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Open research questions in Cardiovascular Health and Disease Prevention

38 unresolved questions extracted from the limitations and future-work sections of 317 Cardiovascular Health and Disease Prevention papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Ultrasonics 52:402–411 Kim SJ, Nogueira RG, Haussen DC (2019) Current understanding and gaps in research of carotid webs in ischemic strokes: a review.

    Haemodynamic and biomechanical biomarker analysis of carotid fibromuscular dysplasia via fluid–structure interaction · 2026 · DOI

  • , for major adverse cardiovascular events or mortality) could not be assessed. SYNTAX scoring was performed by a single invigila- tor who remained blinded to the patients’ haematological indices to avoid observer bias; however, inter-observer variability could not be assessed and potential observer bias cannot be fully excluded.

    Association of Haematological and Biochemical Inflammatory Indices with Angiographic Severity of Coronary Artery Disease in Chronic Stable Angina · 2026 · DOI

  • This study has several limitations. 1. The methodological quality of the included trials was not consistently high, with the main concerns involving the randomization process, outcome measurement, and selective reporting, which may have affected the precision of the effect estimates.

    Can resistance training alone or resistance training combined with aerobic training improve arterial stiffness, endothelial function, and other vascular function indicators in adults with hypertension or overweight/obesity-related vascular risk? A systematic review and meta-analysis of randomized controlled trials · 2026 · DOI

  • This review has several limitations. Evidence for wave reflection and peripheral haemodynamics was based on only two studies, resulting in imprecise estimates. Although more studies were available for arterial stiffness and flow-mediated dilation, several subgroup analyses still relied on few effect sizes. Reporting of exercise-prescription variables was also incomplete across studies: while modality, frequency, session duration, and programme dura- tion were usually available, repetitions, sets, supervision, progres- sion, and achieved dose/adherence were less consistently reported, limiting the robustness of moderator analyses and the strength of practical prescription inferences. Heterogeneity in intervention characteristics and comparator conditions may also have influenced the pooled results despite the use of random-effects models and subgroup analyses. In addition, incomplete reporting of randomisation, allocation concealment, blinding, and selective reporting in several trials increases concerns about risk of bias. Finally, study-level moderator analyses were constrained by collin- earity and limited statistical power and should therefore be inter- preted as exploratory.

    Does resistance training alone or in combination with aerobic training improve vascular function indices in adults with type 2 diabetes? A systematic review and meta-analysis of randomized controlled trials · 2026 · DOI

  • Future studies should prioritise under-represented outcomes, particularly wave reflection and peripheral haemodynamics. More rigorous and standardised trials are needed to clarify the effects of different exercise modes and prescriptions, improve measurement consistency, and integrate vascular outcomes with mechanistic measures such as nitric oxide-related indices, insulin sensitivity, glycaemic control, blood pressure, and inflammatory and oxidative stress biomarkers. Standardised and transparent reporting of exer- including supervision, progression, cise-prescription variables, achieved dose, and adherence, will also be essential to improve the interpretability of dose-related moderator analyses. Greater inclusion of women and older adults, together with longer follow- up, is needed to enhance generalisability and clinical relevance.

    Does resistance training alone or in combination with aerobic training improve vascular function indices in adults with type 2 diabetes? A systematic review and meta-analysis of randomized controlled trials · 2026 · DOI

  • By mapping the limited but methodologically diverse body of evidence available, this scoping review provides a structured overview of how ventricular–arterial coupling has been assessed in exercise-related research and identifies key gaps that warrant further investigation.

    Mapping the evidence on exercise-related ventricular–arterial coupling adaptations in male adults: a scoping review · 2026 · DOI

  • study designs synthesis. Sex-specific analyses were This scoping review has several limitations. The inclusion of and populations precludes heterogeneous quantitative limited, reflecting gaps in the existing literature rather than selection bias. Additionally, the absence of formal quality appraisal aligns with scoping review methodology but limits evaluation of internal validity.

    Mapping the evidence on exercise-related ventricular–arterial coupling adaptations in male adults: a scoping review · 2026 · DOI

  • Panvascular aging constitutes a systemic failure of the vascular hierarchy - spanning conduit, resistance, and capillary vessels - rather than a mere byproduct of chronological aging. Common pathogenic drivers, including endothelial dysfunction, mitochondrial impairment, NAD+ depletion, oxidative stress, low-grade inflammation, ECM remodeling, and cellular senescence, converge across diverse clinical spectrums such as cardiovascular disease, neurodegeneration, and CKD. This shared vascular foundation suggests that local injuries are not isolated; rather, epigenetic and metabolic dysregulation allow vascular decline to propagate multisystem effects, ultimately driving multimorbidity. Consequently, the therapeutic paradigm must shift from organ- specific interventions toward integrated, system-level approaches. Promising strategies involve restoring metabolic homeostasis - - specifically via NAD+ boosters and senolytics - alongside lifestyle modifications to ensure sustained protection. However, translating these insights into clinical practice requires addressing critical knowledge gaps. Future research must prioritize the development of cross-organ biomarker panels - integrating proteomics and epigenetic clocks - to quantify systemic biological age. Furthermore, longitudinal cohorts utilizing harmonized imaging (e.g., cfPWV, retinal Optical coherence tomography angiography (OCTA), and Page 20 of 28 Wu et al. Vessel Plus. 2026;10:20 hemodynamic MRI) are essential to identify signatures that predict multi-organ decline. By leveraging large-animal models and organ-on-chip technologies, the field can better dissect inter-organ communication. Ultimately, establishing a coherent framework for panvascular biology will depend on standardized composite endpoints and biomarker-stratified clinical trials to reverse coordinated vascular decline across the lifespan.

    Panvascular aging as a unifying framework: convergent mechanisms across age-related diseases · 2026 · DOI

  • Funding Several limitations of this study should be acknowledged. First, we did not directly measure reactive oxygen species production or eNOS coupling status; therefore, any interpretation regarding oxidative stress as an explanation for the increased ox-LDL The author(s) declared that financial support was received for this work and/or its publication.

    High-fat diet-induced obesity impairs endothelium-dependent relaxation in rabbits: association with MLCK upregulation and partial ex vivo improvement by ML-7 · 2026 · DOI

  • obesity, diet-induced extrapolation calculation was performed; levels remains speculative. Second, no formal a priori sample size should incorporate sample size estimation based on the effect sizes reported here. Third, our study was conducted in a rabbit model human so of pathophysiology should be made with caution. Fourth, although ML-7 is a selective MLCK inhibitor, we cannot completely rule out off-target effects that may have contributed to the observed changes. Fifth, the dissociation between ex vivo and in vivo findings (ACh-induced relaxation vs. FMD) indicates that the partial benefit of ML-7 does not improved endothelial function in conductance arteries in living animals, which limits the physiological and translational significance of the ex vivo results.

    High-fat diet-induced obesity impairs endothelium-dependent relaxation in rabbits: association with MLCK upregulation and partial ex vivo improvement by ML-7 · 2026 · DOI

  • The participants in this study were Chinese residents in Chengdu who voluntarily underwent a physical check-up in a single center, so the results are difficult to generalize to other ethnicities or other regions. Moreover, this study is a crosssectional study. Although some confounding factors were adjusted, there may still be some potential confounding factors affecting the results. The cross-sectional study could only prove the correlation between blood lipids and CIMT or carotid lipid temporal relationship between the plaque but not parameters the progression of CIMT or plaque and development. So the conclusion we draw is correlation rather than causation. This study did not analyze the relationship between blood lipids and plaque quantity, type, area, thickness, and so on. Carotid artery ultrasound during physical examination is a preliminary screening and does not describe the number and extent of plaques. Carotid ultrasound examinations were performed by experienced physicians and reviewed by senior operators; however, this does not substitute for formal assessment of measurement reproducibility, which might be one of the potential factors influencing the outcome. remnant Furthermore, non-fasting lipoprotein quantification may affect association between TG and HDL-C. Therefore, prospective multicenter studies with higher quality are needed to further confirm causality.

    Correlation of blood lipid parameters with newly diagnosed carotid intima media thickness and carotid plaque in primary health care of populations · 2026 · DOI

  • Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to lack of consensus on how to characterize VA as physiological vs.

    Vascular ageing: moving from bench towards bedside · 2023 · DOI

  • Introduction: There is a bulk of literature data on the physiological roles of nitric oxide (NO) and endothelin- 1 (ET-1), but many facts remain unknown, especially in certain diseases such as peripheral arterial disease.

    Impact of risk factors on serum levels of vasoactive substances in patients with peripheral arterial occlusive disease at different Fontaine’s stages · 2021 · DOI

  • Limited data regarding the influence of hyperglycemia on valvular calcification are available while understanding the cross-talk between them is pivotal in designing an effective therapeutic approach to prevent or at least retard AS development and/or progression in DM patients.

    Diabetes mellitus as a risk factor for aortic stenosis: from new mechanisms to clinical implications · 2021 · DOI

  • Several limitations of this study warrant consideration. Furthermore, as this study exclusively involved Chinese rural hypertensive adults, the extent to which these findings can be generalized to other ethnic groups and populations at risk remains uncertain.

    Association between the triglyceride-glucose index and carotid-femoral pulse wave velocity in rural hypertensive adults · 2026 · DOI

  • Abstract Background The role of the microcirculation in cardiovascular health in males and females is not fully understood.

    Sex differences in microvascular patterns associated with low- and high-risk for cardiovascular disease · 2026 · DOI

  • Whether the lower amplitudes of shear spectra contributed to ASCVD, or arise as a consequence of disease progression remains unknown.

    Arterial Shear Spectra Influence Endothelial Function and Are Regulated by Vascular Resistance · 2026 · DOI

  • However, the relationship between dietary vitamin intake and vascular stiffness parameters in patients with LC remains poorly understood.

    Dietary Vitamin Intake and Central and Peripheral Arterial Stiffness in Patients with Long COVID: The BioICOPER Study · 2026 · DOI

  • The present pipeline already applies the same formal metric definitions to venous waveforms, but the corresponding physiological interpretation and optimal integra- tion into composite scores remain to be developed.

    Composite waveform biomarkers for microvascular function stratification using retinal laser Doppler holography · 2026 · DOI

  • The impact of multiparity on ASI, AVP, and EFT has not been previously reported in the literature.

    The Effect of Number of Pregnancies on Aortic Stiffness Index, Aortic Velocity Propagation, and Epicardial Fat Thickness · 2024 · DOI

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38 open questions have been extracted from the limitations and future-work passages of 317 Cardiovascular Health and Disease Prevention papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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