Introduction

Progression of coronary artery disease (CAD) is the worsening of the narrowing of the coronary arteries over time.

• This narrowing is caused by the buildup of plaque, which is a fatty substance that can block the flow of blood to the heart.
• The progression of CAD can lead to heart attacks, heart failure, and sudden cardiac death.
• There are a number of risk factors for CAD progression, including high cholesterol, especially elevated ldl levels, high blood pressure, smoking, and diabetes.
• Treatment for CAD progression includes lifestyle changes, medications, and, in some cases, surgery
• Elevated LDL cholesterol is considered as the primary risk factor because, excess LDL may damage the blood vessels and “MAY deposit” in the arteries forming an arterial plaque.
• However, research has shown that there is another form of lipid called as lp(a) which is more dangerous than ldl. Lp(a) is a deadly risk factor for CAD progression. Structurally lp(a) is similar to ldl.

The two risk factors of heart disease: LDL & lp(a)?

LDL cholesterol is designated as the primary Risk Factor of heart disease

The complexity on what deposits in the arteries has increased ever since lipoprotein(a) was discovered in the blood stream of patients suffering from heart disease.[Ref: 1, 2, 3]. Even people suffering from diabetes may have higher levels of lp(a) in their blood stream.

The two lipid constituents that are thought to deposit in arteries are:

a) LDL (bad) Cholesterol:

The first lipid component is LDL cholesterol. Ankev Keys  first proposed proposed that if serum ldl levels are higher, then excess LDL cholesterol may damages the arteries and may deposit in the arteries forming a plaque deposit. This plaque eventually over time grows in size and causes heart disease, stroke or peripheral artery disease.

Of all the Risk factors, like smoking. alcohol consumption, high blood pressure, diabetes, obesity and poor diet, high serum LDL levels is considered as the primary risk factor of heart disease.

With the discovery of lp(a)[Ref: 1] as a more dangerous risk factor for progression of atherosclerosis, we may have to call it as the secondary risk factor for heart disease. Therefore,  I have already written a blog article called think before you start lowering your cholesterol.

b) Lp(a) Cholesterol:

The second lipid component is lipoprotein(a) or lp(a), that has been shown to deposit in the arteries. It is more dangerous than LDL. It is shown to be an emerging and independent risk factor for heart disease.

There are several other risk factors that have been identified in the blood stream of patients suffering from heart disease. They are called as “Emerging Risk Factors of Heart Disease”.

An article published by Mehta JL has published a review article “Role of Emerging Risk factors in Cardiovascular Outcomes“.  This article reviews the evidence for emerging risk factors for heart disease, including C-reactive protein, homocysteine, lipoprotein(a), and carotid intima-media thickness. The authors conclude that these factors may be useful in identifying people at high risk for heart disease, and that they may also be targets for preventive interventions.

c) What actually is present in the arteries?

Everyone thinks that LDL cholesterol deposits in arteries and hence the major component of plaque deposit consists of LDL cholesterol. The other components deposited are some debris floating in the blood, calcium deposit and mass growth.

But now it has been conclusively proved that the plaque deposit mainly (about 94%) consists of lipoprotein(a), with some calcium deposit and some debris for the blood.

The structure of lp(a) has been determined. It is similar to ldl but consists of an additional protein molecule is attached to it. This additional protein molecule is apo(a).

Its presence in the arteries has been confirmed in the laboratory by a technique called Gel Chromatography.

d)Difference in properties of LDL and Lp(a):

Lp(a) contains additional protein molecule attached to ldl.

Lp(a) is 300 times more atherogenic than LDL.  Therefore lp(a) binds more strongly to the arteries.

What you can learn from this blog article?

You are made to believe that when cholesterol levels are high, excess  LDL cholesterol may deposit in arteries.  In recent years, researchers have changed their mind about how LDL cholesterol influences the risk of cardiovascular disease. It used to be thought that excess cholesterol simply builds up on the walls of blood vessels. But that has turned out not to be true.

The purpose of this blog is to show how important is Lp(a) in causing atherosclerosis. I am presenting a few clinical trial data to show the relation between lipoprotein(a), atherosclerosis and heart disease.

Association of elevated serum lipoprotein(a) with plaque deposition:

Several scientific studies show the importance of lp(a) serum levels in the formation of atherosclerotic deposits in arteries. They have been proved by clinical trials.

Clinical studies data:

Example 1-–

This is the first example of clinical data published in Journal of Atherosclerosis and Thrombosis:

The following is the finding of the studies:

• Background: Elevated levels of lipoprotein (a) [Lp(a)] are associated with an increased risk of atherosclerosis and thrombosis. However, little is known about the influence of Lp(a) on the progression of coronary artery disease (CAD).
• Study: Researchers conducted a clinical trial to evaluate the association of serum Lp(a) and the long-term changes of angiographic severity in patients who underwent repeated coronary angiography at intervals of more than 2 years.
• Results: The study found that patients with higher levels of Lp(a) were more likely to have progression of CAD over time. In particular, patients with Lp(a) levels greater than 30 mg/dL were more likely to have progression of CAD than patients with Lp(a) levels below 30 mg/dL.
• Conclusion: The study findings suggest that serum Lp(a) level is a significant predictor of CAD progression.

The study findings are important because they provide further evidence that Lp(a) is a significant risk factor for CAD. This means that doctors should consider Lp(a) levels when assessing a patient’s risk of CAD and developing treatment plans.

Example 2

The second example is published in Clinical Cardiology Journal:

The following is the study findings:

Background: Coronary artery disease (CAD) is a major cause of death worldwide. Elevated levels of lipoprotein(a) [Lp(a)] are a known risk factor for CAD, but the association between Lp(a) and CAD progression is not well understood.

Methods: This study included 814 patients who had undergone two or more coronary computed tomography angiography (CCTA) scans at least 6 months apart. The patients were stratified into two groups based on their Lp(a) levels: those with Lp(a) levels greater than 300 mg/dL and those with Lp(a) levels less than or equal to 300 mg/dL. The patients were also classified as “progressors” or “non-progressors” based on the rate of change in their Gensini score, a measure of the severity of CAD.

Results: The study found that patients with higher levels of Lp(a) were more likely to be classified as “progressors” than patients with lower levels of Lp(a). In addition, the study found that the association between Lp(a) and CAD progression was stronger in patients with lower body mass index (BMI).

Conclusion

These studies suggest that Lp(a) is a major risk factor for progression of CAD. If you have high levels of Lp(a), it is important to talk to your doctor about your risk of CAD and how to manage your cholesterol levels.

Here are some tips for managing your Lp(a) levels:

• Eat a healthy diet that is low in saturated fat and cholesterol.
• Exercise regularly.
• Maintain a healthy weight.
• If you smoke, quit.
• Take medication if prescribed by your doctor.

You can also read these articles:

Urgent: Think Before You Start Lowering Cholesterol

References

1. Ginsberg H, Albers JJ, Hamazaki T, Utermann G. Lipoprotein(a): a unique risk factor for atherosclerotic vascular disease. Arteriosclerosis. 1987;7:123-132.
2. Packard CJ, Morrisett JD, Shepherd J, Gotto AM Jr. Lipoprotein(a): a unique lipoprotein associated with premature vascular disease. Am J Med. 1987;82:724-733.
3. **Davignon J, Gregg RE, McNamara JR, Ordovas JM. Lipoprotein(a) and atherothrombosis. Arterioscler Thromb Vasc Biol. 1997;17:1529-1546.
4. Keys A. Coronary heart disease: The dietary hypothesis. Am J Med. 1953;11:155-174.
5. Berg K. A new serum lipoprotein antigen. Acta Med Scand. 1963;173:251-26
6. Lp(a) (Lipoprotein[a]) Concentrations and Incident Atherosclerotic Cardiovascular Disease:Arteriosclerosis, Thrombosis, and Vascular Biology. 2021;41:465–474

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