An internal jugular venous thrombus in an astronaut was first identified in 2020 following a two-month microgravity exposure. This raised concerns about thromboembolic events (TE) during spaceflights. Studies have suggested that microgravity can induce changes in blood composition, venous flow and endothelial dysfunction, which might all contribute to a hypercoagulable state. However, whether these proposed mechanisms translate into a clinically significant increase in TE risk remains unclear since, even though humans have spent >200 person-years in space, no studies of blood coagulation in microgravity have been carried out. Additionally, the specific risks and implications of microgravity-induced coagulation changes in diverse populations, including future spacefarers with varying health conditions and ages, remain unclear. The precise risks and effects of microgravity-induced coagulation, especially as they relate to diverse groups such as future space travellers with different health conditions and age ranges, remain ambiguous and require further exploration. Thrombelastography (TEG), often used in trauma, surgery and anesthesiology, offers a comprehensive assessment of whole blood coagulation dynamics, providing a more holistic view compared to traditional coagulation assays. In particular, TEG has the ability to predict the hypercoagulable state associated with TE. A previous study of coagulation disorders in a 60-day bedrest setting has provided valuable insights into blood coagulation dynamics, although TEG did not differ in this specific study. However, the transferability of these findings to true microgravity environments remains to be elucidated. Understanding the effects of microgravity on the coagulation process is crucial for ensuring the health and safety of astronauts during space missions. By leveraging thrombelastography to study the end-result of the coagulation cascade, we can obtain valuable insights into the impact of microgravity on the coagulation system and comprehensively evaluate the risk of TE. Furthermore, this knowledge could inform preventive strategies and enhance the safety of future long-duration missions and diverse populations participating in future low-cost spaceflight ventures.

Although the impact of obstructive sleep apnea syndrome (OSA) on cardiovascular morbidity is well documented, ocular complications remain an uncertain topic. Eye diseases represent a problem of modern society, being one of the main causes of disability and decrease of quality of life.

The objective of this review is to analyze the specialized literature regarding ocular manifestations in OSA patients and the ophthalmological conditions associated with this sleep disorder. Underlying pathophysiological mechanisms and the impact of OSA treatment on ocular outcomes will also be discussed.

This work is a narrative review of articles published between 2000-2024 on databases such as PubMed, Google Scholar and HINARI. The articles were searched using combinations of the following keywords and search terms: obstructive sleep apnea, ocular complications, sleep disorders, eye disorders. Eligible publications were limited to English-language articles and comprised original research, reviews, meta-analyses, and clinical guidelines. Given the low prevalence of sleep apnea in children, only studies involving adult populations were included. Animal studies, non-English papers, case reports with insufficient data, and conference abstracts without full text were excluded.

OSA has been identified as a significant risk factor for various eye conditions, including glaucoma (GC), keratoconus, and diabetic retinopathy (DR). The prevalence of these conditions among patients with OSA is higher than in the general population. Although some studies suggest a link between OSA and ophthalmologic disorders, others dispute this association, as they can occur secondary to reduced blood flow through the internal carotid artery independent of OSA, such as in obesity, diabetes, and hypertension. However, positive dynamics were observed in GC and DR patients following CPAP treatment. The pathogeny involved in eye damage is uncertain, but studies suggest that both indirect and direct pathways are possible. Intermittent hypoxia induces hyperactivity of the sympathetic nervous system with the onset of vascular autonomic dysfunction, and the imbalance of vasoactive substances and oxidative stress disrupts the integrity of the blood-retinal barrier.

Although the correlation between OSA and eye diseases needs to be further studied, recognizing the potential of this association is essential for the prevention of ophthalmopathies.

To assess the association between domain-specific physical activity (physical activity, PA; occupation-related PA, OPA; transportation-related PA, TPA; leisure-time PA, LTPA) and sedentary behavior and mortality among participants with chest pain.

Cohort observational studies examined the associations between domain-specific PA and sedentary behaviors with mortality among participants with chest pain, adjusting for age, sex, race, and other medical comorbidities among chest pain adults (the National Health and Nutrition Examination Survey [NHANES]).

Community setting.

Participants aged 40 to 80 years were asked by well-trained staff whether they had ever felt pain or discomfort in their chest. If the answer was yes, they were diagnosed with chest pain. This study included 4,412 participants with complete data who had chest pain; their average age was 57.99 ± 0.26 years, and 51.90% (2,283) of them were female.

None.

Domain-specific physical activity (OPA, TPA, LTPA) and sedentary behaviors were assessed by using the Global Physical Activity Questionnaire, categorizing participants by 2018 physical activity guidelines and daily sitting time. Mortality outcomes (all-cause and cardiovascular) were determined via National Death Index records linked to ICD-10 codes up to December 2019.

Among chest pain participants, higher levels of total or domain-specific PA were associated with reduced all-cause and cardiovascular-related mortality risks. Conversely, sitting time exceeding 480 minutes daily significantly increased these risks. Regular leisure-time PA mitigated mortality risks, even with mortality risk associated with sedentary behaviors.

In adults with chest pain, regular leisure-time physical activity proved more effective than weekend warrior patterns in reducing mortality risks and mitigating the mortality risk token by sedentary behaviors.

Socioeconomic deprivation is a well-recognized determinant of cardiovascular health. We evaluated its influence on cardiovascular risk and damage in patients with systemic lupus erythematosus (SLE) in the Basque Country, where universal healthcare coverage is guaranteed.

Observational cohort study including 293 SLE patients with a 5-year follow-up. The association between the Basque Country's Socioeconomic Deprivation Index and cardiovascular risk factors and damage (SLICC index) was analyzed using multilevel generalized linear mixed models.

No significant associations were found between deprivation levels and the number of cardiovascular risk factors at diagnosis or at 5 years, nor with cardiovascular damage. Age at diagnosis and disease activity were the main predictors of cardiovascular outcomes.

In a universal healthcare setting, socioeconomic deprivation was not associated with worse cardiovascular risk or damage in SLE patients. These findings do not establish causality but are consistent with the hypothesis that universal healthcare may mitigate socioeconomic gradients in SLE cardiovascular outcomes.

Calcific aortic valve disease (CAVD) shares the same risk factors as atherosclerotic vascular diseases (ASVD). However, in contrast to ASVD, treating the risk factors has not been shown to be effective in preventing CAVD and its progression to aortic stenosis (AS). Thus, the ultimate pathophysiology of CAVD remains unknown. This study aimed to evaluate metabolic signatures associated with CAVD.

We carried out metabolomic analyses on a total of 255 subjects: 82 patients with AS, 72 patients with aortic valve sclerosis (ASc) and 101 healthy controls. Blood lipoproteins and metabolites, including lipids, amino acids, and inflammatory markers, were measured using nuclear magnetic resonance (NMR) metabolomics.

There were no significant differences in total cholesterol, HDL cholesterol, LDL cholesterol, or triglycerides. However, levels of small HDL particles were significantly lower in the AS group compared to the ASc and control groups, whereas no differences were found between the ASc and control groups. In addition, the levels of albumin and several amino acids were lower in the AS group when compared to the ASc group. These results suggest that patients with AS and ASc have different metabolic profiles.

Our study is the first to show that the levels of small HDL rather than plasma HDL concentration are significantly lower in AS patients. This suggests that small HDL may be one missing link in the pathophysiologic process between dyslipidemia and CAVD and generate innovative approaches for preventing CAVD. The results also prompt the question whether AS and ASc are distinct diseases.

A magnesium-rich diet (MRD), a novel dietary pattern emphasizing the synergistic benefits of magnesium-dense foods, has been linked to reduced risk of cardiovascular diseases (CVD). However, its association with CVD mortality remains uncertain. This study aimed to examine the relationship between MRD and CVD-related mortality.

A total of 91,891 adults were enrolled from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake was assessed using a validated food frequency questionnaire, and MRD scores were derived from consumption of whole grains, nuts, vegetables, fruits, legumes, coffee, and tea to evaluate adherence to the dietary pattern. Cox proportional hazards regression was applied to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). During a median follow-up of 15.0 years, 5848 CVD deaths were recorded, comprising 4236 from heart disease and 1213 from cerebrovascular disease.

In the multivariable-adjusted model, individuals in the highest MRD quartile had significantly lower risks of death from overall CVD (adjusted HR: 0.74, 95 % CI: 0.68, 0.81), heart disease (adjusted HR: 0.74, 95 % CI:0.67, 0.82), and cerebrovascular disease (adjusted HR: 0.67, 95 % CI:0.56, 0.81), compared with those in the lowest quartile. Dose-response analyses indicated a linear inverse relationship between MRD and mortality from CVD, heart disease, and cerebrovascular disease. Subgroup analyses revealed a more pronounced protective association in heavy drinkers relative to non-drinkers, light drinkers, or moderate drinkers. Notably, the oxidative balance score (OBS) mediated 18.53 % of the association between MRD and CVD mortality.

High adherence to MRD was associated with a substantially reduced risk of CVD mortality, including both heart disease and cerebrovascular disease, with oxidative balance playing a potential mediating role.

To investigate age-related differences in the pharmacokinetics (PK) and pharmacodynamics (PD) of perindopril.

We compared the PK/PD of perindopril between younger (<50 years) and older (>70 years) participants in a prospective study. The primary outcome was the difference in area under the concentration-time curve (AUC), both dose uncorrected (AUC_24h, in µg/L/24h) and dose corrected (AUC_cor, in µg/L/24h/mg). We calculated the AUCs of both perindopril and its metabolite perindoprilat. Secondary outcomes included the difference in blood pressure (BP) drop between the two groups, using ΔBP between blank (pre-perindopril) and non-blank (post-perindopril).

We included 26 participants, of whom 15 (58%) were aged <50 years. The median age in the younger group was 34 years (interquartile range(IQR)=27-41) and 74 in the older group (IQR = 71-77). For both the perindopril AUC_24h and AUC_cor we did not find statistically significant differences between the younger and older group. For perindoprilat AUC_24h, there was a statistically significant difference in the median between the younger [45.8,IQR = 32.0-57.4] and the older group [77.0, 62.5-96.5;p = 0.008], as well as for perindoprilat AUC_cor [respectively 15.2, 12.2-20.0 and 23.1, 18.5-23.5;p = 0.027]. We found a higher but statistically non-significant median Systolic BP drop between the blank and non-blank measurements in the older versus younger group (-9 mmHg vs -5 mmHg; p > 0.05).

Older adults exhibited higher perindoprilat exposure than younger adults, alongside an exploratory, non-significant trend toward greater systolic BP reduction. Given the limited sample size, no causal inference can be drawn from our data; nevertheless, these findings support consideration of age-related factors and individualised dosing in hypertension management.

Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease (CVD). Related mutations contributing to hypercontractility and poor relaxation in HCM are not completely understood.

This study aimed to explore and verify a novel variant of cardiac myosin-binding protein C (cMyBP-C, encoded by MYBPC3) in an HCM family.

Clinical information and cardiac parameters were collected in the pedigree. Genomic DNA was extracted from peripheral blood and second-generation sequencing technology was used to investigate the proband and his family members. Subsequent sequence analysis was performed with DNAMAN software. The cardiac expression levels of MYBPC3 mRNA and cMyBP-C protein were assessed using RT-qPCR and Western blot analysis, respectively.

Typical interventricular septal thickening was detected in all four HCM patients without left ventricular outflow tract obstruction. The c.1042_1043insCGGCA mutation in MYBPC3 was verified in the proband and family members. In silico analysis of the mutation revealed that c.1042_1043insCGGCA led to a shift in the sequence of nucleotides, creating a premature stop codon at the new reading frame. RT-qPCR analysis of MYBPC3 mRNA revealed a marked reduction in HCM heart compared to the normal controls (P < 0.05). Consistently, Western blot analysis showed significantly reduced expression of cMyBP-C in the pedigree in comparison with the controls (P < 0.05).

The novel c.1042_1043insCGGCA MYBPC3 mutation is a genetic basis for HCM due to c-MyBP-C haploinsufficiency.

Renal dysfunction in heart failure increases mortality, limits treatment options and blunts responses to therapy. Angiotensin receptor-blocker and neprilysin inhibitors (ARNI) may preserve renal function by modulating both the renin-angiotensin-aldosterone system and the natriuretic peptide system. We investigated the renal effects of the ARNI Sacubitril/valsartan (Sac/Val) in rats with systolic dysfunction secondary to myocardial infarction. Male Sprague-Dawley rats underwent surgical MI induction and were randomized to six weeks of treatment with vehicle, valsartan or Sac/Val, and compared to sham operated animals. Renal function was evaluated by creatinine clearance, mean arterial pressure (MAP) by tail-cuff measurements, and cardiac function by magnetic resonance imaging and echocardiography. Vehicle treated animals developed cardiorenal syndrome, with impaired cardiac systolic function and mild renal dysfunction. Both valsartan and Sac/Val preserved renal function compared to vehicle (creatinine clearance mL/min [median with interquartile range]; sham 5.4 [4.8-6.0], vehicle 4.5 [4.1-5.1], valsartan 5.1 [5.1-5.5], Sac/Val 5.1 [5.0-5.6]; vehicle vs valsartan p = 0.034 and vehicle vs Sac/Val p = 0.044). MAP was reduced by both treatments compared to sham and vehicle groups (MAP mmHg; sham 131 [116-138], vehicle 123 [115-132], valsartan 108 [99-112], Sac/Val 111 [99-119]; sham vs valsartan p < 0.001 and sham vs Sac/Val p = 0.003, vehicle vs valsartan p = 0.006 and vehicle vs Sac/Val p = 0.041). Only Sac/Val reduced left atrial dilatation (diameter mm; sham 4.1 [3.7-4.4], vehicle 4.6 [3.8-5.6], valsartan 4.6 [4.1-5.5], Sac/Val 3.9 [3.6-4.5]; vehicle vs Sac/Val p = 0.047, valsartan vs Sac/Val p = 0.017) despite no improvement in systolic function in either treatment group. Sac/Val initiated in the acute post-MI phase preserved renal function to the same extent as valsartan alone and uniquely reduced left atrial dilatation, suggesting additional benefits beyond renoprotection in the setting of persistent systolic dysfunction.

Noninvasive and objective biomarkers for disease-associated pathology are critical for clinical trials. For Fabry disease, one important pathological change due to the deficiency of the lysosomal enzyme α-galactosidase A (α-GAL) caused is accumulation of globotriaosylceramide (Gb3) in dorsal root ganglion (DRG) neurons, which manifests as the overall DRG hypertrophy. Magnetic resonance imaging (MRI) has been successfully used to noninvasively measure DRG enlargement in Fabry patients, and DRG volumetric MRI can be a potential noninvasive biomarker for Gb3 accumulations in DRG neurons in clinical trials. To evaluate disease progression and treatment response in preclinical proof-of-concept studies, we developed an in vivo MRI method to measure DRG size in the G3Stg/GLA knockout mouse model of Fabry disease. Compared to the wild type mice, the DRG enlargement in the Fabry mice was observed as early as 8 weeks of age, and a single administration of the human α-GAL-encoding adeno-associated virus (AAVGLA) normalized the enlarged DRG to the age-matched wild type mice. The DRG normalization was observed within 4 weeks of gene therapy (12 weeks of age) and was sustained up to 24 weeks of age. Furthermore, behavioral testing and histological/immunohistochemistry analyses of the DRG tissues corroborated the MRI findings. Volumetric DRG MRI has the sensitivity to measure Gb3 pathology-induced DRG volume changes and treatment response in live mice and can be a translational imaging biomarker in clinical trials for Fabry disease.