Dyslipidemia Induced Vascular Disease
The “cholesterol –centric” approach to cardiovascular disease is an obsolete concept for many reasons. There are infinite numbers of insults (risk factors and mediators) for coronary heart disease (CHD) but only three finite vascular responses: inflammation, oxidative stress and immune vascular dysfunction. There are over 400 well described cardiovascular risk factors, but most clinicians are taught to evaluate and treat only the top five: hypertension, dyslipidemia, diabetes mellitus, obesity, and smoking. Decades of concentrating only on these five has not resulted in optimal reduction in CHD. In fact, there exists a large “CHD gap” by treating only these five CHD risk factors. This means that over 50% of patients still have CHD and myocardial infarction (MI) despite what is considered good treatment. However, the definition of each of these risk factors and the details of how to properly assess and treat them is severely lacking in clinical medicine.
Measurement of serum lipids must be done using advanced lipid testing (Spectracell, Liposcience, Berkeley Heart Labs and Atherotec), to measure the various lipid particle numbers and size in order to predict risk and proper treatment. Total measures of cholesterol, LDL, HDL, and TG are no longer adequate. LDL P (particle number) and LDL size (small dense LDL B) drive the risk for CHD. Once the LDL P is below 700 the CHD risk drops and the LDL size is no longer a predictor. Many drugs such as statins do not decrease LDL P by more than 30-50%. Goals set by NECP 3 to decrease LDL to 100 or 60 mg % depending on clinical risk, leaves a large number of patients not at their LDL P goal and thus at risk for CHD (the CHD gap). This is particularly true of those with insulin resistance, metabolic syndrome and diabetes mellitus who have increased LDL P, dense LDL B, decreased HDL P and small dense HDL. In addition, HDL P is the most protective for CHD and large HDL 2 b with functional HDL are also important. HDL functionality can be indirectly assessed by measuring myeloperoxidase (MPO) from Cleveland Clinic. MPO will oxidize many of the proteins in HDL and it will not perform its various metabolic duties. A very high HDL, over 85mg%, may be a clue to dysfunctional HDL in patients.
Native LDL is not usually atherogenic and must by modified to oxLDL or glycated LDL or acetylated LDL in order to be ingested by macrophages with scavenger receptors. This is the beginning of the inflammatory, oxidative, and immune response in the subendothelial layer. Reverse cholesterol transport by HDL will modify these responses.
There are 38 mechanisms to interrupt the dyslipidemic-induced vascular disease with nutrition, nutritional supplements and drugs. This will be the new approach to decrease the vascular disease in the future.