During the 1960s, in a pioneering way, plasmapheresis was used to treat children with homozygous familial hypercholesterolaemia (HoFH). Over the years, apheresis has evolved to increasingly selective methods, which have been used in paediatric HoFH since the 1990s. Today, lipoprotein apheresis (LA) is able to selectively remove atherogenic apoB100-containing lipoproteins from the blood: the main component of LDL-cholesterol, VLDL-cholesterol, and lipoprotein(a). Lipoprotein apheresis has demonstrated protective effects in the endothelium and microcirculation, prevention of the development of new aortic and coronary lesions in HoFH, reducing the incidence of major cardiovascular events, and proving helpful in subjects who fail to reach the LDL-cholesterol target or who have elevated lipoprotein(a) levels in secondary prevention. Although advances in pharmacological therapies (proprotein convertase subtilisin/kexin Type 9 inhibitors, antisense oligonucleotides, and siRNA-based treatments) have expanded the options for lipid management, LA remains a safe therapeutic approach for patients with severe lipid disorders, including HoFH, to reduce their cardiovascular risks. Currently, to put LA into perspective, some obstacles need to be overcome, including (i) the underdiagnosis of HoFH and high lipoprotein(a) level; (ii) therapeutic inertia resulting from the use of new lipid-lowering drugs with partial achievement of lipid targets; and (iii) availability of qualified LA centres and practitioners. Further prospective studies may prove useful to identify other therapeutic scenarios for LA, such as renal disease, diabetic foot ulcer, peripheral arterial disease, pre-eclampsia, macular degeneration, or sudden sensorineural hearing loss. In these clinical settings, prospective, randomized clinical trials are therefore warranted.

Ageing is accompanied by progressive microvascular dysfunction, a key determinant of organ performance and longevity. The molecular drivers of this process remain incompletely defined, and the mechanisms by which exercise counters vascular ageing are unclear. This study investigated whether exercise-regulated long noncoding RNAs (lncRNAs) contribute to microvascular ageing and age-related cardiac dysfunction. RNA sequencing was performed in naturally aged mice with and without voluntary exercise. Functional studies of candidate lncRNAs were conducted using AAV-mediated overexpression, antisense oligonucleotides, and CRISPR-based knockdown, both in vivo and in endothelial cells (ECs). A novel set of lncRNAs altered in hearts from exercised aged mice was identified and termed Senescence Associated LncRNA Transcripts in Exercise (SALTes). Among these, SALTe1 is evolutionarily conserved and enriched in ECs. SALTe1 expression is elevated in hearts from aged mice and in patients with various types of heart failure but suppressed by exercise. In 20-month-old mice, SALTe1 inhibition, via antisense GapmeRs or EC-specific deletion, attenuated endothelial senescence, restored microvascular perfusion, and improved diastolic function. Mechanistic studies showed that SALTe1 acts, at least in part, through upregulation of PARP9. These findings establish SALTe1 as a pivotal regulator of endothelial senescence as well as microvascular and cardiac dysfunction in ageing. Targeted inhibition of SALTe1 recapitulates the vasculoprotective effects of exercise, highlighting a tractable antisense-based therapeutic strategy for combating age-related cardiac decline.

This 2025 report from the ESC Atlas project is the fifth in a biennial series. It presents and compares updated cardiovascular disease (CVD) statistics for more than 50 of the ESC member countries. The statistics are for 2024 or latest available year and are stratified by sex and World Bank national income status to identify inequalities in the risk, management, and outcomes of CVD across ESC member countries. A key objective of the ESC Atlas project has been to inform EU-level policy initiatives aimed at reducing the burden of CVD, contributing to the evidence base underpinning the European Union's cardiovascular health plan ("Safe Hearts Plan"), adopted in December 2025. Population ageing is a major contributor to the continuing high prevalence of CVD across ESC member countries. The Atlas reports 68 million disability-adjusted life years attributable to CVD in association with more than 3 million deaths per year. These statistics identify CVD as the leading cause of death across ESC member countries. However, substantial variation exists by national income status, with middle-income countries exhibiting age-standardized mortality rates that are roughly twice those observed in high-income countries. Marked disparities in healthcare delivery-particularly in workforce capacity and access to advanced interventions-are also evident. These inequalities by national income status are recurrent throughout this Atlas report. They highlight clear priorities for policymakers as they develop strategies to reduce the burden of CVD in the regions where the need is greatest. This 2025 report provides a detailed picture of the complex interplay between demography, the environment, socio-economic status, and clinical factors in shaping cardiovascular (CV) risk. It underscores how the progress that has been made in reducing the CVD burden across ESC member countries is at risk of being offset by new challenges, particularly the epidemic of obesity and diabetes that continues to undermine CV health. The findings presented in this report emphasize the need for coordinated policies to combat these challenges in order to sustain the progress that has been made in reducing the burden of CVD across ESC member countries.

Dyslipidaemia in cancer patients presents several challenges with increasing survival of cancer patients. Dyslipidaemia and cancer treatments both increase atherosclerotic cardiovascular disease (ASCVD) risk; yet, most risk prediction scores for ASCVD do not include important cancer factors and thus underestimate true ASCVD. Some cancer therapies cause transient elevations of low-density lipoprotein cholesterol or triglycerides, or reduction in high-density lipoprotein cholesterol, occasionally to extreme levels requiring specific treatment and monitoring strategies. A range of lipid-lowering therapies can be used in cancer patients to manage cholesterol and triglycerides but of these, reliable data only exist for statins and ezetimibe for managing low-density lipoprotein cholesterol, and fibrates and Omega 3 fish oils for hypertriglyceridaemia. There are no robust randomized controlled trials conducted in cancer patients for reduction of adverse cardiovascular events and therefore current recommendations have been extrapolated from non-cancer trials. Cancer survivors may require combination therapies; yet, trials of newer lipid-lowering therapies excluded cancer patients and hence safety and efficacy data are limited. The initiation of lipid-lowering therapy in cancer patients requires an integration of several factors, which includes a careful assessment of ASCVD risk, drug-drug interactions, side-effect profiles, and prognosis. Further work is required to personalize individualized risk scores for ASCVD in cancer patients and survivors and new trials and 'real-world' or registry data would inform these existing data gaps. Beyond lipid management, the putative role of therapies such for statins as cardioprotective agent for anthracycline chemotherapy open novel avenues for further research as survival from many cancers continues to improve.

Emerging data suggest that, in patients with chronic coronary syndromes (CCS), clopidogrel provides superior antithrombotic protection compared with aspirin for secondary prevention, without an associated increase in bleeding risk. The consistency of the observed benefits across ethnicities remains uncertain. Randomized controlled trials (RCTs) comparing aspirin vs clopidogrel for secondary prevention in patients with CCS were screened. The primary endpoint was trial-defined major adverse cardiovascular events (MACE). Prespecified subgroup interaction by ethnicity (East Asian vs non-East Asian) was performed. Trial sequential analysis was used to assess the statistical power of the results. Seven RCTs were included, encompassing 30 165 patients, of whom 75.1% were East Asians. Median follow-up was 36.0 months. Overall, clopidogrel was associated with significant reductions in MACE (incidence rate ratio [IRR] 0.83, 95% confidence interval [CI] 0.69-0.99) and net adverse clinical events (IRR 0.83, 95% CI 0.69-0.99), compared with aspirin. There were no differences between groups in major bleeding, myocardial infarction, or mortality. The results were consistent in the East Asian population, whereas a significant interaction by ethnicity was observed for MACE (East Asians: IRR 0.76, 95% CI 0.59-0.98; non-East Asians: IRR 1.00, 95% CI 0.74-1.36; Pint = 0.010) and mortality (Pint = 0.014), with no significant benefits observed in non-East Asian patients. The analyses were statistically powered for most outcomes in East Asian populations but for none in non-East Asian populations. In patients with CCS, the overall body of evidence suggests improved outcomes with clopidogrel compared with aspirin, without an apparent effect on mortality. However, a high level of confidence in these findings is currently limited to East Asian populations, and additional evidence is needed to clarify their applicability to non-East Asian patients. PROSPERO (CRD420251145176).