Circulating N-terminal pro-B-type natriuretic peptide (NT pro-BNP), high- sensitivity C-reactive protein (hs-CRP) and big endothelin (big-ET) have been shown to be increased in heart failure and to contribute to both hemodynamic deterioration and cardiovascular remodeling. Here, we examined the prognostic value of the three neurohormones at admission in a population of hospitalized patients with dilated cardiomyopathy (DCM).

The effects of chlorogenic acid (CGA) on growth performance, intestinal morphology, antioxidant capacity, and the autophagy-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in oxidatively stressed broilers were investigated. A total of 400 one-day-old male Cobb broilers were divided randomly into 4 groups using a 2 × 2 factorial arrangement with 2 CGA supplemental levels (0 and 500 mg/kg) and 2 dexamethasone (DEX) challenge levels (0 and 3 mg/kg body weight). All the broilers were injected intraperitoneally with DEX or sterile saline beginning at the age of 15 d for 6 consecutive days. The experiment lasted for 21 d. The CGA increased average daily gain (ADG), villus height, villus height/crypt depth (V/C) value, and the protein expressions of Occludin and ZO-1 in the ileum and decreased the feed:gain (F:G) ratio, which were impaired by the DEX challenge. Superoxide dismutase (SOD), catalase (CAT), gutathione S-transferase (GST), and heme oxygenase-1 (HO-1) activities in the serum and ileum were increased by CGA, whereas protein carboxyl (PCO) level in the serum and ileum, and malondialdehyde (MDA) level in the ileum were decreased of the DEX challenged broilers. The DEX challenge decreased microtubule-associated protein 1 light chain 3 ( LC3 )-II, Beclin1, and autophagy-related gene ( ATG ) 7 mRNA expressions, and the LC3-II/LC3-I value and increased LC3-I, cysteinyl aspartate specific proteinase ( Caspase )-3 and Caspase-9 mRNA expressions in the ileum, which were improved by CGA. DEX also decreased the protein expressions of Kelch-like ECH-associated protein-1 (Keap1), Nrf2, HO-1, NADPH quinone oxidoreductase-1(NQO-1) and increased sequestosome 1 (p62) in the ileum, which were improved by CGA. Interactions occurred between DEX and CGA for the ADG, F:G ratio, villus height, crypt depth, V/C value, and SOD, CAT, GST, and HO-1 activities, MDA and PCO levels, LC3-II/LC3-I value, and expressions of LC3-I, LC3-II, Beclin1, ATG7, Caspase-3, Caspase-9, Occludin, ZO-1, Keap1, Nrf2, HO-1, NQO-1, and p62. In conclusion, CGA improved the growth performance and intestinal health of oxidatively stressed broilers by activating the autophagy-mediated Nrf2 pathway.

The mechanisms whereby ambient air pollution and temperature changes promote cardiac events remain incompletely described. Seventy-three nonsmoking healthy adults (mean age 23.3, SD 5.4 years) were followed with up to four repeated visits across 15 months in Beijing in 2014–2016. Biomarkers relevant to myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI]), inflammation (growth differentiation factor-15 [GDF-15]), and oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG]) were measured at each visit, while ambient air pollution and temperature were monitored throughout the study. Linear mixed-effects models coupled with distributed lag nonlinear models were used to assess the impacts of each exposure measure on study outcomes. During follow-up, average daily concentrations of fine particulate matter and outdoor temperature were 62.9 µg/m³ (8.1–331.0 µg/m³) and 10.1 °C (−6.5°C to 29.5°C). Serum hs-cTnI levels were detectable in 18.2% of blood samples, with 27.4% of individuals having ≥1 detectable values. Higher levels of ambient particulates and gaseous pollutants (per interquartile range) up to 14 days before clinical visits were associated with significant alterations in hs-cTnI levels of 22.9% (95% CI, 6.4, 39.4) to 154.7% (95% CI, 94.4, 215.1). These changes were accompanied by elevations of circulating GDF-15 and urinary 8-OHdG levels. Both low (5th percentile, −2.5 °C) and high (95th percentile, 24.8°C) outdoor temperatures, with breakpoint at ~13.0°C as the reference level, were also associated with elevations of hs-cTnI levels. Short-term exposure to ambient air pollution and temperature was associated with cardiac troponin, a biomarker of myocardial damage, along with increased inflammation and oxidative stress responses. These findings extend our understanding of the biological mechanisms linking pervasive environmental exposure to adverse cardiac events.

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) showed significant reductions in death and cardiovascular disease (CVD) risk with a systolic blood pressure (SBP) goal of <120 mm Hg compared with a SBP goal of <140 mm Hg. Our study aimed to assess the applicability of SPRINT to Chinese adults. Additionally, we sought to predict the medical and economic implications of this intensive SBP treatment among those meeting SPRINT eligibility.Methods and findings: We used nationally representative baseline data from the China Health and Retirement Longitudinal Study (CHARLS) (2011–2012) to estimate the prevalence and number of Chinese adults aged 45 years and older who meet SPRINT criteria. A validated microsimulation model was employed to project costs, clinical outcomes, and quality-adjusted life-years (QALYs) among SPRINT-eligible adults, under 2 alternative treatment strategies (SBP goal of <120 mm Hg [intensive treatment] and SBP goal of <140 mm Hg [standard treatment]). Overall, 22.2% met the SPRINT criteria, representing 116.2 (95% CI 107.5 to 124.8) million people in China. Of these, 66.4%, representing 77.2 (95% CI 69.3 to 85.0) million, were not being treated for hypertension, and 22.9%, representing 26.6 (95% CI 22.4 to 30.7) million, had a SBP between 130 and 139 mm Hg, yet were not taking antihypertensive medication. We estimated that over 5 years, compared to standard treatment, intensive treatment would reduce heart failure incidence by 0.84 (95% CI 0.42 to 1.25) million cases, reduce CVD deaths by 2.03 (95% CI 1.44 to 2.63) million cases, and save 3.84 (95% CI 1.53 to 6.34) million life-years. Estimated reductions of 0.069 (95% CI −0.28, 0.42) million myocardial infarction cases and 0.36 (95% CI −0.10, 0.82) million stroke cases were not statistically significant. Furthermore, over a lifetime, moving from standard to intensive treatment increased the mean QALYs from 9.51 to 9.87 (an increment of 0.38 [95% CI 0.13 to 0.71]), at a cost of Int$10,997 per QALY gained. Of all 1-way sensitivity analyses, high antihypertensive drug cost and lower treatment efficacy for CVD death resulted in the 2 most unfavorable results (Int$25,291 and Int$18,995 per QALY were gained, respectively). Simulation results indicated that intensive treatment could be cost-effective (82.8% probability of being below the willingness-to-pay threshold of Int$16,782 [1× GDP per capita in China in 2017]), with a lower probability in people with SBP 130–139 mm Hg (72.9%) but a higher probability among females (91.2%). Main limitations include lack of specific SPRINT eligibility information in the CHARLS survey, uncertainty about the implications of different blood pressure measurement techniques, the use of several sources of data with large reliance on findings from SPPRINT, limited information about the serious adverse event rate, and lack of information and evidence for medication effectiveness on renal disease.Conclusions: Although adoption of the SPRINT treatment strategy would increase the number of Chinese adults requiring SBP treatment intensification, this approach has the potential to prevent CVD events, to produce gains in life-years, and to be cost-effective under common thresholds.

Evidence on whether an excess risk of incidence and mortality of cardiovascular disease (CVD) among people exposed to a high level of ambient PM_2.5 in low- and middle-income countries (LMICs) is lacking. This study aimed to investigate the associations between long-term exposure to ambient fine particulate matter<2.5 µm (PM_2.5) concentrations and the risk of incidence and mortality of CVD in a large cohort study from 115 communities. In this cohort study, we followed 42 160 adults aged 35-75 years at baseline who enrolled in the Prospective Urban and Rural Epidemiology Study conducted in China (PURE-China) between 2005 and 2009 with ambient PM_2.5 estimates, and followed up until August 2021. Cox proportional hazards frailty models were used to estimate the associations between long-term mean outdoor PM_2.5 concentrations and CVD events, CVD mortality, and all-cause mortality. During a median follow-up period of 11.8 years, we documented 2 190 deaths, including 732 CVD deaths. There were 4 559 (10.8 %) of 42 160 participants who experienced incident total CVD, among them there were 861 myocardial infarctions (MI) and 2 338 S. The 3-year median concentration of ambient PM_2.5 before the cohort commencement was 52.7 µg/m³ (interquartile range [IQR] 30.3-74.6). In full adjusted model, a 10 µg/m³ increase in PM_2.5 was associated with a hazard ratio (HR) of 1.12 (95 % CI 1.11-1.14) for major CVD and 1.03 (95 % CI 1.01-1.05) for all-cause mortality. Besides, long-term PM_2.5 concentrations had a significantly positive gradient association with total CVD and a similar pattern of associations with other CVD outcomes was observed. This study demonstrated that long-term ambient PM_2.5 concentrations is positively associated with increased risks of CVD in adults aged 35-70 years from China. This finding reinforces the need for policymakers to adopt more effective strategies to improve air quality.

Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is essential for normal heart function and protects the heart from ischemia-reperfusion (I/R) injury. It is known that protein kinase-A (PKA)-mediated phosphorylation of cMyBP-C prevents I/R-dependent proteolysis, whereas dephosphorylation of cMyBP-C at PKA sites correlates with its degradation. While sites on cMyBP-C associated with phosphorylation and proteolysis co-localize, the mechanisms that link cMyBP-C phosphorylation and proteolysis during cardioprotection are not well understood. Therefore, we aimed to determine if abrogation of cMyBP-C proteolysis in association with calpain, a calcium-activated protease, confers cardioprotection during I/R injury. Calpain is activated in both human ischemic heart samples and ischemic mouse myocardium where cMyBP-C is dephosphorylated and undergoes proteolysis. Moreover, cMyBP-C is a substrate for calpain proteolysis and cleaved by calpain at residues 272-TSLAGAGRR-280, a domain termed as the calpain-target site (CTS). Cardiac-specific transgenic (Tg) mice in which the CTS motif was ablated were bred into a cMyBP-C null background. These Tg mice were conclusively shown to possess a normal basal structure and function by analysis of histology, electron microscopy, immunofluorescence microscopy, Q-space MRI of tissue architecture, echocardiography, and hemodynamics. However, the genetic ablation of the CTS motif conferred resistance to calpain-mediated proteolysis of cMyBP-C. Following I/R injury, the loss of the CTS reduced infarct size compared to non-transgenic controls. Collectively, these findings demonstrate the physiological significance of calpain-targeted cMyBP-C proteolysis and provide a rationale for studying inhibition of calpain-mediated proteolysis of cMyBP-C as a therapeutic target for cardioprotection.