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Biomarkers in Cardiovascular System

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Presentation on theme: "Biomarkers in Cardiovascular System"— Presentation transcript:

1 Biomarkers in Cardiovascular System
Dr. Bibi Kulsoom

2 Cardiovascular Biomarkers
KULSOOM Cardio Blood Substances that Lead to Involved in process of Released as a result of cardiovascular disease Appearance of abnormal substances and/OR ed level of normal substances Detected or measured in blood as a marker Sampling Vascular

3 Cardiovascular Biomarkers: Serum Lipid
KULSOOM Lipid profile: Normal Levels LDL : < 100mg/dl HDL: 40-60mg/dl Total chol : <200mg/dl Triglycerides: < 150 mg/dl TG VLDL LDL LDL Lipid profile: Abnormal LDL HDL Total cholesterol Triacylglycerol HDL Chol HDL Extra Chol Increased risk of CVS Disease HDL Blood vessel wall

4 Protein Biomarkers Enzymes Creatine Kinase Lactate Dehydrogenase
KULSOOM Enzymes Creatine Kinase Lactate Dehydrogenase Aspartate Transaminase (AST) Other Proteins Apolipoprotein A Apolipoprotein B Troponin I Troponin T Myoglobin Homocysteine (amino acid) C-reactive Protein Fibrinogen Amyloid A Brain Natriuretic Factor Atrial Natriuretic Factor

5 Creatine (Phospho) Kinase (CK, CPK)
KULSOOM Tissue location & Isoenzymes : Three isoenzymes found CK-MM (97%): found in skeletal muscles CK-MB(2%): found in cardiac muscles CK-BB(traces): found in brain cells Function: Creatine phosphate quickly regenerates ATP in the tissues. Arginine + Glycine + Methionine  Creatine. ATP ADP Creatine Creatine phosphate Creatine kinase

6 Creatine (Phospho) Kinase (CK, CPK)
KULSOOM Main conditions with raised levels of CK-MB is heart tissue damage(e.g. myocardial infarction (MI)). A total CK level will reflect the presence of tissue damage but, specific isoenzyme (CK-MB) can identify the underlying cause or its location. Normal levels of total CK =30 to 180 U/L (units per liter). CK-MB fraction: 0-5% of CK, CK-MB activity: 0-15%

7 Lactate Dehydrogenase
KULSOOM Tissue location & Isoenzyme: five isoezymes mainly distributed as follows: LDH-1: heart muscle and red blood cells. LDH-2: white blood cells. LDH-3: lungs. LDH-4: kidney, placenta, and pancreas. LDH-5 : liver and skeletal muscle.

8 Lactate Dehydrogenase
KULSOOM Function: Main conditions with abnormal levels: tissue damage (e.g. MI), cancers, kidney disease, and liver disease. LDH1 is raised in heart tissue damage. Normal levels: U/L NAD+ NADH Lactate Pyruvate Lactate dehydrogenase

9 Lactate Dehydrogenase
KULSOOM A total LDH level will reflect the presence of tissue damage but, by itself, it cannot be used to identify the underlying cause or its location. LDH too has been superseded by the newer markers and should not be included in the ‘cardiac profile’. But LDH might be used as a marker of cardiac dysfunction where a troponin assay is not available.

10 Aspartate Transaminase (AST)
KULSOOM One of the oldest markers of MI. AST (+ CK and LDH) is still in use. Levels can be elevated in liver diseases as well. Little value as a marker of cardiac dysfunction and has been superseded by newer markers.

11 Cardiovascular Biomarkers: Serum Apolipoproteins
KULSOOM Apolipoprotein A Apolipoprotein B TG VLDL LDL  Apolipoprotein A  Apolipoprotein B LDL HDL Chol HDL Extra Chol Increased risk of cardiovascular Disease HDL Blood vessel wall

12 Troponins KULSOOM Troponin Tropomyosin Actin I C T

13 Troponins Tissue location & types: cytoplasm of the muscle cells
KULSOOM Tissue location & types: cytoplasm of the muscle cells Three types, which regulate muscle contraction. Troponin C (TnC) binds to calcium ions to produce a conformational change in TnI Troponin I (TnI) binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place. Troponin T (TnT) binds to the tropomyosin strand forming a complex.

14 Troponin I & T KULSOOM TnT & TnI are specific (different) for skeletal & heart muscle. They are measured in the blood to differentiate between unstable angina and myocardial infarction (heart attack) in patients with chest pain

15 Myoglobin KULSOOM A protein which stores oxygen inside muscle tissue (cardiac, skeletal & smooth). is the earliest biological marker of myocardial necrosis. This is now replaced by troponin, the more specific one. has the advantage of responding very rapidly, rising and falling earlier than CK-MB or troponin. Raised in muscle damage (e.g. MI, skeletal muscle damage). Normal levels in blood: < 80 ng/mL.

16 Biomarkers Released in Blood after Myocardial Infarction
KULSOOM Myoglobin Total CK LDH CK-MB Troponin I

17 Biomarkers Released in Blood after Myocardial Infarction
KULSOOM Troponin T Troponin I CK-MB & Total CK Myoglobin

18 Biomarkers Released in Blood after Myocardial Infarction
KULSOOM

19 Biomarkers Released in Blood after Myocardial Infarction
KULSOOM MARKER DETECTION PEAK DISAPPEARANCE Myoglobin 1 – 4 h 6 – 7h 24h CK-MB mass 3 – 12 h 12 – 18 h 2– 3 days Total CK 4 – 8 h 12 – 24 h cTnT 4 – 9 h 12 – 48 h 5 – 7 days cTnI LDH 24-48 hrs 48-72 hrs 10-14 days

20 Metabolism of Homocysteine
KULSOOM THF Methionine ATP Methyl THF B12 Pi + PPi Serine Homocysteine S-Adenosylmethionine Adenosine Methyl acceptor B6 Methylated product S-Adenosylhomocysteine Cystathionine B6 -ketobutyrate Cysteine THF = Tetrahydrofolate

21 The normal levels of homocysteine should be less than 10 micromoles/L.
Elevated Homocysteine Levels Increase the Risk for Cardiovascular Disease KULSOOM 3 2 Arterial wall cells proliferate in an effort to heal the lesion, leading to plaque formation. 1 Circulating monocytes rush to the site of injury causing inflammation. Homocysteine injures the arterial wall and fatty substances accumulate. The normal levels of homocysteine should be less than 10 micromoles/L.

22 C-reactive Protein (CRP), Fibrinogen & Amyloid A protein
KULSOOM  C-reactive protein  Fibrinogen  Amyloid A protein Activation certain genes Inflammation in any part of the body IL-6 Increased risk of cardiovascular Disease  C-reactive protein  Fibrinogen  Amyloid A protein Inflammation in atherosclerotic plaque Markers of inflammation Favor more inflammation More coagulobility

23 C-reactive Protein (CRP), Fibrinogen & Amyloid A protein
KULSOOM CRP is a protein present in the blood (secreted by liver) that shows the presence of inflammation in the body. Atherosclerosis is an inflammatory process. CRP can be a marker of atherosclerosis and myocardial infarction. Fibrinogen is a protein present in the blood that shows the predisposition to thrombus formation. Atherosclerosis can rupture and lead to thrombus formation which is the collection of fibrin meshwork of and platelets aggregation. Hence it can be a marker of myocardial infarction. Amyloid A a protein in the blood secreted by liver in response to the presence of inflammation in the body. Amyloid A can be a marker of atherosclerosis.

24 Atrial & Brain Natriuretic Peptide(ANP)
KULSOOM Atrial natriuretic peptide (ANP): Secreted by atrial muscles in response to atrial distention due to any cause. Normal levels: p mol/L Brain natriuretic peptide(BNP): Secreted by ventricular muscles stretching. Normal values of BNP: <50 pg/ml BNP: >100 pg/ml suggests congestive heart failure. Thank You


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