Familial Hypercholesterolemia Among Young Adults With MI

Study Questions:

What is the prevalence and what has been the treatment of familial hypercholesterolemia (FH) among US adults who experience a myocardial infarction (MI) at a young age?


The YOUNG-MI registry conducted at Brigham and Women’s and Massachusetts General Hospitals is a retrospective cohort study that includes patients who experienced an MI at or below age 50 years between 2000 and 2016. Probable or definite FH was defined by the Dutch Lipid Clinic Network (DLCN) criteria. Outcomes included the proportion of patients classified as probable or definite FH, use of lipid-lowering therapy, and low-density lipoprotein cholesterol (LDL-C) achieved 1-year post-MI.


The cohort consisted of 1,996 adults with a median age of 45 years; 19% were women, and 54% had ST-segment elevation MI. Probable + definite FH was present in 180 (9%), of whom 42.8% were not on statins prior to their MI. Of the 1,966 patients surviving until hospital discharge, 89.4% of FH patients and 89.9% of non-FH patients were discharged on statin therapy (p = 0.82). Among FH patients, 63.3% were discharged on high-intensity statin compared with 48.4% for non-FH patients (p < 0.001). At 1-year follow-up, the percent reduction in LDL-C among FH patients was 44.4% compared with 34.5% (p = 0.006) in non-FH patients. The proportion of patients with LDL-C ≥70 mg/dl was higher among FH patients (82.2%) compared with non-FH patients (64.5%; p < 0.001).


Clinically defined FH was present in nearly 1 of 10 patients with MI at a young age. Only two-thirds of FH patients were discharged on high-intensity statin therapy, and the vast majority had elevated LDL-C at 1 year. These findings reinforce the need for more aggressive lipid-lowering therapy in young FH and non-FH patients post-MI.


Suspecting and detecting heterozygous FH (HeFH) is most important and likely underestimated in a retrospective chart review. How many physicians check for tendon xanthomas and arcus senilis? How accurate is the family history? In this important study, 1 in 10 young adults with MI had HeFH by the DLCN, whereas it was 6 in 10 young adults with MI, a family history of premature coronary artery disease, and LDL-C ≥160 mg/dl. But how accurate is that and what would be the implications to family members and third-party payers? Is it time for genetic testing? I think so in select patients, considering DLCN is not sensitive for HeFH. In a sample of 1,377 Italian adults (mean age, 43 years) with genetic proven HeFH, 28.5% were classified as probable FH and 38% were classified as definite HeFH by the DLCN. Consider the very high risk of MI in HeFH compared to polygenic hypercholesterolemia (about four-fold at LDL-C of 190 mg/dl, and two- to three-fold at lower levels), that about 15% of patients with premature MI have HeFH based on genetics, that a significant percentage of those with HeFH have an LDL-C <190 mg/dl, and that it is autosomal dominant, and if positive, it impacts adult first-degree relatives with an LDL-C as low as >130 mg/dl and their offspring. Examples of those with a much higher risk of HeFH would be descendants of French Canadians, Ashkenazi Jews, Lebanese Christians, and South Afrikaners.

Clinical Topics: Acute Coronary Syndromes, Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins

Keywords: Acute Coronary Syndrome, Cholesterol, LDL, Coronary Artery Disease, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, Myocardial Infarction, Primary Prevention, Young Adult

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