The research team analysed data from participants who enrolled in Our Future Health between 2022 and 2025. Hypertension was defined according to World Health Organization criteria: a systolic blood pressure of 140 mmHg or greater, a diastolic blood pressure of 90 mmHg or greater, or the use of blood pressure-lowering medication. Using this standardised definition, the investigators assessed three linked questions: how many participants had high blood pressure, how many of those had been diagnosed and treated, and how many had their blood pressure actually brought under control. The answers reveal a cascade of missed opportunities running through every stage of care.

Overall, just over one-third of participants, 37 percent, had hypertension. That figure varied enormously with age, rising from around one in six people aged 18 to 39 to nearly three-quarters of those aged 80 or older. After age-standardisation, hypertension was almost 50 percent more common in men than in women, affecting 42 percent of men compared with 29 percent of women. These prevalence estimates alone are striking, but the more alarming numbers concern what happened next. For 59 percent of people with hypertension, the condition was undetected: they had never received a diagnosis and were not on any blood pressure-lowering medication.

Detection, however, is only the first hurdle. Among participants who were taking one or more blood pressure medications, half still had elevated readings of 140/90 mmHg or higher. In other words, even when the healthcare system succeeded in identifying hypertension and initiating treatment, it frequently failed to finish the job. Effective hypertension management typically requires titration of drug doses, combination therapy, adherence support and regular monitoring, and the data suggest that these follow-through steps are breaking down for a large share of treated patients. The result is a population in which millions of people carry a major, modifiable cardiovascular risk without knowing it, and many of those who do know remain inadequately protected.

The clinical stakes are difficult to overstate. Hypertension is one of the most important causes of stroke, heart disease and premature death, and, as the British Heart Foundation emphasises, it remains the leading modifiable risk factor for cardiovascular disease, linked to around half of heart attacks and strokes in the United Kingdom. Because elevated blood pressure usually produces no symptoms, the first manifestation for many patients is a catastrophic vascular event. Every undetected case represents a person whose risk could have been reduced, often substantially, with timely diagnosis and appropriate treatment. Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, described the study as painting a concerning picture of the scale of undetected high blood pressure and of the challenge of keeping the condition controlled in those already on treatment.

Perhaps the most provocative aspect of the analysis is the authors’ argument that the problem is not simply one of resources or public awareness, but of clinical policy. Despite longstanding guidance, current estimates of hypertension awareness, treatment and control in England have not improved in recent decades. The researchers contend that current National Institute for Health and Care Excellence guidelines, which require multiple confirmatory blood pressure readings before a diagnosis is confirmed and recommend lifestyle advice ahead of drug treatment, contribute to many cases never being properly detected, treated or controlled. Each additional diagnostic hurdle, the argument runs, creates another point at which a patient can be lost to follow-up, and each delay in pharmacological intervention extends the period during which quietly damaging blood pressure levels go unaddressed.

Wenyu Liu, Medical Statistician at Oxford Population Health and lead author of the study, was blunt in her assessment. While hypertension is largely a silent killer, she said, the current approach to detecting and treating high blood pressure is not fit for purpose. She stressed that the problem is not confined to any particular demographic group but is substantial across almost every category the team examined. Even among younger adults, who are not currently eligible for the NHS Health Check programme, more than 15 percent already had high blood pressure. That finding, she argued, underscores the need for population-wide prevention strategies alongside targeted treatment for people at high cardiovascular risk, rather than relying solely on age-triggered screening.

Clinicians working on the front line say the findings mirror everyday reality in general practice. Iain Turnbull, Deputy Chief Medical Officer at Our Future Health, Clinical Research Fellow at Oxford Population Health and a working GP, noted that many patients with high blood pressure are undetected or sub-optimally treated, and that the study’s results reflect what doctors see day to day. He called for a more proactive approach to detection and suggested that treatment decisions should consider predicted cardiovascular risk in addition to measured blood pressure levels. Such a risk-based strategy would echo approaches used in cardiovascular prevention more broadly, where absolute risk calculators help determine who benefits most from intervention, rather than waiting for a single measurement to cross a fixed threshold.

The scale of the dataset lends unusual weight to these conclusions. Our Future Health is designed to recruit up to five million people and to reflect the diversity of the UK population, collecting and linking multiple sources of health information, including genetic data, within secure, accredited trusted research environments from which identifiable information is removed and stored separately. Standardised clinic blood pressure measurements taken at enrolment, rather than self-reported diagnoses, mean the study captures the true prevalence of hypertension rather than the smaller fraction known to the health system. That methodological strength is precisely what allows the researchers to quantify the detection gap so confidently, and it explains why the findings have resonated across the cardiology and public health communities.

What happens next will depend on whether the health system can translate these numbers into action. The options under discussion include broader and earlier screening, simplified diagnostic pathways that reduce the number of confirmatory visits required, greater use of community and pharmacy-based measurement, and treatment algorithms that weigh overall cardiovascular risk rather than blood pressure readings alone. The British Heart Foundation estimates that better detection and treatment could help tens of thousands of people avoid preventable heart attacks and strokes, but achieving that, Williams cautioned, will require rethinking how at-risk people are identified, treated and supported so that blood pressure checks and effective therapy reach everyone. With hypertension implicated in roughly half of the UK’s heart attacks and strokes, and with the majority of cases still slipping through undetected, the study stands as a data-driven warning that one of medicine’s oldest and simplest interventions is being delivered to far too few of the people who need it.

Subject of Research: Prevalence, detection, treatment and control of hypertension among adults in England

Article Title: Two-thirds of adults with high blood pressure do not know they have it

Article References: Two-thirds of adults with high blood pressure do not know they have it. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: hypertension, blood pressure, cardiovascular disease, Our Future Health, Oxford Population Health, screening, NICE guidelines, public health, stroke, heart disease, BMJ Public Health, England

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

The significance of the finding lies in its dual mechanism. Cardiovascular researchers have traditionally treated endothelial dysfunction and macrophage-driven inflammation as related but distinct strands of the atherosclerosis story. The endothelium, a single-cell-thick lining that governs vascular tone, barrier integrity, and leukocyte trafficking, is often the first casualty of cardiovascular risk factors such as hypertension, hyperlipidemia, and diabetes. When endothelial cells malfunction, they express fewer protective molecules such as nitric oxide and more adhesion molecules that invite circulating monocytes to breach the vessel wall. Meanwhile, once inside the intima, monocytes differentiate into macrophages that gorge on oxidized lipids, transform into foam cells, and release a cascade of inflammatory cytokines that amplify lesion growth. The new work suggests that PLCE1 is a single upstream node that helps orchestrate both of these pathological processes at once.

PLCE1 encodes an enzyme belonging to the phospholipase C family, proteins that cleave the membrane phospholipid PIP2 into two potent second messengers, inositol trisphosphate and diacylglycerol. These messengers mobilize intracellular calcium and activate protein kinase C, triggering a wide range of cellular responses. PLCE1 is unusual among phospholipases because it also carries a Ras-associating domain and a Ras-GEF domain, linking it directly to small GTPase signaling pathways that control cell proliferation, migration, and survival. Genetic studies over the past decade and a half have repeatedly flagged variants within the PLCE1 gene locus in genome-wide association studies of coronary artery disease, and even earlier of stroke risk in some populations. What those association studies could not resolve was whether PLCE1 is merely a bystander genetically linked to true disease drivers, or an active participant in the disease process. The new findings argue firmly for the latter.

Using a combination of cellular models, animal experiments, and mechanistic analyses, the research team demonstrated that elevated PLCE1 activity worsens endothelial dysfunction. In endothelial cells, increased PLCE1 expression was associated with impaired endothelial function markers, disturbed barrier behavior, and a shift toward the pro-inflammatory, pro-adhesive state that characterizes early lesion formation. When the investigators suppressed PLCE1 in experimental models of atherosclerosis, the resulting lesions were less severe, and the endothelial lining displayed healthier functional characteristics. This directional evidence, that manipulation of PLCE1 changes disease severity rather than simply tracking with it, is the kind of causal data that genetic association studies alone can never provide.

The second arm of the mechanism concerns macrophages, the immune workhorses whose transformation into lipid-laden foam cells defines the atherosclerotic plaque. The study found that PLCE1 promotes a pro-inflammatory phenotype in macrophages, driving the production and release of inflammatory mediators that recruit further immune cells and destabilize plaques. Macrophage inflammation is now recognized as a central engine of atherosclerotic progression, a view powerfully validated by the landmark CANTOS clinical trial, which showed that directly targeting the inflammatory cytokine IL-1 beta reduces cardiovascular events independently of cholesterol lowering. By implicating PLCE1 upstream of macrophage inflammatory activation, the new research adds a candidate control point that could, in principle, restrain this inflammatory engine at its source.

The most consequential discovery, however, may be the identification of CTNNB1 as the molecular target linking PLCE1 to both pathologies. CTNNB1 encodes beta-catenin, the central transducer of the canonical Wnt signaling pathway and a transcriptional co-regulator with its finger in countless developmental and inflammatory processes. In the study’s experimental framework, PLCE1 was shown to act on beta-catenin signaling, and beta-catenin in turn mediated the downstream effects on endothelial cells and macrophages. When beta-catenin was experimentally depleted, the harmful consequences of PLCE1 overexpression were blunted. This epistatic relationship, in which removing the target abolishes the effect of the driver, is a classic hallmark of a genuine signaling axis, and it suggests a linear pathway: PLCE1 acts upon beta-catenin, and beta-catenin drives the gene expression programs that produce endothelial dysfunction and macrophage inflammation.

This proposed axis is biologically plausible in light of prior literature. Beta-catenin signaling has been repeatedly implicated in vascular inflammation, with Wnt-beta-catenin activity reported to increase endothelial permeability and to promote inflammatory gene expression in both endothelial cells and macrophages under atherosclerotic conditions. What the new study contributes is the placement of PLCE1 upstream of this pathway in the specific context of arterial disease, transforming scattered mechanistic hints into a coherent, testable model. It also offers a potential explanation for longstanding genetic associations between PLCE1 variants and cardiovascular outcomes: those variants may alter the intensity of beta-catenin signaling in the vessel wall, tuning the inflammatory set point of atherosclerotic tissue.

From a therapeutic standpoint, the findings are provocative but must be tempered by important caveats. Both PLCE1 and beta-catenin are pleiotropic molecules, meaning they perform essential functions far beyond the vascular system. Beta-catenin, in particular, is indispensable for stem cell maintenance in the intestine, bone formation, and a host of developmental processes, which is why systemic Wnt-pathway inhibitors have repeatedly stumbled in cancer trials due to toxicity. Any attempt to translate the PLCE1-beta-catenin axis into a cardiovascular therapy would almost certainly require highly targeted delivery, perhaps to vascular endothelium or lesional macrophages, or the identification of downstream effectors that are more vascular-specific. The study does not itself report a candidate drug or clinical intervention, and its conclusions rest on experimental models whose fidelity to human atherosclerosis, while substantial, is never complete.

Nevertheless, the work exemplifies a broader and encouraging trend in cardiovascular biology: the convergence of human genetics, molecular signaling, and immunology into unified mechanistic accounts of atherosclerosis. For decades, the field’s therapeutic triumphs came almost exclusively from lipid metabolism, embodied by statins and more recently PCSK9 inhibitors. Yet a large residual risk persists in patients whose cholesterol is well controlled, and that residual burden is increasingly attributed to inflammation and vascular dysfunction. Identifying molecules like PLCE1 that couple inflammatory and endothelial pathologies through a defined signaling route gives researchers exactly the kind of targets needed to address this residual risk. It also enriches the interpretation of existing genetic risk scores, which currently aggregate thousands of variants of unknown function. Each variant that is functionally resolved, as PLCE1 variants now partly are, converts statistical prediction into biological insight.

For now, the immediate value of the study lies in its demonstration of a principle: that a single enzyme can coordinate two of the most destructive processes in atherosclerosis through a well-defined molecular partner. Future work will need to confirm the PLCE1-beta-catenin axis in human tissue, map precisely how PLCE1 activity modifies beta-catenin at the molecular level, and determine whether existing or novel pharmacological tools can safely modulate this pathway in patients at risk. If those steps succeed, a gene discovered through population association studies may finally graduate from statistical curiosity to therapeutic target, offering a new angle of attack on the world’s leading cause of death. In a disease as complex and multifactorial as atherosclerosis, every newly charted junction in the signaling map is a potential checkpoint at which progression might be halted, and PLCE1 has just been added to that map in bold.

Subject of Research: The role of PLCE1 in driving atherosclerosis through endothelial dysfunction and macrophage inflammation via CTNNB1

Article Title: PLCE1 exacerbates the development of atherosclerosis by driving endothelial dysfunction and macrophage inflammation via targeting CTNNB1

Article References: Cheng, W.-L., Shi, Y., Zhang, Q., Cai, Z., Jiang, F.-X., Kong, X., Cao, J.-L., Peng, L., Chen, M., He, T., & Wang, H. (2026). PLCE1 exacerbates the development of atherosclerosis by driving endothelial dysfunction and macrophage inflammation via targeting CTNNB1. Cell Death Discovery. https://doi.org/10.1038/s41420-026-03309-2

Image Credits: AI Generated

DOI: 10.1038/s41420-026-03309-2

Keywords: PLCE1, atherosclerosis, CTNNB1, beta-catenin, endothelial dysfunction, macrophage inflammation, cardiovascular disease, Cell Death Discovery, Wnt signaling, foam cells, heart disease, molecular mechanism