Sex-based association between high-density lipoprotein cholesterol and adverse outcomes after coronary artery bypass grafting.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is shown to be an independent protective factor against coronary artery diseases (CAD). Yet there are limited studies focusing on the association between HDL-C and coronary artery bypass graft (CABG) surgery outcomes. HYPOTHESIS: Low levels of HDL-C are associated with higher incidence of adverse outcomes in patients undergoing CABG. METHODS: This registry-based study included 17,772 patients who underwent elective isolated CABG between 2007 and 2017. Patients were classified into low and desirable HDL-C groups based on their serum HDL-C levels at admission and were followed for one-year post-surgery. The study population included 13,321 patients with low HDL-C and 4,451 with desirable HDL-C. proportional hazard Cox models were performed to evaluate the association between HDL-C levels and incidence of mortality as well as major adverse cardiovascular and cerebrovascular events (MACCE), while adjusting for potential confounders. Moreover, participants were stratified based on sex and the association was also investigated in each subgroup separately. RESULTS: No significant difference was found between the groups regarding incidence of both mortality and MACCE, after adjusting with Inverse Probability Weighting (IPW) [HR (95%CI): 0.84 (0.46-1.53), p-value:0.575 and HR (95% CI): 0.91 (0.56-1.50), p-value:0.733, respectively]. According to the sex-based subgroup analysis, no significant association was observed after adjustment with IPW analysis. However, as we examined the association between the interaction of HDL-C levels, sex and cardiovascular outcomes, we found a significant association (HR;1.19 (95%CI: 1.04-1.45); p = 0.030). CONCLUSION: HDL-C level was not associated with either mortality or MACCE during one year after CABG procedure. Sex-based analysis showed that in males, HDL-C is significantly more protective against these outcomes, compared to females. Further studies are necessary to elucidate the exact mechanisms mediating such association.

Effectiveness of conduction system pacing for cardiac resynchronization therapy: A systematic review and network meta-analysis.

INTRODUCTION: Cardiac resynchronization therapy (CRT) with biventricular pacing (BiV-CRT) is ineffective in approximately one-third of patients. CRT with Conduction system pacing (CSP-CRT) may achieve greater synchronization. We aimed to assess the effectiveness of CRT with His pacing (His-CRT) or left bundle branch pacing (LBB-CRT) in lieu of biventricular CRT. METHODS AND RESULTS: The PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were systematically searched until August 19, 2023, for original studies including patients with reduced left ventricular ejection fraction (LVEF) who received His- or LBB-CRT, that reported either CSP-CRT success, LVEF, QRS duration (QRSd), or New York Heart Association (NYHA) classification. Effect measures were compared with frequentist network meta-analysis. Thirty-seven publications, including 20 comparative studies, were included. Success rates were 73.5% (95% CI: 61.2-83.0) for His-CRT and 91.5% (95% CI: 88.0-94.1) for LBB-CRT. Compared to BiV-CRT, greater improvements were observed for LVEF (mean difference [MD] for His-CRT +3.4%; 95% CI [1.0; 5.7], and LBB-CRT: +4.4%; [2.5; 6.2]), LV end-systolic volume (His-CRT:17.2mL [29.7; 4.8]; LBB-CRT:15.3mL [28.3; 2.2]), QRSd (His-CRT: -17.1ms [-25.0; -9.2]; LBB-CRT: -17.4ms [-23.2; -11.6]), and NYHA (Standardized MD [SMD]: His-CRT:0.4 [0.8; 0.1]; LBB-CRT:0.4 [-0.7; -0.2]). Pacing thresholds at baseline and follow-up were significantly lower with LBB-CRT versus both His-CRT and BiV-CRT. CSP-CRT was associated with reduced mortality (R = 0.75 [0.61-0.91]) and hospitalizations risk (RR = 0.63 [0.42-0.96]). CONCLUSION: This study found that CSP-CRT is associated with greater improvements in QRSd, echocardiographic, and clinical response. LBB-CRT was associated with lower pacing thresholds. Future randomized trials are needed to determine CSP-CRT efficacy.

Brain MRI and EEG overemployment in patients with vasovagal syncope: results from a tertiary syncope unit.

BACKGROUND: The diagnosis of vasovagal syncope (VVS) is mainly based on history-taking and physical examination. However, brain Magnetic Resonance Imaging (MRI) and Electroencephalogram (EEG) are commonly used in the diagnostic course of VVS, despite not being indicated in the guidelines. This study aims to find the possible associated factors with the administration of brain MRI and EEG in patients with VVS. METHODS: Patients with a diagnosis of VVS from 2017 to 2022 were included. Several demographic and syncope features were recorded. The association of these was assessed with undergoing MRI, EEG, and either MRI or EEG. Univariate and multivariable logistic regression models were also used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 1882 patients with VVS were analyzed, among which 810 underwent MRI (43.04%), 985 underwent EEG (52.34%), and 1166 underwent MRI or EEG (61.96%). Head trauma (OR 1.38, 95% CI 1.06 to 1.80), previous neurologist visit (OR 6.28, 95% CI 4.24 to 9.64), and gaze disturbance during syncope (OR 1.75, 95% CI 1.13 to 2.78) were all positively associated to the performance of brain MRI/EEG. Similar results were found for urinary incontinence (OR 2.415, 95% CI 1.494 to 4.055), amnesia (OR 1.421, 95% CI 1.053 to 1.930), headache after syncope (OR 1.321, 95% CI 1.046 to 1.672), and tonic-clonic movements in head-up tilt table test (OR 1.501, 95% CI 1.087 to 2.093). However, male sex (OR 0.655, 95% CI 0.535 to 0.800) and chest pain before syncope (OR 0.628, 95% CI 0.459 to 0.860) had significant negative associations with performing brain MRI/EEG. CONCLUSION: Based on our findings, performing MRI or EEG was common among VVS patients while it is not indicated in the majority of cases. This should be taken into consideration to prevent inappropriate MRI/EEG when there is a typical history compatible with VVS.

Compression stockings for treating vasovagal syncope (COMFORTS-II) trial: Rationale and design of a triple-blind, multi-center, randomized controlled trial.

BACKGROUND: Reduced venous return is an important trigger of vasovagal syncope (VVS). Elastic compression stockings (ECS) can modify venous return and be of therapeutic interest; however, evidence for ECS efficacy in VVS is scarce. This randomized controlled trial was designed to address the issue. METHODS: COMFORTS-II is a multicenter, triple-blind, parallel design, randomized controlled trial aimed to assess the efficacy of ECS in preventing VVS recurrences. Using central online randomization, 268 participants will be allocated to 2 arms (1:1 ratio), wearing intervention ECS (25-30 mm Hg pressure) or sham ECS (≤10 mm Hg pressure). All participants will receive standard VVS treatment in the form of education, and lifestyle modification recommendations (drinking 2-3 l/d of fluids and consuming 10 g/d-roughly half a tablespoon-of table salt). Adherence to ECS treatment will be evaluated through diary sheets, and compared between study arms. Follow-up continues for 1 year, and is conducted via a 24/7 phone line available to patients and trimonthly visits. The co-primary outcomes are proportion of participants with any syncopal recurrence and time to first syncopal episode. Secondary outcomes include frequency of VVS spells, time intervals between recurrences, and incidence of any patient-reported adverse effects. CONCLUSION: To the best of our knowledge, COMFORTS-II is the first clinical trial to assess ECS efficacy among patients with VVS, addressing an important gap in evidence for VVS treatments.

Implementation of supervised physical training to reduce vasovagal syncope recurrence: A randomized controlled trial.

INTRODUCTION: Physical techniques used for the prevention of vasovagal syncope have limited evidence for efficacy. We aimed to evaluate multimodal supervised physical training as a treatment approach. METHODS: In this 1:1 randomized trial, patients with ≥2 episodes of clinically diagnosed vasovagal syncope were included. On top of standard care, the intervention arm performed supervised tilt training and aerobic exercise in six sessions at a cardiac rehabilitation center (three sessions during the first month, and then at 3-month intervals), plus home tilt training. The control arm received standard care with a similar protocol of home tilt training. The primary outcome was time to first syncopal recurrence during 1 year of follow-up. RESULTS: Fifty participants were randomized (mean age: 34.5 ± 14.8 years; 64% female). The rate of syncopal recurrence was 28% and 64% within the intervention and control arms, respectively, with significantly higher syncope-free survival at 1 year in the intervention arm (Log-rank p = .003). The frequency of recurrent syncopal events was significantly lower with physical training (p = .017). Participants in the intervention arm reported significantly higher adherence to the home tilt training program (80% vs. 52%; p = .037). CONCLUSION: Among patients with recurrent vasovagal syncope, a supervised program of tilt training and aerobic exercise reduced syncopal recurrence. Future trials are warranted to further investigate multimodal supervised physical techniques as a therapeutic approach in treating vasovagal syncope.

BMI modifies HDL-C effects on coronary artery bypass grafting outcomes.

BACKGROUND: Despite the recognized implications of high-density lipoprotein cholesterol (HDL-C) in cardiovascular diseases, the role of body mass index (BMI) in HDL-C association with cardiovascular outcomes remains unclear. This study investigated the possible modifying implications of BMI on the correlation between HDL-C and coronary artery bypass grafting (CABG) outcomes. METHODS: The present cohort included isolated CABG patients (median follow-up: 76.58 [75.79-77.38] months). The participants were classified into three groups: 18.5 ≤ BMI < 25 (normal), 25 ≤ BMI < 30 (overweight), and 30 ≤ BMI < 35 (obese) kg/m2. Cox proportional hazard models (CPHs) and restricted cubic splines (RCSs) were applied to evaluate the relationship between HDL-C and all-cause mortality as well as major adverse cardio-cerebrovascular events (MACCEs) in different BMI categories. RESULTS: This study enrolled a total of 15,639 patients. Considering the final Cox analysis among the normal and overweight groups, HDL-C ≥ 60 was a significant protective factor compared to 40 < HDL-C < 60 for all-cause mortality (adjusted hazard ratio (aHR): 0.47, P: 0.027; and aHR: 0.64, P: 0.007, respectively). However, the protective effect of HDL-C ≥ 60 was no longer observed among patients with 30 ≤ BMI < 35 (aHR: 1.16, P = 0.668). RCS trend analyses recapitulated these findings; among 30 ≤ BMI < 35, no uniform inverse linear association was observed; after approximately HDL-C≈55, its increase was no longer associated with reduced mortality risk. RCS analyses on MACCE revealed a plateau effect followed by a modest rise in overweight and obese patients from HDL-C = 40 onward (nonlinear association). CONCLUSIONS: Very high HDL-C (≥ 60 mg/dL) was not related to better outcomes among obese CABG patients. Furthermore, HDL-C was related to the post-CABG outcomes in a nonlinear manner, and the magnitude of its effects also differed across BMI subgroups.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients. METHODS: A systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta-analysis. RESULTS: Ultimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68-2.34) and disease/progression/recurrence-free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85-2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40-0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28-0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively. CONCLUSION: CircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial.

BACKGROUND: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. METHODS: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. CONCLUSION: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Prevalence and trends of coronary artery disease risk factors and their effect on age of diagnosis in patients with established coronary artery disease: Tehran Heart Center (2005-2015).

BACKGROUND: Coronary artery disease (CAD) is a universal public health challenge, more prominently so in the low- and middle-income countries. In this study, we aimed to determine prevalence and trends of CAD risk factors in patients with documented CAD and to determine their effects on the age of CAD diagnosis. MATERIALS AND METHODS: We conducted a registry-based, serial cross-sectional study using the coronary angiography data bank of the Tehran Heart Center. Adult patients who had obstructive (> 50% stenosis) CAD were included in the study. The prevalence and 11-year trends of conventional CAD risk factors were analyzed by sex and age, and their adjusted effects on the age of CAD diagnosis were calculated. RESULTS: From January 2005 to December 2015, data for 90,094 patients were included in this analysis. A total of 61,684 (68.5%) were men and 28,410 (31.5%) were women. Men were younger at diagnosis than women, with a mean age of 60.1 in men and 63.2 in women (p < 0.001), and had fewer risk factors at the time of diagnosis. Mean age at diagnosis had an overall increasing trend during the study period. Increasing trend was seen in body-mass index, hypertension prevalence, diabetes mellitus. All lipid profile components (total cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-density lipoprotein cholesterol) decreased over time. Of particular interest, opium consumption was associated with 2.2 year earlier age of CAD diagnosis. CONCLUSION: The major results of this study (lower age of CAD diagnosis in men, lower age of diagnosis associated with most risk factors, and lower prevalence of serum lipids over time) were expected. A prominent finding of this study is confirming opium use was associated with a much younger age of CAD onset, even after adjusting for all other risk factors. In addition to recommendations for control of the traditional risk factors, spreading information about the potential adverse effect of opium use, which has only recently been associated with higher risk of CAD, may be necessary.

Risk scores for prediction of paroxysmal atrial fibrillation after acute ischemic stroke or transient ischemic attack: A systematic review and meta-analysis.

Introduction: Detection of paroxysmal atrial fibrillation (PAF) is crucial for secondary prevention in patients with recent strokes of unknown etiology. This systematic review and meta-analysis assess the predictive power of available risk scores for detecting new PAF after acute ischemic stroke (AIS). Methods: PubMed, Embase, Scopus, and Web of Science databases were searched until September 2023 to identify relevant studies. A bivariate random effects meta-analysis model pooled data on sensitivity, specificity, and area under the curve (AUC) for each score. The QUADAS-2 tool was used for the quality assessment. Results: Eventually, 21 studies with 18 original risk scores were identified. Age, left atrial enlargement, and NIHSS score were the most common predictive factors, respectively. Seven risk scores were meta-analyzed, with iPAB showing the highest pooled sensitivity and AUC (sensitivity: 89.4%, specificity: 74.2%, AUC: 0.83), and HAVOC having the highest pooled specificity (sensitivity: 46.3%, specificity: 82.0%, AUC: 0.82). Altogether, seven risk scores displayed good discriminatory power (AUC ≥0.80) with four of them (HAVOC, iPAB, Fujii, and MVP scores) being externally validated. Conclusion: Available risk scores demonstrate moderate to good predictive accuracy and can help identify patients who would benefit from extended cardiac monitoring after AIS. External validation is essential before widespread clinical adoption.

Burden of Ischemic Heart Disease and Its Attributable Risk Factors in North Africa and the Middle East, 1990 to 2019: Results From the GBD Study 2019.

BACKGROUND: The North Africa and Middle East (NAME) region has one of the highest burdens of ischemic heart disease (IHD) worldwide. This study reports the contemporary epidemiology of IHD in NAME. METHODS AND RESULTS: We estimated the incidence, prevalence, deaths, years of life lost, years lived with disability, disability-adjusted life years (DALYs), and premature mortality of IHD, and its attributable risk factors in NAME from 1990 to 2019 using the results of the GBD (Global Burden of Disease study 2019). In 2019, 0.8 million lives and 18.0 million DALYs were lost due to IHD in NAME. From 1990 to 2019, the age-standardized DALY rate of IHD significantly decreased by 33.3%, mostly due to the reduction of years of life lost rather than years lived with disability. In 2019, the proportion of premature death attributable to IHD was higher in NAME compared with global measures: 26.8% versus 16.9% for women and 18.4% versus 14.8% for men, respectively. The age-standardized DALY rate of IHD attributed to metabolic risks, behavioral risks, and environmental/occupational risks significantly decreased by 28.7%, 37.8%, and 36.4%, respectively. Dietary risk factors, high systolic blood pressure, and high low-density lipoprotein cholesterol were the top 3 risks contributing to the IHD burden in most countries of NAME in 2019. CONCLUSIONS: In 2019, IHD was the leading cause of death and lost DALYs in NAME, where premature death due to IHD was greater than the global average. Despite the great reduction in the age-standardized DALYs of IHD in NAME from 1990 to 2019, this region still had the second-highest burden of IHD in 2019 globally.

Epidemiology and Prevalence of Dyslipidemia Among Adult Population of Tehran: The Tehran Cohort Study.

BACKGROUND: Dyslipidemia is among the leading risk factors for cardiovascular diseases (CVDs), with an increasing global burden, especially in developing countries. We investigated the prevalence of dyslipidemia and abnormal lipid profiles in Tehran. METHODS: We used data from 8072 individuals aged≥35 from the Tehran Cohort Study (TeCS) recruitment phase. Fasting serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglyceride were measured. Dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, and high LDL/HDL was defined as a ratio>2.5. The age-sex standardized prevalence rates were calculated based on the 2016 national census. Furthermore, the geographical distribution of dyslipidemia and lipid abnormalities was investigated across Tehran's zip code districts. RESULTS: The age-sex standardized prevalence was 82.7% (95% CI: 80.1%, 85.0%) for dyslipidemia, 36.9% (95% CI: 33.8%, 40.1%) for hypertriglyceridemia, 22.5% (95% CI: 19.9%, 25.4%) for hypercholesterolemia, 29.0% (95% CI: 26.1%, 32.1%) for high LDL-C, 55.9% (95% CI: 52.6%, 59.2%) for low HDL-C, and 54.1% (95% CI: 50.9%, 57.3%) for high LDL/HDL ratio in the Tehran adult population. The prevalence of dyslipidemia, low HDL-C, and high LDL/HDL ratio was higher in the northern regions, hypercholesterolemia was higher in the southern half, and high LDL-C was more prevalent in the middle-northern and southern areas of Tehran. CONCLUSION: We found a high prevalence of dyslipidemia, mainly high LDL/HDL in the Tehran adult population. This dyslipidemia profiling provides important information for public health policy to improve preventive interventions and reduce dyslipidemiarelated morbidity and mortality in the future.

Meta-Analysis on the Association Between Nutritional Status and Outcomes After Transcatheter Aortic Valve Implantation.

Malnutrition is a common co-morbidity among candidates for transcatheter aortic valve implantation (TAVI). This study aimed to investigate the association between nutritional status determined by objective nutritional indices and outcomes of patients who underwent TAVI. We systematically searched PubMed, Embase, Web of Science, Scopus, and Cochrane Library from inception until April 18, 2022 to identify studies examining the association of preprocedural nutritional status with post-TAVI outcomes. Malnutrition was defined by objective nutritional indices-controlling nutritional index, nutritional risk index, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). The primary end point was 1-year all-cause mortality. The review included 13 observational studies and 6,785 patients who underwent TAVI. Malnutrition was associated with a higher risk of 1-year all-cause mortality, as defined by either the controlling nutritional index (hazard ratio [HR] 2.70, 95% confidence interval [CI] 1.21 to 6.03, p = 0.015), GNRI (HR 1.79, 95% CI 1.09 to 2.93, p = 0.021), or PNI (HR 1.17, 95% CI 1.11 to 1.23, p <0.001). In the meta-analysis of adjusted results, lower GNRI was independently associated with higher 1-year mortality (HR 1.70, 95% CI 1.16 to 2.50, p = 0.006). Lower GNRI was associated with increased risk of acute kidney injury (relative risk [RR] 2.21, 95% CI 1.63 to 2.99, p <0.001) and 1-year cardiovascular mortality (RR 2.50, 95% CI 1.66 to 3.78, p <0.001). Lower PNI was associated with a higher risk of major vascular complications (RR 2.99, 95% CI 1.38 to 6.51, p = 0.006). In conclusion, baseline malnutrition, as assessed by objective indices, is associated with worse outcomes after TAVI. Future studies should focus on the value of nutritional assessment and interventions to improve nutritional status in patients who underwent TAVI.

Pharmacologic prevention of recurrent vasovagal syncope: A systematic review and network meta-analysis of randomized controlled trials.

Vasovagal syncope (VVS) is a transient loss of consciousness that currently imposes a high burden on health care systems with limited evidence of the comparative efficacy of available pharmacologic interventions. This study aims to compare all pharmacologic therapies suggested in randomized controlled trials (RCTs) through systematic review and network meta-analysis. A systematic search in PubMed, Embase, Web of Science, and Cochrane Library was conducted to identify RCTs evaluating pharmacologic therapies for patients with VVS. The primary outcome was spontaneous VVS recurrence. The secondary outcome was a positive head-up tilt test (HUTT) after receiving intervention, regarded as a lower level of evidence. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using random-effect network meta-analysis. Pairwise meta-analysis for comparison with placebo was also performed when applicable. The surface under the cumulative ranking curve analysis was conducted to rank the treatments for each outcome. Twenty-eight studies with 1744 patients allocated to different medications or placebo were included. Network meta-analysis of the reduction in the primary outcome showed efficacy for midodrine (RR 0.55; 95% CI 0.35-0.85) and fluoxetine (especially in patients with concomitant anxiety) (RR 0.36; 95% CI 0.16-0.84). In addition, midodrine and atomoxetine were superior to other treatment options, considering positive HUTT (RR 0.37; 95% CI 0.23-0.59; and RR 0.49; 95% CI 0.28-0.86, respectively). Overall, midodrine was the only agent shown to reduce spontaneous syncopal events. Fluoxetine also seems to be beneficial but should be studied further in RCTs. Our network meta-analysis did not find evidence of the efficacy of any other medication.

Clinical Associations of Injuries Caused by Vasovagal Syncope: A Cohort Study From a Tertiary Syncope Unit.

Background Recent research has revealed that vasovagal syncope (VVS) leads to a high incidence of injuries; however, clinical associations of injury are not well-established. We present data from an ongoing VVS cohort and aimed to determine characteristics associated with VVS-related injury. Methods and Results Between 2017 and 2020, consecutive patients ≥18 years of age presenting to a tertiary syncope unit and diagnosed with VVS were included. Clinical characteristics relevant to syncope were obtained for the index episode. The outcome was incidence of injury during VVS, documented by clinical evaluation at the syncope clinic. Among 1115 patients (mean age, 45.9 years; 48% women), 260 injuries (23%) occurred. History of VVS-related injuries (adjusted relative risk [aRR], 1.80 [95% CI, 1.42-2.29]), standing position (aRR, 1.34 [95% CI, 1.06-1.68]), and female sex (aRR, 1.30 [95% CI, 1.06-1.60]) were associated with injury, whereas recurrent VVS (aRR, 0.63 [95% CI, 0.49-0.81]) and syncope in the noon/afternoon (aRR, 0.70 [95% CI, 0.56-0.87]) and evening/night (aRR, 0.43 [95% CI, 0.33-0.57]) compared with morning hours were associated with lower risk. There was a trend for higher rates of injury with overweight/obesity (aRR, 1.23 [95% CI, 0.99-1.54]) and syncope occurring at home (aRR, 1.22 [95% CI, 0.98-1.51]). In a per-syncope analysis considering up to 3 previous episodes (n=2518, 36% traumatic), syncope at home (aRR, 1.33 [95% CI, 1.17-1.51]) and absence of prodromes (aRR, 1.34 [95% CI, 1.09-1.61]) were associated with injury. Conclusions Patient characteristics, VVS presentations, the circumstances, and surroundings can determine the risk of injury. These associations of VVS-related injury identify at-risk individuals and high-risk situations. Future prospective studies are needed to investigate potential strategies for prevention of post-VVS injury in recurrent cases.

Particulate Matter Pollution Remains a Threat for Cardiovascular Health: Findings From the Global Burden of Disease 2019.

Background Particulate matter (PM) pollution is a significant risk factor for cardiovascular diseases, causing substantial disease burden and deaths worldwide. This study aimed to investigate the global burden of cardiovascular diseases attributed to PM from 1990 to 2019. Methods and Results We used the GBD (Global Burden of Disease) study 2019 to investigate disability-adjusted life-years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to PM as well as its subgroups. It was shown that all burden measures' age-standardized rates for PM were in the same decreasing trend, with the highest decline recorded for deaths (-36.7%). However, the all-age DALYs increased by 31%, reaching 8.9 million in 2019, to which YLLs contributed the most (8.2 million [95% uncertainty interval, 7.3 million-9.2 million]). Men had higher deaths, DALYs, and YLLs despite lower years lived with disability in 2019 compared with women. There was an 8.1% increase in the age-standardized rate of DALYs for ambient PM; however, household air pollution from solid fuels decreased by 65.4% in the assessed period. Although higher in men, the low and high sociodemographic index regions had the highest and lowest attributed YLLs/YLDs ratio for PM pollution in 2019, respectively. Conclusions Although the total age-standardized rate of DALYs for PM-attributed cardiovascular diseases diminished from 1990 to 2019, the global burden of PM on cardiovascular diseases has increased. The differences between men and women and between regions have clinical and policy implications in global health planning toward more exact funding and resource allocation, in addition to addressing inequity in health care access.

A 30-year trend of ischemic heart disease burden in a developing country; a systematic analysis of the global burden of disease study 2019 in Iran.

BACKGROUND: Evaluating the burden of ischemic heart disease (IHD) as the first cause of mortality worldwide is necessary to develop healthcare policies. This study aimed to report the national and subnational IHD burden and risk factors in Iran according to the Global Burden of Disease (GBD) study 2019. METHODS: We extracted, processed, and presented the results of the GBD 2019 study regarding incidence, prevalence, deaths, years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and attributable burden to risk factors of IHD in Iran during 1990-2019. RESULTS: Age-standardized death and DALY rates decreased by 42.7% (95% uncertainty interval, 38.1-47.9) and 47.7% (43.6-52.9) during 1990-2019, slower since 2011 and reached 163.6 deaths (149.0-176.2), 2842.7 DALYs (2657.0-3103.1) per 100,000 persons in 2019. Meanwhile, with a lower reduction of 7.7% (6.0-9.5), the incidence rate reached 829.1 new cases (719.9-945.2) per 100,000 persons in 2019. High systolic blood pressure and elevated low-density lipoprotein cholesterol (LDL-C) contributed to the highest deaths, and DALYs age-standardized rates in 1990 and 2019. They followed by high fasting plasma glucose (FPG), and high body-mass index (BMI) with an upward trend of contribution from 1990 to 2019. A convergence pattern in the provincial death age-standardized rate was observed, with the lowest rate in Iran's capital city; 84.7 deaths per 100,000 (70.6-99.4) in 2019. CONCLUSION: The incidence rate reduced remarkably lower than the mortality rate, which necessitates promoting primary prevention strategies. Also, interventions should be adopted to control growing risk factors like high FPG, and high BMI.

Redefining the health system: A proposed updated framework of a systems approach to health.

Defining the health system, as a multidimensional and complex structure, is challenging, and the existing definitions often fail to incorporate the various levels and functions involved in a single system definition. An ideal framework should be easy to evaluate, allow for comparison, and be divisible into smaller sub-systems for easier interpretation. This paper concisely explores a novel framework to perceive health systems. As in any system, it is important to accurately define the health system's input, process, and output, as the cornerstone of evaluating any system is to assess outputs with regard to inputs besides analyzing outcomes, impact, objectives, and values. Since the raison d'être of the health system is to improve health in society, it is proposed that the input can be considered as the population subject to the system's process, and the output as the population with improved health status. This paper also proposes defining support systems, whose input and output are needs and parts of the process in the main system, respectively. Example support systems include the health evidence production or education and development of human resources systems. Instead of considering all functions as part of the main system, this concept allows implementation and assessment of policies in various levels of health systems to be simplified, as each support system can be separately evaluated with clear functions.

Long non-coding RNAs (lncRNAs) as prognostic and diagnostic biomarkers in multiple myeloma: A systematic review and meta-analysis.

BACKGROUND: Recently, emerging studies have demonstrated the utility of particular long non-coding RNAs (lncRNAs) as useful biomarkers for the diagnosis and prognosis of multiple myeloma (MM). We systematically reviewed the literature and conducted a meta-analysis to quantify the predictive effectiveness of lncRNAs in the prognosis and diagnosis of MM. METHODS: A systematic search was performed in PubMed, Embase, and Web of Science until March 24, 2021. A meta-analysis was conducted to explore the correlation between the expression of lncRNAs and prognostic endpoints, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) or event-free survival (EFS). Moreover, the diagnostic performance of lncRNAs in MM was investigated by calculating accuracy metrics. RESULTS: Overall, 43 studies were included in this systematic review, amongst which 36 studies assessed prognostic endpoints (including 5499 participants and 69 lncRNAs), and 11 studies evaluated diagnostic outcomes (with 1723 participants and 11 lncRNAs). The overexpression of CRNDE (hazard ratio (HR)= 1.94, 95% confidence interval (CI) 1.61, 2.34), NEAT1 (HR=1.97, 95%CI 1.36, 2.85), PVT1 (HR=1.92, 95%CI 1.25, 2.97), and TCF7 (HR=1.98, 95%CI 1.42, 2.76) was significantly associated with reduced OS. Furthermore, upregulation of PVT1 was significantly correlated with poor PFS (HR=1.86, 95%CI 1.29, 2.68). The pooled diagnostic performance of lncRNAs was as follows: sensitivity 0.78 (95%CI 0.73, 0.82), specificity 0.88 (95%CI 0.83, 0.92), and area under the curve 0.89 (95%CI 0.86, 0.92). CONCLUSIONS: Our results revealed the potential significance of lncRNAs in MM as diagnostic and prognostic markers, which may be the future targets for individualized therapy.