Even with coronary revascularization and secondary prevention, individuals with premature coronary artery disease (CAD) are at high risk for recurrent events and death, with much of the risk attributable to poor risk-factor control.
The 880 patients prospectively studied in this trial, published online in the October15 issue of the Journal of the American College of Cardiology, were younger than 45 years at the time of their first hospital admission for a coronary event.
Gilles Montalescot (Source: Fredy Perojo/Medscape)
"This population shows us an accelerated story of atherothrombosis with devastating medical and social complications," Gilles Montalescot, MD, PhD, Sorbonne Universit and Hpital Piti-Salptrire, Paris, told theheart.org| Medscape Cardiology.
"Some patients have turned into heart failure already, a few got a heart transplant, and, unfortunately, some have also died from their atherothrombotic disease at a very young age," he added.
The majority of patients in the registry called AFIJI (Appraisal of Risk Factors in Young Ischemic Patients Justifying Aggressive Intervention) presented with STEMI and underwent coronary revascularization. Of those who did not, their MIs were most often caused by coronary dissection (mostly in women) or acute coronary thrombosis without evidence of underlying stenosis.
In the 20 years after their first event, 30% of patients with premature CAD had a second event. Most recurrences were nonfatal MIs (2.6 events per 100 patient-years), with all-cause death (1.6 per 100 patient-years) and stroke being less frequent (0.70 per 100 patient-years).
About half of recurrences occurred within the first 4 years of follow-up and 75% within the first 10 years. Of those who had nonfatal recurrences, 36% went on to have at least a second MACE event.
"The young CAD patients have a good hospital prognosis with a low death rate, but the atherothrombotic disease is very aggressive in the long term," said Montalescot, who was the senior author on the study. Jean-Phillipe Collet, MD, PhD, also from the Sorbonne and Hpital Piti-Salptrire, was the first author.
"Prevention measures are paramount and not at their best in these patients," Montalescot added.
The strongest predictors of a first recurrent event included ethnic origin (sub-Saharan African vs Caucasian; adjusted hazard ratio [aHR], 1.95; P= .02), the presence of inflammatory disease (aHR, 1.58; P= .03), and persistent smoking (aHR, 2.32; P< .01).
The same factors plus Asian ethnicity predicted multiple recurrences events, with smoking having the greatest impact on prognosis (aHR, 2.70; P< .01).
"We need to underline that smoking and prior family history of CAD are strong risk factors for premature CAD and for recurrent events of this disease," said Montalescot.
One of 10 patients in the registry had a chronic inflammatory or immunosuppressive disease, most often HIV (4.0%) or cancer (3.5%), but including viral hepatitis (1.3%) and systemic autoimmune disease, including polyarthritis and systemic lupus with antiphospholipid syndrome (1.3%).
Interestingly, one of three who had multiple MACE events during follow-up eventually developed diabetes, compared with one in ten event-free patients.
"This was a half-surprise," said Montalescot. "Diabetes is a major risk factor and even if only 10.7% of patients had diabetes on admission, this rate goes up to 31.7% in the patients with three recurrent events over the 20-year follow-up period. Nutrition, education, and exercise need to be promoted more in these young patients."
The long-term evolution of CAD in young patients with premature disease in the setting on contemporary secondary prevention is poorly defined. Collet and colleagues sought to determine whether to better define prognosis and to determine whether secondary events were more likely to be related to new coronary lesions or to the initial culprit lesion.
Myocardial infarction, which was most often the first recurrent event, was more likely to be caused by a new lesion rather than the initial culprit lesion (17.3% vs 7.8%; P= .01).
To Montalescot, this is an indication that revascularization works well, but secondary prevention is not strong enough or adherence is not good enough.
The researchers will continue to follow these patients, "most of whom have not yet reached the average age of CAD onset in the general population," they note, and are still enrolling patients in the registry.
In an interview with theheart.org| Medscape Cardiology, Erin Michos, MD, MHS, Johns Hopkins Medical Institute, Baltimore, who, along with AndrewD Choi, MD, George Washington University School of Medicine, Washington, DC, coauthored an editorial accompanying the publication, appreciated the uniqueness of the study cohort.
"Usually when we think about premature coronary artery disease, a man before 55 or a woman before 65 is labeled premature, so this population of 880 patients who had events before the age of 45 is very premature, we call it AMI in the young," reported Michos.
"That this group in France has followed these individuals for 20 years is really interesting and lets us see what happens to these young adults who have this event so early in life."
And what happens is pretty dramatic, she noted. "The recurrent event rates are really high one out of three people having events over 20 years on a background of what was good standard secondary prevention," noted Michos.
"So, while there may have been genetic factors contributing to the initial event, that smoking turned out to be the strongest prognostic factor for both first recurrent event and multiple recurrent events, this just highlights how an entirely modifiable risk factor is the biggest driver of recurrent events."
She added that better implementation of smoking-cessation programs, but also cardiac rehabilitation and team-based care, and aggressive lowering of LDL should be emphasized, particularly in patients with added risk associated with ethnicity or the presence of inflammatory disease.
"In the US, we've identified South Asian ancestry as an independent predictor of risk, so these are patients we need to follow more closely and consider trying to get LDL cholesterol down very low to prevent plaque progression and recurrent events."
This study was led by the ACTION Study Group at the Institute of Cardiology of Hpital Piti-Salptrire. Montalescot has received research grants from a number of industry and academic entities, along with Elsevier and WebMD. Michos is supported by the Blumenthal Scholars Fund for Preventive Cardiology at Johns Hopkins .
J Am Coll Cardiol. 2019;74:1868-1878. Abstract, Editorial
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