Table of Contents
Every 40 seconds, someone in the US has a heart attack. Every 33 seconds, someone dies from cardiovascular disease. Yet most people think heart disease starts with a bad cholesterol number. Here's what's really happening: the damage often begins decades earlier, before you feel it, before you see it, and before your doctor catches it.
Key Takeaways
- Heart disease damage starts decades before symptoms appear, often beginning with injury to the endothelial glycocalyx - your arteries' protective "force field"
- Standard cholesterol labs miss critical markers like nitric oxide function, arterial stiffness, and inflammatory indicators that predict heart attacks better than LDL alone
- Blood pressure should ideally stay under 115/75 - anything higher increases atherosclerosis risk regardless of age
- Your skeletal muscle health directly impacts heart disease risk, with sarcopenia accelerating cardiovascular aging significantly
- Simple at-home tests like nitric oxide strips and pulse wave velocity devices can reveal arterial dysfunction years before a heart attack
- The endothelial glycocalyx acts as your first line of defense - when healthy, it prevents cholesterol particles from sticking to artery walls
- Most heart attacks are actually the first symptom people experience, occurring when arteries are already 70-80% blocked with plaque
- Advanced testing like calcium scoring can detect heart disease risk in people as young as their 30s with strong family histories
- Nitric oxide pathways can be supported through specific lifestyle interventions including exercise, sunlight exposure, and green leafy vegetables
- Recent research suggests some popular diets may increase arterial plaque despite improving other health markers
The Invisible Enemy: Understanding Endothelial Dysfunction
Think of your arteries like a fish fresh out of water - they're covered in a protective, slimy coating called the endothelial glycocalyx. Dr. Michael Twyman, a preventive cardiologist specializing in mitochondrial optimization, describes this layer as "like the canary in the coal mine for your arteries."
This gel-like coating isn't just some medical curiosity. It's your cardiovascular system's first line of defense, acting like a force field that prevents cholesterol particles and white blood cells from penetrating the artery walls. Underneath this protective barrier lies the endothelium - a single cell layer that, if spread out, would cover about six tennis courts.
"Once things start getting deposited in the intima, then you're off to the races, developing plaque in the arteries," explains Dr. Twyman. The body's repair mechanisms kick in, depositing smooth muscle and eventually calcium to form what's essentially a bone-like structure to prevent plaque rupture.
But here's what's concerning: traditional medicine focuses heavily on treating end-stage disease rather than protecting this critical first layer. Most cardiologists don't routinely test for endothelial function, nitric oxide levels, or arterial stiffness. They're missing the early warning signs that could prevent heart attacks decades down the road.
The connection between this protective layer and nitric oxide is crucial. When your endothelial glycocalyx is healthy, it helps release nitric oxide - a gas molecule that won the Nobel Prize in Medicine in 1998 for its cardiovascular importance. This molecule acts like arterial Teflon, keeping blood pressure normal and preventing sticky substances from adhering to vessel walls.
Beyond Cholesterol: The Tests Your Doctor Isn't Ordering
Most people leave their doctor's office thinking they're heart-healthy because their cholesterol numbers look decent. But Dr. Twyman uses a completely different approach, organizing tests into three critical buckets that paint a much clearer picture.
The first bucket examines nitric oxide pathways. This includes testing uric acid and homocysteine levels - amino acids that can damage nitric oxide production when elevated. "If you have high uric acid from drinking too much alcohol or ingesting too much fructose, that uric acid can damage the glycocalyx, affecting the nitric oxide pathway," notes Dr. Twyman.
He also looks at urine microalbumin, traditionally used to detect kidney disease. But there's a deeper story here: "If you have protein in your urine, you're damaging the glycocalyx in the kidneys. If you're damaging that, potentially you're damaging the heart artery ones too."
The second bucket focuses on oxidative stress and inflammatory markers. Tests like high-sensitivity C-reactive protein (hsCRP), LP-PLA2 activity, and myeloperoxidase reveal whether inflammation is actively damaging your arteries. Myeloperoxidase is particularly interesting - it's a marker of white blood cell activation that can damage HDL cholesterol and the arterial lining.
"I've seen many of these patients over the years," Dr. Twyman explains about people with concerning inflammatory markers. "Almost every woman seems to have higher levels of myeloperoxidase. It's associated with autoimmune conditions, and women are at higher risk for autoimmune conditions."
Only after examining these foundational systems does Dr. Twyman move to the third bucket: lipoproteins themselves. While he still checks traditional cholesterol panels, he focuses more on advanced markers like apolipoprotein B (apoB) and lipoprotein(a) - often called Lp(a).
The Blood Pressure Revolution: Why 120/80 Isn't Good Enough
Forget everything you thought you knew about healthy blood pressure. The new target that Dr. Twyman aims for might surprise you: 115/75. "That should be optimal. 120 is quote normal," he clarifies, but explains that once blood pressure starts climbing above 115/75, atherosclerosis risk begins increasing.
This revelation comes from more recent studies like the SPRINT trial, which showed that regardless of age, treating to lower blood pressure targets provides better outcomes. This contradicts older thinking that suggested letting elderly patients run higher pressures for brain perfusion.
But here's where it gets really interesting: not all blood pressure is created equal. Dr. Twyman uses advanced devices that measure both arm blood pressure (what you get at your doctor's office) and central blood pressure - the pressure actually hitting your brain, heart, and kidney arteries.
"If your central blood pressure is normal, less than 120 over 80, but the arm is 150, leave them alone. Their perfusion to the brain is perfect," explains Dr. Twyman. This explains why some people feel dizzy and lightheaded on blood pressure medications even when their arm readings seem high.
The measurement technique matters too. You need to sit quietly for at least five minutes, avoid caffeine and nicotine, keep feet on the ground with back supported, and measure on the bicep rather than the wrist. "Stick away from the ones that are on the wrist because they're generally highly inaccurate," advises Dr. Twyman.
The Muscle-Heart Connection: Why Sarcopenia Kills
Here's something most cardiologists never discuss: your skeletal muscle health directly impacts your heart disease risk. Dr. Twyman has observed this connection throughout his career, noting that heart failure patients heading to transplant lists are typically sarcopenic and cachectic.
"When their heart is failing, their body is demanding all the energy resources being sent to this weakening heart. Their skeletal muscles are getting eaten up by all the inflammatory compounds coming from a failing heart," he explains.
The relationship works both ways. When you have low muscle mass, you're more likely to become insulin resistant and develop chronic inflammation - both major cardiovascular risk factors. This is why Dr. Twyman routinely checks grip strength in almost every patient, considering it a valuable marker of overall health status.
The connection extends to testosterone levels in men. Low testosterone often correlates with higher calcium scores, increased diabetes risk, and higher all-cause mortality. But here's the interesting part: "It's the estrogen for men that's probably more cardioprotective," notes Dr. Twyman. When testosterone is low, men can't aromatize it into estrogen, missing out on estrogen's benefits for nitric oxide levels, lipoproteins, brain function, and bone health.
V2 max testing, while not essential for everyone, provides valuable insight into mitochondrial function and aerobic capacity. Dr. Twyman explains that scores under 14 were historically used as cutoffs for heart transplant eligibility, while anything above 40 indicates you're doing something right with your cardiovascular fitness.
At-Home Testing: Taking Control of Your Heart Health
You don't need a fancy cardiology office to start monitoring your cardiovascular health. Dr. Twyman recommends several at-home tools that can provide valuable insights years before problems become obvious.
Nitric oxide test strips look like little litmus paper and provide immediate feedback about your nitric oxide production. You place saliva on the pad, bend it over to a developer section, and watch for color changes. "The brighter red they are, the more nitrates you're potentially getting in your diet," explains Dr. Twyman. These nitrates from foods like beets and green leafy vegetables convert to nitric oxide in your stomach.
However, there's a caveat: "If you have an oral infection, they'll be falsely positively high. So you can't rely on just one data point." The strips work best when you haven't used mouthwash or fluoride products that can disrupt the oral bacteria needed for nitrate conversion.
Pulse wave velocity testing, available through devices like the Oura Ring or the iHeart device, measures arterial stiffness. "As blood flows across that artery lining, that glycocalyx, it stimulates the underlying endothelium to release nitric oxide. The arteries dilate," describes Dr. Twyman. When arteries become stiff like lead pipes instead of flexible like accordions, it indicates accelerated aging.
The newest addition to Dr. Twyman's toolkit is the ConnectQT device, which measures both traditional arm blood pressure and central blood pressure. This technology, previously only available during invasive cardiac procedures, can now be assessed non-invasively at home.
The Nitric Oxide Protocol: Nature's Heart Medicine
Nitric oxide might be the most important molecule you've never heard of. This gas exists for only about a second but acts as both a signaling molecule and hormone with profound cardiovascular effects. The 1998 Nobel Prize in Medicine recognized its discovery, yet most doctors rarely discuss it with patients.
Dr. Twyman outlines three primary ways to boost nitric oxide production. First is exercise: "As blood's flowing across that artery lining, that glycocalyx, it stimulates the underlying endothelium to release nitric oxide." The mechanical force of blood flow literally turns on your body's nitric oxide production.
Second is sunlight exposure, particularly UVA wavelengths that hit your skin and liberate nitrates, releasing nitric oxide systemically. This provides yet another reason why getting outside daily benefits your cardiovascular system beyond just vitamin D production.
Third is dietary nitrates from green leafy vegetables like spinach, kale, arugula, and beets. But here's the catch: you need the right oral bacteria to convert these dietary nitrates into nitrites and eventually nitric oxide. "If you chew them, and you have the right oral microbiome, the nitrate-reducing bacteria break down the nitrates," explains Dr. Twyman.
This is where mouthwash becomes problematic. Regular use of antibacterial mouthwash can disrupt the beneficial bacteria needed for this conversion process. It's like sterilizing the very ecosystem your body relies on for cardiovascular protection.
The Controversial Keto Connection: When Good Diets Go Wrong
The recent Keto-CTA trial has sparked intense debate in cardiovascular circles, and Dr. Twyman has seen many of these "lean mass hyper-responders" in his practice. These are typically lean individuals with BMIs under 25, no insulin resistance, and normal cholesterol levels who adopt ketogenic diets and see their LDL cholesterol skyrocket to 300, 400, or even 500 mg/dL.
"I've seen them as high as 500 in my practice," notes Dr. Twyman about LDL levels in these patients. The controversial part isn't just the numbers - it's what happens to their arteries over time.
The study followed 100 volunteers who maintained ketogenic diets for a full year while monitoring their arterial health with advanced CT angiography and AI analysis. The primary outcome was supposed to measure changes in non-calcified (soft) plaque - the type more likely to rupture and cause heart attacks.
"When you actually look at the actual graphs, the non-calcified plaque increased in almost every person in the study, and it increased like 18 cubic millimeters of plaque in that timeframe, which would be more than what a general healthy population would develop," explains Dr. Twyman.
This doesn't prove ketogenic diets cause heart attacks, but it raises important questions about long-term cardiovascular effects. Dr. Twyman's approach focuses on the underlying endothelial health: "If that layer is healthy, maybe you can get away with having these LDL cholesterols of 500 for years. But the second you see that the glycocalyx is damaged and dysfunction is happening, that person's a time bomb ready to go off."
Advanced Diagnostics: The Gold Standard Tests
While at-home testing provides valuable insights, Dr. Twyman's office offers more sophisticated assessments. The EndoPAT test represents the gold standard for measuring nitric oxide availability and arterial dilation capacity.
During this 15-minute test, you lie comfortably with finger probes measuring blood flow. After a 5-minute baseline, a blood pressure cuff inflates above systolic pressure for 5 minutes, cutting off circulation to simulate exercise stress. When released, the blood rushes back down, stimulating the glycocalyx to release nitric oxide.
"Your arteries should at least double in size, but optimally triple or quadruple in size," explains Dr. Twyman. "If it's less than 1.68 - so your arteries are only dilating 68% - you have what's known as endothelial dysfunction. The force field is down."
Calcium scoring remains one of the most predictive tests for future heart events. This low-dose CT scan looks specifically at coronary arteries for calcium deposits. "Calcium is supposed to be in your bones and teeth. If you have calcium in your artery walls, that indicates there's hard plaque in your arteries," notes Dr. Twyman.
The scoring system is straightforward: zero means no detectable plaque, over 400 indicates high risk, and over 1,000 represents very high risk. Dr. Twyman has seen scores as high as 7,770 - though he's also seen people in their 80s with scores of zero.
The Lifestyle Foundation: What Actually Works
Despite all the advanced testing and sophisticated interventions, the foundation of heart health remains refreshingly simple. Dr. Twyman emphasizes that successful prevention starts with addressing root causes rather than just managing numbers.
Sleep quality tops his list of concerns. "While you're unconscious with alcohol on board, you're not getting that reparative sleep," he explains about one of the biggest lifestyle saboteurs. During quality sleep, your body repairs mitochondria and processes the day's oxidative stress.
Exercise doesn't just build muscle - it literally turns on your nitric oxide production through blood flow stimulation. But Dr. Twyman warns sedentary individuals to get cardiac evaluation before jumping into high-intensity training, especially if they're planning heavy lifting or HIIT workouts.
Stress management matters more than most people realize. "Stress isn't bad - that's how we're resilient. But are you chronically stressed and not recovering from that stress?" asks Dr. Twyman. Chronic stress without recovery disrupts the very repair mechanisms your cardiovascular system depends on.
Even something as simple as light exposure affects heart health. Dr. Twyman wears blue light blocking glasses consistently to optimize circadian rhythms. "We evolved to be outside in sunlight. We were never evolved to be in front of artificial light that tells our body it's different times of day than it is."
The reality is that most heart attacks are preventable, but only if we look deeper than standard cholesterol panels and challenge outdated testing norms. Your heart doesn't wait for symptoms to appear - by then, you're already decades into the disease process. The tools and knowledge exist today to prevent most cardiovascular events, but it requires a proactive approach that goes far beyond what most doctors currently offer.
