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
)
Abstract.We describe the effect of inorganic mercury on the emergence, hatching and growth of Artemiafraneiscana (commercially obtained). At concentrations as low as 0.01/tmol 1-1, mercury delays development of the organism, but the effect on the final number of developed brine shrimp is small. At higher concentrations, mercury has a dramatic effect, inhibiting the developmental process at the emergence and hatching stages. As recorded by light and scanning electron microscopy, organisms stalled at emergence are not immediately killed. Their eye spots continue to darken and some may hatch although partially enclosed in the cyst shell. Completely emerged prenauplii in the presence of mercury often have an abnormal oval shape while hatched organisms may display shortened and deformed bodies and exhibit restricted movement. The results demonstrate that emerging A. franciscana are very sensitive to inorganic mercury and the potential usefulness of this organism for the study of metal effects upon physiological processes is indicated.
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The need for simple, fast and inexpensive tests to study metal pollution in the marine environment has become more pressing as utilization of coastal waters increases. To address this concern, the influence of four metals, cupric sulfate, lead nitrate, zinc sulfate and nickel sulfate, on emergence and hatching of the brine shrimp, Artemia, has been assessed. Occurrence of these easily recognized developmental milestones provides a convenient method to assay metal effects on development. Copper and lead were about equally toxic, reducing the rate and extent of Artemia development at or below concentrations of 0.1 microM. Zinc was somewhat less toxic than copper and lead, while nickel was the least toxic. Emerging Artemia are much more sensitive to metals than are larvae and adults. Furthermore, in contrast to results obtained with larvae and adults, the toxicity of lead is high when prelarval stages are considered. It is apparent from the findings that use of early stages of Artemia is an alternative to the examination of slower growing animals for the study of metal pollution in coastal marine waters.
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