MD; for the Nordic PCI Study GroupBackground-The optimal stenting strategy in coronary artery bifurcation lesions is unknown. In the present study, a strategy of stenting both the main vessel and the side branch (MVϩSB) was compared with a strategy of stenting the main vessel only, with optional stenting of the side branch (MV), with sirolimus-eluting stents. Methods and Results-A total of 413 patients with a bifurcation lesion were randomized. The primary end point was a major adverse cardiac event: cardiac death, myocardial infarction, target-vessel revascularization, or stent thrombosis after 6 months. At 6 months, there were no significant differences in rates of major adverse cardiac events between the groups (MVϩSB 3.4%, MV 2.9%; PϭNS). In the MVϩSB group, there were significantly longer procedure and fluoroscopy times, higher contrast volumes, and higher rates of procedure-related increases in biomarkers of myocardial injury. A total of 307 patients had a quantitative coronary assessment at the index procedure and after 8 months. The combined angiographic end point of diameter stenosis Ͼ50% of main vessel and occlusion of the side branch after 8 months was found in 5.3% in the MV group and 5.1% in the MVϩSB group (PϭNS). Conclusions-Independent of stenting strategy, excellent clinical and angiographic results were obtained with percutaneous treatment of de novo coronary artery bifurcation lesions with sirolimus-eluting stents. The simple stenting strategy used in the MV group was associated with reduced procedure and fluoroscopy times and lower rates of procedure-related biomarker elevation. Therefore, this strategy can be recommended as the routine bifurcation stenting technique.

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Faber J, Gall\l=o/\eAM. Changes in bone mass during prolonged subclinical hyperthyroidism due to l \ x =r eq-\ thyroxine treatment: a meta-analysis. Eur years and treated with 171 \g=m\gl-T4/day for 9.9 years had 9.02% less bone mass than controls (2p < 0.007), corresponding to a significant excess of annual loss of 0.91% after 9.9 years of treatment. Eighteen papers with a mean of 18 patients showing no difference between postmenopausal patients and controls would have to be published or found before this difference could turn into a non\x=req-\ significant finding (the file drawer problem). In conclusion, the meta-analysis on the available crosssectional studies did not find any significant reduction in bone mass during prolonged l-T4 treatment resulting in reduced serum TSH in premenopausal women. The risk of the present meta-analysis missing a clinically relevant annual loss of at least 1% in premenopausal women was less than 15%. In contrast, l-T4 treatment in postmenopausal women in a dosis leading to reduced serum TSH resulted in a significant excess of annual bone loss of 0.91%/year after 9.9 years in comparison to control women.

BACKGROUNDSeveral sequence variants are known to have effects on serum levels of non-highdensity lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease. METHODSWe sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent. We assessed the effects of an implicated loss-of-function variant on the risk of coronary artery disease in 42,524 case patients and 249,414 controls from five European ancestry populations. An augmented set of genomes was screened for additional loss-of-function variants in a target gene. We evaluated the effect of an implicated variant on protein stability. RESULTSWe found a rare noncoding 12-base-pair (bp) deletion (del12) in intron 4 of ASGR1, which encodes a subunit of the asialoglycoprotein receptor, a lectin that plays a role in the homeostasis of circulating glycoproteins. The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a premature stop codon that renders a truncated protein prone to degradation. Heterozygous carriers of the mutation (1 in 120 persons in our study population) had a lower level of non-HDL cholesterol than noncarriers, a difference of 15.3 mg per deciliter (0.40 mmol per liter) (P = 1.0×10 −16 ), and a lower risk of coronary artery disease (by 34%; 95% confidence interval, 21 to 45; P = 4.0×10 −6 ). In a larger set of sequenced samples from Icelanders, we found another loss-of-function ASGR1 variant (p.W158X, carried by 1 in 1850 persons) that was also associated with lower levels of non-HDL cholesterol (P = 1.8×10 −3 ). CONCLUSIONSASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health and others.)A BS TR AC T

Background-In a number of coronary bifurcation lesions, both the main vessel and the side branch need stent coverage.Using sirolimus eluting stents, we compared 2 dedicated bifurcation stent techniques, the crush and the culotte techniques in a randomized trial with separate clinical and angiographic end-points. Methods and Results-A total of 424 patients with a bifurcation lesion were randomized to crush (nϭ209) and culotte (nϭ215) stenting. The primary end point was major adverse cardiac events; cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis after 6 months. At 6 months there were no significant differences in major adverse cardiac event rates between the groups; crush 4.3%, culotte 3.7% (Pϭ0.87). Procedure and fluoroscopy times and contrast volumes were similar in the 2 groups. The rates of procedure-related increase in biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group (Pϭ0.08). A total of 324 patients had a quantitative coronary assessment at the index procedure and after 8 months. The angiographic end-points of in-segment and in-stent restenosis of main vessel and/or side branch after 8 months were found in 12.1% versus 6.6% (Pϭ0.10) and in 10.5% versus 4.5% (Pϭ0.046) in the crush and culotte groups, respectively. Conclusions-Both the crush and the culotte bifurcation stenting techniques were associated with similar and excellent clinical and angiographic results. Angiographically, there was a trend toward less in-segment restenosis and significantly reduced in-stent restenosis following culotte stenting. (Circ Cardiovasc Intervent. 2009;2:27-34.)