A PRS FOR HYPERCHOLESTEROLEMIA

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 Hypercholesterolemia, characterized by high levels of cholesterol in the blood, is a critical risk factor for cardiovascular diseases such as coronary artery disease and stroke. This condition affects a significant portion of the global population, contributing to a high number of cardiovascular events each year. Prevention and effective management of hypercholesterolemia are crucial in reducing the burden of these diseases. 

Hypercholesterolemia arises from a combination of genetic and lifestyle factors. This multifactorial etiology complicates its prediction and management. Understanding the interplay of these factors is essential for developing effective strategies to manage and prevent hypercholesterolemia. 

Lifestyle factors play a significant role in the development and management of hypercholesterolemia. Unhealthy diet, lack of physical activity, obesity, and smoking are key contributors. These modifiable factors offer potential targets for intervention to manage cholesterol levels effectively. 

 Genetic predisposition significantly influences the risk of developing hypercholesterolemia. Classically, specific gene mutations like those in the LDLR, APOB, or PCSK9 genes have been linked to familial hypercholesterolemia. However, recent insights have highlighted the importance of polygenic factors, which involve multiple genes each contributing incrementally to the risk of developing hypercholesterolemia.

Integrating PRS into hypercholesterolemia risk assessment provides a more personalized approach to predicting and managing this condition. Christoffersen and Tybjærg‐Hansen (2021) showed that PRSs can identify many more individuals at high polygenic risk compared with monogenic mutations, modulating the effect of a monogenic variant on risk and potentially identifying patients who may benefit more from lipid-lowering therapy (Christoffersen & Tybjærg‐Hansen, 2021). Additionally, Wu et al. (2021) found that an LDL-C PRS could be used to identify individuals with a higher probability of harboring familial hypercholesterolemia variants, and the association between ischemic heart disease and the LDL-C PRS was comparable to measured LDL-C (Wu et al., 2021). 

Incorporating polygenic risk scores into hypercholesterolemia risk assessment can lead to more personalized and effective management strategies. By enhancing the understanding of individual risk, PRS can guide targeted interventions, potentially improving outcomes in patients with hypercholesterolemia.