Tuesday, November 13, 2012

Other Cardiac biomarkers (CRP, BNP, OxLDL, Lp(a) etc)


It is an acute phase reactant produced during inflammation. Even a low concentration (so called hsCRP, assay detecting CRP <0.3 mg/L) can be a marker of atherosclerotic process which involves an inflammatory process. TNF, IL-1 which are produced during early inflammation stimulate IL-6 that then cause elaboration of CRP from liver.

For primary prevention, hsCRP values >3 mg/L are considered high risk. Value <1 mg/L is low risk; 1-3 mg/L is intermediate risk.

At present, it is recommended to take two measurements spaced 2 weeks apart, average them, and use the value to monitor risk for atherosclerosis inflammation. If the hs-CRP value is greater than 10 mg/L, the sample is invalid. High values are due to the presence of active infection or another inflammatory stimulus that has elevated the CRP.

The measurement of hs-CRP includes binding of hs-CRP with anti-CRP antibody and the light scatter by the precipitate is quantified.


Brain (or B-type) natriuretic peptide (BNP) is a hormone stored mainly in the myocardium of cardiac left ventricles. Its level is increased in hypervolemic states like congestive heart failure and hypertension. So it is proposed to be a marker of CHF and edema due to heart failure.

Natriuretic peptide regulated fluid volume, blood pressure, and electrolyte balance. The main source of circulating BNP is the heart left ventricle, although isolated from porcine brain. BNP and ANP are released in response to atrial and/or ventricular stretch from volume overload e.g. during CHF.  NPs increases cardiac output by decreasing systemic and pulmonary vascular resistance, they reduce renin and aldosterone production by increasing renal blood flow, GFR and urine output. BNP (T1/2 is 20-40 min) is formed from proBNP which produces NT-proBNP ((T1/2 is 1-2 hr) which is a leader sequence and c-terminal BNP (physiologically active). BNP is degraded by neutral endopeptidase, by receptor mediated clearance, and bit by kidney.

Monoclonal antibody based ELISA test available although not standardized. POCT testing is approved by FDA.

Oxidized LDL:

It is a modified LDL and can enter cell via scavenger receptor especially in macrophage to form foam cells. It is formed in arterial wall where it is sequestered by proteoglycans and other extracellular matrix and protected from plasma antioxidants. This process is a free-radical driven lipi peroxidation chain reaction initiated by free radical attacking and double bond association with PUFA, leading to generation of MDA and 4-hydroxynonenal which then bind to apo B-100, giving it increased negative charge and rendering it unrecognizable by native LDL receptors.

Oxidized LDL (oxLDL) can be taken up by macrophage to form foam cells, it can be chemoattractant for circulating monocytes into macrophages, inhibition of motility of resident macrophages.  It is also cytotoxic and immunogenic since circulating anti-oxLDL antibodies were detected in serum.

ELISA method for determination of oxLDL is currently available. However, at present time the clinical relevance of oxLDL has not been established and so routine measurement is not recommended.

Lipoprotein (a):

Lp(a) is structurally related to LDL, but  has carbohydrate rich protein apo(a) covalently bound to apoB-100 through disulfide linkage. Apo(a) is homologous to plasminogen and  is serine protease. Lp(a) competitively inhibit plasminogen activity inhibiting clot lysis

ELISA based techniques using primary capture polyclonal antibodies against apo(a) and secondary detection monoclonal antibody against apoB-100. Then substrate added for color formation which is measured spectrophotometrically

>30 mg/dl – increased risk of CHD.
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