Lipid characteristics and intensive lipid-regulating strategies in familial hypercholesterolemia

How to treat lipid-lowering disorders in the elderly?

Elderly people over 80 years old often suffer from multiple chronic diseases. Current research shows that elderly patients with hypercholesterolemia combined with cardiovascular disease or diabetes can benefit from lipid-lowering therapy. Because elderly people take multiple medications, attention must be paid to drug interactions and adverse reactions. Most elderly patients have varying degrees of liver and kidney dysfunction, so the choice of lipid-lowering drug dosage needs to be individualized. The starting dose should not be too high, and the dosage should be adjusted according to the treatment effect, with close monitoring of liver and kidney function and creatine kinase. For elderly patients, there are no specific recommendations regarding the target of statin therapy.

How to treat lipid-lowering disorders in patients with familial hypercholesterolemia?

Familial hypercholesterolemia (FH) is an autosomal dominant inherited cholesterol metabolism disorder. The main mechanism is a functional genetic mutation of the LDL receptor, and in a few cases, it is due to functional mutations of Apo B or PCSK9. Its prominent clinical feature is a significantly elevated serum LDL-C level, leading to early-onset coronary heart disease (myocardial infarction or angina).

Based on dominant inheritance, FH phenotypes are divided into homozygous (HoFH) and heterozygous (HeFH). Differentially, HeFH patients typically have serum TC levels >8.5 mmol/L (328 mg/dL), while HoFH patients typically have serum TC levels >13.5 mmol/L (521 mg/dL). Without treatment, HeFH patients often develop cardiovascular disease in their 40s (men) or 50s (women), while HoFH patients often develop serious cardiovascular disease in early childhood. Their cardiovascular disease mortality rate in adolescence is more than 100 times higher than that of non-FH patients.

The goal of FH treatment is to reduce the risk of ASCVD and decrease the incidence of fatal and disabling cardiovascular disease. All patients with fibrocystic heart disease (FH) (including those with HoFH and HeFH) should undergo comprehensive therapeutic lifestyle changes: a balanced diet, low-fat and low-cholesterol diet, appropriate exercise, smoking cessation, and maintaining a healthy weight. FH patients should begin statin therapy in adolescence, which can significantly reduce the risk of ASCVD. The target level for lipid-lowering therapy is the same as for high-risk cardiovascular disease patients. FH patients often require combination therapy with two or more lipid-lowering drugs. For patients whose cholesterol levels do not reach the target level despite combination lipid-lowering therapy and whose cardiovascular disease is progressing, adjunctive lipoprotein plasma exchange may be considered.