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Coronary artery disease

Genetic variant protects against coronary disease

11 Jul, 16 | by flee

The links between cholesterol and coronary artery disease are well established and incontrovertible, with modification of serum LDL cholesterol levels repeatedly shown to reduce risk of myocardial infarction and cardiovascular death. But total non-HDL cholesterol levels, encompassing multiple other lipid fractions including Lp(a) and chylomicrons, have the strongest overall association with the risk of incipient coronary artery disease. In this large genome-wide association study, the authors identify a novel noncoding 12-base-pair deletion in intron 4 of the ASGR1 gene that appears to be associated with lower levels of non-HDL cholesterol.  In an initial discovery cohort of 2636 Icelanders, the polymorphism was associated with a reduced risk of atherosclerotic coronary disease. Further testing in a cohort of 398,000 Icelanders demonstrated a prevalence of heterozygous carriers of approximately 1 in 120. These carriers had lower levels of non-HDL cholesterol and a significant 34% reduction in rates of coronary artery disease (95% CI, 21 to 45; P=4.0×10(-6)).  To further validate these associations, five other large European cohorts containing a total of 42,524 case patients and 249,414 controls were analyzed with results consistent to those seen in the Icelandic cohort.  Finally, the authors describe a second loss of function polymorphism in the same ASGR1 gene that again leads to significantly reduced levels of non-HDL cholesterol in carriers, validating their initial hypothesis that ASGR1 is directly implicated in non-HDL cholesterol homeostasis.


Pre-operative aspirin does not influence CABG outcomes.

28 Apr, 16 | by flee

Aspirin is a common therapy for risk reduction among patients with coronary artery disease.  However, among patients undergoing coronary artery bypass surgery, the benefits of aspirin on the risk of myocardial infarction and stroke may be outweighed by perioperative bleeding risk.   To address this question, the ATACAS trial randomized 2100 patients to either receive 100 mg aspirin daily or matching placebo for 4 days immediately prior to the operation with all patients resuming aspirin within 24 hours of their bypass surgery. The primary outcome was a composite of death and thrombotic episodes (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days.  Overall rates of post-operative myocardial infarction were 14.8%, which is higher than typical for studies of post-bypass outcomes and may reflect use of troponin surveillance for the identification of this outcome.  There were no significant differences in the primary endpoint or individual components of the primary end-point between aspirin treatment and placebo groups.

Conclusions: In this large trial of perioperative aspirin therapy, there was no difference in clinical outcomes from administration or discontinuation of aspirin in the pre-operative period.  Although these findings suggest either strategy is safe, the trail appears to have limited outcomes assessment to the post-operative period.  As a result, this trial may underestimate the impact of aspirin therapy as it relates to events in the immediate preoperative period.  Additional analyses of event rates in this preoperative period may further inform optimal perioperative use of aspirin therapy.

Summarized by Hussain Contractor and Steven M. Bradley

Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, Wallace S; ATACAS Investigators of the ANZCA Clinical Trials Network. Stopping vs. Continuing Aspirin before Coronary Artery Surgery. N Engl J Med. 2016 Feb 25;374(8):728-37.

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