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Endothelial Dysfunction

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The first domino

Your arteries aren't passive plumbing. They're lined with a thin active layer of endothelial cells that produce nitric oxide, regulate clotting, control vascular tone, and keep bad particles out. When the endothelium fails, atherosclerosis starts. Decades before a heart attack, this is where it begins.

Fact

Nitric oxide is the currency

Healthy endothelium produces nitric oxide (NO) on demand — relaxing blood vessels, preventing platelet stickiness, and keeping LDL out. Endothelial dysfunction is essentially a nitric-oxide deficit. Exercise, leafy greens (nitrate), and sunlight all boost NO. Smoking and hyperglycaemia kill it.

NO nitric oxide
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Explore the endothelial inputs

Tap each factor to see whether it helps or harms the lining of your arteries.

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Fact

Zone 2 specifically protects the endothelium

Low-to-moderate intensity aerobic exercise (Zone 2) creates sustained laminar shear stress on the vessel wall — the physical stimulus that upregulates endothelial nitric-oxide synthase. This is why 3–4 hours of Zone 2 per week has outsized impact on vascular health.

3–4 h Zone 2 per week
Fact

FMD — measuring endothelial function in vivo

Flow-mediated dilation (FMD) is the clinical test for endothelial function. The technician inflates a blood-pressure cuff on your forearm, releases it after 5 minutes, and measures how much your brachial artery dilates in response to the rush of blood. Healthy endothelium dilates ≥7 %; dysfunction shows up as <5 %. Each 1 % drop in FMD associates with ~13 % higher CV-event risk over 5 years (Inaba 2010 meta-analysis). Specialty preventive-cardiology clinics offer it; rare in primary care but worth asking about if your CAC is 0 but family history is concerning.

≥7% healthy FMD response
Takeaway

Key Takeaway

Before plaque, before calcium, before lipid abnormalities even register on labs, endothelial dysfunction is happening. Exercise (especially Zone 2), dietary nitrate, sleep, and glycaemic control are the direct levers. FMD lets you measure endothelial function directly. Everything downstream — ApoB, CAC, events — starts here.

References

  1. Nitric oxide and endothelial function — mechanisms reviewFörstermann & Sessa, 2010
  2. Shear stress and endothelial function — molecular mechanismsDavies, 2007
  3. FMD and cardiovascular event prediction — meta-analysisInaba et al., 2010

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