In recent years, industrialized nations have seen a significant decline in cardiovascular mortality. This development is not only due to advances in acute care but also to improved control of risk factors—particularly hypercholesterolemia. There is now no doubt about the causal role of low-density lipoproteins (LDL) in the development of atherosclerosis.

The U.S. Food and Drug Administration (FDA) and current clinical guidelines therefore regard LDL cholesterol (LDL-C) as a validated risk factor for cardiovascular disease. The causal effect of LDL has been consistently demonstrated through experimental studies on the pathogenesis of atherosclerosis and, more importantly, through interventional studies on cholesterol reduction. In particular, HMG-CoA reductase inhibitors (statins) show a linear relationship between the reduction in cardiovascular event risk and the potency of LDL-C lowering.

Interventional studies with other agents—such as ezetimibe and PCSK9 inhibitors—support the concept of a linear reduction in cardiovascular risk with decreasing LDL-C levels and further confirm the essential role of LDL-C in the pathogenesis of atherosclerosis. The atherogenic effects of lipid metabolism disorders are influenced by other, likewise treatable, risk factors like smoking, Hypertension and diabetes mellitus.

Secondary hyperlipoproteinemias are caused by risk factors associated with metabolic syndrome, hormonal changes, kidney diseases, liver diseases, and medications. In such cases, the underlying condition must be treated.

The lipid metabolism disorders associated with metabolic syndrome are the most commonly encountered in clinical practice. Metabolic syndrome, diabetes mellitus, and obesity share the same alterations in lipid profiles:

• LDL-C is normal,
• Triglycerides are elevated,
• HDL-C is reduced.

TheThe lipid metabolism values are influenced by hormones and medications.se should be distinguished from primary lipid metabolism disorders.

1. Hypothyroidism

• LDL-C: ↑ Increased
  → Reduced hepatic LDL receptor activity leads to decreased LDL clearance.
• HDL-C: ↔ or slightly ↑
  → May be normal or slightly elevated.
• Triglycerides: ↔ or ↑
  → VLDL clearance is reduced; a mild increase may occur.

Note: Hypothyroidism is a common secondary cause of hypercholesterolemia.

1. Acromegaly (Excess Growth Hormone in Adults)

• LDL-C: ↓ Decreased or ↔
  → GH enhances LDL receptor expression and lipolysis.
• HDL-C: ↓ Decreased
  → Mechanism unclear; possibly due to increased lipid turnover.
• Triglycerides: ↑ Increased
  → GH-induced lipolysis raises free fatty acids → increased hepatic VLDL production.

Note: Despite lower LDL-C levels, cardiovascular risk is elevated in acromegaly.

1. Growth Hormone Deficiency (in Adults)

• LDL-C: ↑ Increased
  → Reduced GH → decreased LDL receptor activity.
• HDL-C: ↓ Decreased
  → GH deficiency leads to lower HDL production.
• Triglycerides: ↑ Increased
  → Reduced lipolysis and impaired fat metabolism.

Note: GH deficiency is associated with an unfavorable lipid profile and increased cardiovascular risk.

1. Hypercortisolism (e.g., Cushing’s Syndrome)

• LDL-C: ↑ Increased
  → Elevated hepatic lipid synthesis and reduced clearance.
• HDL-C: ↓ Decreased
  → General disruption of lipoprotein metabolism.
• Triglycerides: ↑ Markedly increased
  → Cortisol promotes lipolysis in adipose tissue and increases VLDL production.

Note: Patients with hypercortisolism often develop a lipid profile resembling metabolic syndrome.

Summary Table:

1. Beta-Blockers (especially non-selective, without intrinsic activity)

• LDL-C: ↑ Increased
• HDL-C: ↓ Decreased
• Triglycerides: ↑ Increased

Note:
Conventional beta-blockers (e.g., propranolol) can negatively affect lipid metabolism. Newer vasodilating beta-blockers (e.g., nebivolol, carvedilol) tend to have more favorable or neutral metabolic effects.

1. Thiazide Diuretics (e.g., hydrochlorothiazide)

• LDL-C: ↑ Slightly increased
• HDL-C: ↔ or slightly ↑
• Triglycerides: ↑ Increased

Note:
These effects are dose-dependent. At low doses, changes are often minimal; at higher doses, a rise in triglycerides is more likely.

1. Estrogens (e.g., in oral contraceptives or hormone replacement therapy)

• LDL-C: ↓ Decreased
• HDL-C: ↑ Increased
• Triglycerides: ↑↑ Significantly increased

Note:
Estrogens increase hepatic VLDL production, particularly when taken orally, which can cause marked elevations in triglyceride levels.

1. Progestins (alone or combined with estrogens)

• LDL-C: ↑ or ↔ Increased or neutral
• HDL-C: ↓ or ↔ Decreased or neutral
• Triglycerides: ↔ or ↑

Note:
The effect varies by type. Androgenic progestins (e.g., levonorgestrel) tend to lower HDL-C, while newer types (e.g., drospirenone) are more metabolically neutral.

1. Androgens (e.g., testosterone, anabolic steroids)

• LDL-C: ↑ Increased
• HDL-C: ↓ Decreased
• Triglycerides: ↑ or ↔

Note:
Androgens often lower HDL-C significantly. The effects depend on the dose and route of administration. Anabolic steroid abuse typically causes a pronounced dyslipidemia.

1. Antipsychotics (especially atypical agents like olanzapine, clozapine)

• LDL-C: ↑ Increased
• HDL-C: ↓ Decreased
• Triglycerides: ↑↑ Markedly increased

Note:
Atypical antipsychotics promote weight gain, insulin resistance, and significant hypertriglyceridemia—especially with long-term use.

Summary Table:

Lipid metabolism disorders increase cardiovascular risk. Therefore, in both treatment and prevention, it is essential to assess cardiovascular risk.

The chapter lidid disorders focuses on the treatment of lipid metabolism disorders without downplaying the importance of other risk factors. It also takes into account current debates surrounding the assessment of individual disease risk, the setting of treatment targets, and differential therapy approaches.

The primary goal of treating lipid metabolism disorders is the prevention of cardiovascular events. Prevention means avoiding the occurrence of such events. In order to implement meaningful preventive strategies, the individual cardiovascular risk must first be assessed and classified into risk categories. Once the individual risk is determined, targeted treatment strategies can be developed.

The recommendations based  are on the 2019/2021 ESC/EAS Guidelines for the management of dyslipidemias.