Heterozygous<unk> <unk>  is usually treated with statins. Statins act by inhibiting the enzyme hydroxymethylglutaryl CoA reductase (HMG-CoA-reductase) in the liver. In response, the liver produces more LDL receptors, which remove circulating LDL from the blood. Statins effectively lower cholesterol and LDL levels, although sometimes add-on therapy with other drugs is required, such as bile acid sequestrants (cholestyramine or colestipol), nicotinic acid preparations or fibrates. Control of other risk factors for cardiovascular disease is required, as risk remains somewhat elevated even when cholesterol levels are controlled. Professional guidelines recommend that the decision to treat a person with<unk>  with statins should not be based on the usual risk prediction tools (such as those derived from the Framingham Heart Study), as they are likely to underestimate the risk of cardiovascular disease; unlike the rest of the population,<unk>  have had high levels of cholesterol since birth, probably increasing their relative risk. Prior to the introduction of the statins, clofibrate (an older fibrate that often caused gallstones), probucol (especially in large xanthomas) and thyroxine were used to reduce LDL cholesterol levels. More controversial is the addition of ezetimibe, which inhibits cholesterol absorption in the gut. While it reduces LDL cholesterol, it does not appear to improve a marker of atherosclerosis called the intima-media thickness. Whether this means that ezetimibe is of no overall benefit in<unk>  is unknown. There are no interventional studies that directly show mortality benefit of cholesterol lowering in<unk> . Rather, evidence of benefit is derived from a number of trials conducted in people who have polygenic<unk>  (in which heredity plays a smaller role). Still, a 1999 observational study of a large British registry showed that mortality in people with<unk>  had started to improve in the early 1990s when statins were introduced. A cohort study suggested that treatment of<unk>  with statins leads to a 48% reduction in death from coronary heart disease to a point where people are no more likely to die of coronary heart disease than the general population. However, if the person already had coronary heart disease the reduction was 25%. The results emphasize the importance of early identification of<unk>  and treatment with statins. Alirocumab and evolocumab, both monoclonal antibodies against PCSK9, are specifically indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous<unk> , who require additional lowering of LDL cholesterol. On 22 Dec 2021 USFDA approved new drug containing Inclisiran as new treatment option for<unk>  it is to be given in combination with maximally tolerated statin therapy. Homozygous<unk>  Homozygous<unk>  is harder to treat. The LDL (Low Density Lipoprotein) receptors are minimally functional, if at all. Only high doses of statins, often in combination with other medications, are modestly effective in improving lipid levels. If medical therapy is not successful at reducing cholesterol levels, LDL apheresis may be used; this filters LDL from the bloodstream in a process reminiscent of dialysis. Very severe cases may be considered for a liver transplant; this provides a liver with normally functional LDL receptors, and leads to rapid improvement of the cholesterol levels, but at the risk of complications from any solid organ transplant (such as rejection, infections, or side-effects of the medication required to suppress rejection). Other surgical techniques include partial ileal bypass surgery, in which part of the small bowel is bypassed to decrease the absorption of nutrients and hence cholesterol, and portacaval shunt surgery, in which the portal vein is connected to the vena cava to allow blood with nutrients from the intestine to bypass the liver. Lomitapide, an inhibitor of the microsomal triglyceride transfer protein, was approved by the US FDA in December 2012 as an orphan drug for the treatment of homozygous<unk> . In January 2013, The US FDA also approved mipomersen, which inhibits the action of the gene apolipoprotein B, for the treatment of homozygous<unk> . Gene therapy is a possible future alternative. Evinacumab, monoclonal antibody inhibiting angiopoietin-like protein 3, was approved in 2021 for adjunct therapy. Children Given that<unk>  is present from birth and atherosclerotic changes may begin early in life, it is sometimes necessary to treat adolescents or even teenagers with agents that were originally developed for adults. Due to safety concerns, many physicians prefer to use bile acid sequestrants and fenofibrate as these are licensed in children. Nevertheless, statins seem safe and effective, and in older children may be used as in adults. An expert panel in 2006 advised on early combination therapy with LDL apheresis, statins, and cholesterol absorption inhibitors in children with homozygous<unk>  at the highest risk.
Familial hypercholesterolemia
Familial hypertriglyceridemia
Combined hyperlipidemia
Apolipoprotein B deficiency
Familial multiple lipomatosis
Marfanoid
Fruitarianism
Fabry disease