© 2017 VitalityCardiology

David Freedman Medicine Professional Corporation

6633 Highway #7 East, Markham

Tel: 905.472.7127   email: Ashgrove@cardiomatters.com

398 Steeles Ave West, Thornhill

Tel: 905.881.0334  email: Steeles@cardiomatters.com

INFLAMMATORY MARKERS of HEART DISEASE

Most heart attacks occur in patients without significant blockages.  Often patients aren’t even recognized as having heart disease until they present with a heart attack, or even worse, with sudden death.

The classic  cholesterol panel and the Framingham risk score tells you about long-term risk but, how can you identify who your “hot” patients are? There are emerging biochemical tools which may help us to identify which patients are at risk of developing obstructive coronary disease or a vulnerable plaque instead of remaining normal and healthy. These tests may be useful for us to spot early atherosclerosis, when tests such as stress testing or coronary angiography would still be "normal" in many of these patients.

These inflammatory markers may tell us more about short-term risk and may need to be monitored periodically. These markers are based on what doctors know regarding how athersclerosis develops, Namely, that atherosclerosis starts at a young age with oxidatative stress producing inflammation, which causes the development of lipid-rich fatty streaks (with or without a calcified component), which then goes on to either obstructive coronary disease or a vulnerable plaque with subsequent rupture.  These markers provide an opportunity to capture these patients early on before they have presented with a clinical event , and possibly before they have developed obstructive coronary artery disease. At present, Canadian and American guidelines advocate the use of some of these markers. It is likely that as more becomes known about these different tests, we will learn how to incorporate more of them into our assessments of a given patient's risk.

 

ApolipoproteinB  (apoB) 

This is a protein which is attached to every single non-HDL type of lipid particle (IDL,LDL,VLDL) and is presently considered to be the best way to assess for particle number.  We often measure it when the calculated LDL cholesterol is thought to be unreliable (high triglycerides), and it is thought to be a reflection of the number of atherogenic particles in our blood . Lower levels are associated with lower risk

 

Cholesterol subclassification. 

It turns out that there are approximately 7 subtypes of LDL cholesterol. Some of these are small and dense LDL particles (IIIa/b, IVb)  and are thought to be more causative of atherosclerosis (compared with the larger forms) due to their ability to squeeze between the endothelial cells that line the inner wall of our blood vessels. Similarly, there are approximately 5 subtypes of HDL cholesterol, some of which are better than others at getting the “cholesterol” out of our blood (that's what HDL does). Low levels of HDL2b are associated with an increased risk of atherosclerosis.

hsCRP   

This is a blood protein that is produced in the liver which is a nonspecific marker for vascular disease. When it is elevated in the appropriate setting, it can be associated with 1.5-2x cardiac risk, and even higher risk when the LpPLA2 is also elevated (see below).

 

eGFR  

This is a marker of kidney dysfunction. The most common causes of this are hypertension and diabetes. 

A low level of this test defines the patient as a high risk individual.

 

HbA1C   

People with insulin resistance or metabolic syndrome are at increased risk of cardiovascular events. Even though diabetes is not diagnosed until HbA1C excedes 6.5%, a person's risk is thought to rise at levels above 5% and may increase cardiovascular risk by up to 1.8x even before diabetes is officially considered to be present.

 

F2-Isoprostanes    

These are prostoglandin materials that are a marker of healthy eating and exercise. In other words, they are  elevated when we eat poorly, smoke or are sedentary. They are vasoconstrictor (TXA2 mediated) products that increase cardiovascular risk by 30x. Think of them as a lie detector for telling the truth about how good your "lifestyle" really is.

 

Lp(a) 

This is a different type of LDL cholesterol which is associated with premature onset and advanced atherosclerosis. 

It is inherited and depending on its level of elevation may be associated with up to 1.3-1.5x cardiac risk

 

LpPLA2     

There are inflammatory cells called macrophages that produce LpPLA2. When LDL cholesterol particles enter the vascular endothelium they may oxidize. The  LpPLA2 which may bind to the LDL will contribute to the hydrolysis (or breakdown) of these oxidized LDL particles which then leads to the accumulation of oxidized fatty acids and other bad things. These "bad things" then go on to inflame and damage the vascular endothelium and attract more inflammatory cells to the area. One of the things which occurs, is that as the inflammation accumulates, macrophages will eat the oxidized LDL and transform into foam cells which then go on to deposit and create an actively enlarging inflammatory deposit which we refer to as a vulnerable atherosclerotic plaque. 

The LpPLa2 is very specific for vascular inflammation and is considered to be independent of traditional risk factors and has been shown to be applicable across different patient populations and different levels of cholesterol. An important thing to remember is that it is directly linked to progressive and unstable atherosclerosis and the adverse consequences which may follow (such as heart attack and sudden death).

Higher levels of LpPLA2 are predictors for vascular events (2x risk), especially when there is concurrent hypertension (7x risk), and especially when there is concurrent hypertension and elevated hsCRP (11x risk).

 

MAU    

Microalbumin (urine)  is a measure of determining endothelial dysfunction which once present suggests that the vessel wall in the kidneys is becoming damaged and “leaking” microalbumin into the urine. When the kidneys are leaking microalbumin, one expects that the vessel walls are also “leaking” elsewhere and are more prone to atherosclerosis. Elevated microalbumin levels may be associated with <1.5x cardiac risk.

 

MPO   

Myeloperoxidase is an enzyme that is released into blood when white blood cells are subjected to a vascular injury at a vulnerable plaque which is at increased risk of rupture.  Elevated levels are seen to be associated with a higher risk of coronary disease, heart attack, stroke, and death,

 

Omega3: Omega6 score 

Our diet contains polyunsaturated fatty acids (PUFA) which are important for good health. Unfortunately, the typical Western diet contains too much Omega 6 which creates a distorted balance that increases inflammatory disease processes including atherosclerosis. Consequently, eating Omega 3 fatty acids (EPA and DHA) is  thought to be extremely important for good health. These fatty acids are found in especially in fish, and when our Omega3:Omega6 ratio is low, then this can be associated with an increased risk of cardiovascular events.