What You Should Know About Lipoprotein(a) And Heart Attack Risk

If you have had a heart attack at an early age or one of your parents did but your standard risk factors for coronary heart disease are normal you should consider getting tested for Lipoprotein(a) or Lp(a).
The standard lipid profile that most patients get checks LDL (bad) HDL (good) and total cholesterol along with  triglycerides. While these are useful, I have many patients who have normal standard values but have developed advanced coronary heart disease at an early age despite following a perfect lifestyle (not smoking, regular aerobic exercise, healthy diet.)
The skeptical cardiologist tests such patients for Lp(a) (pronounced LP little a)  and it is quite frequently elevated.
For patients, these are the facts to know about Lp(a)

  1. It is the strongest single inherited (monogenetic) risk factor for the early development of coronary artery disease, heart attacks and strokes.
  2. In addition to increasing risk of atherosclerosis, high Lp(a) is strongly associated with the development of calcific aortic valve disease which can result in narrowing of the aortic valve and aortic stenosis.
  3. Depending on the cut-off used  up to one in five individuals may have elevated Lp(a)
  4. Levels of Lp(a) can be measured with a simple blood test that should cost no more than 50 to 100$. This is not included in standard lipid or cholesterol testing.
  5. Risk for heart attack starts to rise with levels above 30 mg/dl and Canadian guidelines from 2016 (see here)) consider >30 mg/dl to be a risk factor and they recommend measuring Lp(a) in those with a family history of premature CAD or those at intermediate risk.
  6. The European Atherosclerosis Society (EAS, 2010), suggested levels of <50 mg/dl as optimal. The EAS advised measuring Lp(a) once in all patients with premature CVD.
  7. As levels get even higher risk also rises as these graphs show


Treatment For High Lp(a)

The lifestyle changes (both exercise and diet) that improve bad and good cholesterol levels have no effect on Lp(a). Our best drugs, the statins, for reducing risk of heart attack and stroke also don’t lower Lp(a) levels.
Only niacin has been shown to reduce Lp(a) across broad populations but there is no evidence that Lp(a) lowering by niacin lowers cardiovascular risk so it cannot be recommended for treatment.(In the AIM-HIGH study niacin did not reduce cardiovascular events in patients with Lp(a) with levels>50 mg/dl, despite achieving a mean Lp(a) reduction of 39%.)
Cholesteryl ester transfer protein inhibitors which raise HDL levels also reduce lipoprotein(a) concentrations, but three such inhibitors have not shown a clinical benefit.
In fact, currently there are no studies showing that lowering Lp(a) with any drug will effectively lower the associated risk of heart attack, stroke and aortic stenosis.
In the not too distant future, effective therapies may emerge. There are promising newer agents (antisense oligonucleotides or ASOs) currently in clinical trials and in limited populations the PCSK9 inhbitors, mipomersen and estrogen have lowered Lp(a) levels.

Why Test For Lp(a)?

If we have no effective therapies that work by lowering Lp(a) why recommend testing for it?
I test Lp(a) for  two reasons.
First, since it is inherited, patients with high levels should consider having first degree relatives tested for Lp(a) to identify those who are going to be at high risk. This provides an early warning of who in the family is most at risk for cardiovascular complications early in life. Such patients should be considered for early screening for subclinical atherosclerosis. In addition, they should be additionally motivated to do everything possible to reduce their elevated risk by lifestyle changes.
Second, I tend to recommend  more aggressive cholesterol lowering in patients who have evidence for early plaque build up for atherosclerotic events early in life than I otherwise would be.     I tend to agree with the approach diagrammed below:
With this approach for patients who have had events related to atherosclerosis or advanced CAC for age we work super aggressively on optimizing all risk factors. I try to lower LDL to <70 with statins and with the addition of ezetimibe or PCSK9 inhbitors if needed.
If the patient has more problems with atherosclerotic events despite optimizing risk factors and Lp(a) >60 mg/dl, some experts recommend using apheresis a technique which runs the patient’s blood through a filter which removes LDL and Lp(a). Personally, I have not sent any patients for apheresis and await better studies proving its benefit.
Antiproatherogenically Yours,
For those patients seeking more detailed information and references I recommend Dr. Siggurdson’s excellent post on Lp(a)
There is a Lipoprotein(a) Foundation with reasonably informative and accurate website you can peruse here for more information.
Finally, if you want to delve deeply into the data check out this recent JACC review here.
The graphs above and this figure
showing the proposed pro-inflammatory, pro-atherogenic and pro-thrombotic pathways of Lp(a) are from that article.


11 thoughts on “What You Should Know About Lipoprotein(a) And Heart Attack Risk”

  1. To Rick,
    There is Dr by the name of Sam Tsimikas who is a lipidologist that specializes in Lp(a). He is actually working on the ASO trials with Dr Steven Nissen at the Cleveland Heart Clinic and as you mentioned they are moving into stage 3 trials with significant momentum from the trial 2 data in reduction of Lp(a). Dr Tsimikas felt that if stage 3 data lined up with stage 2 results efficacy and safety wise, ASO drug could be out in 4-6 years or maybe sooner. If you want to get more info his twitter handle is @Lpa_doc. Dr. Tsimikas is also a new BOD of Boston Heart, which is what Dr. Pearson’s group uses for their Lp(a) testing. Sam and Boston Heart are developing several other proprietary tests for determining oxidative stress and number of kringle folds on the particles themselves to determine potential atherogenicity.

  2. Dr. P—what is your best guess as to when antisense drug therapy will be available for high LPa? I saw phase 2 trials were recently completed. While off my Lipitor for 6 weeks I had my cholesterol and LPa checked—LPa came in at 87 nmol/l—high. (HDL 63, LDL 106) I just had it rechecked after being back on Lipitor for several months now and it was 110 nmol/l (HDL 68, LDL 66) I had read statins can actually cause an increase, but I wasn’t expecting that much of a jump. By the way, how do you convert nmol/ l to mg/dL? Why are LPa values shown both ways? Thanks for all the great information!

  3. Dr. I just got certified for CPR and during the course the use of an AED was emphasized. I am interested in getting one of these tools for the home and camping. I had no idea there were so many brands and features (and prices). Can you reccommend an appropriate purchase?
    Keep The Faith.
    On Sat, May 12, 2018, 11:18 The Skeptical Cardiologist wrote:
    > Dr. AnthonyP posted: “If you have had a heart attack at an early age or > one of your parents did but your standard risk factors for coronary heart > disease are normal you should consider getting tested for Lipoprotein(a) or > Lp(a). The standard lipid profile that most patients” >

  4. My recent test came in with 89 nmol/L which is high. I practically had to beg my cardiologist to test for LPA. I don’t understand why this isn’t standard operating procedure. Seems like good medical practice and I don’t understand the reluctance to screen for it.

  5. Thanks for this. I think I will be getting my LPa test this week. Depressing to think that even though my LDL dropped to 55 on 10 mg of Lipitor that may not mean much if it turns out my LPa level is high. If it is elevated, I wonder how long it will take for the ASO’s to rech the market?

  6. This is a very balanced and informative posting. I was waiting for the laugh lines but (like mine) sometimes it’s a serious topic and should be treated as such.

    • Oops . I forgot the laugh lines! Actually the amusing aspects of lipoprotein(a) are how it takes a celebrity like Bob Harper (yes, he is apparently a celebrity trainer who was on The Biggest Loser) having an MI and discovering he had high Lp(a) and parlaying his fame and accompanying soapbox to talk on various media including Dr Oz for people to hear about lp(a). That plus the fact that Harper has parlayed his fame and heart attack into a job selling Brillianta. Also, the fact that it takes 7 syllables to pronounce 3 letters.


Please leave your comments. The skeptical cardiologist loves feedback. He reads all and replies to all that warrant a reply.