Non-Lipid Markers of Cardiovascular Disease



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Non-Lipid Markers of Cardiovascular Disease (CVD)*

Test Guide

*Cardiovascular disease includes atherosclerotic coronary heart disease (CHD) and arterial thrombosis (peripheral and cerebral).

A significant percentage of CVD is attributed to non-lipid factors. These include genetic mutations, inflammation, coagulation disorders, infection, autoimmune disease, and unknown factors. The following markers may be useful for assessing cardiovascular risk irrespective of lipid status.

Activated protein C resistance (APCR)
Result (adults)	Interpretation	Therapeutic Options
<1.6 (ratio)^a	Positive; increased risk for venous thromboembolic disease, CVD (particularly in women >50 years of age and in women who smoke), and cerebrovascular disease; associated with acute phase reactions	Anticoagulants
1.6-2.1(ratio)^a	Borderline; repeat or follow-up with factor V Leiden R506Q mutation analysis
>2.1 (ratio)^a	Negative; desirable
Angiotensin converting enzyme (ACE) polymorphism (insertion/deletion)^b
Result (adults)	Interpretation	Therapeutic Options
Insertion Deletion	Normal	Not established
Insertion Deletion	Heterozygous or homozygous: increased risk of cardiovascular disease and restenosis	Not established
Angiotensin II type 1 receptor (AGTR1) gene 1166A→C polymorphism^b
Result (adults)	Interpretation	Therapeutic Options
Negative Positive	Normal	Not established
Negative Positive	Increased risk of hypertension and cardiovascular disease	Not established
B-type natriuretic peptide (BNP)
Result (adults)	Interpretation	Therapeutic Options
<100 pg/mL ≥100 pg/mL	Normal; heart failure unlikely High probability of heart failure (levels correlate with NY heart classification); increased risk of future cardiac events	ACE inhibitor drugs, angiotensin receptor blockers, beta-adrenergic blockers (eg, carvedilol), aldosterone antagonists, BNP
Beta2-Glycoprotein I antibodies
Result (adults)	Interpretation	Therapeutic Options
Negative Positive	Normal	Anticoagulants, antiplatelet therapy, corticosteroids
Negative Positive	Increased risk for CVD, cerebrovascular and thromboembolic disease; associated with recurrent fetal loss, thrombocytopenia, and systemic lupus erythematosus (SLE)	Anticoagulants, antiplatelet therapy, corticosteroids
Cardio CRP^® (high-sensitivity C-reactive protein)
Result (adults)	Interpretation	Therapeutic Options
<1.0 mg/L 1.0-3.0 mg/L 3.1-10.0 mg/L >10.0 mg/L	Low cardiovascular risk Average cardiovascular risk High cardiovascular risk Persistent elevations may represent non- cardiovascular inflammation	Anti-inflammatory drugs (eg, aspirin), statins
Cardiolipin antibody
Result (adults)	Interpretation	Therapeutic Options
Negative	Desirable	Anticoagulants, antiplatelet therapy, corticosteroids
Positive	Increased risk for CVD, cerebrovascular and thromboembolic disease; associated with recurrent fetal loss, thrombocytopenia, and systemic lupus erythematosus (SLE)	Anticoagulants, antiplatelet therapy, corticosteroids
Chlamydia pneumoniae antibodies
Result (adults)	Interpretation	Therapeutic Options
Negative	Probable absence of infection	Antibiotics
Positive	Active or resolved infection; increased CVD risk	Antibiotics
Cytomegalovirus (CMV) antibodies
Result (adults)	Interpretation	Therapeutic Options
Negative	Probable absence of infection	Antiviral drugs
Positive	Active or resolved infection; increased CVD risk	Antiviral drugs
dRVVT Screen with Reflex to dRVVT Confirm and dRVVT 1:1 Mix
Result (adults)	Interpretation	Therapeutic Options
Ratio <1.3	Probable absence of phospholipid anti-bodies/lupus anticoagulant	Anticoagulants, antiplatelet therapy, corticosteroids
Ratio ≥1.3	Increased risk for CVD, cerebrovascular and thromboembolic disease; associated with recurrent fetal loss, thrombocytopenia, and systemic lupus erythematosus (SLE)	Anticoagulants, antiplatelet therapy, corticosteroids
Factor V Leiden mutation (1691G→A, producing R506Q)^b
Result (adults)	Interpretation	Therapeutic Options
No mutation	Normal (wild type)	Anticoagulants
Heterozygote	APCR; 4- to 8-fold increased risk of venous thrombosis; increased risk of CVD (particularly in women who smoke) and cerebrovascular disease
Homozygote	APCR; 80-fold increased risk of venous thrombosis; increased risk of CVD (particularly in women who smoke) and cerebrovascular disease
Factor V HR2 allele DNA mutation analysis^b
Result (adults)	Interpretation	Therapeutic Options
No mutation	Normal (wild type)	Anticoagulants
Heterozygous	Increased risk (3- to 4-fold) of venous thrombosis if factor V Leiden mutation is also present (no increased risk if factor V Leiden mutation absent)	Anticoagulants
Fibrinogen antigen, nephelometry
Result (adults)	Interpretation	Therapeutic Options
<180 mg/dL	Low risk for CHD even in presence of increased cholesterol; associated with hypo- and afibrinogenemia, DIC, systemic fibrinolysis, pancreatitis, severe hepatic dysfunction, treatment with l-asparaginase or valproate	Anti-inflammatory drugs (eg, aspirin)
180-350 mg/dL	Normal
>350 mg/dL	Predicts increased incidence of CVD, CVD-related mortality, and cerebrovascular disease (of limited predictive value for individual patients); also elevated in hyper-coagulability, pregnancy, oral contraceptive use, smoking, postmenopausal status, and systemic inflammation
Helicobacter pylori antibody
Result (adults)	Interpretation	Therapeutic Options
Negative	Probable absence of infection	Antibiotics
Positive	Active or resolved infection; increased CVD risk	Antibiotics
Homocysteine (cardiovascular)
Result (adults)	Interpretation	Therapeutic Options
<11.4 µmol/L (M)	Normal	Folic acid and sometimes cobalamin (vitamin B₁₂), and/or B₆
≥11.4 µmol/L (M)	Increased risk of CVD, stroke, dementia (including Alzheimer disease), B₁₂ and/or folate deficiency, chronic renal disease, and homocystinuria
<10.4 µmol/L (F)	Normal
≥10.4 µmol/L (F)	Increased risk of CVD, stroke, dementia (including Alzheimer disease), B₁₂ and/or folate deficiency, chronic renal disease, and homocystinuria
Lp-PLA₂
Result (adults)	Interpretation	Therapeutic Options
115-245 ng/mL (M) 85-245 ng/mL (F)	Normal	Not established; fenofibrate and atorvastin under evaluation
Methylenetetrahydrofolate reductase (MTHFR) mutation (677C→T, producing A223V)^b
Result (adults)	Interpretation	Therapeutic Options
No mutation	Normal (wild type)	Folic acid and/or cobalamin (vitamin B₁₂)
Heterozygote	Carrier; absence of phenotypic expression
Homozygote	At risk for hyperhomocysteinemia, increased CVD risk, neural tube defects
Microalbumin, Urine
Result (adults)	Interpretation	Therapeutic Options
<30 mg/24 h	Normal	ACE inhibitor drugs, angiotensin receptor blockers
30-299 mg/24 h	Microalbuminuria
≥300 mg/24 h	Clinical albuminuria
ProBNP, N-terminal
Result (adults)	Interpretation	Therapeutic Options
Age 18-49 y:		ACE inhibitor drugs, angiotensin receptor blockers, beta-adrenergic blockers (eg, carvedilol), aldosterone antagonists, BNP
≤300 pg/mL	Normal; heart failure unlikely
≥450 pg/mL	High probability of heart failure (levels correlate with NY heart classification); increased risk of future cardiac events
Age ≥50 y:
≤300 pg/mL	Normal; heart failure unlikely
≥900 pg/mL	High probability of heart failure (levels correlate with NY heart classification); increased risk of future cardiac events
Prothrombin (factor II) 20210G→A mutation analysis^b
Result (adults)	Interpretation	Therapeutic Options
No mutation	Normal (wild type)	Anticoagulants
Heterozygote	Increased risk for venous thrombosis (3- to 6-fold), obstetrical complications, and possibly premature coronary heart
Homozygote	Rare
PTT-LA with Reflex to Hexagonal Phase Confirm
Result (adults)	Interpretation	Therapeutic Options
<8 second reduction in aPTT after addition of hexagonal phase phospholipid	Probable absence of phospholipid antibodies/lupus anticoagulant	Anticoagulants, antiplatelet therapy, corticosteroids
>8 second reduction in aPTT after addition of hexagonal phase phospholipid	Increased risk for CVD, cerebrovascular and thromboembolic disease; associated with recurrent fetal loss, thrombocytopenia, and systemic lupus erythematosus (SLE)
APCR, activated protein C resistance; M, male; F, female; DIC, disseminated intravascular coagulation; CR, creatinine. ^aRatio: aPTT with activated protein C: baseline aPTT. ^bThis test was developed and its performance characteristics have been determined by Quest Diagnostics Nichols Institute. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. Performance characteristics refer to the analytical performance of the test.

References

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Content reviewed 10/2008

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