Our understanding of the regulation of vascular tone has been extended since the identification of vasoactive agents such as the atrial natriuretic peptides, endothelial-derived relaxing factor and endothelin. Unidentified vasopressive agents have been found in platelets. Here we isolate these vasopressors and identify them as diadenosine pentaphosphate (AP5A) and diadenosine hexaphosphate (AP6A) by chromatography, mass spectrometry, ultraviolet spectroscopy and enzymatic cleavage. In the vasculature of isolated perfused rat kidney, both diadenosine phosphates were active at a concentration of 10(-9) M; in aortic rings, contractions were elicited at 10(-8) M. Intra-aortic injection in the rat caused a prolonged increase in blood pressure. We conclude that AP5A and AP6A may play a part in local vasoregulation and possibly in the regulation of blood pressure.

BACKGROUND Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3–74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2–111.0 mg/dL). RESULTS In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [Cl]: 0.52–0.90) and 1.11 (95% Cl: 0.83–1.49), with treatment-lipoprotein(a) interaction on MACE ( P interaction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% Cl: 0.72–0.92) and 0.89 (95% Cl: 0.75–1.06), with P interaction = 0.43. CONCLUSIONS In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402 )

If noncompliance can be excluded, the dosage of antihypertensive drugs should be increased to a maximum if tolerated, or combinations of four or more drugs can be used, including drugs like minoxidil.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. The major cause of GIST is the presence of an abnormal form of tyrosine protein kinase (KIT) protein also known as CD117, which causes uncontrollable growth of the gastrointestinal cells. Most studies report incidences between 10 and 15 cases of GISTs per million. Metastases to the liver and peritoneum are the most frequent. We report a case of advanced GIST with a liver metastasis infiltrating the inferior vena cava (IVC) and extending to the right atrium in the form of a large, floating, isolated intracardiac liver metastasis with diastolic prolapsing through the tricuspid valve. This is a very rare manifestation. One week after heart surgery and removal of a 5×6 cm tumor mass from the right atrium and the IVC, echocardiography depicted an early recurrence.

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