Citations 3
Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program
Klarin, Derek , Judy, Renae , Dikilitas, Ozan , Wolford, Brooke N. , Paranjpe, Ishan , Levin, Michael G. , Pan, Cuiping , Tcheandjieu, Catherine , Spin, Joshua M. , Assimes, Themistocles L. , Nyrønning, Linn Åldstedt , Mattsson, Erney , Denny, Joshua C. , Zhang, Yanfei , Jarvik, Gail P. , Gharavi, Ali G. , Harley, John B. , Mentch, Frank , Håkonarson, Håkon , Skogholt, Anne Heidi , Thomas, Laurent F. , Gabrielsen, Maiken E. , Zhou, Wei , Fritsche, Lars G. , Huang, Jie , Natarajan, Pradeep , Sun, Yan V. , DuVall, Scott L. , Cho, Kelly , Chang, Kyong‐Mi , Wilson, Peter W.F. , O’Donnell, Christopher J., Kathiresan, Sekar , Scali, Salvatore T. , Jones, Gregory T. , Bown, Matthew J. , Nadkarni, Girish N. , Ritchie, Marylyn D. , Tsao, Philip S. , Gaziano, J. Michael , Ramoni, Rachel , Breeling, Jim, Huang, Grant D. , Muralidhar, Sumitra , O’Donnell, Christopher J. , Romero, Jonathan , Tsao, Philip S., Moser, Jennifer , Whitbourne, Stacey B. , Brewer, Jessica V., Warren, Stuart, Argyres, Dean P., Tsao, Philip S., Stephens, Brady, Brophy, Mary T. , Humphries, Donald E., Shayan, Shahpoor, O’Donnell, Christopher J., Pyarajan, Saiju , Tsao, Philip S., Dell’Italia, Louis J. , Zablocki, Clement J., Beckham, Jean, Wells, John A. , Gutierrez, Salvador, Kaminsky, Laurence S., Villareal, Gerardo, Xu, Junzhe, Hamner, Mark B. , Haddock, Kathlyn Sue, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Buford, Malcolm, Mastorides, Stephen , Ratcliffe, Nora, Flórez, Hermes , Swann, Alan C. , Murdoch, Maureen, Yeh, Shing Shing, Washburn, Ronald G., Jhala, Darshana , Aguayo, Samuel M., Cohen, David , Sharma, Satish, Callaghan, John, Oursler, Kris Ann, Ahuja, Sunil K. , Gutierrez, Amparo, Schifman, Ronald, Greco, Jennifer , Oehlert, Mary E. , Wallbom, Agnes, Fernando, Ronald, Morgan, Timothy R. , Stapley, Todd, Anderson, Gwenevere, Sonel, Elif, Fayad, Joseph, Hung, Adriana M. , Lichy, Jack, Hurley, Robin A. , Hakonarson, Hakon , Denny, Joshua C , Jarvik, Gail P , Dikilitas, Ozan , Assimes, Themistocles L , Natarajan, Pradeep , Wolford, Brooke N , Scali, Salvatore , Chang, Kyong-Mi , Tsao, Philip S , Verma, Shefali S. , Lynch, Julie A. , Edwards, Todd L. , Larson, Eric B. , Lee, Ming Ta Michael , Carrell, David , Pacheco, Jennifer A. , Hveem, Kristian , Nielsen, Jonas Bille , Rader, Daniel J , O’Donnell, Christopher J., Berceli, Scott A. , Willer, Cristen J , Kullo, Iftikhar J. , Damrauer, Scott M , Beckham, Jean C , Tsao, Philip S., Concato, John , Tsao, Philip S., Do, Nhan , Nguyen, Xuan‐Mai T. , O’Donnell, Christopher J., Tsao, Philip S., Hauser, Elizabeth R. , Zhao, Hongyu , McArdle, Rachel , Whittle, Jeff , Beckham, Jean, Wells, John, Gibson, Gretchen , Kinlay, Scott , Ballas, Zuhair K. , Klein, Jon , Sriram, Peruvemba , Washburn, Ronald, Whooley, Mary A. , Rauchman, Michael I. , Servatius, Richard J. , Sherman, Scott E. , Boyko, Edward J. , Meyer, Laurence , Gupta, Samir , Robey, R. Brooks , Striker, Rob
Circulation | September 28, 2020 | Volume: 142 | Issue: 17 | Pages: 1633-1646
10.1161/circulationaha.120.047544
Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P =1.6×10 −6 ), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P =0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratio PRS , 1.26 [95% CI, 1.18–1.36]; P PRS =2.7×10 −11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratio PRS+family history+smoking , 1.24 [95% CI, 1.14–1.35]; P PRS =1.27×10 −6 ). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.
Response by Latif et al to Letter Regarding Article, "Stent-Only Versus Adjunctive Balloon Angioplasty Approach for Saphenous Vein Graft Percutaneous Coronary Intervention: Insights From DIVA Trial"
Latif, Faisal , Uyeda, Lauren , Edson, Robert , Bhatt, Deepak L. , Goldman, Steven , Holmes, David R. , Shunk, Kendrick , Aggarwal, Kul, Bolad, Islam, McFalls, Edwards, Irimpen, Anand, Truong, Huu Tam, Kinlay, Scott , Velagaleti, Raghava S. , Rangan, Bavana V. , Mavromatis, Kreton , Shih, Mei-Chiung , Bhatt, Deepak L , Rao, Sunil V. , Uretsky, Barry F. , Ziada, Khaled M. , Papademetriou, Vasilios , Banerjee, Subhash , Brilakis, Emmanouil S.
Circulation: Cardiovascular Interventions | April 13, 2020 | Volume: 13 | Issue: 4 | Pages: No page available
Stent-Only Versus Adjunctive Balloon Angioplasty Approach for Saphenous Vein Graft Percutaneous Coronary Intervention
Latif, Faisal , Uyeda, Lauren , Edson, Robert , Bhatt, Deepak L. , Goldman, Steven , Holmes, David R. , Shunk, Kendrick , Aggarwal, Kul, Bolad, Islam, Ziada, Khaled M. , McFalls, Edward O. , Irimpen, Anand, Truong, Huu Tam, Kinlay, Scott , Velagaleti, Raghava S. , Rangan, Bavana V. , Mavromatis, Kreton , Shih, Mei-Chiung , Ziada, Khaled , Bhatt, Deepak L , Rao, Sunil V. , Uretsky, Barry F. , Papademetriou, Vasilios , Banerjee, Subhash , Brilakis, Emmanouil S.
Circulation: Cardiovascular Interventions | February 5, 2020 | Volume: 13 | Issue: 2 | Pages: No page available
10.1161/circinterventions.119.008494
Background: Direct stenting without pre-dilation or post-dilation has been advocated for saphenous vein graft percutaneous coronary intervention to decrease the incidence of distal embolization, periprocedural myocardial infarction, and target lesion revascularization. Methods: We performed a post hoc analysis of patients enrolled in the DIVA (Drug-Eluting Stents Versus Bare Metal Stents in Saphenous Vein Graft Angioplasty; NCT 01121224) prospective, double-blind, randomized controlled trial. Patients were stratified into stent-only and balloon-stent groups. Primary end point was 12-month incidence of target vessel failure (defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization). Secondary end points included all-cause death, stent thrombosis, myocardial infarction, and target lesion revascularization during follow-up. Results: Of the 575 patients included in this substudy, 185 (32%) patients underwent stent-only percutaneous coronary intervention. Patients in the stent-only versus balloon-stent group had similar baseline characteristics and similar incidence of target vessel failure at 12-months (15% versus 19%; hazard ratio, 1.34 [95% CI, 0.86–2.08]; P =0.19). During long-term follow-up (median of 2.7 years), the incidence of definite stent thrombosis (1% versus 5%; hazard ratio, 9.20 [95% CI, 1.23–68.92]; P =0.0085), the composite of definite or probable stent thrombosis (5% versus 11%; hazard ratio, 2.52 [95% CI, 1.23–5.18]; P =0.009), and target vessel myocardial infarction (8% versus 14%; hazard ratio, 1.92 [95% CI, 1.08–3.40]; P =0.023) was lower in the stent-only group. Multivariable analysis showed that a higher number of years since coronary artery bypass grafting and >1 target saphenous vein graft lesions were associated with increased target vessel failure during entire follow-up, while preintervention Thrombolysis in Myocardial Infarction-3 flow was protective. Conclusions: In patients undergoing percutaneous coronary intervention of de novo saphenous vein graft lesions, there was no difference in target vessel failure at 12 months and long-term follow-up in the stent-only versus the balloon-stent group; however, the incidence of stent thrombosis was lower in the stent-only group, as was target vessel myocardial infarction. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT 01121224.