• Clinical science

Lipid disorders


Lipid disorders encompass a broad spectrum of metabolic conditions that affect blood lipid levels. They are generally characterized by elevated levels of cholesterol, triglycerides, and/or lipoproteins in the blood in association with an increased risk of (or current) cardiovascular disease. The majority of lipid disorders are acquired through unhealthy lifestyles (obesity, inactivity, alcoholism). Congenital causes are less common; examples include familial hypertriglyceridemia, which is associated with extremely high levels of triglycerides that significantly increase the risk of pancreatitis, and familial hypercholesterolemia that results in early atherosclerotic complications. Lipid disorders are usually detected during routine laboratory testing, such as cardiovascular risk factor screening. The blood lipid profile includes total cholesterol, LDL, HDL, and triglycerides. To confirm the diagnosis, a fasting lipid profile must show pathological values on two different occasions. Dyslipidemia is diagnosed if LDL levels > 130 mg/dL and/or HDL levels < 40 mg/dL. The management of lipid disorders involves lifestyle modifications and lipid-lowering agents (primarily statins).


The following terms are often used interchangeably, as they share common causes and are all associated with an increased risk of atherosclerosis and cardiovascular disease. However, the terms have differing meanings.

Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease!



  • In the US, an estimated 50% of the population has elevated cholesterol levels.


Epidemiological data refers to the US, unless otherwise specified.




Dyslipidemia classification according to Frederickson

Fredrickson phenotype I IIa IIb III IV
Condition Familial hyperchylomicronemia [6] Familial hypercholesterolemia [7] Familial combined hyperlipidemia [8] Familial dysbetalipoproteinemia [9] Familial hypertriglyceridemia [10]
Frequency Rare ∼ 10% 1–15% ∼ 5% ∼ 70%
Inheritance Autosomal recessive Autosomal dominant Autosomal recessive Autosomal dominant
  • Hepatic overproduction of VLDL
Clinical manifestations
Lipoprotein defect Chylomicrons LDL LDL and VLDL Remnants of VLDL and chylomicrons VLDL
Total cholesterol Normal to mild ↑ [11] ↑↑ ↑↑ Normal to mild ↑
Total triglycerides ↑↑ [11] Normal ↑↑
Overnight plasma Creamy top layer [11] Clear Clear Turbid Turbid




Clinical features



Parameters of fat metabolism
Laboratory parameter Optimal level (mg/dL) Pathological (mg/dL)
Total cholesterol
  • < 200
  • Borderline: 200–239
  • High: > 240
  • < 150
  • Borderline: 150–199
  • High: > 200
  • Very high: ≥ 500
  • < 100
  • Near optimal: 100–129
  • Borderline high: > 130
  • High: > 160
  • Very high: ≥ 190
  • ≥ 60
  • Low: < 40
LDL/HDL ratio: the ratio of LDL and HDL levels serves as a control measure of cholesterol metabolism



  • Goal: Improve serum lipid levels to reduce the risk of cardiovascular disease.
  • General measures: lifestyle modifications
    • Dietary changes: Reduce saturated fat and cholesterol intake. A low cholesterol intake (< 300 mg per day is recommended in the US dietary guidelines
    • Weight management
    • Physical activity
  • Medical therapy
    • Statins
    • Second-line lipid-lowering agents
  • Treatment of xanthomas and xanthelasmas: Not required in most cases; Surgical removal for cosmetic reasons is possible but is associated with a high rate of recurrence.
  • Management of congenital disorders: : lifestyle modifications and lipid-lowering agents (high-dose statin therapy and ezetimibe for hypercholesterolemia, fibrates for hypertriglyceridemia); LDL apheresis may be required in severe cases.

ACC/AHA guidelines

  • Initiate moderate-intensity or high-intensity statin therapy.
    • Clinical atherosclerotic cardiovascular disease (ASCVD); : high-intensity statin therapy (age > 75 years: moderate-intensity statin therapy)
    • LDL ≥ 190: high-intensity statin therapy
    • Age 40–75 years + Diabetes (if LDL 70–189) → moderate dose statin therapy (consider high-dose statin therapy if > 7.5% 10 year ASCVD risk)
    • Age 40–75 years + 10 year ASCVD risk > 7.5% (if LDL 70–189)
  • See statins for details.

ATP III guidelines (2013)

Guidelines for lipid-lowering therapy (ATP III guidelines)

Risk stratification

LDL goal (mg/dL) Lifestyle modifications indicated (mg/dL) Medical therapy indicated (mg/dL)
ASCVD or risk equivalents (high risk > 20%) < 100 (or < 70 ) > 100 > 130
≥ 2 Risk factors (moderate risk) < 130 > 130 > 160
0–1 Risk factors (low risk) < 160 > 160 > 190



  • The decision to screen for hyperlipidemia primarily depends on the patient's overall risk for cardiovascular disease.
  • Screening high-risk individuals (i.e., with other risk factors for cardiovascular disease): > 20–25 years; > 30–35 years
  • Screening low-risk individuals: > 35 years; > 45 years