Endothelial Dysfunction part 10 - The Optimal Takeaways

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

1. Endothelial Dysfunction - An Overview
2. Endothelial Dysfunction - The Endothelium
3. Endothelial Dysfunction - Nitric Oxide
4. Endothelial Dysfunction - Diseases and Causes
5. Endothelial Dysfunction - Immune Response & Oxidative Stress
6. Endothelial Dysfunction  & Atherosclerosis
7. Endothelial Dysfunction - Assessment Part 1
8. Endothelial Dysfunction - Assessment part 2
9. Endothelial Dysfunction - Functional Naturopathic Approach
10. 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:

Elevated

• Homocysteine
• Blood glucose
• Fibrinogen
• 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)

Decreased

• Omega-3 Index
• Adiponectin
• Testosterone

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.

References

[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