Cholesterol Guidelines Fail Young MI Patients Who Might Have Benefited From Statins

Under current national cholesterol guidelines, only half of younger patients who experience an MI would have been identified as being at high risk and eligible for treatment with lipid-lowering therapy prior to their event, a new study suggests.

“The guidelines do pretty well for older age categories, but not so good with younger age categories,” said Michel Zeitouni, MD, MS (Sorbonne University, Paris and Duke Clinical Research Institute, Durham, NC), lead author of the study published August 3, 2020, in the Journal of the American College of Cardiology. “Interestingly, this failure to identify young patients at risk occurs despite them having a high proportion of several risk factors and risk enhancers.”

Zeitouni’s study also showed that even post-MI, younger patients were less likely to receive statins than middle-age or older adults. “If you follow the guideline, only 28% of them are actually eligible for intensive lipid-lowering therapy compared with a much higher rate of older [patients],” he told TCTMD.

The most recent cholesterol guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) were released in 2018. In addition to reinforcing lifestyle modification and prevention, they emphasize that high cholesterol at any age significantly increases CV disease and advise early risk assessment, even among children and young adults.

In an editorial accompanying Zeitouni’s study, Ron Blankstein, MD (Brigham and Women’s Hospital, Boston, MA) and Avinainder Singh, MD (Yale School of Medicine, New Haven, CT), note that the presence of risk enhancers was not required when considering statins for patients with borderline atherosclerotic cardiovascular disease (ASCVD) risk under the 2013 guidelines, but it was added in to the 2018 guideline. Still, even when the risk enhancer was accounted for in Zeitouni’s study, the proportion of statin-eligible patients only increased by 6.2%, which Blankstein and Singh say illustrates that current risk scores are heavily based on age.

“It is important to recognize that certain risk factors may be particularly important among young individuals, including tobacco use, low high-density lipoprotein cholesterol, obesity, and substance abuse,” they write. Like Blankstein and Singh’s recent research from YOUNG-MI, the study by Zeitouni and colleagues shows that about half of those who had an MI before age 55 were smokers.

Guideline Gaps Revealed

For the study, Zeitouni et all examined data on 6,639 patients with MI from the Duke Databank for Cardiovascular Disease (DDCD). Of these, 41% were patients under age 55. Compared with older (> 65 to ≤ 75) and middle-aged patients (≥ 55 to ≤ 65), younger adults with MI were more often male, African-American, and smokers and tended to have higher levels of LDL cholesterol and triglycerides. They were less likely to have hypertension or diabetes, however.

Younger patients had a lower 10-year ASCVD risk score prior to their index MI than older and middle-aged adults, but they had a greater median lifetime risk (33.9% vs 32.2% vs 31.9%, respectively; P < 0.001). Other risk factors seen more frequently in younger patients were obesity, metabolic syndrome, high triglyceride levels, and familial history of CAD.

Under both the 2013 and the 2018 guidelines, younger adults were less likely to meet a class I or IIa recommendation for statins than older or middle-age patients. While 56.7% of those under age 55 would have been eligible for statins prior to their index event under the 2013 guidelines, only 46.4% were eligible under the 2018 guidelines (P < 0.01). The newer guidelines also affected the middle-aged group, with fewer of them meeting the criteria for statins under the newer versus older guidelines (59.5% vs 70%; P < 0.01). The opposite was true in the older-age group, which had a higher percentage of patients eligible for stain therapy under the newer versus older guidelines (88.2% vs 85.1%; P < 0.01).

Post-MI, only 28.3% of those who had an event before age 55 met the high-risk criteria for intensive secondary prevention with lipid-lowering therapy according to the newer guidelines, compared with 40% of middle-aged and 81.4% of older patients.

Shift in Focus Needed

According to Zeitouni and colleagues, neither the 2013 nor 2018 cholesterol guideline offers “comprehensive recommendations for adults younger than 40 years of age, who can become eligible for statin therapy in primary prevention with a class I indication only if they have an LDL cholesterol level > 190 mg/dL, regardless of their smoking status, body mass index, or other risk factors.” While the 2018 guideline gives a class IIa recommendation for statins in individuals ages 20 to 39 who have an LDL level > 160 mg/dL and a risk enhancer, it still doesn’t seem to be enough to target all at-risk younger people, they write.

The first thing that young patients in the ICU often ask after their MI is: ‘Why me?’ Michel Zeitouni

In their editorial, Blankstein and Singh say Zeitouni et al’s findings combined with those from YOUNG-MI “should force us to reexamine how we allocate statin use among young individuals.” Additionally, they say there are many other opportunities to reduce MI risk that likely are not being utilized in clinical practice.

“Ultimately, greater primordial and primary prevention efforts are needed,” they write. “If our goal is to achieve the greatest possible reduction in cardiovascular events, we should not miss any opportunities  to improve prevention.”

To TCMTD, Zeitouni concurred that the guidelines are not the entirety of the problem.

“Trialists and researchers have to focus on these young patients,” he said, adding that subsets of younger populations, including more young women, need to be pursued to further understanding of why some are more at risk than others of an early MI.

“The first thing that young patients in the ICU often ask after their MI is: ‘Why me?’” Zeitouni said. “The second thing they ask is: ‘What is my life expectancy now?’ This is something we need to do more research on [and] we need to better evaluate secondary prevention therapies in this young population.”