Preserved ratio impaired spirometry (PRISm) findings are a heterogeneous condition characterized by a normal FEV
to FVC ratio with underlying impairment of pulmonary function. Data relating to the ...association of baseline and trajectories of PRISm findings with diverse cardiovascular outcomes are sparse.
How do baseline and trajectories of PRISm findings impact subsequent cardiovascular events?
In the UK Biobank cohort study, we included participants free of cardiovascular disease (CVD) with spirometry (FEV
and FVC values) at baseline (2006-2010). Participants with baseline spirometry and follow-up spirometry (2014-2020) were included in the lung function trajectory analysis. Cox proportional hazards multivariate regression was performed to evaluate the outcomes of major adverse cardiovascular events (MACEs), incident myocardial infarction (MI), stroke, heart failure (HF), and CVD mortality in association with lung function.
For baseline analysis (329,954 participants), the multivariate adjusted hazard ratios (HRs) for participants had PRISm findings (vs normal spirometry findings) were 1.26 (95% CI, 1.17-1.35) for MACE, 1.12 (95% CI, 1.01-1.25) for MI, 1.88 (95% CI, 1.72-2.05) for HF, 1.26 (95% CI, 1.13-1.40) for stroke, and 1.55 (95% CI, 1.37-1.76) for CVD mortality, respectively. A total of 22,781 participants underwent follow-up spirometry after an average of 8.9 years. Trajectory analysis showed that persistent PRISm findings (HR, 1.96; 95% CI, 1.24-3.09) and airflow obstruction (HR, 1.43; 95% CI, 1.00-2.04) was associated with a higher incidence of MACE vs consistently normal lung function. Compared with persistent PRISm findings, changing from PRISm to normal spirometry findings was associated with a lower incidence of MACE (HR, 0.42; 95% CI, 0.19-0.99).
Individuals with baseline or persistent PRISm findings were at a higher risk of diverse cardiovascular outcomes even after adjusting for a wide range of confounding factors. However, individuals who transitioned from PRISm to normal findings showed a similar cardiovascular risk as those with normal lung function.
The disease burden of diabetes mellitus (DM) and its associated cardiovascular complications represent a growing and major global health problem. Recent studies suggest that circulating exogenous ...endothelial progenitor cells (EPCs) play an important role in endothelial repair and neovascularization at sites of injury or ischemia. Both experimental and clinical studies have demonstrated that hyperglycemia related to DM can induce alterations to EPCs. The reduction and dysfunction of EPCs related to DM correlate with the occurrence and severity of microvascular and macrovascular complications, suggesting a close mechanistic link between EPC dysfunction and impaired vascular function/repair in DM. These alterations to EPCs, likely mediated by multiple pathophysiological mechanisms, including inflammation, oxidative stress, and alterations in Akt and the nitric oxide pathway, affect EPCs at multiple stages: differentiation and mobilization in the bone marrow, trafficking and survival in the circulation, and homing and neovascularization. Several different therapeutic approaches have consequently been proposed to reverse the reduction and dysfunction of EPCs in DM and may represent a novel therapeutic approach to prevent and treat DM-related cardiovascular complications.
Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent ...conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD.
MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model.
Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 64.8% of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70-0.96), embolic stroke (RR 0.32, 95% CI 0.12-0.85), AF/AFL (RR 0.82, 95% CI 0.71-0.95), and VT (RR 0.73, 95% CI 0.53-0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58-1.17) and cardiac arrest (RR 0.83, 95% CI 0.61-1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease ASCVD vs no ASCVD) and the SGLT2i used.
SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.
Myocardial infarction arises from an excessive or prolonged inflammatory response, leading to ventricular remodeling or impaired cardiac function. Macrophages exhibit different polarization types ...associated with inflammation both at steady state and after myocardial infarction. Exosomal miR-146a-5p has been identified as an important molecule in the cardiovascular field in recent years. However, the effect of cardiomyocyte-derived exosomal miR-146a-5p on macrophages has not yet been elucidated. Initially, we found that exosomes with low expression of miR-146a-5p derived from myocardial infarction tissues modulated macrophage polarization. To determine whether cardiomyocyte-derived exosomal miR-146a-5p mediated macrophage polarization, we treated macrophages with exosomes rich in miR-146a-5p collected from neonatal mouse cardiomyocytes. The effects of exosomal miR-146a-5p on macrophage polarization were measured using RT-qPCR, transwell assays, and western blotting. The results showed that the increased expression of miR-146a-5p promoted M1 macrophage polarization, inhibited M2 macrophage polarization, and increased the expression of VEGFA. However, the decreased expression of exosomalmiR-146a-5p showed the opposite trends. Interestingly, in contrast to treatment with the solitary miR-146a-5p mimic, exosomal miR-146a-5p derived from neonatal mouse cardiomyocytes reduced TNFα and iNOS expression. In addition, when macrophages were activated by the miR-146a-5p mimic or exosomal miR-146a-5p, the expression of TNF receptor-associated factor 6 (TRAF6), a target gene of miR-146a-5p, was reduced significantly. Taken together, these findings indicate that exosomal miR-146a-5p derived from cardiomyocytes could stimulate M1 macrophage polarization to induce an inflammatory reaction, while targeting TRAF6, exerting an anti-inflammatory effect. Exosomal miR-146a-5p plays important roles in macrophages, illuminating a novel potential therapeutic target in myocardial infarction.
Background and Objective
Subjects with diabetes and periodontitis are at high risk of cardiovascular events, while the subclinical alterations of cardiac function in this cohort remain unclear. This ...cross‐sectional study investigated the association of periodontitis with left ventricle (LV) structural and functional abnormalities in subjects with type 2 diabetes mellitus (T2DM).
Material and Methods
A total of 115 subjects with T2DM were divided into Control group (n = 32) with no or mild periodontitis, and the rest with moderate to severe chronic periodontitis (CP) were further categorized into CP‐1 (n = 41) and CP‐2 (n = 42) based on disease severity. Echocardiography was performed to precisely assess (a) LV hypertrophy by LV mass index (LVMi); (b) LV diastolic function by tissue Doppler imaging index E/e’ ratio; and (c) LV systolic function by speckle tracking derived global longitudinal strain (GLS).
Results
Overall, a linear trend in LVMi, E/e’, and GLS existed among the Control, CP‐1, and CP‐2 groups, respectively (P < 0.05). After adjustments of multiple confounders, CP‐2 subjects showed significantly higher E/e’ (log scale, 2.22 ± 0.05 vs 2.07 ± 0.06, P < 0.01) and GLS (−17.42 ± 0.46% vs −18.95 ± 0.54%, P < 0.05) than the Controls. Multivariate analysis revealed that sites% with probing depth ≥4 mm and sites% with clinical attachment loss ≥5 mm were independent indicators for E/e’ (β = 0.005 and β = 0.002, P < 0.01) and GLS (β = 0.03 and β = 0.02, P < 0.05) , respectively. Moreover, the number of missing teeth was significantly associated with LVMi (β = 0.01, P < 0.01).
Conclusion
This study provides the first evidence that severe periodontitis is significantly associated with the exacerbation of LV diastolic and systolic dysfunction in subjects with T2DM.
Preclinical studies suggest that neuromodulation with thoracic spinal cord stimulation (SCS) improves left ventricular (LV) function and remodeling in systolic heart failure (HF).
The purpose of this ...study was to evaluate the safety and efficacy of a SCS system for the treatment of systolic HF.
We performed a prospective, multicenter pilot trial in patients with New York Heart Association (NYHA) class III HF, left ventricular ejection fraction (LVEF) 20%-35%, and implanted defibrillator device who were prescribed stable optimal medical therapy. Dual thoracic SCS leads were used at the T1-T3 level. The device was programmed to provide SCS for 24 hours per day (50 Hz at pulse width 200 μs).
We enrolled 22 patients from 5 centers:17 patients underwent implantation of a SCS device and 4 patients who did not fulfill the study criteria served as nontreated controls. No deaths or device-device interactions were noted during the 6-month period in the 17 SCS-treated patients. Fifteen of 17 completed the efficacy endpoint assessments: composite score improved by 4.2 ± 1.3, and 11 patients (73%) showed improvement in ≥4 of 6 efficacy parameters. There was significant improvement in NYHA class (3.0 vs 2.1, P = .002; 13/17 improved); Minnesota Living with Heart Failure Questionnaire (42 ± 26 vs 27 ± 22, P = .026; 12/17 improved); peak maximum oxygen consumption (14.6 ± 3.3 vs 16.5 ± 3.9 mL/kg/min, P = .013; 10/15 improved); LVEF (25% ± 6% vs 37% ± 8%, P<.001; 14/16 improved); and LV end-systolic volume (174 ± 57 vs 137 ± 37 mL, P = .002; 11/16 improved) but not in N-terminal prohormone brain natriuretic peptide. No such improvements were observed in the 4 nontreated patients.
The results of this first-in-human trial suggest that high thoracic SCS is safe and feasible and potentially can improve symptoms, functional status, and LV function and remodeling in patients with severe, symptomatic systolic HF.
Iron deficiency is a common comorbidity in heart failure (HF) and is independently associated with a worse quality-of-life and exercise capacity, as well as increased risk of hospitalization, ...regardless of anemia status. Although international guidelines have provided recommendations for the management of iron deficiency in patients with HF, guidelines in Asia are less established, and practical use of guidelines for management of iron deficiency is limited in the region.
A panel comprising cardiologists from China, Hong Kong, India, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, and Thailand convened to share insights and provide guidance for the optimal management of iron deficiency in patients with HF, tailored for the Asian community.
Expert opinions were provided for the screening, diagnosis, treatment and monitoring of iron deficiency in patients with HF. It was recommended that all patients with HF with reduced ejection fraction should be screened for iron deficiency, and iron-deficient patients should be treated with intravenous iron. Monitoring of iron levels in patients with HF should be carried out once or twice yearly. Barriers to the management of iron deficiency in patients with HF in the region include low awareness of iron deficiency amongst general physicians, lack of reimbursement for screening and treatment, and lack of proper facilities for administration of intravenous iron.
These recommendations provide a structured approach to the management of iron deficiency in patients with HF in Asia.
•Iron deficiency in heart failure results in worse outcomes regardless of anemia.•Expert opinions on the optimal management of iron deficiency in Asia are provided.•All patients with heart failure should be screened for iron deficiency.•Preferred treatment is intravenous iron; oral iron was ineffective in clinical trials.•Challenges in Asia include low awareness, cost, and lack of facilities.
Evidence suggests that chronic obstructive pulmonary disease (COPD) is associated with a higher risk of lung carcinoma. Using a territory-wide clinical electronic medical records system, we ...investigated the association between low-dose aspirin use (≤160 mg) among patients with COPD and incidence of lung carcinoma and the corresponding risk of bleeding.
This is a retrospective cohort study conducted utilizing Clinical Data Analysis Reporting System (CDARS), a territory-wide database developed by the Hong Kong Hospital Authority. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between aspirin nonusers (35,049 patients) with new aspirin users (7,679 patients) among all eligible COPD patients from 2005 to 2018 attending any public hospitals. The median age of the cohort was 75.7 years (SD = 11.5), and 80.3% were male. Competing risk regression with Cox proportional hazards model were performed to estimate the subdistribution hazard ratio (SHR) of lung carcinoma with low-dose aspirin and the associated bleeding events. Of all eligible patients, 1,779 (4.2%, 1,526 and 253 among nonusers and users) were diagnosed with lung carcinoma over a median follow-up period of 2.6 years (interquartile range IQR: 1.4 to 4.8). Aspirin use was associated with a 25% lower risk of lung carcinoma (SHR = 0.75, 95% confidence interval CI 0.65 to 0.87, p = <0.001) and 26% decrease in lung carcinoma-related mortality (SHR = 0.74, 95% CI 0.64 to 0.86, p = <0.001). Subgroup analysis revealed that aspirin was beneficial for patients aged above or below 75 years, but was also beneficial among populations who were male, nondiabetic, and nonhypertensive. Aspirin use was not associated with an increased risk of upper gastrointestinal bleeding (UGIB) (SHR = 1.19, 95% CI 0.94 to 1.53, p = 0.16), but was associated with an increased risk of hemoptysis (SHR = 1.96, 95% CI 1.73 to 2.23, p < 0.001). The main limitations of the study were (i) that one group of patients may be more likely to seek additional medical attention, although this was partially mitigated by the use of propensity score analysis; and (ii) the observational nature of the study renders it unable to establish causality between aspirin use and lung carcinoma incidence.
In this study, we observed that low-dose aspirin use was associated with a lower risk of lung carcinoma and lung carcinoma-related mortality among COPD patients. While aspirin was not associated with an increased risk of UGIB, the risk of hemoptysis was elevated.
Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular events. The aim of the study was to assess whether global longitudinal strain (GLS) provides prognostic value in ...these patients.
A total of 247 T2DM patients without history of cardiovascular complications and participated in the CDATS study were prospectively enrolled. Left ventricular (LV) systolic function was assessed by LV ejection fraction and speckle tracking derived LV systolic GLS. Diastolic function was assessed by E/E' ratio defined as the passive trans-mitral LV inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus. Cardiovascular event included acute coronary syndrome, cerebrovascular stroke, hospitalization for heart failure and cardiovascular death.
A total of 18 cardiovascular events occurred during a median follow-up duration of 33 months. Both E/E' ratio hazard ratio (HR) 1.15, P < 0.01 and GLS (HR 1.39, P < 0.01) were independently associated with cardiovascular events. Importantly, GLS provided incremental prognostic information in addition to clinical data, HbA1c and E/E' ratio (Chi square 77.46, P = 0.04). Receiver-operator characteristic curve analysis demonstrated that E/E' ratio area under curve (AUC) 0.66, P = 0.03 and GLS (AUC 0.72, P < 0.01) were strong predictors of cardiovascular events. Kaplan-Meier analysis showed that patients with E/E' > 13.6 or GLS > -17.9 % were associated with cardiovascular events. The presence of either a high E/E' ratio or an impaired GLS provides an excellent negative predictive value of cardiovascular events in these patients.
In T2DM patients with no history of cardiovascular disease, impaired GLS was associated with cardiovascular events and provided incremental prognostic value.
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