Familial combined hyperlipidemia (FCHL) is an inherited disorder causing elevated levels of both cholesterol and triglycerides in the blood. The term “hyperlipidemia” refers to having too many lipids or fats in the bloodstream. It is “familial” because it passes down through generations and “combined” as it affects multiple types of lipids, specifically increasing low-density lipoprotein (LDL) cholesterol (“bad” cholesterol) and triglycerides. FCHL is a common genetic disorder that can increase blood fat levels, potentially leading to health concerns. High lipid levels often appear in teenage years or young adulthood, typically in their 20s and 30s, and remain elevated throughout life.
Genetic Causes of FCHL
Familial combined hyperlipidemia has a complex genetic foundation, distinguishing it from disorders caused by a single gene mutation. While initially thought to follow a single-gene inheritance pattern, research indicates FCHL is predominantly polygenic. This means multiple genes contribute to an individual’s predisposition, with each making a small contribution. It is often described as having an autosomal dominant inheritance pattern in some cases, suggesting that if one parent has the genetic predisposition, each child has about a 50% chance of inheriting it. The polygenic nature implies that the accumulation of many common genetic variations, known as single nucleotide polymorphisms (SNPs), influences triglyceride and LDL cholesterol levels. Over 30 different genetic variants have been identified.
Environmental factors also play a significant role in FCHL’s expression and severity. Lifestyle elements such as diet, body weight, and alcohol consumption can worsen lipid abnormalities. For instance, obesity, diabetes, and hypothyroidism are known to exacerbate the condition.
Diagnosing Familial Combined Hyperlipidemia
Diagnosing familial combined hyperlipidemia relies on a comprehensive clinical assessment. Diagnosis is typically made by evaluating blood test results and a detailed family medical history. This approach helps identify characteristic lipid abnormalities and familial patterns.
A blood lipid profile is a cornerstone of diagnosis, revealing elevated LDL cholesterol and triglycerides. Apolipoprotein B (ApoB) levels are also generally high, reflecting an increased number of atherogenic lipoprotein particles. Elevated ApoB has been shown to improve FCHL diagnosis and is often more consistently elevated than total cholesterol or triglycerides over time.
A strong family history of high cholesterol, high triglycerides, or premature atherosclerotic cardiovascular disease (e.g., heart attacks or strokes at a younger age) is a significant indicator. Doctors inquire about lipid disorders and cardiovascular events in close relatives to identify this pattern.
It is also important to rule out other “secondary” causes of elevated lipids that can mimic FCHL. These include poorly controlled diabetes, an underactive thyroid (hypothyroidism), excessive alcohol intake, or certain medications. Unlike some other inherited lipid disorders, FCHL typically does not present with obvious physical signs, such as cholesterol deposits on the skin or around the eyes (xanthomas or xanthelasmas), making laboratory tests and family history more important for accurate diagnosis.
Health Complications from FCHL
Familial combined hyperlipidemia increases susceptibility to serious health complications, primarily cardiovascular. Persistently high LDL cholesterol and triglycerides contribute directly to atherosclerosis, where fatty plaques build up inside arteries. This plaque accumulation narrows and hardens arteries, impeding blood flow.
Reduced blood flow can lead to atherosclerotic cardiovascular disease (ASCVD), including heart attacks and strokes. High LDL cholesterol directly contributes to plaque formation, and elevated triglycerides also increase cardiovascular risk. Individuals with FCHL have a heightened risk of experiencing these cardiovascular events at a younger age.
Beyond cardiovascular risks, very high triglyceride levels can cause acute pancreatitis. This condition involves inflammation of the pancreas. Acute pancreatitis can cause severe abdominal pain and may lead to serious complications.
Treatment and Management Approaches
Managing familial combined hyperlipidemia involves a comprehensive strategy combining lifestyle adjustments with medical treatments. Lifestyle interventions form the foundation of care for all individuals with FCHL. These changes aim to improve lipid levels and reduce cardiovascular risk.
Adopting a heart-healthy diet is a primary recommendation, focusing on reducing saturated and trans fats, sugars, and refined carbohydrates. Regular physical activity helps manage body weight and can positively influence cholesterol and triglyceride levels. Maintaining a healthy weight is also beneficial, as excess weight can worsen lipid profiles.
Limiting alcohol consumption is particularly important for individuals with elevated triglycerides, as alcohol can significantly raise these levels. While lifestyle modifications are beneficial, they are often insufficient to achieve target lipid levels in FCHL due to the genetic component.
Medical therapies are often necessary to manage the condition effectively. Statins are typically the first-line medication prescribed for FCHL, as they lower LDL cholesterol by reducing its production in the liver. Other medications may be added to statins, depending on the lipid profile and treatment goals. Fibrates, such as fenofibrate or gemfibrozil, are used to lower high triglyceride levels and can also lower LDL. Ezetimibe works by inhibiting cholesterol absorption in the intestine and is often used with statins to further reduce LDL cholesterol. Niacin, a B vitamin, can also improve lipid profiles by limiting the liver’s production of blood fats, though its use is sometimes limited by side effects.