Abstract
The purpose of this review article was to describe recent advances in our knowledge about how diabetes and metabolic syndrome are changing the face of familial hypercholesterolemia. Heterozygous familial hypercholesterolemia, most commonly caused by disruption to LDL receptor function, leads to lifelong elevation of LDL cholesterol and increased risk of atherosclerotic cardiovascular disease. Familial hypercholesterolemia was originally described as a form of 'pure' hypercholesterolemia, in the sense that levels of LDL were uniquely affected. Studies of familial hypercholesterolemia among individuals of predominantly Western European descent conformed to the perception that individuals with familial hypercholesterolemia tended to be lean and otherwise metabolically healthy. More recently, as we have studied familial hypercholesterolemia in more diverse global populations, we have learned that in some regions, rates of diabetes and obesity among familial hypercholesterolemia patients are very high, mirroring the global increases in the prevalence of metabolic disease. When diabetes and metabolic disease coexist, they amplify the cardiovascular risk in familial hypercholesterolemia, and may require more aggressive treatment.
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