The study’s central innovation is methodological. Rather than relying on mortality rates alone, which can be misleading when disease prevalence differs sharply between countries and sexes, the team calculated the mortality-to-prevalence ratio, or MPR, dividing the age-standardised mortality rate by the age-standardised prevalence rate. Because ischaemic heart disease is a chronic condition, the population at risk of dying includes both newly diagnosed patients and the millions living with established disease, making prevalence a more appropriate denominator than incidence. A high MPR signals that, relative to the number of people living with the disease, deaths are excessive, a pattern that often points to weaknesses in prevention, treatment or both. The researchers also normalised risk-attributable mortality by prevalence to construct a case-fatality index, or CFI, which asks whether deaths attributable to a specific risk factor, such as tobacco or high blood pressure, are high or low among those actually living with the disease.

The headline numbers show genuine progress. Between 2011 and 2023, age-standardised mortality from ischaemic heart disease fell across the region in both sexes, with relative reductions of 2.6 percent in men and 3.7 percent in women, and regional mean MPRs declined from 5.32 percent to 4.32 percent in men and from 5.84 percent to 4.48 percent in women. Yet the averages conceal extraordinary heterogeneity. In 2023, mortality rates among men ranged from 216.93 per 100,000 in Hungary and 210.50 in Bulgaria down to just 63.55 in Slovenia, with women showing a parallel spread from 158.62 in Serbia to 29.17 in Slovenia. Slovenia’s case-fatality levels were statistically indistinguishable from those of the six founding members of the European Union, demonstrating that Western European outcomes are achievable within the region.

When the researchers applied formal Z-score testing to sex differences in MPR, a clear geography of inequality emerged. In 2011, women had significantly worse outcomes in Croatia, Serbia, Czechia and Bosnia and Herzegovina, while men fared worse in Poland and Bulgaria. By 2023, the disparities had narrowed but persisted in Croatia, Serbia and Czechia, with Z-scores of 5.55, 2.55 and 2.18 respectively, while Poland showed a significant reversal, with men now experiencing the higher mortality burden relative to prevalence. In Croatia and Serbia, women’s case-fatality was 46 percent and 38 percent higher than men’s, respectively. More modest but still meaningful female disadvantages appeared in Slovakia, Montenegro, North Macedonia and Bosnia and Herzegovina, whereas Bulgaria and Poland were the only countries where women-to-men ratios fell below one.

What drives these divergent patterns? The analysis points to two opposing domains of risk. In most countries, women exhibited higher case-fatality indices than men for the major metabolic risks, including elevated systolic blood pressure, fasting plasma glucose, LDL cholesterol and body mass index, with Croatia, Serbia and Slovakia showing the most pronounced female disadvantage, exceeding 20 percent for all four. Physical inactivity exerted a proportionally far greater impact on women, particularly in the Balkans, where the female-to-male CFI ratio reached 4.57 in Croatia and 4.11 in Serbia. Tobacco, by contrast, remained an overwhelmingly male hazard, with Albania’s tobacco-attributable male burden nearly six times that of women. In countries such as Croatia and Serbia, the female disadvantage domain of inactivity, metabolic vulnerability and dietary deficits predominates, while in Poland the absence of a strong female disadvantage leaves the universal male hazard from tobacco unopposed, helping to explain the reversal of the sex gap there.

Diet emerged as a critical and underappreciated component of the female disadvantage. Because dietary estimates carry wide uncertainty intervals, the team used Slovenia, the country with the lowest case-fatality, as an empirical benchmark, a choice validated by the finding that Slovenia’s MPR is statistically comparable to those of Belgium, France, Germany, Italy, Luxembourg and the Netherlands. This benchmarking revealed significant sex differences for seven dietary risks: low intake of whole grains, fruits, nuts and seeds, vegetables, seafood omega-3 fatty acids and fibre, along with high sodium intake. Low intake of nuts and seeds was the only dietary factor consistently associated with a significant female disadvantage in all three high-disparity countries, Croatia, Serbia and Czechia, suggesting a shared and potentially tractable population-level pattern. Country-specific deficits added further risk, most notably low fruit and vegetable intake in Croatia and low omega-3 intake in Romania, while male-specific dietary excesses were confined to isolated exposures such as high sodium in Romania and low whole grains in Bulgaria.

The biological plausibility of these dietary effects is well supported. Low intake of fruit, vegetables, nuts, seeds and omega-3-rich foods has been linked to higher blood pressure, impaired vascular function, inflammation and adverse cardiometabolic profiles, and these foods are foundational to the Mediterranean, DASH and Nordic dietary patterns with strong outcome evidence. The authors also point to possible physiological amplification in women, noting that the menopausal transition, with declining oestrogen levels, is associated with adverse lipid changes and vascular dysfunction that may heighten the impact of inadequate intake of omega-3-rich foods and micronutrient-dense sources such as nuts and seeds. Weight-promoting medications, including certain antidepressants, beta-blockers and insulin, may further compound cardiometabolic risk in midlife and older women, although medication use was not directly assessed in this ecological analysis.

Socioeconomic forces appear to compound these physiological vulnerabilities in a structural paradox: women with heart disease may experience relative deprivation of protective foods despite potentially greater nutritional needs. Croatia, though a high-income country, maintains one of the highest at-risk-of-poverty rates in the European Union at 21.7 percent, while upper-middle-income Serbia shows similarly high social vulnerability at 24.3 percent. Food insecurity, unequal household food allocation, gendered norms influencing food selection and time poverty from unequal domestic and caregiving responsibilities may all restrict women’s consistent access to nutrient-dense foods. Czechia offers a contrasting case, where excess female risk emerges despite low poverty levels of roughly 9.5 percent, suggesting that even a comparatively modest additional female shortfall in nuts and seeds, within a population-wide deficit of whole grains and fibre, may be sufficient to produce measurable sex differences in case-fatality.

Health-system capacity alone does not explain the patterns either. The researchers examined coronary revascularisation rates relative to disease prevalence and found that a country’s procedural capacity does not predict its pattern of sex disparity. Croatia and Bulgaria had among the highest procedure-to-prevalence ratios in the region, yet Croatia exhibited a significant disparity disadvantaging women while Bulgaria showed near-identical case-fatality between the sexes. This indicates that equitable outcomes depend not only on system capacity but on the fairness of clinical pathways determining who receives treatment. The findings align with individual-level data: Poland’s male disadvantage corresponds with registry evidence of higher sudden out-of-hospital cardiac arrest in men, while Serbia’s female disadvantage is consistent with Belgrade coronary care data showing higher in-hospital mortality in women with ST-elevation myocardial infarction even after adjustment for age and comorbidities.

The authors are careful to note the limitations of their approach. The analysis relies on modelled GBD estimates rather than primary clinical datasets, its ecological design precludes causal inference at the individual level, and the mortality and prevalence inputs of the MPR are structurally interrelated within the GBD modelling framework, meaning the ratio should be interpreted as a comparative indicator rather than a direct survival estimate. Nevertheless, the message for policymakers is clear: declining mortality does not automatically translate into equitable survival. The researchers call for cardiovascular surveillance systems to complement traditional mortality statistics with sex-specific, prevalence-adjusted indicators, and for a dual-track prevention strategy that confronts the pervasive male tobacco epidemic while addressing the female triad of physical inactivity, poor diet and metabolic risk. Slovenia demonstrates that low case-fatality is achievable in the region; the task now is to translate that benchmark into targeted, sex-sensitive action in the countries where preventable risks continue to drive excess deaths.

Subject of Research: Sex differences in ischaemic heart disease case-fatality and their dietary and lifestyle determinants across Central Europe

Article Title: Contributions of diet and lifestyle to sex differences in ischaemic heart disease burden in Central Europe: an analysis of the Global Burden of Disease Study 2023

Article References: Bugiardini, R., Rahaman, T., Badimon, L., Cenko, E., Anand, S. S., Manfrini, O., Merkely, B., Milicic, D., Townsend, N., Vaccarino, V., Gulati, M., & Gale, C. P. (2026). Contributions of diet and lifestyle to sex differences in ischaemic heart disease burden in Central Europe: an analysis of the Global Burden of Disease Study 2023. The Lancet Regional Health – Europe, 70, Article 101846. https://doi.org/10.1016/j.lanepe.2026.101846

Image Credits: AI Generated

DOI: 10.1016/j.lanepe.2026.101846

Keywords: ischaemic heart disease, Global Burden of Disease, Central Europe, sex disparities, case-fatality, dietary risk factors, physical inactivity, tobacco, hypertension, mortality-to-prevalence ratio, cardiovascular prevention, nutrition policy