Risk profile and prognosis of myocardial infarction in young adults: a comparative study

This retrospective monocentric comparative study included consecutive patients admitted with a first STEMI within 48 hr of symptom onset between January 2020 and January 2024. All patients underwent percutaneous coronary intervention (PCI) during the index hospitalisation (primary PCI, rescue PCI or following successful thrombolysis) and were followed for a minimum of 12 months.

Patients were stratified according to age: >50 years and ≤50 years. Age thresholds used to define ‘young’ in cardiovascular disease are inconsistent, typically set at ≤45 years and extended to ≤55 years in studies focusing on women [3]. In light of recent data showing an increase in MI hospitalisations among women <50 years, unlike men of similar age, we defined young patients as ≤50 years, irrespective of sex.

Exclusion criteria included prior known coronary artery disease (CAD), presentation with non-ST-segment elevation myocardial infarction (NSTEMI), known cardiomyopathy or reduced left ventricular ejection fraction (LVEF) ≤40%, a final retained diagnosis of myocarditis during hospitalisation, advanced chronic kidney disease (eGFR <30 mL/min) and active malignancy with life expectancy <6 months [1,4].

This study was conducted in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines.

Clinical records, including physician notes, laboratory tests, imaging studies, procedural results and discharge summaries, were reviewed.

Cardiovascular risk factors were defined as follows: family history of premature CAD (first-degree relative <55 years in men, <60 years in women); diabetes mellitus (prior diagnosis, HbA1c ≥6.5%, fasting glucose ≥7.0 mmol/L or on treatment); hypertension (≥140/90 mmHg, prior diagnosis or on treatment); dyslipidaemia (prior diagnosis, lipid-lowering therapy or abnormal lipid profile); obesity (BMI ≥30 kg/m²); active smoking (within 12 months); substance use (cannabis or cocaine) and chronic heavy alcohol use (CHAU) (>14 units/week in women and >21 units/week in men). A history of cerebrovascular accident and chronic kidney disease (eGFR <60 mL/min/1.73 m² for ≥3 months) was also recorded [4].

Baseline clinical presentation included infarct territory, haemodynamic status and acute complications [1,4].

Angiographic data were prospectively collected using CardioReport software. Coronary flow was assessed according to the thrombolysis in myocardial infarction (TIMI) classification. Significant coronary stenosis was defined as ≥70% luminal narrowing in major epicardial vessels or ≥50% in the left main coronary artery [4]. The infarct-related artery (IRA) and extent of vessel disease were determined from angiographic analysis.

In accordance with STEMI guidelines, all patients received loading doses of aspirin (300 mg) and a P2Y12 inhibitor (clopidogrel 300–600 mg or ticagrelor 180 mg), along with unfractionated heparin (50–70 U/kg) following STEMI confirmation [4]. PCI strategy was recorded as either stent implantation or a stentless conservative approach for culprit lesion management. Stents were classified as bare-metal or drug-eluting stents [1,4]. The use of glycoprotein IIb/IIIa inhibitors and aspiration thrombectomy was left to operator discretion, mainly in cases of high thrombus burden or as bail-out therapy [1,4].

Procedural success was defined as residual stenosis <30% with restoration of TIMI 3 flow [1]. In patients with post-PCI reduced LVEF ≤ 40%, guideline-directed medical therapy for heart failure was initiated according to current recommendations [5].

Early follow-up included in-hospital and 30-day outcomes, with assessment of adverse events including contrast-induced nephropathy (CIN), acute heart failure (AHF), stent thrombosis and cardiovascular mortality [4].

Patients were followed through outpatient visits or telephone contact. Follow-up assessments included symptom recurrence, functional status and clinical events including AHF, as well as major adverse cardiovascular events (MACE), defined as death, non-fatal stroke and non-fatal MI [6].

The primary endpoint of the study was early and long-term cardiovascular mortality. Early mortality was defined as in-hospital and 30-day mortality, as long-term cardiovascular mortality was recorded during follow-up. Death was regarded as cardiac unless an unequivocal non-cardiac cause of death was established [6].

The secondary endpoint was a composite of hospitalisation for non-fatal MI, hospitalisation for AHF, stent thrombosis or in-stent restenosis at the target lesion or any stented coronary segment [6].

Statistical analyses were performed using IBM SPSS Statistics (version 22.0). Continuous variables were compared using Student’s t test or the Mann–Whitney U test, as appropriate. Categorical variables were analysed using the χ² test or Fisher’s exact test. Factors associated with younger age among STEMI patients were assessed using logistic regression analysis, with results expressed as odds ratios (OR) and 95% confidence intervals (95% CIs). Cardiovascular mortality was analysed using Kaplan–Meier survival curves and compared between groups using the log-rank test. Cox proportional hazards models were constructed to evaluate the association between selected baseline variables and cardiovascular mortality. Multivariable models included clinically relevant covariates. Results are reported as hazard ratios (HR) with 95% CIs.

For the secondary composite endpoint, time-to-event analyses were based on the time to first occurrence of any component event. All tests were two-sided, and statistical significance was set at p < 0.05.

This study adhered to the ethical principles set forth by the institutional ethics committee of Mongi Slim Hospital and complied with the Declaration of Helsinki.

A total of 206 patients were enrolled, including 100 patients in Group 1 (G1) and 106 patients in Group 2 (G2) (Figure 1).

Figure 1

Study flowchart. A total of 303 patients were initially screened for eligibility. Of these, 97 were excluded based on the predefined exclusion criteria. The final study population comprised 206 patients, stratified according to age into two groups: 100 patients in the older STEMI group (G1, age >50 years) and 106 patients in the younger STEMI group (G2, age ≤50 years). STEMI, ST-segment elevation myocardial infarction.

The mean age was 52.8 ± 11.6 years, with a predominance of males (82.5%) and a higher proportion of females in the older group. Smoking (72.8%), diabetes mellitus (49%) and hypertension (31.1%) were the most common cardiovascular risk factors. In older patients, diabetes (58%) and hypertension (39%) were more frequent. In contrast, younger patients exhibited higher rates of smoking (84.9%) and family history of CAD (22.6%). Lifestyle-related exposures were also more prominent in the younger group, including CHAU (30.2%) and cannabis use (11.3%).

All baseline characteristics are summarised in Table 1.

Most patients presented with ongoing (<12 hr) STEMI, accounting for 74.8% of the population, while 25.2% had subacute presentation (12–48 h). Time from symptom onset to first medical contact was shorter in younger patients compared with older patients (8.78 ± 12.25 vs 12.72 ± 14.62, p < 0.05). Anterior MI was the most common presentation in both groups (43% vs 44.3%, p = 0.57). AHF occurred at similar rates (20% vs 21.7%, p = 0.76). Cardiogenic shock (CS) requiring inotropic support was more frequent in older patients (11% vs 6.6%, p = 0.25), although the difference did not reach statistical significance (Table 2). The prevalence of reduced LVEF at initial evaluation was comparable between groups (34% vs 31.1%, p = 0.89). No significant difference was observed in low-density lipoprotein cholesterol (LDL-C) levels. Etiological investigations revealed prothrombotic conditions exclusively in the younger group, including two cases of hyperhomocysteinaemia, two cases of thrombophilia and one case of antiphospholipid syndrome (Table 2).

Angiographic findings and therapeutics are described in Table 3.

Primary PCI was performed in 62.6% of patients, with TIMI 0 flow observed in 34.5% before revascularisation. The left anterior descending coronary artery (LAD) was the most frequent culprit artery in both groups (44% vs 49.1%, p = 0.45), followed by the right coronary artery (RCA) (36% vs 29.2%, p = 0.31). Singlevessel disease was more prevalent in younger patients (57.5% vs 31%, p < 0.05), whereas multivessel disease predominated in older patients (66% vs 36.8%, p > 0.05). Non-atherosclerotic causes were significantly more frequent in the younger group (18.9% vs 5%, p < 0.05), including coronary vasospasm, spontaneous coronary artery dissection (SCAD) and embolic phenomena.

Overall, stenting was performed in 87.4% of cases, while a stentless strategy was used in 12.6%, with final TIMI 3 flow achieved in 93.2% of procedures. Stenting strategy was more frequent in older patients (95% vs 80.2%, p = 0.08), whereas a stentless conservative approach was more common in younger patients (19.8% vs 5%, p < 0.05). The use of glycoprotein IIb/IIIa inhibitors and thrombectomy was higher in younger patients (10.4% vs 3% and 3.8% vs 0%, p < 0.05).

In the general population, dual antiplatelet therapy was predominantly prescribed with clopidogrel (88.3%) and aspirin (96.6%). The remaining pharmacological treatments are summarised in Table 4.

Early cardiovascular mortality was significantly higher in older patients (7% vs 0.9%, p < 0.05). Other adverse events were comparable between groups, including AHF (9% vs 3.8%, p = 0.46), CIN (3% vs 0.9%, p = 0.28), stent thrombosis (1% vs 0.9%, p = 0.96) and stroke (3% vs 0%, p = 0.07) (Table 5).

During a mean follow-up period of 38.7 ± 19.3 months, there were no differences in symptom occurrence between groups. Smoking cessation was more frequent in younger patients (42.9% vs 16.1%, p < 0.05), whereas therapeutic adherence was similar between the two groups (80% vs 75.3%, p = 0.98). No significant differences were observed in LDL-C levels (0.8 vs 0.9 g/L, p = 0.2) or mean LVEF (49% vs 48.5%, p = 0.78) (Table 6).

The primary endpoint of cardiovascular mortality was higher in older patients, occurring in 11 cases (11%) compared with 1 case in younger patients (0.9%). Secondary endpoints occurred at similar rates in both groups (26% vs 25.5%, p = 0.96) (Table 7). Kaplan–Meier analysis demonstrated a significant difference in survival between groups (p < 0.05), with a hazard ratio of 0.09. Five-year survival was lower in older patients (87.7% vs 99%) (Figure 2).

Figure 2

Survival curves in young and old STEMI patients based on Kaplan-Meier estimates. Younger patients (G2) exhibited significantly higher survival rates compared with older patients (G1) (log-rank p < 0.05). HR, hazard ratio; STEMI, ST-segment elevation myocardial infarction.

In multivariable analysis, smoking (OR 2.58, 95% CI 1.19–5.60, p = 0.016), CHAU (OR 4.13, 95% CI 1.63–10.5, p = 0.003) and family history of CAD (OR 2.85, 95% CI 1.08–7.50, p = 0.034) were independently associated with younger age among STEMI patients (Table 8).

Cox regression analysis, restricted to clinically relevant variables, showed that CS at presentation (HR 5.92, 95% CI 1.81–19.33, p = 0.003) and reduced LVEF (HR 7.04, 95% CI 1.45–34.17, p = 0.015) were associated with increased cardiovascular mortality. Age >50 years was also associated with a higher risk of cardiovascular death (HR 8.98, 95% CI 1.15–69.94, p = 0.036), supporting the prognostic impact of age in this population (Figure 3).

Figure 3

Multivariable Cox survival regression plot. CS, reduced LVEF and age >50 years were independently associated with increased cardiovascular mortality. CI, confidence interval; CS: cardiogenic shock; HR, LVEF, left ventricular ejection fraction; MI: myocardial infarction.

In line with previous studies, smoking emerged as the predominant cardiovascular risk factor in our cohort, particularly among younger patients [2,7]. Our study confirmed a significantly higher prevalence of active smoking in young individuals compared with older patients, consistent with large registries reporting a substantial burden of tobacco exposure in early-onset STEMI [2,7–9]. This finding likely reflects the increasing exposure to tobacco in our region, where smoking remains a major contributor to cardiovascular mortality [10].

Beyond smoking, our study identified a higher prevalence of lifestyle-related exposures in younger patients, including CHAU and substance use, supporting the central role of modifiable behavioural factors in premature coronary events. These observations are in agreement with previous data demonstrating a strong association between lifestyle factors and early-onset MI [11–13].

In contrast, traditional cardiovascular risk factors such as hypertension and diabetes were more prevalent among older patients in our cohort, as also observed in previous studies, reflecting the cumulative burden of long-standing atherosclerotic disease [2,14]. Nevertheless, their presence in younger patients, although less frequent, remains clinically relevant, as they contribute to endothelial dysfunction and accelerated atherogenesis, as highlighted in prior reports [2,7,8].

Notably, our study demonstrated a significantly higher prevalence of family history of CAD in younger patients, suggesting an underlying genetic predisposition to premature coronary events. This observation is consistent with previous studies reporting a strong association between hereditary factors and early atherosclerosis [2,14,15]. In addition, our cohort identified cases of inherited and acquired thrombophilia exclusively in younger patients, further supporting the contribution of prothrombotic and genetic mechanisms in this population, as previously described [16,17].

These results suggest that STEMI in young patients follows a distinct risk profile, and, therefore, prevention strategies should be adapted rather than directly extrapolated from older populations, with a greater focus on modifiable lifestyle factors and early identification of at-risk individuals.

Atherosclerosis remains the predominant underlying mechanism of MI across all age groups, including in younger individuals, as observed in our cohort [2,7,8]. In addition to traditional cardiovascular risk factors, younger patients are frequently exposed to accelerating factors that may promote premature atherogenesis, including lifestyle-related determinants as well as chronic inflammatory and autoimmune conditions contributing to endothelial dysfunction and vascular injury [16,17]. Genetic susceptibility, particularly involving lipid metabolism and thrombogenic pathways, may further modulate this early disease process [17,18].

Nevertheless, non-atherosclerotic mechanisms appear to be relatively more frequent in younger patients compared with older individuals [17,19]. In our population, these mechanisms were more commonly identified in younger patients and mainly included cases of coronary vasospasm, SCAD and thromboembolic events, reflecting a broader and more heterogeneous pathophysiological spectrum of STEMI in this group. This supports the concept that STEMI in young patients represents a distinct entity, requiring a tailored diagnostic approach, particularly through the use of intracoronary imaging, to refine diagnosis strategies.

Our study demonstrated that younger patients exhibited significantly lower lesion complexity, more frequent single-vessel disease and lower SYNTAX scores compared with older individuals, consistent with previous studies highlighting less advanced atherosclerotic substrates in early-onset STEMI [14,15].

This angiographic profile likely contributes to the higher use of conservative, stentless strategies observed in younger patients in our cohort. Our study showed that such approaches were more frequently adopted in younger individuals, particularly in the presence of a high thrombotic burden and less complex lesions, reflecting a more selective and lesion-adapted interventional strategy. These findings are consistent with previous studies suggesting that plaque erosion and thrombotic lesions, more prevalent in younger patients, may be amenable to conservative management [21].

The EROSION trial further supports this concept, demonstrating the feasibility of a non-stenting strategy with intensive antithrombotic therapy in selected patients with acute coronary syndromes [21]. However, available data remain heterogeneous and sometimes conflicting, with other studies suggesting potential benefits of systematic stenting in selected high-risk lesions [21,22].

Importantly, in the absence of intracoronary imaging in our study, the underlying plaque morphology cannot be definitively established. Therefore, the use of stentless strategies in our cohort likely reflects individualised operator decision-making rather than a standardised therapeutic approach, underscoring the current lack of consensus in this setting.

Taken together, these findings reinforce the concept that STEMI in young patients is associated with a detached angiographic profile. This heterogeneity supports the need for a tailored interventional approach rather than a uniform strategy, with a central role for intracoronary imaging to guide decision-making and optimise patient-specific management.

Consistent with existing literature, younger patients exhibited more favourable short- and long-term survival compared with older individuals, likely reflecting a lower burden of comorbidities and less extensive CAD [23–26].

This survival advantage is likely explained by a lower cumulative atherosclerotic burden, fewer comorbidities and less complex coronary disease, as reflected in the angiographic profile of younger patients. However, despite this favourable prognosis, our study demonstrated that the incidence of recurrent cardiovascular events – including non-fatal MI, hospitalisation for AHF and stent-related complications – remained comparable between younger and older patients.

These findings highlight a dissociation between survival and recurrence, as younger patients continue to experience a non-negligible risk of subsequent cardiovascular events despite lower mortality, consistent with current large-scale registry data [26,27]. This paradox may be partly explained by persistent exposure to modifiable risk factors, suboptimal long-term risk factor control and the presence of underlying genetic or metabolic predispositions in younger individuals.

In line with established data, CS at presentation and reduced LVEF were strong predictors of mortality [27–29]. Age also remained independently associated with worse outcomes, further supporting its prognostic significance in STEMI.

These findings highlight the need for targeted prevention strategies in young patients, with a particular focus on modifiable lifestyle-related risk factors, including smoking and alcohol consumption, as well as early identification of individuals with a family history of coronary artery disease.

Taken together, our results support a more individualised approach to cardiovascular prevention, acknowledging that the risk profile of younger patients differs substantially from that of older populations and requires specific preventive interventions. Importantly, this approach should extend beyond primary prevention to include aggressive secondary prevention following the index event, with strict control of risk factors, optimisation of medical therapy and reinforcement of long-term adherence to lifestyle and pharmacological measures.