The heart is the muscular organ of the circulatory system that constantly pumps blood throughout the body.

Approximately the size of a clenched fist, the heart is composed of cardiac muscle tissue that is very strong and able to contract and relax rhythmically throughout a person's lifetime. It has four separate compartments or chamber used in circulating the blood through the body. The Cardiac Profile is a series of tests which would assess the function of the heart and evaluate any injuries obtained. SEVEN CLASSIC SYMPTOMS OF HEART DISEASE AND THEIR MOST COMMON CAUSE SYMPTOM MOST COMMON CAUSE Dyspnea Diminished heart function Chest pain Coronary artery disease Palpitations Extra heart beats Syncope Disturbance of heart rhythm Edema Diminished cardiac function Cyanosis Pulmonary insufficiency Fatigue Lack of sleep Ischemia is the lack of adequate blood supply; it is the most disease process. Atherosclerosis is the buildup of plaques in the blood vessels and causes damage to the endothelium. Early stages of atherosclerosis (less than 10-20% reduced in coronary artery diameter) can lead to angina. A more rapid reduction I n blood flow can stimulate the production of thrombus which would lead to Acute Coronary Syndrome. When there is a complete blockage of supply to the cardiac muscle, this would lead to irreversible ischemia and then MI would occur. But if the blockage is incomplete, the person may only suffer unstable angina. The heart diseases which are the results of impaired coronary blood flow is termed as Coronary Heart Disease. Myocardial infarction is a myocardial necrosis due to prolonged ischemia. It may be categorized according to size of infarct or pathologically categorized.

Size of Infarct 1. 2. 3. 4. Microscopic focal necrosis Small - <10% of the left ventricular myocardium Moderate 10%-30% of the left ventricular myocardium Large - >30% of the left ventricular myocardium

Pathologically categorized as: 1. Acute MI presence of PMNs 2. Healing MI no PMNs but with Mononuclear cells and fibroblasts 3. Healed presence of scar tissue, 5-6 weeks. Diagnosis of MI 1. Rise or fall of cardiac biomarkers with atleast one value above the 99 th percentile, evident ischemia and atleast one of the following. a. Symptoms of ischemia b. ECG changes c. Development of pathologic Q waves d. New loss of viable myocardium, or new regional wall motion abnormality 2. Unexpected cardiac death 3. Percutaneous coronary interventions a. Periprocedural myocardial necrosis is indicated by normal troponin level, cardiac biomarker above the 99th percentile. b. 3 times the 99th percentile is used to define PCI-related MI. 4. Coronary artery bypass grafting a. Periprocedural myocardial necrosis is indicated by normal troponin level, cardiac biomarker above the 99th percentile. b. 5 times the 99th percentile is used to define CABG-related MI. c. Plus either new pathologic Q waves, or new LBBB, or angiographically documented new graft or native coronary artery occlusion or imaging device of new loss of viable myocardium. 5. Pathologic findings of AMI

Troponins I and T are the currently preferred cardiac markers. An ideal cardiac marker should be: 1. 2. 3. 4. 5. 6. 7. High specificity for myocardial damage in presence of skeletal injury. High sensitivity to detect very minor cardiac damage Capability to differentiate reversible from irreversible cardiac damage. Ability to be used as a monitor of prognosis and therapy. Ability of rapid, easy-to-perform, and cost-effective quantitative assays Absent or not detectable in patients without myocardial damage. Increased within six to nine hours after onset of symptoms and remains abnormal for several days.

The measurement of proteins specific to cardiac cells is for the diagnosis and management of acute coronary syndromes, the measurement of substances that are damaging the arteries for assessing risk of coronary heart disease and the measurement of natriuretic peptides for Congestive heart failure. MARKERS OF MYOCARDIAL DAMAGE Enzymes -AST, LDH and LDH isoenzymes are examples of enzymes which were in the past, but are not currently recommended. Blood levels of CK rise when muscle or heart cells are injured. The doctors may test for CK if you have chest pain or other signs and symptoms of a heart attack. In the first 4 to 6 hours after a heart attack, the concentration of CK in blood begins to rise. It reaches its highest level in 18 to 24 hours and returns to normal within 2 to 3 days. The amount of CK in blood also rises when skeletal muscles are damaged. A high CK, or one that goes up from the first to the second or later samples, generally indicates that there has been some damage to the heart or other muscles. It can also indicate that your muscles have experienced heavy use. If the doctors suspects a heart attack and your CK is high, they will usually order a more specific test (troponin) to see if your heart is damaged. Normal value:38-120 ng/mL

CK and its isoenzyme CK-MB is not recommended because of large skeletal muscle distribution and lacks specificity. CK has 3 cytosolic isoenzymes: 1. CK-MM(CK-3) skeletal muscle and heart 2. CK-MB(CK-2) myocardium 3. CK-BB(CK-1) brain and not in the blood CK-MB Rises: within 4-6 hrs after onset of angina Peaks: 12-24 hrs Returns to Normal: within 2-3 days CK-MB mass assays replaced the CK-MB activity assays because the mass assays increases an hour earlier than activity-based assays.CK-MB Mass Assay is an immunometric assay using monoclonal antibody. The protein is simply measured as an antigen. The test can be performed rapidly and can be done in under an hour, but it is not specific for the myocardium. Relative Index (RI) is the ratio of CK-MB mass to total CK activity. It suggests cardiac damage if the RI is high, and if the CK-MB mass exceeds 5ng/mL with an RI of 2% this suggests myocardial infarction. If the value of CK-MB is elevated and the ratio of CKMB to total CK (relative index) is more than 2.53, it is likely that the heart was damaged. A high CK with a relative index below this value suggests that skeletal muscles were damaged. CKMB levels, along with total CK, are tested in persons who have chest pain to diagnose whether they have had a heart attack. Since a high total CK could indicate damage to either the heart or other muscles, CKMB helps to distinguish between these two sources. CK-MB is usually ordered along with total CK in persons with chest pain to determine whether the pain is due to a heart attack. It may also be ordered in a person with a high CK to determine whether damage is to the heart or other muscles. Although CK-MB is a very good test, it has been largely replaced by troponin, which is more specific for damage to the heart. Normal value: 0-3 ng/mL

Cardiac proteins - monitored in cases of AMI which includes myoglobin, cardiac troponins and cardiac myosin light chains. Myoglobin is present in both skeletal and cardiac muscle damage. Rises: 1-4 hrs after onset Peaks: 6-9 hrs Returns to Normal: 18-24 hrs. *Normal Myoglobin levels within 8hrs rules out AMI because it is found in all AMI patients between 6-9 hrs after onset. Due to the size of Myoglobin, there is also a rapid clearance by the kidneys which would rule out reinfarction. Myoglobin binds oxygen within cardiac and skeletal muscles. With a small molecular weight, it is the first to leak whenever MI occurs. It is elevated in the serum 2-3 hrs it peaks after 6 hours. With a half life of 4 hours it hits the baseline after a day. It is mainly cleared by renal filtration. Men have higher myoglobin plasma level than in women, because myoglobin is related to muscle mass. Its advantage over other markers is that it turns positive sooner than troponin. However, myoglobin may come from either heart or skeletal muscle, so an increase in serum myoglobin is not specific for damage to the heart. Consequently, a negative myoglobin result effectively rules out a heart attack, but a positive result must be confirmed by testing for troponin. An increase in blood myoglobin means that there has been very recent injury to the heart or skeletal muscle tissue. Additional tests, such as troponin, are necessary to determine where the damage has occurred. If myoglobin does not increase within 12 hours following the onset of chest pain, a heart attack is very unlikely, unless the symptoms began more than a day earlier. Since this blood test is used to detect increased levels in people with chest pain, a low or normal level of myoglobin means that either a heart attack has not occurred or myoglobin has already cleared the bloodstream. A test for troponin or other cardiac markers may be used as follow-up to a low or normal result.

Normal value: - myoglobin (Male) 10 95 ng/ml (onset: 1-3 hrs, peak: 6-10 hrs, return to normal: 12-24 hrs) - myoglobin (Female) 10 65 ng/ml (onset: 1-3 hrs, peak: 6-10 hrs, return to normal: 12-24 hrs) Troponin is the preferred bio marker, it binds to calcium and regulates muscle contraction. After injury, troponin subunits are released into the bloodstream and they are highly specific and sensitive for myocardial damage. Unlike CK-MB, troponin is not found in healthy individuals. It is an organ specific protein marker with no enzymatic activity. The most important laboratory test for cardiac diagnosis is cTn or the cardiac troponin. Troponin is a complex of three proteins: TnT, TnI and TnC. TnI has a cardio specific form the cTnI which differs from types 1 and 2 skeletal muscle fibers by a separate gene. TnT also has distinct form in the myocardium, the cTnT it is faster twitched than that of a skeletal muscle fiber. But there is a complication, where c TnT may also be found in fetal skeletal muscle and diseased skeletal muscle. cTnT and cTnI are predominantly attached to muscle fibers which are then released slowly 1-2 weeks following the Myocardial Infarction. It peaks in about 24 hours due to the slow release, the rapid decline is usually followed by a plateau and a secondary small increase, this does not suggest reinfarction. The cTn declines in about 5-10 days depending on the infract size. cTnT and cTnI are nearly absent in the serum and an increase of which need not be caused by ischemic damage. Smaller elevations are seen in pericarditis, myocarditis, pulmonary embolism, renal failure, sepsis and other critical illness. Troponin tests are primarily ordered for people who have chest pain to see if they have had a heart attack or other damage to their heart. Either a troponin I or a troponin T test can be performed; usually a laboratory will offer one test or the other. Troponins are sometimes ordered along with other cardiac biomarkers, such as CKMB or myoglobin. However, troponins are the preferred tests for a suspected heart attack because they are more specific for heart injury than other tests (which may become positive in skeletal muscle injury) and remain elevated for a longer period of time. The troponin test is used to help diagnose a heart attack, to detect and evaluate mild to severe heart injury, and to distinguish chest pain that may be due

to other causes. In patients who experience heart-related chest pain, discomfort, or other symptoms and do not seek medical attention for a day or more, the troponin test will still be positive if the symptoms are due to heart damage. In patients with stable angina, a troponin test may be ordered if the patients symptoms get worse, occur when the patient is at rest, and/or no longer ease with treatment. These are all signs that the angina is becoming unstable, which increases the risk of a heart attack or other serious heart problem in the near future. Normally, cardiac troponin levels are so low that they cannot be measured. Even slight elevations may indicate some degree of damage to the heart. When a patient has significantly elevated troponin concentrations, then it is likely that the patient has had a heart attack or some other form of damage to the heart. When a patient with chest pain and/or known stable angina has normal troponin values, then it is likely that their heart has not been injured. Rises: 4-10 hrs Peaks: 12-48 hrs Remains elevated: 4-10 days (this sustained elevations serves as definitive markers for AMI) 1. TnT (Tropomyosin Binding Unit) Its measurement is usefeul to those who dont need medication during the 2- to 3-day window of CK-MB. It shows similarity with TnI but TnT may show biphasic relase, meaning it could have a second peak 4 days after the admission. Rises: few hours after onset. Peaks: 2 days Remains elevated: 7-10 days 2. Cardiac TnI (Inhibitory Subunit) It is released in the circulation similar to TnT and CK-MB. It has an advantage over CK-MB because it is not found in the serum of patients with multiple injuries, engaged in strenuous exercise, renal failure, and those with

acute/ chronic skeletal muscle disease. TnI is helpful in monitoring patients after treatment. Rises: 4-6 hours after onset Peaks: 12-18 hour Returns: 6 days Normal Value: - troponin I: 0 0.1 ng/ml (onset: 4-6 hrs, peak: 12-24 hrs, return to normal: 4-7 days) - troponin T: 0 0.2 ng/ml (onset: 3-4 hrs, peak: 10-24 hrs, return to normal: 10-14 days) MARKERS OF INFLAMMATION, COAGULATION DISORDERS AND CORONARY RISKS Potential Markers for Risk Assessment: -because they play a role in atherogenesis, atherosclerotic plaque formation and acute coronary syndrome. 1. Inflammatory cells 2. Cytokines 3. Other biomolecules CRP is named such because of the ability to bind to C-polysaccharide of pneumococcus. It is a member of the pentraxin family of proteins and appears during infectious or inflammatory conditions. Normal median of plasma CRP is 1mg/L and the 99th percentile is about 10mg/L it can have an increase of upto 300 mg/L after MI. Higher levels of CRP may increase the risk of CHD and stroke. Studies show that increase in CRP due to coronary risk is minute compared to an increase in CRP due to inflammatory or infectious disease, which could reach upto 100 to 1000 folds. For this, testing of CRP related to cardiac risk had a misleading name of hsCRP(high-sensitivity C-reactive Protein), with a main difference in the dilution and calibration. CRP elevation is also related to cytokine production of

adipocytes and an inflammatory response associated with atheromatous lesions which would trigger cytokine production. The unclear role of CRP in the pathogenesis of vascular disease, lack of treatment for high levels of CRP and the variations in risk estimates makes the hsCRP test controversial. hsCRP, High-Sensitivity C-reactive protein, is a general marker of inflammation but with a high predictive value for coronary artery disease. Elevated hsCRP gives a higher risk of future cardiovascular morbidity and mortality. To those with established vascular disease, a 45% increase in risk of nonfatal MI per standard deviation increase of hsCRP. Sometimes leads to cardiac death 2 years after of follow-up. To those healthy patients, a mild elevation is associated to higher long-term risk of future cardiovascular events, and still has the chance to receive treatment. The hsCRP test can more accurately detect lower concentrations of the protein, which makes it more useful than the CRP test in predicting a healthy person's risk for cardiovascular disease. hsCRP is promoted by some as a test for determining the potential risk level for cardiovascular disease, heart attacks, and strokes. The current thinking is that hsCRP can play a role in the evaluation process before one encounters one of these health problems. More clinical trials that involve measuring hsCRP levels are currently underway in an effort to better understand its role in cardiovascular events and may eventually lead to guidelines on its use in screening and treatment decisions. People with higher hsCRP values have the highest risk of cardiovascular disease, and those with lower values have less of a risk. Specifically, individuals who have hsCRP results in the high end of the normal range have 1.5 to 4 times the risk of having a heart attack as those with hsCRP values at the low end of the normal range. Risk values: - Low risk (less than 1.0 milligrams per liter, or mg/L) - Average risk (1.0 to 3.0 mg/L) - High risk (above 3.0 mg/L)

Pregnancy-Associated Plasma Protein A or PAPP-A has high concentration is women during advanced stages of pregnancy. It is a major contributor to the progression of atherosclerosis. It is found out that there are high concentrations of PAPP-A in the cells and ECM of plaques. Comparing the PAPPA concentration, its concentration is higher in an unstable plaque than in a stable one. Therefore plays a role as a marker of unstable atherosclerotic plaque Lipoprotein-Associated Phospholipase A2 also known as LP-PLA2 and platelet-activating factor acetyl hydrolase. Elevated LP-PLA2 is associated in increased risk of heart disease and stroke. When analyzed with CRP, it has a additive effect on increasing risk of CVD. Homocysteine excess in the levels of homocysteine shows a decrease in one of the enzymes involved in its metabolism, an example of which is cystathionine-B-synthase, leading to homoycystinuria. Homocysteine is parallels that of cholesterol as a CHD risk marker. The regular occurrence of atherosclerosis in massive elevation is due to an inborn error of metabolism which leads to an increase in risk. Elevated homocysteine levels can have a risk three- to fourfold higher. Homocysteine maybe a part of a cardiac risk assessment, depending on the patient's age and other risk factors. It may also be tested following a heart attack or stroke to help guide treatment. Homocysteine may also be a part of a screen for people at high risk for heart attack or stroke. It may be useful in someone who has a family history of coronary artery disease but no other known risk factors. Its utility for this purpose, however, continues to be questioned because the role, if any, that homocysteine plays in the progression of cardiovascular disease (CVD) has not been established. Routine screening, such as that done for total cholesterol, is not yet recommended. People who have elevated homocysteine levels have a much greater risk of heart attack or stroke than those with average levels. At present, however, the use of homscysteine levels for risk assessment of cardiovascular disease (CVD), peripheral vascular disease, and stroke is uncertain given that several trials investigating folic acid and B vitamin supplementation indicate no benefit or lowering of CVD risk. The AHA does acknowledge strong evidence of a relationship between homocysteine levels and heart attack/stroke survival rates but stops short of calling elevated homocysteine a major risk factor for cardiovascular disease. Blockage of a coronary artery, a precursor to a heart attack, occurs with

more than double the average frequency in people with homocysteine levels in the highest 25% as compared to those in the lowest 25%. Normal values:between 4.4 and 10.8 micromoles per liter (mol/L).

MARKERS OF CONGESITVE HEART FAILURE Natriuretic Peptides includes: 1. 2. 3. 4. Atrial Natriuretic Peptide B-type Natriuretic Peptide C-type Natriuretic Peptide D-type Natriuretic Peptide

They play an important role regulation of cardiovascular homeostasis. BNP are released on stress to the myocytes in the absence of necrosis. BNP and NTproBNP (terminal fragment of BNPs prohormone.) is increased in diseases characterized by expanded fluid volume like CHF. It can help assess the diagnosis of CHF because CHF, having nonspecific symptoms, can cause an increase in BNP. It can help differentiate patients who should further undergo diagnostic assessments from those who are unlikely to have cardiac failure.

LIPID PROFILE Total Cholesterol Cholesterol is different from most tests in that it is not used to diagnose or monitor a disease but is used to estimate risk of developing a disease specifically heart disease. Because high blood cholesterol has been associated with hardening of the arteries (atherosclerosis), heart disease, and a raised risk of death from heart attacks, cholesterol testing is considered a routine part of preventive health care. Cholesterol is tested at more frequent intervals (often several times per year) in patients who have been prescribed diet and/or drugs to lower their cholesterol. The test is used to track how well these measures are succeeding in lowering cholesterol to desired levels and in turn lowering the risk of developing heart

disease. Cholesterol testing may be ordered more frequently for those who have one or more risk factors for heart disease For adults, in a routine setting where testing is done to screen for risk, the test results are grouped in three categories of risk:

Desirable: A cholesterol below 200 mg/dL (5.18 mmol/L) is considered desirable and reflects a low risk of heart disease. Borderline high: A cholesterol of 200 to 239 mg/dL (5.18 to 6.18 mmol/L) is considered to reflect moderate risk. Your doctor may decide to order a lipid profile to see if your high cholesterol is due to the amount of bad cholesterol (high LDL-C) or good cholesterol (high HDL-C) in your blood. Depending on the results of the lipid profile (and any other risk factors you may have), your doctor will decide what to do. High Risk: A cholesterol greater than or equal to 240 mg/dL(6.22 mmol/L) is considered high risk. Your doctor may order a lipid profile (as well as other tests) to try to determine the cause of your high cholesterol. Once the cause is known, an appropriate treatment will be prescribed.

Normal value: <200 mg/dL(5.20 mmol/L) Triglycerides Blood tests for triglycerides are usually part of a lipid profile used to identify the risk of developing heart disease. As part of a lipid profile, it may be used to monitor those who have risk factors for heart disease, those who have had a heart attack, or those who are being treated for high lipid and/or triglyceride levels. Lipid profiles, including triglycerides, are recommended every 5 years to evaluate risk of heart disease in healthy adults. The test for triglycerides is not often ordered alone since risk of heart disease is based also on cholesterol levels (see total cholesterol, HDL-C, LDL-C). Testing may be ordered more frequently for people who have identified risk factors for heart disease or who have been found to have high triglycerides and are being treated for it, to monitor treatment. screening with a lipid profile is recommended for children and youths who are at an increased risk of developing heart disease as adults. Some of the risk factors are similar to those in adults and include a family history of heart disease or health problems such as diabetes, high blood pressure, or being overweight. A triglyceride test is usually performed as part of a fasting lipid profile, and your doctor will take into consideration the results of each component of the lipid panel.

For adults, triglyceride test results are categorized as follows:

Desirable: Less than 150 mg/dL (1.7 mmol/L) Borderline high: 150 to 199 mg/dL (1.7-2.2 mmol/L) High: 200 to 499 mg/dL (2.3-5.6 mmol/L) Very high: Greater than 500 mg/dL (5.6 mmol/L)

Note: These values are based on fasting triglyceride levels Normal value:<150 mg/dL(1.70 mmol/L LDL The test for LDL cholesterol is used to predict your risk of developing heart disease. Of all the forms of cholesterol in the blood, the LDL cholesterol is considered the most important form in determining risk of heart disease. Since treatment decisions are often based on LDL values, this test may be used to monitor levels after the start of diet or exercise programs or to determine whether or not prescribing one of the lipid-lowering drugs would be useful. LDL-C levels are ordered as part a lipid profile, along with total cholesterol, HDL, and triglycerides. A fasting lipid profile may be ordered more frequently on those who have one or more major risk factors for heart disease. It may be ordered on someone who has had a high screening cholesterol result to see if the total cholesterol is high because of too much LDL-C. Elevated levels of LDL cholesterol can indicate risk for heart disease, so your LDL-C result is evaluated with respect to the upper limits that are desired for you. According to the National Cholesterol Education Program, if you have no other risk factors, your LDL-C level can be evaluated as follows: Less than 100 mg/dL (2.59 mmol/L) Optimal 100-129 mg/dL (2.59-3.34 mmol/L) Near optimal, above optimal 130-159 mg/dL (3.37-4.12 mmol/L) Borderline high 160-189 mg/dL (4.15-4.90 mmol/L) High Greater than 189 mg/dL (4.90 mmol/L) Very high

Normal value:<100 mg/dL(2.60 mmol/L)

HDL The test for HDL cholesterol (HDL-C) is used along with other lipid tests to screen for unhealthy levels of lipids and to determine your risk of developing heart disease. Your HDL-C level may also be monitored by your doctor on a regular basis if previous test results have shown you to have an increased risk for heart disease or if you have had a heart attack or if you are undergoing treatment for high cholesterol levels. HDL-C may be ordered as a follow up test to a high result on a cholesterol screening test. HDL-C is usually not ordered by itself but with other tests, including cholesterol, LDL cholesterol (LDL-C), and triglycerides as part of a lipid profile during a health check-up. It is recommended that all adults be tested at least once every five years. HDL-C, as part of the lipid profile, may be ordered more frequently for those who have one or more risk factors for heart disease. For adults:

If HDL-C is less than 40 mg/dL (1.0 mmol/L) for men and less than 50 mg/dL(1.3 mmol/L) for women, there is an increased risk of heart disease that is independent of other risk factors, including the LDL level. A typical level of HDL-C is between 40-50 mg/dL (1.0-1.3 mmol/L) for men and between 50-59 mg/dl (1.3-1.5 mmol/L) for women and is associated with average risk of heart disease. Based on many epidemiologic studies, HDL-C of 60 mg/dL(1.55 mmol/L) or higher is associated with a less than average risk of heart disease. The National Cholesterol Education Panel Adult Treatment Guidelines suggest that an HDL cholesterol value greater than 60 mg/dL is protective and should be treated as a negative risk factor. However, some recent studies suggest that high HDl-C is not universally

Normal value:> 40 mg/dL (1.0 mmol/L)