Understanding Cardiovascular Risk: The Role of LDL-C, Comorbidities and Early Intervention

There are many determinants that can elevate an individual’s risk of having a cardiovascular (CV) event, such as a heart attack or stroke. However, having levels of high low-density lipoprotein cholesterol (LDL-C) – or “bad” cholesterol – is one of the most significant modifiable risk factors.^1-5

For someone with established cardiovascular disease (CVD), the presence of an additional CV condition, or comorbidity, can put them at an even higher risk of experiencing a CV event.⁶ Common comorbidities associated with CVD include diabetes, coronary artery disease (CAD), and pulmonary artery disease (PAD).^7,8

Amgen spoke with Lisa Head, the new U.S. Medical Lead for the Cardiovascular Metabolic Therapeutic Area, ahead of this year’s American Heart Association (AHA) Annual Scientific Sessions, to discuss how comorbid conditions can impact those already at high-risk for CV events, like people with CVD and diabetes, and why early intervention is so important.

1. What factors put someone at high risk for a CV event?

   Elevated levels of LDL-C are a major factor that can significantly increase the risk for CV events. Over time, high levels of LDL-C can lead to a buildup of plaque in the arteries and block blood flow, putting an individual at risk of a heart attack or stroke.

   An essential characteristic of LDL-C is that it is a modifiable risk factor, meaning that its levels can be influenced by lifestyle changes, treatment and other interventions. Unlike non-modifiable risk factors such as age and genetics, the ability to modify LDL-C levels provides a tangible and proactive means to reduce CV risk.

2. Can you explain how conditions such as diabetes, coronary artery disease (CAD), and peripheral artery disease (PAD) elevate CV risk?

   Diabetes, CAD and PAD all elevate CV risk through mechanisms that damage or narrow blood vessels, limiting blood flow and increasing the likelihood of atherosclerosis, a condition where arteries become clogged and restrict blood flow:

   • With diabetes, chronic high blood sugar levels can damage blood vessels and the nerves that control the heart, increasing the risk of developing atherosclerosis. People with diabetes often have higher levels of LDL-C, which exacerbates this buildup and increases the risk of CV events.
   • CAD happens when arteries supplying blood to the heart become narrowed or blocked, often due to plaque buildup, which can cause chest pain and raise heart attack risk. Similarly, PAD affects arteries in areas like the legs, restricting blood flow to the limbs. Both conditions indicate widespread plaque buildup, increasing the risk of heart attack and stroke.

3. What warning signs and symptoms of CV events should patients with these conditions be most aware of?

   Patients can experience a variety of warning signs and symptoms, depending on which arteries are affected. For heart attacks, these can include chest pain or discomfort, which can radiate to the shoulders, arms, neck, jaw, or back, and pain or cramping in the legs or hips during walking or physical activity.

   It’s important to remember that women may have different symptoms than men, including more subtle signs like shortness of breath, nausea and fatigue.

   For strokes, traditional symptoms are similar for women and men and can be remembered through the acronym FAST: "F" for face drooping; "A" for arm weakness; "S" for speech difficulty; and "T" for time to call 911.

4. Why is early intervention in lipid management so critical for preventing CV events in high-risk patients?

   Early intervention is important because it directly addresses one of the primary causes of atherosclerosis and CVD: the buildup of cholesterol-rich plaques in the arteries. Managing cholesterol levels by lowering LDL-C can significantly reduce the risk of CV events like heart attacks and strokes – especially for people living with CVD. This is crucial because once substantial plaque buildup occurs, it not only narrows the arteries but also sets the stage for potential CV events to occur.

5. What advice do you have for high-risk patients with comorbidities to better manage their CV risk?

   It’s important to stay informed and proactive about your heart health. Individuals at high-risk, especially those living with CVD and/or comorbid conditions like diabetes, should consult with their doctor to determine if their LDL-C levels are within the target threshold and if lipid lowering therapies could be beneficial.

   Additionally, adopting a heart-healthy lifestyle can make a significant difference. This includes a balanced diet and physical activity. Exercising or doing some type of physical activity – even for 20 minutes a day – will not only strengthen your heart but can also help manage weight, blood pressure and cholesterol levels.

   Visit AttackHeartDisease.com for more information, including how to get a free LDL-C test. Terms and conditions apply.

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References

1. Grundy SM, et al. J Am Coll Cardiol. 2019;73:3168-3209.
2. McKinley EC, et al. Cardiovasc Drugs Ther. 2023;37:107-116.
3. Wilkinson MJ, et al. J Am Heart Assoc. 2023;12:11:e028892:1-22.
4. AHA Understanding and Managing LDL (Bad) Cholesterol. 2023;1-18.
5. Underberg J, et al. Postgrad Med. 2022;134:752-762.
6. Kendir C, et al. Eur J Gen Pract. 2018 Dec;24(1):45-50.
7. Buddeke J, et al., Br J Gen Pract. 2019 Jun;69(683):e398-e406.
8. Islam F, et al., BMJ Open 2024;14:e083982.