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Endothelial Dysfunction - The Optimal Takeaways
Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN
The early intervention and prevention of endothelial dysfunction includes the following:
The Endothelial Dysfunction Series
- Endothelial Dysfunction - An Overview
- Endothelial Dysfunction - The Endothelium
- Endothelial Dysfunction - Nitric Oxide
- Endothelial Dysfunction - Diseases and Causes
- Endothelial Dysfunction - Immune Response & Oxidative Stress
- Endothelial Dysfunction & Atherosclerosis
- Endothelial Dysfunction - Assessment Part 1
- Endothelial Dysfunction - Assessment part 2
- Endothelial Dysfunction - Functional Naturopathic Approach
- Endothelial Dysfunction part 10 - Optimal Takeaways
- An optimal flow-mediated dilation (FMD) reading, a reflection of nitric oxide production
- A healthy diet rich in fresh fruits and vegetables, antioxidants, omega-3 fatty acids, monounsaturated fats, anti-inflammatory herbs and spices, vitamins, minerals, and phytonutrients
- Targeted nutrition supplementation
- Minimization of exposure to toxins, pollution, cigarette smoke, and stress
- Regular robust physical activity
- Maintain a desirable body weight and lean body mass
- Stress management
- Address biomarkers out of the optimal range including those related to oxidative stress, inflammation, and blood glucose regulation:
- Blood glucose
- C-reactive protein (CRP, hs-CRP)
- Iron levels
- Neutrophil:Lymphocyte Ratio (NLR)
- Oxidized LDL (OxLDL)
- Asymmetric dimethylarginine (ADMA)
- Myeloperoxidase (MPO)
- Malondialdehyde (MDA)
- Gamma-glutamyl transferase (GGT)
- Omega-3 Index
Overview - Optimal Takeaways
- The vascular endothelium is considered the largest endocrine organ in the body.
- It signals underlying smooth muscle to constrict and relax and protects it from toxins and oxidative stress.
- The vascular endothelium regulates a wide variety of metabolic activities including thrombosis, inflammation, leukocyte adhesion, vasomotor tone, blood flow, and blood vessel constriction and relaxation.
- Cardiovascular disease is the primary cause of death worldwide… and endothelial dysfunction is the primary cause of CVD and an underlying contributor to diabetes and hypertension.
- Causes of endothelial dysfunction overlap with those of atherosclerosis CVD and include immune activation, pro-inflammatory cytokines, oxidative stress, hyperglycemia, toxin exposure, pollution, homocysteine, poor diet, sedentary lifestyle, etc.
- Nitric oxide helps to maintain reduced vascular tension and low oxidative stress, conditions required for healthy blood vessels. Disruption of nitric oxide metabolism causes a disruption of the vascular endothelium.
Dysfunction - Optimal Takeaways
- Immune activation and immune cell infiltration can promote endothelial dysfunction, especially neutrophil activity.
- Oxidative stress is a significant contributor to endothelial dysfunction due to increased free radicals and oxidized LDL, and decreased superoxide dismutase and nitric oxide bioavailability.
- Endothelial dysfunction leads to atherosclerosis, a culmination of antioxidant insufficiency, oxidative stress, chronic inflammation, elevated homocysteine, and undesirable lifestyle factors.
- Pollution and particulate matter contribute to endothelial dysfunction.
- Early detection of endothelial dysfunction is critical to preventing atherosclerosis and CVD.
Assessment - Optimal Takeaways
- Endothelial dysfunction itself may not have overt symptoms, and atherosclerosis has a “silent phase” and can go undetected until telltale signs such as angina occur.
- Clinical measurement of endothelial dysfunction may be achieved through a variety of techniques, with flow-mediated dilation (FMD) being the most common tool.
- FMD reflects nitric oxide production and can be instrumental in predicting CVD events in seemingly low-risk individuals.
- The “cold pressor test” is a non-invasive method of evaluating the sympathetic-mediated release of nitric oxide. In endothelial dysfunction, vasoconstriction occurs and hyperreactors will mount a hypertensive response.
- Biomarker characteristics of endothelial dysfunction include:
- Elevated homocysteine, glucose, fibrinogen, CRP/hs-CRP, iron, ferritin, neutrophil:lymphocyte ratio, oxidized LDL, asymmetric dimethylarginine, myeloperoxidase, malondialdehyde, gamma-glutamyl transferase, and increased inflammatory markers.
- Insufficient testosterone, low omega-3 index, low adiponectin
- Advanced biomarkers may also be measured (e.g., cellular adhesion molecules, von Willebrand factor, sNOX2-dp, 8-isoPFG2a, EPCs, MVs)
Treatment - Optimal Takeaways
- Hypertension, diabetes, obesity, hyperlipidemia, and smoking are risk factors for thrombosis, atherosclerosis, and endothelial dysfunction.[i]
- Combined with oxidative stress and a pro-inflammatory milieu, these risk factors form the main pillars underlying cardiovascular risk.
- Major modifiable factors include diet, activity, lifestyle, nutrient insufficiencies, supplementation, exposure to toxins and pollutants, and stress management.
- Failure to address these factors will propel individuals down the road from metabolic disturbance to chronic, life-threatening disease.
- Basically, a healthy lifestyle makes for a healthy life.
- Allopathic treatments are based on identification of endothelial dysfunction once it occurs instead of early preventative measures.
- Functional naturopathic approaches to endothelial dysfunction rely on recognizing and addressing contributing factors and associated biomarkers.
[i] Qi, Haozhe et al. “Neutrophil Extracellular Traps and Endothelial Dysfunction in Atherosclerosis and Thrombosis.” Frontiers in immunology vol. 8 928. 7 Aug. 2017, doi:10.3389/fimmu.2017.00928