CV labs

Question 1

CPK

Answer 1

transfers high energy phosphate between creatine and ADP. Fraction MM from muscle and BB from brain, yet myocardial infarct = increased MB fraction, ie. CPK-MB.

Question 2

Troponin

Answer 2

Calcium causes a conformational change in tropomysin that allows the reaction between actin and myosin to proceed. A free fraction in cytoplasm allows early leakage during an MI, resulting in a rise with the CPK. The troponin stays elevated for 5-10 days whereas the CPK usually hits normal at 3 days. Higher sensitivity test for troponin are now available.

Question 3

Reinfarction after 3 days could be diagnosed with

Answer 3

a CK-MB elevation

Question 4

different types of troponin

Answer 4

Troponin consists of three single chain polypeptides which regulate muscle contraction: troponin C (binds Ca2+), troponin I (binds actin-inhibiting actin–myosin interaction), and troponin T (binds tropomyosin and facilitates contraction). Cardiac muscle contains specific cTnI and cTnT isoforms. Most cTn is bound, but a small amount is free in the cytosol. The initial rise of cTn after myocyte damage is thought to be release of the unbound cytosolic cTn. This is followed by more prolonged appearance of troponin from damage to the myofilament structures.*

Question 5

what causes changes in troponin?

Answer 5

AMI = elevated or falling troponin I or T* on the basis of ischemia in the presence of appropriate clinical information, EKG changes or new wall motion abnormality.

Elevation may be due to an acute injury (ie, pericarditis, myocardititis, pulmonary embolism, sepsis), or a chronic process (ie LVH, CHF, CKD, or DM); rather than an infarction which is based on ischemia.

Troponins can be used to diagnose cardiac injury after PCI (5 fold increase) or CABG (must have 10 fold increase).

Question 6

The diagnosis of an acute myocardial infarction depends on

Answer 6

observation of a rise and/or fall of blood biomarkers with at least one value above the 99th percentile. Cardiac troponins are preferred to CK-MB measurements for diagnostic and prognostic purposes. A change in troponin levels is needed to diagnose myocardial infarction because troponin elevation can also be seen in a variety of other diseases, such as sepsis, hypovolemia, atrial fibrillation, heart failure, pulmonary embolism, myocarditis, myocardial contusion, and renal failure.
**Thus, an increased or falling troponin must be accompanied with symptomatic, electrocardiographic, nuclear, or echocardiographic evidence of myocardial ischemia in order to diagnose a myocardial infarction!. **

Question 7

A 45 y/o male presents with substernal chest pain of three hours duration. A highly sensitive troponin I assay is elevated. EKG is as shown. What should be done next?

Answer 7

Repeat the troponin in 2 hours

Question 8

MI/hs-cTnT When are they sensitive enough to detect an MI?

Answer 8

High sensitivity troponins* (hs-cTnT) are now able to confirm MI in 2 hours.

Some patients who present 2 hours or more after onset of chest pain, with a TIMI of 0 or 1, and with a negative one hour hs-cTNT (no changes in an hour) can be sent home.

Question 9

what does cTnT of more than 14 ng/L indicate?

Answer 9

In patients with stable ischemic heart disease, a highly sensitive troponin (cTnT) of > 14 ng/L indicates an increased risk of MI, stroke, CHF, or CV death.

Question 10

hsCRP

Answer 10

Released by hepatocytes under influence of cytokines IL6 and TNF alpha.

May bind to oxidized LDL particles for macrophage ingestion.

Useful in “stable” CHD in that a level > 3 mg/L = worse prognosis.

Useful in ACS where a level > 10 mg/L = worse prognosis.

hsCRP is decreased by statins and thiozolinediones.

Best level of hsCRP is

Question 11

Lipids lab testing

Answer 11

Total cholesterol, triglycerides and HDL-C (done fasting due to triglycerides).

LDL-C = total-C – [VLDL-C (1/5 trig) + HDL-C]. This only works for triglycerides

Question 12

Non-HDL-C

Answer 12

= total C – HDL-C = cholesterol in LDL, lipoprotein (a), IDL and VLDL. Better measurement of risk than LDL-C

Question 13

LDL-C

Answer 13

level does not reveal the number of LDL particles, ie one may have a relatively normal LDL-C with level of 100 mg/dL and yet have many more small dense and dangerous particles than someone else with an LDL-C level of 100*.

*LDL-P (a core of lipid surrounded by phospholipid) measured by NMR
spectroscopy is a better assessment of lipid status than LDL-C or
Apo-B.

Question 14

Which of the following lab test is best for supporting the
diagnosis of cardiovascular disease?

hs CRP
Myeloperoxidase 
Homocysteine
Cholesterol 
Fibrinogen

Answer 14

Cholesterol

Question 15

BNP*

Answer 15

Brain naturetic peptide – mainly from cardiac ventricles (ANP mainly from atria) and activates G-protein coupled receptors.
BNP inhibits RAAS, endothelin secretion and sympathetic activity (norepinephrine), and increases renal blood flow and sodium excretion.
Useful in accessing severity in ACS, stable angina, mitral regurgitation, and aortic stenosis, but not to be used to guide treatment.

***Aberrantly low in obesity.

Uses:
Evaluation of dyspnea: 100 – 400 pg/mL = No value. Greater than 400 pg/mL = possible CHF. Less than 100 pg/mL = no CHF.***
Monitoring of established HF (fair) and prognosis in CHF (better).
May be of use in heart failure therapy, ie nesiritide

Question 16

N-terminal Pro-BNP*

Answer 16

NT proBNP useful to suggest CHF in in patients with dyspnea less than 50 , 50-75 and > 75 yoa at levels of 450pg/mL, 900 pg/mL and 1800 pg/mL respectively.

Age > 70, NT proBNP less than 400 pg/ml excludes CHF, and NT proBNP > 2000 pg/ml suggest CHF when diagnosis is uncertain.

Question 17

Acute heart failure can be ruled out with normal levels of

Answer 17

BNP and NTproBNP

Question 18

Serum Sodium

Answer 18

A marker for a poor prognosis in CHF.

Na below 135 meq/L indicates that a CHF patient has an increased chance of falls as well as more likely reoccurrence of CHF episodes.

Related to excess vasopressin (ADH)

Question 19

Which of the following would be the best marker for the severity of CHF?

Serum sodium
BNP 
NT Pro-BNP
Uric acid
Fibrinogen

Answer 19

Serum sodium

Question 20

Which of the following cardiac markers is useful in excluding congestive heart failure?

hsCRP
myeloperoxidase 
homocysteine
Cholesterol
NT-pro BNP

Answer 20

NT-pro BNP

Question 21

Other Lab Methods of Risk Assessment

Answer 21

TC/HDL-C
Non-HDL-C
Apolipoprotein B
Apolipoprotein (a)
Small dense LDL-C
LDL-P

Question 22

High Cholesterol with High LDL-C

Answer 22

High cholesterol with high LDL-C (Fredrickson type 2A) is a lab presentation that includes Familial and Polygenic Hypercholesterolemia*.

All relate to high LDL-C (with essentially normal triglycerides) because of a **defective LDL receptor or problems with LDL-C attachment **(defective apo B ligand) to the receptor or various combinations thereof.

Patients have corneal arcus, xanthelasma and tendinous xanthomata, premature CAD, and aortic stenosis.

Question 23

Type IIa Hyperlipidemia

Answer 23

Familial or Polygenic Hyperlipidemia

Mutation in LDL receptors or defective Apo B 100 ligand (90% Type II a ). LDL - C usually > 250 mg/dl. Tendon xanthomas, arcus, premature CAD, PVD, strong family history.

Question 24

High Cholesterol with High Triglycerides

Answer 24

High Cholesterol with High Triglycerides = Fredrickson Types 2B or Familial Combined Hyperlipidemia (most common primary hyperlipidemia, though usually no skin findings).

Question 25

Type II B Hyperlipidemia

Answer 25

Familial Combined Hyperlipidemia

Increased hepatic secretion of VLDL with Apo B 100 and conversion to LDL with Apo B 100 [10% of type II a (increased LDL); IIb (inc. LDL and inc. VLDL); Type IV]. Common, often hypertensive and obese, no xanthomas, early CAD, PVD, stroke. Acquired type in diabetics. Most common cause of lactescent plasma and primary hyperlipidemia.

Question 26

A 50 y/o obese diabetic female presents with BP of 160/86. Pedal pulses are diminished. Past history is positive for a TIA. There are no xanthomas. Serum is lactescent with LDL cholesterol of 210 mg/dL and triglycerides of 340 mg/dL. This patient most likely has:

Answer 26

familial combined hyperlipidemia.

Question 27

High Cholesterol with equally High Triglycerides

Answer 27

High Cholesterol with High Triglycerides = Type 3 (dysbetalipoproteinemia or “broad beta disease” with an abnormal IDL). This combination is seen in:

**Dysbetalipoproteinemia (E2/E2 – equal elevation of cholesterol and triglycerides).

**Hepatic lipase deficiency which can present like “Broad Beta disease” also plays a role in ineffective clearance of IDL.

Question 28

A 45 y/o male with a history of gout and the metabolic syndrome presents with intermittent claudication and a strange rash on the hands and elbows. Lipid profile shows a cholesterol of 680 mg/dL with triglyceride of 700 mg/dL. Serum is turbid with standing.
This patient has which hyperlipoproteinemia?

Answer 28

III

Question 29

When do I have my cholesterol tested?”

Answer 29

USPFTS
Lipid screening should start at age 35 in men without other risk factors for coronary artery disease and at age 20 to 35 in men with risk factors (FH, smoking, HTN).

Lipid screening should start at age 45 in women, and maybe at age 20 in those with risk.

Question 30

CHD equivalents

Answer 30

DM, TIA, PAD, AAA, 10-year risk of CHD > 20%

Question 31

Risk Stratification (ATP III)

Answer 31

Fasting lipid profile

Identify CHD equivalents (DM, TIA, PAD, AAA, 10-year risk of CHD > 20%). If present, the cholesterol goal is LDL-C

Question 32

ACC, AHA, and NHLB Cholesterol Guidelines

Answer 32

Clinical atherosclerotic cardiovascular disease:
High intensity treatment/atorvastatin 40-80 mg or rosuvastatin 20 – 40
mg.

Primary elevations of LDL-C > 190 mg/dL:
High intensity treatment/atorvastatin 40-80 mg or rosuvastatin 20 - 40 mg.

Diabetic patients without clinical ASCVD aged 40-75 years with LDL-C 70-189 mg/dL, but with 10-year atherosclerotic CVD > 7.5%: High intensity treatment/atorvastatin 40-80 mg or rosuvastatin 20 - 40 mg.

Diabetic patients without clinical ASCVD aged 40-75 years with LDL-C 70-189 mg/dL, and 10-year ASCVD less than 7.5%: Moderate intensity treatment/atorvastatin 10-20 mg or rosuvastatin 5-10 mg.

Primary prevention patients with LDL-C 70-189 mg/dL and estimated 10-
year atherosclerotic CV risk > 7.5 %:

Primary prevention patients with LDL-C 70-189 mg/dL and estimated 10-
year atherosclerotic CV risk less than 7.5 %: Observe*

Question 33

2013 ACC/AHA Assessment of CV Risk

Answer 33

10 year risk based on: Sex; Age; **Race; HDL-C; TC; BP(untreated or treated); Smoker; Diabetes.

• Statin therapy for :
  1. Individuals with clinical ASCVD.
  2. Individuals with primary elevations of LDL ≥ 190 mg/dL.***
  3. Individuals 40 to 75 **years of age with diabetes and an LDL 70 to 189 mg/dL without clinical ASCVD.
  4. Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with LDL 70 to 189 mg/dL and a 10-year ASCVD risk of 7.5% or higher.

Question 34

10 year risk evaluation for ages 40-79

Answer 34

*Gender
Age
*Race –AA or whites and others
TC
HDL-chol
SBP
*Treatment for HBP
Diabetes
Smoker

Question 35

PCSK9

Answer 35

The first genetically based therapy for lipids, approved by the FDA late 2015

PCSK9 appears to be twice as effective as statins in reducing CV outcomes
Statins reduce outcomes by 35%, PCSK9 by 85%
Only available by injection q 2 weeks. Two drugs approved late in 2015. Insurance companies starting to approve these drugs