Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Radiation of the Australian Salicornioideae (Chenopodiaceae)—based on evidence from nuclear and chloroplast DNA sequences

In phylogenetic analyses of nuclear ITS and chloroplast trnL DNA sequences, the mostly endemic Australian genera; Halosarcia, Pachycornia, Sclerostegia, Tecticornia, and Tegicornia of the subfamily Salicornioideae (Chenopodiaceae) together form a monophyletic group, congruent with the hypothesis that they evolved from a common ancestor. However, limited genetic differentiation evident in both nrDNA and cpDNA sequences among these taxa suggests a possible rapid radiation. Based on fossil pollen records and climatic models of other authors, it is hypothesized that the expansion of the Australian endemic Salicornioideae most likely occurred during the Late Miocene to Pliocene, when increasing aridity caused the formation of extensive salt lakes along endorheic paleodrainage channels. Moreover, Australian Sarcocornia representatives were supported as monophyletic, nested within a paraphyletic Sarcocornia clade that also comprised European Salicornia in the ITS analysis. This suggests that Sarcocornia arrived in Australia subsequent to the ancestor of the Australian endemic genera most likely via long-distance dispersal

Salicornia L. (Salicornia pusilla J. Woods, S. ramosissima J. Woods, S. europaea L., S. obscura P.W. Ball & Tutin, S. nitens P.W. Ball & Tutin, S. fragilis P.W. Ball & Tutin and S. dolichostachya Moss)

Submitted by Bruna Vieira ([email protected]) on 2012-02-28T02:31:58Z No. of bitstreams: 1 Salicornia L.pdf: 2791228 bytes, checksum: d77351b34bcbc7e26f7df0c9da9757b2 (MD5)Approved for entry into archive by Barbara Milbrath([email protected]) on 2012-03-09T23:47:34Z (GMT) No. of bitstreams: 1 Salicornia L.pdf: 2791228 bytes, checksum: d77351b34bcbc7e26f7df0c9da9757b2 (MD5)Made available in DSpace on 2012-03-09T23:47:34Z (GMT). No. of bitstreams: 1 Salicornia L.pdf: 2791228 bytes, checksum: d77351b34bcbc7e26f7df0c9da9757b2 (MD5) Previous issue date: 200

Ribosomal DNA variation and population differentiation in Salicornia L.

Analysis of nuclear rDNA variation within and between populations of Salicornia from the salt marsh at Stiffkey, Norfolk has detected new patterns of genetic differentiation. Individual plants may have alternative 10.5 and 12 kb repeat units. A strong association between the frequency of particular genetic variants and the environmental gradient of tidal inundation was evident. Salicornia dolichostachya Moss from sandy flats on the lowest parts of the marsh, near to the seaward edge, and S. fragilis Ball & Tutin from deep creeks were both monomorphic for the 12 kb variant; in contrast, S. pusilla J. Woods, characteristic of the highest parts of the tidal range, was monomorphic for the 10–5 kb variant. The more phenotypically variable S. europaea L. and S. ramosissima J. Woods populations that are found in large areas of lower and upper marsh, respectively, were heterogeneous for rDNA variant type. Nevertheless, the frequency of the 12 kb variant was significantly higher in plants from the lower marsh than in those from upper marsh, and in plants from low-lying pans than in those from raised interfluves; the 10.5 kb variant had the converse distribution. Variation in rDNA was not obviously associated with variation in morphology, or with variations in isozyme frequency established previously. Comparison of these results with those for populations from an extensive study, ranging from Anglesey (N. Wales) to S.W. Spain and the Gulf coast of Saudi Arabia, suggested that the rDNA variation and its association with environmental variation are complex and site-dependent. Plants from Anglesey had 10.5 and 11.5 kb variants, whereas only a 10–75 kb variant was detected in material from Spain and Saudi Arabia. rDNA variants were used as genetic markers in order to test the hypothesis that Salicornia is predominantly an inbreeder; conventional breeding experiments have been hampered by its highly specialized morphology and this represents the first direct, sensitive test of an idea that has been suggested mainly on morphological and phenological grounds. Analysis of rDNA in 38 maternal plants from Stiffkey and 2112 of their progeny provided no evidence for out-crossing