Advanced inflammatory marker testing

Doctor assessing for cardiovascular disease in patient

The response to injury hypothesis in cardiovascular disease

In 1976, Dr. Russell Ross published his “Response to Injury Hypothesis,” which brought to light the role of inflammation in atherosclerosis and cardiovascular disease (CVD).1 The evolution of Dr. Ross’s concepts have advanced from the initial endothelial injury to marked inflammatory changes. This concept, that atherosclerosis is driven by inflammation, the critical response to the retention of cholesterol containing lipoprotein particles, has been supported in many studies in animal models and observational studies in humans.2 Briefly:

  • Cardiovascular disease and atherogenesis begins with the subendothelial retention of cholesterol containing apoB-lipoproteins. This initial event commences a series of complex biological processes termed atherosclerosis in the artery wall.
  • The body responds to the injury with an inflammatory response designed to remove cholesterol from the artery wall.
  • This process becomes dysregulated and ultimately potentiates the progression of cholesterol deposition and vulnerable plaque formation, placing an individual at increased risk of plaque rupture and subsequent heart attack or stroke.

Uncovering hidden risk: the importance of inflammatory markers

Routine lipid screening plays an important role in cardiovascular risk assessment, but it may not adequately identify risk of adverse events. In fact, nearly 50% of all heart attacks and strokes occur in patients who had “normal” cholesterol levels.3 Evidence suggests that inflammation within the artery wall is a key contributor to residual risk for heart attack and stroke, contributing to both vulnerable plaque formation and to plaque rupture.

Inflammation can be easily measured with advanced testing to more fully assess cardiovascular risk. Monitoring a patient’s inflammatory status may help you to uncover hidden risk from early to advanced stages of cardiovascular disease. With deeper insights, you can take further action to help reduce your patients’ cardiovascular risk.

Expanded Cardio IQ® advanced inflammatory testing

Through its Cleveland HeartLab Cardiometabolic Center of Excellence, Quest Diagnostics now offers expanded, unique inflammation testing that provides additional and complementary insight into cardiovascular risk beyond lipid testing alone. Cardio IQ inflammation testing consists of easy to perform blood and urine biomarkers that identify inflammatory risk across the disease spectrum. This additional information allows for targeted treatment to reduce risk over one’s lifetime.

From potential risk to disease development and progression

Cardio IQ® inflammatory marker testing covers a patient’s biomarker profile, ranging from markers resulting from lifestyle concerns (f2-IsoPs, OxLDL) to the development of metabolic or cardiovascular disease (ADMA/SDMA, microalbumin, hsCRP), and formation of vulnerable plaque and increased risk for an adverse event (Lp-PLA2, MPO).

A multimarker approach that includes inflammatory markers can aid in risk stratification

Numerous studies have demonstrated the utility of a multimarker approach to stratifying cardiovascular disease risk.4-6 When combined with standard lipid testing, inflammatory marker testing allows for additional risk stratification, and may be considered for:7

  • Low-to-moderate risk, identified as >5% by the estimated CVD risk
  • Established cardiovascular disease
  • Diabetes
  • Hypertension
  • Metabolic syndrome, as defined by having any 3 of 5 conditions: central obesity, elevated triglycerides, low HDL-C, elevated blood pressure, or elevated plasma glucose
  • Dyslipidemia

Our advanced inflammatory testing menu

Quest Diagnostics offers a comprehensive menu of advanced inflammatory marker testing to help you assess cardiovascular risk more completely.

Test Name Clinical Utility
Cardio IQ® Myeloperoxidase (MPO) MPO, or myeloperoxidase, is an inflammatory enzyme released within the vascular lumen during white blood cell activation in response to fissures, erosions, or degradation of the fibrous cap. MPO is a specific marker of vascular inflammation and is a measure of vulnerable plaque. Elevated levels of MPO independently predict 2.0–2.4x increased risk of future cardiovascular events (MI, coronary revascularization, or CVD-related death).8,9
Cardio IQ® Lp-PLA2 Lp-PLA2 is an enzyme produced by macrophages and foam cells within the necrotic core of arterial plaque. Lp-PLA2 measures the disease within the arterial wall under the calcified cap of the plaque. Elevated Lp-PLA2 has been associated with a 2.0x increased risk for developing CHD independent of non-HDL cholesterol levels. Also, elevated Lp-PLA2 levels indicate a 2.0x risk of having a CHD event (MI, coronary revascularization or CHD-related death).10
Cardio IQ® hs-CRP hs-CRP is a highly sensitive measurement of C-reactive protein, an acute-phase reactant protein that increases in response to inflammation. In large epidemiologic studies, elevated levels of CRP have been shown to be a strong indicator of CVD. Patients with high CRP have a 1.5-2.0x increased risk of developing subsequent atherosclerotic disease compared with patients with low CRP levels. It’s also been demonstrated that lowering hs-CRP, independent of lipid levels, results in a 15% risk reduction of recurrent cardiovascular events.7,11,12
Cardio IQ® ADMA/SDMA ADMA/SDMA, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are derivatives of the amino acid L-arginine and produced via protein degradation. ADMA is a competitive inhibitor of nitric oxide synthase and can reduce the production of nitric oxide. Nitric oxide deficiency is an early manifestation of endothelial dysfunction and atherosclerotic disease. Elevated ADMA indicates a 1.4x increased risk of CVD and coronary heart disease (CHD) and a 1.6x increased risk of stroke. SDMA is primarily excreted in the urine and strongly correlates with reduced renal function.13
Cardio IQ® Oxidized LDL OxLDL, or oxidized LDL, measures damage of the ApoB protein subunit on the surface of LDL due to oxidative modification. Oxidation of ApoB is an initiating factor in macrophage recruitment, foam cell formation, and vascular inflammation within the arterial wall. Elevated OxLDL levels indicate a 4.3x increased risk of having a CHD event and a 3.5x increased risk of developing metabolic syndrome (MetS).14,15
Cardio IQ® F2-Isoprostane/Creatinine F2-IsoPs, or F2-Isoprostanes, are prostaglandin-like compounds formed from free radical-mediated oxidation of arachidonic acid. F2-IsoPs measure oxidative stress induced by lifestyle risk factors for CVD including smoking, poor diet, high red meat intake, and a sedentary lifestyle. F2-IsoPs contribute to CVD progression through increased vasoconstriction via thromboxane production, platelet aggregation, and thrombus formation. Elevated levels of F2-IsoPs indicate a 2.6x increased risk for CAD and a 1.8x increased risk of CVD mortality.16
Cardio IQ® Fibrinogen Antigen, Nephelometry Fibrinogen is a plasma glycoprotein that can be transformed into a fibrin clot in response to vascular or tissue injury. The combination of elevated fibrinogen with other CVD risk factors produces an additive risk and can substantially increase disease potential.17

Go beyond traditional risk factors. Learn more about inflammatory marker testing.

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