Physicians' Academy for Cardiovascular Education

Almost 1 in 10 of young adults with MI has clinically defined FH

Familial Hypercholesterolemia Among Young Adults With Myocardial Infarction

Literature - Singh A, Gupta A, Collins BL et al., - J Am Coll Cardiol. 2019. DOI: 10.1016/j.jacc.2019.02.059

Introduction and methods

It is estimated that familial hypercholesterolemia (FH) remains undiagnosed in >90% of patients [1]. While the prevalence of FH in the US general population is thought to range from 1 in 212 to 1 in 250 [2,3], it is unclear what this is among individuals who experience a CV event at a young age. Statin use is low in young adults with elevated LDL-c (≥190 mg/dL), despite their high CV risk [4]. Also young patients with FH are undertreated [2]. This is not in line with the new 2018 guideline on the management of blood cholesterol, which considers severe hypercholesterolemia as a very high risk condition, and recommends maximally tolerated statin therapy in all with LDL-c ≥190 mg/dL [5].

The YOUNG-MI [6] is a retrospective cohort study from the Brigham and Women’s Hospital and Massachusetts General Hospital, which included patients who were admitted with a myocardial infarction (MI) at or before 50 years of age, between 2000 and 2016. For this analysis, only type I MI were considered. Individuals with known coronary artery disease (CAD, prior MI or revascularization) or missing LDL-c were excluded. Patients with FH were identified based on the Dutch Lipid Clinic (DLC) Network criteria [1]. For this analysis, patients classified as probable or definite FH were considered as clinically defined FH.

In the YOUNG-MI registry, the proportion of patients was evaluated that met standard clinical criteria for FH among a cohort of patients that had an MI at a young age. The frequency and intensity of lipid-lowering therapy was also evaluated, as well as the LDL-c achieved 1 year post MI. Moreover, long-term, all-cause and CV mortality were compared between patients with and without FH.

Main results


This analysis of the YOUNG-MI cohort showed that 9% of young adults who experienced an MI, had clinically defined FH. Over 40% of FH patients were not on statin therapy prior to MI. After discharge, 10% of FH patients were not prescribed a statin, and only two-thirds were prescribed a high-intensity statin. The majority of FH patients still had elevated LDL-c at 1 year. Mortality did not differ between FH and non-FH patients over long-term follow-up.

Editorial comment

Although evidence from both post hoc analyses of trial data and observational studies have consistently shown a clinical benefit of statin therapy in patients with FH, a large gap exists between clinical science and clinical practice, note Hovingh and colleaugues [7]. FH is underdiagnosed and undertreated in most countries, likely resulting in preventable morbidity and mortality in FH patients. The study by Singh et al. adds information to the concept of ‘early detection and early treatment’ that is relevant to FH. But, Hovingh et al. note that the findings merit closer attention. Autosomal dominant FH has a defined genetic basis and is, in addition to high LDL-c levels, associated with physical manifestations and salient features in the family history. ‘While some have attempted to simplify the definition to one based on LDL-C levels alone, this is potentially misleading as hypercholesterolemia per se often has a polygenic basis or even reflects elevated Lp(a) levels.’ The chosen definition affects the conclusion that can be drawn.

The DLCN uses points to identify the likelihood of FH, and 6-7 points is considered probable and ≥8 points definite FH. In this study, everybody already started out with 2 points due to premature MI. This may have lead to overestimation of the number of FH cases in this cohort. Moreover, cases were not validated with the gold standard of genetic testing for FH. Thus, the true prevalence in this cohort may be smaller than 1 in 10. ‘Indeed, unbiased estimates suggest that insulin resistance, diabetes, and smoking contribute to a greater extent to the risk for young MI at population level.’ And indeed the “FH cohort” showed high prevalences of these risk conditions. This is usually not observed in unselected longitudinal studies of FH.

The authors conclude that the present study shows that hypercholesterolemia is common in survivors of premature MI. ‘Among those who are probable or definite FH, genetic testing should be offered to assess whether autosomal dominant FH is present, as this will open the door to cascade testing and treatment of FH.’


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