Familial Hypercholesterolemia Seen in 10% of Young MI Patients

Even after MI, too many FH patients, as well as non-FH patients, aren’t treated with high-intensity statins, according to experts.

Familial Hypercholesterolemia Seen in 10% of Young MI Patients

Nearly one in 10 young adults hospitalized with acute myocardial infarction have probable or definite familial hypercholesterolemia (FH), according to the results of a new study. While the majority of individuals who survived the MI were discharged on statins, roughly one-third of FH patients and more than half of patients without FH are discharged home without a high-intensity statin.

At 1-year follow-up, more than 80% of FH patients and nearly 65% of patients without FH have LDL cholesterol levels still considered too high by the current guidelines.

“When we actually look at the LDL reduction, regardless of whether or not people had FH or didn’t have FH, the overall reduction in LDL cholesterol was rather modest,” said senior investigator Ron Blankstein, MD (Brigham and Women’s Hospital, Boston, MA). “You’d think: these individuals already had a heart attack, they’re young, and that clinicians would be very aggressive in treating their LDL down as low as possible. The reality is that the vast majority of them had LDL cholesterol levels greater than 70 [mg/dL] a year after their heart attack.”

The new analysis, which was led by Avinainder Singh, MD (Brigham and Women’s Hospital), and published online May 13, 2019, in the Journal of the American College of Cardiology, is based on 1,996 adults included in the YOUNG-MI registry. The registry, explained Blankstein, includes patients 50 years or younger hospitalized at his institution and Massachusetts General Hospital and was designed to assess the clinical characteristics of young MI patients.

While overall MI rates are declining in the United States, events in younger individuals are on the rise, which Blankstein called “an alarming statistic.”

“It’s interesting, because when young people come in they’re very surprised they’ve had a heart attack,” he told TCTMD. “They ask, ‘Why did this happen to me? I’m totally healthy. I’m in my 40s.’ When you look, a lot of these individuals might not be as healthy as they think. They smoke, they might be overweight, some have diabetes or very high cholesterol. In the vast majority of cases when we look back, we find there are underlying risk factors.”

Analysis Based on Lipid Criteria, Not Genes

Of the 1,996 adults hospitalized with MI, 180 patients (9%) had probable/definite FH as defined by the Dutch Lipid Clinic Criteria. Blankstein said that some might have expected the prevalence of FH to be higher in these young patients, especially since FH is the most common cardiac genetic abnormality and has been strongly linked with early cardiovascular events; he, however, considers it relatively low.

“It’s important to acknowledge that the vast majority of events are not necessarily in these patients with familial hypercholesterolemia but are occurring in individuals with many other underlying risk factors,” he said.  

For patients with and without FH in the present analysis, diabetes was observed in roughly 20% of people. More than 50% were smokers, and one-third were obese. 

For patients with FH, the baseline LDL cholesterol upon hospitalization for MI was 179.8 mg/dL, but only 57.2% were currently taking a statin. Blankstein said that potentially all FH patients should be on statins but noted the relatively low rate of use might be because FH was not diagnosed prior to the MI. At discharge, 63.3% of FH patients and 48.4% of non-FH patients were discharged on a high-intensity statin. At 1 year, the mean LDL cholesterol level was 96.0 and 80.0 mg/dL in patients with and without FH, respectively, but more FH patients had inadequately controlled LDL levels. For example, 82.2% had LDL levels 70 mg/dL or higher and 43.0% had levels 100 mg/dL or higher.

“It shows us that we probably need to be more aggressive when lowering LDL cholesterol based on the plethora of data showing that the lower we reduce LDL cholesterol the more we can decrease events,” said Blankstein. “It’s also in keeping with the 2018 cholesterol guidelines. For individuals at high risk, such as those who had events, there is an opportunity to further lower LDL cholesterol.”

In clinical practice, physicians often start with a single agent and assess the initial LDL response, adding a second agent, like ezetimibe or a PCSK9 inhibitor, if needed. The PCSK9 inhibitors were not approved at the time of this analysis, but just 5.0% of FH patients were sent home from hospital on ezetimibe. “Often it’s easy to start something in the hospital and there is an intention of intensifying therapy in follow-up, but it doesn’t always happen,” said Blankstein.

Underdiagnosed and Underestimated

“FH remains underdiagnosed and underestimated in most countries, likely resulting in preventable long-term morbidity and mortality in FH patients,” G. Kees Hovingh, MD, PhD; Laurens Reeskamp, MD (Academic Medical Center, Amsterdam, the Netherlands), and Kausik Ray, MD (Imperial College London, England), state in an editorial accompanying the study. For this reason, they say, the goal with FH is “early detection and early treatment.”

Joshua Knowles, MD, PhD (Stanford University, CA), who was not involved in the study, said that the US experience is paralleled in countries around the world, with physicians and health systems missing opportunities to find FH patients before the onset of adverse cardiovascular events. For example, in a Spanish study published in 2017, investigators identified a near identical prevalence of FH (8.7%) in adults 65 years and younger who presented with ACS and elevated LDL cholesterol levels.

If these patients were identified, and treatment was initiated, mostly with generic statins, the vast majority of these myocardial infarctions could be prevented. Joshua Knowles

“This is a huge missed opportunity for prevention,” he told TCTMD. “If these patients were identified, and treatment was initiated, mostly with generic statins, the vast majority of these myocardial infarctions could be prevented,” he told TCTMD.

FH patients with a prior MI are at an “extraordinarily high risk” for recurrent events, added Knowles, noting that the new American Heart Association/American College of Cardiology cholesterol guidelines identify this risk group as candidates for therapy with non-statin agents, such as the PCSK9 inhibitors.

For Howard Weintraub, MD (New York University School of Medicine, New York, NY), the implications of the research go beyond FH. He noted there is an abundance of data showing the benefits of aggressively reducing LDL cholesterol following MI and said these new data are consistent with previous studies showing that only a very small proportion of patients at high risk for atherosclerotic cardiovascular disease attain the target of less than 70 mg/dL. More contemporary evidence has suggested that only a small percentage of patients are started on the now available PCSK9 inhibitors, “which could easily improve their LDL and significantly lower their future cardiovascular risk, particularly in patients with a recent MI,” Weintraub said in an email.  

The editorialists point out that there was no difference in all-cause mortality in long-term follow-up between the FH and non-FH patients, adding that for this reason it’s hard to justify add-on lipid-lowering therapy, such as ezetimibe or the PCSK9 inhibitors. However, like the researchers, they caution against drawing firm conclusions because the study was underpowered for fatal events in this relatively young patient population.     

Sources
Disclosures
  • Blankstein reports serving on the advisory board of Amgen and research support from Amgen, Astellas, and Sanofi.
  • Hovingh reports receiving honoraria for consulting, advisory boards, and conduct of clinical trials from Amgen, Aegerion, Pfizer, AstraZeneca, Sanofi, Regeneron, KOWA, Ionis, and Cerenis. Since April 2019, he has been a part-time employee of Novo Nordisk AS.
  • Ray reports personal fees for serving on steering committees from Sanofi, consulting lecture, and personal fees from Abbvie, and grants and personal fees from Amgen, Sanofi, Regeneron, Merck Sharp & Dohme, and Pfizer. He also reports support from Imperial BRC and personal fees from AstraZeneca, Medco, Resverlogix, Akcea, Boehringer Ingelheim, Novo Nordisk, Takeda, Kowa, Algorithm, Cipla, Cerenis, Dr Reddy’s, Lilly, and Zuellig Pharma outside of the submitted work.
  • Reeskamp and Knowles report no relevant conflicts of interest.

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