Desmophyllum dianthus (Esper, 1794) in the scleractinian phylogeny and its intraspecific diversity

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 7 (2012): e50215, doi:10.1371/journal.pone.0050215.The cosmopolitan solitary deep-water scleractinian coral Desmophyllum dianthus (Esper, 1794) was selected as a representative model species of the polyphyletic Caryophylliidae family to (1) examine phylogenetic relationships with respect to the principal Scleractinia taxa, (2) check population structure, (3) test the widespread connectivity hypothesis and (4) assess the utility of different nuclear and mitochondrial markers currently in use. To carry out these goals, DNA sequence data from nuclear (ITS and 28S) and mitochondrial (16S and COI) markers were analyzed for several coral species and for Mediterranean populations of D. dianthus. Three phylogenetic methodologies (ML, MP and BI), based on data from the four molecular markers, all supported D. dianthus as clearly belonging to the “robust” clade, in which the species Lophelia pertusa and D. dianthus not only grouped together, but also shared haplotypes for some DNA markers. Molecular results also showed shared haplotypes among D. dianthus populations distributed in regions separated by several thousands of kilometers and by clear geographic barriers. These results could reflect limited molecular and morphological taxonomic resolution rather than real widespread connectivity. Additional studies are needed in order to find molecular markers and morphological features able to disentangle the complex phylogenetic relationship in the Order Scleractinia and to differentiate isolated populations, thus avoiding the homoplasy found in some morphological characters that are still considered in the literature.This study was funded by CTM2009-00496 and CGL2011-23306 projects of the “Ministerio de Ciencia e Innovación” (Spain). Research at sea was partly supported by the European Commission F. P.VI Project HERMES Contract No. GOCE-CT-2005-511234-1) and the EU F.P. VII Project HERMIONE(contract number no. 226354)

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

Risk categorization using New American College of Cardiology/American Heart Association guidelines for cholesterol management and its relation to alirocumab treatment following acute coronary syndromes

Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non−high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor. Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category. Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; Pinteraction=0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; Pinteraction=0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; Pinteraction=0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; Pinteraction=0.661). Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402