• Clinical science

Lipid disorders

Abstract

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).

Definition

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!

References:[1][2]

Epidemiology

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

References:[2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[3][3][4][1][5]

Classification

Dyslipidemia classification according to Frederickson

Fredrickson Phenotype Condition Relative frequency Mode of inheritance Pathogenesis Increased lipoproteins Total cholesterol (mg/dL) Triglyceride (mg/dL)
I Hyperchylomicronemia rare Chylomicrons normal > 1000
IIa Familial hypercholesterinemia ∼ 10%
  • Defective LDL receptors
    OR
  • Defective ApoB-100
LDL > 300 < 150
IIb Combined hyperlipidemia 1–15% LDL and VLDL > 300 150–300
III Remnant hyperlipidemia ∼ 5% Remnants of VLDL and chylomicrons 350–500 350–500
IV Hypertriglyceridemia ∼ 70%
  • Hepatic overproduction of VLDL
    OR
  • Defective ApoA-V
VLDL normal 200–1000
V Mixed hyperlipidemia ∼ 5% Chylomicrons and VLDL < 300 > 1000

References:[6]

Pathophysiology

References:[7]

Clinical features

References:[4][1][8][9]

Diagnostics

  • Laboratory analysis
    • Fasting lipid profile : total cholesterol, HDL, and triglycerides are measured
      • LDL level can be measured directly using assays or estimated using the Friedewald formula
      • Pathological values from two different occasions are required to confirm the diagnosis.
      • Dyslipidemia; is diagnosed if LDL > 130 mg/dL. and/or if HDL levels < 40 mg/dL
    • Identify underlying cause
Parameters of fat metabolism
Laboratory parameter Optimal level (mg/dL) Pathological (mg/dL)
Total cholesterol
  • < 200
  • Borderline: 200–239
  • High: > 240
Triglycerides
  • < 150
  • Borderline: 150–199
  • High: > 200
  • Very high: ≥ 500
LDL
  • < 100
  • Near optimal: 100–129
  • Borderline high: > 130
  • High: > 160
  • Very high: ≥ 190
HDL
  • ≥ 60
  • Low: < 40
LDL/HDL ratio: the ratio of LDL and HDL levels serves as a control measure of cholesterol metabolism

References:[4][1][10][11][12]

Treatment

  • 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

References:[4][1][13][14][15][16][8]

Prevention

  • 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

References:[2]

Abetalipoproteinemia