A model for universal testing and the important data that it generates comes from Cleveland Clinic's decision to test Lp(a) levels in all patients in their cardiology prevention clinics. Invaluable contributions to our understanding of Lp(a)'s inheritance pattern, epidemiology, enhanced risk for early ASCVD. and CAS, its associated morbidity and early mortality rates and failed early trials of a variety of therapies took place 15+ years ago.
Universal testing has been done in Canada and many European countries for a number of years. These are countries with universal heath care which prioritize prevention and have centralized patient data bases that have contributed to formulating strategies for managing the CV risks of inidviduals with high Lp(a)- notably aggressively treating the malicious synergy that elevated LDL presents in the settiing of elevated Lp(a). A promising primary prevention supported by the following
1.The only treatment that has proved to lower Lp(a) levels by 70-80% and similarly lower recurrent CV events by a similar % in a high risk population is apheresis. This observational data comes primarily from Germany's 30 years of apheresis experience. These spectacular outcomes are likely the result of the removal of both LDL and Lp(a) to ultra low levels. Certainly we have effective ways to pharmacologically attain aggressive LDL goals.
2. The UK Biobank review of 450,000 individuals with high Lp(a) levels were found to have a lower incidence of CV events if LDL was addressed aggressively and early.This does not refute that Lp(a) is an independent RF for ASCVD at any level of LDL but that risk appears to be ameliorated by measures we have at hand to lower LDL
3. The recent delay (for the second time) of the meticulously designed event driven HORIZON Lp(a) trial suggests the residual risk in the placebo group may be lower than anticipated since all trial participants maintained LDLs< 55mg/dl. This speculation can only be answered when the trial is readout.
For 20% of those tested ,their true cardiovascular risks may be more accurately assessed and risk factor management adjusted appropriately. Knowing you have an elevated Lp(a) level should be less of a worry than missing the opportunity to have a chance to put your level in context with your health provider. and make informed decisions on how to proceed. Knowing you have this risk can influence early recognition of symptoms, particularly in women. Women often have atypical presentations of coronary events which can delay timely interventions especially in younger females.Knowing you carry this risk can be life saving.
There will be many Lp(a) related clinical trials in the future and the U.S. has literally tens of millions potential participants. With testing rates< 1% in the past decade we have been essentially non participants. This was a contributing factor in the enrollment struggles of the HORIZON trial.
The ROI for this high yield test is difficult to calculate but has to be substantial.The annual direct expenditure in the USA for ASCVD is ~$390 billion.If everyone in the U.S. over the age of 30 were to have an Lp(a) test tomorrow at $50/test the cost would be ~$9.5 billion - a trivial non-recurring expense for a test that IDs a large population at risk for the disease that leads all causes of mortality year after year. There are things available right now to ameliorate their risk.If the genomic interventions currently in trial are successful then a secondary prevention will be a significant step forward.
This made me think. But I still use the Lp (a) to indicate which patients to treat risk more aggressively. I have several young patients with only mild risk factors, borderline elevated LDL, who were not treated with a statin and who went on to have an MI. After the MI they were found to have very high Lp (a). I’d suppose the MI would have been prevented if they had known earlier. They would have taken the statin, aspirin, etc. And knowing their phenotype allowed me to enhance prevention for their siblings.
Will I check Lp (a) in an 85 year old diabetic? No. It won’t change anything. But for a 40 year old man with LDL of 110 and a family history of CAD? You bet.
Agree that testing for Lp(a) (like almost any other test) should be individualized, have a rationale, and be associated with a plan of action depending on the result.
Thank you for remembering us primary care physicians! With something like Lp(a) my struggle as a teacher for family medicine residents is that when the ACC AHA recommends it, it puts me in an awkward position to try to argue that I know more than the specialists.
Joseph, this makes you a very sensible doctor in my opinion. Fundamentally, medical tests ask patient relevant questions with a view to changing some aspect of patient care. Questions have a What and a Why. The only rational question I can come up with is 'I want to know the patient's Lp(a) (What) so that I can advise them on their cardiovascular prognosis (Why)'. Understanding a prognosis is not inherently bad, it could encourage behaviours that independently reduce risk eg quit smoking, but it can also induce anxiety (as in the case you describe). It would be difficult to power an RCT of Lp(a) to test this. So in my view it comes down to clinician judgement. Is knowing more about risk in the patient in front of me likely to do more good (behaviour change) than harm (anxiety)? (taking into account costs of course). Mostly I think the answer will be no.
I wonder… if it’s genetic, and “there’s nothing you can do about it,” how are we explaining away the fact that people who WERE NOT dying of heart disease 60, 100, 200 years ago had to have high LP(a) in order to genetically pass it on?? This either calls into question LP(a) as a tremendous problem, or calls into question the genetic argument, or both.
Makes you a sensible doctor. as someone you a very high healthy lpa . I wish that I didn't know about this and like you said it's a risk factor even if there was a drug I don't think I would take it. sometimes having too much information can be a bad thing
Fantastic piece for which one “like” is woefully inadequate. I could not agree more with this piece, in its entirety.
I’m a general card. The next time I order Lp(a) will be the first time. For precisely the reason you noted in Point 1. Medicine 101 is to only order a test for which the result “should” change your management (where “should” incorporates the demand for adequate evidence to demonstrate that such a change in management positively affects outcomes). The entire push to use Lp(a) as a “risk enhancer” to then call for more aggressive lowering of (totally unrelated) LDL levels stands without any RCT derived outcome evidence.
And of course, as you highlighted, what stands as a “level 1” recommendation is on the basis of a foundation of evidence (B-NR) that should and could never sustain such a strength of recommendation to begin with.
Which of course leads to your point 3….which is to say how on earth can “top people” (h/t JMM), who definitely know better, decree something in guideline format that is so entirely devoid of proper evidence? If one wonders how cynics and skeptics are made, look no further.
Like you, I am eagerly awaiting trial reporting of SIRNA and ASO agents (Horizon, Ocean, Acclaim) to see if there is any “there” there. The funniest part is, if these trials are negative, then the guideline (wrt Lp(a)) will simply be wrong; but even if these trials are positive, it will for me simply highlight how incredulous and premature the guideline writers had been, in taking a leap of faith whilst there had been an absence of evidence.
As someone who was harmed by a particular branch of Medicine, so far as I’m concerned, “undermin[ed] public confidence in other guideline recommendations” is well past due and totally warranted. Bring it on.
Hi Dr. Marine. Thank you so much for sharing your professional opinions and asking those questions, which I expect are very unpopular in your field. I saw a cardiologist for the first time last year. I'm 54 and in very good health with good cholesterol and blood pressure levels. I thought I should get a baseline with a cardiologist because my maternal grandfather and maternal uncles all died from heart attacks. All of the standard tests came back normal. Then the doc asked if I wanted to do a "new" test - the Lp(a). It came back very high. His recommendation (via his nurse through an email on the patient portal) was to go on a statin, so I started doing some research. The asterisk at the bottom of my test results page cited the source for the Lp(a) cut off numbers (Low, Normal, High) from study, "A test in Context: Lipoprotein: Diagnosis, Prognosis, Controversies and Emerging Therapies." In the abstract it said this >"Statins tend to increase Lp(a) levels, possibly contributing to the "residual risk" noted in outcomes trials and at the bedside." I emailed this to the cardiologist and his response? "That's fine. You do not have to take a statin. It's a personal decision for sure." He didn't even acknowledge the finding in the study. I bet he never even read it, or knew it was cited as a source on the test results page. Needless to say, I made the medical decision to not go on a statin and I no longer have a cardiologist.
Clearly you are a sensible doctor. In 1975 Dr Eliot Corday and his son published an editorial in the American Journal of Cardiology titled "Prevention of Heart Disease by Control of Risk Factors: The Time has Come to Face the Facts". Nothing since then has contradicted the wisdom expressed in that article. The task of the doctor is to diagnose disease and recommend treatments to ameliorate or cure it. This is tough enough. With rare exceptions, no one knows how to prevent disease---particularly those degenerative disorders that come with age. But those that think they do can do immeasurable harm.
So what is a layperson with "high" LP(a) (mine is 109, which was flagged as high) to do? I had a calcium score done (zero), and a cardiologist recommended my LDL be under 100 (currently 102, brought down by red yeast rice and berberine, apparently, since I won't take statins). Now I hear stations can raise LDL. Since red yeast rice has the same active ingredient as statins (monacolin k), do I need to get my Lp(a) retested only to find out it's gone higher? Good grief, this is rather maddening.
I went down this path because my mom had heart disease and a couple of strokes and died at 78, and my dad had heart disease and died at 92 of a failed valve replacement.
My sister says her Lp(a) is normal, I guess I got the bad genes.
109nmol/L is still in the moderate range. I would not be too concerned about this and would focus on healthy lifestyle. I am not aware of any recommendation to recheck Lp(a).
Well, based on the reaction of my doctor and the cardiologist (who at first wanted my LDL below 50, until I got a calcium score of zero, and then he was ok with LDL below 100), it was practically a death sentence.
I have a healthy diet, exercise a lot, am not overweight, and never smoked/drank. Good to know I don't need to have Lp(a) rechecked.
I think you are an example of several things that are important to note. While it's not well understood, there are many high Lp(a) individuals with calcium scores of zero, who when they undergo CT scans with contrast have a significant volume of plaque. The inheritance pattern for Lp(a) is such that in most cases there is a 50% chance of siblings having elevated levels.If you are reluctant to take statins, you might discuss using a PCSK9 inhibitior which will get your LDL <55 and might reduce your Lp(a) level 20-30 %.
I believe it about the plaque. I was able to drop my overall cholesterol to 177 and my LDL down to 102 (from a high of 144) with red yeast rice (PCP prescribed) and berberine. I realized that red yeast rice has the same active ingredient as a statin. Because my mom's legs were apparently ruined by statins, I am not inclined to take them. I was just beginning to learn about pcsk9 inhibitors. I don't know if my PCP knows anything about them, but I'll ask. I'm not under the care of a cardiologist other than my PCP consulting with one.
I love this so much! In my large cardiology group I have felt like I’m the outlier as I make exactly this arguments against routine testing. Had a completely healthy 44 year old woman crying in my office because she was convinced she wouldn’t see her kids grow up after PCP found elevated Lp(a). The harm is real!
Love this by Dr Marine: “Labeling patients with a new disease (? Lp(a)-itis) has psychological consequences, especially if there is no specific treatment for it.”
Lp(a)-itis is the new disease that warrants expensive R and D of new fancy, expensive and lucrative (for pharmaceutical companies) drugs!
I’m so grateful for Sensible Medicine Substack to provide solid direction.
A model for universal testing and the important data that it generates comes from Cleveland Clinic's decision to test Lp(a) levels in all patients in their cardiology prevention clinics. Invaluable contributions to our understanding of Lp(a)'s inheritance pattern, epidemiology, enhanced risk for early ASCVD. and CAS, its associated morbidity and early mortality rates and failed early trials of a variety of therapies took place 15+ years ago.
Universal testing has been done in Canada and many European countries for a number of years. These are countries with universal heath care which prioritize prevention and have centralized patient data bases that have contributed to formulating strategies for managing the CV risks of inidviduals with high Lp(a)- notably aggressively treating the malicious synergy that elevated LDL presents in the settiing of elevated Lp(a). A promising primary prevention supported by the following
1.The only treatment that has proved to lower Lp(a) levels by 70-80% and similarly lower recurrent CV events by a similar % in a high risk population is apheresis. This observational data comes primarily from Germany's 30 years of apheresis experience. These spectacular outcomes are likely the result of the removal of both LDL and Lp(a) to ultra low levels. Certainly we have effective ways to pharmacologically attain aggressive LDL goals.
2. The UK Biobank review of 450,000 individuals with high Lp(a) levels were found to have a lower incidence of CV events if LDL was addressed aggressively and early.This does not refute that Lp(a) is an independent RF for ASCVD at any level of LDL but that risk appears to be ameliorated by measures we have at hand to lower LDL
3. The recent delay (for the second time) of the meticulously designed event driven HORIZON Lp(a) trial suggests the residual risk in the placebo group may be lower than anticipated since all trial participants maintained LDLs< 55mg/dl. This speculation can only be answered when the trial is readout.
For 20% of those tested ,their true cardiovascular risks may be more accurately assessed and risk factor management adjusted appropriately. Knowing you have an elevated Lp(a) level should be less of a worry than missing the opportunity to have a chance to put your level in context with your health provider. and make informed decisions on how to proceed. Knowing you have this risk can influence early recognition of symptoms, particularly in women. Women often have atypical presentations of coronary events which can delay timely interventions especially in younger females.Knowing you carry this risk can be life saving.
There will be many Lp(a) related clinical trials in the future and the U.S. has literally tens of millions potential participants. With testing rates< 1% in the past decade we have been essentially non participants. This was a contributing factor in the enrollment struggles of the HORIZON trial.
The ROI for this high yield test is difficult to calculate but has to be substantial.The annual direct expenditure in the USA for ASCVD is ~$390 billion.If everyone in the U.S. over the age of 30 were to have an Lp(a) test tomorrow at $50/test the cost would be ~$9.5 billion - a trivial non-recurring expense for a test that IDs a large population at risk for the disease that leads all causes of mortality year after year. There are things available right now to ameliorate their risk.If the genomic interventions currently in trial are successful then a secondary prevention will be a significant step forward.
Dennis Leahy MD FACC
It makes you a responsible physician!
A wise man’s approach and one I’m following. We need ‘mo data’.
The profession too often favors action over deliberation and restraint. And we know which strategy the public prefers.
This made me think. But I still use the Lp (a) to indicate which patients to treat risk more aggressively. I have several young patients with only mild risk factors, borderline elevated LDL, who were not treated with a statin and who went on to have an MI. After the MI they were found to have very high Lp (a). I’d suppose the MI would have been prevented if they had known earlier. They would have taken the statin, aspirin, etc. And knowing their phenotype allowed me to enhance prevention for their siblings.
Will I check Lp (a) in an 85 year old diabetic? No. It won’t change anything. But for a 40 year old man with LDL of 110 and a family history of CAD? You bet.
Agree that testing for Lp(a) (like almost any other test) should be individualized, have a rationale, and be associated with a plan of action depending on the result.
Thank you for remembering us primary care physicians! With something like Lp(a) my struggle as a teacher for family medicine residents is that when the ACC AHA recommends it, it puts me in an awkward position to try to argue that I know more than the specialists.
Joseph, this makes you a very sensible doctor in my opinion. Fundamentally, medical tests ask patient relevant questions with a view to changing some aspect of patient care. Questions have a What and a Why. The only rational question I can come up with is 'I want to know the patient's Lp(a) (What) so that I can advise them on their cardiovascular prognosis (Why)'. Understanding a prognosis is not inherently bad, it could encourage behaviours that independently reduce risk eg quit smoking, but it can also induce anxiety (as in the case you describe). It would be difficult to power an RCT of Lp(a) to test this. So in my view it comes down to clinician judgement. Is knowing more about risk in the patient in front of me likely to do more good (behaviour change) than harm (anxiety)? (taking into account costs of course). Mostly I think the answer will be no.
I wonder… if it’s genetic, and “there’s nothing you can do about it,” how are we explaining away the fact that people who WERE NOT dying of heart disease 60, 100, 200 years ago had to have high LP(a) in order to genetically pass it on?? This either calls into question LP(a) as a tremendous problem, or calls into question the genetic argument, or both.
Makes you a sensible doctor. as someone you a very high healthy lpa . I wish that I didn't know about this and like you said it's a risk factor even if there was a drug I don't think I would take it. sometimes having too much information can be a bad thing
Fantastic piece for which one “like” is woefully inadequate. I could not agree more with this piece, in its entirety.
I’m a general card. The next time I order Lp(a) will be the first time. For precisely the reason you noted in Point 1. Medicine 101 is to only order a test for which the result “should” change your management (where “should” incorporates the demand for adequate evidence to demonstrate that such a change in management positively affects outcomes). The entire push to use Lp(a) as a “risk enhancer” to then call for more aggressive lowering of (totally unrelated) LDL levels stands without any RCT derived outcome evidence.
And of course, as you highlighted, what stands as a “level 1” recommendation is on the basis of a foundation of evidence (B-NR) that should and could never sustain such a strength of recommendation to begin with.
Which of course leads to your point 3….which is to say how on earth can “top people” (h/t JMM), who definitely know better, decree something in guideline format that is so entirely devoid of proper evidence? If one wonders how cynics and skeptics are made, look no further.
Like you, I am eagerly awaiting trial reporting of SIRNA and ASO agents (Horizon, Ocean, Acclaim) to see if there is any “there” there. The funniest part is, if these trials are negative, then the guideline (wrt Lp(a)) will simply be wrong; but even if these trials are positive, it will for me simply highlight how incredulous and premature the guideline writers had been, in taking a leap of faith whilst there had been an absence of evidence.
As someone who was harmed by a particular branch of Medicine, so far as I’m concerned, “undermin[ed] public confidence in other guideline recommendations” is well past due and totally warranted. Bring it on.
Hi Dr. Marine. Thank you so much for sharing your professional opinions and asking those questions, which I expect are very unpopular in your field. I saw a cardiologist for the first time last year. I'm 54 and in very good health with good cholesterol and blood pressure levels. I thought I should get a baseline with a cardiologist because my maternal grandfather and maternal uncles all died from heart attacks. All of the standard tests came back normal. Then the doc asked if I wanted to do a "new" test - the Lp(a). It came back very high. His recommendation (via his nurse through an email on the patient portal) was to go on a statin, so I started doing some research. The asterisk at the bottom of my test results page cited the source for the Lp(a) cut off numbers (Low, Normal, High) from study, "A test in Context: Lipoprotein: Diagnosis, Prognosis, Controversies and Emerging Therapies." In the abstract it said this >"Statins tend to increase Lp(a) levels, possibly contributing to the "residual risk" noted in outcomes trials and at the bedside." I emailed this to the cardiologist and his response? "That's fine. You do not have to take a statin. It's a personal decision for sure." He didn't even acknowledge the finding in the study. I bet he never even read it, or knew it was cited as a source on the test results page. Needless to say, I made the medical decision to not go on a statin and I no longer have a cardiologist.
This is the link to the full study > https://www.jacc.org/doi/10.1016/j.jacc.2016.11.042
Thank you for the reference- I will check it out.
Clearly you are a sensible doctor. In 1975 Dr Eliot Corday and his son published an editorial in the American Journal of Cardiology titled "Prevention of Heart Disease by Control of Risk Factors: The Time has Come to Face the Facts". Nothing since then has contradicted the wisdom expressed in that article. The task of the doctor is to diagnose disease and recommend treatments to ameliorate or cure it. This is tough enough. With rare exceptions, no one knows how to prevent disease---particularly those degenerative disorders that come with age. But those that think they do can do immeasurable harm.
Thank you for the interesting reference- I will read it.
So what is a layperson with "high" LP(a) (mine is 109, which was flagged as high) to do? I had a calcium score done (zero), and a cardiologist recommended my LDL be under 100 (currently 102, brought down by red yeast rice and berberine, apparently, since I won't take statins). Now I hear stations can raise LDL. Since red yeast rice has the same active ingredient as statins (monacolin k), do I need to get my Lp(a) retested only to find out it's gone higher? Good grief, this is rather maddening.
I went down this path because my mom had heart disease and a couple of strokes and died at 78, and my dad had heart disease and died at 92 of a failed valve replacement.
My sister says her Lp(a) is normal, I guess I got the bad genes.
109nmol/L is still in the moderate range. I would not be too concerned about this and would focus on healthy lifestyle. I am not aware of any recommendation to recheck Lp(a).
Well, based on the reaction of my doctor and the cardiologist (who at first wanted my LDL below 50, until I got a calcium score of zero, and then he was ok with LDL below 100), it was practically a death sentence.
I have a healthy diet, exercise a lot, am not overweight, and never smoked/drank. Good to know I don't need to have Lp(a) rechecked.
it's not clear if the Lp(a) value of 109 was measured in nmol/L -which would not be of concern- or mg/dl which would be. an important distinction.
Dennis Leahy MD FACC
It was mg/l. On the bloodwork results, it said recommended less than 30 mg/l. So yes, it's a concern.
I think you are an example of several things that are important to note. While it's not well understood, there are many high Lp(a) individuals with calcium scores of zero, who when they undergo CT scans with contrast have a significant volume of plaque. The inheritance pattern for Lp(a) is such that in most cases there is a 50% chance of siblings having elevated levels.If you are reluctant to take statins, you might discuss using a PCSK9 inhibitior which will get your LDL <55 and might reduce your Lp(a) level 20-30 %.
I believe it about the plaque. I was able to drop my overall cholesterol to 177 and my LDL down to 102 (from a high of 144) with red yeast rice (PCP prescribed) and berberine. I realized that red yeast rice has the same active ingredient as a statin. Because my mom's legs were apparently ruined by statins, I am not inclined to take them. I was just beginning to learn about pcsk9 inhibitors. I don't know if my PCP knows anything about them, but I'll ask. I'm not under the care of a cardiologist other than my PCP consulting with one.
I love this so much! In my large cardiology group I have felt like I’m the outlier as I make exactly this arguments against routine testing. Had a completely healthy 44 year old woman crying in my office because she was convinced she wouldn’t see her kids grow up after PCP found elevated Lp(a). The harm is real!
Love this by Dr Marine: “Labeling patients with a new disease (? Lp(a)-itis) has psychological consequences, especially if there is no specific treatment for it.”
Lp(a)-itis is the new disease that warrants expensive R and D of new fancy, expensive and lucrative (for pharmaceutical companies) drugs!
I’m so grateful for Sensible Medicine Substack to provide solid direction.