BACKGROUND: Night eating has been associated with an elevated risk of obesity, dyslipidemia, and cardiovascular disease. However, there is no longitudinal study on whether habitual night eating, regardless of diet quality and energy intake, is associated with arterial stiffness, a major etiological factor in the development of cardiovascular disease. METHODS AND RESULTS: The study included 7771 adult participants without cardiovascular disease, cancer, or diabetes mellitus prior to dietary assessment by a validated food frequency questionnaire in 2014 through 2015. Participants were categorized into 3 groups based on self-reported night-eating habits: never or rarely, some days (1-5 times per week), or most days (6+ times per week). Arterial stiffness was assessed by brachial-ankle pulse wave velocity at baseline and repeatedly during follow-ups. Mean differences and 95% CIs in the yearly change rate of brachial-ankle pulse wave velocity across the 3 groups were calculated, adjusting for age, sex, socioeconomic status, total energy intake, diet quality, sleep quality, and other cardiovascular disease risk factors. At baseline, 6625 (85.2%), 610 (7.8%), and 536 (6.9%) participants reported night eating as never or rarely, some days, or most days, respectively. During a mean 3.19 years, we observed a positive association between night-eating frequency and progression of arterial stiffness (Ptrend=0.01). The adjusted difference in brachial-ankle pulse wave velocity change rate between the group that ate at night most days and the group that never or rarely ate at night was 14.1 (95% CI, 0.6-27.5) cm/s per year. This association was only significant in women, but not in men (Pinteraction=0.03). CONCLUSIONS: In an adult population free of major chronic diseases, habitual night eating was positively associated with the progression of arterial stiffness, a hallmark of arteriosclerosis and biological aging.
Background We aimed to investigate the association between blood pressure (BP) and outcomes in intracerebral hemorrhage (ICH) subtypes with different etiologies. Methods and Results A total of 5656 in-hospital patients with spontaneous ICH were included between January 2012 and December 2016 in a prospective multicenter cohort study. Etiological subtypes of ICH were assigned using SMASH-U (structural lesion, medication, amyloid angiopathy, systemic/other disease, hypertension, undetermined) classification. Elevated systolic BP was defined as >= 140 mm Hg. Hypertension was defined as elevated BP for >1 month before the onset of ICH. The primary outcomes were measured as 1-month survival rate and 3-month mortality. A total of 5380 patients with ICH were analyzed, of whom 4052 (75.3%) had elevated systolic BP on admission and 3015 (56.0%) had hypertension. In multinomial analysis of patients who passed away by 3 months, systolic BP on admission was significantly different in cerebral amyloid angiopathy (P<0.001), structural lesion (P<0.001), and undetermined subtypes (P=0.003), compared with the hypertensive angiopathy subtype. Elevated systolic BP was dose-responsively associated with higher 3-month mortality in hypertensive angiopathy (P-trend=0.013) and undetermined (P-trend=0.005) subtypes. In cerebral amyloid angiopathy, hypertension history had significant inverse association with 3-month mortality (adjusted odds ratio, 0.37, 95% CI, 0.20-0.65;P<0.001). Similarly, adjusted Cox regression indicated decreased risk of 1-month survival rate in the presence of hypertension in patients with cerebral amyloid angiopathy (adjusted hazard ratio, 0.47; 95% CI, 0.24-0.92;P=0.027). Conclusions This study suggests that the association between BP and ICH outcomes might specifically depend on its subtypes, and cerebral amyloid angiopathy might be pathologically distinctive from the others. Future studies of individualized BP-lowering strategy are needed to validate our findings.
Background The purpose of this study was to determine whether the presence of antegrade blood flow was related to stroke subtype in patients with acute intracranial large artery occlusion. Methods and Results The prospectively collected data for consecutive patients who had occlusion of the unilateral M1 segment of the middle cerebral artery with or without internal carotid artery and received reperfusion therapy were retrospectively reviewed. Stroke causes were determined according to the Trial ofORG10172 in Acute Stroke Treatment standard. We defined antegrade flow as early opacification at the distal interface of the clot with subsequent distal extension on 4-dimensional computed tomography angiography. A total of 387large artery occlusionpatients were analyzed (229 men and 158 women; mean age, 71 +/- 14 years), including 77 (19.9%) with large artery atherosclerosis (LAA), 206 (53.2%) with cardioembolism, and 104 (26.9%) with undetermined causes. Antegrade flow was found in 206 (53.2%) patients, and 181 (46.8%) presented with retrograde flow. The rate of antegrade flow was much higher in patients withLAAthan in those with cardioembolism (85.7% versus 42.2%,P<0.001). Multivariable logistic regression revealed that presence of antegrade flow was significantly associated with cuse ofLAAafter adjusting for confounding factors, when setting cardioembolism as reference (odds ratio, 5.650; 95% confidence interval, 2.451-13.158;P<0.001). The sensitivity, specificity, and positive and negative predictive values of the antegrade flow for predictingLAAwere 43.1%, 91.5%, 85.7%, and 57.8%, respectively. Conclusions Using 4-dimensional computed tomography angiography, antegrade flow can be identified in more than half of acute anteriorlarge artery occlusionpatients and occurs more frequently in those withLAAas the cause of stroke.
Background Food insecurity is a global leading public health challenge that affects not only developing countries but also developed countries, including the United States. About 50 million Americans are food insecure. In this study we examined the associations of the adult food insecurity with all-cause and cardiovascular disease mortality in a nationally representative sample of US adults. Methods and Results We included 27 188 US adults (age >= 40 years of age) who participated in the US National Health and Nutrition Examination Survey from 1999 to 2014. Food insecurity status was assessed using the Food Security Survey Module developed by the US Department of Agriculture. Mortality from all causes and cardovascular disease was ascertained through data linkage to the National Death Index through December 31, 2015. We used multivariable Cox proportional hazards regression with sampling weights to estimate hazard ratios (HRs) and 95% CIs of all-cause and cardiovascular disease mortality, according to food security status. During 205 389 person-years of the period, 5039 deaths occurred, including 1084 cardiovascular disease deaths. After adjustment for age, sex, race/ethnicity, education, income, and dietary and lifestyle factors, participants with very low food security had higher risk of all-cause and cardiovascular disease mortality, with multivariable-adjustedHRs of 1.32 (95%CI, 1.07-1.62), and 1.53 (95% CI, 1.04-2.26), respectively, compared with those with high food security. Conclusions Food insecurity is significantly associated with increased risk of excess death from cardiovascular disease and all causes in US adults.
BACKGROUND: The coronavirus disease 2019 (COVID-19) has developed into a global outbreak. Patients with cardiovascular disease (CVD) with COVID-19 have different clinical characteristics and prognostic outcomes. This study aimed to summarize the clinical characteristics and laboratory indicators of patients with COVID-19 with CVD, especially the critically ill patients. METHODS AND RESULTS: This study included 244 patients diagnosed with COVID-19 and CVD (hypertension, coronary heart disease, or heart failure). The patients were categorized into critical (n=36) and noncritical (n=208) groups according to the interim guidance of China's National Health Commission. Clinical, laboratory, and outcome data were collected from the patients' medical records and compared between the 2 groups. The average body mass index of patients was significantly higher in the critical group than in the noncritical group. Neutrophil/lymphocyte ratio, and C-reactive protein, procalcitonin, and fibrinogen, andd-dimer levels at admission were significantly increased in the critical group. The all-cause mortality rate among cases of COVID-19 combined with CVD was 19.26%; the proportion of coronary heart disease and heart failure was significantly higher in deceased patients than in recovered patients. High body mass index, previous history of coronary heart disease, lactic acid accumulation, and a decrease in the partial pressure of oxygen were associated with death. CONCLUSIONS: All-cause mortality in patients with COVID-19 with CVD in hospitals is high. The high neutrophil/lymphocyte ratio may be a predictor of critical patients. Overweight/obesity combined with coronary heart disease, severe hypoxia, and lactic acid accumulation resulting from respiratory failure are related to poor outcomes.
Background Oxygen plays a pivotal role in cardiopulmonary resuscitation (CPR) and postresuscitation intervention for cardiac arrest. However, the optimal method to reoxygenate patients has not been determined. This study investigated the effect of timing of hyperoxygenation on neurological outcomes in cardiac arrest/CPR rats treated with targeted temperature management. Methods and Results After induction of ventricular fibrillation, male Sprague-Dawley rats were randomized into 4 groups (n=16/group): (1) normoxic control; (2) O-2_CPR, ventilated with 100% O(2)during CPR; (3) O-2_CPR+postresuscitation, ventilated with 100% O(2)during CPR and the first 3 hours of postresuscitation; and (4) O-2_postresuscitation, ventilated with 100% O(2)during the first 3 hours of postresuscitation. Targeted temperature management was induced immediately after resuscitation and maintained for 3 hours in all animals. Postresuscitation hemodynamics, neurological recovery, and pathological analysis were assessed. Brain tissues of additional rats undergoing the same experimental procedure were harvested for ELISA-based quantification assays of oxidative stress-related biomarkers and compared with the sham-operated rats (n=6/group). We found that postresuscitation mean arterial pressure and quantitative electroencephalogram activity were significantly increased, whereas astroglial protein S100B, degenerated neurons, oxidative stress-related biomarkers, and neurologic deficit scores were significantly reduced in the O-2_CPR+postresuscitation group compared with the normoxic control group. In addition, 96-hour survival rates were significantly improved in all of the hyperoxygenation groups. Conclusions In this cardiac arrest/CPR rat model, hyperoxygenation coupled with targeted temperature management attenuates ischemia/reperfusion-induced injuries and improves survival rates. The beneficial effects of high-concentration oxygen are timing and duration dependent. Hyperoxygenation commenced with CPR, which improves outcomes when administered during hypothermia.
Background Nonpharmacologic interventions that modify lifestyle can lower blood pressure (BP) and have been assessed in numerous randomized controlled trials and pairwise meta-analyses. It is still unclear which intervention would be most efficacious. Methods and Results Bayesian network meta-analyses were performed to estimate the comparative effectiveness of different interventions for lowering BP. From 60 166 potentially relevant articles, 120 eligible articles (14 923 participants) with a median follow-up of 12 weeks, assessing 22 nonpharmacologic interventions, were included. According to the surface under the cumulative ranking probabilities and Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality of evidence, for adults with prehypertension to established hypertension, high-quality evidence indicated that the Dietary Approach to Stop Hypertension (DASH) was superior to usual care and all other nonpharmacologic interventions in lowering systolic BP (weighted mean difference, 6.97 mm Hg; 95% credible interval, 4.50-9.47) and diastolic BP (weighted mean difference, 3.54 mm Hg; 95% credible interval, 1.80-5.28). Compared with usual care, moderate- to high-quality evidence indicated that aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, breathing-control, and meditation could lower systolic BP and diastolic BP. For patients with hypertension, moderate- to high-quality evidence suggested that the interventions listed (except comprehensive lifestyle modification) were associated with greater systolic BP and diastolic BP reduction than usual care; salt restriction was also effective in lowering both systolic BP and diastolic BP. Among overweight and obese participants, low-calorie diet and low-calorie diet plus exercise could lower more BP than exercise. Conclusions DASH might be the most effective intervention in lowering BP for adults with prehypertension to established hypertension. Aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, salt restriction, breathing-control, meditation and low-calorie diet also have obvious effects on BP reduction.
BACKGROUND: Moderate hypothermic circulatory arrest (MHCA) has been widely used in aortic arch surgery. However, the renal function after MHCA remains controversial. We performed a systematic review and meta-analysis direct comparison of the postoperative renal function of MHCA versus deep hypothermic circulatory arrest (DHCA) in aortic arch surgery. METHODS AND RESULTS: We searched PubMed, Embase, and the Cochrane Library for postoperative renal function after aortic arch surgery with using MHCA and DHCA, published from inception to January 31, 2020. The primary outcome was renal failure. Secondary outcomes were the need for renal therapy and other major postoperative outcomes. The random-effects model was used for all comparisons to pool the estimates. A total of 14 observational studies with 4142 patients were included. Compared with DHCA, MHCA significantly reduced the incidence of renal failure (odds ratio [OR], 0.76; 95% CI, 0.61-0.94;P=0.011; I-2=0.0%) and the need of renal replacement (OR, 0.68; 95% CI, 0.48-0.97;P=0.034; I-2=0.0%). Subgroup analysis showed that when the hypothermic circulatory arrest time was <30 minutes, the incidence of renal failure in MHCA group was significantly lower than that in DHCA group (OR, 0.73; 95% CI, 0.54-0.99;P=0.040; I-2=1.1%), whereas an insignificant difference between 2 groups when hypothermic circulatory arrest time was >30 minutes (OR, 0.76; 95% CI, 0.51-1.13;P=0.169; I-2=17.3%). CONCLUSIONS: MHCA compared with DHCA reduces the incidence of renal failure and the need for renal replacement.
Background To understand the intrinsic cardiac developmental and functional abnormalities in pulmonary atresia with intact ventricular septum (PAIVS) free from effects secondary to anatomic defects, we performed and compared single-cell transcriptomic and phenotypic analyses of patient- and healthy subject-derived human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and engineered tissue models. Methods and Results We derived hiPSC lines from 3 patients with PAIVS and 3 healthy subjects and differentiated them into hiPSC-CMs, which were then bioengineered into the human cardiac anisotropic sheet and human cardiac tissue strip custom-designed for electrophysiological and contractile assessments, respectively. Single-cell RNA sequencing (scRNA-seq) of hiPSC-CMs, human cardiac anisotropic sheet, and human cardiac tissue strip was performed to examine the transcriptomic basis for any phenotypic abnormalities using pseudotime and differential expression analyses. Through pseudotime analysis, we demonstrated that bioengineered tissue constructs provide pro-maturational cues to hiPSC-CMs, although the maturation and development were attenuated in PAIVS hiPSC-CMs. Furthermore, reduced contractility and prolonged contractile kinetics were observed with PAIVS human cardiac tissue strips. Consistently, single-cell RNA sequencing of PAIVS human cardiac tissue strips and hiPSC-CMs exhibited diminished expression of cardiac contractile apparatus genes. By contrast, electrophysiological aberrancies were absent in PAIVS human cardiac anisotropic sheets. Conclusions Our findings were the first to reveal intrinsic abnormalities of cardiomyocyte development and function in PAIVS free from secondary effects. We conclude that hiPSC-derived engineered tissues offer a unique method for studying primary cardiac abnormalities and uncovering pathogenic mechanisms that underlie sporadic congenital heart diseases.
Background Managing risk factors is crucial to prevent stroke. However, few cohort studies have evaluated socioeconomic factors together with conventional factors affecting incident stroke and its subtypes in China. Methods and Results A 2014 to 2016 prospective study from the China National Stroke Screening and Intervention Program comprised 437 318 adults aged >= 40 years without stroke at baseline. There were 2429 cases of first-ever stroke during a median follow-up period of 2.1 years, including 2206 ischemic strokes and 237 hemorrhagic strokes. The multivariable Cox regression analysis indicated that age 50 to 59 years (versus 40-49 years), primary school or no formal education (versus middle school), having >1 child (versus 1 child), living in Northeast, Central, East, or North China (versus Southwest China), physical inactivity, hypertension, diabetes mellitus, and obesity were positively associated with the risk of total and ischemic stroke, whereas age 60 to 69 years and living with spouse or children (versus living alone) were negatively associated with the risk of total and ischemic stroke. Men, vegetable-based diet, underweight, physical inactivity, hypertension, living in a high-income region, having Urban Resident Basic Medical Insurance, and New Rural Cooperative Medical System were positively associated with the risk of hemorrhagic stroke, whereas age 60 to 69 years was negatively associated with the risk of hemorrhagic stroke. Conclusions We identified socioeconomic factors that complement traditional risk factors for incident stroke and its subtypes, allowing targeting these factors to reduce stroke burden.
Background There has been significant controversy regarding the effects of pre-hospitalization use of renin-angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID-19 patients. Methods and Results We retrospectively assessed 2,297 hospitalized COVID-19 patients at Tongji Hospital in Wuhan, China, from January 10(th) to March 30(th), 2020; and identified 1,182 patients with known hypertension on pre-hospitalization therapy. We compared the baseline characteristics and in-hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non-RAS inhibitors (N=827). Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs. 95/827 (11.5%) patients in the non-RAS inhibitors group (p<0.0001). Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15-0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non-RAS inhibitors group. Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non-RAS inhibitors group. The RAS inhibitors group compared with non-RAS inhibitors group had lower levels of C-reactive protein (median 13.5 vs. 24.4 pg/mL; p=0.007) and interleukin-6 (median 6.0 vs. 8.5 pg/mL; p=0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta-analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29-0.65, p<0.0001). Conclusions In a large single center retrospective analysis we observed a protective effect of pre-hospitalization use of RAS inhibitors on mortality in hypertensive COVID-19 patients; which might be associated with reduced inflammatory response.
Background Cardiac hypertrophy (CH) is a physiological response that compensates for blood pressure overload. Under pathological conditions, hypertrophy can progress to heart failure as a consequence of the disorganized growth of cardiomyocytes and cardiac tissue. USP10 (ubiquitin-specific protease 10) is a member of the ubiquitin-specific protease family of cysteine proteases, which are involved in viral infection, oxidative stress, lipid drop formation, and heat shock. However, the role of USP10 in CH remains largely unclear. Here, we investigated the roles of USP10 in CH. Methods and Results Cardiac-specific USP10 knockout (USP10-CKO) mice and USP10-transgenic (USP10-TG) mice were used to examined the role of USP10 in CH following aortic banding. The specific functions of USP10 were further examined in isolated cardiomyocytes. USP10 expression was increased in murine hypertrophic hearts following aortic banding and in isolated cardiomyocytes in response to hypertrophic agonist. Mice deficient in USP10 in the heart exhibited exaggerated cardiac hypertrophy and fibrosis following pressure overload stress, which resulted in worsening of cardiac contractile function. In contrast, cardiac overexpression of USP10 protected against pressure overload-induced maladaptive CH. Mechanistically, we demonstrated that USP10 activation and interaction with Sirt6 in response to angiotensin II led to a marked increase in the ubiquitination of Sirt6 and resulted in Akt signaling downregulation and attenuation of cardiomyocyte hypertrophy. Accordingly, inactivation of USP10 reduced Sirt6 abundance and stability and diminished Sirt6-induced downstream signaling in cardiomyocytes. Conclusions USP10 functions as a Sirt6 deubiquitinase that induces cardiac myocyte hypertrophy and triggers maladaptive CH.
Background A combination of clinical and electrocardiographic risk factors is used for risk stratification in Brugada syndrome. In this study, we tested the hypothesis that the incorporation of latent variables between variables using nonnegative matrix factorization can improve risk stratification compared with logistic regression. Methods and Results This was a retrospective cohort study of patients presented with Brugada electrocardiographic patterns between 2000 and 2016 from Hong Kong, China. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation. The external validation cohort included patients from 3 countries. A total of 149 patients with Brugada syndrome (84% males, median age of presentation 50 [38-61] years) were included. Compared with the nonarrhythmic group (n=117, 79%), the spontaneous ventricular tachycardia/ ventricular fibrillation group (n=32, 21%) were more likely to suffer from syncope (69% versus 37%, P=0.001) and atrial fibrillation (16% versus 4%, P=0.023) as well as displayed longer QTc intervals (424 [399-449] versus 408 [386-425]; P=0.020). No difference in QRS interval was observed (108 [98-114] versus 102 [95-110], P=0.104). Logistic regression found that syncope (odds ratio, 3.79; 95% CI, 1.64-8.74; P=0.002), atrial fibrillation (odds ratio, 4.15; 95% CI, 1.12-15.36; P=0.033), QRS duration (odds ratio, 1.03; 95% CI, 1.002-1.06; P=0.037) and QTc interval (odds ratio, 1.02; 95% CI, 1.01-1.03; P=0.009) were significant predictors of spontaneous ventricular tachycardia/ventricular fibrillation. Increasing the number of latent variables of these electrocardiographic indices incorporated from n=0 (logistic regression) to n=6 by nonnegative matrix factorization improved the area under the curve of the receiving operating characteristics curve from 0.71 to 0.80. The model improves area under the curve of external validation cohort (n=227) from 0.64 to 0.71. Conclusions Nonnegative matrix factorization improves the predictive performance of arrhythmic outcomes by extracting latent features between different variables.
Background Long-term use of antiplatelet agents after acute coronary syndrome in diabetic patients is not well known. Here, we describe antiplatelet use and outcomes in such patients enrolled in the EPICOR Asia (Long-Term Follow-up of Antithrombotic Management Patterns in Acute Coronary Syndrome Patients in Asia) registry. Methods and Results EPICOR Asia is a prospective, observational study of 12 922 patients with acute coronary syndrome surviving to discharge, from 8 countries/regions in Asia. The present analysis included 3162 patients with diabetes mellitus (DM) and 9602 patients without DM. The impact of DM on use of antiplatelet agents and events (composite of death, myocardial infarction, and stroke, with or without any revascularization; individual components, and bleeding) was evaluated. Significant baseline differences were seen between patients with DM and patients without DM for age, sex, body mass index, cardiovascular history, angiographic findings, and use of percutaneous coronary intervention. At discharge, approximate to 90% of patients in each group received dual antiplatelet therapy. At 2-year follow-up, more patients with DM tended to still receive dual antiplatelet therapy (60% versus 56%). DM was associated with increased risk from ischemic but not major bleeding events. Independent predictors of the composite end point of death, myocardial infarction, and stroke in patients with DM were age >= 65 years and use of diuretics at discharge. Conclusions Antiplatelet agent use is broadly comparable in patients with DM and patients without DM, although patients with DM are more likely to be on dual antiplatelet therapy at 2 years. Patients with DM are at increased risk of ischemic events, suggesting an unmet need for improved antithrombotic treatment. Registration URL: ; Unique identifier: NCT01361386.