Type 2 diabetes mellitus (T2DM) is a cardiovascular risk factor which leads to atherosclerosis, an inflammatory disease characterized by the infiltration of mononuclear cells in the vessel. Bone morphogenetic protein (BMP)‐2 is a cytokine which has been recently shown to be elevated in atherosclerosis and T2DM and to contribute to vascular inflammation. However, the role of BMP‐2 in the regulation of mononuclear cell function remains to be established. Herein, we demonstrate that BMP‐2 induced human monocyte chemotaxis via phosphoinositide 3 kinase and mitogen‐activated protein kinases. Inhibition of endogenous BMP‐2 signalling, by Noggin or a BMP receptor inhibitor, interfered with monocyte migration. Although BMP‐2 expression was increased in monocytes from T2DM patients, it could still stimulate their migration. Furthermore, BMP‐2 interfered with their differentiation into M2 macrophages. Finally, BMP‐2 both induced the adhesion of monocytes to fibronectin and endothelial cells (ECs), and promoted the adhesive properties of ECs, by increasing expression of adhesion and pro‐inflammatory molecules. Our data demonstrate that BMP‐2 could exert its pro‐inflammatory effects by inducing monocyte migration and adhesiveness to ECs and by interfering with the monocyte differentiation into M2 macrophages. Our findings provide novel insights into the mechanisms by which BMP‐2 may contribute to the development of atherosclerosis.

Aims To evaluate the use of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in adult congenital heart disease (ACHD) and assess outcome in a nationwide analysis. Methods and results Using data from one of Germany’s largest Health Insurers, all ACHD patients treated with VKAs or NOACs were identified and changes in prescription patterns were assessed. Furthermore, the association between anticoagulation regimen and complications including mortality was studied. Between 2005 and 2018, the use of oral anticoagulants in ACHD increased from 6.3% to 12.4%. Since NOACs became available their utilization increased constantly, accounting for 45% of prescribed anticoagulants in ACHD in 2018. Adult congenital heart disease patients on NOACs had higher thromboembolic (3.8% vs. 2.8%), MACE (7.8% vs. 6.0%), bleeding rates (11.7% vs. 9.0%), and all-cause mortality (4.0% vs. 2.8%; all P < 0.05) after 1 year of therapy compared with VKAs. After comprehensive adjustment for patient characteristics, NOACs were still associated with increased risk of MACE (hazard rate—HR 1.22; 95% CI 1.09–1.36) and increased all-cause mortality (HR 1.43; 95% CI 1.24–1.65; both P < 0.001), but also bleeding (HR 1.16; 95% CI 1.04–1.29; P = 0.007) during long-term follow-up. Conclusion Despite the lack of prospective studies in ACHD, NOACs are increasingly replacing VKAs and now account for almost half of all oral anticoagulant prescriptions. Particularly, NOACs were associated with excess long-term risk of MACE, and mortality in this nationwide analysis, emphasizing the need for prospective studies before solid recommendations for their use in ACHD can be provided.

Background Female sex was reported to be associated with an unfavorable outcome in acute myocardial infarction (AMI). In this nationwide analysis we assessed sex differences in acute outcomes of AMI and recent trends in patient healthcare. Methods We analyzed 875 735 German cases hospitalized with a main diagnosis of ST‐ (STEMI) and non ST‐elevation myocardial infarction (NSTEMI) between January 01 2014 and December 31 2017 regarding morbidity, in‐hospital mortality and treatments. A multivariable logistic regression model was designed to evaluate the use of interventions and their impact on in‐hospital mortality. Results STEMI cases decreased from 72 894 in 2014 to 68 213 in 2017, with 70% assignable to men. Female sex was associated with older age (74 vs. 62 years), and higher prevalence of cardiovascular risk factors such as chronic kidney disease (19.2% vs. 12.5%), hypertension (69.0% vs. 65.0%) and left ventricular heart failure (36.0% vs. 32.1%). In NSTEMI, female sex was also associated with older age (78 vs. 71 years), and higher prevalence of cardiovascular risk factors such as chronic kidney disease (29.7% vs. 23.9%), hypertension (77.4% vs. 74.5%) and left ventricular heart failure (40.5% vs. 36.4%). Overall, 74.3% of female and 81.3% of male STEMI cases received percutaneous coronary intervention (PCI, p < 0.001). In NSTEMI, PCI was performed in 40.8% of female and 52.0% of male cases (p < 0.001). In‐hospital mortality was notably increased in female patients with STEMI (15.0% vs. 9.6%; p < 0.001; OR 1.07; 95% CI 1.03–1.10) and NSTEMI (8.3% vs. 6.3%; p < 0.001; OR 0.91; 95% CI 0.89–0.93) compared to males. Conclusions Our nationwide real‐world data document that in‐patient STEMI cases continue to decrease in women and men. The observed higher in‐hospital mortality in women was largely attributed to a more unfavorable risk and age distribution rather than to female‐intrinsic factors. Women with AMI continue to be less likely to receive revascularization therapies.

Background and aims: The prevalence of lower extremity artery disease (LEAD) is increasing worldwide and sexrelated differences are a current matter of debate. Methods: We analysed claims data on unselected patients with in-patient treatment for LEAD with intermittent claudication (IC; Rutherford grade 1-3) from 01.01.2014 to 31.12.2015. Data files included diagnostic and procedural information from two years before index, and a five-year follow-up. Results: Our analysis comprised 42,197 IC patients, thereof 28,520 (68%) male. Male patients were younger (median: 66.4 years vs. 72.6 years) but presented with higher frequency of cardiovascular risk factors such as diabetes (40% female vs. 46% male), atrial fibrillation (13% vs. 17%), chronic coronary syndrome (41% vs. 53%), chronic heart failure (23% vs. 27%), or chronic kidney disease (29% vs. 32%; all p < 0.001; age adjusted). Revascularisation applied in 80% of patients, thereof endovascular approach predominantly in female and surgery in male patients. Concomitant pharmacotherapy with statins (74% at 2 years) and platelet inhibitors (75% respectively) were long lasting below guideline recommendation, under-use being more pronounced in women. Two years after index, one-third of IC patients had subsequent revascularisation, one-quarter progressed to chronic limb threatening ischemia (CLTI), and 2% underwent amputation. Male sex was an independent risk factor for long-term mortality (female HR 0.75; 95%-CI 0.72-0.79; p < 0.001) and CLTI (female HR 0.89; 95%-CI 0.86-0.92; p < 0.001) during follow-up. Conclusions: The majority of in-patient treated patients for IC are male, presenting with worse cardiovascular risk profiles. In view of a general under-supply with statins and platelet inhibitors, women received somewhat less often preventive medication. Despite low LEAD stages at index, serious prognosis was observed in the long term. Particularly male patients were at high risk for all-cause mortality and the combined endpoint CLTI and death.

Aims The prevalence of chronic limb-threatening ischaemia (CLTI) is increasing and available data often derive from cohorts with various selection criteria. In the present study, we included CLTI patients and studied sex-related differences in their risk profile, vascular procedures, and long-term outcome. Methods and results We analysed 199 953 unselected patients of the largest public health insurance in Germany (AOK: Local healthcare funds), hospitalized between 2010 and 2017 for a main diagnosis of CLTI. A baseline period of 2 years before index hospitalization to assess comorbidities and previous procedures, and a follow-up period until 2018 were included. Female CLTI patients were older (median 81.4 vs. 73.8 years in males; P &lt; 0.001) and more often diagnosed with hypertension, atrial fibrillation, chronic heart failure, and chronic kidney disease. Male patients suffered more frequently from diabetes mellitus, dyslipidaemia, smoking, cerebrovascular disease, and chronic coronary syndrome (all P &lt; 0.001). Within hospitalized CLTI patients, females represent the minority (43% vs. 57%; P &lt; 0.001) and during index hospitalization, women underwent less frequently diagnostic angiographies (67 vs. 70%) and revascularization procedures (61 vs. 65%; both P &lt; 0.001). Moreover, women received less frequently guideline-recommended drugs like statins (35 vs. 43%) and antithrombotic therapy (48 vs. 53%; both P &lt; 0.001) at baseline. Interestingly, after including age and comorbidities in a Cox regression analysis, female sex was associated with increased overall-survival (OS) [hazard ratio (HR) 0.95; 95% confidence interval (CI) 0.94–0.96] and amputation-free survival (AFS) (HR 0.84; 95% CI 0.83–0.85; both P &lt; 0.001). Conclusion Female patients with CLTI were older, underwent less often vascular procedures, and received less frequently guideline-recommended medication. Nevertheless, female sex was independently associated with better OS and AFS during follow-up. Key question Analysis of sex-related differences in patients with chronic limb-threatening ischaemia (CLTI), with a focus on their risk profile, treatment, and long-term outcome. Key finding Female CLTI patients were older, underwent vascular procedures less often, and received less frequently guideline-recommended drugs, but female sex was associated with better outcome. Take-home message Chronic limb-threatening ischaemia should be considered as a multi-organ disease with an ever increasing prevalence and a poor prognosis. Chronic limb-threatening ischaemia patients partly do not receive optimal therapy, and this is more prominent in females.

Type 2 diabetes mellitus (T2DM) is one of the main risk factors for the development of atherosclerosis. Moreover, the formation of collateral arteries is decreased in patients with T2DM. 1,2 Monocytes play an important role in vascular biology during angiogenesis and arteriogenesis including the development of collateral vessels following coronary artery occlusion. 3,4 Any imbalance of number or function of monocytes has detrimental consequences for vascular healing and may lead to cardiovascular pathology such as atherosclerosis. 5 It

ObjectivesTo investigate the clinical benefit of endovascular revascularisation (EVR) in octogenarian (aged ≥80 years) patients with lower extremity artery disease (LEAD).DesignRetrospective single-centre study.SettingUniversity hospital with a specialised centre for vascular medicine.Participants681 LEAD patients undergoing EVR between 2010 and 2016 were stratified by age.Main outcome measureTechnical success, complications and mortality.ResultsThe cohort comprised 172 (25.3%) octogenarian and 509 (74.7%) non-octogenarian patients. Despite higher LEAD stages and complexity of EVR in octogenarians, primary technical success rate (79% octogenarians vs 86% non-octogenarians, p=0.006) and 1-year survival (87% vs 96%, p<0.001) were overall on high levels. Especially for the octogenarians, 1-year survival depends on the presence of chronic limb-threatening ischaemia (CLTI) (octogenarians: non-CLTI 98%; CLTI 79% p<0.001 vs non-octogenarians: non-CLTI 99%; CLTI 91%, p<0.001). In octogenarians, female sex (HR 0.45; 95% CI (0.24 to 0.86); p=0.015), the intake of statins (HR 0.34; 95% CI 0.19 to 0.65; p=0.001) and platelet aggregation inhibitors (HR 0.10; 95% CI 0.02 to 0.45; p=0.003) were independently associated with improved survival after EVR.ConclusionEVR can be performed safely and with sustained clinical benefit also in octogenarian patients with LEAD. After-care including medical adherence is of particular importance to improve long-term survival.

Background: Acute myocardial infarction (AMI) and cancer are common and serious diseases. As the prognosis and treatment of both diseases has improved, more cancer patients will suffer an AMI. Unfortunately, data on these “double hit” patients is scarce. Methods: From the largest public German health insurance, anonymized data of all patients with pre-existing cancer who were hospitalized due to ST-elevation MI (STEMI) between 2010 and 2017 were analyzed and followed-up until 2018. Results: Of 175,262 STEMI patients, 27,213 had pre-existing cancer (15.5%). Most frequent were skin (24.9%), prostate (17.0%), colon (11.0%), breast (10.9%), urinary tract (10.6%), and lung cancer (5.2%). STEMI patients with malignancies were older and presented more often with coronary three-vessel disease, atrial arrhythmias, chronic kidney disease, chronic heart failure, cerebrovascular and peripheral artery disease (PAD, each p < 0.001). They showed more often previous AMI, percutaneous coronary interventions (PCI), cardiac surgery, and stroke (all p < 0.001). Acute PCIs were applied between 2 and 6% less frequently compared to those without cancer. In-hospital adverse events occurred more frequently in cancer. Eight-year survival was 57.3% (95% CI 57.0–57.7%) without cancer and ranged between 41.2% and 19.2% in distinct cancer types. Multivariable Cox regression for all-cause mortality found, e.g., lung cancer (HR 2.04), PAD stage 4–6 (HR 1.78), metastasis (HR 1.72), and previous stroke (HR 1.44) to have the strongest impact (all p < 0.001). Conclusion: In this large “real world” data, prognosis after STEMI in cancer patients was markedly reduced but differed widely between cancer types. Of note, no withholding of interventional treatments in cancer patients could be observed.