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17. A Nerdy Cardiologist's Research on Lp(a): Does it Cause Heart Disease?

Updated: Jun 24, 2023

According to mainstream medicine, if you have a high Lp(a) level, you are doomed, because the Lp(a) levels are genetically determined. But is it just this simple? Dr. Nadir Ali is a practicing interventional cardiologist for 30+ years. He has a different opinion. Let's hear what he says here (What is LP(a)? Does It Cause Heart Disease?).

First of all, what is Lp(a)? Lp(a) is pronounced “L-P-little-A”). It stands for Lipoprotein(a), which is a type of lipoprotein particle found in the blood. It is composed of a low-density lipoprotein (LDL) particle attached to a specific protein called apolipoprotein(a) or apo(a). Apo(a) is bound covalently to the apoB-100 contained in the outer shell of the LDL particle. This apo(a) particle is similar to plasminogen. The variability in size of apo(a) comes from the number of kringle IV (KIV) Type 2 repeats, as shown in the yellow highlighted region in the figure below. The upper-left sample has 4 KIV2's, the rest have 8, 24 and 40 KIV2's, respectively.

Because apo(a) looks similar to plasminogen, it is supposed to act like a decoy for plasminogen and prevent plasminogen from working so the question is what does plasminogen do. In short, plasminogen (the blue hexagon in the figure below) when activated to plasmin can break own blood clots in blood vessels.


When apo(a) occupies the site where plasminogen is supposed to be, as shown below, no plasmin is generated. As a result, blood clot cannot be dissolved. Even worse, blood clot can also propagate along the vessel. Eventually the blood vessel may completely close and end up causing a heart attack. So if LDL is bad, Lp(a) is worse, because it not only causes plaque buildup but it also leads to clot propagation.

Apparently, having higher number of apo(a) particleIs is not good for you, based on the explanation above. How is apo(a) particle number measured in the lab? It is done indirectly by a method called immuno-turbutometric, which measures the concentration of Lp(a). Then through a series of assumptions, the number of Lp(a) particles is inferred. Remember, Lp(a) has many varieties with different KIV2 length. The longer the kringle is, the larger the Lp(a) size is. The more larger Lp(a)'s there are, the fewer Lp(a) particle numbers are. You will be surprised to know that Lp(a) tail length is determined by literally only one gene that you inherit from your mother and one gene that you inherit from your father. So if you are unlucky enough to get two copies of the bad genes from both of your parents, you will have more short-tailed Lp(a) and high Lp(a) particle level. Mainstream medical doctors will tell you Lp(a) level changes minimally with inflammation, diet, exercise or fasting. So you are doomed if you have a high level. Period.

What about statin then? Statins are considered to be wonder drugs, but would you be surprised to know that statins increase Lp(a) level? He showed two plots below from one study. The plot on the left shows for the group not treated with statin, their Lp(a) levels do not change, while for the group that is treated with statin, their Lp(a) levels go up significantly. The plot on the right shows for people going through burn injury, their oxidized LDL levels also increase with statins. So statins increase CVD risk in clinical study. That sounds scary to me!

Besides, to me this is contradictory to the mainstream consensus that we just heard, i.e. that the Lp(a) level is dominantly determined by genetics and minimally affected by anything else. What is the main purpose the human body produces Lp(a)? Is it all bad? If it is, why does the human body produces something that only hurts us? There must be some benefits that we have not discovered yet. Dr. Ali did some research and here are his findings.

The figure below shows the healing process of wounded tissues. There are four stages, hemostasis, inflammation, proliferation and remodeling. The first stage is hemostasis. There is an injury which leads to bleeding and clot formation. The inflammation has not set in yet. It's just blood clot with fibrin. In the second stage, macrophage come in and cause inflammation. Then the next stage is proliferation, in which a new lining is being formed to cover the wound but the scab on the top is still there to protect the new lining. Under the new lining, blood vessels are growing and scar tissues are creating with some blood vessels. In the last stage called remodeling, the lining, either the skin lining or the blood vessel lining is complete and the scab is gone.

What is the biologic function of Lp(a) during this wound healing process? Let's take a closer look. In the initial stages of blood clot formation, you can find plasmin, fibrin and blood cells, but very little Lp(a). So there is no interference from Lp(a) to make the blood clot dissolve. In the second and third stages, you don't want the fibrous cap which is composed of fibrin to get dissolved because if it gets dissolved, then the healing part is exposed. This is when you find the Lp(a) (the green hexagons in the figure below) covering and protecting the scab. The protection for the scab continues, while the new lining is being formed. There is also a little bit of Lp(a) in the interior of the wound in order to prevent an excessive amount of blood vessels from forming. Then finally at the healed stage of the wound, scar tissue and new epithelium are formed. The scab is gone, and there is no Lp(a) either. So one could say that Lp(a) was designed by the human body as a method to help with wound healing.

Next, he presented several studies that show high Lp(a) level is beneficial to us. The first one is a cohort study from Japan. More than 10,000 people were recruited at an average age of 55 and were followed for about 12 years. They found high Lp(a) level 80 - 270mg/dL reduces the all-cause mortality rate, including cardiovascular deaths and cancer deaths, as shown in figure below. This is exactly opposite to what we have heard before the high level of Lp(a) increases the risk of CVD and stroke.


Another study on French centenarians shows that the centenarians have higher Lp(a) level and smaller apo(a) isoforms, i.e. shorter tails, than the control group. So high level of Lp(a) is associated with longevity. A third study examined more than 100,000 people in Denmark. It concludes that higher Lp(a) lever lowers the risk of major bleeding in brain and airways. What is more interesting is that if you inherit "bad" genes of shorter tails from your parents, your risk of bleeding is lowered by 40%, which is wonderful.

Now, what about the myth of Lp(a) level is genetically determined and does not change with infection, inflammation etc. There is a study done in the 1990's on a group of people undergoing major surgeries. The plot below shows that after surgery their CRP level went up first and peaked at around day 3. Their Lp(a) level went up next after CRP peaked. Its level increased 2.5x from 40 to 100mg/dL and peaked at around day 9.


On the same study, it shows people after heart attack, their Lp(a) level also increased dramatically from 48 to 107mg/dL and peaked at day 10. What a coincidence! The last evidence he presented is another study that shows Lp(a) levels fall dramatically in patients who are in the ICU with severe septic shock. Septic shock is the last stage of sepsis. Sepsis is life-threatening. It happens when your immune system overreacts to an infection. One example is Covid infection with sars-cov-2 virus. The patient is on a respirator

with elevated white count, severe inflammation and infections. Those patients in the study showed their Lp(a) levels fall dramatically. Not only Lp(a), their LDL cholesterol levels also fall dramatically. This paper is not very clear as to why that happens. Dr. Ali's opinion is that both LDL and Lp(a) are host defense mechanisms, through which we can fight infection and inflammation. Perhaps in the setting of severe infection, these are being consumed and that is why their levels are dropped drastically. As the infection and inflammation got better, Lp(a) and LDL levels went back up, as shown in the plots below.

Now let's look at the people who came in with the same kind of an infection who died (pink rows in the table below). They had almost zero Lp(a) and almost absent level of ldl cholesterol. So having low levels of cholesterol if you have a severe infection is a bad prognostic sign.


In summary, Lp(a) helps with wound healing. Higher levels of Lp(a) reduce all cause mortality, and are associated with reduced brain and lung bleeding, and reduced cancer risk. Lp(a) levels fluctuate with infection and inflammation and perhaps also with fasting and nutrition as well as during heart attacks and surgery. And perhaps the Lp(a) is a fire fighter rather than an arsonist. It's going to the site where there is injury in order to help prepare it in order to help dampen the inflammation and not cause further injury.

. At the end, he added that pharma is always looking to find some culprit to make money without completely understanding what a certain biologic substance does, whether it does any harm, and what the good it does. This is sad.

My take home message is that the baseline level of Lp(a) may not be that important. But once there is a change to that level, something bad is happening inside our body. Traditional lab test only gives you a snapshot of your biomarkers. To completely understand and track what is going on, more advanced real time sensing technology is needed. As a scientist working on health sensors, this is my ultimate goal.


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