Lipoprotein(a) also known as Lp(a) is an independent, genetic, and causal risk factor for heart attack and stroke (1). So, even if our LDL cholesterol (or ApoB) are normal, Lp(a) can still significantly increase our risk for heart attack and stroke (1).
"Data confirm that the relationship of Lp(a) level to elevated Cardiovascular Disease risk is log–linear with risk beginning at ≥20–30 mg/dl" (1). This risk accelerates exponentially as levels rise above 50 mg/dl (1). This means that just taking a statin medication to lower our LDL-cholesterol may not be enough (2). At an Lp(a) level above 20, our risk of heart attack and stroke essentially doubles (13). So ideally, we want our ApoB to be below 50-70 and our Lp(a) to be below 20 mg/dl.
What exactly is Lp(a)? Lp(a) is an LDL-like particle composed of an apolipoprotein(a) bound to an apoB (shown in the first picture below). Picture ApoB is a sort of like a tag on different sizes of LDL cholesterol particles in the blood (second image below), with Lp(a) attaching itself like a tail.
Lp(a) and ApoB are both markers that can be easy be checked during a blood draw. As the relationship between ApoB and Lp(a) appear to be the most predictive blood markers of who will go on to have a heart attack or stroke (4), these tests will likely become routine in the clinic over the coming years - but they haven't yet. Lifestyle Medicine Maine offers at-home phlebotomy (lab draws) for those of us residing within 30 minutes of the Greater Portland area (request lab testing here). High-sensitivity C-Reactive Protein (hs-CRP) also plays a significant role. More on what we can do about that in a coming blog post.
As Bras wrote in the Journal Nature Reviews Cardiology, "A substantial number of patients treated with statins for the primary or secondary prevention of CVD can still experience cardiovascular events even if the target level of plasma LDL cholesterol (LDL-C) has been achieved" (2). I have personally seen this happen and it is tragic. As of late 2023, we do have studies showing that some of our cholesterol lowing medications can lower levels of Lp(a) significantly in the blood (2).
Which medications?
Statin medication averages a drop of Lp(a) around 0 - 7% (15)
PSK9 inhibitors appear to have the most profound reduction in Lp(a) averaging a 25 - 29% drop (14) (15).
Okay, but what if we are already on a statin and a PSK9 inhibitor AND our levels are still too high? If only there was some diet or lifestyle intervention that we could use to lower our Lp(a)...
Turns out there is. We can reduce naturally occurring transfats in the diet.
In 2018 the US banned industrially produced transfats in food products (5), a huge win! But that doesn't mean that we are not still consuming trans fats. Vaccenic acid (VA) is a type of transfat that is found to be naturally occurring in red meat and dairy products (6).
While there are a handful of epidemiologist studies with mixed results, Gebauer and team conducted the first randomized, double-blind, crossover, controlled feeding study in humans, to determine the effect of this type of transfat, found in meat and dairy (VA), on risk factors for cardiovascular disease like Lp(a) (6). Consuming as little as 3.7% of total daily calories from naturally occurring transfats in meat and dairy increased ApoB and Lp(a) by 2-6% (6). If we understand that our risk is logarithmically increased as Lp(a) increases, a 6% reduction is not insignificant.
Transforming this into meaningful data. The average adult female consumes around 2400 kcal per day. If about 90 kcal were coming only from the transfat found in meat/dairy, 1 cup of whole milk would almost get us there (7). A single serving of sirloin steak at a restaurant would easily surpass this amount (8). As does a single serving of chicken thighs or drumsticks (9). Choosing skinless chicken breast does appear to reduce the transfat (10). Thus, reducing the amount of whole milk, red meat, and dark meat chicken can lower Lp(a) levels.
I was surprised by how quickly we could reach that 3.7% of daily calories amount. Most of us are likely consuming much more than 1 serving or a combination of multiple servings of those items on a daily basis. The assumption is that reducing our overall consumption could potentially make a larger difference on a personal level. Would fully avoiding naturally occurring transfat in the diet further increase Lp(a)?
Just as New York lead the ban in industrially produced transfat, New York Hospitals are now offering patients plant based meals, with their newest campaign "Eat a lot more plants!" (11). There is a slow but growing awareness that more plants and less meat, dairy and eggs in the diet can significantly improve our healthspans.
Okay, but back to Lp(a)... If transitioning to a dietary pattern that reduces naturally occuring transfat in meat and dairy products can further reduce our risk some, how far do we need to go if our Lp(a) is significantly elevated?
As with most things that we have discussed so far, any transition along the dietary spectrum tends to make a difference in health outcomes, but what about for Lp(a)? We've known since the 1980's that a lacto-ovo vegetarian dietary pattern doesn't seem to be enough to significantly reduce Lp(a) levels (12). Could a fully plant predominant diet make a difference?
In 2018 researchers placed a group of people on a mostly-raw plant based diet (with a rather extreme intervention), to evaluate whether an effect could be made on Lp(a) (13). "Briefly, excluded were animal products, cooked foods, free oils, soda, alcohol, and coffee. Allowed for consumption were raw fruits, vegetables, seeds, and avocado. Small amounts of raw buckwheat and oats were also permitted" (13). I can only imagine how grumpy participants were when told that they were taking away their coffee, let alone that they'd need to munch on dried grains!
On a serious note, I personally follow an 80% plant predominant eating pattern (with cooked food), and this sounds like it would be difficult to follow, even to me. Okay, but maybe we've exhausted all of our options. Did it make a difference? After 4 weeks, Lp(a) dropped on average 16% (13). Pretty impressive! We are starting to see research suggesting that diet likely plays a role in modulating Lp(a) levels.
Here's what they were eating...
So what do I think? When we talk about risk factors for heart attack and stroke, we commonly hear about the role of genetics, diet and lifestyle, tossed around ephemerally like we should know what to do. While these things do determine our risk, knowing the actual risk factors that place us personally in the moderate to high risk category are important. Having this knowledge allows us to best determine where we can make improvements and, more importantly, what to actually do about it. We are not a victim of our genes. We can take an active role to reduce our risk.
If you've been keeping up with the blog so far (thank you -- I appreciate you!), you'll know that any reduction in saturated fat and transition towards a more plant predominant dietary pattern can significantly lower our ApoB. Reducing animal products by lowering our intake of naturally occurring transfats makes a difference, even when when we look at people who are consuming on average 1 serving per day. Much less than most of us are currently eating. Dietary pattern matters.
We may also want to talk to our PCP or Cardiologist to see if medication options are right for us if our Lp(a) levels are elevated (there are risks and benefits to everything).
In addition to Lp(a), we need to take further steps to reduce our other risk factors (hypertension, obesity, hr-CRP, ApoB, stress levels, alcohol intake, and exercise habits). Get started by knowing your risk and working with Lifestyle Medicine Maine to come up with a personalized guided therapeutic lifestyle plan to improve your health span.
Here at Lifestyle Medicine Maine, we are not bound by insurance companies dictating when and how often lab tests can be performed. Members have an option to make a dietary intervention and repeat Lp(a), hr-CRP and/or ApoB testing after 4-12 weeks of significant dietary intervention. Don't forget that at-home phlebotomy is included with your membership.
Up next: Keep an eye out for the next blog in this series focusing on hr-CRP and what we can do to improve it. Don't forget to like and subscribe to the Lifestyle Medicine Maine blog: the Veggie Press. And if you're looking for more information on Weight loss, Prediabetes or Type 2 Diabetes, there are free courses available on the website that go into detail on what is possible for reversal and remission. As always, stay healthy and "Eat your Veggies!"
References
Lipoprotein(a): An independent, genetic, and causal factor for cardiovascular disease and acute myocardial infarction. Enas et al. Indian Heart Journal. (2019) 10.1016/j.ihj.2019.03.004
Lipoprotein(a) is an independent predictor of CVD. Bras. Journal Nature Reviews Cardiology (2018) https://doi.org/10.1038/s41569-018-0120-y
Image source: Lp(a) and cardiovascular disease. GB Health Watch. (n.d.) https://www.gbhealthwatch.com/genes-me-newsletter-4-2022.php
Physiological Bases for the Superiority of Apolipoprotein B Over Low‐Density Lipoprotein Cholesterol and Non–High‐Density Lipoprotein Cholesterol as a Marker of Cardiovascular Risk. Galvinovic et al. Journal of the American Heart Association. (2022) https://doi.org/10.1161/JAHA.122.025858
Artificial trans fats banned in U.S. Harvard T. H. Chan school of Public Health. (2018). https://www.hsph.harvard.edu/news/hsph-in-the-news/us-bans-artificial-trans-fats/
Vaccenic acid and trans fatty acid isomers from partially hydrogenated oil both adversely affect LDL cholesterol: a double-blind, randomized controlled trial. Gebauer et al. American Journal of Clinical Nutrition. (2015). 10.3945/ajcn.115.116129
Whole Milk. Nutrition Value. (acccessed December 2023). https://www.nutritionvalue.org/Whole_milk_735370_nutritional_value.html
Restaurant Sirloin Steak, Family Style. Nutrition Value. (acccessed December 2023). https://www.nutritionvalue.org/Restaurant%2C_sirloin_steak%2C_family_style_nutritional_value.html
Chicken, raw, skin (thigh or drumstick). Nutrition Value. (acccessed December 2023). https://www.nutritionvalue.org/Chicken%2C_raw%2C_skin_%28drumsticks_and_thighs%29_nutritional_value.html
Chicken, raw, meat, boneless, skinless, breast, broilers or fryers. (acccessed December 2023). https://www.nutritionvalue.org/Chicken%2C_raw%2C_meat_only%2C_boneless%2C_skinless%2C_breast%2C_broiler_or_fryers_nutritional_value.html
Eat Plants! New York City Health. Press Release. (2023). https://www.nyc.gov/site/doh/about/press/pr2023/nyc-launches-eat-a-whole-lot-more-plants.page
Effects of a lacto-ovo vegetarian diet on serum concentrations of cholesterol, triglyceride, HDL-C, HDL2-C, HDL3-C, apoprotein-B, and Lp(a). Masarei et al. American Journal of Clinical Nutrition. (1984). 10.1093/ajcn/40.3.468
Consumption of a defined, plant-based diet reduces lipoprotein(a), inflammation, and other atherogenic lipoproteins and particles within 4 weeks. Najjar et al. Clinical Cardiology. (2018) 10.1002/clc.23027
Effects of Ezetimibe on Remnant-Like Particle Cholesterol, Lipoprotein (a), and Oxidized Low-Density Lipoprotein in Patients with Dyslipidemia. Nozue et al. Journal of Atherosclerosis and Thrombosis. (2010) https://doi.org/10.5551/jat.1651
Current therapies for lowering lipoprotein (a). Capelleveen et al. Journal of Lipid Research. (2016) 10.1194/jlr.R053066
An Update on Lipoprotein(a): The Latest on Testing, Treatment, and Guideline Recommendations. Alebna et al. American College of Cardiology. (2023) https://www.acc.org/Latest-in-Cardiology/Articles/2023/09/19/10/54/An-Update-on-Lipoprotein-a
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