Cardiovascular Risk Inflammatory Marker: Risk Assessment for Coronary Heart Disease and Ischemic Stroke – Atherosclerosis
Reporter: Aviva Lev-Ari, PhD, RN
Updated on 10/3/2018
Treatment concentration of high-sensitivity C-reactive protein
Interleukin 1β has multiple potential mechanisms that contribute to the pathogenesis of atherothrombotic cardiovascular disease.
Induction of interleukin 6 leads to the release of acute phase reactants including hsCRP. Thus, hsCRP serves as a surrogate marker of the overall inflammatory milieu,
often in situations where patients have multiple co-morbidities,
with a cumulative dose-response indicating a higher risk.
References
N Engl J Med. 2017; 377: 1119-1131
J Am Coll Cardiol. 2017; 70: 2278-2289
Atherosclerosis. 2017; 266: 16-23
J Am Heart Assoc. 2017; 6: e005610
on behalf of the CANTOS Trial Group
Lancet. 2017; (published online Nov 13.)
Cardiovascular Risk Inflammatory Marker: Risk Assessment for Coronary Heart Disease and Ischemic Stroke – Atherosclerosis.
Watch VIDEO
Lp-PLA2 Overview Webinar
Source: http://www.plactest.com/healthcare/webinar
Watch VIDEO
american-heart-association-2007-lppla2-highlights
American Heart Association 2007 Lp-PLA2 Presentation
Source: http://www.plactest.com/healthcare/american-heart-association-2007-lppla2-highlights
diaDexus’s PLAC, the test measuting Lp-PLA2 as a novel and valuable cardiovascular risk inflammatory marker a vascular-specific inflammatory marker implicated in the formation of rupture-prone plaque, and is the only blood test cleared by the FDA to assess risk for coronary heart disease and ischemic stroke associated with atherosclerosis. (2003 and in 2005 received additional clearance as an aid in the assessment of risk for ischemic stroke associated with atherosclerosis.)
In 2007 the PLAC Test was granted a Category I CPT Code (83698) by the American Medical Association and is reimbursed by the Centers for Medicare and Medicaid Services (CMS) with a National Limitation Amount (NLA) of $47.77 in the 2011 CMS Clinical Laboratory Fee Schedule.
In July 2010, diaDexus completed a reverse merger with VaxGen. diaDexus currently trades on the OTC Bulletin Board (DDXS.OB).
PLAC Test is an alternative to C- Reactive Protein Test
The PLAC® Test is a simple blood test to detect Lp-PLA2 in the bloodstream. It is used to help predict risk for coronary heart disease and ischemic stroke associated with atherosclerosis.
- The PLAC Test measures Lp-PLA2
(lipoprotein-associated phospholipase A2), a vascular-specific inflammatory enzyme implicated in the formation of rupture-prone plaque. It is plaque rupture and thrombosis, not stenosis, that causes the majority of cardiac events. - A substantial body of evidence, including over 100 studies and abstracts in peer-reviewed journals and conferences, support Lp-PLA2 as a cardiovascular risk marker that provides new information, over and above traditional risk factors.
- Consistent with ATP III and European guidelines, the PLAC Test should be used as an adjunct to traditional risk factor assessment to identify which moderate or high risk patients, as initially assessed by traditional risk factors, may actually be at higher risk.
- An elevated PLAC Test may indicate a need for more aggressive patient management.
- 50% of cardiovascular events strike in patients with unremarkable lipid levels, highlighting the prevalence of hidden cardiovascular risk.
- LDL-C and total cholesterol have proven not to be reliable predictors of stroke; the PLAC Test addresses this unmet clinical need.
- Lipid lowering therapies, including statins, are proven to reduce cardiovascular events regardless of baseline LDL-C levels.
Basic Science of Lp-PLA2
The PLAC® Test measures Lp-PLA2 (lipoprotein-associated phospholipase A2) a vascular-specific inflammatory enzyme implicated in the formation of rupture-prone plaque. It is plaque rupture and thrombosis that cause the majority of cardiac events, not stenosis.
Lp-PLA2 is a calcium-independent serine lipase that is associated with both low-density lipoprotein (LDL) and, to a lesser extent, high-density lipoprotein (HDL) in human plasma and serum and is distinct from other phospholipases such as cPLA2 and sPLA2. Lp-PLA2 is produced by macrophages and other inflammatory cells and is expressed in greater concentrations in advanced atherosclerotic lesions than early-stage lesions.
Lp-PLA2 has demonstrated modest intra- and inter-individual variation, commensurate with other cardiovascular lipid markers and substantially less than C-reactive protein (CRP). In addition, Lp-PLA2 is not elevated in systemic inflammatory conditions, and may be a more specific marker of vascular inflammation. The relatively small biological variation of Lp-PLA2 and its specificity are of value in the detection and monitoring of cardiovascular risk.
SOURCE:
http://www.plactest.com/healthcare/basic-science.html
Clinical Utility of the PLAC Test
The PLAC® Test Measures Lp-PLA2, a Unique Marker The PLAC Test for Lp-PLA2 is the only blood test cleared by the FDA to aid in assessing risk for both coronary heart disease and ischemic stroke associated with atherosclerosis. The PLAC Test measures lipoprotein-associated phospholipase A2 (Lp-PLA2), a vascular-specific biomarker implicated in the formation of rupture-prone plaque. The majority of all heart attacks and strokes are caused by plaque rupture and thrombosis (clots) – not stenosis (narrowing of arteries).
Lp-PLA2 is a unique marker for vascular-specific inflammation and is produced by macrophages in inflamed plaque. Lp-PLA2 provides additive risk information when combined with other markers such as hs-CRP to help you personalize your treatment options, beyond the limitations of the traditional cardiovascular (CV) risk factors.
The PLAC Test Helps Identify Hidden Risk Lp-PLA2 is an independent risk marker for stroke. At every level of blood pressure, an Lp-PLA2 value above the median almost doubles the risk for stroke. Current stroke guidelines include consideration of Lp-PLA2 measurement in asymptomatic patients to identify those who may be at increased risk of stroke.
The PLAC Test Helps Improve Patient Management Periodic measurement of the amount of Lp-PLA2 in the blood for patients with 2 or more CVD risk factors can aid clinical decisions for at-risk patients, allowing you to assess or reassess the effect of lipid lowering therapies on vascular inflammation, intensify therapeutic lifestyle changes, and reinforces doctors’ recommendations for patient management.
Essential Information to Guide Treatment
In accordance with ATP III Guidelines, patients with 2 or more CV risk factors may be candidates for advanced lipid testing.
Measure the amount of Lp-PLA2 in your patient’s blood stream with the PLAC Test to determine whether they may be at increased risk for heart attack or stroke.
If the PLAC Test results are 200 ng/mL or greater, cardiovascular disease may be present. Review your patient’s advanced lipid panel results to determine where more aggressive patient management may be needed.
* additional reduction of Lp-PLA2 seen when added to statin therapy.
Based on:
Shalwitz R, et al. ATVB Annual Mtg. 2007.
Kuvin J, et al. Am J Cardiol. 2006.
Albert M, et al. Atherosclerosis 2005.
Schaefer EJ, et al. Am J Cardiol. 2005.
Saougos VG, et al. ATVB 2007.
Muhlestein JB, et al. JACC 2006.
Early detection and more aggressive treatment can help prevent cardiovascular events.
SOURCE:
http://www.plactest.com/Default.aspx?PageID=4620488&A=PrinterView
REFERENCES
Pathophysiology and Genetics Studies
A Twin Study of Heritability of Plasma Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Mass and Activity Lenzini L, Antezza K, Caroccia B, Wolfert RL, Szczech R, Cesari M, Narkiewicz K, Williams CJ, Rossi GP. A Twin Study of Heritability of Plasma Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Mass and Activity. Atherosclerosis. 2009; 205(1): 181-5.
Enhanced Expression of Lp-PLA2 and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaque Mannheim D, Herrmann J, Versari D, Gössl M, Meyer FB, McConnell JP, Lerman LO, Lerman A. Enhanced Expression of Lp-PLA2 and Lysophosphatidylcholine in Symptomatic Carotid Atherosclerotic Plaque. Stroke. 2008; 39: 1448-55.
Expression of Lipoprotein-Associated Phospholipase A2 in Carotid Artery Plaques Predicts Long-term Cardiac Outc Herrmann J, Mannheim D, Wohlert C, Versari D, Meyer FB, McConnell JP, Gössl M, Lerman LO, Lerman A. Expression of Lipoprotein-Associated Phospholipase A2 in Carotid Artery Plaques Predicts Long-term Cardiac Outcome. Eur. Heart J. 2009 Dec; 30(23): 2930-8.
Lipoprotein-Associated Phospholipase A2 is an Independent Marker for Coronary Endothelial Dysfunction in Humans Yang EH, McConnell JP, Lennon RJ, Barsness GW, Pumper G, Hartman SJ, Rihal CS, Lerman LO, Lerman A. Lipoprotein-Associated Phospholipase A2 is an Independent Marker for Coronary Endothelial Dysfunction in Humans. Arterioscler Thromb Vasc Biol. 2006; 26(1): 106-11.
Lipoprotein-Associated Phospholipase A2 Protein Expression in the Natural Progression of Human Coronary Atherosclerosis Kolodgie FD, Burke AP, Skorija KS, Ladich E, Kutys R, Makuria AT, Virmani R. Lipoprotein-Associated Phospholipase A2 Protein Expression in the Natural Progression of Human Coronary Atherosclerosis. Arterioscler Thromb Vasc Biol. 2006; 26: 2523-9.
Therapeutic Modulation Studies
Cardiovascular Events With Increased Lipoprotein-Associated Phospholipase A2 and Low High-Density Lipoprotein-Cholesterol. The Veterans Affairs HDL Intervention Trial. Robins SJ, Collins D, JJ, Bloomfield HE, Asztalos BF. Cardiovascular Events With Increased Lipoprotein-Associated Phospholipase A2 and Low High-Density Lipoprotein-Cholesterol. The Veterans Affairs HDL Intervention Trial. Arterioscler Thromb Vasc Biol. 2008; 28(6): 1172-8.
Changes in Lp-PLA2 activity in secondary prevention predict coronary events and treatment effect by pravastatin in long term intervention with pravastatin in ischemic disease (LIPID) Trial White HD, Simes J, Barnes, E et al. Changes in Lp-PLA2 activity in secondary prevention predict coronary events and treatment effect by pravastatin in long term intervention with pravastatin in ischemic disease (LIPID) Trial. Circulation, abstract 14857, AHA 2011
Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2 Saougos VG, Tambaki AP, Kalogirou M, Kostapanos M, Gazi IF, Wolfert RL, Elisaf M, Tselepis AD. Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2. Arterioscler Thromb Vasc Biol. 2007; 27: 2236-43.
Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease Kuvin JT, Dave DM, Sliney KA, Mooney P, Patel AR, Kimmelstiel CD, Karas RH. Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease. Am J Cardiol. 2006; 98: 743-5.
Changes in Lp-PLA2 activity in secondary prevention predict coronary events and treatment effect by pravastatin in long term intervention with pravastatin in ischemic disease (LIPID) Trial White HD, Simes J, Barnes, E et al. Changes in Lp-PLA2 activity in secondary prevention predict coronary events and treatment effect by pravastatin in long term intervention with pravastatin in ischemic disease (LIPID) Trial. Circulation, abstract 14857, AHA 2011
Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2 Saougos VG, Tambaki AP, Kalogirou M, Kostapanos M, Gazi IF, Wolfert RL, Elisaf M, Tselepis AD. Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2. Arterioscler Thromb Vasc Biol. 2007; 27: 2236-43.
Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease Kuvin JT, Dave DM, Sliney KA, Mooney P, Patel AR, Kimmelstiel CD, Karas RH. Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease. Am J Cardiol. 2006; 98: 743-5.
Changes in Lp-PLA2 activity in secondary prevention predict coronary events and treatment effect by pravastatin in long term intervention with pravastatin in ischemic disease (LIPID) Trial White HD, Simes J, Barnes, E et al. Changes in Lp-PLA2 activity in secondary prevention predict coronary events and treatment effect by pravastatin in long term intervention with pravastatin in ischemic disease (LIPID) Trial. Circulation, abstract 14857, AHA 2011
Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2 Saougos VG, Tambaki AP, Kalogirou M, Kostapanos M, Gazi IF, Wolfert RL, Elisaf M, Tselepis AD. Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2. Arterioscler Thromb Vasc Biol. 2007; 27: 2236-43.
Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease Kuvin JT, Dave DM, Sliney KA, Mooney P, Patel AR, Kimmelstiel CD, Karas RH. Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease. Am J Cardiol. 2006; 98: 743-5.
[…] Reporter: Aviva Lev-Ari, PhD, RN http://pharmaceuticalintelligence.com/2012/10/30/cardiovascular-risk-inflammatory-marker-risk-assess… […]
[…] http://pharmaceuticalintelligence.com/2012/10/30/cardiovascular-risk-inflammatory-marker-risk-assess… […]
[…] Cardiovascular Risk Inflammatory Marker: Risk Assessment for Coronary Heart Disease and Ischemic Str… […]
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette