Clinical Presentation and In-Hospital Outcomes of Acute Myocardial Infarction in Young Patients

Background Acute myocardial infarction (AMI) in young patients is a concerning issue because of its adverse health and social impacts. Nevertheless, risk factors and prognosis of AMI in young patients are yet to be characterized. Objectives This study aimed to characterize AMI in young patients who underwent primary percutaneous coronary intervention (PCI) using large-scale nationwide all-comer registry data in Japan, the Japanese Percutaneous Coronary Intervention (J-PCI). Methods This retrospective cohort study evaluated the J-PCI registry data of patients with AMI aged 20 to 79 years who underwent primary PCI between January 2014 and December 2018. Data on risk factor profiles, clinical features, post-procedural complications, and in-hospital outcomes were reviewed. Results Among 213,297 patients with AMI who underwent primary PCI, 23,985 (11.2%) were young (ages 20 to 49 years). Compared with the older group (ages 50 to 79 years; n = 189,312), the younger group included a higher number of men, smokers, patients with dyslipidemia, and patients with single-vessel disease, and a lower number of patients with hypertension and diabetes. Despite favorable clinical profiles, younger age was associated with a higher rate of presentation with cardiopulmonary arrest (CPA). Further, concomitant CPA was strongly associated with in-hospital mortality in young patients (odds ratio: 14.2; 95% CI: 9.2 - 21.9). Conclusions Younger patients with AMI presented a higher risk of CPA, which was strongly associated with in-hospital mortality. The results of this study highlight the importance of primary AMI prevention strategies in young individuals.

T he incidence of acute myocardial infarction (AMI) has decreased in older patients largely because of advances in primary and secondary prevention of cardiovascular disease; however, this trend has not been observed in younger patients. [1][2][3] Previous studies have consistently reported that 4% to 10% of AMI cases occur in younger patients. 4 We extracted patient-level data from the Japanese Percutaneous Coronary Intervention (J-PCI) registry.
The J-PCI is a prospective multicenter Japanese nationwide registry of PCI maintained by the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT). 7 It primarily aims to document the clinical backgrounds and outcomes of patients who undergo PCI. [8][9][10][11][12] Cardiac catheterization procedures are performed in publicly and privately funded hospitals in Japan, but as registration in the J-PCI registry is mandatory for the application for board certification and renewal under both systems, data completion is high. 13 Today, more than 200,000 PCI cases are registered annually from approximately 900 facilities that account for more than 90% of PCIperforming hospitals in Japan. 8,9 Each hospital has a data manager responsible for the collection and entry of PCI data into the online database. The accuracy of submitted data is validated by a data audit (20 sites per year) performed by the members of the CVIT Registry Subcommittee, and a meeting of data managers is held annually to ensure appropriate data collection. The CVIT publicly advertises research proposals in the J-PCI registry annually. 14     Patients with missing data were excluded from the multivariable analyses.
In the younger group, the baseline clinical characteristics were compared between patients with and without CPA. Multivariable logistic regression mixed models were also constructed to identify independent predictors of CPA, in-hospital mortality, and bleeding complications in this group. All statistical analyses were performed using R statistical software,

RESULTS
In total, data from 277,015 patients were initially evaluated. After excluding the data from 63,718 patients with missing information on age or sex (n ¼ 796; 0.2%) and those aged #19 and $80 years The baseline demographic data, lesion characteristics, procedure details, and in-hospital outcomes stratified by age groups of 10 years are summarized in Table 1. Prevalence of risk factor profiles between the younger and older groups is shown in Figure 2.
Concerning the overall trend, the younger age group included a higher number of male patients and had a lower prevalence of traditional coronary risk factors, such as hypertension, diabetes, and CKD, but a high prevalence of smoking and dyslipidemia. Furthermore, the younger age group had a lower frequency of comorbidities, such as heart failure, previous MI, and peripheral artery disease. In addition, angiographic data showed that the younger age group had fewer complex lesions, such as multivessel disease and LMT lesions. With respect to clinical presentation, CPA was more frequent in the younger age group, whereas cases of acute heart failure and cardiogenic shock were less common. Regarding in-hospital outcomes, the younger age group had a lower rate of in-hospital mortality and bleeding complications.
The results of the multivariable logistic regression analysis of CPA, in-hospital mortality, and bleeding complications are presented in Table 2. There was no multicollinearity for any of the variables. Younger age, male sex, CKD, history of heart failure, multivessel disease, and LMT lesions were independent predictors of CPA. Moreover, hypertension, diabetes, dyslipidemia, smoking, and history of MI were inversely associated with CPA. For in-hospital outcomes, LMT lesions, CPA, and acute heart failure were strongly associated with both in-hospital mortality and bleeding complications. Younger age and a radial approach were inversely associated with inhospital mortality, whereas male sex and radial approach were inversely associated with bleeding complications. The OR for CPA increased inversely with age, whereas the OR for in-hospital mortality decreased (Central Illustration). Table 3 presents the baseline demographic characteristics, lesion characteristics, procedure details, and in-hospital outcomes of patients with and without CPA in the young group. Younger patients with CPA had a higher prevalence of CKD, 3-vessel disease, and LMT lesions, and a lower prevalence of hypertension, dyslipidemia, smoking, history of PCI, and previous MI. With respect to in-hospital outcomes, younger patients with CPA had significantly higher incidence rates of in-hospital mortality (14% vs 0.46%; P < 0.001) and bleeding complications (2.9% vs 0.15%; P < 0.001).
The results of the multivariable logistic regression analyses of CPA, in-hospital mortality, and bleeding complications in the younger group are presented in Table 4. There was no multicollinearity for any of the variables. CKD, history of heart failure, multivessel disease, and LMT lesions were independent predictors of CPA. Meanwhile, hypertension, dyslipidemia, smoking, and history of MI were inversely associated with CPA. CPA and LMT lesions were strongly associated with both inhospital mortality and bleeding complications.
Meanwhile, a radial approach was inversely associated with both in-hospital mortality and bleeding complications.

DISCUSSION
The characteristics and outcomes of AMI in younger patients are yet to be completely clarified. Within a nationwide registration system that mandated recording of clinical information on consecutive patients who underwent PCI, we were able to assess real-world data from almost all younger patients with AMI who underwent primary PCI in Japan. The results of the present study show that AMI is relatively uncommon in younger patients, and younger patients have low in-hospital mortality. However, CPA occurs more frequently in these patients, and concomitant CPA significantly increases the risk of in-hospital mortality. These findings underscore the importance of primary prevention of AMI in younger individuals.
To the best of our knowledge, this is the largest study to evaluate the risk factors, clinical presentation, and short-term outcomes of AMI in younger patients who underwent contemporary primary PCI.
We found that younger patients with AMI were less likely to have complex coronary lesions (eg, 3-vessel disease or LMT lesions) than older patients. Nevertheless, CPA was more frequently observed in younger (7.1% to 9.0%) than in older patients (6.0% to 6.9%). Further, the adjusted ORs for CPA were >1.5fold higher in younger patients than in those aged 70 to 79 years. Although the precise mechanisms were evaluated. After excluding the data from 63,718 patients with missing information on age or sex and those aged #19 and $80 years, the data from 213,297 patients were included in the analysis. Among them, 23,985 (11.2%) and 189,312 patients (88.8%) were further classified into the younger and older groups, respectively. MI ¼ myocardial infarction, PCI ¼ percutaneous coronary intervention.

FIGURE 2 Prevalence of Risk Factors According to Age Group
The prevalence of risk factor profiles between the younger and older groups is presented. Concerning the overall trend, the younger age groups included a higher number of male patients and had a lower prevalence of traditional coronary risk factors, such as hypertension, diabetes, and chronic kidney disease (CKD), but a high prevalence of smoking and dyslipidemia.  Values are mean AE SD or n (%) unless otherwise indicated.
Abbreviations as in Tables 1 and 2. and reduces those fatal arrhythmias that result from coronary artery occlusion and reperfusion. 24,25 Collectively, our findings and those of previous studies indicate that younger patients may be at higher risk of fatal arrhythmias because of immature ischemic preconditioning, resulting in a higher incidence of CPA. Further investigations are needed to examine the relationship between the etiologies of AMI and incidence of CPA.
In the present study, in-hospital mortality was shown to be considerably lower in younger vs older patients, which was consistent with previous findings in Asian, American, and Italian populations. [26][27][28][29] However, in the younger group, the in-hospital mortality rate was 10-fold higher in patients with concomitant CPA than in those without CPA.
Concomitant CPA was also strongly associated with bleeding complications. Importantly, most young patients do not experience preceding chest pain, and acute coronary syndrome is often the first manifestation in younger patients with AMI. 5   Furthermore, there may be significant differences in clinical characteristics between patients who underwent PCI and those who did not. In particular, women have been reported to be less likely to undergo revascularization procedures than men, and we should be cautious about applying the results of this study to women. 45,46 Second, data on oral contraceptive use, drug abuse, and history of Kawasaki disease, which are known risk factors for AMI in younger patients, were also not included in the J-PCI registry. Finally, obesity and a family history of premature AMI are other important risk factors for AMI in younger patients, but the J-PCI registry does not include these data as input items. 27 Thus, we did not have access to this information.

CONCLUSIONS
Younger patients with AMI are at a higher risk of CPA, which is strongly associated with in-hospital mortality. The results of this study highlight the importance of primary AMI prevention strategies in younger individuals.
ACKNOWLEDGMENTS The authors thank all the members of the CVIT, the CVIT secretariat, and the patients who were included in the analysis. with AMI are at a higher risk of cardiopulmonary arrest, which is strongly associated with in-hospital mortality. The results of this study highlight the importance of primary AMI prevention strategies in young individuals.

FUNDING SUPPORT AND AUTHOR DISCLOSURES
TRANSLATIONAL OUTLOOK: Establishing an effective primary prevention strategy for AMI in young patients will make a significant contribution to the reduction of sudden cardiac death and mortality.