Labs for prevention?

[JustPlainBill]

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So I've just been invited to a dinner to discuss case studies for the clinical utility of inflammation studies....which led me to a question:

Now that I'm out in the real world, I've noticed a few colleagues doing a lot of "specialized" labs that are supposed to have great predictive value for future cardiac events/prevention type of studies and one which posits that it is a gene test with better predictive value than a treadmill stress for future MI risk.

So, me being me, I asked for the studies and evidence and got a lot of heming/hawing/foot shuffling but a paucity of studies and evidence to back up the claims. I went to my next layer which was to call my cardiology attending and ask him about it...his response was something along the lines of " the tests are out there but we don't have a good enough idea as to their actual value to use them instead of treadmill stuff as of yet"....and then I called a practicing, non-academic cardiologist that I know well and pretty much got the same response.

Does anyone on this forum currently use specialized labs for prevention i.e. ClevelandHeartLab or Boston's? Can anyone speak to the evidence for these labs?

Moderator - don't know if this is appropriate. If not, please shut it down or move the thread.

 

[VA Hopeful Dr]

I just got handed an article by the Liposcience people in response to my identical question about NMR lipid studies. It did show that treating particle size made a bigger difference than just treating the LDL numbers....

Sadly, the new guidelines say we shouldn't be treating numbers now anyway so the study is worthless.

Now that I'm out, I do one of 2 things. I use the new risk calculator pretty heavily. Beyond that, if someone is worried about MI/CVA type stuff (with or without good reason) I'll often just go ahead and give them a statin. I have never used those inflammatory markers (I'm assuming you mean stuff like hs-CRP and homocysteine), nor will I until there is good data supporting it.

 

[JustPlainBill]

If you've ever seen a Cleveland, Boston or Corus, there's a whole plethora of information regarding all sorts of fun and mundane serum markers down to subparticulate matter. Some are fairly fancy with red/yellow/green zones for patient consumption but in my experience (not the be all/end all I'm sure as I'm relatively new at this), it generally winds up being a 'you need a statin or a fibrate, eat better and get some aerobics and weight resistance training in and get down to your ideal body weight' type of deal.

I am in no way slandering/mocking anyone who uses these labs but I tend to be a basic, grind it out type of guy -- for example, my rules for my diet are really simple -- as in my personal diet, not my patients --1) Don't eat anything bigger than you are (red meat is out except on rare occasions, chicken, fish, turkey are good -- smaller than I am) 2) If it can sit on your shelf for more than 5 days without spoiling, you probably don't want to eat it 3) If you can see through it and it doesn't fizz, have alcohol or come out of a body, it's probably ok to drink (just developed that last one) 4) Be concerned if what you're eating has an ingredient list......

Now, while I recognize the value of the Boston/Cleveland/Corus, my question is -- are we going to be able to really do anything about the subparticles that we're not already doing?

Which is why I asked about the evidence -- is it valid and more importantly, how will it change what I'm currently doing.....

 

[VA Hopeful Dr]

Now, while I recognize the value of the Boston/Cleveland/Corus, my question is -- are we going to be able to really do anything about the subparticles that we're not already doing?

Which is why I asked about the evidence -- is it valid and more importantly, how will it change what I'm currently doing.....

Won't do anything differently (especially with new lipid guidelines) and we can't do anything about all the extra variables those tests show us anyway.

 

[deleted87716]

I just got handed an article by the Liposcience people in response to my identical question about NMR lipid studies. It did show that treating particle size made a bigger difference than just treating the LDL numbers....

Sadly, the new guidelines say we shouldn't be treating numbers now anyway so the study is worthless.

Whoa, there. Guidelines don't tell you where to stop. They tell you where to start. The 2013 ACC/AHA guidelines aren't "the" new guidelines. They're "a" guideline. They are NOT ATP-4, and shouldn't be treated as such. They're almost completely worthless, not only in my opinion, but in the opinion of most of the lipidology community. They completely disregard the entirety of the data on cardiovascular risk factors in favor of a handful of LDL studies that met their narrow, evidence-based criteria. The risk calculator is also highly suspect.

In fact, a study presented at the ACC on April 1 (soon to be published in the JACC) showed that patients achieving LDL-p <1000 received more aggressive lipid-lowering treatment than patients achieving LDL-c <100, and that these treatment differences are associated with a reduction in CV event rates over 12-36 months of follow-up.

http://www.prnewswire.com/news-rele...cholesterol-according-to-study-253192121.html

https://www.lipid.org/nla/2013-acca...ol-reduce-atherosclerotic-cardiovascular-risk

http://www.lecturepad.org/pdf/tomdayspring/Commentary_on_2013_ACC_AHA_Guidelines.pdf

http://www.liposcience.com/sites/default/files/news/LipoScience_Position_ACC-AHA_Guidelines.pdf

 

[deleted87716]

...better predictive value than a treadmill stress for future MI risk.

A treadmill stress test has ZERO predictive value as a screening test for cardiovascular disease. Where did you hear otherwise..?

http://www.uspreventiveservicestaskforce.org/uspstf/uspsacad.htm

http://www.kevinmd.com/blog/2013/02/myth-screening-heart-disease.html

http://www.consumerreports.org/health/conditions-and-treatments/heart-health/heart-test.htm

 

[VA Hopeful Dr]

Whoa, there. Guidelines don't tell you where to stop. They tell you where to start. The 2013 ACC/AHA guidelines aren't "the" new guidelines. They're "a" guideline. They are NOT ATP-4, and shouldn't be treated as such. They're almost completely worthless, not only in my opinion, but in the opinion of most of the lipidology community. They completely disregard the entirety of the data on cardiovascular risk factors in favor of a handful of LDL studies that met their narrow, evidence-based criteria. The risk calculator is also highly suspect.

In fact, a study presented at the ACC on April 1 (soon to be published in the JACC) showed that patients achieving LDL-p <1000 received more aggressive lipid-lowering treatment than patients achieving LDL-c <100, and that these treatment differences are associated with a reduction in CV event rates over 12-36 months of follow-up.

http://www.prnewswire.com/news-rele...cholesterol-according-to-study-253192121.html

https://www.lipid.org/nla/2013-acca...ol-reduce-atherosclerotic-cardiovascular-risk

http://www.lecturepad.org/pdf/tomdayspring/Commentary_on_2013_ACC_AHA_Guidelines.pdf

http://www.liposcience.com/sites/default/files/news/LipoScience_Position_ACC-AHA_Guidelines.pdf

OK, I'll bite...

First, the liposciences particle size study used patients already at high risk for CV events. Currently my practice (and this was the case even before the new guidelines, or "a" new guideline is you want to get particular), was to put said patients on either lipitor or crestor straight away. In my population, even if I did the NMR lipid profile that showed a high particle size, what would I then do differently? The reason, to my mind, behind the liposcience study was that you treated high risk people more aggressively since they knew they had a high particle count (or size). If I already treat high risk patients aggressively, what would I add to that? We know that zetia is essentially worthless from a morbidity/mortality standpoint, and I haven't seen any really convincing evidence behind niacin either.

Second, my understanding was that most of the literature about prevention events came from trial that used set doses and just watched the patients over time so see both what their lipid profiles did and how many events they had. Are there studies that titrate to certain goals which show good evidence compared to that?

Third, I'll agree that the lack of other CV risk factors in the calculator is probably unwise. In my practice, I do pay much more attention to other things - particularly family history. But, as you say, that's why guidelines are not the end all be all. I do, however, like the treatment approach that's suggested in them.

 

[VA Hopeful Dr]

A treadmill stress test has ZERO predictive value as a screening test for cardiovascular disease. Where did you hear otherwise..?

http://www.uspreventiveservicestaskforce.org/uspstf/uspsacad.htm

http://www.kevinmd.com/blog/2013/02/myth-screening-heart-disease.html

http://www.consumerreports.org/health/conditions-and-treatments/heart-health/heart-test.htm

A cardiologist who does several of those every day before going out on his boat every evening 😉

 

[deleted87716]

even if I did the NMR lipid profile that showed a high particle size, what would I then do differently?

You'd treat to LDL-p goal. The LDL-c is completely irrelevant. There is a huge discordance between FLP and LDL-p (50% in people with a completely normal FLP, and 75% in people with an abnormal FLP - which is most people). That's the only thing that the ACC/AHA guideline gets right: LDL-c doesn't matter. They missed the forest for the trees, unfortunately.

http://www.liposcience.com/nmr-lipoprofile-test/health-care-professionals/clinical-evidence

 

[deleted87716]

A cardiologist who does several of those every day before going out on his boat every evening 😉

Well, there ya' go. Don't be that guy.

 

[JustPlainBill]

A treadmill stress test has ZERO predictive value as a screening test for cardiovascular disease. Where did you hear otherwise..?

http://www.uspreventiveservicestaskforce.org/uspstf/uspsacad.htm

http://www.kevinmd.com/blog/2013/02/myth-screening-heart-disease.html

http://www.consumerreports.org/health/conditions-and-treatments/heart-health/heart-test.htm

You are correct Blue Dog -- perhaps I upgefucht and muddled the issue -- The local Corus rep sells his test somewhat as follows: Patient with angina that you would normally use a treadmill stress to look for ischemia -- the Corus Gene test has a higher level sensitivity/specificity than a treadmill stress and if the gene test comes back "negative" you can rest relatively assured that your patient is not having a precursor to an MI.

When I specifically asked what the ACC had to say, the answer I received was that the Corus people were allowed to present their data 4 years in a row which is unheard of and means that it must be undergoing real consideration...along with the fact that Medicare pays for the test.....

Lil' ole me is like -- WTF? Just because you present data and get your test paid for isn't going to do me a lot of good when I'm across the table at a deposition having to 'splain why I didn't do a treadmill stress on this patient or pack them off to a cardiologist for further management if appropriate....

At which point I was told I was being unreasonable and there was no study that would ever meet my standard.....

 

[VA Hopeful Dr]

You'd treat to LDL-p goal. The LDL-c is completely irrelevant. There is a huge discordance between FLP and LDL-p (50% in people with a completely normal FLP, and 75% in people with an abnormal FLP - which is most people). That's the only thing that the ACC/AHA guideline gets right: LDL-c doesn't matter. They missed the forest for the trees, unfortunately.

http://www.liposcience.com/nmr-lipoprofile-test/health-care-professionals/clinical-evidence

You didn't even read my post, did you?

If my patient is already on 80mg of lipitor (which they would be if they met the criteria for that liposciences study in the first place), even if the LDL-p is high, what would you have me do differently?

 

[deleted87716]

You didn't even read my post, did you?

If my patient is already on 80mg of lipitor (which they would be if they met the criteria for that liposciences study in the first place), even if the LDL-p is high, what would you have me do differently?

Of course I read your post. Clearly, you aren't reading any of the numerous links I've posted, because they answer your questions.

The answer, of course, is combination therapy. What would I do? First, I'd almost never use a max-dose statin. If they weren't at goal on Lipitor 40mg as monotherapy, I'd switch to Crestor 20mg and add Zetia (you could also just add Zetia to Lipitor 40mg or 80mg, but you asked what I'd do - I'd rather use a more potent statin at a lower dose in order to minimize the potential for side effects, such as myalgias). Ezetimibe is a potent reducer of LDL-p as well as LDL-c when used in combination with a statin, and safer (in terms of potential drug-drug interactions and hepatotoxicity) than combining a statin with fenofibrate (although that's also an option, as both are "gut agents" - e.g., reabsorption inhibitors). As far as evidence is concerned, there's ample evidence showing that LDL-p is a better predictor of CV events than LDL-c, so go for goal. It doesn't matter how you get there.

I should add that we're just talking about drugs here, but therapeutic lifestyle changes (TLC) should be the foundation of any treatment plan. I've had plenty of patients drop their LDL-p by 50% with lifestyle modifications alone. Even if they can't get all the way to goal, they'll reduce their medication burden considerably.

 

[deleted87716]

The local Corus rep sells his test somewhat as follows: Patient with angina that you would normally use a treadmill stress to look for ischemia -- the Corus Gene test has a higher level sensitivity/specificity than a treadmill stress and if the gene test comes back "negative" you can rest relatively assured that your patient is not having a precursor to an MI.

Yeah, well...until that sort of thing becomes the commonly-accepted standard of care, that Corus rep won't be standing at the defendant's table with you during your malpractice suit, so tell him/her to suck it. If you think somebody is having cardiac ischemia, stick to whatever the "gold standard" is in your community. If you don't know what that is, you'd best send 'em to the ER.

http://www.uptodate.com/contents/selecting-the-optimal-cardiac-stress-test

 

[VA Hopeful Dr]

Of course I read your post. Clearly, you aren't reading any of the numerous links I've posted, because they answer your questions.

The answer, of course, is combination therapy. What would I do? First, I'd almost never use a max-dose statin. If they weren't at goal on Lipitor 40mg as monotherapy, I'd switch to Crestor 20mg and add Zetia (you could also just add Zetia to Lipitor 40mg or 80mg, but you asked what I'd do - I'd rather use a more potent statin at a lower dose in order to minimize the potential for side effects, such as myalgias). Ezetimibe is a potent reducer of LDL-p as well as LDL-c when used in combination with a statin, and safer (in terms of potential drug-drug interactions and hepatotoxicity) than combining a statin with fenofibrate (although that's also an option, as both are "gut agents" - e.g., reabsorption inhibitors). As far as evidence is concerned, there's ample evidence showing that LDL-p is a better predictor of CV events than LDL-c, so go for goal. It doesn't matter how you get there.

I should add that we're just talking about drugs here, but therapeutic lifestyle changes (TLC) should be the foundation of any treatment plan. I've had plenty of patients drop their LDL-p by 50% with lifestyle modifications alone. Even if they can't get all the way to goal, they'll reduce their medication burden considerably.

Agree on lifestyle, I just rarely include it in discussions like this because I have yet to meet anyone who disagrees with its effectiveness.

It was my understanding that zetia didn't have any data showing that it affected actual outcomes. Same with fibrates outside of diabetics with elevated triglycerides. I would love any info to the contrary about that if you have it.

I can rarely use Crestor given my patient population (about 90% medicaid) which is why I generally go for max dose lipitor. Haven't had much issue with side effects - maybe 3 patients since I started in August and I couldn't even get them to tolerate 40 of pravachol.

 

[deleted87716]

It was my understanding that zetia didn't have any data showing that it affected actual outcomes. Same with fibrates outside of diabetics with elevated triglycerides.

Our treatment decisions shouldn't be based solely on the presence or absence of outcomes data for individual lipid-lowering agents. As the saying goes, absence of evidence is not evidence of absence. We lack outcomes data for most of our individual blood pressure lowering agents, but there's ample evidence that lowering blood pressure to target levels reduces morbidity and mortality. It's no different where lipids are concerned.

 

[deleted87716]

Does anyone on this forum currently use specialized labs for prevention i.e. ClevelandHeartLab or Boston's? Can anyone speak to the evidence for these labs?

I selectively utilize Health Diagnostic Laboratory's test panels. I don't think they're appropriate for mass screening, but in patients who have a significant family history of cardiovascular disease or other compelling risk factors, they can provide additional information to aid in risk modification and treatment selection. A lot of these tests relate to inflammation and insulin resistance, both of which have ample evidence for their role in cardiovascular disease.

Clinicians have to be motivated in order to learn about this stuff, however, and apply it to clinical practice. It's a lot easier to follow outdated guidelines that focus on cholesterol, especially when that's all you're being measured on in terms of "quality." Guidelines are based on population data. We treat patients one at a time.

http://www.hdlabinc.com

 

[VA Hopeful Dr]

Our treatment decisions shouldn't be based solely on the presence or absence of outcomes data for individual lipid-lowering agents. As the saying goes, absence of evidence is not evidence of absence. We lack outcomes data for most of our individual blood pressure lowering agents, but there's ample evidence that lowering blood pressure to target levels reduces morbidity and mortality. It's no different where lipids are concerned.

There are numerous RCTs showing that, in terms of preventing cardiovascular events, most blood pressure agents are equally effective. We also know that certain agents, despite lowering BP, either don't decrease mortality as well as the others (beta blockers first line) or may actually increase it (alpha-blockers).

As soon as someone can show me equal outcome data between statins and zetia, I'll be glad to get on board. The evidence we do have shows that zetia, while lowering LDL fairly well, seems to increase artery wall thickness. Now, I know that's not really an outcome measure but its enough to make me really question using it in my practice.

 

[VA Hopeful Dr]

Clinicians have to be motivated in order to learn about this stuff, however, and apply it to clinical practice. It's a lot easier to follow outdated guidelines that focus on cholesterol, especially when that's all you're being measured on in terms of "quality."

http://www.hdlabinc.com

That's not really very fair. I happen to be one of those high risk by family history people, and am not convinced for myself that adding anything other than a statin helps. If I won't do it to myself, why would I do it for my patients?

 

[deleted87716]

That's not really very fair. I happen to be one of those high risk by family history people, and am not convinced for myself that adding anything other than a statin helps. If I won't do it to myself, why would I do it for my patients?

If that's the case, you owe it to yourself to see somebody who really knows their lipids. As another old saying goes, "a physician who treats himself has a fool for a patient." 😉

As for being "fair," I have conversations like this with people I work with all the time. So many primary care physicians and cardiologists alike are years behind the curve when it comes to lipid management. With cardiovascular disease being the number one killer of men and women alike (more than all cancers combined), a burgeoning epidemic of obesity and diabetes, and heart attack incidence in women on the rise, we owe it to our patients to pull our collective heads out of the sand and get into the twenty-first century where lipid management is concerned. I can think of nothing more worthy of our time and effort than working to decrease the risk of the one thing that's most likely to take us all out (cardiovascular disease).

 

[deleted87716]

The evidence we do have shows that zetia, while lowering LDL fairly well, seems to increase artery wall thickness. Now, I know that's not really an outcome measure but its enough to make me really question using it in my practice.

If you're talking about ENHANCE, the small difference in intimal thickness (a flawed measure in and of itself) was not statistically significant.

 

[VA Hopeful Dr]

If you're talking about ENHANCE, the small difference in intimal thickness (a flawed measure in and of itself) was not statistically significant.

I was talking about ARBITER 6-HALTS, and I did qualify my statement about that not being a real outcome measure but that its all we have at the moment.

 

[VA Hopeful Dr]

If that's the case, you owe it to yourself to see somebody who really knows their lipids. As another old saying goes, "a physician who treats himself has a fool for a patient." 😉

As for being "fair," I have conversations like this with people I work with all the time. So many primary care physicians and cardiologists alike are years behind the curve when it comes to lipid management. With cardiovascular disease being the number one killer of men and women alike (more than all cancers combined), a burgeoning epidemic of obesity and diabetes, and heart attack incidence in women on the rise, we owe it to our patients to pull our collective heads out of the sand and get into the twenty-first century where lipid management is concerned. I can think of nothing more worthy of our time and effort than working to decrease the risk of the one thing that's most likely to take us all out (cardiovascular disease).

I would say that I'm just waiting for proof that something works before I start using it. Luckily, from my reading this morning for this debate, I see that there are several outcomes-based studies about zetia due to come out in the near future. I also will admit that the new liposciences article that you posted and I saw last week does have me rethinking screening lipids in asymptomatic adults.

 

[deleted87716]

I was talking about ARBITER 6-HALTS, and I did qualify my statement about that not being a real outcome measure but that its all we have at the moment.

ARBITER 6-HALTS isn't a very impressive trial (small, short, terminated early, utilized a dubious secondary endpoint, etc.) It's certainly not something worthy of changing the way we practice.

I use Niaspan (I use everything, pretty much), but rarely at the doses studied in most trials (2 grams or more) due to tolerability (flushing), despite extensive counseling about preventive measures. I have difficulty getting patients to tolerate anything > 1 gram/day, and most won't even take that much. Unfortunately, a lot of insurance companies are refusing to pay for prescription Niaspan or Niaspan-containing products such as Advicor these days. I suppose they want people to take OTC niacin, which I don't think is a great idea, as immediate-release niacin is potentially more hepatotoxic than extended-release Niaspan, and OTC formulations are inconsistent in terms of potency. I generally advise against using the OTC stuff altogether.

 

[deleted87716]

I also will admit that the new liposciences article that you posted and I saw last week does have me rethinking screening lipids in asymptomatic adults.

Kids, too. I just saw a 17-y/o boy with a baseline LDL-p of >3600 (optimal is <1000, and anything >2000 is very high). He's overweight, and his FLP looked like crap (mixed dyslipidemia with elevated trigs, low HDL-c, and a measured LDL-c of nearly 200), which is what prompted me to order the NMR. Cardiovascular disease isn't an event, it's a process that develops over one's lifetime. If we don't identify and treat modifiable risk factors early, it'll be too late by the time these folks reach adulthood. The real trick is identifying who's at risk. Lots of these folks have normal lipid profiles, so we can't just leave it at that. I won't start this kid on meds right away, however. I'm going to push lifestyle modification for now. But at least we've identified him as somebody who needs to be treated and followed.

 

[VA Hopeful Dr]

Kids, too. I just saw a 17-y/o boy with a baseline LDL-p of >3600 (optimal is <1000, and anything >2000 is very high). He's overweight, and his FLP looked like crap (mixed dyslipidemia with elevated trigs, low HDL-c, and a measured LDL-c of nearly 200), which is what prompted me to order the NMR. Cardiovascular disease isn't an event, it's a process that develops over one's lifetime. If we don't identify and treat modifiable risk factors early, it'll be too late by the time these folks reach adulthood. The real trick is identifying who's at risk. Lots of these folks have normal lipid profiles, so we can't just leave it at that. I won't start this kid on meds right away, however. I'm going to push lifestyle modification for now. But at least we've identified him as somebody who needs to be treated.

You've hit on an issue that I keep battling with - kids. I certainly don't want to start kids, especially before puberty, on any type of cholesterol med. But at what point do we start treating? This is an area where I honestly don't expect much research so I go back in forth in my own head about it.

 

[VA Hopeful Dr]

ARBITER 6-HALTS isn't a very impressive trial (small, short, terminated early, utilized a dubious secondary endpoint, etc.) It's certainly not something worthy of changing the way we practice.

I use Niaspan (I use everything, pretty much), but rarely at the doses studied in most trials (2 grams or more) due to tolerability (flushing), despite extensive counseling about preventive measures. I have difficulty getting patients to tolerate anything > 1 gram/day, and most won't even take that much. Unfortunately, a lot of insurance companies are refusing to pay for prescription Niaspan or Niaspan-containing products such as Advicor these days. I suppose they want people to take OTC niacin, which I don't think is a great idea, as immediate-release niacin is potentially more hepatotoxic than extended-release Niaspan, and OTC formulations are inconsistent in terms of potency. I generally advise against using the OTC stuff altogether.

It didn't change anything for me, I'm still new enough that I've never really used much besides statins.

I go back and forth about niacin (completely agree about avoiding OTC). It is, after all, looking like HDL is a more important predictor than LDL in some people but the niacin trials, again, have yet to impress me. My reading of the literature seems to lead me to think that HDL is more lifestyle dependent and its that lifestyle that's the key to prevention, not just the HDL numbers.

 

[deleted87716]

You've hit on an issue that I keep battling with - kids. I certainly don't want to start kids, especially before puberty, on any type of cholesterol med. But at what point do we start treating? This is an area where I honestly don't expect much research so I go back in forth in my own head about it.

If they have a familial dyslipidemia, treat them early, even with meds. Most, however, are lifestyle-related and respond well to diet and exercise...if they'll do it. With kids, you've got to get the parents on board, too. Frequently, they're part of the problem.

 

[deleted87716]

It is, after all, looking like HDL is a more important predictor than LDL in some people but the niacin trials, again, have yet to impress me. My reading of the literature seems to lead me to think that HDL is more lifestyle dependent and its that lifestyle that's the key to prevention, not just the HDL numbers.

If somebody's HDL-c is low, you know you've got a problem that you need to look into in more detail. If it's normal, however (>40 in men or >50 in women), you can't assume anything, because lots of people have predominantly small HDL particles, which are not as protective. Again, there's a very high discordance rate between cholesterol and particle number/size. When there is discordance, particles predict risk better than cholesterol. If you don't check, you won't know.

See this link for graphs related to discordance: http://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-vi

 

[VA Hopeful Dr]

If somebody's HDL-c is low, you know you've got a problem that you need to look into in more detail. If it's normal, however (>40 in men or >50 in women), you can't assume anything, because lots of people have predominantly small HDL particles, which are not as protective. Again, there's a very high discordance rate between cholesterol and particle number/size. When there is discordance, particles predict risk better than cholesterol. If you don't check, you won't know.

See this link for graphs related to discordance: http://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-vi

Does niacin have any effect on HDL particle size?

 

[deleted87716]

Does niacin have any effect on HDL particle size?

It does ( here's one link, but there are others: http://www.ncbi.nlm.nih.gov/pubmed/16950175 ), but particle number (not size) is the real risk factor. Once you've reached your LDL-p target, particle size doesn't matter.

http://eatingacademy.com/nutrition/the-straight-dope-on-cholesterol-part-v

 

[teacherman84]

Nothing to contribute... Great thread. I got a brief lecture on this at a state AFP conference but haven't seen this from many (any) attendings thus far in school and is very educational. Thanks from those of us here to learn.

 

[JustPlainBill]

Yeah, well...until that sort of thing becomes the commonly-accepted standard of care, that Corus rep won't be standing at the defendant's table with you during your malpractice suit, so tell him/her to suck it. If you think somebody is having cardiac ischemia, stick to whatever the "gold standard" is in your community. If you don't know what that is, you'd best send 'em to the ER.

http://www.uptodate.com/contents/selecting-the-optimal-cardiac-stress-test

It was a rather interesting case from a different standpoint -- Both the Corus rep and a local colleague were arguing FOR using Corus (local colleague is a speaker for and uses Corus) and both thought I was being hardheaded for not using it and wanting to stick to what two practicing cardiologists (one at an academic institution) advised -- wound up doing what was best for the patient based on current evidence and shipped them over to one of the cardiologists for a treadmill stress due to FH, presentation, age and other RFs......

BTW - thank you for the article links -- when I'm done with boards, I'll go back and read them.

 

[deleted87716]

It was a rather interesting case from a different standpoint -- Both the Corus rep and a local colleague were arguing FOR using Corus (local colleague is a speaker for and uses Corus) and both thought I was being hardheaded for not using it and wanting to stick to what two practicing cardiologists (one at an academic institution) advised -- wound up doing what was best for the patient based on current evidence and shipped them over to one of the cardiologists for a treadmill stress due to FH, presentation, age and other RFs......

Interesting stuff: https://www.bcidaho.com/providers/medical_policies/Med/mp_20472.asp

 

[styphon]

Kids, too. I just saw a 17-y/o boy with a baseline LDL-p of >3600 (optimal is <1000, and anything >2000 is very high). He's overweight, and his FLP looked like crap (mixed dyslipidemia with elevated trigs, low HDL-c, and a measured LDL-c of nearly 200), which is what prompted me to order the NMR. Cardiovascular disease isn't an event, it's a process that develops over one's lifetime. If we don't identify and treat modifiable risk factors early, it'll be too late by the time these folks reach adulthood. The real trick is identifying who's at risk. Lots of these folks have normal lipid profiles, so we can't just leave it at that. I won't start this kid on meds right away, however. I'm going to push lifestyle modification for now. But at least we've identified him as somebody who needs to be treated and followed.

I don't see how the NMR would make any difference in the kid above. If I saw a chubby boy with the above lipid panel - I would begin lifestyle modification/counseling and start bringing him in more often.

I also have a problem with zetia in 2nd/3ry CAD prevention. Where did it ever show benefit,beyond changing numbers, for diabetes or those with established CAD?

 

[deleted87716]

I don't see how the NMR would make any difference in the kid above. If I saw a chubby boy with the above lipid panel - I would begin lifestyle modification/counseling and start bringing him in more often.

It lets us know how serious the problem is, which can (hopefully) aid in motivation as far as our first intervention (TLC) is concerned. Our therapeutic target is LDL-p <1300. His FLP doesn't really matter. If you just got him to LDL-c goal (<130), he'd likely still have significant residual risk given how high his baseline LDL-p was to start with. Again, if you don't check, you don't know.

I also have a problem with zetia in 2nd/3ry CAD prevention. Where did it ever show benefit,beyond changing numbers, for diabetes or those with established CAD?

I suggest reading the articles in the links posted throughout this thread. "Changing the numbers," at least where LDL-p is concerned, is directly correlated with events, and LDL-p is superior to LDL-c as a therapeutic target. You should aim for LDL-p <1000 in high-risk patients (e.g., those with diabetes or known cardiovascular disease). It doesn't matter how you get there, although statins should be your first-line treatment after lifestyle modifications. Zetia, when added to a statin, will further lower LDL-p with less risk of drug-drug interactions and hepatotoxicity compared to most of the alternatives. It's not particularly potent as monotherapy, however. If a patient is statin-intolerant, I would use something else (e.g., Welchol, fenofibrate, Niaspan, etc.)

http://www.prnewswire.com/news-rele...cholesterol-according-to-study-253192121.html

 

[styphon]

Blue dog do you have a financial connection to Liposcience?

When searching for LDL-p or LDL particle size the first links you will get are Liposcience - a company that makes the NMR LDL particle size test and labs that run the liposcience test - of course these companies have vested interest in this test as it will bring in a much better profit than a lipid panel.

The other links you will encounter are "paleo" websites.

But if you did deeper or use search engines (pubmed) to avoid Drug companies, blogs, and paleo websites you can get to actual articles with references.

Of interest
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070150/
A study in 2012 linking discordance in LDL-C and LDL-P to CV events - 5 year follow up, small size (300).

http://content.onlinejacc.org/article.aspx?articleID=1855684
A study from 2014 trying to link LDL-P to CV events - 2-3 year f/u, larger study size than above.

http://www.ncbi.nlm.nih.gov/pubmed/24569029
2014 particle size study - showing small and large LDL particles correlate with CV events

Uptodate recommends: (taken from their LDL measurement page)
"Other measurements of LDL — We suggest measurement of LDL particle concentration, or the surrogate measure of apolipoprotein B, in individuals with insulin resistance disorders who have achieved their minimal acceptable LDL-C targets. In such patients, this information may provide guidance as to treatment decisions, such as an increased dose of statins or combination lipid altering therapy with statin plus either niacin or fibrate."

This is uptodates view on use ApoB levels
"Lipoproteins — Lipoproteins particles, which carry cholesterol and triglycerides, are comprised in part of apolipoproteins. For instance, each LDL particle contains one molecule of apolipoprotein B. Some have proposed that the measurement of lipoproteins or apolipoproteins may be useful in some patients. We agree with the 2010 American College of Cardiology Foundation/American Heart Association guideline for assessment of cardiovascular risk in asymptomatic adults, which does not recommend the use of these tests for cardiovascular risk assessment in asymptomatic adults"

I think I will have to read further as how to apply this to my current practice...

Also this is probably the most informative SDN thread I have been in..

 

[deleted87716]

Blue dog do you have a financial connection to Liposcience?

No. I don't have any financial connections to anyone. Even if I did, that wouldn't change the data.

I should add that most of the NMRs I'm getting these days are coming from Health Diagnostic Laboratory, which recently introduced its own NMR test (they previously used the LipoScience test). There are a few third-party payers that don't cover advanced lipid testing, and Health Diagnostic Laboratory won't balance-bill the patient if a test isn't covered by their insurance (LipoScience would).

I think I will have to read further as how to apply this to my current practice...

Also this is probably the most informative SDN thread I have been in..

I encourage you to learn more about it. I've been using NMR for over ten years.

 

[VA Hopeful Dr]

No. I don't have any financial connections to anyone. Even if I did, that wouldn't change the data.

I should add that most of the NMRs I'm getting these days are coming from Health Diagnostic Laboratory, which recently introduced its own NMR test (they previously used the LipoScience test). There are a few third-party payers that don't cover advanced lipid testing, and Health Diagnostic Laboratory won't balance-bill the patient if a test isn't covered by their insurance (LipoScience would).



I encourage you to learn more about it. I've been using NMR for over ten years.

The liposcience rep told me last fall that they didn't balance bill.

 

[deleted87716]

The liposcience rep told me last fall that they didn't balance bill.

Here, they charge $85 for self-pay or non-covered tests.

 

[deleted87716]

this is probably the most informative SDN thread I have been in..

I've enjoyed it myself. I wish we would have more threads here in the FM forum like this one. Not necessarily about lipids, but any sort of clinical topic.

 

[DPCsoon]

For BD, these issues are unresolved in my analysis:

1) As VAHD pointed out in #18 above, all LDL-p lowering agents may not be equal RR reduction. It would seem most prudent then, until better data is obtained, to maximize the use of potent statins before adding ezetimibe or TG agents. All statins (I don't know about pitavastatin) seem to induce atrogin-1 et al, can increase TAs, but IF the only problem with high dose (vs low dose) high potency statin is an otherwise insignificant bump in the lab section in the chart, why not eek every last particle reduction from the statin first? I think a fair side-effect comparison between high dose ator/rosuv and ezetimibe is theoretical cirrhosis vs the observed (or at least less theoretical) intimal issue. I don't know how we can legitimately discount the intimal issue yet at the same time promote concern for theoretical liver fibrosis. Maybe I missed a paper or three on this?

2) I don't understand what I see to be entusiasm for ezetimibe. With ENHANCE and ARBITER 6–HALTS results, and the delayed design of IMPROVE-IT, it seems that ezetimibe is well positioned to be the atenolol of the lipid community. As the little lady said "where's the beef?" If we can capture 12-36 month outcome improvement data with LDL-p, why shouldn't we be given outcomes data by now? If zetia doesn't come out of IMPROVE-IT doing well, Merck can blame the process/DSMB. FWIW I only use ezetimibe with genuine familial hyperC with positive family event history or for patients with more than one event, and then only after maximizing statins. The local cardiologist community operates the same (who tend to driving the ship for the multi-event patients). But I agree with the logic. I also give it for people who read on this stuff and want it for LDL-p reduction. But in every instance I still review the trials and controversy and let the patient decide if they want it. I recognize that I'm providing a negative bias and I would like to be corrected if I'm wrong to better inform my patients. But in my gut it's gonna be an atenolol.

2) "Immediate-release niacin is potentially more hepatotoxic than extended-release Niaspan" Keeping slo-niacin (SR) out of the picture, I don't think that it is prudent to knock IR as potentially more hepatotoxic that ER without a lot of qualification. Tolerance is another issue altogether, as is cost, but very motivated (i.e. crazy) would be the patient to get into danger with IR niacin.

 

[deleted87716]

all LDL-p lowering agents may not be equal RR reduction. It would seem most prudent then, until better data is obtained, to maximize the use of potent statins before adding ezetimibe or TG agents.

The lipid reduction that you typically see from that final titration to max dose is usually pretty minimal. Now that Lipitor is generic, however, I'm tending to use it more frequently at the 80mg dose for those patients who can't afford Crestor. FWIW, there is a significant increase in the incidence of transaminase elevation with the 80mg dose compared to the other doses of atorvastatin (0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40, and 80 mg, respectively, as stated in the PI.)

I don't understand what I see to be entusiasm for ezetimibe...But I agree with the logic.

It's not so much enthusiasm for Zetia as it is enthusiasm for lowering LDL-p.

"Immediate-release niacin is potentially more hepatotoxic than extended-release Niaspan" Keeping slo-niacin (SR) out of the picture, I don't think that it is prudent to knock IR as potentially more hepatotoxic that ER without a lot of qualification. Tolerance is another issue altogether, as is cost, but very motivated (i.e. crazy) would be the patient to get into danger with IR niacin.

You're probably right: http://www.jfponline.com/index.php?id=22143&tx_ttnews[tt_news]=167572

If you're going to go all evidence-based, however, the recent studies on niacin aren't very compelling. It does lower LDL-p, though. However, as I mentioned earlier, I've never had much luck keeping people on it due to side effects.

 

[VA Hopeful Dr]

The lipid reduction that you typically see from that final titration to max dose is usually pretty minimal. Now that Lipitor is generic, however, I'm tending to use it more frequently at the 80mg dose for those patients who can't afford Crestor. FWIW, there is a significant increase in the incidence of transaminase elevation with the 80mg dose compared to the other doses of atorvastatin (0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40, and 80 mg, respectively, as stated in the PI.)

I thought that there was fairly good evidence about not really worrying about LFTs in statin patients, barring actual liver failure. If memory serves, and I'll look this up when I get to work, while the rate of elevated transaminases is decently high, the rate of actual liver failure is incredibly rare.

That said, if patients have LFT issues from known liver disease other than NASH, I'm usually pretty reluctant to start statins other than pravachol but that's just my opinion - I'm not sure there's much evidence behind that one.

 

[JustPlainBill]

I've enjoyed it myself. I wish we would have more threads here in the FM forum like this one. Not necessarily about lipids, but any sort of clinical topic.

No need to thank me, BD, just send a $50 gift card to Ruth's Cris Steakhouse or 3 Forks Dallas-- or you can let me remove both of your great toenails for practice ... ;o>

Seriously, thank you for your lucid and informative responses -- this is the sort of topic/thread/engagement I wish I had during residency rather than listening to a community organizer come in and talk to us about how evil people were who made more than $200K -- yes, it did happen....or having an anemia talk where a pathologist explained cell lines to us.....

Oh well --

So what's the next topic?

PSA testing? -- when/how/what do we tell patient's
Breast self-exams?


I'd really like to discuss some inpatient topics if possible --

My question has always been -- so I've got a patient with CHF with an LVEF of around 20-30%, on Lasix who goes into ARF and then becomes hypotensive -- how the hell do I know how much to bolus this person without sending them into pulmonary edema?

Or another case -- 35 y/o morbidly obese WF with cellulitis, CHF with an LVEF of 40%, VSS, refusing CPAP becomes more obtunded, on vanc/zosyn for cellulitis, diabetic on NPH insulin at home with home SSI also. Becomes febrile refractory to antipyretics....cultures cooking and new cultures/CXR done. CXR negative for infiltrates, acute chest processes -- patient then starts becoming hypotensive and temperatures increasing to 102-103 range.....

Sorry -- both of those happened and the first one has always been a conundrum for me....and when I asked questions, I was told to "go look it up" -- uh, this really isn't in the book. When I repeated the question, my medical competence was questioned during residency.

Can anyone help a brotha' out?

Or another topic -- BNP -- most of us were taught it's an indicator of CHF exacerbations -- but is it really?

and note that I'm trying to engender clinical discussions for the benefit of all. I really learned a lot from this thread...

 

[deleted87716]

I thought that there was fairly good evidence about not really worrying about LFTs in statin patients, barring actual liver failure.

With monotherapy, perhaps. Most of my patients aren't on monotherapy, however.

 

[deleted87716]

So what's the next topic?

It would probably be better to start a new thread for a new topic. That way, we can (hopefully) keep the discussion from getting too tangential.

 

[DPCsoon]

Can anyone help a brotha' out?

Some general thoughts:

1. Loops: for volume management, not BP control. If IVVD you shouldn't have a loop on board. Used to talk about a loop to "stimulate" output, now maybe not so much.
2. Hypotensive people should have there blood pressure lowering medication held (sorry but had to say it).
3. Where is the fluid, where do you need it, and what's the albumin? Need intravascular fluid with dry tissue give IV fluid. Need intravascular water with wet tissues
consider albumin. If albumin is low consider that added IV water may leak to tissues.
4. A can of soda is 350ml. If scared, consider a 250ml bolus. Anyone sick enough to crump after a 250ml bolus over 30-45 minutes should be recognized outright and
ought to be in the unit all plugged in. In no race here, just watch I/O and pressure response.
5. Swan: Wedge pressure generally 18+ is needed for cap pressure pulm edema.
6. Pulm edema: Present because of left failure or leaky lung parenchyma/ARDS etc?
7. Pulm HTN: think about it in obese Pickwikians who don't use CPAP. In modern times get in the habit of paying attention to right side details on the echo.
8. Bipap isn't optional. If needed, use it. [[Edited this point. Originally typed completely incorrect "bipap isn't an option"]]
9. BNP. Depends on what for. For AKI vs CHF, consider: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132842/
10. Screening CBE no way. SBE no way (might help women with remarkably aggressive cancer live a little longer).

Fluid mgmt in ALI/ARDS:
http://www.annalsofintensivecare.com/content/1/1/16

 

[deleted87716]

I just bumped two more people from 40 to 80mg of Lipitor today. Y'all are a bad influence. J/K. 😛