SummaryBackground Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest antiischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT).

Objective: Reduced numbers of regulatory T (T reg ) cells have been observed in visceral adipose tissue of obese mice and humans. However, it is unknown whether human obesity affects circulating Treg cells and whether their number is associated with markers of systemic inflammation or glucose intolerance. Design and Methods: Peripheral blood mononuclear cells were isolated from venous blood of obese (BMI ! 27 kg/m 2 ; n ¼ 30) and nonobese (BMI ! 27 kg/m 2 ; n ¼ 13) individuals and analyzed using flow cytometry for the expression of CD4, CD25, and Foxp3. Results: Reduced circulating T reg -cell numbers were detected in obese compared with nonobese study participants (P ¼ 0.038). Circulating CD4 þ CD25 þ CD127 À Foxp3 T reg cells inversely correlated with body weight (P ¼ 0.009), BMI (P ¼ 0.004) and plasma leptin levels (P ¼ 0.004) and were reduced in subjects with hsCRP ! 3.0 mg/L (P ¼ 0.034) or HbA1c ! 5.5% (P < 0.005). Receiver operating characteristic curve analysis revealed a cutoff of circulating Treg cells < 1.06% to be predictive for hsCRP levels ! 3.0 mg/L, and logistic regression showed that the risk of having hsCRP levels ! 3.0 mg/L was increased 9.6-fold (P ¼ 0.008), if T reg cells were below this threshold. The T reg cutoff for HbA1c levels ! 5.5% was 0.73%, and this cutoff also predicted an increased risk of having elevated levels of both hsCRP and HbA1c, if only obese subjects were examined. Conclusion: Our findings thus reveal an association between circulating T reg cells and measures of adiposity, inflammation, and glucose intolerance. Although further prospective studies are needed, we present data suggesting that the determination of T reg cells might be useful to identify obese subjects at increased risk of developing cardiovascular and/or metabolic complications.

Our findings suggest that locally elevated leptin levels may promote neointima formation, independent of obesity and systemic hyperleptinemia, but also underline the importance of perivascular inflammation in mediating the increased cardiovascular risk in obesity.

Abstract. Czepluch FS, Kuschicke H, Dellas C, Riggert J, Hasenfuss G, Sch€ afer K (University Medical Center G€ ottingen, G€ ottingen, Germany ++ cells, which differ in their functional properties. The aim of this study was to examine monocyte subset distribution, monocyte-platelet aggregate (MPA) formation and expression of CCR5, the receptor of the platelet-derived chemokine CCL5, and to determine whether these parameters are altered in individuals with coronary atherosclerosis.

The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so‐called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next‐generation sequencing – NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing. Due to this development, genetic testing has become increasingly accessible and NGS‐based sequencing is now applied in clinical routine diagnostics. One of the most common reasons of heart failure are cardiomyopathies such as the dilated or the hypertrophic cardiomyopathy. Nearly 100 disease‐associated genes have been identified for cardiomyopathies. The knowledge of a pathogenic mutation can be used for genetic counselling, risk and prognosis determination, therapy guidance and hence for a more effective treatment. Besides, family cascade screening for a known familial, pathogenic mutation can lead to an early diagnosis in affected individuals. At that timepoint, a preventative intervention could be used to avoid or delay disease onset or delay disease progression. Understanding the cellular basis of genetic heart failure syndromes in more detail may provide new insights into the molecular biology of physiological and impaired cardiac (cell) function. As our understanding of the molecular and genetic pathophysiology of heart failure will increase, this might help to identify novel therapeutic targets and may lead to the development of new and specific treatment options in patients with heart failure.