Saturday Morning Class #3: Saturday Morning Class #3: Lp(a) and the questionable paradox of longevity in centenarians

OK got this done today, here it is: 1/16

First, it is well established that Lp(a) is a risk factor for cardiovascular disease and aortic stenosis. This means that if Lp(a) is elevated chances are higher one will have these events and die from them. 2/16

Like other CV risk factors, one is less likely to live a long life than those that are otherwise the same but don’t have these risk factors. As far back as ~400 BCE, Hippocrates noted that “sudden death is more common in those who are naturally fat than in the lean”. 3/16

Fun fact: Hippocrates was born in the Greek island of Kos and taught under a plane tree in center of town. Among other things, he was the first chest surgeon to drain a lung empyema (pus in lungs): he would place wet clay on the back and look for the place that dried first, 4/16

..then open that site and place a cloth dipped in honey to keep wound from closing and re-accumulating the empyema. Honey acts as antiseptic- due to high sugar content (18%), nothing can grow in it, which is why you can keep on the shelf for thousands of years). 5/16

So, then why are there reports of people with high Lp(a) living into 100s? A review of literature:

1-The reports are mainly in centenarians (>100 yo)
2-There are no reports that I could find of people in 80s and 90s with high Lp(a). 6/16

So, to get to >100 yo with high Lp(a), you either had to have high Lp(a) in your 80s and 90s, or the Lp(a) went up in 100s.
3-There is no longitudinal data to see what happens to Lp(a) when one goes from 80s to 100s, 7/16

4-Studies are very small, largest is 109 centenarians (but that is good number considering how few of these there are
5-These do have control groups, but obviously can’t be matched to age, so the control groups are not adequate.
6-Centenarians tend to have lower LDL 8/16

7-One hint though is that the mean/median Lp(a) in the public is about 10-15 mg/dL, centenarians have mean Lp(a) 30-40 mg/dL +/- 40, so we can at conclude they have higher levels than population means. Guessing at the SDs likely some people had Lp(a) ~80-100. 9/16

8-In my clinical experience, I only one female centenarian with Lp(a) ~65 mg/dL. She had DVT and stroke due paradoxical embolus (small clot in leg crossed from right atrium to left atrium and went to brain in 80s but did quite well for next 15 years 10/16

My take:
1-More studies are needed, and can be done if centenarian researchers share data/samples
2-Data can best be described as hypothesis generating
3-If real, potential hypotheses include anti-angiogenic effects that may limit cancer spread, would healing effects 11/16

binding of OxPL as a protective mechanism to limit inflammation (it would be interesting to see how much OxPL is present in the Lp(a) of these centenarians), increases in Lp(a) with aging, possibly due to change in diet/natural weight loss with aging, others 12/16

My bottom line, if anyone is lucky to live to be >100 and still be healthy, I hope you enjoy the ride along the way. 13/16

Question: 5 points
In the movie It’s a Wonderful Life (apropos for longevity), one of my fav movies of all time, Mr Bailey died of what disease associated with elevated Lp(a). Choose the best answer: Hint- the answer comes after this great scene: 14/16

Bonus Question- 1 point. Fun fact: George cuts in on Mary’s date while they were dancing in the gym. Interestingly, this was a child actor previously in the Little Rascals. Which child actor did Mary’s date play: 15/16

Fun fact 3: Mr Gauer learned by telegram that his son died of the Spanish Flu May 3 1919- similar to our COVID times

Fun fact 4: Nick the bartender’s real first and last names gave rise to what 2 characters’ first names in a recent famous sitcom. Answer next week, 16/16