Young MI Patients’ Ischemic Risk Extends at Least Two Decades

An Italian registry study found that 36% experienced stroke, MI, or CV death, disputing the idea that youth equals low risk.

Young MI Patients’ Ischemic Risk Extends at Least Two Decades

More than a third of people who have an MI before the age of 45 go on to have a recurrent ischemic event in the ensuing 20 years, according to Italian registry data unveiled at the European Society of Cardiology Congress 2019. One-fifth of these events are fatal, speaking to the need to better predict and prevent outcomes in this unique patient population.

Early-onset MI can be a “major cause of physical and psychological morbidity,” Diego Ardissino, MD (Azienda Ospedaliero-Universitaria di Parma, Italy), said in his presentation, adding that “the chronic and degenerative nature” of atherosclerosis carries long-lasting implications.

Yet, Ardissino continued, “there is surprisingly little information that can be used to quantify and characterize the long-term risk of recurrent ischemic events in this specific population.”

Commenting on the findings for TCTMD, Ron Blankstein, MD (Brigham and Women’s Hospital, Boston, MA), described the length of follow-up as “quite remarkable” and the age cutoff of 45 years as particularly informative. “The event rates are fairly striking, and it’s also interesting to note the type of events,” he observed, adding, “By far the most common events were nonfatal myocardial infarctions, which occurred in about a quarter of patients. [One in four] is actually a significant number.”

The results were also published online in the Journal of the American College of Cardiology, with Giuseppe Maglietta, MSc (Azienda Ospedaliero-Universitaria di Parma), as lead author.

Large Italian Database

For the Italian Genetic Study on Early-onset Myocardial Infarction, Maglietta and colleagues looked at 2,000 patients (89% men) who experienced a type 1 MI before age 45 (median age 41 years). Nearly 86% of the events were STEMIs, and 86.7% had significant coronary stenosis that included not only single-vessel but also multivessel and left main disease.

Over the median follow-up of 19.9 years (39,535 person-years), 36% of patients had an ischemic event: 153 CV deaths, 479 recurrent nonfatal MIs, and 82 acute ischemic strokes. Cumulative event rates at 20 years were 6.7%, 23%, and 4%, respectively, for these endpoints and 11.5% for all-cause mortality. Six factors were independently associated with worse outcomes over follow-up.

Independent Predictors of Long-term MACE Risk



95% CI

Baseline Ejection Fraction






Baseline Duke Coronary Score Index



Male Sex



Previous Arterial/Venous Thromboembolic Event






Male sex predicted higher risk of MI (OR 2.10; 95% CI 1.38-3.25), whereas female sex predicted higher risk of ischemic stroke (OR 1.90; 95% 1.00-3.35).

“Future studies addressing the impact of early aggressive treatments in this highly selected, high-risk patient population are required, in order to establish the clinical impact of risk characterization on long-term recurrence outcomes,” the investigators conclude.

Blankstein pointed out that many patients experienced ischemic events despite being on medical therapy; all were on statins, 96.2% on aspirin, 89.2% on beta-blockers, 74.9% on P2Y12 inhibitors, and 48.0% on ACE inhibitors or angiotensin receptor blockers. What’s unclear is specifically when the patients took these medications, he noted. “When you have a study that follows patients over 20 years, it is challenging to know exactly what the treatment was.”

Young patients’ high risk means that secondary prevention is important and, based on the above numbers, may need to be more aggressive, he suggested. “Anecdotally, we have observed that sometimes young patients are not treated as aggressively because people still view youth as low risk.”

The “big question” in looking at these data, said Blankstein, is why the index MIs occurred in such young patients. His own research, as reported by TCTMD, has shown that the “vast majority of these patients actually have underlying risk factors. These are not just events that are happening out of the blue,” he said, adding that he would have been interested in seeing what risk factors were present in the Italian cohort. With YOUNG-MI, the strongest predictors were dyslipidemia and smoking, Blankstein noted.

How best to treat younger patients is growing ever important, he said. In the United States, “despite an overall reduction the rate of myocardial infarction, we’ve seen a recent increase in young individuals, which we think has been driven by risk factors like obesity and diabetes [growing] over time,” as well as by substance abuse, Blankstein observed.


  • Maglietta G, Ardissino M, Tagliazucchi GM, et al. Long-term outcomes after early-onset myocardial infarction. J Am Coll Cardiol. 2019;Epub ahead of print.

  • Ardissino D. Long-term prognosis of early-onset myocardial infarction: results from the multicenter, prospective, longitudinal Italian Genetic Study on Early-onset Myocardial Infarction. Presented at: ESC 2019. September 1, 2019. Paris, France.

  • Maglietta and Ardissino report no relevant conflicts of interest.
  • Blankstein reports receiving research support from Amgen.

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