Independent Predictor Of Cardiovascular Mortality Research Articles

Serum angiopoietin-2/angiopoietin-1 ratio is associated with cardiovascular and all-cause mortality in peritoneal dialysis patients: a prospective cohort study

Introduction Our objective was to examine the factors associated with the serum angiopoietin-2/angiopoietin-1 (Angpt-2/Angpt-1) ratio in peritoneal dialysis (PD) patients and to investigate the association between Angpt-2/Angpt-1 ratio and cardiovascular and all-cause mortality. Methods Patients on PD who were prevalent between January 2014 and April 2015 in the center of Renji Hospital were enrolled. At the time of enrollment, serum and dialysate samples were collected to detect biochemical parameters, serum angiopoietin-2 and angiopoietin-1 levels. Patients were dichotomized into two groups according to a median of Angpt-2/Angpt-1 ratio and followed up prospectively until the end of the study. Results A total of 325 patients were enrolled, including 168 males (51.7%) with a mean age of 56.9 ± 14.2 years and a median PD duration of 32.4 (9.8-55.9) months. Multiple linear regression showed pulse pressure (β = 0.206, p < .001) and high-sensitivity C-reactive protein (hs-CRP) (β = 0.149, p = .011) were positively correlated with serum Angpt-2/Angpt-1 ratio, while residual renal function (RRF) (β= −0.219, p < .001) was negatively correlated with serum Angpt-2/Angpt-1 ratio. Multivariate Cox regression analysis showed the high serum Angpt-2/Angpt-1 ratio was an independent predictor of cardiovascular mortality (hazard ratio (HR)=2.467, 95% confidence interval (CI) 1.243–4.895, p = .010) and all-cause mortality (HR = 1.486, 95%CI 1.038–2.127, p = .031). In further subgroup analysis by gender, a significant association was shown in high Angpt-2/Angpt-1 ratio with all-cause mortality in male (p < .05), but not in female patients (p>.05). Conclusions High Angpt-2/Angpt-1 ratio is an independent risk factor for cardiovascular and all-cause mortality in PD patients.

Cardiovascular Mortality Risk among Patients with Liver Cancer: A SEER Database Study.

Data sourced from the Surveillance, Epidemiology, and End Results (SEER) database encompassing liver cancer diagnoses from 2000 to 2017 were utilized. The standardized mortality rate (SMR) was computed using general population reference data, and multivariate competing risk models were employed for analysis. Analysis of 70,733 liver cancer patient records revealed 1,954 instances of CVM. The overall CVM SMR for liver cancer patients was 12.01 (95% CI: 11.48-12.55). Various demographic and clinical factors, including sex, race, age, year of diagnosis, pathological type, general stage, treatment modalities, and matrimonial status, emerged as liver cancer pa-tients` independent predictors of CVM. Liver cancer patients have a notably heightened susceptibility to cardiovascular mortality (CVM) in contrast to the general populace. It is imperative to promptly recognize high-risk subcategories and execute tailored cardiovascular interventions as crucial measures to bolster survival rates within this cohort of patients.

Left ventricular late diastolic strain rate predicts cardiovascular mortality in patients with heart failure with reduced ejection fraction

Abstract Background Left ventricular (LV) strain rate measures provide detailed information regarding LV contraction and filling pressures. These include global systolic strain rate (GSRs), early and late diastolic strain rates (GSRe and GSRa), and ratio of transmitral early filling velocity to GSRe (E/GSRe). Purpose To investigate the prognostic value of strain rate measures with regard to cardiovascular mortality in patients with heart failure with reduced ejection fraction (HFrEF). Methods The study population was retrospectively included from a HF clinic and consisted of patients with LV ejection fraction (LVEF) ≤45%. Echocardiography was obtained within 1 year of referral. The study endpoint was cardiovascular mortality, which was analysed using univariable and adjusted Cox proportional hazards models. Incremental prognostic information was assessed using Harrell’s C-index and continuous net reclassification improvement (NRI). Cubic spline analysis was used to dichotomise variables at a hazard ratio (HR) of 1 for better interpretability. Results The final study population consisted of 1160 patients with HFrEF (mean age 68±11.8 years, 72.7% male, LV ejection fraction (LVEF) 28.6±9.9%). During follow-up (median 10.1 years, IQR: 4.7-13.0), 333 (28.7%) met the outcome. Subjects who met the outcome generally had higher age and prevalence of male sex, a higher burden of comorbidities, and more severely impaired conventional echocardiographic parameters. All four strain rate measures were significantly associated with cardiovascular mortality (GSRs: HR 16.88 95% CI [8.42, 33.84] per 1 s-1 increase, GSRe: HR 0.29 [0.18, 0.47] per 1 s-1 increase, E/GSRe ratio: HR 1.31 [1.22, 1.41] per 1 unit increase, GSRa: HR 0.15 95% CI [0.23, 0.65] per 1 s-1 increase, p&amp;lt;0.0001 for all). However, only GSRa remained an independent predictor in multivariable Cox regression after adjustment for clinical risk factors including sex, age, mean arterial pressure, heart rate, body mass index, cigarette pack years, diabetes mellitus, total cholesterol, ischemic heart disease, and echocardiographic factors including LVEF, global longitudinal strain, tricuspid annular plane systolic excursion, LV mass index, LV internal diameter index, E/e’ ratio and left atrial volume index (HR 0.39 [0.23,0.65], p=0.0003). Furthermore, GSRa provided incremental prognostic information to a model containing all aforementioned parameters (Harrell’s C-index 0.789 vs. 0.792 and continuous NRI 0.158). GSRa was dichotomised at 0.5 s-1, and a Kaplan-Meier curve stratified according to this was plotted (log rank p&amp;lt;0.0001)(Figure 2). Conclusion GSRa is an independent predictor of cardiovascular mortality in patients with HFrEF after multivariable adjustment. GSRa provides incremental prognostic value over conventional echocardiographic measures in risk stratification of HFrEF patients. Our results suggest an increased risk of cardiovascular mortality associated with a GSRa below 0.5 s-1.Figure 1:Spline of HR according to GSRaFigure 2:Kaplan-Meier curve

Lifestyle Habits and Risk of Cardiovascular Mortality in Menopausal Women with Cardiovascular Risk Factors: A Retrospective Cohort Study.

Current cardiovascular prevention guidelines emphasise considering sex, gender, and gender identity in risk assessment. This study evaluated the impact of lifestyle habits and chronic diseases on cardiovascular mortality risk in women over 50 with high vascular risk and developed a predictive model for menopausal women with cardiovascular risk factors. A retrospective cohort study used data from the 2011 Spanish National Health Survey and the national death register, focusing on menopausal and postmenopausal women without prior cardiovascular events but with at least one major risk factor. Participants were followed for up to 10 years, assessing mortality from circulatory system diseases and other causes. Exposure variables included socio-demographics, lifestyle habits, health status, self-perceived health, health service use, and pharmacological treatments. Of the 21,007 respondents, 3057 women met the inclusion criteria. The 10-year cumulative incidence of mortality from circulatory causes was 5.9%, and from other causes, 12.7%. Independent predictors of cardiovascular mortality were never consuming legumes, poor self-perceived health, diabetes treatment, lack of physical activity, and older age. Lipid-lowering treatment was protective. The model demonstrated good fit and predictive capacity (C-index = 0.773). This study highlights the significant influence of physical activity, legume consumption, self-perceived health, and specific treatments on cardiovascular mortality risk in menopausal women.

Arterial stiffness as a screening tool for cardiovascular risk in health and disease.

Cardiovascular diseases (CVD) account for approximately one-third of all deaths worldwide. The incidence of cardiovascular events such as myocardial infraction has been reported to be progressively increasing with age, especially with existing comorbidities such as hypertension, diabetes and obesity. Assessing arterial stiffness indices may serve as a screening tool in identification of population at risk of cardiovascular diseases and assist in implementation of preventive measures and early treatment in this population. To measure and compare the arterial stiffness indices in healthy adults with diabetes, hypertension and obesity. A total of 184 adults in the age group of 30-50 years were included in the study who were divided into 4 groups: Group I (n = 64) (diabetic), group II (n = 40) (hypertensives), group III (n = 40) (obese) and group IV (n = 40) (control). The arterial stiffness indices were measured by using a certified oscillometric device in all the participants. The arterial stiffness indices were assessed by using a certified oscillometric device in all the participants. The mean values of right baPWV and left baPWV are found to be significantly higher in hypertensive subjects compared with obese, diabetic and healthy controls. The pulse wave velocity, ASI and pulse pressure serve as independent predictors of cardiovascular mortality and outcomes in hypertension, diabetes and obesity as well as healthy individuals.

Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

Estimated Pulse Wave Velocity and All-Cause and Cardiovascular Mortality in the General Population.

Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 - 0.402 × age + 4.560 × 10-3 × age2 - 2.621 × 10-5 × age2 × MBP + 3.176 × 10-3 × age × MBP - 1.832 × 10-2 × MBP. MBP= (DBP) + 0.4(SBP - DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118-8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.

#452 Cardiac troponins are independent predictors of cardiovascular mortality in haemodialysis patients

Abstract Background and Aims Patients with end-stage kidney disease (ESKD) and haemodialysis treatment (HD) have a high risk of cardiovascular (CV) events. The underlying pathophysiology is complex and multifactorial. This study aimed to explore the role of high-sensitivity cardiac Troponin I (hs-cTnI) as a predictor of major adverse cardiac events (MACE), CV- and all-cause mortality. Method A retrospective analysis using data from the AURORA study (CT00240331). Association with baseline hs-cTnI and MACE, CV- and all-cause mortality were assessed using Cox-regression analyses. The analyses were adjusted for multiple background factors and available biomarkers. hs-cTnI was log2 transformed and modelled using a four knot restricted cubic spline. The hazard ratio [HR] estimates are presented for the upper quartile (32.6 pg/mL) vs the lower quartile (10.1 pg/mL) of the distribution of hs-cTnI. Variables were ordered by variable importance in the models using χ2 value minus degrees of freedom. Results During the follow-up, there were 1094 total deaths of which 598 were CV deaths, and 734 MACE in patients with hsTnI measurements available at baseline. Baseline hs-cTnI was associated with an increased risk for MACE (HR 1.92; 95% Confidence interval [CI] 1.57-2.35), CV mortality (HR 2.12; 95% CI 1.69-2.66), all-cause mortality (HR 1.84; 95% CI 1.55-2.17) and non-CV mortality (HR 1.59; 95% CI 1.23-2.05) after adjustments for age, ethnicity, sex, smoking status, diabetes status, history of coronary heart disease, atrial fibrillation, blood pressure, heart rate, height, weight, years on HD, hemoglobin, cholesterol, LDL-C, HDL-C, triglycerides, hs-CRP, creatinine, albumin, phosphate, erythropoietin treatment, ACE -inhibitor use, anticoagulation treatment, treatment with rosuvastatin, sevelamer use, iron supplements, ferritin, transferrin, galectin-3, pro-BNP, CICP and SCF. When ranking variables by variable importance, hs-cTnI was the strongest predictor for MACE (Fig. 1), CV- and all-cause mortality. For non-CV mortality age was the most important variable. Conclusion Baseline hs-cTnI, is a strong and independent risk marker for MACE and all-cause mortality in patients with haemodialysis treatment.

Social Isolation, Loneliness, and Cardiovascular Mortality: The Role of Health Care System Interventions.

The world is proliferating rapidly, with science and technology advancing at an incredible rate. These advances have, however, ushered in an age with a rise in social isolation (SI) and loneliness. SI is an objective term that refers to lacking social contact or support. On the other hand, loneliness is subjective and refers to feeling alone or isolated. These concepts are rapidly gaining prominence mainly due to their negative impact on the physical and psychological health of the population, mainly through behavioural modifications that encompass substance abuse, decreased physical activity and unhealthy food habits, and poor sleep hygiene. This review summarizes the pathophysiology, evaluates the evidence behind impact of SI on cardiovascular mortality, and interventions to overcome SI. Through proposed mechanisms, such as activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, both SI and loneliness have strong evidence linking them to cardiovascular morbidity and mortality. A systematic review and meta-analysis of 90 prospective cohort studies including 2,205,199 individuals reported that SI was independent predictor of cardiovascular mortality with a point estimate of 1.34 (95% confidence interval:1.25-1.44). The evidence so far is compelling and necessitates urgent action with the implementation of strict policies to tackle this issue. As healthcare professionals, it becomes even more critical to remain vigilant, recognize this insidious pandemic, and take appropriate action.

Coronary microvascular dysfunction in patients undergoing transcatheter aortic valve implantation

ObjectivesThis study aimed to evaluate the prognostic value of coronary microvascular dysfunction (CMD) at long term after transcatheter aortic valve implantation (TAVI) and to explore its relationship with extravalvular cardiac...

Association between estimated pulse wave velocity and in-hospital mortality of patients with acute kidney injury: a retrospective cohort analysis of the MIMIC-IV database

Background Estimated pulse wave velocity (ePWV) has been found to be an independent predictor of cardiovascular mortality and kidney injury, which can be estimated noninvasively. This study aimed to investigate the association between ePWV and in-hospital mortality in critically ill patients with acute kidney injury (AKI). Methods This study included 5960 patients with AKI from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The low and high ePWV groups were compared using a Kaplan-Meier survival curve to evaluate the differences in survival status. Cox proportional hazards models were used to explore the association between ePWV and in-hospital mortality in critically ill patients with AKI. To further examine the dose-response relationship, we used a restricted cubic spline (RCS) model. Stratification analyses were conducted to investigate the effect of ePWV on hospital mortality across various subgroups. Results Survival analysis indicated that patients with high ePWV had a lower survival rate than those with low ePWV. Following adjustment, high ePWV demonstrated a statistically significant association with an increased risk of in-hospital mortality among AKI patients (HR = 1.53, 95% CI = 1.36-1.71, p < 0.001). Analysis using the RCS model confirmed a linear increase in the risk of hospital mortality as the ePWV values increased (P for nonlinearity = 0.602). Conclusions A high ePWV was significantly associated with an increased risk of in-hospital mortality among patients with AKI. Furthermore, ePWV was an independent predictor of in-hospital mortality in critically ill patients with AKI.

Increased cardiovascular mortality in patients with mechanically expandable transcatheter aortic valve and without permanent pacemaker

IntroductionUse of the mechanically expandable transcatheter aortic valve (MEV) has been recently linked to increased risks of valve dysfunction and cardiovascular mortality. The risk of developing conduction disturbance with the...

Competing risk analysis of cardiovascular death in breast cancer: evidence from the SEER database.

Cardiovascular disease (CVD) is the leading cause of death for all non-cancer deaths among breast cancer (BC) patients. The aim of this study was to investigate the risk of cardiovascular mortality (CVM) in patients with BC. Patients diagnosed with primary BC between 2010 and 2018 were identified through the Surveillance, Epidemiology and End Results (SEER) database. The standardized mortality ratio (SMR) for CVD was calculated to compare the CVM of BC patients with that of the general population. Multivariate competing risk models were performed to identify predictors of CVM in BC patients. Overall, 399,014 BC patients were included from the SEER database, of whom 7,023 (1.8%) suffered death from CVD. The significantly higher overall SMR of CVM was observed in BC patients [SMR =4.84, 95% confidence interval (CI): 4.72-4.95]. Multivariate competing risk regression analysis revealed that age, race, American Joint Committee on Cancer (AJCC) stage, year of diagnosis, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, BC subtype, surgery, chemotherapy, radiation therapy, and median household income as independent predictors of CVM in BC patients. Compared to the general population, BC patients have a higher risk of experiencing CVM during the follow-up period after diagnosis. Early detection and intervention of cardiovascular risk factors would improve overall survival (OS) of BC patients.

Meteorin-like plasma levels as a novel biomarker for heart failure

Abstract Introduction Meteorin-like (metrnl), a new adipokine with insulin-sensitizing and anti-inflammatory action, has recently drawn much attention due to its protective effects in the cardiovascular system. Metrnl promotes heart repair after insults like ischemia/reperfusion, cardiotoxicity, or diabetic cardiomyopathy in mice, and its circulating levels in patients have been associated with the presence and severity of coronary artery disease and heart failure, although in the latter with contradictory results. Purpose Our aim was to study the correlation between plasma metrnl levels and biochemical and echocardiographic parameters in patients hospitalized with de novo heart failure (HF) to determine whether this adipokine could be a useful biomarker/therapeutic target for HF. Methods Blood samples of 400 patients hospitalized with de novo HF were collected in a multicenter clinical study. Plasma levels of metrnl were measured by enzyme-linked immunosorbent assay. Results In de novo HF patients, metrnl plasma levels were positively correlated with age (r = 0.322, P &amp;lt; 0.0001), NT-proBNP (r = 0.293, P &amp;lt; 0.0001), troponin (r = 0.192, P &amp;lt; 0.001), creatinine (r = 0.353, P &amp;lt; 0.0001) and urea (r = 0.322, P &amp;lt; 0.0001), while negatively correlated with albumin (r = -0.308, P &amp;lt; 0.0001) and alanine aminotransferase (r = -0.183, P &amp;lt; 0.0001). Metrnl plasma levels were also positively correlated with echocardiographic data of cardiac morphology as intraventricular septum thickness (r = 0.197, P &amp;lt; 0.0001) and left ventricular posterior wall thickness (r = 0.150, P &amp;lt; 0.004). On the other hand, Cox regression analysis suggested that higher plasma metrnl was associated with increased cardiovascular mortality (HR, 1.004, P &amp;lt; 0.004)) and rate of readmission for HF (HR, 1.002, P &amp;lt; 0.008). Regarding the different types of HF, we found that metrnl plasma levels were lower in HF with reduced ejection fraction (HFrEF) in comparison those with preserved ejection fraction (HFpEF) [408.06 (354.05 - 537.71) pg/mL vs. 486.06 (391.94 – 607.80), median (interquartile range), respectively; P &amp;lt; 0.0001]. Conclusion Metrnl plasma levels were associated with markers of cardiac (troponin), renal (creatinine and urea) and hepatic (alanine aminotransferase and albumin) damage. The HF marker NT-proBNP and the echocardiographic parameters intraventricular septum thickness and left ventricular posterior wall thickness are also linked to metrnl plasma levels. Moreover, metrnl levels were found to be independent predictors of cardiovascular mortality and readmission for heart failure. And finally, metrnl plasma levels in patients hospitalized with de novo HF were increased in patients with HFpEF vs. HFrEF. Our results reinforce the relevance of the adipokine metrnl in the pathophysiology and diagnosis of HF, and supports its possible use in the future as biomarker/therapeutic target for HF.

Abstract 13430: Cardiovascular Magnetic Resonance Imaging for Comprehensive Risk Assessment in Patients With Aortic Stenosis

Introduction: Precise risk assessment is essential for accurate management of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). This study aimed to assess the prognostic implications of cardiovascular magnetic resonance (CMR)-derived imaging biomarkers in a large cohort of AS patients. Methods: 145 patients with severe AS underwent CMR imaging before TAVR. Image analyses included myocardial volumes, CMR-feature-tracking derived left and right atrial (LA &amp; RA) as well as left and right ventricular (LV &amp; RV) strain, myocardial T1 mapping as well as late gadolinium enhancement analyses. Cardiovascular (CV) mortality was defined as primary clinical endpoint. Results: Patients with CV death during follow-up had significantly enlarged RV enddiastolic volumes (82.9ml/ml 2 [70.8-96.0] vs. 62.8ml/ml 2 [54.7-76.0], p&lt;0.001) and impaired strain values of all cardiac chambers compared to patients that survived (LV GLS: -18.1% [-13.1- -20.4] vs. -22.5% [-16.1- -27.3], p=0.019; RV GLS: -22.9% [-18.6 - -25.4] vs. -27.9% [-22.9- -32.0], p=0.002; LA Es: 9.5% [7.2 - 15.4] vs. 14.3% [9.0-18.1], p=0.036; RA Es: 12.4% [6.8-14.4] vs. 16.2% [11.2-22.1], p&lt;0.001). RA reservoir strain independently predicted CV mortality after adjusting for other CMR imaging biomarkers and clinical parameters of heart failure. Within patients with high ECV values especially RA strain further identified AS patients at high-risk for CV mortality (p=0.001 on log-rank testing). Conclusion: Comprehensive CMR-imaging allows accurate outcome assessment and additional identification of high-risk groups in AS patients. Especially RA strain emerged as independent predictor for cardiovascular mortality and might serve for future optimized patient management.

State-level economic uncertainty and cardiovascular disease deaths: evidence from the United States

The relationship between economic recessions and cardiovascular mortality has been widely explored. However, there is limited evidence on whether economic uncertainty alone is linked to cardiovascular disease deaths. This study examines the association between economic uncertainty and mortality from diseases of the circulatory system in the United States. We obtained monthly state-level mortality data from 2008 to 2017 and used indices capturing economic uncertainty from national/international sources and local sources. Panel data modelling was used to account for unobserved time-invariant differences between the states. Our findings suggest that economic uncertainty is independently linked to cardiovascular mortality. Uncertainty arising from national/international sources is associated with cardiovascular deaths, whereas the respective index capturing uncertainty from state/local sources is not. Deaths respond asymmetrically with respect to uncertainty fluctuations – with high levels of uncertainty driving the association. One- and two-month lagged uncertainty levels are also associated with mortality. Several robustness checks further validate the baseline findings. Overall, economic uncertainty is an independent predictor of cardiovascular mortality which appears to act as a psychosocial stressor and a short-term trigger. Public health strategies for cardiovascular disease need to consider factors driving economic uncertainty. Preventive measures and raising awareness can intensify in periods of economic uncertainty.

VEGFC ameliorates salt-sensitive hypertension and hypertensive nephropathy by inhibiting NLRP3 inflammasome via activating VEGFR3-AMPK dependent autophagy pathway.

Salt-sensitivity hypertension (SSHTN) is an independent predictor for cardiovascular mortality. VEGFC has been reported to be a protective role in SSHTN and hypertensive kidney injury. However, the underlying mechanisms remain largely unclear. The current study aimed to explore the protective effects and mechanisms of VEGFC against SSHTN and hypertensive nephropathy. Here, we reported that VEGFC attenuated high blood pressure as well as protected against renal inflammation and fibrosis in SSHTN mice. Moreover, VEGFC suppressed the activation of renal NLRP3 inflammasome in SSHTN mice. In vitro, we found VEGFC inhibited NLRP3 inflammasome activation, meanwhile, upregulated autophagy in high-salt-induced macrophages, while these effects were reversed by an autophagy inhibitor 3MA. Furthermore, in vivo, 3MA pretreatment weakened the protective effects of VEGFC on SSHTN and hypertensive nephropathy. Mechanistically, VEGF receptor 3 (VEGFR3) kinase domain activated AMPK by promoting the phosphorylation at Thr183 via binding to AMPK, thus enhancing autophagy activity in the context of high-salt-induced macrophages. These findings indicated that VEGFC inhibited NLRP3 inflammasome activation by promoting VEGFR3-AMPK-dependent autophagy pathway in high-salt-induced macrophages, which provided a mechanistic basis for the therapeutic target in SSHTN and hypertensive kidney injury.

Low levels of circulating methylated IRX3 are related to worse outcome after transcatheter aortic valve implantation in patients with severe aortic stenosis

BackgroundAortic stenosis (AS) is one of the most common cardiac diseases and major cause of morbidity and mortality in the elderly. Transcatheter aortic valve implantation (TAVI) is performed in such patients with symptomatic severe AS and reduces mortality for the majority of these patients. However, a significant percentage dies within the first two years after TAVI, such that there is an interest to identify parameters, which predict outcome and could guide pre-TAVI patient selection. High levels of cardiac fibrosis have been identified as such independent predictor of cardiovascular mortality after TAVI. Promoter hypermethylation commonly leads to gene downregulation, and the Iroquois homeobox 3 (IRX3) gene was identified in a genome-wide transcriptome and methylome to be hypermethylated and downregulated in AS patients. In a well-described cohort of 100 TAVI patients in which cardiac fibrosis levels were quantified histologically in cardiac biopsies, and which had a follow-up of up to two years, we investigated if circulating methylated DNA of IRX3 in the peripheral blood is associated with cardiac fibrosis and/or mortality in AS patients undergoing TAVI and thus could serve as a biomarker to add information on outcome after TAVI.ResultsPatients with high levels of methylation in circulating IRX3 show a significantly increased survival as compared to patients with low levels of IRX3 methylation indicating that high peripheral IRX3 methylation is associated with an improved outcome. In the multivariable setting, peripheral IRX3 methylation acts as an independent predictor of all-cause mortality. While there is no significant correlation of levels of IRX3 methylation with cardiac death, there is a significant but very weak inverse correlation between circulating IRX3 promoter methylation level and the amount of cardiac fibrosis. Higher levels of peripheral IRX3 methylation further correlated with decreased cardiac IRX3 expression and vice versa.ConclusionsHigh levels of IRX3 methylation in the blood of AS patients at the time of TAVI are associated with better overall survival after TAVI and at least partially reflect myocardial IRX3 expression. Circulating methylated IRX3 might aid as a potential biomarker to help guide both pre-TAVI patient selection and post-TAVI monitoring.Graphical abstract

Arterial Stiffness and its Impact on Cardiovascular Health.

Cardiovascular diseases are the leading cause of mortality globally. Identifying patients at risk is important to initiate preventive strategies. Over the last few decades, the role of the endothelium and its impact on arterial stiffness have been recognised as playing a pivotal role in cardiovascular disease. This review will focus on the effect of arterial stiffness in different patient cohorts with regard to cardiovascular morbidity and mortality, as well as its use in clinical practice. Arterial stiffness is associated with a range of cardiovascular risk factors and is an independent predictor of cardiovascular mortality. The gold standard for evaluating arterial stiffness is pulse wave velocity. Recently, cardio-ankle vascular index has been implemented as an easy and highly reproducible measure of arterial stiffness. Moreover, certain pharmacologic agents may modify arterial stiffness and alter progression of cardiovascular disease. The endothelium plays an important role in cardiovascular disease. Implementing assessment of arterial stiffness in clinical practice will improve stratification of patients at risk of cardiovascular disease and help modify disease progression.

Prevalence, Characteristics, and Prognostic Relevance of Donor-Transmitted Coronary Artery Disease in Heart Transplant Recipients

BackgroundThe reported prevalence of donor-transmitted coronary artery disease (TCAD) in heart transplantation (HT) is variable, and its prognostic impact remains unclear. ObjectivesThe goal of this study was to characterize TCAD in a contemporary multicentric cohort and to study its prognostic relevance. MethodsThis was a retrospective study of consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. Only patients with a coronary angiography (c-angio) within the first 3 months after HT were studied. Significant TCAD (s-TCAD) was defined as any stenosis ≥50% in epicardial coronary arteries, and nonsignificant TCAD (ns-TCAD) as stenosis <50%. Clinical outcomes were assessed by means of Cox regression and competing risks regression. Patients were followed-up for a median period of 6.3 years after c-angio. ResultsFrom a cohort of 1,918 patients, 937 underwent c-angio. TCAD was found in 172 patients (18.3%): s-TCAD in 65 (6.9%) and ns-TCAD in 107 (11.4%). Multivariable Cox regression analysis did not show a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P = 0.141); however, it was an independent predictor of cardiovascular mortality (adjusted HR: 2.25; 95% CI: 1.20-4.19; P = 0.011) and the combined event cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). No statistically significant impact of ns-TCAD on clinical outcomes was detected. The results were similar when reassessed by means of competing risks regression. ConclusionsTCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months; however, s-TCAD patients showed increased risk of cardiovascular death and MACE.