Introduction
Establishing individualized reference values
Core laboratory panels
Useful add-on panels based on risk
Emerging and optional advanced biomarkers
References
Further reading
Why smarter baseline lab testing, grounded in biological variation and clinical evidence, matters more than broad annual screening panels.
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Introduction
Routine annual examinations often fail to improve patient outcomes and may even lead to overdiagnosis. Consequently, regulatory bodies such as the United States Preventive Services Task Force (USPSTF) now prioritize targeted, risk-based screening rather than indiscriminate testing.1
This article discusses recent evidence from both peer-reviewed research and public health agency recommendations to distinguish between medically necessary screening and actionable health monitoring.
Establishing individualized reference values
A critical limitation of conventional laboratory reporting is the reliance on population-based reference intervals that are typically based on data from the central 95% of a healthy population. However, growing evidence indicates that the range of values for a specific analyte within-subject biological variation (CVI) is narrower.2
For example, a systematic review and meta-analysis of biological variation previously established that the CVI for serum creatinine is approximately 5%. Based on this tight homeostatic control, the reference change value (RCV) for estimated glomerular filtration rate (eGFR) is conservatively estimated at approximately ±12.5%.2
Consequently, a rise in creatinine from 0.8 mg/dL to 1.0 mg/dL represents a statistically significant decline in renal function, even if both values remain within the normal population range of 0.6–1.2 mg/dL.2
Family history, chronic conditions, and new lifestyle interventions
Baseline testing is strongly recommended for individuals with genetic predispositions to chronic diseases, particularly cardiovascular diseases (CVDs) and diabetes, where early deviations from individual baselines may inform preventive care strategies.1
Public health agencies further support baseline testing and follow-up in individuals with chronic conditions or those experiencing major lifestyle transitions, such as weight loss or intensive physical training, which can meaningfully alter metabolic parameters.1,5
Core laboratory panels
Core laboratory panels refer to standardized groupings of diagnostic tests that constitute the foundation of metabolic baseline health.
Complete blood count (CBC)
The CBC metric is used to quantify an individual’s oxygen-carrying capacity, immune status, and hemostatic potential. The CBC includes indices such as mean corpuscular volume (MCV) and red cell distribution width (RDW), which provide mechanistic insights into an individual’s hematopoietic health.1
CBC also measures the white blood cell (WBC) differential that encompasses immune cells like neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Persistent deviations in specific subtypes may indicate allergic disease, chronic infection, or inflammatory conditions.4
Recent evidence-based clinical guidelines emphasize that ferritin levels should be assessed in conjunction with hemoglobin, as iron deficiency can present with nonspecific symptoms like fatigue before anemia develops.4
Full blood count – what it tells your doctor about your health
Comprehensive metabolic panel (CMP)
The CMP consists of a series of tests that assess renal filtration, hepatic integrity, electrolyte levels, and glucose concentrations. Kidney function assessment is based on blood urea nitrogen (BUN), creatinine, and estimated glomerular filtration rate (eGFR). Since creatinine has a low CVI of about 5%, establishing a baseline is crucial for detecting early deviations.2
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular injury. Persistent elevations may warrant further evaluation for underlying metabolic or hepatic conditions.1
Lipid profile
CVD remains the leading cause of death globally, thus emphasizing the importance of routine lipid assessments for mitigating both the direct burden of CVD and its numerous comorbidities. Lipid profile tests include atherosclerotic CVD (ASCVD) predictors like low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and non-HDL cholesterol.
Non-HDL cholesterol, calculated by subtracting HDL from total cholesterol, is increasingly recognized as a significant predictor of CVD risk because it encompasses all atherogenic lipoproteins. Evidence demonstrates that nonfasting lipid measurements provide clinically acceptable accuracy for LDL-C estimation, particularly when modern calculation methods are used.6
HbA1c and fasting glucose
Hemoglobin A1c (HbA1c) is widely used for diabetes screening in clinical practice. HbA1c levels exceeding 6.5% indicate diabetes, whereas values between 5.7% and 6.4% reflect prediabetes.1
Thyroid function tests
Thyroid-stimulating hormone (TSH) is the primary laboratory marker for thyroid dysfunction. While population-wide screening in asymptomatic adults remains controversial, targeted testing is commonly applied in individuals with symptoms or clinical risk factors.1
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Useful add-on panels based on risk
Vitamin D
The 2024 Endocrine Society Clinical Practice Guidelines recommend against routine 25-hydroxyvitamin D testing in healthy populations aged 75 or younger, given the lack of clear benefit for disease prevention. However, for higher-risk groups such as pregnant individuals, adults aged 75 years and older, and those with high-risk prediabetes, empiric supplementation without routine testing may reduce adverse outcomes.7
Inflammation Markers: hs-CRP
The 2025 Scientific Statement from the American College of Cardiology (ACC) identifies high-sensitivity C-reactive protein (hs-CRP) as a validated marker of residual inflammatory risk, particularly in individuals with well-controlled LDL-C.3
In the JUPITER trial, rosuvastatin therapy among individuals with normal LDL-C but elevated hs-CRP resulted in a significant reduction in the primary combined endpoint compared with placebo, demonstrating the utility of hs-CRP in refining cardiovascular risk stratification.3
Iron studies
Ferritin is the most sensitive conventional test for iron stores, with values below 30 µg/L diagnostic of iron deficiency in adults. Contemporary guidance emphasizes that iron deficiency – particularly in females – often precedes anemia and warrants early detection and treatment.4
Emerging and optional advanced biomarkers
ApoB and lipoprotein(a)
Apolipoprotein B (ApoB) provides a direct measurement of atherogenic particle number. Research indicates that a lower LDL-C/ApoB ratio is an independent predictor of cardiovascular and all-cause mortality, reflecting discordance between cholesterol mass and particle burden.8
Lipoprotein(a) is a genetically determined risk factor implicated in ASCVD. Specifically, each 50 nmol/L increment in lipoprotein(a) has been associated with an approximately 11% increased risk of ASCVD.9
References
- Araujo, G. C., Ribeiro, C. B., Costa, M. C. M., et al. (2025). Evidence-Based Periodic Health Examinations for Adults: A Practical Guide. Cureus. DOI:10.7759/cureus.79963, https://www.cureus.com/articles/344597-evidence-based-periodic-health-examinations-for-adults-a-practical-guide#!/
- Thöni, S., Keller, F., Denicolò, S., et al. (2022). Biological variation and reference change value of the estimated glomerular filtration rate in humans: A systematic review and meta-analysis. Frontiers in Medicine 9. DOI:10.3389/fmed.2022.1009358, https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.1009358/full
- Mensah, G. A., Arnold, N., Prabhu, S. D., et al. (2025). Inflammation and Cardiovascular Disease: 2025 ACC Scientific Statement. JACC. DOI:10.1016/j.jacc.2025.08.047, https://www.sciencedirect.com/science/article/pii/S0735109725075552
- Sholzberg, M., Hillis, C., Crowther, M., & Selby, R. (2025). Diagnosis and management of iron deficiency in females. Canadian Medical Association Journal 197(24); E680-E687. DOI:10.1503/cmaj.240570, https://www.cmaj.ca/content/197/24/E680
- American Diabetes Association Professional Practice Committee for Diabetes (2025). Introduction and Methodology: Standards of Care in Diabetes – 2026. Diabetes Care 49(1) S1–S5. DOI:10.2337/dc26-sint, https://diabetesjournals.org/care/article/49/Supplement_1/S1/163916/Introduction-and-Methodology-Standards-of-Care-in
- Sathiyakumar, V., Park, J., Golozar, A., et al. (2018). Fasting Versus Nonfasting and Low-Density Lipoprotein Cholesterol Accuracy. Circulation 137(1); 10-19. DOI:10.1161/circulationaha.117.030677, https://www.ahajournals.org/doi/10.1161/circulationaha.117.030677
- Demay, M. B., Pittas, A. G., Bikle, D. D., et al. (2024). Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism 109(8); 1907-1947. DOI:10.1210/clinem/dgae290, https://academic.oup.com/jcem/article/109/8/1907/7685305
- Xiao, L., Zhang, K., Wang, F., et al. (2023). The LDL-C/ApoB ratio predicts cardiovascular and all-cause mortality in the general population. Lipids in Health and Disease 22(1). DOI:10.1186/s12944-023-01869-1, https://lipidworld.biomedcentral.com/articles/10.1186/s12944-023-01869-1
- Al-Dalakta, A., Cho, L. S., & Sarraju, A. (2025). Lipoprotein(a) in clinical practice: What clinicians need to know. Cleveland Clinic Journal of Medicine 92(11); 679-685. DOI:10.3949/ccjm.92a.25020, https://www.ccjm.org/content/92/11/679
- Drago, L. (2025). Navigating microbiome variability: implications for research, diagnostics, and direct-to-consumer testing. Frontiers in Microbiology 16. DOI:10.3389/fmicb.2025.1580531, https://www.frontiersin.org/articles/10.3389/fmicb.2025.1580531/full
Further Reading
Last Updated: Jan 20, 2026
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