Temporal trends and outcomes of percutaneous coronary intervention in young patients ( aged ≤ 40 years )

Background: The prevalence of coronary artery disease and percutaneous coronary intervention in young patients is not well established. The objective of this study was to investigate the profile of young patients undergoing percutaneous coronary intervention in Brazil. Methods: A cross-sectional study was performed with data from the Central Nacional de Intervenções Cardiovasculares (CENIC), collected between 2006 and 2016, for patients aged ≤40 years undergoing percutaneous coronary intervention. Results: We enrolled 2,806 patients, mean age of 35.3±3.9 years. Most lesions on angiography were single-vessel (66.6%), in the left anterior descending artery (50.8%), and complex (68%). In respect to procedures, there was a difference over the years in the use of drug-eluting stents (p<0.0001), vessel diameter (p=0.015), stent length (p<0.0001), type of intervention (p=0.036), use of glycoprotein IIb/IIIa inhibitors (p<0.0001), thromboaspiration (p=0.0003), post-procedural TIMI flow (p=0.007), and post-procedural stenosis (p<0.001). As for in-hospital clinical outcomes, there were no significant differences among the periods. In the multivariate analysis, female sex (OR: 3.45; 95%CI: 1.25-9.5; p=0.016), hypertension (OR: 4.84; 95%CI: 1.34-17.52; p=0.016), previous coronary artery bypass graft (OR: 16.42; 95%CI: 1.62-166.45; p=0.018), primary percutaneous coronary intervention (OR: 25.67; 95%CI: 5.19-126.99; p=0.0001) and rescue percutaneous coronary intervention (OR: 26.44; 95%CI: 2.11-330.82; p=0.011) were independent predictors of in-hospital mortality. Conclusion: Percutaneous coronary intervention in young patients, in the CENIC registry, shows cases of high angiographic complexity, high success rates and low in-hospital complication rates over a 10-year period.


INTRODUCTION
.3 Genetic mutations associated with familial hypercholesterolemia 4 and hyperhomocysteinemia, 5 in addition to classic risk factors, such as smoking, hypertension, insulin resistance, obesity and family history of premature CAD, show a correlation with early atherosclerotic events. 6he Central Nacional de Intervenções Cardiovasculares (CENIC; http://www.corehemo.net/) is an online registry maintained by the Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista (SBHCI).In this registry, patient and procedural characteristics are voluntarily submitted by members of the SBHCI as per an established protocol.Detailed information is collected about PCI procedures conducted at approximately 200 interventional cardiology centers in the country.
This study aimed to outline the national scenario of PCI in young patients (aged ≤40 years), as recorded in the CENIC database, looking at different periods and regions of Brazil, regarding patient profile, procedural characteristics, and in-hospital outcomes.

Patient selection
In this analysis, we included all patients ≤40 years of age undergoing PCI in the period from June 2006 to March 2016.This is a retrospective cross-sectional study based on the CENIC registry.The data were collected on standardized forms and stored in an electronic database.
The temporal analysis of the 2006-2016 period was conducted by breaking down the sample into three groups: Group A (2006-2008), Group B (2009-2011) and Group C (2012-2016).
For analysis of clinical variables, the individual patient was considered as the sample unit.Some patients underwent to more than one procedure.In these cases, the procedure to be considered was randomly selected.
Our work was submitted to the Research Ethics Committee of the Hospital Leforte (5485) and was approved, under the CAEE 90669518.6.0000.5485.

Clinical characteristics
With respect to clinical presentation, patients were divided into asymptomatic (those with positive functional tests for myocardial ischemia), stable angina, non-STsegment elevation acute coronary syndrome (NSTE-ACS) (comprising patients with unstable angina, and non-STsegment elevation myocardial infarction -NSTEMI), as well as ST-segment elevation myocardial infarction (STEMI).The myocardial infarction (MI) classification and diag-nostic criteria were defined according to a pre-established protocol. 7Left ventricular dysfunction was defined as left ventricular ejection fraction <50% on echocar diography.To define the functional class, we used the Killip/Kimball classification. 8

Angiographic and procedural characteristics
Multivessel coronary artery disease was defined as the presence of ≥50% stenosis in more than one coronary artery.The coronary flow pre and post-procedure was assessed and described as per the Thrombolysis in Myocardial Infarction (TIMI) grade flow. 9.11 Procedural success was visually defined, encompassing the achievement of residual stenosis <20% and absence of death, periprocedural MI, or the need for emergency heart surgery, defined as major adverse cardiovascular events (MACE).

Statistical analysis
Continuous variables with normal distribution were described as mean and standard deviation.Categorical variables were described as absolute numbers and percentages.For comparison of continuous variables in relation to the 2006-2016 groups, the Chi-square test was employed.When required, we used the likelihood ratio test.For comparison of categorical variables in relation to the 2006-2016 groups, we used the analysis of variance (ANOVA).For multiple comparisons, the Bonferroni correction was used.To assess the influence of variables of interest regarding mortality, we used the simple logistic regression model.Also, multiple logistic regression was performed by forward selection to determine the independent variables that better explained the occurrence of death.Variables with many missing data were not considered in the multiple logistic regression analysis (e.g.: left ventricular dysfunction and collateral circulation).When looking at mortality-related variables, if the patient had been submitted to more than one procedure, we used random selection to narrow down to one procedure per patient.P-values ≤0.05 were considered statistically significant.We used the software Statistical Package for Social Science (SPSS), version 20.0.

RESULTS
The sample in this study had a total of 2,806 patients, with a mean age of 35.3± 3.9 years, and a higher prevalence of males in all groups (74.4% on average), with no difference between the groups over the years.Hypertension, dyslipidemia, acute coronary syndrome (ACS) and Killip 1 class were very prevalent in the three groups (58.2%, 44.1%, 62.2% and 81.7%, respectively), unlike type 2 diabetes mellitus, with a small prevalence in the groups (15% on average).It is worth noting that there was signi-ficant and progressive reduction of smoking over the years (p<0.0001)(Table 1).
As for in-hospital clinical outcomes (death, emergency revascularization, periprocedural MI or MACE), there were no significant differences between the groups (Table 4).The univariate analysis of predictors of in-hospital mortality is shown in table 5.In the multivariate analysis, female sex (OR: 3.45; 95%CI 1. 25

DISCUSSION
In this study we describe the profile of PCI procedures in young patients in Brazil, recorded in the CENIC-SBHCI registry.The main findings of the study were low prevalence of type 2 diabetes (15%) and high smoking rates (35 to 40%), predominantly single-vessel, highly complex lesions, of which 68% were AHA/ACC type B 2 /C, and a prevalence of up to 30% of bifurcation lesions.
Data about MI in young patients are still scarce in the literature when compared with data on CAD in general.Perhaps the most widely known of all epidemiological studies in cardiovascular medicine is the Framingham Heart Study, which reported, over a 10-year period, an incidence of MI in young adults (defined in the study as <55 years) of 51.1/1,000 in men and 7.4/1,000 in women. 12The literature diverges when it comes to the definition of young adults in the context of early CAD and AMI, ranging from <40 to <55 years of age. 13,14Other authors have suggested 45 years as a cutoff in MI cases. 6,15,16][19] Aging appears to have deleterious effects both on endothelial function and vascular remodeling, including increased intima-media thickness and increased wall stiffness. 20,21hus, younger age was implicitly considered a positive prognostic factor.However, with the growing prevalence of risk factors at younger ages, the age factor has been less associated with the absence of CAD or less complex lesions, and most patients have more than one conventional cardiovascular risk factor. 22In addition, young patients who do not control their risk factors have recurring disease over time, including the need for new CABG. 235][26] The present study reports the prevalence of smoking at roughly 35 to 40%, with progressive reduction over the 10 year-period (2006-2016).In a population of young adults diagnosed with MI, the percentage of smokers can reach up to 74%, like in the CRAGS (Coronary Artery Disease in Young Adults) study. 23ith regard to angiographic characteristics, the lower atherosclerotic burden among young adults explains the higher prevalence of single-vessel coronary artery disease, as seen in the present study, which is consistent with previous publications. 16][32] Overall, younger patients are not different from older patients with regard to PCI procedures, and it is of utmost importance to encourage aggressive management of risk factors, medical treatment and careful follow-up, since these patients have high-complexity CAD.

Limitations of the study
This was a retrospective and observational analysis, based on a registry and, therefore, there are limitations inherent to the study model.Procedures were performed at several centers and by different interventional cardiologists with diverse levels of experience, which could influence results.There is also the issue of underreporting of PCI cases in Brazil (given the voluntary nature of contributions), some variables with incomplete data, the non-adjudication of the CENIC registry data, and the failure to compare characteristics and events with patients aged >40 years.In addition, we only used data corresponding to the in-hospital period, and we do not have 30-day or later follow-up (>1 year) data, which makes it impossible to conduct a long-term procedure-related survival analysis.

CONCLUSIONS
Percutaneous coronary intervention in young patients (aged ≤40 years) in the CENIC registry showed a high degree of complexity, with a high prevalence of bifurcation, single-vessel lesions, high success rates, and low rates of in-hospital complications.Hence, all patients warrant the same aggressive management, modification of risk factors, and close follow-up, regardless of age of presentation of coronary artery disease.

Table 3 .
Characteristics of procedures Results expressed as mean±standard deviation, or n (%).PCI: percutaneous coronary intervention; TIMI: Thrombolysis in Myocardial Infarction.

Table 6 .
Multivariate analysis of independent predictors of in-hospital mortality