Cholesterol: Beyond the Basics

Cardiovascular disease (CVD) remains the leading cause of death worldwide. One in every five deaths (22%) in the US is due to heart disease.¹ An estimated 80% or more of cardiovascular disease is preventable, making this a critical area of intervention for health care providers.² Blood lipid management remains a cornerstone of prevention, and healthcare providers are a critical part of dietary and lifestyle education and interventions. 

While traditional cholesterol measures are important, current guidelines emphasize an individualized approach that considers additional biomarkers, family history, lifestyle, and overall cardiometabolic risk.^3,4 Patients are also increasingly seeking advanced testing through direct-to-consumer laboratory companies, bringing new questions into clinical practice.⁵ This review highlights key lipid markers and evidence-based nutrition and exercise strategies that healthcare providers can use to support cardiovascular health.

Cholesterol Basics

Cholesterol is essential for hormone production, vitamin D synthesis, cell membrane integrity, and bile acid production.⁶ Elevated levels of atherogenic lipoproteins (which carry cholesterol and contribute to plaque buildup in the arteries) increase the risk of atherosclerotic cardiovascular disease (ASCVD).^7,8

Risk increases with age, and females often experience a rise in LDL cholesterol after menopause as estrogen levels decline.^2,7,8 Genetics also play an important role, with familial hypercholesterolemia and elevated lipoprotein(a) [Lp(a)] increasing lifetime cardiovascular risk regardless of lifestyle.^2,7,8

Traditional lipid testing^2,6-8 

Marker	Ideal Range	Clinical Significance
Total Cholesterol	<200 mg/dL desirable	A general screening marker that should be interpreted in addition to LDL-C, HDL-C, triglycerides, and overall ASCVD risk.
LDL Cholesterol (LDL-C)	<100 mg/dL optimal (<70 mg/dL for patients at very high ASCVD risk)	Primary target of most lipid-lowering therapies because elevated LDL-C promotes atherosclerotic plaque formation (the buildup of cholesterol-rich deposits within artery walls).
HDL Cholesterol (HDL-C)	≥50 mg/dL (females)≥40 mg/dL (males)	Lower HDL-C is associated with increased cardiovascular risk.
Triglycerides	<150 mg/dL normal	Elevated triglycerides are associated with increased ASCVD risk and often occur with other cardiometabolic risk factors (insulin resistance, type 2 diabetes(DMII)/blood sugar dysregulation, etc)

Emerging Markers and Considerations

The 2026 Guideline on the Management of Dyslipidemia, developed by the American College of Cardiology and American Heart Association in collaboration with several other professional organizations, replaces the 2018 Guideline on the Management of Blood Cholesterol.^2,7,8 Although LDL-C remains a primary treatment target, the updated guideline also addresses triglyceride-rich remnant particles, non-high-density lipoprotein cholesterol, apolipoprotein B (apoB), and Lp(a).^2,7,8,10

The new recommendations emphasize earlier risk assessment and intervention, renewed low-density lipoprotein and non-high-density lipoprotein treatment goals, using the Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) risk calculator, Lp(a) testing, selective apoB measurements, and expanded use of coronary artery calcium (CAC) scoring.^2,7,8,10 It’s critical that the interdisciplinary health care team stay aware of these updates and changes to stay relevant and provide the most modern care possible. Consider the following when supporting patients with cardiovascular risk or questions: 

Emerging cardiovascular testing^2,7,8,10,11 

Marker	Ideal Range/ Threshhold	Clinical Significance	Testing
Apolipoprotein B (ApoB)	Individualized based on ASCVD risk	Reflects the total number of atherogenic lipoprotein particles (those that carry cholesterol and can contribute to plaque buildup in the arteries) and may better predict ASCVD risk than LDL-C alone, especially in patients with metabolic syndrome or DMII.	ApoB may help identify cardiovascular risk after LDL-C and non-HDL-C goals are met.
Lipoprotein(a) [Lp(a)]	<125 nmol/L or <50 mg/dL	Genetically determined lipoprotein associated with premature cardiovascular disease. Levels ≥125 nmol/L or ≥50 mg/dL are associated with ~1.4-fold higher long-term cardiovascular risk, while 250 nmol/L is associated with at least twice the risk.	Current guidelines recommend measuring Lp(a) at least once in adulthood, especially for patients with a strong family history of early ASCVD. Lifestyle interventions have little to no effect on Lp(a), so repeat testing is generally not needed.
LDL particle number (LDL-P) + particle size	No standardized target	Provides additional information about lipoprotein burden. Small, dense LDL particles are associated with increased cardiovascular risk because they remain in circulation longer, oxidize more readily, and bind more strongly to arterial walls.	Testing methods are not standardized, and it remains unclear whether measuring LDL particle number and size improves risk assessment beyond ApoB and other established markers.
Coronary artery calcium (CAC) scan	CAC score = 0 indicates no detectable coronary calcium	Non-contrast CAC scanning can detect subclinical plaque when cardiovascular risk remains uncertain or other risk factors are present.	This test can help guide statin decisions in women ≥45 and men ≥40 who have borderline or intermediate 10-year risk levels.

Other biomarkers include:

• High-sensitivity C-reactive protein (hs-CRP): A marker of systemic inflammation associated with inflammation-related ASCVD risk.(Alebna) <2 mg/L is considered lower risk, while ≥2 mg/L is an ASCVD risk-enhancing level.¹²
  
  
• Homocysteine: Produced by the metabolism of the amino acid methionine, elevated concentrations have been linked to an increased risk for coronary heart disease, heart failure, stroke, and mortality.^13,14In a study (N=6,765 participants) elevated total homocysteine (>12 μmol/L) was associated with a greater risk of heart failure and heart failure with preserved ejection fraction, especially in people with impaired fasting glucose or type 2 diabetes.¹⁴
  
  
• Omega-3 Index and omega-6:omega-3 ratio: These may offer insight into dietary fat intake and inflammation, but standardized clinical use continues to evolve. Higher intake or circulating levels of Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with reduced cardiovascular event risk, improved lipid levels, inflammation, platelet function, and endothelial function.¹⁵ High-dose supplementation may increase atrial fibrillation risk.¹⁵ A meta-analysis (N=20 randomized controlled trials with 2,676 participants) found that omega-3 supplementation significantly reduced homocysteine by ~1.34 μmol/L (P<0.001), with greater reductions observed with shorter interventions (<12 weeks) and doses of 3 g/day.¹³

Patients are increasingly arriving with laboratory reports from companies offering expanded biomarker panels and may have questions about interpretation and its impact on their cardiovascular risk. Providers can help interpret results within the broader context of cardiovascular risk, clinical history, and current evidence-based practice.

Nutrition Strategies for Cholesterol Management

The 2026 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association outlines nine features of a heart-healthy dietary pattern: balance energy intake and expenditure to maintain a healthy body weight; eat plenty of vegetables and fruits; choose mostly whole grains; choose healthy protein sources; replace saturated fats with unsaturated fats; choose minimally processed foods over ultraprocessed foods; minimize added sugars; reduce sodium; and, if alcohol is not consumed, do not start, or limit intake if it is consumed.¹⁶

High-fiber, plant-forward, minimally processed dietary patterns such as the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and vegetarian/vegan diets are examples of evidence-based patterns shown to improve lipid profiles while supporting blood pressure, glycemic control, and weight management.¹⁷ 

Replacing saturated fat with unsaturated fats remains one of the strongest dietary recommendations. The American Heart Association recommends limiting saturated fat to less than 6% of total daily calories for patients who need to lower LDL-C.¹⁸ Consider substitutions such as olive oil, avocado, nuts, seeds, and fatty fish in place of butter, processed meats, and high-fat animal products.

In a study (N=6,645 adults with high cholesterol), participants were advised to eat less fat, and 80.9% reported following the advice.¹⁹ Compared with non-adherents, adherents to the lower-fat diet had lower LDL-C by 0.16 mmol/L (~6.2 mg/dL), as well as lower total cholesterol, non-HDL-C, and total cholesterol/HDL-C ratio, and higher HDL-C.¹⁹

Exercise and Cardiometabolic Health

Regular physical activity remains one of the most effective lifestyle interventions for reducing cardiovascular risk.¹ This is a place where healthcare providers can educate and help patients set goals around increasing their fitness. 

Aerobic exercise can lower triglycerides, modestly increase HDL-C, improve insulin sensitivity, and support weight management. Current recommendations advise at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous activity per week, plus muscle-strengthening exercise on two or more days weekly.²⁰

A meta-analysis (N=148 randomized controlled trials with 8,673 participants) found that aerobic, resistance, and combined exercise training significantly improved lipid levels: total cholesterol −5.9 mg/dL, LDL-C −7.2 mg/dL, triglycerides −8.0 mg/dL, and HDL-C +2.1 mg/dL.²¹ Combined aerobic and resistance training was the most effective for managing dyslipidemia in this analysis.²¹

Key Takeaways for Practitioners

Cholesterol management has evolved beyond simply lowering LDL-C – though that also remains important. Traditional lipid panels remain the foundation of cardiovascular risk assessment, but biomarkers such as ApoB and Lp(a) can provide additional insight for patients with a strong family history or other risk factors. 

Lifestyle interventions should continue to serve as first-line therapy for most patients, with an emphasis on overall dietary patterns and consistent physical activity. Making and sustaining dietary and lifestyle changes can be difficult for patients, highlighting an important opportunity for healthcare providers to offer goal setting, accountability, and ongoing education.^17,19

Healthcare providers can help patients interpret the growing number of advanced laboratory tests and direct-to-consumer results within the context of evidence-based care, while recognizing when pharmacologic therapies are appropriate. Ultimately, individualized recommendations that combine nutrition, exercise, clinical risk factors, and patient preferences remain the most effective strategy for reducing long-term cardiovascular risk.

References

1. Centers for Disease Control and Prevention. About heart disease. Updated May 15, 2024. Accessed August 2, 2026. https://www.cdc.gov/heart-disease/about/index.html
2. American Heart Association. ACC/AHA issue updated guideline for managing lipids, cholesterol. Published November 10, 2018. Accessed May 16, 2026. https://newsroom.heart.org/news/accaha-issue-updated-guideline-for-managing-lipids-cholesterol
3. Piazza G, Desai NR, Baber U, Exter J, Kalich B, Monteleone P. Practical solutions for implementation of blood cholesterol guidelines in clinical practice. Trends in Cardiovascular Medicine. 2024 Aug 1;34(6):371-8.
4. Martins J, Steyn N, Rossouw HM, Pillay TS. Best practice for LDL-cholesterol: when and how to calculate. Journal of Clinical Pathology. 2023 Mar 1;76(3):145-52.
5. Hull LE, Aday AW, Bui QM, Luzum JA, Muchira JM, Wand H, Chahal CA, Chung MK, Kwitek AE, Molossi S, Natarajan P. Direct-to-consumer genetic testing for cardiovascular disease: A scientific statement from the American Heart Association. Circulation. 2025 Apr 8;151(14):e905-17.
6. American Heart Association. What is cholesterol? Last reviewed March 13, 2026. Accessed August 13, 2026. https://www.heart.org/en/health-topics/cholesterol/about-cholesterol
7. Wiggins BS, Barac A, Benziger CP, et al. 2026 dyslipidemia guideline-at-a-glance. J Am Coll Cardiol. 2026;87(19):2617-2623.
8. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. JACC. 2026;87(19):2624-2757.
9. American Heart Association. What your cholesterol levels mean. Reviewed March 16, 2026. Accessed August 2, 2026. https://www.heart.org/en/health-topics/cholesterol/about-cholesterol/what-your-cholesterol-levels-mean
10. Alebna PL, Han CY, Ambrosio M, et al. Association of lipoprotein (a) with major adverse cardiovascular events across hs-CRP: a systematic review and meta-analysis. JACC: Advances. 2024 Dec 1;3(12_Part_1):101409.
11. Krauss RM. Small dense LDL particles: Clinically relevant? Current Opinion in Lipidology. 2022 Mar 11;33(3):160.
12. Mehta A, Blumenthal RS, Gluckman TJ, Feldman DI, Kohli P. High-sensitivity C-reactive protein in atherosclerotic cardiovascular disease: to measure or not to measure? US Cardiology Review. 2025 Mar 21;19:e06.
13. Sohouli MH, Roshan MM, Olusola OF, et al. Impact of Omega-3 supplementation on homocysteine levels in humans: A systematic review and meta-regression analysis of randomized controlled trials. Nutrition, Metabolism and Cardiovascular Diseases. 2022 Sep 1;32(9):2013-25.
14. Karger AB, Nomura SO, Guan W, et al. Association between elevated total homocysteine and heart failure risk in the multi-ethnic study of atherosclerosis cohort. Journal of the American Heart Association. 2025 Mar 4;14(5):e038168.
15. Djuricic I, Calder PC. N-3 Fatty Acids (EPA and DHA) and Cardiovascular Health – Updated Review of Mechanisms and Clinical Outcomes. Curr Atheroscler Rep. 2025 Nov 17;27(1):116.
16. Lichtenstein AH, Khera A, Anderson CA, et al. 2026 dietary guidance to improve cardiovascular health: a scientific statement from the American Heart Association. Circulation. 2026 May 5;153(18):e1285-95.
17. Diab A, Dastmalchi LN, Gulati M, Michos ED. A Heart-Healthy Diet for Cardiovascular Disease Prevention: Where Are We Now? Vasc Health Risk Manag. 2023 Apr 21;19:237-253.
18. American Heart Association. Saturated fats. Last reviewed August 23, 2024. Accessed August 15, 2026. https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/fats/saturated-fats
19. Guo J, Sun Q, Wu C, Wu J. Adherence to lifestyle advice and its related cardiovascular disease risk among US adults with high cholesterol. Clinical Nutrition ESPEN. 2022 Oct 1;51:267-73.
20. American Heart Association. American Heart Association recommendations for physical activity in adults and kids. Last reviewed January 19, 2024. Accessed August 15, 2026. https://www.heart.org/en/healthy-living/exercise-and-physical-activity/fitness-basics/aha-recs-for-physical-activity-in-adults
21. Smart NA, Downes D, Van Der Touw T, et al. The effect of exercise training on blood lipids: a systematic review and meta-analysis. Sports Medicine. 2025 Jan;55(1):67-78.