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Context: Aortic stiffness is increased in Marfan syndrome contributing to aortic dilatation and rupture, the major cause of premature death in this population. Angiotensin-converting enzyme inhibitors have been shown to reduce arterial stiffness.Objective: To determine whether perindopril therapy reduces aortic stiffness and attenuates aortic dilatation in patients with Marfan syndrome.Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial of 17 patients with Marfan syndrome (mean [SD], 33 [6] years) taking standard beta-blocker therapy, initiated in January 2004 and completed in September 2006, at Alfred Hospital Marfan Syndrome Clinic, Melbourne, Australia.Intervention: Patients were administered 8 mg/d of perindopril (n = 10) or placebo (n = 7) for 24 weeks.Main Outcome Measures: Indices of arterial stiffness were assessed via systemic arterial compliance, and central and peripheral pulse wave velocities. Aortic root diameters were assessed at 4 sites via transthoracic echocardiography.Results: Perindopril reduced arterial stiffness as indicated by increased systemic arterial compliance (mean [SEM], 0.33 [0.01] mL/mm Hg at baseline to 0.54 [0.04] mL/mm Hg at 24 weeks in perindopril group vs 0.30 [0.01] mL/mm Hg to 0.29 [0.01] mL/mm Hg in placebo group, P = .004), and reduced central (7.6 [0.4] m/s to 5.9 [0.3] m/s in perindopril group, P < .001 vs placebo) and peripheral (10.9 [0.4] m/s to 8.7 [0.4] m/s in perindopril group, P < .001 vs placebo) pulse wave velocities. In addition, perindopril significantly reduced aortic root diameters relative to placebo in both end-systole and end-diastole (P<.01 to P < .001 for all comparisons between groups). Although perindopril marginally reduced mean arterial pressure (from 81 [2] mm Hg to 80 [1] mm Hg in perindopril group vs 83 [2] mm Hg to 84 [3] mm Hg in placebo group, P = .004), the observed changes in both stiffness and left ventricular outflow tract diameter remained significant when mean arterial pressure was included as a covariate. Transforming growth factor beta (TGF-beta), which contributes to aortic degeneration in Marfan syndrome, was reduced by perindopril compared with placebo in both latent (59 [6] ng/mL to 45 [3] ng/mL in perindopril group, P = .01 vs placebo) and active (46 [2] ng/mL to 42 [1] ng/mL in perindopril group, P = .02 vs placebo) forms.Conclusions: Perindopril reduced both aortic stiffness and aortic root diameter in patients with Marfan syndrome taking standard beta-blocker therapy, possibly through attenuation of TGF-beta signaling. Large clinical trials are needed to assess the clinical benefit of angiotensin II blockade in Marfan syndrome.Trial Registration: clinicaltrials.gov Identifier: NCT00485368. [ABSTRACT FROM AUTHOR]

BACKGROUND: Folic acid reduces plasma homocysteine and may be an important therapy for preventing cardiovascular disease. A key mechanism may be the reduction of arterial stiffness. OBJECTIVE: The effect of folic acid supplementation on blood pressure and large artery stiffness was examined in relation to methylenetetrahydrofolate reductase (MTHFR) genotype. DESIGN: Forty-one asymptomatic men with normal or high-normal ambulatory blood pressure (systolic: >130 to <145 mm Hg; diastolic: >80 to <90 mm Hg) participated. The study had a randomized, placebo-controlled, double-blind, crossover design that incorporated 3-wk treatments with 5 mg folic acid/d or matching placebo; each treatment was separated by a 4-wk washout phase. RESULTS: Folic acid reduced brachial pulse pressure by 4.7 +/- 1.6 mm Hg (P < 0.05) without changing mean arterial pressure. Systemic arterial compliance increased by 0.15 +/- 0.03 mL/mm Hg (P < 0.05) after folic acid treatment but did not change after placebo treatment. These responses did not significantly correlate with either homocysteine or folate plasma concentrations. MTHFR genotype CC homozygotes (without the 677C-->T polymorphism) with normal blood pressure had a larger reduction in homocysteine concentrations in response to folic acid than did T allele carriers. Blood pressure and arterial stiffness responses were independent of MTHFR genotype. CONCLUSION: Folic acid is a safe and effective supplement that targets large artery stiffness and may prevent isolated systolic hypertension. Copyright © 2005 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

1 Treatment of eight healthy males with propranolol (80 mg twice daily) for 6 weeks resulted in a significant reduction in overnight plasma levels of prolactin and LH. 2 Plasma testosterone levels were elevated whilst GH and cortisol were unchanged by such treatment. 3 Measurement of overnight hormone levels 48 h after discontinuing treatment showed no evidence of a 'rebound' phenomenon. 4 Cortisol, GH, prolactin, and testosterone plasma levels all showed time dependent changes: propranolol treatment significantly altered the time course of cortisol but not of the other hormones. 5 The effects of chronic propranolol treatment are discussed in terms of a probable direct central action of the drug. In addition the lowered plasma prolactin levels may directly contribute to the hypotensive action of propranolol. [ABSTRACT FROM AUTHOR]

We have measured the psychological effects of acebutolol and atenolol in sixteen patients with essential hypertension. The drugs were administered in a randomized, placebo-controlled, double-blind manner, in single daily doses of 100 mg atenolol, 400 mg acebutolol or placebo for periods of 6 weeks, each drug period being separated by a placebo period. At each 2 weekly clinic visit, a questionnaire designed for assessment of state anxiety and state arousal was administered for self- completion. Arousal was significantly reduced by atenolol over the whole 6 weeks of administration. It was not affected by acebutolol. Anxiety was significantly reduced by acebutolol but only at the first of the three 2 weekly assessments on treatment. It was not affected by atenolol. Differences in the psychological effects of these two beta- adrenoceptor blockers are discussed in terms of their lipid solubility and haemodynamic effects. [ABSTRACT FROM AUTHOR]

1 Chronic propranolol treatment has been previously shown to lower the plasma concentrations of LH and prolactin in normal male volunteers. 2 The effect of 2 weeks treatment with propranolol (80 mg twice daily) on the plasma concentrations of LH and prolactin has now been investigated in five post menopausal hypertensive women. 3 There was no significant effect of propranolol treatment on the basal plasma concentrations of either hormone. Both hormones showed significant increases in plasma concentration following GnRH stimulation and these increases were also unaffected by propranolol treatment. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to determine factors contributing to the biomechanical properties of coronary arteries in people with and without angiographic coronary artery disease (CAD).Background: The stiffness of the aorta is known to increase with increasing age and in the presence of CAD. However, little is known about the mechanics of coronary arteries, which may have important clinical consequences.Methods: Intravascular ultrasound was used to determine the mechanical properties of coronary arteries and plaque behavior in subjects with CAD (n = 38), those with chest pain but angiographically normal coronary arteries (N) (n = 9) and those early (<2 weeks) after cardiac transplant (T) (n = 14).Results: Coronary arteries dilated during systole in all groups, but cross-sectional compliance and distensibility were lowest in the proximal left anterior descending artery (LAD) in the subjects with CAD compared with the N and T groups (compliance: 1.2 +/- 0.2 vs. 1.7 +/- 0.5 and 2.7 +/- 0.6 x 10(-2) mm(2) mm Hg(-1) [mean +/- SEM] respectively, p < 0.02 CAD vs. T; distensibility: 0.8 +/- 0.2 vs. 1.7 +/- 0.5 and 1.7 +/- 0.3 x 10(-3) mm Hg(-1), p < 0.05 CAD vs. T). There was extensive plaque in the CAD group, and plaque was also present in the N group, but minimal atheroma was present in the T group. Plaque cross-sectional area diminished significantly during systole in both the LAD and circumflex arteries. Absolute changes were: 0.50 +/- 0.30, 0.33 +/- 0.11 and 0.68 +/- 0.13 mm(2) in the proximal LAD, distal LAD and proximal circumflex arteries, respectively. In subjects with atheroma, there was a significant correlation between cross-sectional compliance and plaque compression at all sites, and plaque compression was a significant determinant of cross-sectional compliance at both proximal sites in multiple regression analyses with age, mean arterial pressure and extent of plaque as the other independent variables.Conclusions: A major determinant of the systolic increase in coronary luminal area in patients with atheroma is a reduction in plaque cross-sectional area during systole. [ABSTRACT FROM AUTHOR]

Objectives: We sought to investigate the effects of intensive cholesterol reduction on large artery stiffness and blood pressure in normolipidemic patients with isolated systolic hypertension (ISH).Background: Isolated systolic hypertension is associated with elevated cardiovascular morbidity and mortality and is primarily due to large artery stiffening, which has been independently related to cardiovascular mortality. Cholesterol-lowering therapy has been efficacious in reducing arterial stiffness in patients with hypercholesterolemia, and thus may be beneficial in ISH.Methods: In a randomized, double-blinded, cross-over study design, 22 patients with stage I ISH received three months of atorvastatin therapy (80 mg/day) and three months of placebo treatment. Systemic arterial compliance was measured noninvasively using carotid applanation tonometry and Doppler velocimetry of the ascending aorta.Results: Atorvastatin treatment reduced total and low-density lipoprotein cholesterol and triglyceride levels by 36 +/- 2% (p < 0.001), 48 +/- 3% (p < 0.001) and 23 +/- 5% (p = 0.003), respectively, and increased high density lipoprotein cholesterol by 7 +/- 3% (p = 0.03). Systemic arterial compliance was higher after treatment (placebo vs. atorvastatin: 0.36 +/- 0.03 vs. 0.43 +/- 0.05 ml/mm Hg, p = 0.03). Brachial systolic blood pressure was lower after atorvastatin treatment (154 +/- 3 vs. 148 +/- 2 mm Hg, p = 0.03), as were mean (111 +/- 2 vs. 107 +/- 2 mm Hg, p = 0.04) and diastolic blood pressures (83 +/- 1 vs. 81 +/- 2 mm Hg, p = 0.04). There was a trend toward a reduction in pulse pressure (71 +/- 3 vs. 67 +/- 2 mm Hg, p = 0.08).Conclusions: Intensive cholesterol reduction may be beneficial in the treatment of patients with ISH and normal lipid levels, through a reduction in large artery stiffness. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD)., Methods: Patients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac blood sampling during graded exercise with adenosine-mediated hyperaemia. We measured MR at rest and following supine cycle ergometry. Patients (n=24) were stratified by the resting index of MR (IMR) into normal-IMR (IMR<22U, n=12) and high-IMR groups (IMR≥22U, n=12)., Results: The mean age was 57 years; 67% were males and 38% had hypertension. The normal-IMR group had increased IMR response to exercise (16±5 vs 23±12U, p=0.03) compared with the high-IMR group, who had persistently elevated IMR at rest and following exercise (38±19 vs 33±15U, p=0.39) despite similar exercise duration and rate-pressure product between the groups, both p>0.05. The normal-IMR group had augmented oxygen extraction ratio following exercise (53±18 vs 64±11%, p=0.03) compared with the high-IMR group (65±14 vs 59±11%, p=0.26). The postexercise lactate uptake was greater in the high-IMR (0.04±0.05 vs 0.11±0.07 mmol/L, p=0.004) compared with normal-IMR group (0.08±0.06 vs 0.09±0.09 mmol/L, p=0.67). The high-IMR group demonstrated greater troponin release following exercise compared with the normal-IMR group (0.13±0.12 vs 0.001±0.05 ng/L, p=0.03)., Conclusions: Patients with suspected CMD appear to have distinctive microcirculatory resistive and myocardial metabolic profiles at rest and in response to exercise. These differences in phenotypes may permit individualised therapies targeting microvascular responsiveness (normal-IMR group) and/or myocardial metabolic adaptations (normal-IMR and high-IMR groups)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The coronavirus disease 2019 (COVID-19) outbreak within China has been well controlled and stabilized since early April 2020. Therefore, the current major focus in China is to prevent the introduction of COVID into China from international arrivals. To achieve this, pre-Hospital COVID-19 Response Teams (pHCRTs) have been established., Context: The pHRCTs were established in Xi'an, China in early 2020. During the 12 months covered in this report, there were 356 international flight arrivals with over 5,000 COVID-19 Nucleic Acid Test (NAT) positive people, 500 of them with symptomatic COVID-19 and requiring admission to special hospitals. All other arrivals were managed in dedicated facilities by pHRCTs. The outcome measure of this report was the number of positive cases among the pHRCT members., Details: Four hundred forty-two staff worked in the pHCRTs during the reporting period. Despite multiple throat swab PCR tests during their pHRCTs tour of duty, and the subsequent mandatory 14-day quarantine required before return to the general community, no staff became NAT positive., Conclusion: The prevention of community transmission from imported cases is a vital part of the strategy to maintain the low numbers of cases in countries which have achieved control, or suppression of local internal cases. The program of pHCRTs described in this article gives successful protocols for transportation of patients who are infectious based on the minimal transmission of virus and staff safety. The strategies employed may prove useful in future pandemics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zou, Zou, Dart, Zhang, Wang and Fan.)

Background: Similarities in the biology of pulmonary hypertension and cancer suggest that anticancer therapies, such as sanguinarine, may also be effective in treating pulmonary hypertension. This, along with underlying biochemical pathways, is investigated in this study. Methods: Rats were subjected to 4-week hypoxia (or control) with or without sanguinarine treatment. In addition, pulmonary artery smooth muscle cells (PASMCs) were examined after 24-48 h hypoxia (with normoxic controls) and with or without sanguinirine. Pulmonary artery pressures and plasma survivin levels were measured in vivo . Ex vivo tissues were examined histologically with appropriate staining. mRNA and protein levels of survivin, HIF-1α, TGFb1, BMPR2, Smad3, P53, and Kv 1.2, 1.5, 2.1 were determined by real-time PCR and Western blot in PASMCs and distal PAs tissue. PASMC proliferation and changes of TGFb1 and pSmad3 induced by sanguinarine were studied using MTT and Western blot. Electrophysiology for Kv functions was measured by patch-clamp experiments. Results: Four-week hypoxia resulted in an increase in serum survivin and HIF-1α, pulmonary artery pressures, and pulmonary vascular remodeling with hypertrophy. These changes were all decreased by treatment with sanguinarine. Hypoxia induced a rise of proliferation in PASMCs which was prevented by sanguinarine treatment. Hypoxic PASMCs had elevated TGFb1, pSmad3, BMPR2, and HIF1α. These increases were all ameliorated by sanguinarine treatment. Hypoxia treatment resulted in reduced expression and function of Kv 1.2, 1.5, 2.1 channels, and these changes were also modulated by sanguinarine. Conclusion: Sanguinarine is effective in modulating hypoxic pulmonary vascular hypertrophy via the survivin pathway and Kv channels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fan, Zou, Wang, Zhang, Wang, Dart and Zou.)

Purpose: In ambulant patients with lower limb DVT managed with Warfarin, there is a need for initial treatment and short time "bridging" with a rapidly acting anticoagulant until there is a stable therapeutic INR. In this study, results from bridging with subcutaneous low molecular weight heparin (LMWH) or oral Rivaroxaban were compared., Methods: One hundred and twenty-four patients received LMWH and 98 patients received Rivaroxaban, both in addition to Warfarin. Patients were assessed at 1 and 4 weeks after treatment initiation for thrombus progression, bleeding, clinic attendance and INR., Findings: The treatment groups were well matched. There were no significant differences between the treatment groups for any of the end-points at either 1 week or 4 weeks., Implications: In ambulant patients with DVT treated with Warfarin both Rivaroxaban and LMWH are suitable for use in the early phase of Warfarin treatment until therapeutic INR is achieved. Rivaroxaban is a suitable alternative to LMWH for patients who prefer not to have injections., (© 2021 John Wiley & Sons Ltd.)

Objective: The cause of perioperative myocardial infarction (PMI) is postulated to involve hemodynamic stress or coronary plaque destabilization. We aimed to evaluate perioperative factors in patients with peripheral artery disease (PAD) undergoing major vascular surgery to determine the likely mechanisms and predictors of PMI., Methods: This was a prospective cohort study of 133 patients undergoing major vascular surgery including open abdominal aortic aneurysm (AAA) repair (n = 40) and major suprainguinal or infrainguinal arterial bypasses (non-AAA; n = 93). Preoperative assessment with history, physical examination, and peripheral artery tonometry was performed in addition to plasma sampling of biomarkers associated with inflammation and coronary plaque instability. The primary outcome was occurrence of a 30-day cardiovascular event (CVE; composite of PMI [troponin I elevation >99th percentile reference of ≥0.1 μg/L], stroke, or death)., Results: Of 133 patients, 36 patients (27%) developed a 30-day CVE after vascular surgery, and all were PMI. Patients with 30-day CVE were older (75 ± 8 years vs 69 ± 10 years, mean ± standard deviation; P = .001), had higher prevalence of hypertension (94% vs 79%; P = .01) and preoperative beta-blocker therapy (50% vs 29%; P = .02), and had longer duration of surgery (5.1 ± 1.8 hours vs 4.0 ± 1.1 hours; P < .0001). Significant elevations in cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin I, high-sensitivity troponin T, matrix metalloproteinase 3, and osteoprotegerin occurred in those who developed 30-day CVE (all P < .05). Multivariate binary logistic regression identified AAA surgery and log-transformed NT-proBNP to be independent preoperative predictors of 30-day CVE (area under the receiver operating characteristic curve = 0.81)., Conclusions: In patients with peripheral artery disease undergoing major vascular surgery, the likely mechanism of PMI appears to be the hemodynamic stress related to the type and duration of surgery. NT-proBNP was a useful independent predictor of CVE and thus may serve as an important biomarker of cardiovascular fitness for surgery., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: High systolic blood pressure (SBP) increases cardiac afterload, whereas low diastolic blood pressure (DBP) may lead to impaired coronary perfusion. Thus, wide pulse pressure (high systolic, low diastolic [HSLD]) may contribute to myocardial ischemia and also be a predictor of adverse cardiovascular events., Objectives: The purpose of this study was to determine the relationship between pre-procedural blood pressure and long-term outcome following percutaneous coronary intervention (PCI)., Methods: The study included 10,876 consecutive patients between August 2009 and December 2016 from the Melbourne Interventional Group registry undergoing PCI with pre-procedural blood pressure recorded. Patients with ST-segment elevation myocardial infarction, cardiogenic shock, and out-of-hospital cardiac arrest were excluded. Patients were divided into 4 groups according to SBP (high ≥120 mm Hg, low <120 mm Hg) and DBP (high >70 mm Hg, low ≤70 mm Hg)., Results: Mean pulse pressure was 60 ± 21 mm Hg. Patients with HSLD were older and more frequently women, with higher rates of hypercholesterolemia, renal impairment, diabetes, and multivessel and left main disease (all p ≤ 0.0001). There was no difference in 30-day major adverse cardiac events, but at 12 months the HSLD group had a greater incidence of myocardial infarction (p = 0.018) and stroke (p = 0.013). Long-term mortality was highest for HSLD (7.9%) and lowest for low systolic, high diastolic (narrow pulse pressure) at 2.1% (p = 0.0002). Cox regression analysis demonstrated significantly lower long-term mortality in the low systolic, high diastolic cohort (hazard ratio: 0.50; 99% confidence interval: 0.25 to 0.98; p = 0.04)., Conclusions: Pulse pressure at the time of index PCI is associated with long-term outcomes following PCI. A wide pulse pressure may serve as a surrogate marker for risk following PCI and represents a potential target for future therapies., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Background: Repeat hospitalizations for recurrent acute coronary syndrome (ACS) or unplanned revascularization after acute myocardial infarction (MI) are common, costly and potentially preventable. We aim to describe 10-year trends and identify independent risk factors of these repeat hospitalizations., Methods: We analyzed data from 9615 patients from the Melbourne Interventional Group registry (2005-2014) who underwent percutaneous coronary intervention (PCI) for their index MI and survived to discharge. Patients with ≥1 hospitalization for recurrent ACS events and/or unplanned revascularization in the year after discharge were included in the recurrent coronary hospitalization group. We assessed yearly trends of recurrent coronary events and identified independent predictors using multivariate analysis., Results: Recurrent coronary hospitalization occurred in 1175 (12.2%) patients. There was a significant decrease in the rate of recurrent ACS hospitalization (15.3%-7.6%, P for trend <.001) and unplanned revascularization (4.2%-2.1%, P for trend = .01), but not in all-cause re-hospitalizations (P for trend = .28). On multivariate analysis, female gender, diabetes mellitus, previous coronary bypass surgery, previous PCI, reduced ejection fraction, heart failure, multi-vessel coronary disease and obstructive sleep apnea were independent predictors of recurrent coronary hospitalizations (all P < .05)., Conclusions: Recurrent hospitalization for ACS or unplanned revascularization has decreased significantly over the past decade. Risk factors for such events are numerous and largely non-modifiable, however they identify a cohort of patients in whom non-culprit vessel PCI in multi-vessel disease, optimization of left ventricular dysfunction and diabetes management may improve outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The purpose of this study is to elucidate mechanism(s) by which the orally active PGI2 analog, Beraprost (BPS), ameliorates pulmonary hypertension (PH). Prostaglandins are an important treatment for PH. Mechanisms of their action are not fully elucidated in relation to receptor subtype and effects on O 2 sensitive Kv channels. Methods: Distal (3rd order and beyond) pulmonary arteries from chronically hypoxic rats and from humans with established PH were studied. Measurements included pulmonary haemodynamics and histology, vascular reactivity, prostanoid receptor expression and activity of the O 2 sensitive Kv channels. Results: Prostacyclin receptor (IP), prostaglandin receptor E3 (EP3) and prostaglandin receptor E4 (EP4) are the main pulmonary artery receptor subtypes in both rat and human pulmonary arteries. Circulating levels of PGI2 and PGE2 were reduced in PH. PH was also associated with reduced receptor expression of IP but not of EP4. The effects on IP expression were overcome with BPS. Dilatory responses in PH to BPS were reduced in the presence of EP4 blockade. Expression and activity of oxygen sensitive Kv channels were reduced in pulmonary artery smooth muscle cell from rats with PH and humans with PAH and were also overcome by administration of BPS. Effects of BPS on oxygen sensitive Kv channels were reduced in the presence of EP4 blockade implicating the EP4 receptor, as well as the IP receptor, in mediating BPS effects. Conclusion: Reduced expression of pulmonary IP receptors and reduced activity of O 2 sensitive Kv channels are found in PH in both humans and rats. The orally active prostacyclin analogue, BPS, is able to reverse these changes, partly through binding to the EP4 receptor.

Data from previous studies of patients with heart failure and coronary artery disease suggest that those with higher resting heart rates (HRs) have worse cardiovascular outcomes. We sought to evaluate whether HR immediately before percutaneous coronary intervention (PCI) is an independent predictor for 30-day outcome. We analyzed the outcome of 3,720 patients who had HR recorded before PCI from the Melbourne Interventional Group registry. HR and outcomes were analyzed by quintiles, and secondarily by dichotomizing into <70 or ≥70 beats/min. Patients with cardiogenic shock, intra-aortic balloon pump or inotropic support, and out-of-hospital arrest were excluded. The mean ± SD HR was 70.9 ± 14.7 beats/min. HR by quintile was 55 ± 5, 64 ± 2, 70 ± 1, 77 ± 3, and 93 ± 13 beats/min, respectively. Patients with higher HR were more likely to be women, current smokers, have higher systolic and diastolic blood pressure, atrial fibrillation, recent heart failure, lower ejection fraction, and ST-elevation myocardial infarction as the indication for the PCI (all p ≤0.002). However, rates of treated hypertension, multivessel disease, previous myocardial infarction, PCI, and coronary bypass surgery were lower (all p ≤0.004). Increased HR was associated with higher 30-day mortality (p for trend = 0.04), target vessel revascularization (p for trend = 0.003), and 30-day major adverse cardiac events (MACE) (p for trend = 0.004). In a multivariable analysis, HR was an independent predictor of 30-day MACE (OR 1.21 per quintile; 95% confidence interval (CI): 1.06 to 1.39, p = 0.004). When dichotomized into <70 or ≥70 beats/min, HR independently predicted both 30-day MACE (OR 1.59, 95% CI 1.08 to 2.36, p = 0.02) and 30-day mortality (OR 2.80, 95% CI 1.10 to 7.08, p = 0.03). In conclusion, HR immediately before PCI is an independent predictor of adverse 30-day cardiovascular outcomes., (Copyright © 2018. Published by Elsevier Inc.)

Aims: We previously showed in patients with ST-segment elevated myocardial infarction (STEMI) that admission levels of macrophage migration inhibitory factor (MIF) predict infarct size. We studied whether admission MIF alone or in combination with other biomarkers is useful for risk assessment of acute and chronic clinical outcomes in STEMI patients., Methods and Results: A total of 658 STEMI patients treated with primary percutaneous coronary intervention (PCI) were consecutively recruited. MIF level was determined at admission and echocardiography performed on day-3 and then 12 months post-MI. Patients were followed for a median period of 64 months. Major endpoints included ST-segment resolution, all-cause mortality, and major adverse cardiovascular events (MACE). High MIF level was associated with larger enzymatic infarct size, incomplete resolution of ST-segment elevation post-PCI, impaired left ventricular ejection fraction (LVEF), and poorer improvement of LVEF (all P < 0.001). After adjustment for classical risk factors standard biomarkers and day-3 LVEF, admission MIF remained independently prognostic for all-cause mortality [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.43-3.22], and MACE (HR 1.39, 95% CI 1.12-1.71, both P < 0.05). MIF was a significant additive predictor of all-cause mortality with a net reclassification improvement of 0.34 (P = 0.02). Furthermore, patients in high tertile of both admission MIF and day-3 Nt-proBNP had the highest mortality risk relative to other tertile groups (HR 11.28, 95% CI 4.82-26.94; P < 0.001)., Conclusion: STEMI patients with high admission MIF level experienced a poorer recovery of cardiac function and worse long-term adverse outcomes. Combination of Nt-proBNP with MIF further improves prognostic capability.

Background: To determine the relationship between maternal anxiety and cortisol values and birth weight at various stages of pregnancy., Methods: Two hundred sixteen pregnant Chinese women were assessed for anxiety and depression and had measurement of morning fasting serum cortisol. Women were assessed either in the first (71), second (72) or third (73) trimester. Birth weights of all children were recorded., Results: There were significant negative correlations between anxiety level and birth weight of - 0.507 (p < 0.01) and - 0.275 (p < 0.05) in trimesters 1and 2. In trimester 3 the negative relation between anxiety and birth weight of -.209 failed to reach significance (p = 0.070). There was no relation between depression and birth weight in any trimester (p > 0.5 for all). Maternal cortisol was significantly inversely related to birth weight in trimester 1 (r = - 0.322) and with borderline significance in trimester 2 (r = - 0.229). Anxiety score and maternal cortisol were significantly correlated in each trimester (r = 0.551, 0.650, 0.537). When both anxiety score and maternal cortisol were simultaneously included in multiple regression analyses only anxiety score remained significant., Conclusion: Whilst both maternal anxiety score and maternal cortisol are inversely related to birth weight the associations with anxiety score were more robust perhaps indicating the importance of mechanisms other than, or in addition to, maternal cortisol in mediating the effects of anxiety. The findings indicate the importance of measures to reduce maternal anxiety, particularly of a severe degree, at all stages of pregnancy., Trial Registration: The study was approved by the Ethics Committee of the 1st Affiliated Hospital of Xi'an Jiaotong University.

Preclinical studies have demonstrated that anti-galectin-3 (Gal-3) interventions are effective in attenuating cardiac remodeling, fibrosis, and dysfunction. We determined, in a transgenic (TG) mouse model of fibrotic cardiomyopathy, whether Gal-3 expression was elevated and whether Gal-3 played a critical role in disease development. We studied mice with fibrotic cardiomyopathy attributable to cardiac overexpression of human β 2 -adrenoceptors (β 2 -TG). Cardiac expression levels of Gal-3 and fibrotic or inflammatory genes were determined. The effect of Gal-3 inhibition in β 2 -TG mice was studied by treatment with Gal-3 inhibitors ( N-acetyllactosamine and modified citrus pectin) or by deletion of Gal-3 through crossing β 2 -TG and Gal-3 knockout mice. Changes in cardiomyopathy phenotypes were assessed by echocardiography and biochemical assays. In β 2 -TG mice at 3, 6, and 9 mo of age, upregulation of Gal-3 expression was observed at mRNA (~6- to 15-fold) and protein (~4- to 8-fold) levels. Treatment of β 2 -TG mice with N-acetyllactosamine (3 wk) or modified citrus pectin (3 mo) did not reverse cardiac fibrosis, inflammation, and cardiomyopathy. Similarly, Gal-3 gene deletion in β 2 -TG mice aged 3 and 9 mo did not rescue the cardiomyopathy phenotype. In conclusion, the β 2 -TG model of cardiomyopathy showed a robust upregulation of Gal-3 that correlated with disease severity, but Gal-3 inhibitors or Gal-3 gene deletion had no effect in halting myocardial fibrosis, remodeling, and dysfunction. Gal-3 may not be critical for cardiac fibrogenesis and remodeling in this cardiomyopathy model. NEW & NOTEWORTHY We showed a robust upregulation of cardiac galectin-3 (Gal-3) expression in a mouse model of cardiomyopathy attributable to cardiomyocyte-restricted transgenic activation of β 2 -adrenoceptors. However, pharmacological and genetic inhibition of Gal-3 did not confer benefit in this model, implying that Gal-3 may not be a critical disease mediator of cardiac remodeling in this model.

Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease and in patients with cardiomyopathy. All mouse models (dilated cardiomyopathy, DCM; fibrotic cardiomyopathy, ischemia-reperfusion, I/R; treatment with β-adrenergic agonist isoproterenol) showed multi-fold increases in cardiac galectin-3 expression and preserved renal function. In mice with fibrotic cardiomyopathy, I/R or isoproterenol treatment, plasma galectin-3 levels and density of cardiac inflammatory cells were elevated. These models also exhibited parallel changes in cardiac and plasma galectin-3 levels and presence of trans-cardiac galectin-3 gradient, indicating cardiac release of galectin-3. DCM mice showed no change in circulating galectin-3 levels nor trans-cardiac galectin-3 gradient or myocardial inflammatory infiltration despite a 50-fold increase in cardiac galectin-3 content. In patients with hypertrophic cardiomyopathy or DCM, plasma galectin-3 increased only in those with renal dysfunction and a trans-cardiac galectin-3 gradient was not present. Collectively, this study documents the aetiology-dependency and diverse mechanisms of increment in circulating galectin-3 levels. Our findings highlight cardiac inflammation and enhanced β-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism.

Background: Regional or diffuse fibrosis is an early feature of hypertrophic cardiomyopathy (HCM) and is related to poor prognosis. Previous studies have documented low-grade inflammation in HCM. The aim of this study was to examine the relationships between circulating inflammatory markers and myocardial fibrosis, systolic and diastolic dysfunction, and the degree of cardiac hypertrophy in HCM patients., Methods and Results: Fifty HCM patients were recruited while 20 healthy subjects served as the control group. Seventeen inflammatory cytokines/chemokines were measured in plasma. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac phenotypes. Tumour necrosis factor (TNF)-α, interleukin (IL)-6 and serum amyloid P (SAP) were significantly increased in HCM patients compared to controls. IL-6, IL-4, and monocyte chemotactic protein (MCP)-1 were correlated with regional fibrosis while stromal cell-derived factor-1 and MCP-1 were correlated with diffuse fibrosis. Fractalkine and interferon-γ were associated with left ventricular wall thickness. The above associations remained significant in a linear regression model including age, gender, body mass index and family history. TNF-α, IL-6, SAP, MCP-1 and IL-10 were associated with parameters of diastolic dysfunction. White blood cells were also increased in HCM patients and correlated with diffuse fibrosis and diastolic dysfunction. However the associations between parameters of systemic inflammation and diastolic dysfunction were weakened in the linear regression analysis., Conclusions: Systemic inflammation is associated with parameters of the disease severity of HCM patients, particularly regional and diffuse fibrosis. Modifying inflammation may reduce myocardial fibrosis in HCM patients., Competing Interests: None.

Purpose: Peripherally inserted central catheters (PICCs) are frequently used for prolonged drug administration, but their use is commonly complicated by the development of upper extremity deep venous thrombosis (UEDVT) requiring anticoagulation. Here, we compared the efficacy and safety profile of rivaroxaban (20 mg/d) with low molecular weight (LMW) heparin and vitamin K antagonists in the treatment of PICC-associated UEDVT., Methods: Patients (N = 84) with PICC-associated UEDVT were studied. All had UEDVT identified by ultrasound scanning. Further ultrasound images were obtained at 1, 2, and 3 months after the start of treatment. Forty-four patients were treated with rivaroxaban and 40 with initial LMW heparin and vitamin K antagonist with continuation of vitamin K antagonists alone once international normalized ratio was therapeutic FINDINGS: In the rivaroxaban group mean (SD) age was 51 (16) years and 57% were men, whereas in the other group respective values were 50 (16) years and 56%. All patients were receiving treatment for cancer. Resolution of thrombus had occurred in 53.5% at 1 month, 76.1% at 2 months, and 92.6% at 3 months in the rivaroxaban-treated patients. Corresponding values in the LMW heparin/vitamin antagonist-treated patients were 34.2%, 55.5%, and 88.5%, respectively. Differences between groups were significant at 1 month (P < 0.01) and 2 months (P < 0.05). There were no major bleeds in either group, and cumulative bleeding rates by 3 months were 7.3% in the rivaroxaban group and 11.4% in the LMW heparin/vitamin K antagonist group., Implications: Rivaroxaban led to faster resolution of PICC-associated UEDVT than LMW/vitamin K antagonists without any increase in bleeding., (Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.)

Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials. A majority of clinical studies are of small size or have not been maintained for long enough periods. In addition, although some conventional therapies, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to reduce cardiac fibrosis in humans, cardiac fibrosis persists in patients with heart failure even when treated with these conventional therapies, indicating a need to develop novel and effective anti-fibrotic therapies in cardiovascular disease. In this review article, we summarize anti-fibrotic therapies for cardiovascular disease in humans, discuss the limitations of currently used therapies, along with possible reasons for the failure of so many anti-fibrotic drugs at the clinical level. We will then explore the future directions of anti-fibrotic therapies on cardiovascular disease, and this will include emerging anti-fibrotics that show promise, such as relaxin. A better understanding of the differences between animal models and human pathology, and improved insight into carefully designed trials on appropriate end-points and appropriate dosing need to be considered to identify more effective anti-fibrotics for treating cardiovascular fibrosis in human patients.

Purpose: Inhibition of the renin-angiotensin system (RAS) is beneficial in patient management after myocardial infarction (MI). However, whether RAS inhibition also provides cardiac protection in the acute phase of MI is unclear., Methods: Male 129sv mice underwent coronary artery occlusion to induce MI, followed by treatment with losartan (L, 20 and 60 mg/kg), perindopril (P, 2 and 6 mg/kg), amlodipine (20 mg/kg as a BP-lowering agent) or vehicle as control. Drug effects on hemodynamics were examined. Effects of treatments on incidence of cardiac rupture, haematological profile, monocyte and neutrophil population in the spleen and the heart, cardiac leukocyte density, expression of inflammatory genes and activity of MMPs were studied after MI., Results: Incidence of cardiac rupture within 2 weeks was significantly and similarly reduced by both losartan (L) and perindopril (P) in a dose-dependent manner [75% (27/36) in vehicle, 40-45% in low-dose (L 10/22, P 8/20) and 16-20% (L 5/32, P 4/20) in high-dose groups, all P < 0.05]. This action was independent of their BP-lowering action, as amlodipine reduced BP to a similar degree without effect on rupture (70%, 21/30). Compared to the control group, high dose losartan and perindopril decreased counts of white blood cells, neutrophils and lymphocytes (all P < 0.05), and inhibited splenic monocyte and neutrophil release into the circulation. Consequently, monocyte, neutrophil and leukocyte infiltration, inflammatory gene expressions (IL-1β, IL-6, MMP9, MCP-1, TNF-α and TGFβ1) and activity of MMP2 and MMP9 in the infarct tissue were attenuated by losartan and/or perindopril treatment (all P < 0.05)., Conclusions: RAS inhibition by losartan or perindopril prevented cardiac rupture at the acute phase of MI through blockade of splenic release of monocytes and neutrophils and consequently attenuation of systemic and regional inflammatory responses.

Competing Interests: Conflict of interest: none declared