Oxidative stress

Oxidation produces damaging free radicals. Oxidation is actually normal and occurs in common human functions such as when our immune system fights an infection. What we need is a balance between the oxidative formation of free radicals and their clearance by antioxidants which scavenge the free radicals. Examples of antioxidants are cruciferous vegetables, HDL cholesterol, and chemicals produced by aerobic exercise. It may or may not add to vascular inflammation.

F2 Isoprostane- Measures oxidative stress. If elevated, we need to determine why and consider treating other risk factors more aggressively.

Inflammatory Markers

Inflammation is the primary destabilizing force on arterial linings that leads to most chronic disease. Think of inflammation as fire. We need to detect the fire and extinguish it with medication, supplements, and lifestyle changes. We also need to search for causes of the fire and treat them too. Causes include insulin resistance, sleep apnea, and periodontal disease, gout, and other inflammatory diseases.

Inflammation can occur in the arterial lining called the endothelium, or it can occur under the lining called the intima. There are markers that look at both locations, and together give us an idea of how hot your arteries are, and how at risk you are of a heart attack or stroke.

LpPLAC-2- this marker measures inflammation of the intima layer underneath the endothelium. It is very specific for vascular inflammation and is an important target of treatment to reduce stroke and heart attack risk.

Myeloperoxidase (MPO)- Low levels of MPO are necessary to fight infectious diseases. Moderately Elevated levels (>480) lead to a flow of cholesterol into the arterial wall. It also makes HDL cholesterol dysfunctional, which inhibits its ability to “shovel” cholesterol particles out of the arterial walls. High levels also weaken the fibrous cap of plaque and are predictive of a heart attack and stroke. MPO is a very important target of treatment.

HS CRP- HS CRP measures general inflammation somewhat specific to arterial linings. It is helpful if low (< 1.0). Other conditions can raise its level, so it is just a marker, not a target of treatment. However, if both HS CRP and MPO are elevated, we must be very aggressive because the combination suggests a 5 fold increased risk of heart attack.

Fibrinogen- Elevated fibrinogen (>350-400) suggests inflammation of the endothelial lining. The problem is that there are several other causes of fibrinogen elevation, so it is also only a piece of the puzzle, not a target of treatment.

Endothelial Dysfunction

Microalbumin/creatinine ratio (MACR)- Dysfunction of the endothelium adds to instability of a plaque. MACR is an indirect measure of endothelial function. Microalbumin is a protein. It measures how well your endothelium is actually functioning by measuring how much microalbumin is “slipping through” the arteries in your kidneys. If elevated, it places you at a 3 fold risk of heart attack or stroke in the next 6 years. Like MPO, MACR is a target of treatment. When you look at your MACR result, ignore the “normal” value of < 30. That is for diagnosing kidney disease in a diabetic, not for identifying endothelial dysfunction. The appropriate normals are < 4.0 in men and < 7.5 in women.

Summary

 All markers are important to assess for vulnerable plaque. We will specifically target treatment to normalize the MPO, MACR, and LpPLAC-2.