Chem p3

Cardiovascular disease (CVD)

Leading cause of death globally. Includes range of conditions including MI, angina, heart failure, stroke, etc. Clinical lab test plays critical role in early detection, diagnosis and management.

Atherosclerosis

Initial manifestation of most MI (in coronary arteries). Involves lipid accumulation, inflammation, and plaque formation in the vessel wall. Plaque can remain stable or become vulnerable and rupture which trigger thrombosis and reduce or block blood flow.

Angina

Present as chest discomfort or pressure, often triggered by exertion or stress. Relief with rest or nitroglycerin. Can be stable (predictable, exertional) or unstable (new onset, worsening or at rest)

Cardiac biomarkers

Substances released into blood when heart muscle is damaged. Help detect myocardial injury, determine severity and monitor treatment. Includes troponin, CK-MB, myoglobin, LDH. Used alongside ECH for diagnosis. 

Troponin

Regulates cardiac muscle contraction. Composed of 3 subunits: C (binds calcium ions), I (inhibits actomyosin ATPase), T (binds to tropomyosin). C is identical in cardiac and skeletal muscle. I and T have cardiac-specific isoforms unique to heart muscle. I and T are biomarkers of myocardial injury

Cardiac troponin (cTnI, cTnT)

High cardiac specificity minimizes false positives from skeletal muscle injury. High sensitivity detects even minor myocardial injury. Rapid release into blood within 3-6 hours of injury and level remain elevated 7-10 days, aiding diagnosis day after symptom onset.

99th percentile upper reference limit (URL)

Cut off for MI diagnosis. Based on healthy population - assay specific. hs-cTnI > 26 ng/L, hs-cTnT > 14 ng/Lz.

Serial troponin testing

Single troponin value may not confirm or rule out MI. Dynasmic change indicates acute myocardial injury. Begins rising 3-6 hours after myocardial injury and peaks at 12-24 hrs, remains elevated 7-14 days. Measured at 0 hr (baseline) and repeat at 1, 3, 6 hrs and absolute or relative change measured to help differentiate chronic elevation from acute MI

Significant delta troponin change

Absolute change of >5 for hs-cTnT (within 1-3 hrs) or >6-10 for hs-cTnI. Relative change of 20% increase from baseline. Low delta can represent chronic or non-ischemic elevation - consider renal failure, CHF, etc. High baseline with no change may reflect chronic myocardial injury. High delta with symptoms is likely AMI.

Reference interval

Range of values from a healthy population. Typically the central 95%. Used for screening and general assessment.

Decision limit

Based on clinical outcome data (not just population stats). Indicates high risk or diagnostic threshold. Often the 99th percentile for cardiac markers

Creatine Kinase-MB (CK-MB)

isoenzyme of creatine kinase found predominantly in cardiac muscle. Appears in blood 4-6 hours after myocardial injury. Peaks 18-24 hours and returns to baseline within 2-3 days. Less specific than troponin but useful for detecting reinfarction and subsequent cardiac events. Elevated levels may also be seen in skeletal muscle injury.

Myoglobin

Small heme protein found in cardiac and skeletal muscle. Released rapidly into blood within 1-3 hours after muscle injury. Peaks at 6-9 hours and returns to baseline within 24 hours. Very sensitive but not specific to cardiac injury. May rule help rule out myocardial infarction when levels remain normal. Used as an adjunct marker in trauma and rhabdomyolysis diagnosis. 

BNP / NT-proBNP

Hormones secreted by the ventricular myocardium in response to stretch and increased pressure. Released when the heart is under stress, especially in heart failure or volume overload. BNP is the active hormone, NT-proBNP is an inactive fragment with longer half life - both useful as biomarkers for heart failure diagnosis, prognosis and management. Low BNP rules out heart failure in patients with dyspnea. Reference range varies with age, sec and renal function

Electrocardiogram (ECG/EKG)

Records electrical activity of the heart. Detects arrhythmias, ischemia, infarction, conduction abnormalities.

Echocardiography

Ultrasound imaging of heart structures and function. Assesses chamber size, wall motion, valvular function, ejection fraction.

Chest x-ray

visualizes heart size, pulmonary vasculature, signs of heart failure or edema

Stress testing

Assesses cardiac function under physical or pharmacologic stress. Detects ischemia and exercise tolerance

Coronary angiography

Invasive imaging to visualize coronary artery blockages. Gold standard for detecting coronary artery disease

Cardiac MRI and CT scan

Detailed anatomical and functional imaging. Useful for complex cases, viability assessment and structural abnormalities

Coronary artery disease (CAD)

Primary cause of MI and angina. Atherosclerosis leads to plaque buildup, narrowing coronary arteries. Risk factor includes age, sex, family history (non-modifiable); smoking, hypertension, hyperlipidemia, diabetes, obesity, sedentary lifestyle (modifiable).

Atherosclerosis process

Endothelial injury leads to lipid accumulation causing inflammatory response. Formation of fibrous plaques with lipid cores

Plaque stability

stable plaques cause predictable angina due to fixed obstruction. Unstable plaques prone to rupture cause acute coronary syndromes (ACS)

Ischemia and infarction

MResults from reduced blood flow; occurs when ischemia causes irreversible myocardial cell death

Myocardinal infarction (MI)

Presents as severe, persistent chest pain (>20 minutes), not relieved by rest or nitroglycerin. May radiate to jaw, neck, left arm. Associated with diaphoresis, nausea, dyspnea, anxiety

Acute coronary syndrome (ACS) lab testing

Initial assessment includes clinical evaluation, ECG and troponin testing. First troponin sample collected at patient presentation (0 hr). If initial hs-troponin is below 99th percentile and low risk - early rule out protocols with serial testing at 1-3 hours. If initial hs-troponin is elevated or suspicion is high - repeat testing at 3 and 6 hours.

Cardiac emergencies

Early diagnosis is crytical for effective ACS treatment. Lab prioritize cardiac biomarker testing for suspected ACS patients

Structured testing algorithm for cardiac testing

Initial assessment of patient with non-specific symptoms such as chest pain or discomfort. Includes detailed history and physical exam, ECG within 10 min of arrival, baseline blood sample for troponin. Use of clinical risk scores such as HEART (History, ECG, Age, Risk factor, Troponin) to stratify patients, and additional testing may be added for complex cases or heart failure suspicion.

Lipids

Fat-like substances essential for many biological function. Transported in blood as lipoproteins. Imabalance is associated with atherosclerosis and CVD. Main fractions includes HDL-C, triglycerides, Non-HDL cholesterols which are measured using enzymatic colorimetric assay (Except LDL).

Dyslipidemia

Abnormal levels of lipids in the blood. Major types include elevated LDL-C and triglyceride, or low HDL-C.

Total cholesterol (TC)

Sum of cholesterol carried by all lipoprotein (LDL, HDL, VLDL etc). Elevated level is associated with increased cardiovascular risk. Measured using enzymatic colorimetric assay. Esters are hydrolyzed, then oxidized which produces color change.

Low density lipoprotein cholesterol (LDL-C)

Small, dense particles that deposits cholesterol in arterial walls. Main carrier of cholesterol to peripheral tissues. Strongest predictor of cardiovascular events. Often calculated using Friedewald equation instead of directly measured unless high triglyceride is present.

Friedewald Equation

Used to calculate LDL. Less accurate and not used when TG > 4.5 mmol/L as TG/2.2 is used as an estimate of levels of other cholesterols.

Lipid measuring method

Measured using enzymatic colorimetric assay.

Triglycerides

Measured using enzymatic colorimetric method. Broken down into glycerol and fatty acid followed by enzymatic reaction that produces color proportional to concentration

Primary dyslipidemia

Usually genetic. Includes familial hypercholesterolemia and familial combined hyperlipidemia

Secondary dyslipidemia

Usually acquired. Caused by diabetes mellitus, hypothyroidism, nephrotic syndrome, obesity, metabolic syndrome or certain medications. 

High density lipoprotein (HDL-C)

Removes cholesterol from tissues and arteries → Reverse cholesterol transport. Protective against atherosclerosis

Atherosclerosis

Lipid accumulation in arterial walls → foam cell formation. Plaque development and progression. Inflammatory response contributes to plaque instability. Narrowing of arteries from plaque reduces blood flow. Plaque rupture can cause clot formation, leading to MI or stroke

CVD associated with dyslipidemia

Includes MI, ischemic stroke, peripheral artery disease, heart failure with chronic dyslipidemia

Apolipoprotein A1 (ApoA1)

Emerging marker not frequently used. Main protein in HDL; reflects protective cholesterol.

Apolipoprotein B (ApoB)

Emerging marker not frequently used. Main protein in atherogenic lipoproteins; indicates particle number

Lipoprotein(a) [Lp(a)]

Emerging marker not frequently used. LDL-like particle with additional apolipoprotein(a); genetically determined risk factor

Remnant cholesterol

Emerging marker not frequently used. Cholesterol in triglyceride-rich particles (VLDL, LDL); linked to residual cardiovascular risk.

Dyslipidemia risk calculator

Includes Framingham Risk Score (FRS), QRISK and ASCVD pooled cohort equations. Input includes age, sex, BP, smoking status, diabetes, lipid levels. Adults typically screened every 4-6 years - more frequent for high-risk individuals

Lipid testing Pre-analytical variables

Morning samples preferred - fasting vs non-fasting impacts TG. Avoid hemolysis, lipemia and prolonged storage. May be affected by statins, hormones and acute illness.

Lipid testing

3 different levels QC commonly used to cover different risk ranges. TC assay is stable for weeks when refrigerated, HDL-C assay has moderate stability that is sensitive to freeze-thaw cycles. TG assay is less stable and prone to variability such as glycerol interference and lipemia. Serum preferred for most panels, plasma with LiHeparin or EDTA can be used depending on assay. Reflect testing not done routinely. Add-on test such as ApoA1 may be ordered

Icteric Lipid sample

Use alternate assay methods or dilution protocols

Lipemic Lipid samples

Use ultracentrifugation, dilution, or use TG-insensitive methods

Glycerol interference

Use glycerol-blanked assays or fasting samples

Lipid-lowering therapy

Common therapy includes Statins, fibrates, PCSK9 inhibitors or lifestyle interventions. Expected trends are reduction of LDL-C, triglyceride lowering, HDL-C maintenance.

Lipid panel and glucose testing

Elevated triglycerides often co-occur with hyperglycemia or insulin resistance 

Lipid panel and live function test

Dyslipidemia may be associated with non-alcoholic fatty liver disease

Lipid panel and kidney function test

Chronic kidney disease can alter lipid metabolism; HDL often decreases

Lipid panel and inflammatory markers

High triglycerides and low HDL correlate with systemic inflammation and atherogenesis

Lipid panel and thyroid test

Hypothyroidism can cause elevated LDL-C and TC