Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation.

RATIONALE: The disruption of the balance between fatty acid (FA) uptake and oxidation (FAO) leads to cardiac lipotoxicity, serving as the driving force behind diabetic cardiomyopathy (DbCM). Sirtuin 5 (Sirt5), a lysine de-succinylase, could impact diverse metabolic pathways, including FA metabolism. Nevertheless, the precise roles of Sirt5 in cardiac lipotoxicity and DbCM remain unknown. OBJECTIVE: This study aims to elucidate the role and underlying mechanism of Sirt5 in the context of cardiac lipotoxicity and DbCM. METHODS AND RESULTS: The expression of myocardial Sirt5 was found to be modestly elevated in diabetic heart failure patients and mice. Cardiac dysfunction, hypertrophy and lipotoxicity were exacerbated by ablation of Sirt5 but improved by forced expression of Sirt5 in diabetic mice. Notably, Sirt5 deficiency impaired FAO without affecting the capacity of FA uptake in the diabetic heart, leading to accumulation of FA intermediate metabolites, which mainly included medium- and long-chain fatty acyl-carnitines. Mechanistically, succinylomics analyses identified carnitine palmitoyltransferase 2 (CPT2), a crucial enzyme involved in the reconversion of fatty acyl-carnitines to fatty acyl-CoA and facilitating FAO, as the functional succinylated substrate mediator of Sirt5. Succinylation of Lys424 in CPT2 was significantly increased by Sirt5 deficiency, leading to the inactivation of its enzymatic activity and the subsequent accumulation of fatty acyl-carnitines. CPT2 K424R mutation, which mitigated succinylation modification, counteracted the reduction of enzymatic activity in CPT2 mediated by Sirt5 deficiency, thereby attenuating Sirt5 knockout-induced FAO impairment and lipid deposition. CONCLUSIONS: Sirt5 deficiency impairs FAO, leading to cardiac lipotoxicity in the diabetic heart through the succinylation of Lys424 in CPT2. This underscores the potential roles of Sirt5 and CPT2 as therapeutic targets for addressing DbCM.

Low remnant cholesterol and the subsequent risk of new-onset atrial fibrillation: A prospective cohort study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia with high morbidity and mortality implications. Several studies have described a paradoxical inverse relationship between serum cholesterol and the risk of AF, but it remains unknown whether remnant cholesterol (RC) is associated with AF incidence. OBJECTIVE: This study aims to prospectively investigate the association between RC and AF. METHODS: A total of 392,783 participants free of AF at baseline from the UK Biobank were included for the analysis. Cox proportional hazards model, subgroup analysis, and sensitivity analyses were used to evaluate the independent association between RC levels and the risk of new-onset AF. Furthermore, we performed a discordance analysis by using the median cutoff points of low-density lipoprotein cholesterol (LDL-C) and RC. RESULTS: After a median follow-up of 12.8 years (interquartile range 12.0-13.6 years), a total of 23,558 participants experienced incident AF. Compared with the highest RC level, the lower RC level was associated with an increased risk of AF incidence (quartile 1 vs quartile 4: hazard ratio 1.396; 95% confidence interval [CI] 1.343-1.452). The results remained robust across a series of sensitivity analyses. In the discordance analyses, a significantly higher risk of AF was observed in participants with discordant low RC/high LDL-C levels than in those with concordant high RC/LDL-C levels. In the low LDL-C group, RC reduction even contributed to an additional 15.8% increased rate of incident AF (low RC/low LDL-C: hazard ratio 1.303; 95% CI 1.260-1.348 vs high RC/low LDL-C: hazard ratio 1.125; 95% CI 1.079-1.172). CONCLUSION: Low RC levels were associated with an increased risk of incident AF independent of traditional cardiovascular risk factors.

AHA Life's Essential 8 and new-onset CKD: a prospective cohort study from the UK Biobank.

BACKGROUND: The AHA has recently introduced a novel metric, Life's Essential 8, to assess cardiovascular health (CVH). Nevertheless, the association between varying levels of LE8 and the propensity for CKD is still unclear from a large prospective cohort. Our objective is to meticulously examine the relationship between LE8 and its associated susceptibilities to CKD. METHODS: A total of 251,825 participants free of CKD from the UK Biobank were included. Cardiovascular health was scored using LE8 and categorized as low, moderate, and high. Cox proportional hazard models were employed to evaluate the associations of LE8 scores with new-onset CKD. The genetic risk score for CKD was calculated by a weighted method. RESULTS: Over a median follow-up of 12.8 years, we meticulously documented 10,124 incident cases of CKD. Remarkably, an increased LE8 score correlated with a significant reduction of risk in new-onset CKD (high LE8 score vs. low LE8 score: HR = 0.300, 95% CI 0.270-0.330, p < 0.001; median LE8 score vs. low LE8 score: HR = 0.531, 95% CI 0.487-0.580, p < 0.001). This strong LE8-CKD association remained robust in extensive subgroup assessments and sensitivity analysis. Additionally, these noteworthy associations between LE8 scores and CKD remained unaffected by genetic predispositions to CKD. CONCLUSIONS: An elevated degree of CVH, as delineated by the discerning metric LE8, exhibited a pronounced and statistically significant correlation with a marked reduction in the likelihood of CKD occurrence.

Age at job initiation and risk of coronary heart disease: findings from the UK biobank cohort study.

BACKGROUND: Commencing work at an early age has been linked to various risk factors for coronary heart disease (CHD), such as shift work and intensive job strain. However, the relationship between starting work too early and CHD risk remains largely unclear. We examined the association between age at job initiation and the risk of CHD. METHODS: UK Biobank participants aged 38 to 70 years without cardiovascular disease who provided data on their age at job initiation were included. The primary outcome was CHD, which was ascertained using hospital and death records. The hazard ratios (HRs) and 95% confidence interval (CIs) for the association between age at job initiation and CHD were calculated using multivariable Cox regression. RESULTS: Of the 501,971 participants, 114,418 eligible participants were included in the final analysis. The median age at job initiation was 19.0 years. During the mean follow-up of 12.6 years, 6,130 (5.4%) first CHD events occurred. We observed that age at job initiation was inversely associated with CHD (HR 0.98, 95% CI 0.97-0.99), and the association was potentially J-shaped. The HRs for the < 17-year, 17-18-year, and 19-21-year age groups were 1.29 (95%CI 1.18-1.41), 1.12 (95% CI 1.03-1.22) and 1.05 (95% CI 0.97-1.14), respectively, compared with those of the ≥ 22-year group. CONCLUSIONS: Age at job initiation was associated with incident CHD, which was independent of socioeconomic status. Participants who commenced employment before the age of 19 years exhibited a higher risk of developing CHD later in adulthood.

Measurement of the [Formula: see text]Ta([Formula: see text]) cross sections up to stellar s-process temperatures at the CSNS Back-n.

The neutron capture cross section of [Formula: see text]Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The [Formula: see text]Ta([Formula: see text]) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and [Formula: see text] liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1-700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of [Formula: see text]Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of [Formula: see text]Ta([Formula: see text]) reaction in the stellar s-process temperatures.

U-shaped association between the triglyceride-glucose index and atrial fibrillation incidence in a general population without known cardiovascular disease.

OBJECTIVE: The triglyceride-glucose (TyG) index has been shown to be a new alternative measure for insulin resistance. However, no study has attempted to investigate the association of the TyG index with incident atrial fibrillation (AF) in the general population without known cardiovascular diseases. METHODS: Individuals without known cardiovascular diseases (heart failure, coronary heart disease, or stroke) from the Atherosclerosis Risk in Communities (ARIC) cohort were recruited. The baseline TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The association between the baseline TyG index and incident AF was examined using Cox regression. RESULTS: Of 11,851 participants, the mean age was 54.0 years; 6586 (55.6%) were female. During a median follow-up of 24.26 years, 1925 incidents of AF cases (0.78/per 100 person-years) occurred. An increased AF incidence with a graded TyG index was found by Kaplan‒Meier curves (P < 0.001). In multivariable-adjusted analysis, both < 8.80 (adjusted hazard ratio [aHR] = 1.15, 95% confidence interval [CI] 1.02, 1.29) and > 9.20 levels (aHR 1.18, 95% CI 1.03, 1.37) of the TyG index were associated with an increased risk of AF compared with the middle TyG index category (8.80-9.20). The exposure-effect analysis confirmed the U-shaped association between the TyG index and AF incidence (P = 0.041). Further sex-specific analysis showed that a U-shaped association between the TyG index and incident AF still existed in females but not in males. CONCLUSIONS: A U-shaped association between the TyG index and AF incidence is observed in Americans without known cardiovascular diseases. Female sex may be a modifier in the association between the TyG index and AF incidence.

Dental Diseases Increase Risk of Aortic Arch Calcification Independent of Renal Dysfunction in Older Adults: Shenzhen Community Cohort Study.

Many studies have documented that dental diseases were associated with an increased risk of cardiovascular diseases. Aortic arch calcification (AoAC) is a powerful predictor of cardiovascular diseases. However, whether the status of dental health is associated with AoAC is still unknown. 9463 participants over the age of 60 from Shenzhen community centers were included in the cross-sectional analysis. Physical examination data, blood biochemical tests, and AoAC scores calculated by chest radiography were collected and analyzed. Among them, 2630 participants were followed up for AoAC progression up to 36 months. Participants with AoAC suffered more tooth loss than those without AoAC (77.62% vs. 72.91%; p < 0.001). Association rule analysis suggested a strong association between dental diseases and AoAC. Tooth loss or decay increased the risk of AoAC progression (HR 1.459; 95%CI 1.284−1.658) after adjusting other risk factors including renal dysfunction. Dental diseases are potential predictors for AoAC in elderly people, which are independent of renal dysfunction.

Abnormal Calcium Metabolism Mediated Increased Risk of Cardiovascular Events Estimated by High Ankle-Brachial Index in Patients on Peritoneal Dialysis.

Cardiovascular disease (CVD) is the leading cause of death in peritoneal dialysis (PD) patients. But the relationship between regular PD and the risk of major adverse cardiovascular events (MACE) remains controversial. The possible risk factors are not fully elucidated. This study aims to investigate the possible factors affecting the risk of MACE estimated by high ankle-brachial index (ABI) in PD patients. A total of 243 patients were enrolled and divided into chronic kidney diseases (CKD) stage 1, non-dialyzed CKD stages 2-5, and PD groups. The prevalence of high ABI, indicating increased MACE, was elevated with CKD progression but not further increased in PD patients. Systolic blood pressure was closely correlated with high ABI in non-dialyzed CKD patients (ß = 0.059, P = 0.001). But in PD patients, serum calcium had a crucial effect on high ABI (ß = -9.853, P < 0.001). Additionally, PD patients with high ABI tended to dialyze inadequately (Kt/V <1.7) compared to those with normal ABI (29.0 vs. 13.3%, P = 0.031). Further mediation analysis revealed that ~86.2% of the relationship between Kt/V and high ABI was mediated by serum calcium in PD patients (mediation effect = 86.2%, ab = -0.220, 95% CI: -0.381 to -0.059, P = 0.008), especially in those starting PD before 55 years of age and with normal body mass index. This present study indicated that improvement of PD adequacy by maintaining calcium balance might be a promising method to reduce the risk of MACE estimated by high ABI for PD patients.

Online prediction model for primary aldosteronism in patients with hypertension in Chinese population: A two-center retrospective study.

Background: The prevalence of primary aldosteronism (PA) varies from 5% to 20% in patients with hypertension but is largely underdiagnosed. Expanding screening for PA to all patients with hypertension to improve diagnostic efficiency is needed. A novel and portable prediction tool that can expand screening for PA is highly desirable. Methods: Clinical characteristics and laboratory data of 1,314 patients with hypertension were collected for modeling and randomly divided into a training cohort (919 of 1,314, 70%) and an internal validation cohort (395 of 1,314, 30%). Additionally, an external dataset (n = 285) was used for model validation. Machine learning algorithms were applied to develop a discriminant model. Sensitivity, specificity, and accuracy were used to evaluate the performance of the model. Results: Seven independent risk factors for predicting PA were identified, including age, sex, hypokalemia, serum sodium, serum sodium-to-potassium ratio, anion gap, and alkaline urine. The prediction model showed sufficient predictive accuracy, with area under the curve (AUC) values of 0.839 (95% CI: 0.81-0.87), 0.814 (95% CI: 0.77-0.86), and 0.839 (95% CI: 0.79-0.89) in the training set, internal validation, and external validation set, respectively. The calibration curves exhibited good agreement between the predictive risk of the model and the actual risk. An online prediction model was developed to make the model more portable to use. Conclusion: The online prediction model we constructed using conventional clinical characteristics and laboratory tests is portable and reliable. This allowed it to be widely used not only in the hospital but also in community health service centers and may help to improve the diagnostic efficiency of PA.

Liver fibrosis scores and atrial fibrillation incidence in heart failure with preserved ejection fraction.

AIM: Non-alcoholic fatty liver disease (NAFLD)-related advanced liver fibrosis (Stage 3 or 4) was reported to be linked to worse prognosis in patients with heart failure with preserved ejection fraction (HFpEF). This study aims to assess the relationship between liver fibrosis scores and new-onset atrial fibrillation (AF) incidence in patients with HFpEF in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. METHODS AND RESULTS: Baseline liver fibrosis levels, assessed by NAFLD fibrosis score (NFS) or Fibrosis-4 index (FIB-4), with AF incidence were expressed as hazard ratios (HRs) using the Cox proportional hazard model. The risk for advanced fibrosis was estimated to be 21.5% (447/2072) as assessed by FIB-4 (>3.25) and 4.2% (88/2072) as assessed by NFS (>0.676) in HFpEF patients without baseline AF. After a median follow-up of 3.11 years, 106 new-onset AF cases occurred. In multivariate analysis, elevated NFS [NFS = -1.455-0.676: HR 2.44, 95% confidence interval (CI) 1.27-4.68; NFS > 0.676: HR 3.36, 95% CI 1.27-6.80; per 1 unit increase: HR 1.15, 95% CI 1.01-1.32], not FIB-4 (FIB-4 = 1.45-3.25: HR 1.02, 95% CI 0.67-1.55; FIB-4 > 3.25: HR 1.69, 95% CI 0.76-3.79; per 1 unit increase: HR 1.13, 95% CI 0.93-1.37), was associated with increased AF incidence. The NFS (C-index 0.662), not FIB-4 (C-index 0.531), had a moderate predictive ability in predicting incident AF. CONCLUSIONS: Among patients with HFpEF, the risk of advanced liver fibrosis is associated with an increased incidence of new-onset AF and may be a novel predictor for new-onset AF. Additional studies are needed to confirm our results.

A LASSO-derived clinical score to predict severe acute kidney injury in the cardiac surgery recovery unit: a large retrospective cohort study using the MIMIC database.

OBJECTIVES: We aimed to develop an effective tool for predicting severe acute kidney injury (AKI) in patients admitted to the cardiac surgery recovery unit (CSRU). DESIGN: A retrospective cohort study. SETTING: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-III database, consisting of critically ill participants between 2001 and 2012 in the USA. PARTICIPANTS: A total of 6271 patients admitted to the CSRU were enrolled from the MIMIC-III database. PRIMARY AND SECONDARY OUTCOME: Stages 2-3 AKI. RESULT: As identified by least absolute shrinkage and selection operator (LASSO) and logistic regression, risk factors for AKI included age, sex, weight, respiratory rate, systolic blood pressure, diastolic blood pressure, central venous pressure, urine output, partial pressure of oxygen, sedative use, furosemide use, atrial fibrillation, congestive heart failure and left heart catheterisation, all of which were used to establish a clinical score. The areas under the receiver operating characteristic curve of the model were 0.779 (95% CI: 0.766 to 0.793) for the primary cohort and 0.778 (95% CI: 0.757 to 0.799) for the validation cohort. The calibration curves showed good agreement between the predictions and observations. Decision curve analysis demonstrated that the model could achieve a net benefit. CONCLUSION: A clinical score built by using LASSO regression and logistic regression to screen multiple clinical risk factors was established to estimate the probability of severe AKI in CSRU patients. This may be an intuitive and practical tool for severe AKI prediction in the CSRU.

Inflammatory Cells Accelerated Carotid Artery Calcification via MMP9: Evidences From Single-Cell Analysis.

Background: Vascular calcification (VC) is an important predictor of prognosis in atherosclerosis, the phenotypic transformation of vascular smooth muscle cells (VSMCs) is thought to be a process of VC. However, the implications and potential mechanisms for VSMCs phenotypic transition remain unknown. Methods: To study the transformation of vascular smooth muscle cells (VSMCs) in the calcification early period, we analyzed single-cell sequencing data from carotid artery calcified core and paracellular tissue, based on the results of enrichment analysis and protein-protein interaction analysis. Upstream transcription factors were tracked and finally the results were validated using the MESA database. Results: We successfully identified a subpopulation of inflammatory macrophage-like VSMCs and determined that MMP9 is an important factor in the phenotypic transformation of VSMCs. We found that RELA regulates MMP9 expression and that knockdown of RELA attenuated MMP9 expression and reduced the expression of BMP2 and the macrophage marker LGALS3 in vascular smooth muscle in inflammatory states, while serum levels of MMP9 correlated significantly with the inflammatory response. Conclusion: This study reveals that the phenotypic transformation of VSMCs can be regulated by modulating MMP9, providing a new idea for the early treatment of VC.

Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression.

Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2-/- and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention.

Olanzapine: Association Between a Typical Antipsychotic Drug and Aortic Calcification.

Aims: This study concentrates on the relationship between antipsychotic drugs (APDs) and aortic calcification. Methods: All 56 patients with schizophrenia were divided into two groups according to aortic calcification index. APD equivalent dose was calculated via defined daily doses method. Results: In schizophrenia patients with higher aortic calcification index scores, APD equivalent doses were lower. APD equivalent dose was negatively related to aortic calcification index. Although equivalent APD dose in patients without olanzapine treatment was negatively related to aortic calcification index, it seems that equivalent APD dose did not associate with aortic calcification. Conclusion: Aortic calcification is negatively associated with APD dose in schizophrenia patients. Olanzapine seems to be vital to the relationship between aortic calcification and APD treatment.

ß-Hydroxybutyric Inhibits Vascular Calcification via Autophagy Enhancement in Models Induced by High Phosphate.

Background: Vascular calcification (VC) is a landmark of aging, while ß-hydroxybutyric acid (BHB) induced by calorie restriction has been identified as a promising factor to extend the lifespan. However, the effect of BHB on VC and the potential mechanism remain unknown. Methods: A total of 160 subjects with or without metabolic abnormalities (MAs) were assigned to four groups according to different calcification severities. The association between BHB, MAs, and VC was investigated via mediation analysis. Then, with high phosphate-induced calcification models, the effect of BHB on arterial ring calcification and osteogenic phenotypic differentiation of vascular smooth muscle cells (VSMCs) was investigated. Hereafter the expressions of autophagy biomarkers, autophagy flux, and effects of autophagy inhibitors on VC were detected. Results: Severe VC was observed in the elderly, accompanied with a higher proportion of hypertension, chronic kidney disease, and lower estimated glomerular filtration rate. The serum BHB level was an independent influencing factor of VC severities. With mediation analysis, BHB was determined as a significant mediator in the effects of MAs on VC, and the indirect effect of BHB accounted for 23% of the total effect. Furthermore, BHB directly inhibited arterial ring calcification and osteogenic phenotypic differentiation in VSMCs, accompanied with autophagy enhancement in VSMCs. In accordance, the inhibition of autophagy counteracted the protective effect of BHB on VC. Conclusion: The present study demonstrated that BHB mediated the effects of MAs on VC; then, it further elucidated that BHB could inhibit arterial and VSMC calcification via autophagy enhancement.

Intermittent concurrent use of clopidogrel and proton pump inhibitors did not increase risk of adverse clinical outcomes in Chinese patients with coronary artery disease.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed to patients with coronary heart disease (CHD) under antiplatelet therapy to prevent gastrointestinal (GI) bleeding. However, its clinical impact is still under debate, especially in Asian population. This study was undertaken to explore the effects of concurrent use of clopidogrel and PPIs on the clinical outcomes in Chinese patients with CHD in secondary prevention. METHODS: A single-center retrospective study was conducted in 638 patients with CHD on consecutive clopidogrel therapy for at least 1 year. After 18-month follow-up, adverse clinical events were collected. Cox regression was used to calculate hazard ratios (HR) and 95% confidence interval (CI) for the effect of PPI use on the outcomes. A total of 638 patients were recruited from 2014 to 2015 in this study, among whom 201 were sustained PPI users, 188 were intermittent PPI users and the remaining 249 were non-PPI users. RESULTS: Compared with sustained PPI users, intermittent use of PPIs was associated with a lower risk of stroke, major adverse cardiac events (MACE) and net adverse clinical event (NACE) (stroke: adjusted HR: 0.109, 95% CI 0.014-0.878, p = 0.037; MACE: adjusted HR: 0.293, 95% CI 0.119-0.722; p = 0.008; NACE: adjusted HR: 0.357, 95% CI 0.162-0.786, p = 0.011). Subgroup analysis further revealed the benefit of intermittent PPI use was significant in male CHD patients over 60 years old, with hypertension or chronic kidney disease, and undergoing percutaneous coronary intervention during hospitalization. CONCLUSION: The current findings suggest that the intermittent concurrent use of PPIs and clopidogrel is not associated with an increased risk of 18-month adverse clinical outcomes, and intermittent use of PPIs is associated with a lower rate of MACE and NACE.

Longitudinal Changes in Macular Optical Coherence Tomography Angiography Metrics in Primary Open-Angle Glaucoma With High Myopia: A Prospective Study.

Purpose: To characterize longitudinal changes in macular microvasculature as quantified from optical coherence tomography angiography (OCTA) metrics in primary open-angle glaucoma (POAG) eyes with and without high myopia. Methods: In total, 63 and 61 POAG eyes with and without high myopia, respectively, underwent swept-source OCTA imaging in at least four follow-up visits at an ophthalmic center, with a scanning protocol of 3- × 3-mm centered at the fovea. The foveal avascular zone (FAZ) area, FAZ circularity, and vessel density (VD) in both the superficial (SCP) and deep capillary plexuses (DCP) were measured. The rate of change in macular OCTA metrics over time was estimated using linear mixed-effects models in both groups of POAG eyes. Results: The mean follow-up time and number of visits were 27.72 ± 8.57 months and 8.5 (8 to 13) times, and 30.95 ± 10.19 months and 10 (8‒13) times in POAG eyes with and without high myopia, respectively. VD in the DCP reduced significantly more quickly in POAG eyes with high myopia than in those without high myopia (-5.14%/year vs. -3.71%/year, P = 0.008). Moreover, lower baseline VD in the DCP was significantly associated with faster VD reduction in POAG with high myopia eyes (P < 0.001). Conversely, the VD reduction rate in the SCP, FAZ area, and FAZ circularity in both the SCP and DCP were similar in both groups (all Ps > 0.05). Conclusions: VD in DCP reduced significantly more quickly in POAG eyes with high myopia over time. Density in the DCP reduced more quickly when baseline VD was low.

Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it. METHODS: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam. RESULTS: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression. CONCLUSIONS: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views.