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Atherosclerosis lipids inflammation endothelium

We only get one life on this earth and to make the most of it we need to know how to live a better quality of life and longer.  To understand longevity we have to understand what disorders and processes that shorten our life span and reduce our quality of life.  The 3 main disorders that eventually cause our morbidity and mortality are atherosclerotic cardiovascular disease, neurodegenerative disease and cancer. The processes that cause these begin when we are young adults and slowly advance as we age. We all have variable genetic predisposition to atherosclerosis (ASCVD) and environmental factors modify this process. Therefore daily preventative habits, practices, supplements, nutrition and lifestyle are necessary to slow the inevitable progression of these disorders. Preventative measures can slow down, delay or prevent the onset of heart attack, stroke, dementia, cancer and premature death.

Cholesterol has a bad reputation because it is found in atherosclerotic plaque but in reality it is a fundamental building block in all animal cells and necessary component of life.  In fact it is an essential molecule for many vital functions such as building cell walls, transporting triglycerides to our organs for energy, involved with our immune response, is a powerful antioxidant and is the building blocks of vital hormones such as estrogen, progesterone, testosterone and cortisol.

The vascular endothelium forms the inner lining of arteries, veins and capillaries. Atherosclerosis (ASCVD) occurs when cholesterol penetrates the endothelial lining and accumulates in the wall of our blood vessels. An inflammatory reaction ensues as the body tries to remove the cholesterol molecule. This process creates plaque consisting of cholesterol, macrophages, lymphocytes, platelets, fibrinogen and inflammatory mediators.  When these plaques rupture they expel their content into the artery which causes a thrombosis (blood clot) that occludes arteries and causes heart attack and stroke. The risk of ASCVD varies greatly among individuals and is influenced by many factors including hypercholesterolemia, high blood pressure, smoking, obesity, diabetes and family history.

Three main factors influence the development of ASCVD including elevated LDL-P (LDL particle number), chronic inflammation and the health of your vascular endothelium. We don’t absorb much cholesterol in the gut and the livers produce the vast majority of cholesterol needed by our bodies. Ingested cholesterol and fat does not significantly raise the cholesterol level. A high sugar and high carbohydrate diet overloads the glucose storage system and causes de novo lipogenesis (new cholesterol production) in the liver then elevated insulin causes this to be stored as fat in the adipose tissue. The lipid panel tested in conventional doctor’s offices only measures total cholesterol, LDL-C, HDL and triglycerides.  This panel is not powerful enough to accurately assess cardiovascular (CV) risk. Total cholesterol does not correlate to CV risk at all. Scientific studies on HDL show it is not cardioprotective as once thought. LDL-C loosely correlates with CV risk and is not specific enough for decision making when it comes to long term treatment with statins. LDL-P and APO-B correlate well with CV risk and is our best biomarker for assessing this. LP(a) is another lipoprotein that should be measured as it is the most atherogenic lipoprotein and present in about 20% of people. Since the treatment of elevated LDL cholesterol would include statins, which may have long-term unintended consequences yet TBD, fine tuning your cardiovascular risk is very important to this decision making process.  

Inflammation is the 2nd pillar of the development of ASCVD. Once LDL cholesterol has penetrated the endothelial lining of the blood vessel into the subendothelial space the body’s immune system sees this as a foreign invader and sends in white blood cells like macrophages and lymphocytes to remove the cholesterol.  These immune cells secrete inflammatory chemicals that recruit more cells, fibrinogen and platelets thus causing the formation of plaque. Inflammatory conditions in particular chronic obesity play a role in promoting plaque formation. We can measure inflammatory biomarkers such as CRP and fibrinogen to add to our understanding of a person’s risk of cardiovascular disease and plaque formation.  Treating inflammation is not as easy as taking an anti-inflammatory drug but rather can be accomplished by avoiding factors that activate your body’s inflammatory response such as smoking and obesity and increasing exercise and eating a low carbohydrate, low sugar diet rich in antioxidants from vegetables and whole foods. This requires an advanced lipid blood panel, NMR lipoprotein and LP(a) is another important biomarker that is the most atherogenic lipoprotein.

The 3rd contributing factor is the health of your endothelium. The vascular endothelium forms the inner lining of arteries, veins and capillaries. The endothelium is a one cell layer thick, highly metabolically active organ that is adaptive, flexible, and critical to many physiological processes such as vascular tone (blood pressure), leukocyte adhesion, cell migration, inflammation, hemostasis (clotting), and also serves as a barrier to infection. Nitric oxide is synthesized in endothelial cells from L-arginine which diffuses rapidly into the smooth muscle cell layers of the arteries and promotes vascular relaxation and inhibits platelet clotting, maintaining the equilibrium between clotting or not. Endothelial dysfunction is associated with the development of diabetes, hypertension, atherosclerosis, erectile dysfunction and sleep apnea. Maintaining a healthy endothelium can be accomplished through lifestyle choices: daily exercise, antioxidant rich diet (polyphenols in berries, vitamin C, flavonoids in fruits and vegetables), omega 3 fatty acids, nut consumption, control of blood pressure, cholesterol and weight. 

In summary ASCVD is a slowly progressive process that needs to be combated over the long hall by addressing the following factors.

  1. Reduce LDL-P cholesterol
  2. Reduce inflammation and improve endothelial health through a healthy, nutritious, low carb/sugar, high antioxidant diet combined with exercise.
  3. Control blood pressure
  4. Avoid type 2 diabetes through healthy lifestyle and weight control.
  5. Avoid smoking and toxic sugar in our diet such as high fructose corn syrup.
  6. Eat whole foods and avoid processed foods.

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