The skeptical cardiologist wrote about the importance of testing patients with premature atherosclerosis or strong family history of cardiovascular disease for Lipoprotein(a) here.
The National Lipid Association (NLA) published their scientific statement on Lipoprotein(a) (Lp(a)) (Use of Lipoprotein(a) in Clinical Practice: A Biomarker Whose Time Has Come) last summer (summarized nicely here) and I’ve listed their key recommendations below.
- For diagnosing high Lp(a) they chose a universal cut point of >100 nmol/L (approximately >50 mg/dl) which is at the 80th percentile in white Americans. This cut-off is not written in stone and may vary depending on risk, ethnicity, and comorbidities. Some labs report out Lp(a) in mg/dl, others in nmol/L. Pay attention to the units.
An individual’s Lp(a) level is 80-90% genetically determined in an autosomal codominant inheritance pattern with full expression by 1-2 years of age and adult-like levels achieved by approximately 5 years of age. Outside of acute inflammatory states, the Lp(a) level remains stable through an individual’s lifetime regardless of lifestyle.
- High-quality evidence supports a link between Lp(a) levels and a variety of cardiovascular-related outcomes. See Table 1. The risk of heart attack and aortic stenosis is increased 3 to 4 fold.
4. The following populations should be considered for testing.
5. Neither diet nor lifestyle influences Lp(a) levels.
6. PCSK9 inhibitor drugs and niacin lower Lp(a) levels and but there are no data showing this changes clinical outcomes.
7. Similar to my approach, “the authors recommend initiating a moderate- to high-intensity statin therapy in adults aged 40-75 years with a 10-year ASCVD risk of 7.5% to ≤20% with a Lp(a) ≥100 nmol/L. High-risk patients with LDL-C ≥70 mg/dL (non-HDL-C ≥100 mg/dL) and a Lp(a) ≥100 nmol/L on maximally tolerated statin should be considered for more intensive therapies (ezetimibe and PCSK9 inhibitors) to lower LDL-C.”
8. Currently, novel therapies are being studied that selectively target Lp(a). A phase 2 trial of AKCEA apo(a)-LRx, an apo(a) antisense oligonucleotide, reduced Lp(a) up to 80%. A phase 3 study is being planned. Additionally, an oxPL antibody that binds and inactivates the pro-osteogenic activity of Lp(a) has promising in vitro data. These therapies, while promising, require additional research prior to becoming mainstream therapies.
The cost of the blood test for Lp(a) should be minimal. Medicare reimburses $14 for it. You can order it from Boston Heart Diagnostics for $11. Unfortunately, there is no telling what your local hospital lab will charge.
Since Lp(a) 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.
Proantiatherogenically Yours,
-ACP
N.B. In 2018 the Centers for Disease Control and Prevention (CDC) approved two ICD-10 codes for the diagnosis of elevated Lipoprotein(a), or Lp(a). The ICD-10 diagnosis codes help to identify asymptomatic patients with elevated Lipoprotein(a) (E78.41) and a family history of elevated Lipoprotein(a) (Z83.430)
N.B.2. Don’t confuse Lp(a) with Apolipoprotein A1 which is the major protein component of HDL particles in plasma. Also, please note that WordPress converted my little a into a capital A in the title and I have no idea how to prevent that conversion.
10 thoughts on “Should You Get Tested For Lipoprotein(a), The “Hidden” Risk Factor For Cardiovascular Disease?”
Some Centenarians have elevated levels of Lipoprotein (a) so it might be protective or a good thing?
https://pubmed.ncbi.nlm.nih.gov/9543111/
https://pubmed.ncbi.nlm.nih.gov/9535215/
RESPONSE TO: “Bob Guthrie’
oxPL [Oxidized Phospholipids] is apparently the connection to the ‘virulence’, see the publication on RE” Unified Theory”
I have high Lp(a) 970 nmol/L.
I am commenting because I have no family history of cardiovascular disease.
No CVD history in my parents or grand parents. My son, my sister, and her daughters do not have high Lp(a).
As the cost of the test is so small, I suggest it should be routine at least once.
Testing is routine in Australia. My GP of 25 years always said while statistically a high Lp(A) meant early death, I was symptom-free so it was of no concern.
My LDL has always been low and my HDL high. I have never smoked, always active, strong and slim, resting pulse 45. Good BP.
At 67 I was fortunate to meet a consultant cardiologist who could well be a soulmate of the Skeptical Cardiologist.
He ordered a CAC test – 8,108. LDL subfraction profile very bad even though the total LDL was low.
He prescribed pravachol, nicotinic acid, ubiquinol, etc, and regular monitoring. I continued basketball , weightlifting, etc. but at age 70 needed a quintuple bypass.
Back at basketball 6 months later, still playing, now 75.
Knowing about the high Lp(a) was one thing, acting on it saved my life.
Hi, have you looked at this study in JACC:
http://www.onlinejacc.org/content/74/24/2982
The top 21% had an increased CAD risk of only 11% over the population median.
There is an instructive thread by Sek Kathiresan:
https://twitter.com/skathire/status/1204212647924838401
Marilyn,
I hadn’t looked closely at that study and thanks for sharing it and the tweetorial from Sek. Important to understand his opening statement that if you define high Lp(a) as those with levels at the 80th percentile than of course 20% of the population have high Lp(a)! But the relationship is graded and any cut point is somewhat arbitrary. That study suggests 150 nmol/l in this Icelandic population corresponds to 50% increased risk and 7% of the population are higher than 150. I’m OK with 150 nm/l
Excellent synopsis of Lp(a). It is interesting to me how this protein’s structure is very similar to plasminogen (the inactive precursor of plasmin). Plasminogen is important because it binds to fibrin clots and then becomes activated as plasmin which is an effective in the lysis of fibrin clots. Since the Lp(a) protein is so similar in structure it can bind to fibrin clots like plasminogen, but does not become activated, which in turn prevents the declotting effect of plasmin. Since thrombosis causes MI’s, this little protein could potentially drive up one’s risk for that.
Christian,
thank you. And thanks for making the point about structural similarity to plasminogen. That prothrombotic effect is definitely one of the hypotheses for the impacct of Lp(a).
Are there RCTs in process to determine if lipoprotein(a) reduction effects clinical outcomes?
(“6. PCSK9 inhibitor drugs and niacin lower Lp(a) levels and but there are no data showing this changes clinical outcomes.”)
‘Cause otherwise, I don’t see the point in doing the test. Too many times the seeming clear logic behind a treatment doesn’t pan out.
https://www.mayoclinicproceedings.org/article/S0025-6196%2813%2900405-9/fulltext
Improving one’s lifestyle is always an… improvement. But, to worry in futility over further lifestyle modification because of lipoprotein (a) – thereby increasing stress and consequent cardiovascular risk??
(“5. Neither diet nor lifestyle influences Lp(a) levels.”
vs:
“In addition, they should be additionally motivated to do everything possible to reduce their elevated risk by lifestyle changes.”)
Equanimously yours,
Jeff Patten
Jeff,
good questions which I answered to some extent in my first post on Lp(a).
1. Although not confirmed yet by RCTs because individuals with Lp(a) are at such high risk a more aggressive approach to drug treatment with statins, non-statins and experimental agents is warranted.Many of these patients’ parents and sibling have already died of sudden death or had stents or bypass operations I don’t want my patient to have a similar experience while we wait for the results of these clinical trials or for the newer antisense drugs to emerge..My clinical experience suggests that achieving lower LDL-C goals in high Lpa) patients mitigates the higher risk and substantially improves outcomes.And
2. Testing of first-degree relatives is important. Early knowledge of this risk factor should result in them being evaluated for premature subclinical atherosclosis and awareness of Lp(a) developments.
Dear SC,
THANK YOU for publishing this! I have high lp(a) of 200 nmol/L.
I also have high LDL-C cholesterol of 200 mg/dL, and total cholesterol of 300. My doctor put me on Crestor 20 mg, and my LDL-C dropped down to 80 mg/dL, and total cholesterol is now 170.
My follow-up question to you is what LDL-C goal do we aim for? Is 80 OK enough?
I did get a CMIT and CAC tests, and there is no evidence of plaque. At the same time I am only 38 years old.
I am very concerned about my high lp(a). What are your thoughts?
Thanks!