In a large observational cohort, we observed that increased lipoprotein(a) is independently associated with future risk for ASCVD but with modest discrimination in addition to clinical risk scores at the level of population screening for primary prevention.
Because single risk markers have not added substantially to risk prediction, a number of investigators have examined the addition of multiple markers simultaneously to traditional risk equations. In the Cardiovascular Health Study, Shlipak et al43 reported that the addition of 6 novel biomarkers [including interleukin-6, CRP, fibrinogen, lipoprotein(a) and factor VIII levels, plus presence of anemia] to a traditional risk model improved the C statistic from 0.73 to 0.74 in older individuals with chronic kidney disease but decreased the C statistic from 0.73 to 0.72 in those with normal renal function.
In the Framingham study, the addition of brain natriuretic peptide levels plus microalbuminuria to a traditional risk model for CVD events yielded an increase in the C statistic from 0.76 to 0.77.44
Seems like the good ole Framingham Risk Score and Qrisk3 are sufficient predictors.
@Radiata and @Davin8r this is an honest question. I understand that higher serum levels of Lp(a) have been associated with an increased risk of CVD, but even aggressively lowering them with PCKS9i reduces the risk only by 15%. You both seem relatively young and focusing on other factors, like metabolic syndrome, low body weight, BS and BP, keeping blood lipids low, exercise, adopting a healthy lifestyle and monitoring inflammation seem more rational to me. Statins even accelerate calcification, thus making in more stable, but still. Statins even make Lp(a) levels go higher. PCKS9i reduce Lp(a) only about 20% but don’t lower inflammation which is associated with creating plaques in the first place which shows as a minimally reduced risk of CVD. So why use them in healthy adults? I know that prevention is much better than treating, but as I understand Lp(a) is considered a risk factor for CVD but is not an absolute predictor.
PCSK9 inhibitors cut ApoB in half (give or take), with essentially no side effects. The slight drop in Lp(a) is just a bonus. I never said nor implied that PCSK9 inhibitors should be given to a cardiovascularly healthy (e.g. calcium score of 0) adult. CVD has multiple modifiable risk factors, so IMO it makes sense to pay attention to all of them.
If I am not mistaken, you said you are on PCKS9i? What was guiding your decision? Did you have any health problems or other risk factors or just elevated serum lipids?
ps. I would like to understand this issue of lipids and lipid lowering more. As I briefly discussed this aggressive serum lipids lowering a while ago as a “hypothetical scenario” (fearing that my lipids will go up using rapamycin) with a friend (his head of cardiology dept. in hospital) he said to me, that there is absolutely no rational reason if one is healthy and has no other CVD risk factors. If any of the risk factors is present it changes and should be considered case by case (if we leave out national treatment guidelines and insurance guidelines which are another story).
Sounds like we’re in a similar predicament @Radiata. It sucks but the way I’m looking at it is that it’s ‘better the devil you know, than the one you don’t’. At least we can take steps to do something.
Your numbers (apart from Lp(a)) look fantastic so hopefully there’s no damage. I’ve had an echo (no evidence of stenosis thankfully) and my CAC score was zero (phew). However, my understanding is that CAC only really shows damage that has already occurred and not occurring so to speak. I’m going to ask the Doctor about a coronary angiogram too.
Hope your Doctor is open to PCKS9i. It just seems crazy that we have to wait for something to go wrong before getting the help needed….
15% of the biggest killer seems quite massive and not an “only”.
Already today most old people who don’t die of cardiovascular disease still die WITH cardiovascular disease.
The reasoning of your cardio physician friend might make sense when thinking about how to treat a large group of people based on historical patterns or how he is tasked by clinical and national health (funding) guidelines to use the hospitals and health care systems resources.
But did he really analyze and give you that answer in the context of how someone who is trying to live healthily to 95 years of age and not just 75-80 - or even shooting for 120 or longevity escape velocity - should think about things?
@Neo what I hear you saying is that if we take two twins, both living a healthy lifestyle and having no associated risk factors for CVD other than high serum lipids, the one that will aggressively lower them will live longer and develop CVD later in life? On some level that probably makes sense but I still believe that lifestyle and other associated risk factors play a more important role. If I would reverse and say the twin who aggressively lowers his lipids to a physiological minimum, but doesn’t exercise or is stressed, smokes, drinks, is overweight has elevated BP and BS would the above still be valid?
And I did not discuss it in depth, but still, 15% is personal risk reduction (calculated in a high risk population), so we have no idea if this would be true for a low risk individual too and by how much. So it is really speculative.
Hello @DMac I took my 21 year old daughter (Lp(a) over 400 and LDL of 118 and ApoB 89) to a lipidologist recently who was referred to me by Tom Dayspring, a key opinion leader in lipidology. He suggested that in the absence of any other risk factors or symptoms, we do nothing until she is 35 and then she should get a CAC test done and if zero and still no other risk factors, we will probably do nothing, esle we will figure it out then.
So…treating high Lp(a) in the absence of other risk factors or symptoms in a healthy, active 21 year old female is not something these folks were interested in doing.
That seems like a huge mistake to not get a CAC now rather than wait until she’s 35, especially given how low the radiation dose is from CAC screen. What if her CAC is 400 when she’s 35? “Oops, guess we should have treated her earlier, but too late now!” (???). Doesn’t seem like an approach Tom Dayspring would agree with at all, at least from what I’ve heard on his podcast appearances.
I dont’ necessarily disagree with you at all about getting a calcium score just as a baseline, but there were two docs and both were very clear that in the absence of any other risk factors, Lp(a) alone was of no concern at her age, and they convinced me that the chances of her showing CAC>0 is remote. I can get her one for $150 (cash price locally), just not sure its worth the time based on their extremely confident assessment.
Interesting. Just seems so standard for the cardiology establishment in terms of waiting until there’s a problem and then trying to fix it rather than go hard on the prevention aspect of things. This week’s Peter Attia podcast is with an expert on familial hypercholesterolemia. With FH, these kids are on statins and ezetimibe starting at age 6 or 8, and the data shows that when these kids are NOT treated preventibly, they can have heart attacks/strokes starting at age 25. Maybe the Lp(a) of 400 isn’t as strong of a risk factor as LDL of 300, or maybe we just don’t have the data yet and these guys are being too conservative.
Their is a PDF copy of Parsons book, titled "Cholesterol Control Without Diet!”. At no cost, all the information required and references are in that book.
You could make the same argument above and swap “lipid lowering” with “smoking”. So then the twin’s smoking isn’t important as long as he keeps all his other risk factors low? It doesn’t have to be one or the other. It’s a straw man to claim that any of us are claiming that lipids are the only thing that matters.
Fortunately or unfortunately, who knows, your genes probably have more to do with this than anything else. My LP(a) has always been below the limit that Quest Labs measures.
That is why I don’t rely on it as much as other factors such as triglycerides etc.
From more than one article I have read the relevance of LP(a) is still unclear despite studies that would suggest otherwise. I wouldn’t lose too much sleep over your readings.
“Lp(a) lipoprotein vary substantially among persons, and most of this variation reflects the effects of genetic variation in LPA”
“However, the genetic determinants of Lp(a) lipoprotein levels and of isoform size are incompletely understood, as is the relevance of both measures for coronary artery disease.”
“Results showed that almost all of the variance in Lp(a) concentrations was accounted for by genetic heritability”
The main thing that concerns me is that Lp(a) is more atherogenic than LDL-C
Furthermore, Lp(a) is more atherogenic than LDL cholesterol, because it consists of all of the atherogenic components of both LDL cholesterol and apo(a) [4,15,16].
It seems low-dose aspirin may help reduce risk by 50-80%
8.2. Low-dose aspirin
The Women’s Health Study used carriers of an apo(a) genetic variant (rs3798220) as a proxy for elevated Lp(a). The study found double the CVD risk in carriers compared with non-carriers. More importantly, low-dose aspirin therapy markedly reduced CVD risk in carriers (56%) but not in non-carriers.18 Others have shown up to 80% reduction with low-dose aspirin in those with very high serum Lp(a) concentrations (>30 mg/dl).185
Mainly discusses Lp(a) as a risk factor, and is working on 5 year old and ‘standard of care’ info
Elevated Lp(a): A relative indication for its measurement is family history of premature ASCVD. An Lp(a) ≥50 mg/dL or ≥125 nmol/L constitutes a risk-enhancing factor especially at higher levels of Lp(a).