cholesterol levels normal

There’s More to Lipids Than Cholesterol: What You Need to Know

I received a lovely message from one of you asking me some questions about cholesterol, lipids, and what all of it means. Most of the messaging about cholesterol has been caveman-esque: LDL= bad, HDL = good. But there is far more nuance that than. I did a brief introduction on cholesterol about a year ago. Given the additional question asked and my recent personal Lp(a) discovery, I decided to go a little bit deeper and translate lipid data into something that will hopefully make more sense.

Cholesterol and Triglycerides: Structural Differences and Distinct Roles

While cholesterol, triglycerides, and lipoproteins contain fat molecules, they are very different in structure and function. At the most basic level, cholesterol and triglycerides are molecules of fat. Rather than relive organic chemistry nightmares and describe the structural differences between cholesterol and triglyceride, see the pictures below.

Cholesterol

Triglyceride

The reason I include these photos is to visually demonstrate how different these two really are in structure. They are also quite different in function as well. Cholesterol is a building block and serves three primary physiologic functions: maintaining cell membrane structure, acting as a precursor for steroid hormones and vitamin D, and serving as a precursor for bile acid synthesis.1 Triglycerides are predominantly used for energy storage. They are transported to cells and then broken down through a process called lipolysis, allowing the cells to use the fatty acids (blue sections in the molecular structure above) for energy. As mentioned, these are both fat molecules which makes them hydrophobic, meaning, they don’t mix well with water. Blood is mostly water so neither cholesterol nor triglycerides can dissolve in it. This presents challenges because both need to be delivered to different parts of the body. This is where lipoproteins come into play.

What is a Lipoprotein and What Does it Do?

Lipoproteins are a combination of cholesterol and triglycerides surrounding by an apolipoprotein, which is a hydrophilic protein structure.2 To better understand a lipoprotein,  visualize a tennis ball. In the case of a lipoprotein, the inside of the ball is a combination of cholesterol and triglyceride, and the outside green part of the ball is the apolipoprotein (more or less). Packaging the cholesterol and triglycerides into a lipoprotein allows them to be transported through the blood and into their target tissues. There are many different apolipoproteins. The ones most mentioned in cardiovascular health are apolipoprotein B (apo B) and apolipoprotein (apo A). The packaging process for circulating lipoproteins occurs predominantly in the liver.

Lipoprotein Particles and Their Functions

You’ve probably heard of HDL, LDL, VLDL, and many other letter combinations when it comes to cholesterol. These are all lipoprotein particles. If we go back to the tennis ball analogy, they each are a combination of cholesterol and triglyceride packaged with an apolipoprotein. The type of apolipoprotein along with the amount of cholesterol and triglyceride determines the particle. Let’s first discuss the atherogenic ones which are the apo B particles.

Atherogenic Lipoproteins: Apo B–Containing Particles

Very low-density lipoprotein (VLDL) – These particles are made by the liver. Their cores typically contain more triglyceride than cholesterol. These particles are the main way the body receives fatty acids for energy production at the cellular level.2,3

Intermediate-density lipoprotein (IDL) – The removal of triglyceride from VLDL by muscle and adipose cells results in the formation of IDL particles. The ratio of triglyceride to cholesterol cores can vary but in general, IDLs still contain some amount of triglyceride.2

Low-density lipoprotein (LDL) – LDL is also a remnant from triglyceride removal from both VLDL and IDL particles. Their core is almost entirely cholesterol. In fact, LDL carries the majority of circulating cholesterol. While all apo B particles are atherogenic, LDL particles are more so because they are higher in quantity, easily enter the arterial walls, and get trapped within the walls. They are also more susceptible to oxidation.2

Lipoprotein a (Lp(a)) – Lp(a) is a very small LDL particle that has apolipoprotein (a) (not be confused with apo A) attached to the apo B.2 Lp(a) is genetically determined and levels currently cannot be modified with lifestyle modifications or medications, although some pharmaceutical trials are currently underway.4

High-Density Lipoprotein (HDL) and Reverse Cholesterol Transport

High-density lipoprotein (HDL) is bound to apo A not apo B. Unlike the above particles, it is not atherogenic. It is the opposite and can remove cholesterol from arterial walls through a process called reverse cholesterol transport.5 This is why HDL has been traditionally called the “good” cholesterol, but this is an over simplification of HDL. There is more nuance to all of these lipoproteins and how they affect the cardiovascular system.

Why Cholesterol Lab “Normal Ranges” Can Be Misleading

Clinical laboratory values are a bit misleading because cutoffs for normal lab values are not so clear. Instead, what is considered “normal” is based on thresholds for risk. Basically, the American Heart Association (AHA) and American College of Cardiology (ACC) published guidelines over the course of several years and in those guidelines, they identified values associated with higher risk of atherosclerotic cardiovascular disease (ASCVD). What is considered normal is really the values identified as risk factors for ASCVD. The other challenge is that those values change based on someone’s existing burden of disease.

The 2018 AHA/ACC guideline identified the following values as risk factors for ASCVD: LDL ≥160 mg/dL, apo B >130 mg/dL, triglycerides ≥200mg/dL, and Lp(a) ≥50 mg/dL or ≥125 nmol/L, HDL <40 mg/dL in men and HDL <50 mg/dL in women.6 An earlier 2011 guideline recommended LDL<70 mg/dL for patients at high risk and <100 mg/dL for everyone else.7 There is no mention of total cholesterol values or VLDL. Some of these values are inconsistent with what is considered normal clinical lab values, however. For example, LabCorp uses the following reference ranges: Lp(a) <75 nmol/L, total cholesterol <200 mg/dL, triglycerides <150 mg/dL, HDL > 40 mg/dL, VLDL <40 mg/dL, LDL <100 mg/dL, and an apo B < 90 mg/dL.

Lipoproteins and Cardiovascular Risk: Beyond LDL and HDL

The traditional thinking has been LDL is bad and leads to arterial plaque formation, while HDL is good and reverses plaques or prevents them from developing. More recent data informs us that this is just part of the picture. There is a lot more to our lipids and ASCVD.

Apolipoprotein B and Atherosclerotic Risk

Apo B plays a significant role in atherosclerosis. As previously mentioned, apolipoproteins are the particles on the outside of lipoproteins that allow lipids to circulate in the blood. Apo B is important because every atherogenic particle is attached to apo B.2 Additionally, apo B binds to proteins inside arterial walls.3,8 So apo B not only serves as a carrier particle but it is also responsible for keeping lipid particles trapped in arterial walls which is the first step of atherosclerosis.

Cholesterol alone gives an incomplete picture of what is occurring with lipids. The reason is because apo B particles can have a variable amount of cholesterol with them. Sometimes there is discordance. Someone may have an average apo B but high cholesterol. Another may have a high apo B but low cholesterol. In discordant groups with high cholesterol, but low apo B, cholesterol will predict high risk and apo B predicts low risk. In groups with low cholesterol but high apo B, the reverse is the case. One marker will be right and the other will be wrong. In these settings, apo B particles are a more accurate marker of cardiovascular risk than cholesterol.3

To better understand this, imagine apo B is a cab and cholesterol is the passenger. A high apo B with low cholesterol suggests two possible scenarios. One is that each apo B (cab) is traveling with a small amount of cholesterol (passengers). This is concerning because smaller particles pass into the arterial walls easier.3,8,9 The other explanation is there are a lot of other lipid particles traveling with apo B that aren’t otherwise measured.3,9 Many of these particles bind to the insides of arterial walls much stronger than LDL does.8 Measuring apo B gives a measure of all atherogenic particle burden.9

Lipoprotein(a): Genetic Risk and Clinical Implications

Lp(a) is six times more atherogenic than LDL particles. This is because they have a high concentration of oxidized phospholipids which increase the expression of molecules that bind to arterial walls.8 Oxidized phospholipids also trigger an inflammatory cascade that promotes calcifications associated with ASCVD.4 Lp(a) levels are genetic and there is little variability over a lifetime.4,9 It is also associated with aortic stenosis.3,10

People with plasma Lp(a) levels above 50 mg/dL (105 nmol/L) are at high risk of cardiovascular disease.10  At time of writing this blog, there are no FDA approved medications to reduce Lp(a). Monoclonal antibodies directed at a receptor called PCSK9 demonstrate dramatic lowering of LDL and 25-30% of Lp(a),4 but they are only approved for lowering LDL. Emerging RNA-based therapies show promise and are currently undergoing phase 3 clinical trials.10 As of now, the only FDA approved therapy is lipoprotein apheresis which is done every two weeks. However, data is limited on whether lowering Lp(a) reduces cardiovascular events.4 

HDL Function Versus HDL Levels

HDL is a key component of reverse cholesterol transport which removes cholesterol from arterial walls. However, high HDL doesn’t necessarily mean a high functioning reverse cholesterol transport. Several studies have demonstrated HDL function is a better predictor of cardiovascular events.11-14 Unfortunately, there are no approved assays for routine clinical use.

What Standard Lipid Panels Measure and What They Miss

Most standard lipid panels include the following: total cholesterol, LDL, VLDL, HDL and triglyceride levels. Apo B and Lp(a) are not routinely tested. In fact, current guidelines do not recommend their routine testing.6 However, without these values, the entire picture of lipid related risk for ASCVD is incomplete. I order these values on all of my patients because they are valuable data points that guide health goals and management.

How to Lower Lipids

Diet, exercise, and medications are the mainstays for lipid control. I won’t discuss medications here because that can be a blog post all on its own. The truth is medications provide the most profound reductions, but I will leave that as a discussion between you and your doctor. I will say that as a physician, I often start patients on medications, but my goal is to always keep my patients on the lowest dose possible. This is typically done with weight loss and incorporating lifestyle modifications.

Dietary interventions can reduce LDL by 30-40 mg/dL.15 The most effective diets are low in saturated fats, low in refined carbohydrates, rich in unsaturated fats and plant-based proteins, enriched with nuts and high in fiber.15 Replacing saturated fats with unsaturated fats or proteins can reduce LDL while avoiding triglyceride elevation. Triglycerides can be reduced by replacing simple, refined carbohydrates with whole grains and complex carbohydrates. Alcohol consumption can increase triglyceride levels so avoidance can improve levels. Fish oils can also decrease triglyceride levels. 16

Both aerobic and resistance training have a positive impact on lipids. A 2025 systematic review and meta-analysis found that exercise training significantly improved all five major lipid parameters. Although, all reductions were less than 10 mg/dL.17 Resistance training appears more effective for triglyceride reduction than aerobic exercise alone.18

Putting It All Together

If there is one takeaway from this deep dive, it’s that cholesterol numbers alone don’t tell the full story. Lipoproteins, apolipoproteins, and particle burden matter and in many cases, they matter more than the traditional “HDL good/LDL bad” framing most of us grew up know. Understanding cardiovascular risk requires context and individualized interpretation rather than chasing a single “perfect” number. Your lipid panel is less like a report card and more like a set of clues: genetics, metabolism, lifestyle, and long-term risk all show up in the pattern. The goal isn’t perfection. It’s better data, better questions, better goal setting, and smarter decisions made with your health care team.

Disclaimer: Even though I’m a doctor, I’m not your doctor—and reading this blog does not establish a doctor–patient relationship. This information is intended for general educational purposes only and should not be taken as personalized medical advice. Always speak with your own healthcare provider before making decisions about your health.

References

  1. Cortes VA, Busso D, Maiz A, Arteaga A, Nervi F, Rigotti A. Physiological and pathological implications of cholesterol. Front Biosci (Landmark Ed). Jan 1 2014;19(3):416-28. doi:10.2741/4216
  2. Feingold KR. Introduction to lipids and lipoproteins. Endotext [internet]. 2024;
  3. Sniderman AD, Thanassoulis G, Glavinovic T, et al. Apolipoprotein B particles and cardiovascular disease: a narrative review. JAMA cardiology. 2019;4(12):1287-1295.
  4. Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Lipoprotein (a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the American Heart Association. Arteriosclerosis, Thrombosis, and vascular biology. 2022;42(1):e48-e60.
  5. Pownall HJ, Rosales C, Gillard BK, Gotto AM, Jr. High-density lipoproteins, reverse cholesterol transport and atherogenesis. Nat Rev Cardiol. Oct 2021;18(10):712-723. doi:10.1038/s41569-021-00538-z
  6. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2019;73(24):e285-e350.
  7. Smith SC, Benjamin EJ, Bonow RO, et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update. Circulation. 2011;124(22):2458-2473. doi:doi:10.1161/CIR.0b013e318235eb4d
  8. Borén J, Packard CJ, Binder CJ. Apolipoprotein B-containing lipoproteins in atherogenesis. Nature Reviews Cardiology. 2025:1-15.
  9. Glavinovic T, Thanassoulis G, de Graaf J, Couture P, Hegele RA, Sniderman AD. Physiological bases for the superiority of apolipoprotein b over low‐density lipoprotein cholesterol and non–high‐density lipoprotein cholesterol as a marker of cardiovascular risk. Journal of the American Heart Association. 2022;11(20):e025858.
  10. Nordestgaard BG, Langsted A. Lipoprotein (a) and cardiovascular disease. The Lancet. 2024;404(10459):1255-1264.
  11. Rohatgi A, Khera A, Berry JD, et al. HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events. New England Journal of Medicine. 2014;371(25):2383-2393. doi:doi:10.1056/NEJMoa1409065
  12. von Eckardstein A, Nordestgaard BG, Remaley AT, Catapano AL. High-density lipoprotein revisited: biological functions and clinical relevance. Eur Heart J. Apr 21 2023;44(16):1394-1407. doi:10.1093/eurheartj/ehac605
  13. Fisher EA, Feig JE, Hewing B, Hazen SL, Smith JD. High-density lipoprotein function, dysfunction, and reverse cholesterol transport. Arterioscler Thromb Vasc Biol. Dec 2012;32(12):2813-20. doi:10.1161/atvbaha.112.300133
  14. Endo Y, Sasaki K, Ikewaki K. Beyond High-density Lipoprotein-cholesterol: Unraveling the Complexity of High-density Lipoprotein Functionality. J Atheroscler Thromb. Nov 1 2025;32(11):1359-1367. doi:10.5551/jat.RV22042
  15. Ference BA, Graham I, Tokgozoglu L, Catapano AL. Impact of Lipids on Cardiovascular Health: JACC Health Promotion Series. J Am Coll Cardiol. Sep 4 2018;72(10):1141-1156. doi:10.1016/j.jacc.2018.06.046
  16. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease. Endocrine Practice. 2017;23:1-87. doi:10.4158/EP171764.APPGL
  17. 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 Med. Jan 2025;55(1):67-78. doi:10.1007/s40279-024-02115-z
  18. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk. JACC. 2014;63(25_Part_B):2960-2984. doi:doi:10.1016/j.jacc.2013.11.003

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