AstraZeneca, Biosensors, and The Medicines Company.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, nineteen associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biologic pathways.

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).

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Basel Cardiovascular Research Foundation, and B Braun Medical AG.

No abstract

In 1992 Conconi et al. (20) presented an indirect and noninvasive method for the determination of anaerobic threshold (AnT) in an incremental field test for runners. This noninvasive method for the determination of anaerobic threshold is dependent on the occurrence of a deflection of the heart rate performance curve (HRPC). The aim of our study was to evaluate the degree and direction of the deflection of the HRPC and the relationship of the heart rate threshold (HRT) to the lactate turn point in a group of 227 healthy young subjects (age: 23 +/- 4 yr). The subjects were divided into three groups by means of second degree polynomial fitting (GI: regular deflection, kHR > 0.1; G II: no deflection, 0 < kHR < 0.1; G II: inverse deflection, k < -0.1). No significant differences between the groups were found in the anthropometric data or in the power output and the blood lactate concentration at both the first (LTP1) and second (LTP2) lactate turn points and at maximum performance (Pmax). Using the method of Conconi et al. (20), 85.9% of the subjects showed a "regular" deflection, 6.2% showed no deflection at all, and 7.9% showed even an inverted deflection of the HRPC. An HRT could be obtained in both G I and G III, and power output at HRT was not significantly different in comparison to that at the LTP2. No HRT could be assessed in G II. The heart rate at HRT and the LTP2 were significantly lower in G III compared with G I. The phenomenon of heart rate break point may be attractive in training regulation, but its application is limited because a heart rate deflection cannot be found even in young subjects in some cases.

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These findings indicate that beta-blockers decrease melatonin release via specific inhibition of adrenergic beta1-receptors. Since lower nocturnal melatonin levels might be the reason for sleep disturbances, further clinical studies should investigate whether or not oral administration of melatonin might avoid this well-known side-effect of beta-blockers. The reason why (R,S)-carvedilol does not influence melatonin production remains to be determined.