Faculty of Medicine

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Age and sex differences in the efficacy of early invasive strategy for non-ST-elevation acute coronary syndrome: A comparative analysis in stable patients
(Elsevier BV, 2025-06)
Cenko, Edina
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Bergami, Maria
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Yoon, Jinsung
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Vadalà, Giuseppe
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Abstract 18529: Early Coronary Revascularization Among "Stable" Patients With Non-ST-Segment Elevation Acute Coronary Syndromes: The Role of Diabetes and Age
(Ovid Technologies (Wolters Kluwer Health), 2023-11-07)
Fabin, Natalia
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Cenko, Edina
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Vadalà, Giuseppe
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Mendieta Badimon, Guiomar
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Diet and sex inequities in ischemic heart disease mortality across Europe: findings from the global burden of disease study
(Oxford University Press (OUP), 2025-11)
Bugiardini, Raffaele
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Rahaman, Tania
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Manfrini, Olivia
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Maas, Angela
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Bergami, Maria
Aims Sex differences in ischemic heart disease (IHD) mortality remain underexplored from a population-level case fatality perspective. This study evaluates sex-specific disparities in IHD mortality and risk-attributable causes across 27 European Union (EU) countries using Global Burden of Disease (GBD) 2021 data. Methods and results We calculated age-standardized mortality rates (ASMRs), prevalence rates (ASPRs), and mortality-to-prevalence ratios (MPRs) as a proxy for population-level case fatality. To quantify mortality attributable to specific exposures among individuals with IHD, we derived a case fatality index (CFI) by normalizing risk-attributable ASMRs to ASPRs. Z-scores quantified the magnitude and statistical significance of sex differences in MPRs and CFIs (|Z| ≥ 1.96 = P < 0.05; |Z| ≥ 2.58 = P < 0.01). From 2011 to 2021, IHD ASMRs declined by 24.0% in men and 19.1% in women. In 2011, 12 countries showed significantly higher MPRs in women than men. By 2021, Austria (MPR 6.0% vs. 3.6%), Greece (9.4% vs. 5.3%), and Malta (9.3% vs. 4.2%) remained outliers, with Z-scores >2.58 (P < 0.01). CFIs showed that women in these countries faced 40 to 60% higher mortality burdens from hypertension, hyperglycemia, and poor dietary intake. Low intake of omega-3 fatty acids, fibers, vegetables, and nuts/seeds accounted for the largest dietary disparities. Conclusion Despite declining IHD mortality rates, Austria, Greece, and Malta continue to exhibit significant sex disparities, with women experiencing disproportionately higher case fatality. These disparities are largely driven by modifiable cardiometabolic and dietary risks, underscoring the need for sex-specific, regionally tailored prevention strategies.
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The Paradox of SMURF-less Outcomes and its Implication for Diabetes
(Oxford University Press (OUP), 2026-01-28)
Cenko, Edina
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Manfrini, Olivia
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Yoon, Jinsung
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Bergami, Maria
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Vasiljevic, Zorana
Individuals without standardized modifiable risk factors (SMuRF), which implicitly include those with diabetes, have been paradoxically reported to experience higher mortality following acute coronary syndromes (ACS). We aim to clarify the independent impact of diabetes on 30-day mortality after ACS and explore how grouping it with other SMuRF might obscure its true effect.
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Sex and gender differences in coronary pathophysiology and ischaemic heart disease
(Oxford University Press (OUP), 2026-01-23)
Manfrini, Olivia
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Tousoulis, Dimitris
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Antoniades, Charalambos
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Badimon, Lina
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Bugiardini, Raffaele
Ischaemic heart disease shows important differences between men and women, requiring an understanding of sex and gender dissimilarities to improve outcomes. This Scientific Statement provides an updated review of the current knowledge from risk factors to prognosis. It discusses the unequal impact of certain traditional risk factors between men and women, along with additional factors, such as hormonal changes and treatments (including those for transgender people and cancer), pregnancy-related complications, and autoimmune diseases, which contribute to the sex-specific risk profiles. Moreover, it outlines functional and structural sex differences in the pathophysiology (e.g. coronary atheroma plaques and burden, coronary dissection, vasospasm, and microvascular disease) with women being more prone to microvascular disease and endothelial dysfunction, while paradoxically experiencing less severe myocardial ischaemia at similar levels of coronary stenosis. The document further addresses the evaluation of diagnostic tools, which often have a male-centric bias, resulting in underdiagnosis in women who also tend to receive less guideline-recommended treatment. Additionally, women can have different responses and side effects to various preventive and therapeutic treatments, potentially contributing to the worse prognosis documented in acute coronary syndromes with obstructive coronary artery disease, particularly at a young age. Considering all these sex and gender differences and the low enrolment of women in randomized controlled trials, questions arise regarding the optimal treatment for women. Addressing sex differences requires conducting sex-specific research to close the knowledge gap. Overall, the Scientific Statement highlights all relevant sex- and gender-specific dissimilarities to advance clinical practice and identify directions for future research to improve guideline recommendations for equitable care.
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Changing clinical perspectives on sex and healthcare disparities in ischaemic heart disease
(Elsevier BV, 2025-09)
Maas, Angela
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Cenko, Edina
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Vaccarino, Viola
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Göttgens, Irene
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Bergami, Maria
Ischaemic heart disease (IHD) has historically been under-researched in women, leading to significant gaps in understanding sex-specific risk factors and outcomes. To address this issue, The Lancet Regional Health–Europe convened experts from a broad range of countries to evaluate sex-related cardiovascular inequalities and propose recommendations to address these disparities. Despite developing IHD a decade later than men, women experience higher mortality rates. Global Burden of Disease data highlight persistent sex differences in IHD mortality, with women showing higher mortality despite lower prevalence. Factors such as psychosocial stress, reproductive health, and physical inactivity disproportionately impact women's cardiovascular health, while caregiving responsibilities and delayed healthcare access further exacerbate these disparities. There is an urgent need to recognize chest pain symptoms in women and to reduce the time lag between symptom onset and hospital presentation. Addressing these gaps requires targeted public health interventions, expanded research, and improved clinical practices, emphasizing equitable healthcare access and greater inclusion of women in clinical trials. Tailoring treatment guidelines to account for sex differences in outcomes could significantly improve survival rates for women with IHD.
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Age and sex differences in the efficacy of early invasive strategy for non-ST-elevation acute coronary syndrome: A comparative analysis in stable patients
(Elsevier BV, 2025-06)
Cenko, Edina
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Bergami, Maria
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Yoon, Jinsung
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Vadalà, Giuseppe
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Objective: Previous works have struggled to clearly define sex-specific outcomes based on initial management in NSTE-ACS patients. We examined whether early revascularization (<24 h) versus conservative strategy impacts differently based on sex and age in stable NSTE-ACS patients upon hospital admission. Methods: We identified 8905 patients with diagnosis of non-ST elevation acute coronary syndromes (NSTE-ACS) in the ISACS-TC database. Patients with cardiac arrest, hemodynamic instability, and serious ventricular arrhythmias were excluded. The final cohort consisted of 7589 patients. The characteristics between groups were adjusted using inverse probability of treatment weighting models. Primary outcome measure was all-cause 30-day mortality. Risk ratios (RRs) with their 95 % CIs were employed. Results: Of the 7589 NSTE-ACS patients identified, 2450 (32.3 %) were women. The data show a notable reduction in mortality for the older women (aged 65 years and older) undergoing early invasive strategy compared to those receiving an initial conservative (3.0 % versus 5.1 %; RR: 0.57; 95 % CI: 0.32 - 0.99) Conversely, younger women did not exhibit a significant association between early invasive strategy and mortality reduction (2.0 % versus 0.9 %; RR: 2.27; 95 % CI: 0.73 - 7.04). For men, age stratification did not markedly alter the observed benefits of an early invasive strategy over a conservative approach in the overall population, with reduced death rates in both older (3.1 % versus 5.7 %; RR: 0.52; 95 % CI: 0.34 - 0.80) and younger age groups (0.8 % versus 1.7 %; RR: 0.46; 95 % CI: 0.22 - 0.94). These age and sex-specific mortality patterns did not significantly change within subgroups stratified by the presence of NSTEMI or a GRACE risk score>140. Conclusion: Early coronary revascularization is associated with improved 30-day survival in older men and women and younger men who present to the hospital in stable conditions after NSTE-ACS. It does not confer a survival advantage in young women. Further studies are needed to more accurately risk-stratify young women to guide treatment strategies.
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Early coronary revascularization among 'stable' patients with non-ST-segment elevation acute coronary syndromes: the role of diabetes and age
(Oxford Academic, 2024-12-14)
Fabin, Natalia
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Cenko, Edina
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Bergami, Maria
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Yoon, Jinsung
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Vadalà, Giuseppe
To investigate the impact of an early coronary revascularization (<24 h) compared with initial conservative strategy on clinical outcomes in diabetic patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who are in stable condition at hospital admission.
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TRADITIONAL RISK FACTORS AND PREMATURE ACUTE CORONARY SYNDROMES IN SOUTH EASTERN EUROPE
(Elsevier BV, 2024-04)
Cenko, Edina
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Bergami, Maria
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Vasiljevic, Zorana
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Zdravkovic, Marija
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Background The age-standardized death rates under 65 years from ischemic heart disease (IHD) in South Eastern Europe are approximately twice as high than the Western Europe average, but the reasons are unknown. Methods We enrolled 70,953 Caucasian patients with first acute coronary syndrome (ACS), from 40 urban hospitals in 6 South Eastern European countries and assessed their life expectancy free of ACS and mortality within 30 days after hospital admission from ACS as estimated in relation to dichotomous categories of traditional risk factors (current smoking, hypertension, diabetes, and hypercholesterolemia) stratified according to sex. Results Compared with patients without any baseline traditional risk factors, the presence of all four risk factors was associated with a 5-year shorter life expectancy free of ACS (women: from 67.1 ± 12.0 to 61.9 ±10.3 years; r= -0.089; p<0.001 and men: from 62.8 ± 12.2 to 58.9 ± 9.9 years; r= -0.096; p<0.001). Premature ACS (women <67 years and men <63 years) was remarkably related to current smoking and hypercholesterolemia among women (Risk Ratios [RRs]: 3.96; 95% CI,3.72-4.20 and 1.31; 95% CI, 1.21-1.40, respectively) and men (RRs: 2.82; 95% CI, 2.171- 2.95 and 1.39; 95% CI, 1.34-1.45, respectively). Diabetes was most strongly associated with death from premature ACS either in women (RR: 1.52; 95%CI: 1.29-1.79) or men (RR: 1.63; 95%CI: 1.41-1.89). Conclusion Public health policies in Southeastern Europe should place significant emphasis on the four traditional risk factors and the associated lifestyle behaviors to reduce the epidemic of premature IHD.
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Coronary revascularization and sex differences in cardiovascular mortality after myocardial infarction in 12 high and middle-income European countries
(Oxford University Press (OUP), 2024-05-07)
Cenko, Edina
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Yoon, Jinsung
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Bergami, Maria
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Gale, Chris P
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Vasiljevic, Zorana
Existing data on female sex and excess cardiovascular mortality after myocardial infarction (MI) mostly come from high-income countries (HICs). This study aimed to investigate how sex disparities in treatments and outcomes vary across countries with different income levels.

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