familial hypercholesterolemia

It seemed to be very consistent with this lipid hypothesis that indeed this was going to be the case.

And the catch is, until recently, you just didn't get people with LDL levels as high as what Brown and Goldstein saw without something like homozygous FH.

That's changed.

Lean mass hypersponders, I personally know.

It would be assumed that there would be a lot of the same symptoms observed in many of those lean mass hypersponders who have very high, high levels of LDL.

And again, I say this with caution because we really need prospective data to really know.

But thus far, for example, we don't see the xanthomas that were observed anywhere near at the levels that homozygous FH children would see.

They seem typical of general population overall.

Well, it didn't work, still doesn't work.

If you have FH, you are gonna have a heart attack at age 20.

Or if you have type one diabetes, you're gonna have a heart attack at age 30, if it's untreated properly.

Okay.

So, you know, the outliers are always the things we look at.

But FH, you know, for the people that don't know that, that's familiar, hypercholesterolemia, where you have genetically only half the LDL receptors and your total cholesterol is in the 500 range.

And those people are very prone to heart attacks at early age.

So, you know, and I don't go with guidelines when it comes to cholesterol treatment, because I see a lot of women, for instance, who have elevated LDL cholesterols and I don't automatically put them on a statin like a lot of my colleagues do.

Now, does that mean that there, you know, are not people that have a genetic predisposition that means that they'll definitely get it? That's a small number.

It's just like FH for heart disease, uh, familial hypercholesterolemia-

Right

... or, or, or familial hypo- hypolipidemia.

In young Indians, the commonest risk factors are smoking, diabetes, abnormal lipids, obesity, and a family history.

But we must also look for less common causes, familial high cholesterol, known as FH, which is underdiagnosed and should be suspected when the LDL is very high, with family screening of all first-degree relatives, high lipoprotein little a, antiphospholipid syndrome, and other thrombophilias, spontaneous coronary artery dissection, particularly in young women and around pregnancy, coronary embolism from the heart, drug use such as cocaine and amphetamines, and coronary vasculitis, such as taka, yasu arter, itis and Kawasaki disease.

Psychosocial stress, long working hours, poor sleep and shift work are increasingly recognized contributors.

In young patients, I emphasize lifestyle change with great intensity because a thirty-five-year-old has forty or more years of exposure ahead.

Lesson in stable coronary disease, optimal medical therapy is the foundation and revascularization is for symptoms and high-risk anatomy.

Case five, a forty-year-old woman with an LDL of two hundred and sixty milligrams per deciliter and tendon zen.

Though, mass was diagnosed with familial high cholesterol, or FH, after her brother had a heart attack at thirty-eight.

She was started on a high-intensity statin and at zetimibe, and her two teenage children were screened and found to be affected.

But you also might have familial hypercholesterolemia where your cholesterol sits at 7.58, but your HDL's only 1 and your triglycerides might be normal at 1 or 1.2, but your LDL is a, even though it's large, mainly large, it's a different configuration and doesn't fit into the standard receptor as well and it's still very atherogenic.

So that's where the calcium score tells you.

Now, here's the thing about FH, that 50% of people with FH will have a vascular event by age 50.

Wow.

But if you're an opt- if you're an optimist, 50% of people with FH-

Won't

... won't have a vascular event.

...

So as a scientist, let's ask a couple simple questions to test the hypothesis.

That there should be a reduction in lifespan in people diagnosed with FH.

They should die young, which is what you're taught in medical school.

And that a pharmacological reduction of cholesterol should improve outcomes and should enhance lifespan.

So I started looking at the papers.

And this is one of the first ones that I came across.

One of the largest studies on people with FH, ancient study, 1966, very important general medicine, and they're looking at the thousands of people who are diagnosed with FH, and what do they find? No evidence that people with FH actually have a shorter lifespan.

In fact, you find it's routine.

Um, I must say, and maybe to a fault, I am not a huge, uh, genetic screener in this situation when someone like this comes with an LDL cholesterol of 190 or greater, frankly 180, you know, without secondary cause.

Um, the phenotype of FH is very variable.

Um, it's not an all or none phenomenon.

And some of the really recalcitrant high cholesterol syndromes that we all see in patients, um, y- th- many of them are phenotypes that are, you know, variable FH, um, not what we usually think of as the patients we used to put on apheresis and whatnot.

So the answer to the question is, yes, there is value to screening genetically here, and the value would be for patient education, uh, understanding screening of the rest of the family members, making it very clear that this is a genetic, um, a genetic abnormality in the family and th- don't ever get interested in cigarettes, you know, stay active, et cetera, et cetera.

You know, counseling things.

However, we tend to really focus on this in the later stages of life, especially after someone has had a cardiovascular event, and we need to start screening earlier.

So for instance, we should screen young children greater than two years of age if they have a family history of premature ASCVD or severe hypercholesterolemia or familial hypercholesterolemia.

And we should also be screening between ages nine and eleven to identify familial hypercholesterolemia.

Then we should be screening at age, uh, nineteen and rechecking every five years and use evidence-based equations such as PREVENT to identify ASCVD risk.

As we get older, we really want to be aiming for an LDL-C less than one hundred in those who have a PREVENT risk score less than ten percent.

You do have to look deeper.

You have to look for risk enhancers.

You have to look at family history, including if they have a familial hypercholesterolemia.