Lipoprotein (a) used to be the forgotten lipid. Not anymore.

human heart low poly color

Lipoprotein (a) — or its abbreviation, Lp(a), pronounced “el-pee-little-a” — is emerging from obscurity. And for good reason. Among them, Bob Harper, the TV famous trainer from The Biggest Loser, has helped bring Lp(a) to national attention after his heart attack in 2017. Put simply, Lp(a) is a version of LDL that is more dangerous. It is more pro-inflammatory and more pro-thrombotic.

Studies show that elevated Lp(a) levels correlate with increased cardiac risk. So, it makes sense that we would want to lower patients’ elevated Lp(a) levels to reduce cardiac risk, right? So far, that hasn’t been very successful.

Unfortunately, Lp(a) does not respond well to lifestyle changes. Its level is almost entirely genetically determined and cannot be easily manipulated with environmental exposures (nutrition and exercise) the way that LDL can. The best treatments for lowering Lp(a) are niacin and a drug class called CETP inhibitors. The problem, however, is that despite lowering Lp(a), these treatments have not been shown to reduce the outcomes we care about — the risk of heart attack and death.

The conventional wisdom, therefore, is to treat other risk factors more aggressively in those with elevated Lp(a). Top on the list, of course, is treating LDL with statin medications.

That may now change. A new study published in the Lancet looked back at seven statin trials including over 29,000 subjects. The authors found that even with statin treatment, Lp(a) levels above 50mg/dL were still associated with increased cardiac risk. This was despite the reduction of LDL on average by almost 40%. (With Lp(a), it is important to note the units since it is also often reported as a particle count, in nmol/L.)

The Lancet: Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials

It does not appear that statin therapy significantly lowers the risk of cardiovascular disease events in those with elevated Lp(a). The authors concluded that the study “provides rationale for evaluating drugs to specifically lower Lp(a) in cardiovascular outcome trials.” On the one hand, this conclusion makes sense based on the trial data. On the other hand, it should come as no surprise that the trial was sponsored by the pharmaceutical company Novartis, which just happens to have an investigational drug targeting Lp(a), which presents a clear conflict of interest.

Future studies may or may not prove that lowering Lp(a) with drugs reduces cardiac risk. However, we know for certain that regardless of Lp(a) levels, healthy lifestyle habits are always first-line therapy for improving our cardiovascular risks. No matter what drugs we may or may not take, nutrition, exercise, stress management, and other lifestyle interventions are the best place to start.

Thanks for reading,
Bret Scher, MD FACC

Earlier

Does cholesterol cause heart disease? New study says no

Fat: The Documentary – official trailer

Learn more

Peter Attia, MD, Podcast: Deep dive: Lp(a) — what every doctor, and the 10-20% of the population at risk, needs to know (EP.07)

Heart disease

5 comments

  1. BobM
    Any ideal how to convert from mg/dL to nmol/L? Multiply nmol/L by 0.0259? I find that my Lp(a) varies depending on whether I'm fasting or not for instance. I've had values from 226 nmol/L to 329 nmol/L, the highest values (329, 314) when fasting 4.5 days.
  2. Andrew Cleveland
    BobM, mg/dl is a mass-based measure and nmol/L is a particle number. With most chemical compounds, you could just add up the mass total from the periodic table for the compounds and divide the lab measure by that, but the problem with LP(a) is that it has a highly variable weight due to a section of it’s structure that can be either very long or very short. That means that you need the LP(a)-P (lipoprotein a - particle count) lab to get a read on your nmol/L of LP(a) particles vs just a mg/dL value which is less valuable in evaluating risk.
  3. 1 comment removed
  4. Lois
    I found this very interesting article below which seems relevant to this discussion. Would love further discussion / exploration of approaches to reduce LDL-P and address issues with Lp(a) - especially in regard to low carb / ketogenic dietary efforts. I know of at least one study that indicated Diets that are low fat increase Lp(a), regardless of the quantity of vegetables consumed, and, as was stated, physical activity has little effect on these levels - the utilization of Lipid apheresis has been shown to significantly reduce lipoprotein(a) levels compared with available drug therapies but how would this impact someone interested in following a ketogenic diet?
    "Elevated Lp(a) levels and apo(a) production in response to statins"
    Statin therapy increases lipoprotein(a) levels
    Literature - Tsimikas S, Gordts PLSM, Nora C et al. - Eur Heart J 2019; doi:10.1093/eurheartj/ehz310
    link: https://pace-cme.org/2019/06/12/elevated-lp-a-levels-and-apo-a-produc...
  5. Pamela
    I would love to know if fasting can have a positive impact on Lp(a). I understand this is a powerful marker for CVD and yet there seems to be very little that can be done to lower it. Can someone please give me some insight (and hope) about this?
    Thanks!
  6. Jean
    I ran across this n=1 study by a doctor who found that a keto diet decreased his Lp(a) significantly (link below). I would also point out that high Lp(a) impacts other aspects of one's circulation, not only or necessarily the heart. Peripheral artery disease, carotid artery blockages, aortic valve stenosis and stroke are also frequently encountered.
    https://nutrition.bmj.com/content/early/2020/11/19/bmjnph-2020-000189

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