Anthony Michael Dart

Background: Ten‐year risk equations for incident heart failure (HF) are available for the general population, but not for patients with established atherosclerotic cardiovascular disease (ASCVD), which is highly prevalent in HF cohorts. This study aimed to develop and validate 10‐year risk equations for incident HF in patients with known ASCVD. Methods and Results: Ten‐year risk equations for incident HF were developed using the United Kingdom Biobank cohort (recruitment 2006–2010) including participants with established ASCVD but free from HF at baseline. Model performance was validated using the Australian Baker Heart and Diabetes Institute Biobank cohort (recruitment 2000–2011) and compared with the performance of general population risk models. Incident HF occurred in 13.7% of the development cohort (n=31 446, median 63 years, 35% women, follow‐up 10.7±2.7 years) and in 21.3% of the validation cohort (n=1659, median age 65 years, 25% women, follow‐up 9.4±3.7 years). Predictors of HF included in the sex‐specific models were age, body mass index, systolic blood pressure (treated or untreated), glucose (treated or untreated), cholesterol, smoking status, QRS duration, kidney disease, myocardial infarction, and atrial fibrillation. ASCVD‐HF equations had good discrimination and calibration in development and validation cohorts, with superior performance to general population risk equations. Conclusions: ASCVD‐specific 10‐year risk equations for HF outperform general population risk models in individuals with established ASCVD. The ASCVD‐HF equations can be calculated from readily available clinical data and could facilitate screening and preventative treatment decisions in this high‐risk group.

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 124 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 endpoints at either 1 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.

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 O₂ 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 O₂ 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 O₂ 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.

To determine the relationship between maternal anxiety and cortisol values and birth weight at various stages of pregnancy. 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. 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. 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. The study was approved by the Ethics Committee of the 1st Affiliated Hospital of Xi’an Jiaotong University.

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. 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). 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.

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. 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. 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.

Background: Macrophage migration inhibitory factor ( MIF ) is a key regulator of inflammatory responses, including in the heart. Plasma MIF is elevated early in the course of acute myocardial infarction. In this study, we hypothesized that plasma MIF may also be increased in acute myocardial ischemia. Methods and Results: Patients undergoing cardiac stress test (stress nuclear myocardial perfusion scan or stress echocardiography) were recruited. Twenty‐two patients had a stress test indicative of myocardial ischemia and were compared with 62 patients who had a negative stress test. Plasma MIF was measured by ELISA before and after the stress test. MIF was also measured in patients with peripheral arterial occlusive disease before and after exercise causing claudication. Gene and protein expression of MIF was measured in mouse cardiac and skeletal muscle tissue by real‐time polymerase chain reaction and western blot, respectively. Plasma MIF was elevated at 5 and 15 minutes after stress (relative to before stress) in patients with a positive test, compared with those with a negative test. In contrast, high‐sensitivity troponin T and C‐reactive protein were not altered after stress in either group. MIF was not altered after exercise in PAOD patients, despite the occurrence of claudication, suggesting that plasma MIF is not a marker for skeletal muscle ischemia. This may be explained by a lower gene and protein expression of MIF in skeletal muscle than the heart. Conclusions: Our results suggest that plasma MIF is an early marker for acute myocardial ischemia.

In the Review entitled “Diabetes: Advances in Diagnosis and Treatment” published in the September 8, 2015, issue of JAMA, there were incorrect data in Table 1.