Outlive

This is what HDL particles generally do: particles tagged with apoA (HDL) can cross the endothelial barrier easily in both directions, in and out. LDL particles and other particles with the apoB protein are far more prone to getting stuck inside.

This is what actually makes HDL particles potentially “good” and LDL particles potentially “bad”—not the cholesterol, but the particles that carry it. The trouble starts when LDL particles stick in the arterial wall and subsequently become oxidized, meaning the cholesterol (and phospholipid) molecules they contain come into contact with a highly reactive molecule known as a reactive oxygen species, or ROS, the cause of oxidative stress. It’s the oxidation of the lipids on the LDL that kicks off the entire atherosclerotic cascade.

There’s no connection whatsoever between cholesterol in food and cholesterol in blood,” Keys said in a 1997 interview. “None. And we’ve known that all along. Cholesterol in the diet doesn’t matter at all unless you happen to be a chicken or a rabbit.”

Globally, heart disease and stroke (or cerebrovascular disease), which I lump together under the single heading of atherosclerotic cardiovascular disease, or ASCVD, represent the leading cause of death, killing an
estimated
2,300 people every day in the United States, according to the CDC—more than any other cause, including cancer.

When I was in medical school, my first-year pathology professor liked to ask a trick question: What is the most common “presentation” (or symptom) of heart disease? It wasn’t chest pain, left arm pain, or shortness of breath, the most common answers; it was sudden death. You know the patient has heart disease because he or she has just died from it. This is why, he claimed, the only doctors who truly understand cardiovascular disease are pathologists. His point: by the time a pathologist sees your arterial tissue, you are dead.

This means keeping watch for the earliest signs of trouble. In my patients, I monitor several biomarkers related to metabolism, keeping a watchful eye for things like elevated uric acid, elevated homocysteine, chronic inflammation, and even mildly elevated ALT liver enzymes. Lipoproteins, which we will discuss in detail in the next chapter, are also important, especially triglycerides; I watch the ratio of triglycerides to HDL cholesterol (it should be less than 2:1 or better yet, less than 1:1), as well as levels of VLDL, a lipoprotein that carries triglycerides—all of which may show up many years before a patient would meet the textbook definition of metabolic syndrome.

This means keeping watch for the earliest signs of trouble. In my patients, I monitor several biomarkers related to metabolism, keeping a watchful eye for things like elevated uric acid, elevated homocysteine, chronic inflammation, and even mildly elevated ALT liver enzymes.

On a more macro level, consuming large quantities of liquid fructose simply overwhelms the ability of the gut to handle it; the excess is shunted to the liver, where many of those calories are likely to end up as fat.

The mechanisms are a bit complicated, but the bottom line is that even though it is rich in energy, fructose basically tricks our metabolism into thinking that we are depleting energy—and need to take in still more food and store more energy as fat.

Fructose isn’t the only thing that creates uric acid; foods high in chemicals called purines, such as certain meats, cheeses, anchovies, and beer, also generate uric acid.

Today we call this cluster of problems “metabolic syndrome” (or MetSyn), and it is defined in terms of the following five criteria:

high blood pressure (>130/85)

high triglycerides (>150 mg/dL)

low HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women)

central adiposity (waist circumference >40 inches in men or >35 in women)

elevated fasting glucose (>110 mg/dL)

If you meet three or more of these criteria, then you have the metabolic syndrome—along with as many as 120 million other Americans, according to a 2020 article in JAMA.