Methods

We used data from the PL-ACS. The PL-ACS is a nationwide, multicenter, prospective study of consecutively hospitalized patients with ACS in Poland. The registry is a joint initiative of the Silesian Center for Heart Diseases in Zabrze and the Polish Ministry of Health. Logistic support is provided by the National Health Fund (NHF), the nationwide, obligatory public health insurance institution in Poland. The pilot phase of the PL-ACS commenced in October 2003 in Silesia, one of the 16 administrative regions in Poland with >4.8 million inhabitants. The study involved patients recruited in 46 Silesian hospitals. All the data were encoded and sent to the NHF once a month, where they were further compared with the patient reports sent by the hospitals. After the verification of the information, the NHF transferred the data to the central database in the Silesian Center for Heart Diseases in Zabrze, Poland, where further control procedures were applied.

Follow-up data regarding the rates for all-cause mortality, re-hospitalization, recurrent ACS (re-ACS), stroke, and subsequent revascularization were obtained from the NHF. The vital status and follow-up information at 12 months after ACS-related hospitalization were available for all enrolled patients. The follow-up data at 36 months were available for 779 patients, excluding those enrolled from January 2013 to December 2014. The composite end point involved death, recurrence of ACS, a need for percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery within 12 and 36 months after ACS-related hospitalization.

Patients with an initial diagnosis of ACS were considered eligible to enter the registry, yet only those with a confirmed diagnosis of ACS were enrolled. The ACS group included patients with ST-elevation myocardial infarction (STEMI), non–ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA).

The definitions for the initial diagnosis of STEMI, NSTEMI, and UA were as follows:

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  STEMI: the presence of (1) typical anginal pain and/or ischemic symptoms at rest lasting >20 minutes, (2) ST-segment elevation consistent with MI of ≥2 mm in adjacent chest leads and/or ST-segment elevation of ≥1 mm in ≥2 standard leads or new left bundle branch block, and (3) positive markers for cardiac necrosis.

  
  
• ▪
  

  NSTEMI: (1) the absence of ST-segment elevation as defined earlier and (2) positive markers for cardiac necrosis.

  
  
• ▪
  

  UA: (1) the absence of ST-segment elevation as defined earlier, (2) negative markers for cardiac necrosis, and (3) the presence of angina pectoris (or an equivalent type of ischemic discomfort) with any one of the following 3 features: (a) angina occurring at rest or for a prolonged period (usually >20 minutes), (b) new-onset angina of at least class III severity according to the severity scale devised by the Canadian Cardiovascular Society (CCS), or (c) a recent acceleration of angina reflected by an increase in the severity of at least CCS class I to at least CCS class III.

Hypertension was defined as repeated systemic blood pressure measurements exceeding 140/90 mm Hg or treatment with antihypertensive drugs for a known diagnosis of hypertension. Diabetes mellitus was diagnosed by the fasting plasma glucose level >125 mg/dl (7.0 mmol/L), a random plasma glucose level >200 mg/dl (11.1 mmol/L), or a history of diabetes mellitus, including those treated with diet, oral medications, or insulin. Hypercholesterolemia was defined as a baseline cholesterol level >200 mg/dl (5.2 mmol/L) and/or a low-density lipoprotein level >130 mg/dl (3.4 mmol/L) or previously diagnosed and treated hypercholesterolemia. Obesity was diagnosed as a body mass index ≥30 kg/m ² . The invasive treatment was defined as the performance of coronary angiography during the index hospitalization.

The patients were divided into 2 groups: men and women <40 years. We compared the differences in the clinical presentation, characteristics, and cardiovascular risk factors. We analyzed the differences in treatment strategy, including PCI and pharmacotherapy. We compared the inhospital and 12- and 36-month outcomes, including the number of deaths and composite end points.

Continuous variables are presented as the means and SDs. Categorical variables are presented as percentages. We used the chi-squared, Mann-Whitney U , and Student’s t tests where appropriate to test for differences between the patients <40 and >40 years. Yates’ correction of the chi-square test was used in the case of small cell frequency. The association between the age group and long-term mortality was analyzed using the Kaplan-Meier method with log-rank testing. To minimize the impact of the missing data on the Cox regression analysis, the multiple imputation method was used to impute the missing data for the ejection fraction. The covariates used in the stepwise Cox regression included age, gender, medical history data, clinical characteristics on admission, ejection fraction, and treatment during the index hospitalization. The significance level of p <0.02 was used to retain a variable in the model. The hazard ratios and 95% confidence intervals (CIs) were calculated (Number Crunching Statistical Systems 8.0; NCSS, Kaysville, Utah). The graphs were prepared using GraphPad Prism software, version 6.0 (GraphPad, San Diego, California).

Results

Among 75,727 patients with ACS in the Silesia region, 932 (1.2%) were under 40 years from January 2006 to December 2014. All 932 patients were Caucasian and women accounted for 18% of the young patients. The baseline demographic and clinical characteristics of men and women <40 years were similar and are listed in Table 1 . Both treatment strategy and pharmacotherapy during hospitalization were similar in both groups ( Table 2 ). The inhospital, 30-day, and 12- and 36-month outcomes are presented in Table 3 . Females had a higher frequency of re-ACS, and re-ACS combined with death both within 12 and 36 months after index hospitalization ( Figure 1 ). The incidence of composite end point did not vary significantly between the 2 genders both within 30 days and 12 months after the index ACS. A composite end point was observed more frequently in women within 36 months after ACS-related index hospitalization ( Figure 2 ). Although 36-month mortality tended to be higher only in women in univariate analysis (p = 0.055) ( Figure 3 ), the female gender revealed to be an independent risk factor of death in multivariate analysis (hazard ratio 2.76, 95% CI 1.21 to 6.31, p <0.016; Table 4 ). Other independent and significant factors increasing 36-month mortality are listed in Table 4 . Cigarette smoking before and statins intake after ACS-related index hospitalization played a protective role in the 36-month follow-up period.

Table 3

In-hospital, 30-day, 12- and 36-month outcomes

Variable	Men (n = 764)	Women (n = 168)	P
In hospital
Stroke	1 (0.1%)	0 (0%)	–
Re-ACS	12 (1.6%)	1 (0.6%)	0.54
Death all-cause	9 (1.2%)	1 (0.6%)	0.80
Re-ACS + Death	13 (1.7%)	2 (1.2%)	0.89
30-day since discharge
Stroke	0 (0.0 %)	0 (0.0%)	–
Re-ACS	17 (2.2%)	7 (4.2%)	0.24
PCI	14 (1.9%)	3 (1.8%)	0.81
CABG	8 (1.1%)	1 (0.6%)	0.89
Death all-cause	15 (2.0%)	4 (2.4%)	0.73
Re-ACS + Death	30 (3.9%)	11 (6.5%)	0.20
Re-ACS + Death + PCI + CABG	39 (5.1%)	11 (6.5%)	0.62
12-month after discharge
Stroke	2 (0.3%)	2 (1.2%)	0.31
Re-ACS	63 (8.2%)	24 (14.4%)	0.02
PCI	61 (8.2%)	11 (6.5%)	0.58
CABG	25 (3.4%)	3 (1.8%)	0.41
Death all-cause	24 (3.1%)	8 (4.8%)	0.29
Re-ACS + Death	83 (10.9%)	31 (18.6%)	0.01
Re-ACS + Death + PCI + CABG	122 (16.0%)	36 (21.6%)	0.14

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