Familial combined hyperlidemia patients are initially asymptomatic, but need to monitor body weight [1] and waist- to- hip ratio [2] in order to avoid abdominal obesity, that seems to be related to lipid profile modification. These parameters are also in relation with other biochemical abnormalities: decreased leptin and adiponectin [3] and high insulin resistance [4]. Same principles apply to children who come from affected parents, who need to maintain body weight within normal range.

Signs of hepatic suffering may be encountered in the context of fatty liver and non-alcoholic steatohepatitis [5], but they are not specific for familial combined hyperlidemia. Clinical examination is noncontributory in some cases, because xanthoma are almost never present in this disease [6].

Patients may also suffer form arterial hypertension [7], which further increases cardiovascular risk.

The biochemical profile has several specific traits: reduced HDL level (<40 mg/dL), high LDL level (> 160 mg/dL) and/or high triglyceride (TG) level (> 200 mg/dL). High LDL and TG levels (in association) are usually not found in the general population, only one of them is usually present. These parameters must be evaluated in a recurrent manner, keeping in mind that members of the same family may have different phenotypes [8]. Familial combined hyperlidemia is also characterized by increased apo B levels (> 125 mg/dL), which also constitutes a good prognostic factor [9].

Vascular echography is used to measure carotid artery intima-media thickness, which is increased in patients that already had a cardiovascular or cerebrovascular event. Other echography findings, like increased pulse wave velocity and reduced flow mediated dilation are reliable parameters that assess endothelial dysfunction and arterial stiffness, but are unable to increase event prediction [10]. Ultrasound analysis should not be limited to carotid arteries, it should also be performed on femoral arteries and the aorta. Silent myocardial ischemia should also be taken into consideration and evaluated using stress tests. Echography of the heart and the aorta should be performed every year. Computed-tomography coronary angiography is also an option in uncertain cases. Carotid intima medial thickness should also be assessed in children. They can also benefit from positron emission tomography scans in selected cases because if significant plaque is present, hypolipemic treatment may be initialized by a pediatric cardiologist.

Genetic studies reveal a locus on chromosome 1 (1q21-q23) that is linked both to familial combined hyperlidemia and type 2 diabetes [11]. Apo AV gene may also be linked to disease transmission [12], as well as the gene encoding upstream transcription factor 1 [13]. However, gene expression depends on environmental factors, making the diagnosis even more difficult [14].

The primary goal of treating Familial Combined Hyperlipidemia is to reduce the risk of cardiovascular disease by managing lipid levels. Lifestyle modifications, including a healthy diet, regular exercise, and weight management, are foundational. Medications such as statins, fibrates, or niacin may be prescribed to lower cholesterol and triglyceride levels. In some cases, newer medications like PCSK9 inhibitors or omega-3 fatty acids may be considered. Regular monitoring of lipid levels and cardiovascular health is essential to adjust treatment as needed.

With appropriate management, individuals with Familial Combined Hyperlipidemia can lead healthy lives. However, without treatment, the risk of developing cardiovascular diseases increases significantly. Early diagnosis and intervention are key to improving outcomes. Regular follow-up with healthcare providers ensures that lipid levels are controlled and any complications are addressed promptly.

Familial Combined Hyperlipidemia is caused by genetic factors that affect lipid metabolism. It is a polygenic disorder, meaning multiple genes contribute to its development. These genetic variations lead to overproduction or impaired clearance of lipoproteins, resulting in elevated cholesterol and triglyceride levels. Environmental factors, such as diet and lifestyle, can also influence the severity of the condition.

FCHL is one of the most common genetic lipid disorders, affecting approximately 1 in 100 to 1 in 200 individuals worldwide. It is more prevalent in certain populations and families with a history of early-onset cardiovascular disease. Both men and women are affected, although men may develop symptoms earlier. The condition often goes undiagnosed due to its variable presentation.

The pathophysiology of Familial Combined Hyperlipidemia involves complex interactions between genetic and environmental factors. Genetic mutations lead to dysregulation of lipid metabolism, resulting in increased production and decreased clearance of lipoproteins. This imbalance causes elevated levels of cholesterol and triglycerides in the blood, contributing to the development of atherosclerosis (plaque buildup in arteries) and increasing cardiovascular risk.

While Familial Combined Hyperlipidemia is a genetic condition and cannot be prevented entirely, certain measures can help manage its impact. Adopting a heart-healthy lifestyle, including a balanced diet low in saturated fats and cholesterol, regular physical activity, and maintaining a healthy weight, can help control lipid levels. Regular screening and monitoring of lipid profiles, especially in individuals with a family history of FCHL, are crucial for early detection and management.

Familial Combined Hyperlipidemia is a common genetic disorder characterized by elevated cholesterol and triglyceride levels, increasing the risk of cardiovascular diseases. It is inherited and can present in various ways, making diagnosis challenging. Treatment focuses on lifestyle modifications and medications to manage lipid levels and reduce cardiovascular risk. Early diagnosis and regular monitoring are essential for effective management and improved outcomes.

If you or a family member has been diagnosed with Familial Combined Hyperlipidemia, it's important to understand the condition and its implications. FCHL is a genetic disorder that affects how your body processes fats, leading to high cholesterol and triglyceride levels. This increases your risk of heart disease, but with proper management, you can lead a healthy life. Work closely with your healthcare provider to monitor your lipid levels, adopt a heart-healthy lifestyle, and take any prescribed medications. Regular check-ups and a proactive approach to your health can help you manage FCHL effectively.

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