Coronary artery disease (CAD) is the most common cause of death worldwide. Although the overall incidence of acute coronary syndrome (ACS) has decreased in developed countries in the last decade, data from several registries have shown that this trend is not equal for all age subgroups, with a stable, even increasing, incidence of ACS being observed in younger patients.1 So far, there has been no standard definition of “young” age in patients with acute myocardial infarction (AMI). Several cutoff points appear throughout the literature, with the age of ≤ 45 years being the most consistent.2–4 Moreover, it has been reported that 4% to 10% of AMIs occur before the age of 45 years, while the incidence declines if the age limit is lower.4

Cardiovascular risk factors and clinical presentation differ in older compared with younger patients. The most frequent initial manifestation in the latter is ST-segment elevation myocardial infarction (STEMI).5 Sex differences and predictors of mortality have been described in small cohorts of young patients with ACS.6 The young population with ACS, especially women, has been underrepresented in many clinical trials due to their lower incidence of ACS.7 Considering the above, it is essential to have more data on younger patients presenting with STEMI. Clinical STEMI guidelines recommend regional STEMI networks to organize all key stakeholders so that patients can receive optimal and timely reperfusion treatment (primary percutaneous coronary intervention (pPCI), fibrinolysis, or a combination of both).8

Using the database from the Catalonia AMI Code network registry (Codi IAM), this study aimed to analyze and compare clinical characteristics, in-hospital and 2-year outcomes between patients aged<45 years and those aged ≥ 45 years. Given the relevance of a sex bias in diagnosis and the prognostic implications after an ACS in women, we also analyzed sex-based differences in patient characteristics and prognosis.

The key findings of the present study, comparing clinical characteristics, in-hospital and 1- and 2-year outcomes between patients aged<45 and ≥ 45 years, were as follows: a) younger patients with STEMI were more frequently smokers but had a lower disease burden than older patients; b) younger patients with STEMI were more likely to present with cardiac arrest, but the time frame from FMC to wire crossing was shorter than that in the older group; c) all-cause mortality rates, both in-hospital and at 2 years, were lower in patients aged<45 years; and d) despite recent advancements in STEMI treatments, a significant sex gap was noted in this study. Among patients aged<45 years, the time from symptom onset to reperfusion was longer in younger women than in their male counterparts, and they also received less primary PCI. Additionally, the rate of cardiogenic shock as a complication of STEMI at the initial presentation was more prevalent in younger women than in their male counterparts. The main findings are summarized in figure 4.

Figure 4.

Central Illustration. Summary of the main findings of this study. Clinical profile and prognosis of young patients vs older patients with ST-elevation myocardial infarction managed by the emergency-intervention AMI Code Network from 2015 to 2020 in Catalonia, Spain. Despite having high-risk features on admission, patients aged<45 years with STEMI had better outcomes than those aged>45 years. Regarding sex differences among younger patients, women had a higher prevalence of cardiogenic shock, significantly longer times from symptom onset to reperfusion, and were less likely to undergo pPCI than men. FMC, first medical contact; pPCI, primary percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.

(0.38MB).

In keeping with the findings of others, at least 1 modifiable cardiovascular risk factor, hypertension, dyslipidemia, diabetes, or smoking, was identified in our cohort of patients with premature MI.13,14 In the cohort aged between 35 and 45 years, 1 in 2 patients was an active smoker, increasing to 2 in 3 patients in those aged<35 years. Many studies have analyzed the effect of different cardiovascular risk factors on the pattern and severity of CAD. Of these, the most important was smoking.15–17 Additionally, an association has been established between active and passive smoking and the development of premature CAD.18,19 Smoking accelerates atherosclerosis by increasing the oxidation of low-density lipoprotein and damaging coronary endothelial vasodilation.20 These deleterious changes result in a larger MI size, poor recovery from myocardial injury, and persistent inflammation triggering coronary recurrences, heart failure, and cardiovascular mortality.21 Furthermore, inadequate control of cardiovascular risk factors is associated with decreased life expectancy and productivity costs, especially in the younger population.22 Primary and secondary prevention strategies are needed that include education targeting active smoking and lifestyle modification, especially in patients aged<45 years. Evidence demonstrates that smoking cessation is the single most effective intervention for improving long-term outcomes in younger patients, reducing all-cause and cardiovascular mortality by>50%.5 Additionally, a public health policy that embraces zero tolerance of childhood passive tobacco exposure should be pursued as there is sufficient evidence to date demonstrating the detrimental cardiovascular consequences in this group.18

In our cohort, younger patients with STEMI were more likely to have a cardiac arrest on presentation than older patients. Most ventricular fibrillation (VF) and sudden cardiac arrest are thought to occur in asymptomatic individuals without a pre-existing structural cardiac disease and represent the first manifestation of CAD. The GEVAMI study compared the first STEMI with and without VF and identified several independent risk factors for VF, including younger age.23 This finding could also be related to a higher thrombus burden in this cohort with TIMI flow 0 before pPCI. A possible explanation for this result is likely related to plaque rupture, increased blood coagulability, and greater platelet reactivity with a high propensity for thrombus formation rather than a gradual process, such as atherosclerosis in younger smokers.24 In addition, cocaine and other illicit drug use has been reported in 10% of younger patients with an AMI and associated with cardiac arrest at presentation.25

Current and previous studies have shown that young patients had a better prognosis with lower in-hospital and long-term all-cause death rates than older patients.26,27 In several studies, in-hospital mortality in younger patients with MI ranged from 0% to 4%.28–30 We observed a similar rate of all-cause mortality during hospitalization in our study. This could partially be explained by the fact that younger patients more frequently underwent pPCI and had fewer complications during hospital admission than older patients. In addition, in the present registry, there were no significant differences in major bleeding rates between older and younger patients. This absence of statistical significance could be related to a meager rate of major bleeding in the younger.

In the present study, younger patients also had better long-term outcomes after MI, with a low rate (5%) of all-cause mortality at the 2-year follow-up. This finding highlights the relevance of prompt coronary reperfusion and adequate in-hospital treatment in this group. Although there were no significant differences in the time from symptom onset to myocardial reperfusion, independently of the therapeutic strategy undertaken in younger and older patients, the time from symptom onset to reperfusion with the fibrinolysis strategy was numerically longer in the younger group. This discrepancy could be attributed to the preliminary care received in a rural outpatient clinic and the need to transfer the patient to a health care facility to administer thrombolysis. Additionally, time to diagnosis in young patients was more delayed due to diagnostic doubts in more remote primary care areas, which are less accustomed to diagnosing MI.

We found a significant sex gap regarding symptom onset to reperfusion strategy. Among patients aged<45 years, women underwent fewer pPCI than their male counterparts and had higher rates of cardiogenic shock as a complication of STEMI in the initial presentation. This has been extensively analyzed in previous studies and is attributable to many clinical, social, and economic factors. Among them is a misperception that young women are protected against cardiovascular disease, and misinterpretation of clinical symptoms leads to underestimation of cardiac disease risk with critical prognostic implications31 and reduced or delayed access to invasive treatment strategies. Given the lower proportion of women with STEMI, they are also underrepresented in clinical trials.32 Although many women will experience obstructive CAD, other diseases, such as nonobstructive coronary artery disease, spontaneous coronary artery dissection, and coronary vasospasm, are more frequent in women than in men.33 Spontaneous coronary artery dissection is an increasingly recognized cause of AMI, especially in young and middle-aged women. A conservative treatment strategy is recommended in such cases, leading to lower revascularization rates, particularly among younger women.33,34 In our cohort, 11 patients ≤ 45 years were diagnosed with spontaneous coronary artery dissection and did not receive pPCI, which could partially explain the lower revascularization rates primarily seen in younger women.

Despite growing efforts to study cardiovascular disease in women and improve educational and public awareness, a sex disparity in cardiovascular care persists across all age ranges.35,36 Measures to improve the sex gap in AMI diagnosis and access to treatments in women, especially younger women, should be emphasized and improved.

This registry did not collect information on family history of CAD, use of illicit drugs, lipid profile values at admission and follow-up, treatment administered during admission or upon discharge, and nonobstructive CAD (for example, vasospasm). Additionally, the registry recently incorporated details related to therapeutic hypothermia and mechanical support in 2018.

Empowering younger patients to learn and be more actively involved in cardiovascular risk factor prevention, like smoking cessation and awareness of cardiovascular diseases, including ACS, is imperative to prevent and improve clinical outcomes. Additionally, health providers must be competent to mitigate sex disparities and provide accurate diagnosis and treatment in younger women presenting with cardiovascular disease.

Despite showing high-risk features on admission, younger (< 45 years) patients with STEMI have better outcomes than their older counterparts. Differences in ischemia times due to the health system and treatment have been observed between men and women.

None.

M. Roqué and E. Flores-Umanzor conceived and designed the analysis. E. Flores-Umanzor and P.L. Cepas-Guillen performed the analysis. X. Freixa, A. Regueiro, S. Brugaletta, M. Calvo, I. Forado, M. Sabaté, M. Masotti, H. Tizón-Marcos, A. Ariza, X. Carrillo, S. Rojas, J. Muñoz, J. García, R.M. Lidón and M. Roqué reviewed and edited the manuscript.

None.