Abstract Background Approximately 7% of American adults have severe hypercholesterolemia (untreated low-density lipoprotein LDL cholesterol ≥190 mg/dl), which may be due to familial ...hypercholesterolemia (FH). Lifelong LDL cholesterol elevations in FH mutation carriers may confer coronary artery disease (CAD) risk beyond that captured by a single LDL cholesterol measurement. Objectives This study assessed the prevalence of an FH mutation among those with severe hypercholesterolemia and determined whether CAD risk varies according to mutation status beyond the observed LDL cholesterol level. Methods Three genes causative for FH ( LDLR , APOB , and PCSK9 ) were sequenced in 26,025 participants from 7 case-control studies (5,540 CAD case subjects, 8,577 CAD-free control subjects) and 5 prospective cohort studies (11,908 participants). FH mutations included loss-of-function variants in LDLR , missense mutations in LDLR predicted to be damaging, and variants linked to FH in ClinVar, a clinical genetics database. Results Among 20,485 CAD-free control and prospective cohort participants, 1,386 (6.7%) had LDL cholesterol ≥190 mg/dl; of these, only 24 (1.7%) carried an FH mutation. Within any stratum of observed LDL cholesterol, risk of CAD was higher among FH mutation carriers than noncarriers. Compared with a reference group with LDL cholesterol <130 mg/dl and no mutation, participants with LDL cholesterol ≥190 mg/dl and no FH mutation had a 6-fold higher risk for CAD (odds ratio: 6.0; 95% confidence interval: 5.2 to 6.9), whereas those with both LDL cholesterol ≥190 mg/dl and an FH mutation demonstrated a 22-fold increased risk (odds ratio: 22.3; 95% confidence interval: 10.7 to 53.2). In an analysis of participants with serial lipid measurements over many years, FH mutation carriers had higher cumulative exposure to LDL cholesterol than noncarriers. Conclusions Among participants with LDL cholesterol ≥190 mg/dl, gene sequencing identified an FH mutation in <2%. However, for any observed LDL cholesterol, FH mutation carriers had substantially increased risk for CAD.
Abstract Objectives This study investigates the influence of implantation depth and prosthesis oversizing on conduction abnormalities (CA) and permanent pacemaker implantation (PPI) after SAPIEN 3 ...(Edwards Lifesciences, Irvine, California) implantation. Background CA and PPIs are frequent complications after transcatheter aortic valve replacement with a next-generation balloon-expandable transcatheter heart valve (SAPIEN 3). The potential underlying mechanisms are incompletely understood. Methods Of 244 patients treated with SAPIEN 3,208 without a previous pacemaker and 184 without baseline CA were analyzed. We assessed the association of angiographic implantation depth (% of frame height below the annulus) and degree of oversizing with PPI and CA. Results New PPI and new or worsened CA or PPI occurred in 16% (34 of 208) and 31% (57 of 184), respectively. Patients requiring PPI had a higher prevalence of atrial fibrillation (44% vs. 24%; p = 0.017), complete right bundle branch block (27% vs. 5%; p = 0.001), and bradycardia (<60 beats/min, 38% vs. 21%; p = 0.034). In patients with new CA or PPI, implantation depth was lower (at septal side: 29 ± 8% vs. 25 ± 7%; p = 0.003), and rate of oversizing was higher (19% 11 of 57 vs. 6% 8 of 126; p = 0.007). Independent predictors of new or worsened CA or PPI were implantation depth at septal side (odds ratio OR: 1.063 95% confidence interval (CI): 1.017 to 1.110; p = 0.006 per % of frame below the aortic annulus), oversizing (OR: 3.489 95% CI: 1.236 to 9.848; p = 0.018), and QRS duration (OR: 1.033 95% CI: 1.011 to 1.056; p = 0.003 per ms). Conclusions Implantation depth and prosthesis oversizing were associated with a higher rate of new CA or PPI using the SAPIEN 3. Thus, avoidance of deep implantation and extreme oversizing may reduce these complications.
Numerous patients are treated with the MitraClip, although they do not fulfill the stringent inclusion criteria of the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) trials. The outcome of ...those patients is not well known. Therefore, we compared the long-term outcome after MitraClip treatment between patients who matched (group 1) and did not match (group 2) the EVEREST criteria. One hundred thirty-four consecutive patients were treated from September 2009 to July 2012: 59 patients (44%) in group 1 versus 75 patients (56%) in group 2. Investigated end points were acute procedural success (for group 1 vs 2: 97% vs 95%; p = 0.694), all-cause mortality (28% vs 27%; p = 0.656), reintervention (RI) rate (11% vs 37%; p = 0.010), and improvement in mitral regurgitation (MR) (−1.3 ± 1 vs −1.5 ± 1, p = 0.221) and in New York Heart Association functional class (−0.7 ± 1 vs −0.9 ± 0.8, p = 0.253) during the follow-up of 33 months (27.9 to 38.3). The morphologic extent of a flail leaflet was an independent predictor for RI. In conclusion, although the overall outcome was comparable between both groups, recurrent symptomatic MR with need for RI was higher in group 2, mainly because of complex valve pathologies: especially flail width >15 mm and gap ≥10 mm. Improvements in the interventional strategy are warranted for reducing the need for RI in patients with primary MR.
Abstract Background The prognostic value of high-sensitivity troponin T (hs-TnT) elevation after elective percutaneous coronary intervention (PCI) in patients with or without raised baseline hs-TnT ...levels is unclear. Objectives The goal of this study was to assess whether the prognostic value of post-procedural hs-TnT level after elective PCI depends on the baseline hs-TnT level. Methods This study included 5,626 patients undergoing elective PCI who had baseline and peak post-procedural hs-TnT measurements available. The primary outcome was 3-year mortality (with risk estimates calculated per SD increase of the log hs-TnT scale). Results Patients were divided into 4 groups: nonelevated baseline and post-procedural hs-TnT levels (hs-TnT ≤0.014 μg/l; n = 742); nonelevated baseline but elevated post-procedural hs-TnT levels (peak post-procedural hs-TnT >0.014 μg/l; n = 2,721); elevated baseline hs-TnT levels (hs-TnT >0.014 μg/l) with no further rise post-procedure (n = 516); and elevated baseline hs-TnT levels with a further rise post-procedure (n = 1,647). A total of 265 deaths occurred: 6 (1.6%) in patients with nonelevated baseline and post-procedural hs-TnT levels; 54 (3.8%) in patients with nonelevated baseline but elevated post-procedural hs-TnT levels; 50 (16.0%) in patients with elevated baseline hs-TnT levels with no further rise post-procedure; and 155 (18.2%) in patients with elevated baseline hs-TnT levels with a further rise post-procedure (p < 0.001). After adjustment, baseline hs-TnT levels (hazard ratio HR: 1.22; 95% confidence interval CI: 1.09 to 1.38; p < 0.001) but not peak post-procedural hs-TnT levels (HR: 1.04; 95% CI: 0.85 to 1.28; p = 0.679) were associated with an increased risk of mortality. Peak post-procedural hs-TnT findings were not associated with mortality in patients with nonelevated (HR: 0.93; 95% CI: 0.69 to 1.25; p = 0.653) or elevated (HR: 1.24; 95% CI: 0.91 to 1.69; p = 0.165) baseline hs-TnT levels. Conclusions In patients with coronary artery disease undergoing elective PCI, an increase in post-procedural hs-TnT level did not offer prognostic information beyond that provided by the baseline level of the biomarker.
Summary Background A sexual dimorphism exists in the incidence and prevalence of coronary artery disease—men are more commonly affected than are age-matched women. We explored the role of the Y ...chromosome in coronary artery disease in the context of this sexual inequity. Methods We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. Findings Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20–2·54, p=0·004), WOSCOPS (1·45, 1·08–1·95, p=0·012), and joint analysis of both populations (1·56, 1·24–1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. Interpretation The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. Funding British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.
The relation between body mass index (BMI) and bleeding after percutaneous coronary intervention (PCI) remains incompletely understood. This study aimed to assess the association between BMI and ...bleeding and mortality after PCI. The study included 14,178 patients with coronary artery disease treated by PCI. Bleeding within 30 days of PCI was defined using the Bleeding Academic Research Consortium criteria. The primary outcome was 1-year all-cause mortality. BMI quartiles were 14.1 to 24.8 kg/m2 (first quartile Q1), >24.8 to 27.1 kg/m2 (second quartile Q2), >27.1 to 29.8 kg/m2 (third quartile Q3), and >29.8 to 56.3 kg/m2 (fourth quartile Q4). In BMI Q1, Q2, Q3, and Q4, the frequency of bleeding was 13.8%, 10.1%, 10.8%, and 7.7%, respectively (odds ratio OR 1.90, 95% confidence interval CI 1.63 to 2.23, p <0.001, for Q1 vs Q4). Multiple logistic regression showed that BMI was independently associated with bleeding (adjusted OR 1.05, 95% CI 1.04 to 1.07, p <0.001, for any bleeding; adjusted OR 1.07, 95% CI 1.04 to 1.09, p <0.001, for access site bleeding; and adjusted OR 1.03, 95% CI 1.01 to 1.05, p = 0.039, for non–access site bleeding with all 3 risk estimates calculated per 1 kg/m2 decrease in BMI). Analysis by sex showed an increase in the frequency of bleeding with the decrease in BMI for women and men (p for trend <0.001 for women and men) with no sex-by-BMI interaction (p = 0.90). The Cox proportional hazards model showed that bleeding (adjusted hazard ratio HR 2.17, 95% CI 1.67 to 2.82, p <0.001) and BMI (HR 1.03, 95% CI 1.01 to 1.06, p = 0.048, per 1 kg/m2 decrease in the BMI) were independently associated with increased risk of 1-year mortality with no bleeding-by-BMI interaction (p = 0.81). In conclusion, BMI is inversely associated with the increased risk of bleeding and mortality after PCI.
Background Factors underlying the increased risk of bleeding after percutaneous coronary intervention (PCI) in women compared with men remain incompletely understood. Methods The study included 3,351 ...women and 3,351 men matched for age, body mass index, and type of antithrombotic therapy. Bleeding within the 30 days after PCI was defined using the Bleeding Academic Research Consortium criteria. The main outcome was 1-year mortality. Results Bleeding occurred in 518 women and 354 men (15.5% vs 10.6%, odds ratio OR 1.55, 95% CI 1.34-1.79, P < .001). Severe (Bleeding Academic Research Consortium class ≥2) bleeds (9.4% vs 6.5%, P < .001) and access site bleeds (10.1% vs 5.4%, P < .001) were more common in women. After adjustment, female sex remained an independent correlate of any bleeding (adjusted OR 1.61 1.35-1.92, P < .001) and access site (adjusted OR 2.00 1.59-2.50, P < .001) but not of nonaccess site (adjusted OR 1.18 0.91-1.54, P = .205) bleeding. There were 248 deaths: 32 deaths among men with bleeding versus 107 deaths among men with no bleeding (9.1% vs 3.6%, OR 2.68 1.78-4.05, P < .001) and 40 deaths among women with bleeding vs 69 deaths among women with no bleeding (7.8% vs 2.5%, OR 3.35 2.24-5.01, P < .001). No difference in mortality was observed among women and men who bled ( P = .487). Bleeding was independently associated 1-year mortality (adjusted hazard ratio 2.18 1.68-2.84, P < .001) with no bleeding-by-sex interaction ( P = .439). Conclusions Despite matching for age, body mass index, and type of antithrombotic therapy, bleeding risk after PCI remained significantly higher in women than in men. Bleeding was associated with increased risk of 1-year mortality with no bleeding-by-sex interaction.
The prognostic value of gamma-glutamyl transferase (GGT) in patients with acute coronary syndromes (ACS) has been incompletely investigated. We investigated this clinically relevant question in 2,534 ...consecutive patients with ACS who underwent percutaneous coronary intervention (PCI). GGT activity was measured before PCI procedure in all patients. Statin therapy at hospital discharge was prescribed in 94% of the patients. The primary outcome was 3-year mortality. Patients were divided into 3 groups: the group with GGT in the first tertile (GGT <28 U/L; n = 848 patients), the group with GGT in the second tertile (GGT 28 to <50 U/L; n = 843 patients), and the group with GGT in the third tertile (GGT ≥50 U/L; n = 843 patients). The primary outcome (all-cause deaths) occurred in 250 patients: 70 deaths (9.7%) among patients of the first, 69 deaths (9.0%) among patients of the second, and 111 deaths (14.8%) among patients of the third GGT tertile (adjusted hazard ratio HR 1.24, 95% CI 1.08 to 1.42, p = 0.002) and cardiac and noncardiac deaths occurred in 157 (63%) and 93 patients (37%), respectively. GGT was associated with the increased risk of noncardiac mortality (adjusted HR 1.35 1.09 to 1.66, p = 0.005) but not cardiac mortality (adjusted HR 1.16 0.97 to 1.38, p = 0.098; all 3 risk estimates were calculated per SD increase in the logarithmic scale of GGT activity). In conclusion, in contemporary patients with ACS treated with PCI and on statin therapy, elevated GGT activity was associated with the increased risk of all-cause and noncardiac mortality but not with the risk of cardiac mortality.
Abstract Background The association between coronary atherosclerosis progression or regression and long-term prognosis remains poorly defined. We assessed the association of atherosclerosis ...progression or regression with long-term mortality and factors that promote angiographic progression or regression of coronary atherosclerosis in patients with angiographically-proven coronary artery disease. Methods The study included 605 patients with coronary artery disease who underwent coronary angiography at baseline and at 2 years later. Pan-coronary artery tree quantitative coronary angiography was performed. Of 6259 coronary segments (10.3 lesions per patient) analyzed, 1790 non-stented segments with ≥25% diameter stenosis at baseline were included. Atherosclerosis progression or regression was defined as a decrease or increase in the mean minimal lumen diameter (MLD) of the non-stented segments of ≥0.2 mm in the 2-year angiography compared to baseline angiography. The primary outcome was all-cause mortality. Results Based on the change in mean MLD between baseline and 2-year angiography, patients were divided into 3 groups: the group with progression of atherosclerosis (n=53; 8.8%), group with no progression or regression of atherosclerosis (n=472; 78.0%) and the group with regression of atherosclerosis (n=80; 13.2%). There were 126 deaths over 8-year follow-up: 17 deaths among patients with progression, 103 deaths occurred among patients with no progression/regression and 6 deaths among patients with regression (Kaplan-Meier estimates of mortality, 37.5%, 25.2% and 8.9%, respectively; adjusted hazard ratio=1.16, 95% confidence interval 1.05 to 1.29, P=0.004 for 0.1 mm reduction in mean MLD). Conclusions Progression or regression of coronary atherosclerosis in non-treated coronary segments was significantly associated with 8-year mortality.
Background Inhospital stent thrombosis (ST) and cerebrovascular accidents (CVA) are rare but serious adverse events after percutaneous coronary intervention (PCI). The association of ST or CVA with ...long-term outcome after PCI remains poorly investigated. Methods The study included 18,334 consecutive patients who underwent PCI. Patients were divided into 3 groups: the group with ST, the group with CVA, and the group without these events. The primary outcome was all-cause mortality at 3-year follow-up. Results Inhospital ST or CVA occurred in 59 patients (0.32%) and in 90 patients (0. 49%), respectively. There were 2,149 deaths (11.7%) during the follow-up: 26 deaths among patients with ST, 32 deaths among patients with CVA, and 2,091 deaths among patients without ST or CVA (Kaplan-Meier estimates of 3-year mortality 45.3%, 38.0%, and 12.9%, odds ratio 6.1, 95% CI 3.6-10.2, P < .001 for ST group vs the group without ST or CVA and odds ratio 4.2 2.7-6.6, P < .001 for CVA group vs the group without ST or CVA). There was no significant difference in the 3-year mortality between CVA and ST groups ( P = .29). The Cox proportional hazards model showed that ST (adjusted hazard ratio 4.97, 95% CI 2.58-9.56, P < .001) and CVA (adjusted hazard ratio 2.25 1.25-4.04, P = .006) were independently associated with the increased risk of 3-year mortality. Conclusion Inhospital ST and CVA after PCI are associated with the increased risk of 3-year mortality. Both events seem to have a similar impact on long-term survival.
PDF
