Aug 02, 2008
We recently began to offer comprehensive cardiovascular risk factor assessment in our practice. Following is a description of fractionated lipid panel that we have available. Ill present additional information on genetic variant markers which can be measured in a future blog.
Seven regions (subclasses) are determined on LDL-S3GGE®.
The subclasses are defined as LDL I, IIa, IIb, IIIa, IIIb, and IVa, IVb. High levels of subclasses LDL IIIa + LDL IIIb reflect an abundance of small LDL particles and expression of the Atherogenic Lipoprotein Profile (ALP). Reduction of LDL IIIa and LDL IIIb in CAD patients has been associated with arteriographic benefit. Elevated levels of LDL subclass IVb reflect an abundance of the smallest LDL subclass. LDL IVb > 10% is a negative indicator and is associated with arteriographic progression. LDL-S3GGE® is correlated to the gold standard for lipid subclassification – analytical ultracentrifugation (ANUC). Å = Angstrom measurement.
HDL Segmented Gradient Gel Electrophoresis (HDL-S10GGE®) ‡
Five regions (subclasses) are determined on HDL-S10GGE®. The subclasses are defined as HDL 2b, 2a, 3a, 3b, and 3c. HDL2b is the region associated with reverse cholesterol transport efficiency. The average HDL2b in an asymptomatic middle aged male and female population, who are LDL pattern A, is approximately 18% and 26% respectively. The amount of HDL2b (determined by Gradient Gel Electrophoresis) has been associated with coronary artery disease severity, and progression over time (Johansson J, et al. Arteriosclerosis and Thrombosis 1991;11:174-182). HDL-S10GGE® is correlated to the gold standard for lipid subclassification – analytical ultracentrifugation (ANUC). Å = Angstrom measurement.
Apoprotein E Genotype ‡
Apo E Genotypes are genetically fixed and present in combinations of E2, E3, and E4. E 3/3 is the normal genotype. E 2/2, found in less than 1% of the population, predisposes the patient to Type III Hyperlipidemia. E 4/4 and E 4/3 are associated with a predisposition to elevated cholesterol levels and risk of CVD. Genotypes E 3/2, and E 4/2 are not consistently associated with lipid abnormalities. Due to the unique nature of genetic testing, physicians may suggest patients consider genetic counseling. Informed consent is recommended and required for patients residing in the state of New York. Consent forms are available from Berkeley HeartLab, Inc upon request.
Lipoprotein (a) (Lp(a)) is an LDL particle with an abnormal protein attached. High levels of Lipoprotein (a) are associated with an increased risk of developing CAD. Apoprotein A-I
(Apo A-I) is a major apolipoprotein attached to HDL and triglyceride-rich lipoproteins. Lower levels of Apo A-I have been reported in patients with CAD.
Apolipoprotein B (Apo B) is the major apolipoprotein associated with LDL. Higher levels of plasma Apo B may signify increased coronary disease risk even when LDL-cholesterol is not in the high-risk range.
Apoprotein B-Ultra ‡
Apo B–Ultra is designed to remove interference from the ApoB-48 associated with chylomicrons by ultracentrifugation, so an accurate ApoB-100 particle number is reported.
Homocysteine is a metabolic byproduct of methionine metabolism. Elevated levels are associated with a 2-3 fold increased CVD risk. Values in excess of 14 µmol/ml are considered elevated (Graham et al. JAMA 1997;277:1775-1781.; Malinow et al. Circulation 1993;87:1107-1114).
Fibrinogen is a plasma protein, which can be transformed by thrombin into a fibrin clot. Values in excess of 277 mg/dl have been associated with a 2.4 fold increase in coronary events compared to values less than 236 mg/dl (Heinrich et al. Atheriosclerosis and Thrombosis 1994;14:54-59). Subjects with elevated fibrinogen and elevated LDLC (> 163 mg/dl) have a 6.1 fold increase in coronary risk. Each increase of 75 mg/dl of fibrinogen has been reported to increase CAD mortality by 29% (Benderly et al. Arterioscler Thromb Vasc Biol. 1996;16:351-356). Berkeley HeartLab uses nephelometry to measure fibrinogen; results cannot be used to assess coagulation status.
Insulin is a protein involved with carbohydrate metabolism. It is elevated postprandially in proportion to the carbohydrate content in a meal. Elevated fasting insulin levels have been related to atherosclerosis risk particularly in South Asian Men. The upper tertile is > 12.4 µU/ml (McKeigue PM et al. Circulation 1993;87:152-161). The loss of estrogen at menopause is associated with increased insulin levels. There is an overlap between insulin levels in CAD and control patients.
C-Reactive Protein (high sensitivity)
C-Reactive Protein (CRP) is one of a number of “acute phase” proteins and increases in response to some inflammatory stimuli. Elevated hs-CRP levels have been associated with a significant increase in risk for cardiovascular events (Ridker et al. NEJM 2000;342:836-843; Lagrand et al. Circulation 1999;100:96-102). Values >3.0 mg/L are considered high risk, between 1.0 mg/L and 3.0 mg/L intermediate and <1.0 mg/L low risk, corresponding to approximately two thirds and one third (tertiles) of adult population distributions. Due to the wide individual variability, the recommended protocol for individual CRP measurements suggests obtaining samples on three separate occasions (at least one week apart). The mean value of the three is calculated as the “average” value (DeMaat et al. Arterioscler,Thrombo Vasc Biol. 1996;16;1156-1162).
Lp-PLA2 is associated with vascular inflammation specific to CVD. The risk for Cardiovascular Disease events rises sharply when Lp-PLA2 exceeds 223 ng/ml. Values above 200 ng/ml are in the upper 25th percentile for a secondary prevention Cardiovascular Disease-diagnosed American population. Elevated Lp-PLA2 values are known to indicate an active atherogenic process and are associated with prediction of CVD and stroke events.
N-terminal pro-Brain natriuretic peptide (NT-proBNP) is associated with prediction of cardiac events when used as a biomarker of subclinical myocardial stress or stretch (Blankenberg et al.HOPE study. Circ. 2006; 114;3:201-208; McKie et al. Hypertension. 2006; 47:874-880) and is also used to aid CHF diagnosis. When used as a prognostic biomarker, NT-proBNP levels above 125 pg/mL suggest increased CVD risk in which further diagnostic studies may be considered as clinically indicated. Levels above 450 pg/mL suggest structural or functional cardiac dysfunction.
Q-LDL (IIIa+b) and Q-LDL (IVb)
Atherogenic subclass quantitation, Q-LDL(IIIa+b) and Q-LDL(IVb), provides a measure of atherogenic LDL particles in mg/dL and are based upon results from Apo B and LDL-S3GGE®.