Cardiovascular disease (CVD) is the leading cause of mortality in the world, responsible for 17.9 million deaths annually and 31% of deaths globally. This article will discuss a crucial aspect of cardiac risk assessment: advanced lipid testing.
While traditional cholesterol tests offer valuable insights, advanced lipid testing provides a more detailed look at cardiovascular health. This article describes how these tests function, what they measure, and, most importantly, how they empower individuals to understand and manage their cardiac risk.
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Traditional vs. Advanced Lipid Testing
The standard lipid panel includes total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides.
While this panel is crucial for understanding CVD health, it has the potential to misclassify CVD risk, thereby leading to mismanagement and increased mortality (21).
Advanced lipid testing provides greater insight into CVD risk by assessing more specific lipid particles in the bloodstream. It evaluates the size, density, core lipid composition, and particular apolipoproteins involved in the pathogenesis of atherosclerosis and CVD (42).
Key Components of Advanced Lipid Testing
The following advanced lipid markers are essential for assessing cardiovascular health.
LDL Particle Number (LDL-P)
What is this marker?
Low-density lipoprotein particle number (LDL-P) measures the concentration of LDL particles in circulation. LDL-P plays a crucial role in atherosclerosis and cardiovascular disease progression and can be more accurate in diagnosing CVD risk than LDL cholesterol (45).
Why is this an important marker to measure?
The development of atherosclerosis depends on inflammation levels (hs-CRP), insulin resistance, and lipid levels.
LDL is the traditional biological marker for CVD risk. LDL does not account for insulin resistance and can be normal in patients who are still at risk for a cardiovascular event (stroke, heart attack, aneurysm).
LDL-P is more accurate in predicting CVD risk than LDL because it measures the number of atherogenic particles in the blood (47).
HDL Particle Size
What is this marker?
High-density lipoprotein (HDL), or the "good cholesterol," assists in removing atherogenic lipids from the bloodstream. HDL particles can vary in size, with some larger and others smaller.
The size of HDL particles is inversely related to the risk of CVD, with larger HDL particles associated with reduced cardiovascular risk and smaller HDL particles associated with increased risk of CVD (36).
Why is this an important marker to measure?
Measuring HDL particle size can provide valuable insights into an individual's cardiovascular health and risk of heart disease. Understanding the size of HDL particles can help guide treatment more effectively. This test can also show variations in CVD risk for those with normal HDL levels (36).
Lipoprotein(a), or Lp(a)
What is this marker?
Lipoprotein (a), also known as Lp(a), is a form of LDL that is a genetic risk factor for developing atherosclerosis, coronary artery disease, thrombosis, and stroke.
Lp(a) levels are highly correlated with LPA gene mutations. Lp(a) induces atherosclerosis by reducing fibrinolysis, a process that prevents blood clots from growing. Lp(a) also enhances the production of foam cells, which are responsible for plaque formation (26).
Why is this an important marker to measure?
Lp(a) is an important screening tool for those with a family history of cardiovascular disease without other major risk factors. Lp(a) is considered one of the most atherogenic particles in circulation and helps identify patients who may need more intensive lipid-lowering therapy (26).
Apolipoproteins ApoB and ApoA-I
What are these markers?
Apolipoprotein B (ApoB) plays a chief role in plaque formation and contributes to atherogenesis and cardiovascular disease risk. ApoB is a carrier molecule for "bad" cholesterol, such as LDL, very low-density lipoprotein (VLDL), and low-density lipoprotein (IDL).
ApoB levels indicate the atherogenic particle concentration of total cholesterol. It predicts cardiovascular disease risk more accurately than total or LDL cholesterol (7, 26).
Apolipoprotein A1 (ApoA1) is the major protein component of HDL (good cholesterol). ApoA1 removes bad cholesterol from the body, assisting in the prevention of atherosclerosis. ApoA1 also plays a key role in mediating inflammation, immunity, and nitric oxide production (27).
Why are these important markers to measure?
Measuring ApoB and ApoA1 is essential because an individual may have normal LDL and total cholesterol. An imbalance in the ApoB/ApoA1 ratio indicates an increased risk of cardiovascular disease. The ApoB/ApoA1 ratio is a more accurate predictor of cardiovascular disease risk in those with blood lipids within the normal range (39).
How Advanced Lipid Testing Improves Cardiac Risk Assessment
Traditional lipid testing and comorbidities can be used to estimate an individual's 10-year risk for developing future cardiovascular disease. The current model of assessing CVD risk based on traditional lipid testing can misclassify up to 10% of patients.
Incorporating advanced lipid testing may improve risk estimations and identify genetic disorders that may be missed with traditional lipid testing. Utilizing Lp(a) and LDLR gene testing can help identify genetic lipid disorders that would not be diagnosed with traditional lipid testing (9).
Interpreting Advanced Lipid Test Results
Interpreting the results of advanced lipid tests can be complex. The following is a guide to understanding each value and its impact on cardiac health (28, 56):
- LDL Particle Number: A measure of the concentration of LDL particles in circulation. Elevated levels are associated with an increased risk of CAD (even with normal LDL). Elevation in LDL-P should also prompt a workup for metabolic syndrome and insulin resistance.
- HDL Particle Size: Lower HDL particle size correlates with an increased risk of CVD. Practitioners want to see HDL particle size increasing throughout lipid-lowering treatment.
- Lipoprotein (a) or Lp(a): Lp(a) is an independent genetic risk factor for CVD, with little to no influence by lifestyle factors. Inflammatory conditions such as pregnancy, hypothyroidism, growth hormone therapy, and kidney disease may cause elevation.
- ApoB & ApoA1 Ratio: These two markers are generally reported as a ratio. ApoB measures the particles that lead to atherosclerosis, and ApoA1 measures the particles within HDL particles, which aid in removing bad cholesterol from the body. A lower ratio correlates with a lower risk of CVD.
Using Advanced Lipid Tests to Guide Treatment
Lifestyle Modifications
- Regular physical activity increases HDL, aiding in eliminating LDL particles from circulation. To support healthy lipid levels, 150 minutes of moderate-intensity exercise per week is recommended.
- Obesity contributes to elevated lipids through various mechanisms. Weight loss and following a healthy diet increase the proportion of large HDL-P, which is associated with decreased CVD risk.
- LDL particles are more sensitive to dietary modification than other lipid markers. Following a Mediterranean diet can help decrease the number of LDL particles in circulation.
- Reduce alcohol intake: For those with elevated lipid profiles, it is recommended to consume less than 10 g/day (1 drink).
(28)
Pharmacological Interventions
- According to the ASCVD Risk Calculator, statin therapy is the first line of treatment for individuals whose LDL is greater than 190mg/dL, those with diabetes mellitus, and those 40-75 years of age at high risk (6).
- PCSK9 inhibitors are recommended for patients with genetic familial hypercholesterolemia (LPA gene mutation, PCSK9 gene mutation, APOE gene mutation).
- For elevated Lp(a) levels, niacin, PCSK9 inhibitors, and Mipomersen have shown a reduction in Lp(a) levels.
- Nicotinic acid, statins, and bile acid sequestrants are recommended for patients with elevated LDL particle numbers.
- Statins show minimal effects on patients with decreased large HDL particle levels; thus, nicotinic acid and fibrates are recommended.
- Bile acid sequestrants and nicotinic acid are recommended for patients with elevated ApoB levels. (46)
How to Get Advanced Lipid Testing
Rupa Health offers various options for advanced lipid testing:
- CardioPro Advanced by Access Med Labs
- Cardiovascular Risk Profile by Doctor's Data
- CardioMetabolic - Expanded by BostonHeart Diagnostics
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Key Takeaways
- Advanced lipid testing offers a comprehensive cardiac risk assessment beyond a traditional cholesterol panel.
- Analysis of LDL particle size, genetic mutations, and HDL functionality provides a more detailed understanding of individuals' risk factors for heart disease.
- Incorporating lifestyle changes, such as physical exercise and proper diet, is essential in preventing cardiovascular disease.
- Discuss advanced lipid testing with your provider to tailor specific strategies and treatment plans to enhance cardiovascular health.
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