Effect of sodium-glucose cotransporter-2 inhibitors on blood pressure in patients with heart failure: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) can achieve significant improvement in blood pressure in people with diabetes. Furthermore, randomized controlled trials (RCTs) have established that SGLT2i have a cardioprotective effect in adults with heart failure (HF). Therefore, we performed this systematic review an meta-analysis to determine the effect of SGLT2i on blood pressure in patients with HF. METHODS: We used the Medline, Cochrane Library, Embase, and PubMed databases to identify RCTs (published through to April 29, 2022) that evaluated the effect of SGLT2i on HF. The primary endpoint was defined as change in blood pressure. Secondary composite outcomes were heart rate, hematocrit, body weight, and glycated hemoglobin. The N-terminal pro-brain natriuretic peptide level, Kansas City Cardiomyopathy Questionnaire scores, and estimated glomerular filtration rate were also evaluated. RESULTS: After a literature search and detailed evaluation, 16 RCTs were included in the quantitative analysis. Pooled analyses showed that SGLT2i were associated with a statistically significant reduction in systolic blood pressure of 1.68 mmHg (95% confidence interval [CI] - 2.7, - 0.66; P = 0.001; I2 = 45%) but not diastolic blood pressure (mean difference [MD] -1.06 mmHg; 95% CI -3.20, 1.08; P = 0.33; I2 = 43%) in comparison with controls. Furthermore, SGLT2i decreased body weight (MD - 1.36 kg, 95% CI - 1.68, - 1.03; P < 0.001; I2 = 61%) and the glycated hemoglobin level (MD - 0.16%, 95% CI - 0.28, -0.04, P = 0.007; I2 = 91%) but increased hematocrit (MD 1.63%, 95% CI 0.63, 2.62, P = 0.001; I2 = 100%). There was no significant between-group difference in heart rate (MD - 0.35; 95% CI - 2.05, 1.35, P = 0.69; I2 = 0). CONCLUSIONS: SGLT2i decreased systolic blood pressure in patients with HF but had no effect on diastolic blood pressure. These inhibitors may have numerous potentially beneficial clinical effects in patients with HF.

Coronary angiography-derived contrast fractional flow reserve.

BACKGROUND: Based on coronary angiography and mean aortic pressure, a specially designed computational flow dynamics (CFD) method is proposed to determine contrast fractional flow reserve (cFFR) without using invasive pressure wire. This substudy assessed diagnostic performance of coronary angiography-derived cFFR in catheterization laboratory, based on a previous multicenter trial for online assessment of coronary angiography-derived FFR (caFFR). METHODS: Patients with diagnosis of stable angina pectoris or unstable angina pectoris were enrolled in six centers. Wire-based FFR was measured in coronary arteries with 30-90% diameter stenosis. Offline angiography-derived cFFR was computed in blinded fashion against the wire-based FFR and caFFR at an independent core laboratory. RESULTS: A total of 330 patients were enrolled to fulfill inclusion/exclusion criteria from June 26 to December 18, 2018. Offline angiography-derived cFFR and wire-based FFR results were compared in 328 interrogated vessels. The statistical analysis showed the highest diagnostic accuracy of 89.0 and 86.6% for angiography-derived cFFR with a cutoff value of 0.94 and 0.93 against the wire-based FFR with a cutoff value of 0.80 and 0.75, respectively. The corresponding sensitivity and specificity were 92.2 and 87.3% for the cutoff value of 0.94 and 80.0 and 88.4% for the cutoff value of 0.93, which are similar to those against the caFFR. The receiver-operating curve has area under the curve of 0.951 and 0.972 for the wire-based FFR with the cutoff value of 0.80 and 0.75, respectively. CONCLUSIONS: Coronary angiography-derived cFFR showed higher accuracy, sensitivity, and specificity against wired-based FFR and caFFR. Hence, angiography-derived cFFR could enhance the hemodynamic assessment of coronary lesions.

Drug-Coated Balloon Treatment for Possible Sequelae of Kawasaki Disease Evaluated by Multi-Modalities.

The most devastating sequela of Kawasaki disease (KD) is coronary artery complications that may lead to myocardial infarction and cardiac mortality. Percutaneous coronary intervention (PCI) and bypass grafting are recommended for KD patients with inducible myocardial ischemia and amendable coronary anatomy. However, there are few reports about coronary revascularization with drug-eluting balloons among KD patients, especially at an early age. We present a case report of multi-modality guidance of PCI with a drug-coated balloon (DCB) for a young patient with acute coronary syndrome and a history of KD. Post-procedural optical coherence tomography, angiography-derived fractional flow reserve, and 12-month coronary artery magnetic resonance showed favorable outcomes. The present case indicated that DCB therapy with intravascular imaging and physiologic assessment guidance may be an alternative strategy to treat severe coronary artery stenosis in selected patients with KD.

Extreme Levels of Air Pollution Associated With Changes in Biomarkers of Atherosclerotic Plaque Vulnerability and Thrombogenicity in Healthy Adults.

RATIONALE: The pathophysiologic mechanisms of air pollution-associated exacerbation of cardiovascular events remain incompletely understood. OBJECTIVE: To assess whether ambient air pollution can be a trigger of the vulnerable plaque and heightened thrombogenicity through systemic inflammatory pathways. METHODS AND RESULTS: In Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunctions in Healthy Adults Living in Beijing), 73 healthy adults (mean±SD, 23.3±5.4 years) were followed up in 2014 to 2016. We estimated associations between air pollutants and biomarkers relevant to atherosclerotic plaque vulnerability, thrombogenicity, and inflammation using linear mixed-effects models and elucidated the biological pathways involved using mediation analyses. Receiver operating characteristic analyses were conducted to assess the ability of each biomarker to predict ambient air pollution exposures. High average concentrations of particulate matter in diameter <2.5 µm (91.8±63.8 µg/m3) were observed during the study period. Significant increases in circulating biomarkers of plaque vulnerability, namely MMPs (matrix metalloproteinases; MMP-1, 2, 3, 7, 8, and 9), of 8.6% (95% CI, 0.1-17.8) to 141.4% (95% CI, 111.8-171.0) were associated with interquartile range increases in moving averages of particulate matter in diameter <2.5 µm, number concentrations of particles in sizes of 5 to 560 nm and black carbon, during the last 1 to 7 days before each participant's clinic visit. Higher air pollutant levels were also significantly associated with decreases in TIMP (tissue inhibitors of MMPs; TIMP-1 and 2), heightened thrombogenicity (shortened prothrombin time and increases in sCD40L [soluble CD40 ligand], sCD62P [soluble P-selectin], and fibrinogen/fibrin degradation products), and elevations in systemic inflammation (IL-1ß [interleukin-1ß], CRP [C-reactive protein], MIP-1α/ß [macrophage inflammatory protein-1α/ß], sRAGE [soluble receptor for advanced glycation end products], and IGFBP [insulin-like growth factor-binding protein]-1 and 3). Receiver operating characteristic curves showed that several biomarkers can serve as robust pollutant-specific predictors with high versus low black carbon exposure (area under the receiver operating characteristic curve of 0.974 [95% CI, 0.955-0.992] for MMP-8 and 0.962 [95% CI, 0.935-0.988] for sRAGE). Mediation analysis further showed that systemic inflammation can mediate ≤46% of the changes in MMPs and thrombogenicity associated with interquartile range increases in air pollutants. CONCLUSIONS: Our results suggest that air pollution may prompt cardiovascular events by triggering vulnerable plaque along with heightened thrombogenicity possibly through systemic inflammatory pathways.

Perturbation of amino acid metabolism mediates air pollution associated vascular dysfunction in healthy adults.

The molecular mechanisms of air pollution-associated adverse cardiovascular effects remain largely unknown. In the present study, we investigated the impacts of ambient air pollution on vascular function and the potential mediation effects of amino acids in a longitudinal follow-up of 73 healthy adults living in Beijing, China, between 2014 and 2016. We estimated associations between air pollutants and serum soluble intercellular adhesion molecule 1 (sICAM-1) and plasma levels of amino acids using linear mixed-effects models, and elucidated the biological pathways involved using mediation analyses. Higher air pollutant levels were significantly associated with increases in sICAM-1 levels. Metabolomics analysis showed that altered metabolites following short-term air pollution exposure were mainly involved in amino acid metabolism. Significant reductions in levels of plasma alanine, threonine and glutamic acid of 2.1 µM [95% confidence interval (CI): -3.8, -0.3] to 62.0 µM (95% CI: -76.1, -47.9) were associated with interquartile range increases in moving averages of PM2.5, BC, CO and SO2 in 1-7 days prior to clinical visits. Mediation analysis also showed that amino acids can mediate up to 48% of the changes in sICAM-1 associated with increased air pollution exposure. Our results indicated that air pollution may prompt vascular dysfunction through perturbing amino acid metabolism.

Ambient Air Pollution Is Associated With HDL (High-Density Lipoprotein) Dysfunction in Healthy Adults.

Objective- We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results- In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 µm were 62.9 µg/m3 (8.1-331.0 µg/m3). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, -4.3 to -0.3) to 5.0% (95% CI, -7.6 to -2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 µm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant's clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein. Conclusions- Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.

Ambient air pollution is associated with cardiac repolarization abnormalities in healthy adults.

BACKGROUND: Ambient air pollution has been associated with acute cardiovascular events; however, the underlying mechanisms remain incompletely understood. We aimed to examine the impacts of ambient air pollutants on cardiac ventricular repolarization in a highly polluted urban region. METHODS: Seventy-three healthy non-smoking young adults (66% female, mean age of 23.3 ±â€¯5.4 years) were followed with four repeated 24-h electrocardiogram recordings in 2014-2016 in Beijing, China. Continuous concentrations of ambient particulates in size fractions of 5-560 nm diameter, black carbon (BC), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) were measured at a fixed-location air pollution monitoring station. Generalized linear mixed models, with adjustment for individual risk factors, time-varying factors and meteorological parameters, were used to evaluate the effects of air pollution on 5-min segments of heart rate-corrected QT interval (QTc), an index of cardiac ventricular repolarization. RESULTS: During the study period, the mean levels of number concentrations of particulates in size range of 5-560 nm (PNC5-560) were 20,711 particles/cm3. Significant increases in QTc of 0.56% (95% CI: 0.27, 0.84) to 1.76% (95% CI: 0.73, 2.79) were associated with interquartile range increases in PNC50-560 at prior 1-5 moving average days. Significant increases in QTc were also associated with increases in exposures to traffic-related air pollutants (BC, NO2 and CO), a combustion pollutant SO2, and the secondary pollutant O3. The associations were stronger in participants who were male, overweight, with abdominal obesity, and with higher levels of high-sensitivity C-reactive protein. CONCLUSIONS: Our findings suggest that exposures to higher levels of ambient particulates in small size fractions and traffic pollutants were associated with cardiac repolarization abnormalities in healthy adults, and the cardio-metabolic risks may modify the adverse cardiac effects attributable to air pollution.

Health risk assessment of heavy metals in fish and accumulation patterns in food web in the upper Yangtze River, China.

This study aims to concern the distribution of As, Cr, Cd, Hg, Cu, Zn, Pb and Fe in surface sediment, zoobenthos and fishes, and quantify the accumulative ecological risk and human health risk of metals in river ecological system based on the field investigation in the upper Yangtze River. The results revealed high ecological risk of As, Cd, Cu, Hg, Zn and Pb in sediment. As and Cd in fish presented potential human health risk of metals by assessing integrated target hazard quotient results based on average and maximum concentrations, respectively. No detrimental health effects of heavy metals on humans were found by daily fish consumption. While, the total target hazard quotient (1.659) exceeding 1, it meant that the exposed population might experience noncarcinogenic health risks from the accumulative effect of metals. Ecological network analysis model was established to identify the transfer routes and quantify accumulative effects of metals on river ecosystem. Control analysis between compartments showed large predator fish firstly depended on the omnivorous fish. Accumulative ecological risk of metals indicated that zoobenthos had the largest metal propagation risk and compartments located at higher trophic levels were not easier affected by the external environment pollution. CAPSULE: A potential accumulative ecological risk of heavy metal in the food web was quantified, and the noncarcinogenic health risk of fish consumption was revealed for the upper reach of the Yangtze River.

[Adverse effects of ultrafine particles on the cardiovascular system and its mechanisms].

Cardiovascular disease is one of the major threats to human. Air pollution, which , as it become a problem too serious to be ignored in China, is known to be an important risk factor for cardiovascular disease. Among all pollutants, ultrafine particles ( UFPs) , defined as particles with their diameter less than 0. 1 f.Lm, are a specific composition. They are very small in size, large in quantity and surface area, and most important, capable of passing through the air-blood barrier. These unique features of UFPs make them special in their impact on cardiovascular system. Nowadays, the influence of UFPs on the cardiovascular system has become a hot topic. On the one side, studies have shown that UFPs can cause inflammation and oxidative stress in the lung, and then induce systemic inflammation by releasing cytokine and reactive oxygen species into the circulation. On the other side, UFPs themselves can "spillout"into the circulation and interact with their targets. By this way, UFPs directly affect endothelial cells, myocardial cells and the autonomic nervous system, which ultimately result in increased cardiovascular events. We intend to make an overview about the recent progress about the influence of UFPs on human cardiovascular disease and the related mechanisms, and argue for more attention to this issue.

The first in-human study to evaluate the antiplatelet properties of the clopidogrel conjugate DT-678 in acute coronary syndrome patients and healthy volunteers.

BACKGROUND AND PURPOSE: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR. EXPERIMENTAL APPROACH: A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. KEY RESULTS: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678. CONCLUSION AND IMPLICATIONS: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy.

Association between pulse wave velocity and the 10-year risk of atherosclerotic cardiovascular disease in the Chinese population: A community-based study.

Accumulated evidence has shown that carotid-femoral and brachial-ankle PWV well predict cardiovascular events but it is still unclear if the predictability is same or not. In this cross-sectional study based on a community atherosclerosis cohort in Beijing, China, a total of 5282 participants without previous coronary heart disease and stroke were enrolled from a community atherosclerosis cohort in Beijing, China. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk were calculated by the China-PAR model, and < 5%, 5%-10% and > 10% were defined as low, intermediate, and high risk, respectively. The average baPWV and cfPWV values were 16.63 ± 3.35 m/s and 8.45 ± 1.78 m/s, respectively. The mean 10-year ASCVD risk was 6.98% (interquartile range: 3.90%-12.01%). The patients with low, intermediate, and high 10-year ASCVD risk accounted for 34.84% (1840), 31.94% (1687),, and 33.23% (1755) respectively. Multivariate analysis showed that for every 1 m/s increase in baPWV and cfPWV, the 10-year ASCVD risk increased by 0.60% (95% confidence interval: 0.56%-0.65%, p < .001) and 1.17% (95% confidence interval: 1.09%-1.25%, p < .001), respectively. The diagnostic ability of the baPWV was comparable to the cfPWV (area under the curve: 0.870 [0.860-0.879] vs. 0.871 [0.861-0.881], p = .497). In conclusion, baPWV and cfPWV are positively associated with the 10-year risk of ASCVD in the Chinese community-based population, with a nearly identical association with a high 10-year risk of ASCVD.

Renal denervation in management of heart failure with reduced ejection fraction: A systematic review and meta-analysis.

BACKGROUND: Some, but not all, recent studies have shown that renal denervation (RDN) can improve cardiac function and exercise tolerance in people who have heart failure with reduced ejection fraction (HFrEF). This study assessed the efficacy and safety of RDN as a treatment for HFrEF. METHODS: The Medline, Cochrane Library, Embase, and PubMed databases were searched through to September 28, 2022 for clinical studies that evaluated the effect of RDN on HFrEF. The primary endpoints were changes in left ventricular ejection fraction (LVEF) and 6-min walk distance (6MWD). Secondary endpoints were changes in echocardiographic parameters, including left ventricular end-diastolic and end-systolic diameters, left atrial diameter, and interventricular septal thickness. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, New York Heart Association (NYHA) class, heart rate, and systolic and diastolic blood pressure were also evaluated. Major adverse events were defined as death and rehospitalization for heart failure during follow-up. The estimated glomerular filtration rate (eGFR) and serum creatinine level were extracted as measures of renal function. RESULTS: Eleven trials comprising 313 patients were eligible for quantitative analysis. Pooled analyses showed a mean increase in LVEF of 4.25 % (95 % CI 1.77-6.72; p < 0.001, I2 = 69 %) and an increase in 6MWD (mean difference 50.28 m, 95 % CI 8.78-91.78; p = 0.02; I2 = 81 %) after RDN. Left ventricular end-diastolic and end-systolic diameters, left atrial diameter, and interventricular septal thickness also improved after RDN. NT-proBNP, NYHA class, and heart rate were significantly decreased after RDN. There were no significant changes in blood pressure after RDN. Mortality and HF-related hospitalization rates were relatively low. There was no significant change in eGFR or creatinine after RDN. CONCLUSIONS: Our findings suggest that RDN can effectively increase LVEF and 6MWD in patients with HFrEF but require confirmation in studies with larger sample sizes and longer follow-up durations.

Haemodynamic changes of interatrial shunting devices for heart failure: a systematic review and meta-analysis.

AIMS: To assess the efficacy and safety, primarily in relation to the haemodynamic effects, of interatrial shunting devices (ISD) for the treatment of heart failure (HF), we conducted a systematic review and a meta-analysis. METHODS AND RESULTS: We used the MEDLINE, Cochrane Library, Embase, and PubMed databases to identify clinical studies (published to 4 August 2021) that evaluated the effect of ISD on HF. The primary endpoint was defined as changes in pulmonary capillary wedge pressure (PCWP). Secondary endpoints included (i) other haemodynamic indexes, including cardiac output (CO), right atrial pressure (RAP), and mean pulmonary artery pressure (mPAP) by right heart catheterization, and (ii) change from baseline in 6 min walk distance (6MWD). After a literature search and detailed evaluation, six trials enrolling a total of 203 individuals were included in the quantitative analysis. Pooled analyses showed that after ISD implantation, PCWP decreased by a mean 3.10 mmHg [95% confidence interval (CI) -4.56 to -1.64; I2  = 0%; P < 0.0001]. Overall, CO increased by 0.77 L/min (95% CI 0.02 to 1.52; P = 0.04; I2  = 82%), but there were no significant changes in RAP or mPAP. The mean 6MWD increased by 32.33 m (95% CI 10.74 to 53.92; P = 0.003; I2  = 0) after ISD implantation. CONCLUSIONS: Interatrial shunting device can effectively reduce PCWP, increase CO and 6MWD, and has no obvious adverse effects on the right heart and pulmonary pressure. Studies with larger sample size and longer follow-up time are needed for further verification.

Association between plasma vitamin B5 and coronary heart disease: Results from a case-control study.

Aim: The relationship of vitamin B5 and coronary heart disease (CHD) is still uncertain. This case-control study was performed to evaluate the relationship between the plasma vitamin B5 concentration and the risk of CHD. Materials and methods: The study involved 429 patients with >70% stenosis of the coronary arteries on coronary angiography and 429 matched controls were included for age ± 2 years, gender, and date of coronary angiography examination ± 180 days. Logistic regression analyses were performed to evaluate the association between plasma vitamin B5 and the risk of CHD. Results: An L-shaped relationship was found between the plasma vitamin B5 concentration and CHD. Compared with patients with low vitamin B5 (first quartile, <27.6 ng/ml), the odds ratio (OR) and 95% confidence interval (CI) for participants in the third quartile (34.9-44.0 ng/ml) and fourth quartile (≥44.0 ng/ml) were 0.42 (95% CI, 0.26-0.70) and 0.49 (95% CI, 0.29-0.82), respectively. In the threshold effect analysis, the risk of CHD significantly decreased as the vitamin B5 concentration increased (per 10 ng/ml increment: OR, 0.71; 95% CI, 0.57-0.89) in participants with a plasma vitamin B5 concentration of <40.95 ng/ml; however, an increased plasma vitamin B5 concentration was no longer associated with a decreased risk of CHD (per 10 ng/ml increment: OR, 1.00; 95% CI, 0.87-1.14) in participants with a plasma vitamin B5 concentration of ≥40.95 ng/ml. The association between vitamin B5 and CHD was stronger in ever or current smokers than non-smokers (p-interaction = 0.046). Conclusion: Plasma vitamin B5 has an L-shaped relationship with CHD, with a threshold around 40.95 ng/ml. This association was modified by smoking.

Corrigendum: Case report: Primary aldosteronism and subclinical cushing syndrome in a 49-year-old woman with hypertension plus hypokalaemia.

[This corrects the article DOI: 10.3389/fcvm.2022.911333.].

Case Report: Primary Aldosteronism and Subclinical Cushing Syndrome in a 49-Year-Old Woman With Hypertension Plus Hypokalaemia.

Background: Coexisting primary aldosteronism (PA) and subclinical Cushing's syndrome (SCS) caused by bilateral adrenocortical adenomas have occasionally been reported. Precise diagnosis and treatment of the disease pose a challenge to clinicians due to its atypical clinical manifestations and laboratory findings. Case Summary: A 49-year-old woman was admitted to our hospital due to fatigue, increased nocturia and refractory hypertension. The patient had a history of severe left hydronephrosis 6 months prior. Laboratory examinations showed hypokalaemia (2.58 mmol/L) and high urine potassium (71 mmol/24 h). Adrenal computed tomography (CT) showed bilateral adrenal masses. Undetectable ACTH and unsuppressed plasma cortisol levels by dexamethasone indicated ACTH-independent Cushing's syndrome. Although the upright aldosterone-to-renin ratio (ARR) was 3.06 which did not exceed 3.7, elevated plasma aldosterone concentrations (PAC) with unsuppressed PAC after the captopril test still suggested PA. Adrenal venous sampling (AVS) without adrenocorticotropic hormone further revealed hypersecretion of aldosterone from the right side and no dominant side of cortisol secretion. A laparoscopic right adrenal tumor resection was performed. The pathological diagnosis was adrenocortical adenoma. After the operation, the supine and standing PAC were normalized; while the plasma cortisol levels postoperatively were still high and plasma renin was activated. The patient's postoperative serum potassium and 24-h urine potassium returned to normal without any pharmacological treatment. In addition, the patient's blood pressure was controlled normally with irbesartan alone. Conclusion: Patients with refractory hypertension should be screened for the cause of secondary hypertension. AVS should be performed in patients in which PA is highly suspected to determine whether there is the option of surgical treatment. Moreover, patients with PA should be screened for hypercortisolism, which can contribute to a proper understanding of the AVS result.

Effects on Adherence to a Mobile App-Based Self-management Digital Therapeutics Among Patients With Coronary Heart Disease: Pilot Randomized Controlled Trial.

BACKGROUND: The adherence to secondary prevention treatment in patients with coronary heart disease (CHD) is low. Digital therapeutics (DTx) refers to an emerging branch of medicine that delivers medical interventions directly to patients using evidence-based, clinically evaluated, technology-based software algorithms or apps to facilitate disease management, which may be an efficient tool to optimize adherence. OBJECTIVE: This paper aims to investigate the effect of mobile app-based self-management DTx on long-term use of secondary prevention medications in patients with CHD in China. METHODS: This pilot study was a parallel-designed, open-labeled, single-center, randomized controlled trial. Hospitalized patients with CHD admitted to Peking University First Hospital between April 2016 and June 2017 were randomized before discharge on a 1:1 ratio. The intervention group received regular follow-up combined with DTx, which is a self-management mobile app already installed on an Android 5 (Mi Pad 1, Xiaomi Corporation) tablet. Structured data from the hospital informatics system were integrated automatically, and medication, lifestyle intervention plan, follow-up protocol, and patient education materials were also provided according to the diagnosis. Participants could use DTx for self-management at home. The control group was under conventional hospital-based follow-up care. Patients were followed up for 1 year, and the primary end point was the percentage of all guideline-recommended medications at 12 months. The secondary end points included the percentage adhered to standard secondary prevention medications at 6 months, the control rate of lipid profile, and blood pressure at 6 months and 1 year. RESULTS: Among 300 randomized patients with CHD, 290 (96.7%) were included in the final analysis, including 49.3% (143/290) and 50.7% (147/290) of patients from the intervention and control groups, respectively. Baseline characteristics were similar between the 2 groups. There was a statistically significant improvement in the percentage of all guideline-recommended medications at 12 months in the intervention group compared with the control group (relative risk [RR] 1.34, 95% CI 1.12-1.61; P=.001), and there was no interaction with baseline characteristics. The intervention group had a significantly higher proportion of patients achieving blood pressure under control (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg) and low-density lipoprotein cholesterol <1.8 mmol/L (RR 1.45, 95% CI 1.22-1.72; P<.001 and RR 1.40, 95% CI 1.11-1.75; P=.004, respectively) at 12 months. Furthermore, on logistic regression, the intervention group had a lower risk of withdrawing from guideline-recommended medications (odds ratio 0.46, 95% CI 0.27-0.78; P=.004). CONCLUSIONS: Among patients with CHD, using a mobile app-based self-management DTx in addition to traditional care resulted in a significant improvement in guideline-recommended medication adherence at 12 months. The results of the trial will be applicable to primary care centers, especially in rural areas with less medical resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT03565978; https://clinicaltrials.gov/ct2/show/NCT03565978.

The mediating role of vascular inflammation in traffic-related air pollution associated changes in insulin resistance in healthy adults.

AIM: The precise pathophysiologic pathway linking traffic-related air pollution (TRAP) to diabetes mellitus is not well elucidated. We aimed to investigate whether activation of vascular inflammation can be a mechanistic linkage between ambient TRAP and insulin resistance. METHODS: Study outcomes were determined by assessing a series of circulating biomarkers indicative of insulin resistance and vascular inflammation among 73 healthy adults who underwent repeated clinical visits in Beijing, China, 2014-2016. Concomitantly, concentrations of ambient TRAP indices, including particulate matter in diameter <2.5 µm (PM2.5), particles in size fractions of 5-560 nm, black carbon, carbon monoxide, nitrogen dioxide, and oxides of nitrogen, were continuously monitored. RESULTS: Participants experienced extremely high levels of TRAP exposures, with mean (standard deviation) PM2.5 concentrations of 91.8 (48.3) µg/m3, throughout the study. We found that interquartile range increases in exposure to moving average concentrations of various TRAP indices at prior up to 7 days were associated with significant elevations of 8.9-49.6% in insulin levels. Higher pollutant levels were also related to worsening metrics of insulin resistance (soluble insulin receptor ectodomain, adipokines, and homeostasis model assessment of insulin resistance) and heightened vascular inflammatory responses, particularly disruptions of the receptor activator of nuclear factor κB ligand/osteoprotegerin system balance and elevations of monocyte/macrophage and T cell activation markers. Mediation analyses showed that activation of vascular inflammation could explain up to 66% of the alterations in metrics of insulin resistance attributable to air pollution. CONCLUSION: Our results suggest that ambient traffic pollution exposure was capable of promoting insulin resistance possibly via generating vascular inflammation.

Joint Predictive Value of cTnI and NT-proBNP on Mortality in Patients with Coronavirus Disease 2019: A Retrospective Research in Wuhan, China.

BACKGROUND AND OBJECTIVES: The pandemic of coronavirus disease 2019 (COVID-19) remains to be the biggest public threat all over the world. Because of the rapid deterioration in some patients, markers that could predict poor clinical outcomes are urgently required. This study was to evaluate the predictive values of cardiac injury parameters, including cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, on mortality in COVID-19 patients. METHODS: COVID-19 patients in Zhongfaxincheng branch of Tongji Hospital (Wuhan, China) from February 8-28, 2020, were enrolled in this study. We followed up the patients for 30 days after admission. RESULTS: A total of 134 patients were included in the study. Multivariate Cox regression showed that 1) patients with elevated cTnI levels had a higher risk of death (hazard ratio [HR] 7.33, 95% confidence interval [CI] 2.56-21.00) than patients with normal cTnI levels; 2) patients with elevated NT-proBNP levels had a higher risk of death (HR 27.88, 95% CI 3.55-218.78) than patients with normal NT-proBNP levels; 3) patients with both elevated cTnI and NT-proBNP levels had a significantly higher risk of death (HR 53.87, 95% CI 6.31-459.91, P < 0.001) compared to patients without elevated cTnI or NT-proBNP levels; 4) the progressions of cTnI and NT-proBNP levels were also correlated with death (HR 12.70, 95% CI 3.94-40.88, P < 0.001 and HR 51.09, 95% CI 5.82-448.26, P < 0.001). CONCLUSIONS: In COVID-19 patients, cTnI and NT-proBNP levels could be monitored to identify patients at a high risk of death in their later course of disease.

Combustion-derived particulate organic matter associated with hemodynamic abnormality and metabolic dysfunction in healthy adults.

Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6-2.9% in diastolic blood pressure, 6.6-8.1% in soluble ST2, 10.5-14.5% in insulin, 40.9-45.7% in osteoprotegerin, and 36.3-48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.