From the Guidelines
Familial hypercholesterolemia (FH) and hypercholesterolemia are distinct conditions that differ primarily in their causes and severity, with FH being a specific genetic disorder leading to extremely high LDL cholesterol levels from birth, and hypercholesterolemia being a general term for elevated blood cholesterol typically developing over time due to lifestyle factors. The primary difference between the two conditions lies in their etiology, with FH caused by mutations in genes affecting LDL cholesterol processing, particularly the LDL receptor gene 1, and hypercholesterolemia resulting from lifestyle factors such as poor diet, lack of exercise, smoking, or other medical conditions like diabetes or hypothyroidism. Some key characteristics of FH include:
- Extremely high LDL cholesterol levels, often exceeding 190 mg/dL in adults
- Premature cardiovascular disease, sometimes as early as childhood or young adulthood
- Physical signs such as xanthomas (cholesterol deposits) on tendons and yellowish cholesterol deposits around the eyes (xanthelasma) In contrast, regular hypercholesterolemia:
- Typically develops over time due to lifestyle factors
- Usually appears later in life
- Produces less severe elevations in cholesterol levels Treatment approaches also differ between the two conditions, with FH often requiring aggressive approaches with high-potency statins like rosuvastatin or atorvastatin at maximum doses, frequently combined with ezetimibe, PCSK9 inhibitors, or other medications from an early age 1. Regular hypercholesterolemia may respond to lifestyle modifications alone or require less intensive medication regimens. The genetic basis of FH means that family screening is essential when it's diagnosed, as first-degree relatives have a 50% chance of also having the condition. Overall, understanding the differences between FH and hypercholesterolemia is crucial for providing appropriate diagnosis, treatment, and management of these conditions to improve patient outcomes and reduce the risk of cardiovascular disease.
From the Research
Definition and Characteristics
- Familial Hypercholesterolemia (FH) is a genetic disorder of lipid metabolism characterized by a significant elevation in levels of low-density lipoprotein cholesterol (LDL-C) 2, 3, 4, 5.
- Hypercholesterolemia, on the other hand, refers to a general condition of high cholesterol levels in the blood, which can be caused by a variety of factors, including diet, lifestyle, and genetics.
Genetic Causes
- FH is caused by known mutations in the gene of the LDL receptor, LDLR; the gene of apolipoprotein B, apo B; and the proprotein convertase subtilisin/kexin type 9 gene, PCSK9 2, 4, 5.
- Hypercholesterolemia can be caused by a combination of genetic and environmental factors, but it is not necessarily caused by the same genetic mutations as FH.
Clinical Manifestations
- FH can manifest clinically as both the severe homozygous (HoFH) form and the commoner heterozygous (HeFH) form 3, 4, 5.
- Hypercholesterolemia can also have varying levels of severity, but it is not typically classified into homozygous and heterozygous forms.
Treatment and Management
- Patients with FH often require more aggressive treatment, including higher doses of statins, more potent statins, statin-based combination therapy, or adjunctive therapies 2, 3, 4, 5.
- Patients with hypercholesterolemia may also be treated with statins and other lipid-lowering medications, but the treatment approach may be less aggressive than for FH.
- New treatment approaches for FH include mipomersen, lomitapide, and PCSK9 inhibitors, which have shown promise in reducing LDL-C levels 2, 3, 4, 6.