Series: The Real Cost: The Body After Pharmacology - Episode 3: Cholesterol, LDL, HDL and Atherosclerosis

Cholesterol is one of the most demonised molecules in health discussions, even though the body could not function without it. It is part of cell membranes, contributes to steroid hormone synthesis and is used to make bile acids. The cardiovascular problem is not the mere existence of cholesterol, but how it is transported through blood, how many atherogenic particles circulate and how long the arterial wall is exposed to them.

In the context of anabolic-androgenic steroid use, the lipid profile can become one of the most important invisible costs. An athlete may feel strong, perform well and compete at a high level while HDL falls, LDL and ApoB rise, and the endothelium is exposed for years to a more atherogenic environment. Early atherosclerosis does not hurt, and that silence is exactly what makes it dangerous.

This episode separates mythology from physiology. We will follow the path from cholesterol and lipoproteins to particle retention in the arterial wall, plaque formation, the roles of LDL, HDL, ApoB, triglycerides and Lp(a), the effects of AAS on these systems and the limitations of relying on total cholesterol alone.

1. Cholesterol is not the enemy

Cholesterol is essential for life. The liver produces it even when dietary intake is low, and cells use it for structure and signalling. Risk develops when cholesterol transport within atherogenic particles creates sufficiently high and prolonged exposure of the arterial wall. Saying simply that cholesterol is bad hides the mechanism that matters.

2. Cholesterol travels inside lipoproteins

Cholesterol does not dissolve freely in plasma. It is carried inside particles called lipoproteins, which are made from lipids and proteins. LDL, HDL, VLDL and remnant particles are not different kinds of cholesterol. They are different transport vehicles carrying lipids through the body.

3. What LDL-C actually measures

LDL-C estimates the amount of cholesterol carried inside LDL particles. It is a major marker and a well-established causal factor in atherosclerotic cardiovascular disease, but it does not directly tell us how many LDL particles are present. Two people with the same LDL-C may have different numbers of atherogenic particles.

4. ApoB better reflects the number of atherogenic particles

Each major atherogenic particle in the VLDL, IDL and LDL families usually carries one apolipoprotein B molecule. ApoB therefore provides a practical approximation of the total number of particles capable of entering the arterial wall. In some metabolic profiles, ApoB can reveal risk that LDL-C alone underestimates.

5. Non-HDL cholesterol sees more than LDL

Non-HDL-C is calculated by subtracting HDL-C from total cholesterol and includes cholesterol carried by the major atherogenic particles. It is especially useful when triglycerides are elevated or metabolism is disturbed. It does not always replace ApoB, but it offers a broader view than LDL-C alone.

6. HDL is not simply the good cholesterol

HDL participates in reverse cholesterol transport and other vascular processes, but HDL-C measures the amount of cholesterol inside HDL particles, not their functional efficiency. Higher HDL-C is epidemiologically associated with lower risk in many populations, yet artificially increasing HDL-C does not automatically produce cardiovascular protection.

7. High HDL does not cancel high ApoB

A common mistake is to think that high HDL compensates for elevated LDL or ApoB. Atherosclerotic risk is strongly related to exposure to ApoB-containing particles. A profile with favourable HDL but many atherogenic particles remains a profile that deserves serious attention.

8. Triglycerides and VLDL complete the picture

Elevated triglycerides can reflect increased VLDL production and a greater burden of atherogenic remnant particles. In insulin resistance, visceral obesity and prolonged caloric surplus, this component can become important even when LDL-C does not appear dramatically elevated.

9. Lp(a) adds a largely genetic layer of risk

Lipoprotein(a), or Lp(a), is an LDL-like particle containing ApoB plus an additional protein called apolipoprotein(a). Its concentration is largely genetically determined and can increase atherosclerotic risk independently of other markers. A routine lipid profile does not necessarily reveal it.

10. Atherosclerosis begins with particle retention in the arterial wall

A central event in atherogenesis is the entry and retention of ApoB-containing particles within the inner layer of the artery. The higher the concentration of these particles and the longer the exposure, the greater the opportunity for some of them to become trapped and initiate local inflammation.

11. The endothelium is the gateway

The endothelium is the cellular lining of blood vessels. Hypertension, smoking, hyperglycaemia, inflammation and some pharmacological exposures can impair endothelial function. A dysfunctional endothelium favours vasoconstriction, inflammation and the interaction between atherogenic particles and the vessel wall.

12. Retained LDL is modified within the vessel wall

After retention, LDL particles can undergo oxidative and enzymatic modification. These changes stimulate the local immune response. Atherosclerosis is not simply fat being deposited in a pipe. It is an active biological process in which lipids and inflammation reinforce each other.

13. Macrophages become foam cells

Monocytes enter the vessel wall and become macrophages. They ingest modified lipid particles and become filled with cholesterol, forming foam cells. Their accumulation contributes to fatty streaks, among the earliest visible atherosclerotic lesions.

14. Atherosclerotic plaque evolves over years

Plaque develops slowly through accumulation of lipids, inflammatory cells, fibrous tissue and sometimes calcium. The speed varies between individuals, but cumulative exposure matters enormously. Ten years of an atherogenic profile is biologically different from a short isolated disturbance.

15. Calcification records part of the plaque's history

As atherosclerosis evolves, some plaques become calcified. Coronary artery calcium detected on imaging reflects accumulated calcified plaque burden and can refine risk assessment in selected clinical settings. A zero calcium score does not exclude every form of plaque, particularly in younger people.

16. Stable and vulnerable plaques are not the same

Some plaques have a thicker fibrous cap and are relatively stable. Others have a large lipid core, intense inflammation and a thinner cap, making them more prone to rupture. Acute events often arise not only from progressive narrowing but from sudden destabilisation of a plaque.

17. Plaque rupture can trigger thrombosis

When a plaque ruptures or erodes, thrombogenic material is exposed to the blood. Platelets and the coagulation system can rapidly form a clot. If that clot blocks a coronary artery, the result may be myocardial infarction.

18. Coronary arteries are not the only vessels affected

Atherosclerosis can affect the coronary arteries, carotids, cerebral arteries, aorta and arteries of the limbs. It is a systemic disease. A person exposed to atherogenic factors accumulates risk not only for myocardial infarction, but also for stroke and peripheral arterial disease.

19. Cerebrovascular atherosclerosis can lead to stroke

Carotid plaque and intracranial atherosclerosis can contribute to ischaemic stroke. Risk is also influenced by hypertension, smoking, diabetes and other conditions. This is why the lipid profile should never be mentally separated from the rest of the cardiovascular system.

20. Peripheral arterial disease is the same process in another territory

When arteries supplying the limbs are affected, blood flow can become inadequate, especially during exertion. Exercise-induced leg pain is a classic manifestation, but disease may remain silent for a long time. Its presence indicates a significant systemic atherosclerotic burden.

21. AAS can worsen the lipid profile

Anabolic-androgenic steroids can lower HDL-C and raise LDL-C, sometimes quickly and substantially. The magnitude depends on the compound, dose, duration, individual susceptibility and other metabolic variables. These changes are not merely cosmetic abnormalities on a laboratory report; they alter the environment in which atherosclerosis develops.

22. Oral 17-alpha-alkylated steroids can hit HDL hard

Oral 17-alpha-alkylated compounds are well known for often unfavourable lipid effects, particularly marked HDL-C suppression and worsening of atherogenic ratios. Their hepatic effects matter, which is why two regimens containing a similar amount of steroid can have very different consequences for lipoproteins.

23. Injectable compounds are not lipid-neutral

Avoiding first-pass hepatic metabolism does not make an androgen free of lipid effects. Injectable AAS can alter HDL, LDL, blood pressure, haematocrit and vascular function. The magnitude varies, but the idea that injectable automatically means safe for cholesterol is false.

24. Dose and duration matter

Greater and longer supraphysiological exposure tends to increase metabolic burden. There is no simple equation in which doubling the dose precisely doubles lipid deterioration. Individual biology, combinations of compounds, diet and previous exposure all modify the response.

25. Hepatic lipase is one piece of the mechanism

Androgens can influence hepatic lipase activity and HDL metabolism. Increased activity of this enzyme can accelerate the breakdown of certain HDL particles and contribute to lower HDL-C. This is one physiological explanation for the lipid changes seen in AAS users.

26. The liver is the command centre of lipoprotein metabolism

The liver produces, remodels and clears much of the body's lipoprotein traffic. Androgen signalling can alter enzymes and receptors involved in lipid metabolism. This is why AAS effects on cholesterol are systemic even when routine liver enzymes appear normal.

27. Hormonal balance can influence lipids

Oestrogens, androgens, thyroid hormones and insulin all influence lipoprotein metabolism. When pharmacology alters several endocrine axes at once, the resulting lipid profile cannot be explained by one hormone alone. This is one reason simplistic predictions often fail.

28. A good diet cannot fully neutralise a pharmacological effect

Nutrition strongly influences cardiovascular risk, but it cannot guarantee that AAS-induced lipid changes disappear. Adequate fibre intake, sensible fat composition and weight control can improve the overall profile, yet they do not turn an atherogenic pharmacological exposure into a neutral one.

29. Visceral fat changes the equation

Visceral adipose tissue is associated with insulin resistance, higher triglycerides, lower HDL and metabolic inflammation. A very heavy athlete may carry substantial muscle mass, but also a relevant amount of visceral fat. Those two components should not be treated as metabolically equivalent.

30. Insulin resistance creates a characteristic atherogenic profile

Insulin resistance favours elevated triglycerides, increased VLDL, lower HDL and smaller, denser LDL particles. In this setting LDL-C can look only moderately elevated while the number of atherogenic particles is higher than the isolated LDL-C value suggests.

31. Hypertension magnifies lipid-related vascular injury

High blood pressure increases mechanical stress on the vessel wall and promotes endothelial dysfunction. When hypertension coexists with elevated ApoB, risk is not simply the arithmetic sum of two separate problems. Both processes act on the same artery through different and potentially synergistic mechanisms.

32. High haematocrit adds another vascular burden

Markedly elevated haematocrit can increase blood viscosity and haemodynamic load. It does not cause atherosclerosis through the same mechanism as LDL, but it can contribute to a less favourable cardiovascular environment, especially alongside hypertension, dehydration, smoking or other risks.

33. Smoking and atherogenic lipids are an aggressive combination

Smoking damages endothelial function, promotes oxidative stress and increases thrombotic risk. When it overlaps with an atherogenic lipid profile, the effects accumulate. Atherosclerosis is rarely the result of one isolated factor.

34. Genetics can create very different starting points

Familial hypercholesterolaemia and other genetic variants can produce very high LDL from an early age. In that context, additional exposures that worsen lipids matter even more. A family history of premature myocardial infarction should be treated as a major cardiovascular signal.

35. Arterial biological age reflects cumulative exposure

Atherosclerosis is biologically dependent on concentration and time: how many atherogenic particles circulated and for how long. A young adult may have low absolute short-term risk while still accumulating a burden that becomes important ten or twenty years later.

36. Total cholesterol can look acceptable while hiding risk

Total cholesterol combines cholesterol carried in particles with very different meanings. An apparently acceptable total value does not exclude high LDL, very low HDL or elevated ApoB. Useful interpretation requires fractions and context, not the total number alone.

37. Low HDL is a signal, not an isolated verdict

Very low HDL-C is common with some AAS exposures and in metabolic syndrome. It is associated with increased risk, but should be interpreted alongside ApoB, LDL-C, triglycerides, blood pressure, glucose and the rest of the profile. No single number describes the whole atherosclerotic process.

38. Normal LDL-C does not guarantee normal ApoB

When each LDL particle carries less cholesterol, many particles can exist at an LDL-C level that appears modest. This discordance is more common with elevated triglycerides and insulin resistance. ApoB can clarify the true particle burden.

39. Fasting is not always required for lipid testing

For many modern lipid assessments, non-fasting samples are adequate. Very high triglycerides, particular calculations or specific investigations may require standardised fasting conditions. When monitoring change, using comparable sampling conditions improves interpretation.

40. One blood test captures only one moment

The lipid profile can shift with diet, body weight, alcohol, acute illness, training, medication and pharmacological exposure. A single result is useful, but the trend over time is often more informative. Repeated values show direction rather than one isolated snapshot.

41. The standard lipid panel is only the beginning

Total cholesterol, LDL-C, HDL-C and triglycerides form the foundation of lipid assessment. In selected situations, ApoB, non-HDL-C and Lp(a) add important information. Test selection depends on overall risk, family history, metabolic context and clinical interpretation.

42. ApoB is useful when the numbers do not agree

If LDL-C appears reasonable but triglycerides are high, HDL is low and insulin resistance is present, ApoB can show whether the number of atherogenic particles is still elevated. It is particularly useful when cholesterol content and particle number are discordant.

43. Lp(a) is often worth measuring at least once

Because Lp(a) is largely genetically determined and relatively stable across life, modern guidelines commonly support measuring it at least once in adulthood to refine risk. A high value can change how seriously the other modifiable factors are treated.

44. Inflammation can refine risk but does not replace lipid assessment

Markers such as hs-CRP can suggest increased inflammatory activity and may contribute to risk stratification in selected settings. Low inflammation does not neutralise high ApoB. Retention of atherogenic particles remains central to the disease process.

45. Coronary calcium scoring shows calcified plaque burden

Coronary artery calcium CT can detect and quantify calcified coronary plaque. It is a risk-stratification tool, not a universal screening test for every athlete. In younger people, non-calcified plaque may exist even when the calcium score is zero.

46. Coronary CT angiography can see more than calcium

Coronary CT angiography can visualise the lumen and plaques, including non-calcified components, but it requires appropriate medical indication and involves radiation and contrast. It is not a routine test for everyone. It becomes relevant when risk, symptoms or other findings justify anatomical assessment.

47. Carotid ultrasound can reveal atherosclerosis elsewhere

Carotid ultrasound can identify plaques and structural changes in the neck arteries. Plaque presence is a marker of atherosclerotic disease rather than merely a local curiosity. Interpretation should be clinical and it does not replace coronary assessment when coronary imaging is indicated.

48. A normal ECG does not exclude atherosclerosis

An electrocardiogram records the heart's electrical activity and can identify many abnormalities, but it does not visualise arterial plaque. A normal ECG does not mean the coronary arteries are free of disease. It answers a different cardiovascular question.

49. Strong performance does not prove healthy arteries

An athlete can possess exceptional strength and good exercise capacity while carrying atherosclerotic plaque. The body can compensate for a long time, and moderate disease may not visibly limit performance. Absence of athletic decline is not equivalent to absence of cardiovascular disease.

50. Atherosclerosis can be completely silent

Many people experience no chest pain, breathlessness or other symptoms until disease is advanced or an acute event occurs. This silent nature explains why prevention relies on risk factors and appropriate investigation rather than waiting for symptoms.

51. Lowering risk does not make plaque disappear overnight

Reducing exposure to atherogenic particles can slow progression and reduce cardiovascular events. Some plaques can stabilise and their composition can change, but years of accumulated atherosclerosis are not erased instantly. Early prevention remains easier than dealing with a large established burden.

52. Lipids may improve after AAS cessation

In many users, HDL-C and LDL-C improve after AAS exposure ends, especially when the abnormalities were pharmacologically induced and there is no major underlying dyslipidaemia. Recovery time varies according to compounds, duration, exposure and individual metabolism.

53. Normal laboratory values do not erase past exposure

If the lipid profile returns to more favourable values, that is beneficial, but it does not mean previously accumulated risk becomes zero. Plaque formed during years of exposure may persist. The biological history of the arteries still matters even when current blood tests look better.

54. Strongman adds the issue of prolonged caloric surplus

Increasing body mass is sometimes pursued deliberately for performance. Large and prolonged caloric surpluses can also increase visceral fat, triglycerides and insulin resistance. When this strategy overlaps with AAS and hypertension, the cardiovascular profile becomes more complex.

55. Very high body weight is not metabolically neutral

Large muscle mass is not the same as adipose mass, but a very heavy body increases circulatory demand and may coexist with sleep apnoea, hypertension and insulin resistance. Performance should not be confused with metabolic health.

56. Competition periods can distort the profile

Changes in diet, weight, hydration, sleep and pharmacology around competition can temporarily alter lipid values. Longitudinal monitoring and comparison under similar conditions are therefore more useful than treating one blood draw as a definitive verdict.

57. Repeated cycles become cumulative exposure

If the lipid profile is severely disturbed for several months, partly recovers, and is then disturbed again, the arteries do not restart from zero each time. From the perspective of atherosclerosis, the total time spent with elevated atherogenic particles and overlapping risk factors matters.

58. Monitoring should follow the trend, not just laboratory reference ranges

A laboratory reference interval is not the same as optimal risk for every individual. Clinicians integrate LDL-C, ApoB, non-HDL-C, triglycerides, Lp(a), blood pressure, glucose, family history and sometimes imaging. Direction over time may matter more than whether a result is merely labelled within range.

59. Warning symptoms require urgent assessment

Chest pain or pressure, unusual breathlessness, fainting, sudden neurological symptoms or severe exertional pain should not automatically be explained by training. These symptoms have many possible causes and some are urgent. Medical assessment matters more than assumptions about fatigue.

60. Conclusion: arteries keep the record of exposure

Cholesterol is not an enemy, and HDL and LDL are not moral characters. Risk emerges from particle biology, retention within the arterial wall and duration of exposure. AAS can worsen this equation through HDL suppression, increased atherogenic particles and overlap with hypertension, high haematocrit, high body weight and other factors. In atherosclerosis, what cannot be felt today may still matter years later.

In simple terms, atherosclerotic risk is a problem of particles and time. The more ApoB-containing lipoproteins circulate and the longer the exposure continues, the more opportunities they have to become retained in the arterial wall. LDL-C remains a central marker and treatment target, while ApoB and non-HDL-C can add valuable information when metabolism is complex.

HDL is biologically important, but the story of good HDL versus bad LDL is too simplistic. HDL-C does not directly measure HDL function and does not cancel a high burden of atherogenic particles. Serious risk assessment is better informed by the relationship between LDL-C, ApoB, triglycerides, non-HDL-C, Lp(a), blood pressure and metabolic status.

AAS can push this equation in an unfavourable direction by suppressing HDL-C, increasing LDL-C and altering hepatic lipoprotein metabolism. Some changes may improve relatively quickly after cessation, others recover slowly, and plaque accumulated during years of exposure does not disappear simply because laboratory values improve.

For the strength athlete, risk must be viewed as a system: pharmacology, hypertension, body weight, sleep apnoea, glucose control, diet, smoking, genetics and exposure duration. Each factor may appear tolerable in isolation, while their overlap can accelerate vascular disease without producing an obvious decline in performance.

The central message is not that every lipid abnormality inevitably produces disease. It is that atherosclerosis develops silently and cumulatively. Appropriate monitoring, clinical interpretation and reducing exposure to atherogenic factors therefore make sense before symptoms appear, not after the first cardiovascular event.

Sources and recommended reading

1. European Society of Cardiology / European Atherosclerosis Society. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Updated guidance on LDL and ApoB-containing lipoproteins as causal drivers of ASCVD and on cardiovascular risk stratification.

2. Ference BA et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Consensus Statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal. 2017.

3. Borén J et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic and therapeutic insights. European Heart Journal. 2020.

4. Baggish AL et al. Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use. Circulation. 2017;135:1991-2002. Echocardiographic and coronary CT angiography assessment in experienced AAS users.

5. Windfeld-Mathiasen J et al. Cardiovascular Disease in Anabolic Androgenic Steroid Users. Circulation. 2025;151:828-834. Nationwide cohort with long-term follow-up of cardiovascular events.

6. Buhl LF et al. Illicit Anabolic Steroid Use and Cardiovascular Status in Men and Women. JAMA Network Open. 2025. Contemporary data on cardiovascular status associated with illicit AAS exposure.

7. Grundy SM et al. 2018 AHA/ACC Guideline on the Management of Blood Cholesterol. Circulation. Principles of LDL-C assessment, global cardiovascular risk and risk-enhancing factors.

8. Sniderman AD et al. Literature on apolipoprotein B particles, cardiovascular risk and discordance between LDL-C and atherogenic particle number.

9. Toth PP et al. Contemporary literature on high-density lipoprotein biology and the limitations of interpreting HDL-C as an isolated protective marker.

10. European Atherosclerosis Society and contemporary literature on Lp(a), ApoB, non-HDL-C, coronary artery calcium and plaque imaging for refinement of atherosclerotic cardiovascular risk.

Editorial note: this material is educational and explains cardiovascular mechanisms associated with dyslipidaemia and AAS exposure. It does not provide substance-use protocols and does not replace individual medical assessment, diagnosis or treatment. Lipid values and imaging findings should be interpreted in the context of total cardiovascular risk by a qualified clinician.