Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5m genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N≤71,225 European ancestry, N=12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N=29,136). We identified association between systolic or diastolic blood pressure and common variants in 8 regions near the CYP17A1 (P=7×10−24), CYP1A2 (P=1×10−23), FGF5 (P=1×10−21), SH2B3 (P=3×10−18), MTHFR (P=2×10−13), c10orf107 (P=1×10−9), ZNF652 (P=5×10−9) and PLCD3 (P=1×10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

No abstract

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.

T o achieve early and complete reperfusion of the myocardium in acute coronary syndromes is the daily challenge for every physician in clinical cardiology. However, restoration of epicardial blood flow by thrombolysis, primary angioplasty or bypass surgery does not necessarily imply complete reperfusion, even if the target stenosis is adequately removed or bypassed. The amount of microvascular integrity may limit reperfusion to the previously ischaemic tissue despite complete restoration of epicardial vessel diameters.A 74 year old man with acute distress is admitted to the emergency room because of acute onset of severe, substernal, crushing chest pain two hours ago. He has never suffered from similar symptoms before. The ECG shows ST segment elevation in leads I, aVL, V2-V4. After aspirin and heparin, the patient is immediately transferred to the catheterisation laboratory. Coronary angiography confirms a thrombotic occlusion of the proximal left anterior descending artery. The guide wire easily crosses the occlusion. After coronary artery balloon dilatation and stent implantation the epicardial artery appears to have gained sufficient luminal diameter. However, the contrast medium is only slowly conveyed to the distal artery and not adequately washed out. Even the final angiogram after glyceryl trinitrate in different projections shows no satisfactory flow albeit no visible flow limiting obstacles, such as coronary artery dissection or recurrent thrombus formation. The battle, undertaken to restore myocardial blood supply, seems to be lost and won, finally leading to compromised tissue perfusion despite a successful restoration of patency to the epicardial blood vessel.A bolus of abciximab, followed by a continuous infusion, is initiated. ST segment elevations resolve only slightly during the next hours; the patient requires prolonged intensive medical care because of recurrent pulmonary oedema. Finally, the patient is stabilised on cardiovascular medication including an angiotensin converting enzyme (ACE) inhibitor, oxygen, and aspirin. The echocardiography shows a large akinetic segment of the anteroseptal wall with an apical aneurysm, and a global ejection fraction of 30%.Angiographic no-reflow, as described above, may be one of the clinically most obvious manifestations of microvascular damage. The following discussion will set forward that the so-called "noreflow" phenomenon is far more frequent, and has important prognostic implications. Combining results from basic science and clinical research, we try to elucidate major mechanisms of no-reflow, methods of assessing microvascular dysfunction, and its significance in the clinical setting. c WHAT IS KNOWN ABOUT NO-REFLOW FROM ANIMAL STUDIES?Anatomical no-reflow In experimental models of myocardial infarction, injection of various dyes to the circulation has been traditionally used to stain perfused tissue. As shown in fig 1, a substantial part of the myocardium, after being subjected to proximal coronary occlusion and reperfusion of the epicardial artery...