"How Do We Know that Cholesterol Causes Heart Disease?"
It is well accepted that coronary atherosclerosis
is a chronic progressive disease that begins early in life
and slowly progresses over several decades
before symptoms arise.
However, the average age in cholesterol-lowering drug trials is 63,
and therefore, people have already been exposed
to a lifetime of circulating LDL cholesterol.
So, no wonder pharmaceutical therapies typically reduce cardiovascular
disease risk by only 20% to 30%.
We know LDL, so-called bad cholesterol,
plays a central role in the initiation, development, and progression
of our number one killer.
Over 100 prospective studies involving more than a million people
have demonstrated that those with higher LDL levels are at higher risk.
It seems reasonable to assume
that if lowering cholesterol later in life can help,
then keeping LDL levels low early in life
may prevent our arteries from getting clogged
in the first place.
But let’s not just assume.
It would be considered unethical to set up a controlled clinical trial
in which young adults with elevated serum cholesterol levels
were treated or not treated over their lifetime,
just like you couldn’t ethically set up a study
in which half the kids are made to start smoking
to see if smoking really does cause lung cancer.
That’s where observational studies come in.
You can follow people who already smoke
and compare their disease rates to those that don’t.
It was like 40 years ago when the president
of the American Heart Association tried to argue
that we should all stop smoking
even though there were no randomized controlled trials.
Look, those who smoke have a higher risk of heart attack,
the more we smoke the higher the risk,
and after we stop our risk drops.
The same can be said for high cholesterol.
If you look at young men aged 18 through 39,
and follow them for up to 34 years,
cholesterol levels, even when you're young,
predicts long-term risk of heart disease and death.
Men in their 20s and 30s who have a total cholesterol
even just under 200, have a substantially longer
estimated life expectancy— around 4 to 9 years longer—
than those over 240.
Evidence from observational studies, however, is vulnerable
to so-called confounding factors.
Eating a diet plant-based enough to lower cholesterol below average
may add years to our lives regardless of what our cholesterol is.
Ideally, we’d have a long-term randomized controlled trial.
And, nature may have actually set one up for us.
Each of us, at conception, gets a random assortment of genes
from our mother and our father,
and some of those genes may affect our cholesterol levels.
Just like there’s rare genetic mutations
that result in unusually high cholesterol,
there are rare genetic mutations
that lead to unusually low cholesterol,
providing an ideal system to assess the consequences
of low LDL cholesterol levels independent
of confounding diet and lifestyle factors.
Let me show you what I mean.
About 1 in 40 African Americans
have a mutation that drops their LDL cholesterol
from up around 130 down toward more optimal levels.
Now, this group didn’t eat healthy to get there.
It’s just in their genes.
More than half had high blood pressure,
there were lots of smokers and diabetics,
yet those with genetically low LDL levels still had
a significant reduction in the incidence of coronary heart disease
even in the presence of all these other risk factors.
How significant?
How much less heart disease?
How about 88% of heart disease gone.
The astounding finding was that the heart disease risk
in these individuals was reduced by more than 80%;
whereas, the same 20 to 40 point decrease in LDL from drugs
only reduces risk like 30%.
Makes sense, though.
The folks with the mutation had low levels like
that their whole life—
they didn’t just start taking some pill when they were 60 years old.
The magnitude of the effect of long-term exposure
to lower LDL-C concentrations observed in each of these studies
represents a threefold greater reduction in the risk of heart disease
compared to drug treatment started later in life.
For you fellow research nerds out there,
check out that p value.
You'd have to do like a quintillion studies
to get that kind of result by chance.
Therefore, a primary prevention strategy
that promotes keeping LDL cholesterol levels
as low as possible, beginning as early in life as possible,
and sustaining those low levels of LDL
throughout the whole of one’s lifetime
has the potential to dramatically reduce the risk of CHD.
And that's just what a healthy diet can do.