ライフサイエンスコーパス: SCAD

1 SCAD affects a young, predominantly female population, f

2 SCAD incidence between 2010 and 2018 (2.7 per 100,000; 9

3 SCAD is a rare but challenging clinical entity.

4 SCAD mainly affects women and is associated with pregnan

5 SCAD occurring in members of the same family has been de

6 SCAD often occurs in patients with fewer cardiovascular

7 SCAD predominantly occurs in relatively young women and

8 SCAD prevalence was 19% in female STEMI patients age <=5

9 SCAD recurrence was 10% (95% CI: 3% to 16%) at 5 years.

10 SCAD shares some genetic overlap with CTD, even in the a

11 SCADs that prevent neurodegenerative disorders, such as

12 In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) wa

13 ary myocardial infarction [SSDM] 34% vs 19%, SCAD 11% vs 0.7%, embolism 2% vs 2%, vasospasm 3% vs 1%,

14 Finally, 2 SCAD polygenic risk scores were applied to assess the co

15 The authors prospectively followed 327 SCAD patients.

16 We identified 375 SCAD patients of which mortality during the index hospit

17 We sequenced a cohort of 384 SCAD survivors from the United Kingdom, alongside 13 722

18 In a subset of 491 SCAD patients, the OR estimate was found to be higher fo

19 (SSDM 33%, atherothrombosis 8%, embolism 8%, SCAD 0%) with low cardiovascular mortality in all groups

20 obank controls and a validation cohort of 92 SCAD survivors.

21 oth the SCAD normal genetic background and a SCAD-deficient background.

22 regnancy-associated SCAD and pregnancy after SCAD, and highlight high-priority knowledge gaps that mu

23 /enhancer driving a mouse SCAD minigene (ALB-SCAD) on both the SCAD normal genetic background and a S

24 hs-cTnT with 1-year clinical outcomes among SCAD patients undergoing percutaneous coronary intervent

25 sociation between the rs9349379 genotype and SCAD.

26 Both glmmLasso and SCAD reduced the Akaike information criterion (AIC) and

27 h, heart failure, myocardial infarction, and SCAD recurrence) was 47%.

28 ection significantly decreased both MCAD and SCAD expression, which is controlled by FoxA2.

29 ted cells rescued the expression of MCAD and SCAD.

30 -activated systemic platelets from STEMI and SCAD patients, 4 of which were selected for validation s

31 STEMI and SCAD samples were compared by a phosphoproteomics approa

32 Angiographic SCAD diagnosis was confirmed by 2 experienced interventi

33 Majority had type 2 angiographic SCAD (67.0%), only 29.1% had type 1, and 3.9% had type 3

34 romuscular dysplasia and type 2 angiographic SCAD.

35 sistent with a complex genetic architecture, SCAD patients also have a higher burden of common varian

36 iagnosed hereditary syndromes manifesting as SCAD.

37 ing age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.

38 ts with SCAD, including pregnancy-associated SCAD and pregnancy after SCAD, and highlight high-priori

39 Extreme exertion at SCAD onset was more frequent in men (7 of 16 versus 2 of

40 ved in another short-chain enzyme, bacterial SCAD.

41 y contribute to the clinical overlap between SCAD and FMD.

42 Our findings strengthen the overlap between SCAD and renal and connective tissue disorders, and we h

43 went head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year).

44 Individuals in the Canadian SCAD Registry genetics study with a high-risk SCAD pheno

45 nd found it challenging to reliably classify SCAD-associated variants, even A2013T where the evidence

46 The common SCAD polymorphisms may lead to clinically relevant alter

47 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31,

48 87 patients with angiographically confirmed SCAD.

49 Patients with confirmed SCAD (n=246; 45.3+/-8.9 years; 96% women) and 313 contro

50 , highlighting the importance of considering SCAD among patients with acute coronary syndromes.

51 ssion were used to produce the corresponding SCAD variant proteins.

52 AS and SCD1 expression as well as decreasing SCAD and PPARalpha, and promoting lipid accumulation, an

53 n short-chain acyl-coenzyme A dehydrogenase (SCAD) from Megasphaera elsdenii.

54 d short-chain acyl coenzyme A dehydrogenase (SCAD), involved in the regulation of beta-oxidation of f

55 er of the short-chain alcohol dehydrogenase (SCAD) family of proteins.

56 Short chain acyl-CoA dehydrogenase (SCAD) is a homotetrameric flavoenzyme that catalyzes the

57 ion of a short-chain acyl-CoA dehydrogenase (SCAD) transgene in the SCAD-deficient mouse model.

58 icity in short chain acyl-CoA dehydrogenase (SCAD).

59 CP) and smoothly clipped absolute deviation (SCAD) analyses, six seed oil-related traits were found t

60 o), and smoothly clipped absolute deviation (SCAD) implemented on linear mixed models.

61 hat the smoothly clipped absolute deviation (SCAD) penalty consistently outperforms the least absolut

62 a group smoothly clipped absolute deviation (SCAD) regression procedure for selecting the TFs with va

63 ing challenges include accurately diagnosing SCAD and improving outcomes.

64 and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the de

65 atients with stable coronary artery disease (SCAD) treated medically.

66 with spontaneous coronary artery dissection (SCAD) a condition where a tear can form in the wall of a

67 Spontaneous coronary artery dissection (SCAD) has been acknowledged as a significant cause of ac

68 Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (

69 s of spontaneous coronary artery dissection (SCAD) has been defined as both partially complex and mon

70 ade, spontaneous coronary artery dissection (SCAD) has emerged as an important cause of myocardial in

71 Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome that predomi

72 Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of myocardial infar

73 Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic acute coronary syndrome fo

74 Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin.

75 Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI

76 Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coron

77 Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial

78 Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic c

79 Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic c

80 Spontaneous coronary artery dissection (SCAD) is an uncommon idiopathic disorder predominantly a

81 Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction

82 gest spontaneous coronary artery dissection (SCAD) is associated with autoimmune diseases and causes

83 Spontaneous coronary artery dissection (SCAD) is gaining recognition as an important cause of my

84 Spontaneous coronary artery dissection (SCAD) is more common than previously thought and is pres

85 Spontaneous coronary artery dissection (SCAD) is the most common cause of pregnancy-associated m

86 Spontaneous coronary artery dissection (SCAD) is underdiagnosed and an important cause of myocar

87 e of spontaneous coronary artery dissection (SCAD) is variable, and no reliable methods are available

88 Spontaneous coronary artery dissection (SCAD) occurs when an epicardial coronary artery is narro

89 sis, spontaneous coronary artery dissection (SCAD), embolism, vasospasm, myocardial infarction with n

90 cted spontaneous coronary artery dissection (SCAD).

91 spital course, but 9 (10%) experienced early SCAD progression requiring revascularization.

92 ous variants in genes associated with either SCAD or CTD, while new candidate genes were sought using

93 It is not known to what extent SCAD is genetically distinct from other cardiovascular d

94 ing domain of TLN1 segregating with familial SCAD.

95 tudy of 189 patients presenting with a first SCAD episode.

96 lication cohort) with mean (SD) age at first SCAD event of 48.41 (8.76) years in the discovery cohort

97 mmon in patients presenting with their first SCAD event (78% versus 17% in controls; P<0.0001; tortuo

98 In our large prospectively followed SCAD cohort, long-term cardiovascular events were common

99 A genetic component for SCAD is increasingly appreciated, although few genes hav

100 The first genetic risk factor for SCAD was identified in the largest study conducted to da

101 to identify a novel susceptibility gene for SCAD.

102 ic variant in genes currently implicated for SCAD.

103 9,292 controls) identifying 16 risk loci for SCAD.

104 serve as a marker or potential mechanism for SCAD.

105 ion model calculated the odds ratio (OR) for SCAD among patients with a history of autoimmune disease

106 PCI for SCAD is associated with high rates of technical failure

107 ly (n=134), 3 required revascularization for SCAD extension, and all 79 who had repeat angiogram >/=2

108 TS: To prioritize genes influencing risk for SCAD, whole-exome sequencing was performed among individ

109 A polygenic risk score for SCAD was associated with (1) higher risk of SCAD in indi

110 scade initiation, appears to be specific for SCAD risk.

111 ues of the green wild-type, R147W, and G185S SCAD enzymes coexpressed with GroEL/ES were 33, 30, and

112 cases have a significantly elevated genetic SCAD risk compared with controls.

113 The proposed group SCAD regression procedure is very effective for identify

114 integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics

115 grity of the coronary artery cytoskeleton in SCAD susceptibility.

116 e of the extracellular matrix dysfunction in SCAD.

117 ty cardiac troponin T (hs-cTnT) elevation in SCAD patients undergoing elective percutaneous coronary

118 common collagen gene variants identified in SCAD cases, demonstrated increased risk of arterial diss

119 fer a causal role for high blood pressure in SCAD.

120 FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99).

121 ine the prevalence of coronary tortuosity in SCAD and whether it may be implicated in the disease.

122 cularization outcomes are largely unknown in SCAD presenting with ST-segment elevation myocardial inf

123 entification of, further talin-1 variants in SCAD patients.

124 rrent SCAD was low in our contemporary large SCAD cohort that included low revascularization rate and

125 e found no detrimental effects of high liver SCAD expression in transgenic mice on either background.

126 Many SCAD patients experience substantial post-SCAD symptoms,

127 er vasculopathies have been observed in many SCAD patients.

128 months (interquartile range, 18-106 months), SCAD recurred in 15 patients, all female.

129 at albumin promoter/enhancer driving a mouse SCAD minigene (ALB-SCAD) on both the SCAD normal genetic

130 Multivessel SCAD was found in 23%.

131 s. 36%; p = 0.009), left main or multivessel SCAD (24% vs. 5%; p < 0.0001; and 33% vs. 14%; p = 0.002

132 n, Arg, and Lys and the wild type and mutant SCADs were produced in Escherichia coli and purified.

133 NA-SCAD survivors are at risk for recurrent cardiovascular

134 c spontaneous coronary artery dissection (NA-SCAD) is underdiagnosed and an important cause of myocar

135 Majority of patients with NA-SCAD had fibromuscular dysplasia and type 2 angiographic

136 Patients with NA-SCAD prospectively evaluated (retrospectively or prospec

137 prospectively evaluated 168 patients with NA-SCAD.

138 Participants attended the national SCAD referral center for assessment and MRA.

139 Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referr

140 Nonatherosclerotic SCAD patients were prospectively followed at Vancouver G

141 al study of patients with nonatherosclerotic SCAD presenting acutely from 22 North American centers.

142 Clinical predictors for recurrent de novo SCAD were tested using univariate and multivariate Cox r

143 dissection not associated with pregnancy (NP-SCAD).

144 ns and high-risk features than women with NP-SCAD did.

145 Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-

146 nd they were compared with 269 women with NP-SCAD.

147 asive imaging modality for the assessment of SCAD.

148 This study determined the association of SCAD with autoimmune diseases, together with incidence a

149 We sought to clarify the genetic cause of SCAD using targeted and genome-wide methods in a cohort

150 etion in urine, a clinical characteristic of SCAD deficiency.

151 The angiographic characteristics of SCAD are largely undetermined.

152 re variant genetic testing among a cohort of SCAD survivors and to identify genes or gene sets that h

153 By studying the largest sequenced cohort of SCAD survivors, we demonstrate that, based on current kn

154 OCT ruled out the diagnosis of SCAD in 6 patients with coronary artery disease (atheros

155 There has been a surge in the diagnosis of SCAD in recent years, presumably due to an increased use

156 elp to guide clinical genetic evaluations of SCAD.

157 Angiographic features of SCAD are associated with extracoronary vasculopathy, inc

158 tion of hs-cTnT is observed in one fourth of SCAD patients undergoing elective percutaneous coronary

159 m to define the long-term natural history of SCAD.

160 The code-based incidence of SCAD has increased over time, highlighting the importanc

161 Incidence of SCAD was much higher in women (3.2 vs 0.9 per 100,000 pe

162 The majority of SCAD patients were taking aspirin and beta-blocker thera

163 and predominantly conservative management of SCAD make coronary CT angiography a useful noninvasive i

164 underlying pathophysiological mechanisms of SCAD are not well understood.

165 ads toward understanding the pathogenesis of SCAD.

166 2013T, has an extensive familial pedigree of SCAD, which led to the screening for, and identification

167 rs, 9 female), OCT confirmed the presence of SCAD.

168 9379-A) was associated with a higher risk of SCAD in all studies.

169 SCAD was associated with (1) higher risk of SCAD in individuals with fibromuscular dysplasia (P = 0.

170 in-hospital outcomes, and long-term risk of SCAD recurrence or major adverse cardiac events were eva

171 Risks of SCAD recurrence and major adverse cardiac events in the

172 bstrate/product couple in the active site of SCAD.

173 undertook a genome-wide association study of SCAD (N(cases) = 270/N(controls) = 5,263) and identified

174 regnant or </=12 weeks postpartum at time of SCAD.

175 ovide a comprehensive contemporary update of SCAD to aid health care professionals in managing these

176 d screening for autoimmune diseases based on SCAD alone is not warranted.

177 fined by sequencing for vascular CTDs and/or SCAD, as well as genes prioritized by genome-wide associ

178 fined as peripartum SCAD, recurrent SCAD, or SCAD in an individual with family history of arteriopath

179 , and genes related to lipid beta-oxidation (SCAD and PPARalpha) were downregulated, while metformin

180 P-SCAD patients had more acute presentations and high-risk

181 rred during the first postpartum month and P-SCAD patients less often had extracoronary vascular abno

182 ed spontaneous coronary artery dissection (P-SCAD) compared with spontaneous coronary artery dissecti

183 effect of genotype on age at first event, P-SCAD, or recurrence.

184 e for 323 women; 54 women met criteria for P-SCAD (4 during pregnancy) and they were compared with 26

185 The highest frequency of P-SCAD occurred during the first postpartum month and P-SC

186 at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.

187 Compared with NP-SCAD, P-SCAD patients more frequently presented with ST-segment

188 ith imaging of other vascular territories, P-SCAD was less likely with a diagnosis of fibromuscular d

189 nisms might be significant contributors to P-SCAD..

190 Compared with U.S. birth data, women with P-SCAD were more often multiparous (p = 0.0167), had a his

191 Among 5,208 STEMI patients, SCAD was present in 53 (1%; 93% female).

192 nary fibromuscular dysplasia, and peripartum SCAD were independent predictors of long-term MACE.

193 type were selected and defined as peripartum SCAD, recurrent SCAD, or SCAD in an individual with fami

194 Presence of genetic disorders, peripartum SCAD, and extracoronary fibromuscular dysplasia were ind

195 dentified novel associations with peripartum SCAD.

196 ny SCAD patients experience substantial post-SCAD symptoms, recurrent SCAD, and psychosocial distress

197 8%, recurrent MI 9.9% (extension of previous SCAD 3.5%, de novo recurrent SCAD 2.4%, iatrogenic disse

198 comprehensive retrospective and prospective SCAD data.

199 ty of Glu368 as the catalytic residue of rat SCAD and suggest that alteration of the position of the

200 hetical active site catalytic residue of rat SCAD, was replaced with Asp, Gly, Gln, Arg, and Lys and

201 n the SCAD-deficient background, recombinant SCAD activity and antigen in liver mitochondria were fou

202 Recurrent SCAD (n=40) occurred within segments of tortuosity in 80

203 Recurrent SCAD most often occurs within segments of tortuosity.

204 Recurrent SCAD occurred in 10.4% of patients.

205 Recurrent SCAD occurred in 13.1%.

206 ed (hazard ratio: 0.36; p = 0.004) recurrent SCAD.

207 arget vessel revascularization and recurrent SCAD were no different in revascularization versus conse

208 ancy-associated SCAD (P-SCAD), and recurrent SCAD.

209 cardiovascular outcomes, including recurrent SCAD, are inadequately reported.

210 t cardiovascular events, including recurrent SCAD.

211 ion of previous SCAD 3.5%, de novo recurrent SCAD 2.4%, iatrogenic dissection 1.9%), with overall MAC

212 Long-term mortality and de novo recurrent SCAD was low in our contemporary large SCAD cohort that

213 s associated with a higher risk of recurrent SCAD (hazard ratio, 3.29; 95% confidence interval, 0.99-

214 with a trend toward higher risk of recurrent SCAD (P=0.16).

215 Hypertension increased the risk of recurrent SCAD, whereas beta-blocker therapy appeared to be protec

216 comes and assess the predictors of recurrent SCAD.

217 target vessel revascularization or recurrent SCAD.

218 ed and defined as peripartum SCAD, recurrent SCAD, or SCAD in an individual with family history of ar

219 ce substantial post-SCAD symptoms, recurrent SCAD, and psychosocial distress.

220 population and is associated with recurrent SCAD.

221 -term follow-up (median 2.3 years) recurrent SCAD occurred in 51 patients, with no difference in the

222 .0% of individuals (16 of 94) with high-risk SCAD and were enriched (OR, 2.6; 95% CI, 1.6-4.2; P = 7.

223 ximately 1 in 5 individuals with a high-risk SCAD phenotype harbored a rare genetic variant in genes

224 CAD Registry genetics study with a high-risk SCAD phenotype were selected and defined as peripartum S

225 influences has not been defined in high-risk SCAD phenotypes, and the identification of a high-risk s

226 6.4% of individuals (6 of 94) with high-risk SCAD, were also enriched (OR, 3.6; 95% CI, 1.6-8.2; P =

227 DNA sequencing in individuals with high-risk SCAD.

228 annotation among individuals with high-risk SCAD.

229 formance liquid chromatography in a sporadic SCAD cohort of 675 unrelated individuals.

230 ase-associated gene in familial and sporadic SCAD and, together with abnormal vascular phenotypes rep

231 genic risk scores demonstrated that sporadic SCAD cases have a significantly elevated genetic SCAD ri

232 A cohort of 91 unrelated sporadic SCAD cases was investigated for rare, deleterious varian

233 amilial case and 5 individuals with sporadic SCAD from whom parental DNA was available.

234 STEMI-SCAD represents an important STEMI subset, particularly

235 Compared with STEMI-ATH, STEMI-SCAD patients were younger (age 49 +/- 10 years vs. 63 +

236 The 3-year survival was 98% for STEMI-SCAD versus 84% for STEMI-ATH; p < 0.001.

237 Acute revascularization was lower in STEMI-SCAD (70% vs. 97%); p < 0.001.

238 In STEMI-SCAD, acute revascularization included percutaneous coro

239 In STEMI-SCAD, the culprit artery was more commonly left main (13

240 Primary PCI is successful in most STEMI-SCAD patients, with low 3-year mortality.

241 ularization strategies and outcomes of STEMI-SCAD with STEMI atherosclerosis (STEMI-ATH).

242 These findings suggested SCAD pathogenesis is noninflammatory and screening for a

243 Here we report that SCAD-related MI and atherosclerotic MI exist at opposite

244 al and cell biological methods, we show that SCAD-associated variants in talin-1, which would typical

245 a mouse SCAD minigene (ALB-SCAD) on both the SCAD normal genetic background and a SCAD-deficient back

246 artery tortuosity is highly prevalent in the SCAD population and is associated with recurrent SCAD.

247 yl-CoA dehydrogenase (SCAD) transgene in the SCAD-deficient mouse model.

248 wo polymorphisms in the coding region of the SCAD gene, 511C>T (R147W) and 625G>A (G185S), have been

249 In three transgenic lines produced on the SCAD-deficient background, recombinant SCAD activity and

250 logy and other fields to fit models with the SCAD penalty, we implement the algorithm in a Julia pack

251 GPVI agonists in STEMI patients compared to SCAD controls.

252 r identification of patients with ACS due to SCAD prone to early mortality.

253 ported to associate with a predisposition to SCAD and indicate suggestions for the future strategies

254 The recombinant wild type SCAD kcat/K(m) values for butyryl-hexanoyl-, and octanoy

255 Unfortunately, SCAD remains underdiagnosed due to a lack of awareness a

256 of bacteria and 1 animal datum) fitted using SCAD.

257 autoimmune diseases were not associated with SCAD (OR: 0.81; 95% confidence interval [CI]: 0.40 to 1.

258 No genes were significantly associated with SCAD from genome-wide collapsing analysis, however, enri

259 found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to

260 a were analyzed to test the association with SCAD risk, including age at first event, pregnancy-assoc

261 The study identified 114 cases with SCAD (mean age 51 years and 90% women) and 342 matched c

262 mune disease occurred in 13 (11%) cases with SCAD and 40 (12%) control subjects (p = 0.93).

263 The study identified cases with SCAD from diagnosis codes and verified them using corona

264 1.5 x 10-9) enriched among individuals with SCAD compared with a background of 2506 constrained gene

265 uencing was performed among individuals with SCAD in the discovery and replication cohorts from a ter

266 ring aggregated variants in individuals with SCAD to healthy matched controls or the Genome Aggregati

267 iduals from the UK Biobank, individuals with SCAD were 1.75-fold (P = .04) more likely to carry disru

268 e sets was compared between individuals with SCAD with population-based controls comprising 46 468 UK

269 of rare genetic variants in individuals with SCAD.

270 Among patients with SCAD (n=2029), 527 (26%) had elevated preprocedural hs-c

271 Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (

272 ively enrolled 750 consecutive patients with SCAD from June 2014 to June 2018.

273 CT provides unique insights in patients with SCAD that allow an early diagnosis and adequate manageme

274 Unbiased gene discovery in patients with SCAD with independent human and murine validation highli

275 Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis

276 he diagnosis and management of patients with SCAD, including pregnancy-associated SCAD and pregnancy

277 Across all patients with SCAD, rare disruptive variants were found within 10 coll

278 eries with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections

279 f mortality using ML models in patients with SCAD, the AUC ranged from 0.50 with the random forest me

280 edict in-hospital mortality in patients with SCAD.

281 this subgroup of individuals presenting with SCAD may be considered.

282 96% women) and 313 control patients without SCAD or coronary artery disease who underwent coronary a