Endothelial Dysfunction
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.
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.
Explore the endothelial inputs
Tap each factor to see whether it helps or harms the lining of your arteries.
This step is interactive — open the Thier app to try it.
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.
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.
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.