the blood test as hs CRP. THIS IS THE ONLY CRP VALUE TO USE. 2
Elevated CRP Levels Increased risk of heart disease and stroke Increased Alzheimer s risk Depression Diabetes C reactive protein and IL 6 predict death Homocysteine Elevated Homocysteine Causes B vitamin deficiency Genetic factors Remethylation deficits Increasing age Kidney impairment Other factors. 3
Causes: High homocysteine High glucose High fibrinogen High CRP Low testosterone High iron Free radicals Endothelial Dysfunction Homocysteine Reference Ranges Normal reference range: Men: 43 4.3 15.3 μmol/l Women: 3.3 11.6 μmol/l Optimal reference range: Men: <7.2 μmol/l Women <7.2 μmol/l Mortality in Coronary Artery Disease and Homocysteine Homocysteine Risk of Dying Blood Level (3.9-5.3 3 years) Less than 9 µmo/l 3.8% Between 9 and 15 8.6% Greater than 15 24.6% 4
Heart Disease and Homocysteine Coronary Artery Disease Heart Attack Atherosclerosis Ischemic heart disease Elevated Homocysteine Levels and Stroke Homocysteine Level Less than 7 µmol/l Between 7 and 9 Between 9 and 11 Above 11 Stroke Risk Control group 26% increased risk 31% increased risk 74% increased risk Iso H, Moriyama Y, Sato S, et al. Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese. Circulation. 2004 Jun 8;109(22):2766 72. Other Diseases and Homocysteine Birth defects Colorectal cancer Cervical cancer Depression Alzheimer s disease Dementia Inflammatory Bowel Disease Aneurysm Osteoporosis Bipolar disease Macular degeneration Schizophrenia 5
Lowering Homocysteine Nutrients Folic Acid 800 3,200 mcg Vitamin B12 500 2,000 mcg Trimethylglycine (TMG) 500 8000 mg Multivitamin with B Complex and Zinc High doses of Vitamin C CRP, Homocysteine & Recent Studies Fibrinogen 6
Fibrinogen Why is it important? Fibrinogen Reference Ranges The normal range is 193 423 mg/dl or 1.93 4.23 g/l. Optimal 200 300mg/dL 7
Elevated Levels of Fibrinogen A prospective study of fibrinogen and risk of myocardial infarction in the Physicians Health Study Ma J, Hennekens CH, Ridker PM, Stampfer MJ. J Am Coll Cardiol 1999 Apr; 33(5):1347 52 Conclusion: Fibrinogen appears to be an independent risk factor for cardiovascular disease Elevated Levels of Fibrinogen Fibrinogen as a predictor of mortality after acute MI: 42 month follow up study Coppola G, Rizzo M, Abrignani MG, et al. Ital Heart J. 2005 Apr;6(4):315 22 Conclusion: Fibrinogen levels were the only independent predictor of mortality Elevated Levels of Fibrinogen Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual id participant i t meta analysis. Danesh J, Lewington S, Thompson SG, et al. JAMA. 2005 Oct 12;294(14):1799 809. Conclusion: After adjusting for other risk factors, for each 100 mg/dl increase in fibrinogen over the initial baseline there was a 1.8 fold greater likelihood of coronary heart disease 8
4 Ways fibrinogen increases risk of heart disease 1. Binding to LDL 2. Conversion to fibrin 3. Decreased blood flow 4. Facilitating platelet aggregation Drugs and Fibrinogen Drugs that may increase fibrinogen levels include birth control pills and estrogen. Fibrinogen: Summary Fibrinogen levels should be checked in patients at risk for heart disease, stroke, and with cancer, especially colon cancer Try and reduce patients fibrinogen levels to around 200 300 mg/dl or 2 3 g/l. This may be difficult but any reduction in fibrinogen may correlate with a reduced risk of heart attack, stroke, an cancer 9
Nutritional supplements to lower fibrinogen 1. Lumbrokinase (Boluoke) or Natokinase 2. Fish oil 3. Olive oil 4. Niacin 5. High serum vitamin A and beta carotene 6. Reduce homocysteine B12, B6, Trimethylglycine, Folic acid 7. Inhibit platelet aggregation: aspirin, green tea, gingko, garlic, vitamin E Functional Diagnosis of Inflammation LDH Uric Acid ESR LDH and Uric Acid Inflammation and Tissue Destruction 10
Increased Uric Acid and Inflammation Increased Uric Acid ( >5.5, >5.9) can be used as a very strong indicator for: Potential inflammation Metabolic disturbance Circulatory and oxidative stress Increased Uric Acid & Atherosclerosis Increased uric acid level (>5.9 or > 351 mol/dl) Increased triglyceride (>200 or 2.2626 mmol/l) in relation to total cholesterol (>220 or 5.69 mmol/l), Decreased HDL (<45 or 1.16 mmol/l) and an Increased LDL (>120 or 3.1 mmol/l), Platelet levels may also be increased (>385). Uric Acid Clinical Implications HIGH Gout Pre Clinical gout Atherosclerosis Oxidative stress Arthralgias Renal insufficiency Renal disease Circulatory disorders Leaky gut syndrome Dietary purines 11
LDH Normal Optimal LDH 1-240 140 200 Elevated levels of LDH are useful for determining presence of tissue damage Isoenzyme fraction testing LDH Clinical Implications HIGH Non specific tissue inflammation Tissue destruction Liver/biliary dysfunction Cardiovascular disease Anemia B12/folate deficiency Anemia hemolytic Viral infection ESR Erythrocyte Sedimentation Rate 12
ESR Ranges Conventional Laboratory Range: Males: 0 15 mm/hour Females: 0 20 mm/hour Optimal Range Males: <5 mm/hour Females: <10 mm/hour Elevated ESR Clinical Implications Tissue Inflammation Tissue Destruction Musculoskeletal Conditions Cardiovascular Conditions Malignant Diseases Vit. D Def. in Pain & Inflammation Mechanism: Vitamin D deficiency reduces calcium absorption The body increases the output t of Parathyroid Hormone (PTH) Increased PTH causes an increase in urinary excretion of phosphorous causing hypophosphatemia Decrease in the formation of a mineral called calcium phosphate Hydration of the unmineralized collagen matrix causes it to swell and put pressure on the nerve endings in the periosteum. 13
Vitamin D Reference Ranges Deficient levels of vitamin D: <20 mg/ml (<50 nmol/l) Insufficient levels: 20 40 ng/ml (50 100 nmol/l) Optimal levels: 40 65 ng/ml (100 160 nmol/l) Autoimmune Processes A potential developing auto immune processes may be associated with a low triglyceride level Lowtriglycerides havebeen associatedwith anincreased risk of tissue damage. The problem may be inflammatory or destructive in nature. By no means diagnostic for an autoimmune disease, consider a low triglyceride, along with other tests, as a marker for further investigation. Autoimmune Processes Pattern If triglycerides are decreased (<40) with low or normal cholesterol (160 220) and an increased HDL (>70), then some kindof autoimmuneprocess maybe occurring somewhere in the body. Check for increases in LDH levels (>200) and be sure to run an ESR, which will be elevated as a non specific marker for inflammation. Consider further testing to rule out tissue inflammation or destruction (C reactive protein, ANA, rheumatoid factor, serum protein electrophoresis etc.). 14
Impaired cell membrane health Increased serum calcium (>10.0) along with an increased LDH ( >200) can be suggestive of cellular membrane disruption and/or destruction. Potassium mayalso also be elevated (>4.5) Calcium is a vital component of the interstitial matrix facilitating cell to cell adhesion and communication. It will be released into the serum if this matrix is disrupted. Space occupying lesions should be considered and ruled out with appropriate examination and testing. Consider an AMAs test. SUMMARY 15