Metabolic Management
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November 15, 2024

Patients Over 40 With Elevated Cholesterol Should Consider These 5 Lab Tests Yearly

Medically Reviewed by
Updated On
November 20, 2024

Elevated cholesterol is a common health concern, affecting 73.5 million American adults. As cholesterol levels rise, so does cardiovascular disease (CVD) risk. For example, people with high cholesterol have twice the risk for heart disease compared to people with normal levels. 

However, as our understanding of CVD expands, we recognize that cholesterol is just one factor among many that determines cardiovascular risk. Genetic predisposition, lifestyle factors, inflammation, thyroid function, glucose metabolism, and liver health all contribute to an individual's overall heart health. 

Relying solely on traditional lipid panels may not accurately represent cardiovascular risk, especially for patients over 40 with overlapping risk factors. To thoroughly evaluate and effectively manage cardiovascular risk, consider incorporating these five lab tests into routine check-ups for patients over 40 with high cholesterol. 

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Understanding Cholesterol

Cholesterol is a waxy, fat-like substance found in the blood and in every cell of the body. It maintains the integrity and fluidity of cell membranes and serves as a precursor for steroid hormones, bile acids, and vitamin D. The liver produces all the cholesterol the body needs, but it can also be obtained from animal-derived dietary sources.

There are two main types of cholesterol: 

  • Low-density lipoprotein cholesterol (LDL-C), often referred to as "bad" cholesterol
  • High-density lipoprotein cholesterol (HDL-C), known as "good" cholesterol 

Elevated levels of LDL-C can lead to the buildup of plaque in the arteries, increasing the risk of coronary artery disease, heart attack, and stroke. Conversely, HDL-C helps remove cholesterol from the bloodstream, conferring protection against CVD. (36) 

The American College of Cardiology and the American Heart Association (ACC/AHA) emphasize managing blood cholesterol levels to prevent atherosclerotic cardiovascular disease (ASCVD). They recommend regular monitoring and lifestyle modifications, including diet and exercise, to maintain healthy cholesterol levels.

Why Monitor Cholesterol in Patients Over 40?

Elevated LDL-C is a well-established risk factor for ASCVD. Studies consistently show that higher LDL-C levels correlate with increased rates of ASCVD events and cardiovascular mortality:

  • A meta-analysis involving over 1.2 million participants demonstrated that LDL-C levels ≥ 130 mg/dL were associated with a higher risk of all-cause mortality and CVD events compared to LDL-C levels of 70-129 mg/dL.
  • A study with a median follow-up of 26.8 years found that LDL-C levels ≥ 160 mg/dL were independently associated with a 50-80% increased relative risk of cardiovascular mortality.

The risk of high cholesterol increases with age. Physiological changes, such as changes in cholesterol synthesis, lipid metabolism, and hormonal shifts, contribute to higher cholesterol levels as an individual ages. This is why the 2018 AHA/ACC guidelines emphasize ASCVD risk assessment and management in adults aged 40 to 75. 

Top 5 Annual Lab Tests for Patients Over 40 with Elevated Cholesterol

These five lab tests should be ordered at least once a year for patients over 40 with high cholesterol.

Lipid Panel

A lipid panel is a routine blood test that measures the amount of lipids in the blood. A basic lipid panel will include: 

  • Total cholesterol (TC)
  • LDL-C
  • Very-low-density lipoprotein cholesterol (VLDL-C)
  • HDL-C
  • Triglycerides (TG)

Why It's Important

  • Risk Assessment: It helps identify individuals at high risk for atherosclerotic ASCVD and guides the initiation of preventive measures, such as lifestyle modifications and statin therapy. (15, 51) 
  • Monitoring Therapy: It is used to monitor the effectiveness of lipid-lowering therapies and make necessary treatment adjustments. (5, 51) 

Frequency of Ordering a Lipid Panel

  • The ACC and AHA recommend that adults aged 40 to 75 undergo a lipid panel every 4 to 6 years if they are not on lipid-lowering therapy (10). 
  • For patients on statin therapy, a lipid panel should be obtained at baseline, 4-12 weeks after initiation or dose adjustment, and then every 3-12 months as needed to monitor response and adherence (51). 

Examples of Lipid Panels

High-sensitivity C-reactive Protein (hs-CRP)

hs-CRP is an inflammatory biomarker that measures low levels of C-reactive protein in the blood, which is produced by the liver in response to inflammation. It is a more sensitive measure than standard CRP tests and can detect lower levels of inflammation.

Why It's Important

hs-CRP is a strong independent predictor of future cardiovascular events, including myocardial infarction (heart attack) and stroke, even in individuals without overt hyperlipidemia. Elevated hs-CRP levels indicate a higher risk of ASCVD due to underlying inflammation. (69, 70) 

The JUPITER trial demonstrated that statin therapy significantly reduces cardiovascular events in patients with elevated hs-CRP (>2 mg/L) but normal LDL-C levels (<130 mg/dL). This suggests that hs-CRP can help identify patients who may benefit from statin therapy despite not meeting traditional cholesterol criteria. (48) 

Examples of hs-CRP Tests

Thyroid Function Tests 

Thyroid function tests are a series of blood tests used to evaluate the function of the thyroid gland. These tests typically include measurements of:

  • Thyroid-stimulating hormone (TSH)
  • Free thyroxine (fT4)
  • Free triiodothyronine (fT3)

Why It's Important

Thyroid hormones heavily influence lipid metabolism. Hypothyroidism, characterized by elevated TSH and low fT4/fT3, is associated with increased levels of TC, LDL-C, and TG and decreased levels of HDL-C. This relationship is well-documented in the literature, including studies showing that even within the euthyroid range, variations in thyroid hormone levels can influence lipid profiles. (52, 55, 84, 85) 

Thyroid dysfunction should be ruled out as a contributing factor in patients with high cholesterol. Even subclinical hypothyroidism, where TSH is elevated, but fT4 and fT3 are within normal ranges, can also lead to dyslipidemia and increased cardiovascular risk (44). Identifying and treating thyroid dysfunction can help normalize lipid levels and reduce cardiovascular risk.

Frequency of Thyroid Function Testing

Order thyroid function tests at baseline in patients with high cholesterol to identify any underlying thyroid dysfunction. 

The American Thyroid Association recommends screening for thyroid dysfunction every five years in adults, beginning at 35 years. Individuals at high risk for thyroid disorders should be screened more frequently.

If thyroid dysfunction is detected and treated, thyroid hormone levels should be rechecked 6-10 weeks after initiating or modifying treatment, and subsequently every 6-12 months as long as the patient remains stable.

Examples of Thyroid Function Tests

Liver Function Tests 

Liver function tests (LFTs) are blood tests that measure various enzymes produced by the liver. These tests typically include: 

  • Alanine transaminase (ALT)
  • Aspartate transaminase (AST)
  • Alkaline phosphatase (ALP)
  • Gamma-glutamyl transferase (GGT)

Why It's Important

The liver plays a central role in cholesterol synthesis and metabolism. Elevated LFTs can indicate liver dysfunction, such as metabolic-associated fatty liver disease (previously termed non-alcoholic fatty liver disease), which can adversely affect lipid profiles and the body's ability to manage cholesterol.

Assessing and monitoring liver function is also important for patients who require statin therapy. Statins can cause mild elevations in liver enzymes, and monitoring helps ensure that these elevations do not progress to significant liver injury.

Examples of Liver Function Tests

Blood Glucose and Hemoglobin A1c

Blood glucose tests measure the concentration of sugar in the blood at a specific point in time. Tests can either be fasting or random (non-fasting). Elevated blood glucose levels can indicate impaired glucose metabolism, which often coexists with dyslipidemia and increases cardiovascular risk. (12) 

Hemoglobin A1c (HbA1c) measures the percentage of glycated hemoglobin to reflect the average blood glucose levels over the past 2-3 months. It is a reliable marker for chronic hyperglycemia and is used to diagnose diabetes (≥6.5%) and prediabetes (5.7%- 6.4%).

Why It's Important

Hyperglycemia is another major risk factor for CVD. Elevated HbA1c levels are associated with atherogenic dyslipidemia – patients with elevated HbA1c tend to also have higher TC, LDL-C, and TG. 

Effective management of both dyslipidemia and hyperglycemia can significantly reduce the risk of cardiovascular events. Studies demonstrate that improved glycemic control can lead to atheroprotective changes in lipid profiles.

Frequency of Measuring Blood Sugar

According to the American Diabetes Association (ADA), screening for diabetes should begin at age 35 for all adults. If results are normal, testing should be repeated at a minimum of three-year intervals. More frequent testing may be considered based on initial results and risk status. 

Those with prediabetes should be tested annually to monitor blood sugar control and prevent progression to diabetes (68).

HbA1c should be measured in patients who have been diagnosed with diabetes at least twice a year if they are stable and meeting treatment goals and quarterly (every three months) if therapy changes or goals are not being met (4). 

Examples of Blood Glucose and HbA1c Tests

Additional Lab Tests to Consider

Innovations in lipid profiling provide a more nuanced understanding of cardiovascular risk compared to traditional lipid panels. Novel biomarkers offer deeper insights into cardiovascular risk.

Lipoprotein(a)

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein associated with increased ASCVD risk. Elevated Lp(a) levels (>50 mg/dL or >125 nmol/L) are considered a risk-enhancing factor, particularly in individuals with a family history of premature ASCVD or unexplained personal history of ASCVD. Measuring Lp(a) can help stratify cardiovascular risk and guide more aggressive lipid-lowering therapy. (50, 64) 

Examples of Lp(a) Tests

Apolipoprotein B

Apolipoprotein B [ApoB] represents the total number of atherogenic lipoprotein particles, including LDL, VLDL, and intermediate-density lipoprotein (IDL). ApoB is a better predictor of ASCVD risk than LDL-C, especially in patients with hypertriglyceridemia or metabolic syndrome. An ApoB level >130 mg/dL is considered a risk-enhancing factor and can guide the intensification of lipid-lowering therapy. (42, 77) 

Examples of ApoB Tests

Homocysteine Levels

Homocysteine is an amino acid linked to endothelial damage and atherogenesis. Elevated homocysteine levels (>15 µmol/L) are associated with increased ASCVD risk, although lowering homocysteine levels has not consistently shown a reduction in cardiovascular events. (63, 67)

Examples of Homocysteine Tests

Coronary Artery Calcium Score

Coronary artery calcium (CAC) score quantifies the burden of coronary atherosclerosis and is a strong predictor of future cardiovascular events. A CAC score of 0 indicates a low risk of cardiovascular events, while higher scores indicate higher risk and the need for more aggressive preventive measures. CAC scoring is particularly useful in intermediate-risk patients to refine risk assessment and guide treatment decisions. (75)

Blood Pressure Monitoring

Hypertension is another significant risk factor for ASCVD, and the cooccurrence of high blood pressure with high cholesterol synergistically increases the risk of cardiovascular events. Adequate blood pressure (BP) management mitigates this risk and improves cardiovascular outcomes. 

Non-Hypertensive Patients

The U.S. Preventive Services Task Force (USPSTF) recommends annual screening for hypertension for adults aged 40 years or older and for those who are at increased risk for high blood pressure. 

Hypertensive Patients

Once hypertension is diagnosed, BP should be monitored more frequently. The guidelines recommend follow-up visits every 1-6 months (depending on the therapeutic interventions used to treat) until blood pressure is controlled. After achieving the target BP, follow-up visits can be spaced out. (89) 

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Key Takeaways

  • Managing elevated cholesterol is crucial for individuals over 40 to reduce the risk of cardiovascular diseases and prevent adverse cardiovascular events.
  • Regular lab testing, including lipid panels, hs-CRP, thyroid function tests, liver function tests, blood sugar, and blood pressure monitoring, provides the required information to stratify cardiovascular risk.
  • By understanding and interpreting these test results, healthcare providers can develop personalized heart-healthy treatment plans that incorporate dietary modifications, physical activity, medications, and lifestyle changes to optimize lipid profiles and reduce overall risk for cardiovascular disease.
The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.

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Jaime Cloyd
Author
Dr. Jaime Cloyd ND
Naturopathic Physician based in the greater Seattle area
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