A Personalized Medicine Approach is Best for Patients with Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is an autosomal semi-dominant condition characterized by biallelic pathogenic variants impacting low-density lipoprotein receptor (LDLR) function. Affected individuals have severely elevated LDL cholesterol, early onset atherosclerotic heart disease and/or aortic stenosis, and characteristic clinical findings. While the cause is known and diagnosis is relatively simple, real-world HoFH care presents many complexities, including genetic heterogeneity and the diverse personal and social circumstances that influence care. Genetics-informed treatment involves a trial-and-error approach that warrants specific considerations during pregnancy. Thus, HoFH care requires a deep understanding of personal factors, social determinants of health, and a flexible, adaptable approach to treatment, all of which justify the need for personalized care. Framed by complexity theory, this review offers strategies for personalizing HoFH care, including a reconceptualization of the definition of health and implementing a multidisciplinary team approach. We also recommend integrating complexity theory and systems thinking into clinical care. By doing so, we illustrate the advantages of classifying knowledge complexity to inform clinical decision-making. We also demonstrate how openness to relationship-building and time investment is critical to materializing personalized care to HoFH.