Why It Is Vital To Keep Your Lipoprotein In Check

'Thirty per cent of the world's deaths in young people, due to heart disease, are Indians.'

IMAGE: Kindly note the image has been posted only for representational purposes. Photograph: Kind courtesy Pexels/Pixabay.com

You don't smoke.

You don't drink.

You exercise adequately, daily.

You eat heathy, avoiding processed foods, excess carbs and fats.

You are not even half a kilo overweight.

And you are below 40, maybe even in your 20s, and you have elevated cholesterol.

How? Why?

Are there genetic reasons for your high levels of cholesterol? Reasons beyond your control?

Yes, indeed. You may have inherited, from a parent, a tendency for increased values of lipoprotein(a), an LDL that transfers lipid fats to the cells of the human body. It's a genetic burden you unfortunately cannot change that can lead to early heart disease, if you are not mindful.

In 2019, Dr Basil Varkey, Dr Enas A Enas and their colleagues published a research paper titled An under-recognised genetic risk factor for malignant coronary artery disease in young Indians.

The paper spoke about how 'Indians, in general, develop acute myocardial infarction (AMI or obstruction of a coronary artery) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations.

Although established CAD (coronary artery disease) risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians.

Lipoprotein(a) (shortform: Lp(a)) is increasingly recognised as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD'.

In the paper they established that not only is elevated Lp(a) a sort of hidden factor contributing to heart disease, which is not brought on by lifestyle but inherited, it is also more common among South Asians.

Lp(a) is one of factors for why you hear of Indians dying so young of heart disease.

The two physicians, who are friends and went to medical school in Kerala in the same year, but to different colleges, before migrating to America, sort of strayed into this sphere, although Dr Enas was one of the first to show that Indians have a higher incidence of heart disease.

Says Dr Varkey "It was simply hearing, each time, how somebody that I know, family or friends, died early. I would hear the same refrain that 'He was such a healthy man. There was no problem. He didn't have any extra weight. He was so active. What happened?' That was really concerning. Why is it happening?"

Dr Enas and Dr Varkey are in the process of writing a book on Indians and heart disease, that will be out by the year's end.

In this first part of a multi-part interview Dr Varkey, professor emeritus of medicine, Medical College of Wisconsin, Milwaukee, but now based in Atlanta, spoke to Vaihayasi Pande Daniel/Rediff.com on lipoprotein(a), demystifying it and offering plenty of positive advice on how to live healthily and long, in spite of elevated Lp(a) levels that were, by no fault of your own, foisted on you by bad genes.

Like the other three key factors that increase one's risk of heart disease, the most important aspect of preventing CAD brought on by higher values of Lp(a) is being aware of it.

Dr Varkey is therefore loathe to focus entirely on the curse of genetically-acquired Lp(a) because, he says Indians require tremendous awareness and education about all the factors, many controllable, that cause early heart disease (please do definitely see Box 1).

Why are Asians and Africans particularly prone to having this gene that causes high levels of lipoprotein(a), which eventually narrows arteries?

Racial and ethnic variations in diseases cannot be explained as they are genetically determined. Certain groups are more prone to certain diseases.

In this case, it's a much broader and prevalent problem. It is not confined to Asia or Africa. One in five people in the world have high Lp(a).

Amongst Indians, it is higher -- probably one in four.

How important is it to alert people that they may have inherited a gene that makes them more prone to high lipoprotein(a) levels? They would need to know, preferably sooner than later, that they have a higher risk of getting heart disease at a young age?
How important is it to alert people to this not uncommon incidence of high Lp(a)?

You'll be doing a good service in informing your readers on this particular lipoprotein that confers increased risk. But it has to be in the context of information on all the modifiable risk factors.

Information on lipoprotein(a) must be imparted in the right context, without alarming people, at the same time alerting them on how they can help themselves.

Imparted in a way that people don't think that they are beyond hope. Absolutely not. A lot of things can be done.

IMAGE: Kindly note the image has been posted only for representational purposes.
A sample test report posted for representational purposes only.

Nobody talks about doing a lipoprotein(a) test in India. Why are these tests never ordered?
When a GP knows that there is family history, or he is encountering a rather young person with high cholesterol, why are they not ordering this test?

I don't have a precise answer as I cannot get in the mindset of the doctors. But this is not very surprising, as here in the United States also Lp(a) is not routinely ordered, although the most official (medical) societies do recommend it.

But there is increasing awareness of Lp(a) and its role in heart disease (coronary artery disease).

As I mentioned in my statistics (please see Box 1 below), if you consider the extremely premature deaths (defined as people less than 50 years) due to heart disease, India bears a burden out of proportion to its population.

Thirty per cent of the world's deaths in young people, due to heart disease, are Indians.

Coming back to the point: Why the doctors are not doing that? I can only guess.

Number one, is it available? Is it expensive? Are they knowledgeable about Lp(a)? And importantly, they may not know how that test would alter their treatment plan as medication to specifically lower the Lp(a) level is not available.

IMAGE: Dr Basil Varkey. Photograph: Kind courtesy Dr Basil Varkey

Maybe since making Indians aware of their heart disease risks is already an uphill task and doctors are already dealing with patients that don't know much, this slips under the radar?
It's very puzzling because nobody, I spoke to, has heard of the dangers of high Lp(a) or has been asked to take this test should they have a high LDL-C (low density lipoprotein-cholesterol) that does not reflect their lifestyle, their otherwise general healthiness, or age?

First a clarification: Lp(a) can be high even if LDL-C is not. If both are high, the risk is more than additive.

I agree that that there is lack of awareness on the risk factors for heart disease and it follows that the control of modifiable risk factors is very poor.

Specifically, I am not surprised that many people may not heard of Lp(a). If they have, patients should be empowered to ask their physician, 'Doctor, what about Lp(a) tests that I read/heard about?'

I encourage patients to ask questions and to be more engaged in their healthcare.

But you said earlier you were hopeful?

Yes, I am more hopeful, because I am very impressed with the progress India made in reducing tobacco usage and smoking.

There's been a concerted attempt of education -- very impressive advertisements, in movies and media, lead taken by public figures and by governmental action.

So why couldn't it happen in terms of good eating habits, control of cholesterol, a being-aware-of-your numbers campaign (blood pressure, HbA1c and LDL-C).

It would make a huge difference in heart care if every person knew their own numbers.

It seems that the damage from elevated Lp(a) can manifest in different directions. It can block your carotid arteries. It can lead to aortic aneurysm. What are the kind of things that high Lp(a) can lead to?

Lp(a) level in the blood is predominantly (90 per cent) under genetic control.

Basically, it is a lipoprotein that carries cholesterol and other atherogenic lipoproteins like LDL. These are transport vehicles for cholesterol (Please see the (hyperlink) Box 2 on what Lp(a) is).

Cholesterol is a key part of our existence as it is needed for cell structure and production of hormones. Lipoproteins, including Lp(a), are the ones that transport cholesterol to various organs through the blood.

It is not going in and physically blocking arteries by itself, but it plays a significant role in atherogenesis (the rise of atherosclerosis or thickening/hardening of arteries).

Atherosclerosis, is the basic disease process responsible for cardiovascular disease, a blanket term for coronary artery disease (cause of heart disease and heart attacks), peripheral vascular disease, and cerebrovascular disease (strokes).

These three are intimately tied with Lp(a). Lp(a) is not only atherogenic, it is proinflammatory and prothrombotic (clot formation) and causes plaque formation within the arteries.

In other diseases or disorders -- aneurysm, atrial fibrillation, heart failure -- the association with Lp(a) is there, but it's not as tightly established as in heart disease (heart attacks) and carotid artery disease (strokes).

Calcific aortic valve stenosis is also associated with high Lp(a).

• Heart disease is the leading cause of death in Indians and accounts for 17 per cent of all global deaths from heart disease.
• Of particular note: India accounts for 30 per cent global deaths from extremely premature heart disease (in those less than 50 years of age); Heart attacks are threefold higher in young Indians compared to other populations.
• The four major (established beyond doubt) risk factors for heart disease arehypertension, diabetes, high cholesterol (low density lipoprotein- cholesterol or LDL-C) and tobacco smoking. Control of all of these 4 factors is the most important proven step to reduce cardiovascular mortality. With the exception of reducing tobacco smoking, detection and control of the other three are dismally low in India. 1. Hypertension (though high in prevalence) is controlled only in 15 per cent 2. Diabetes affects about 77 million Indians and projected to be over 100 million by the year 2030. In Kerala, the Diabetes Prevention Programme found that only 31 per cent of those tested had normal glucose tolerance test. Uncontrolled diabetes increases cardiovascular risk. A 1 per cent increase in HbA1c is linked to a 40 per cent rise in cardiovascular mortality and conversely good blood sugar control can significantly reduce this risk. 3. In the Kerala project the LDL-C (LDL-Cholesterol) was over 130 mg/dl in two-thirds of the population studied  but only 2 per cent of them were on statin treatment.
• Only 7 per cent of Indians (going up to 10 per cent in those living in affluent areas) achieve recommended control of all three -- hypertension, diabetes and high LDL-C.

The highlighted risk factors, the importance of their control and how poorly we are doing, require utmost focus. While Lp(a) is quite important as it is the most potent atherogenic lipoprotein and has a causal association to premature heart disease, we should not leave the impression that, Lp(a) is the end all for reducing heart disease and heart attacks in Indians.

-- Dr Basil Varkey

What exactly is lipoprotein(a) Is Lp(a) the worst kind of lipoprotein, the worst of bad cholesterol?

Lp(a) is a lipoprotein that carries cholesterol, triglycerides, phospholipids, cholesterol esters, and apolipoproteins and each one of these has disease-causing risk. Lp(a) is atherogenic (meaning causes atherosclerosis that is the basic pathologic process that causes cardiovascular disease) and is the most potent of the four atherogenic lipoproteins, but is not the most dominant one.

The dominant one is low density lipoprotein cholesterol (LDL-C) that has the strongest dose-related causative role in heart disease.

Lp(a) has apolipoprotein(a) covalently linked to an apo B-containing lipoprotein. Both these apolipoproteins contribute to atherosclerosis.

The expression of apo (a) component is controlled by the LPA gene.

Ninety per cent of Lp(a) level is genetically determined. The other 10 per cent is influenced by many factors including diet high in saturated fats, inflammatory states, renal and endocrine diseases, gender, age, medications etc.

-- Dr Basil Varkey

Feature Presentation: Ashish Narsale/Rediff.com