The research drew on one of the world’s most remarkable longitudinal resources, the Copenhagen School Health Records Register. For decades, school physicians in Copenhagen measured the height and weight of virtually every schoolchild in the city, creating a meticulously preserved archive of childhood body size. The investigators harnessed this register to follow 66,906 females and 71,479 males born between 1952 and 1996, all of whom had weight and height measurements recorded between the ages of 6 and 15 years. By linking these childhood records to Danish national registers of hospital diagnoses and causes of death, the team could track which individuals later developed coronary heart disease, defined as diagnoses occurring at age 25 or beyond.

A central methodological strength of the study lies in how it characterized childhood growth. Rather than relying on a single measurement at one age, the researchers used latent class trajectory modelling, a statistical technique that identifies groups of individuals who share similar patterns of change over time. Five sex-specific childhood BMI trajectories emerged from the data, ranging from trajectories that remained within the lower average range to those tracking toward overweight and obesity. This approach captures the dynamics of growth, recognizing that a child whose BMI climbs steadily through the school years may carry a different cardiovascular risk profile than a child whose BMI stays stable, even if their measurements at any single age look similar.

During the follow-up period, 1,642 females and 3,456 males were diagnosed with coronary heart disease. The team then asked a question that had never been answered at this scale: does a parental history of cardiovascular disease modify the relationship between childhood BMI trajectories and early-onset heart disease? Family history is a well-established risk factor in its own right, and previous studies have shown that offspring of parents with cardiovascular disease face higher risks themselves. It was plausible that inherited or shared familial factors might amplify the harm of excess childhood adiposity, or alternatively that a strong family history might dominate risk to the point of overshadowing childhood body size.

The answer was a clear and somewhat surprising negative. Parental cardiovascular disease did not modify the associations between childhood BMI trajectory and later coronary heart disease. In other words, the increased risk conveyed by an overweight or obese childhood trajectory operated independently of whether a child’s parents had experienced heart disease. This statistical independence carries an important clinical message: a child with no family history of cardiovascular disease who follows an obese BMI trajectory is not protected from the cardiovascular consequences of childhood obesity. Excess adiposity in childhood appears to be a risk factor in its own right, not merely a marker that matters only in genetically susceptible families.

The magnitude of the associations was substantial. In models adjusted for parental cardiovascular disease, and compared with children following the average BMI trajectory, females on the overweight trajectory had a 65 percent higher hazard of coronary heart disease at ages 25 to 44 years, with a hazard ratio of 1.65 and a 95 percent confidence interval of 1.21 to 2.26. Females on the obesity trajectory fared worse still, with a hazard ratio of 2.28, meaning their hazard of early-onset disease was more than doubled. The corresponding estimates for males were strikingly similar: 1.70 for the overweight trajectory and 2.23 for the obesity trajectory, both statistically significant. These are large effects for a risk factor measurable in childhood, decades before any symptoms appear.

The age-stratified analysis revealed a pattern with real biological and public health significance. The elevated hazards were concentrated in the youngest age bands. Among both sexes, associations were strongest and clearest at ages 25 to 44 years. Among males, the associations remained evident at ages 45 to 54 years, but by age 55 and beyond, no associations between childhood BMI trajectory and coronary heart disease were found in either sex. This fading of the signal at older ages likely reflects the interplay of competing risks and the accumulation of other exposures across the life course. As people age, smoking, hypertension, diabetes, and adult weight change increasingly shape coronary risk, and the predictive power of childhood body size diminishes relative to these later-life factors. The finding underscores that childhood adiposity is a particularly potent driver of the early-onset form of the disease, precisely the form that is rising and that strikes people in the prime of working and family life.

The study’s conclusions land at a moment of global alarm over early-onset cardiovascular disease. Worldwide analyses have documented that cardiovascular disease remains the leading cause of death, and that rates of heart disease in younger adults have been climbing in many countries. At the same time, childhood obesity has surged: pooled analyses covering 222 million children and adolescents show that obesity has risen sharply since 1990, and in the United States the prevalence of obesity among children aged 2 to 19 has continued to increase through 2023. The Danish findings suggest these two trends are connected. If excess childhood adiposity more than doubles the hazard of coronary heart disease before middle age, then the current generation of children growing up with obesity may face a future wave of heart attacks and other coronary events occurring decades earlier than in their parents’ generation.

Mechanistically, the evidence that childhood obesity leaves lasting cardiovascular fingerprints is not new. Autopsy studies from the Bogalusa Heart Study, conducted decades ago, revealed fatty streaks and early atherosclerotic plaques in the coronary arteries of children and young adults, demonstrating that atherosclerosis begins in childhood. Subsequent cohort studies have linked childhood and adolescent BMI to cardiovascular mortality in midlife, to atrial fibrillation, to ischemic stroke, and to type 2 diabetes and obesity-related cancers. What the new study adds is the demonstration that this childhood risk is not contingent on family history. Children with obese BMI trajectories carry their risk with them regardless of the cardiovascular health of their parents, which strengthens the argument that childhood body size is an independent, modifiable determinant of lifelong cardiovascular health.

The public health implications are difficult to overstate. Clinical risk assessment has traditionally focused on middle-aged and older adults, and family history is often used to decide which younger patients deserve closer scrutiny. These results suggest that childhood BMI deserves a place in that conversation, and that prevention efforts aimed at childhood obesity are, in effect, coronary prevention campaigns with a lead time of several decades. Because the associations were independent of parental cardiovascular disease, interventions need not be targeted only at children with a family history; the entire population of children on elevated BMI trajectories stands to benefit. The authors emphasize that their findings highlight excess childhood adiposity as an important contributor to the early origins of coronary heart disease and reinforce the urgency of addressing the growing burden of childhood obesity. With early-onset cardiovascular disease on the rise worldwide, the trajectory a child’s BMI follows between the ages of 6 and 15 may quietly help determine whether that child, as an adult, becomes one of the growing number of people struck by heart disease in the prime of life.

Subject of Research: Childhood BMI trajectories and early-onset coronary heart disease risk

Article Title: Are associations of childhood body mass index trajectories with early-onset coronary heart disease modified by parental history of cardiovascular disease?

Article References: Aarestrup, J., Andersen, E. W., Twig, G., Jacobsen, R. K., Johnson, W., Bjerregaard, L. G., & Baker, J. L. (2026). Are associations of childhood body mass index trajectories with early-onset coronary heart disease modified by parental history of cardiovascular disease?. International Journal of Obesity. https://doi.org/10.1038/s41366-026-02239-4

Image Credits: AI Generated

DOI: 10.1038/s41366-026-02239-4

Keywords: childhood obesity, body mass index, coronary heart disease, early-onset cardiovascular disease, parental history, Copenhagen School Health Records Register, BMI trajectories, epidemiology, cohort study, risk factors, cardiovascular prevention, Denmark

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