Background
Vascular aging results in stiffer arteries and may have a role in the development of cardiovascular disease (CVD). Arterial stiffness index (ASI), measured by finger photoplethysmography, ...and pulse pressure (PP) are 2 independent vascular aging indices. We investigated whether ASI or PP predict new‐onset CVD and mortality in a large community‐based population.
Methods and Results
We studied 169 613 UK Biobank participants (mean age 56.8 years; 45.8% males) who underwent ASI measurement and blood pressure measurement for PP calculation. Mean±SD ASI was 9.30±3.1 m/s and mean±SD PP was 50.98±13.2 mm Hg. During a median disease follow‐up of 2.8 years (interquartile range 1.4–4.0), 18 190 participants developed CVD, of which 1587 myocardial infarction (MI), 4326 coronary heart disease, 1192 heart failure, and 1319 stroke. During a median mortality follow‐up of 6.1 years (interquartile range 5.8–6.3), 3678 participants died, of which 1180 of CVD. Higher ASI was associated with increased risk of overall CVD (unadjusted hazard ratio 1.27; 95% confidence interval CI, 1.25–1.28), myocardial infarction (1.38; 95% CI, 1.32–1.44), coronary heart disease (1.31; 95% CI, 1.27–1.34), and heart failure (1.31; 95% CI 1.24–1.37). ASI also predicted mortality (all‐cause, CVD, other). Higher PP was associated with overall CVD (1.57; 95% CI, 1.55–1.59), myocardial infarction (1.48; 95% CI, 1.42–1.54), coronary heart disease (1.47; 95% CI, 1.43–1.50), heart failure (1.47; 95% CI, 1.40–1.55), and CVD mortality (1.47; 95% CI, 1.40–1.55). PP improved risk reclassification of CVD in a non–laboratory‐based Framingham Risk Score by 5.4%, ASI by 2.3%.
Conclusions
ASI and PP are independent predictors of CVD and mortality outcomes. Although both improved risk prediction for new‐onset disease, PP appears to have a larger clinical value than ASI.
Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. Ninety-seven genetic risk loci have been identified to date, but the identification of additional ...susceptibility loci might be important to enhance our understanding of the genetic architecture of CAD.
To expand the number of genome-wide significant loci, catalog functional insights, and enhance our understanding of the genetic architecture of CAD.
We performed a genome-wide association study in 34 541 CAD cases and 261 984 controls of UK Biobank resource followed by replication in 88 192 cases and 162 544 controls from CARDIoGRAMplusC4D. We identified 75 loci that replicated and were genome-wide significant (
<5×10
) in meta-analysis, 13 of which had not been reported previously. Next, to further identify novel loci, we identified all promising (
<0.0001) loci in the CARDIoGRAMplusC4D data and performed reciprocal replication and meta-analyses with UK Biobank. This led to the identification of 21 additional novel loci reaching genome-wide significance (
<5×10
) in meta-analysis. Finally, we performed a genome-wide meta-analysis of all available data revealing 30 additional novel loci (
<5×10
) without further replication. The increase in sample size by UK Biobank raised the number of reconstituted gene sets from 4.2% to 13.9% of all gene sets to be involved in CAD. For the 64 novel loci, 155 candidate causal genes were prioritized, many without an obvious connection to CAD. Fine mapping of the 161 CAD loci generated lists of credible sets of single causal variants and genes for functional follow-up. Genetic risk variants of CAD were linked to development of atrial fibrillation, heart failure, and death.
We identified 64 novel genetic risk loci for CAD and performed fine mapping of all 161 risk loci to obtain a credible set of causal variants. The large expansion of reconstituted gene sets argues in favor of an expanded omnigenic model view on the genetic architecture of CAD.
Leisure sedentary behaviours are associated with increased risk of cardiovascular disease, but whether this relationship is causal is unknown. The aim of this study is to identify genetic ...determinants associated with leisure sedentary behaviours and to estimate the potential causal effect on coronary artery disease (CAD). Genome wide association analyses of leisure television watching, leisure computer use and driving behaviour in the UK Biobank identify 145, 36 and 4 genetic loci (P < 1×10
), respectively. High genetic correlations are observed between sedentary behaviours and neurological traits, including education and body mass index (BMI). Two-sample Mendelian randomization (MR) analysis estimates a causal effect between 1.5 hour increase in television watching and CAD (OR 1.44, 95%CI 1.25-1.66, P = 5.63 × 10
), that is partially independent of education and BMI in multivariable MR analyses. This study finds independent observational and genetic support for the hypothesis that increased sedentary behaviour by leisure television watching is a risk factor for CAD.
Aims
Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)‐α were largely unsuccessful. Interleukin (IL)‐6 is an important ...inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL‐6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations.
Methods and results
Interleukin‐6 was measured in 2329 patients 89.4% with a left ventricular ejection fraction (LVEF) ≤ 40% of the BIOSTAT‐CHF cohort. The primary outcome was all‐cause mortality and HF hospitalization during 2 years, with all‐cause, cardiovascular (CV), and non‐CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL‐6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N‐terminal pro‐brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF‐α/IL‐1‐related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL‐6 levels. IL‐6 independently predicted the primary outcome HR (95% confidence interval) per doubling: 1.16 (1.11–1.21), P < 0.001, all‐cause mortality 1.22 (1.16–1.29), P < 0.001 and CV as well as non‐CV mortality 1.16 (1.09–1.24), P < 0.001; 1.31 (1.18–1.45), P < 0.001, but did not improve discrimination in previously published risk models.
Conclusions
In a large, heterogeneous cohort of HF patients, elevated IL‐6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL‐6 as a potential therapeutic target in specific HF subpopulations.
The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication ...for long-term anticoagulation has not been well studied.
In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.
A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval CI, 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial.
Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).
Aging is a biological process that affects most cells, organisms and species. Human aging is associated with increased susceptibility to a variety of chronic diseases, including cardiovascular ...disease, Type 2 diabetes, neurological diseases and cancer. Despite the remarkable progress made during the last two decades, our understanding of the biology of aging remains incomplete. Telomere biology has recently emerged as an important player in the aging and disease process.
Objectives
To determine normal pericoronary adipose tissue mean attenuation (PCAT
MA
) values for left the anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) in ...patients without plaques on coronary CT angiography (cCTA), taking into account tube voltage influence.
Methods
This retrospective study included 192 patients (76 (39.6%) men; median age 49 years (range, 19–79)) who underwent cCTA with third-generation dual-source CT for the suspicion of CAD between 2015 and 2017. We selected patients without plaque on cCTA. PCAT
MA
was measured semi-automatically on cCTA images in the proximal segment of the three main coronary arteries with 10 mm length. Paired
t
-testing was used to compare PCAT
MA
between combinations of two coronary arteries within each patient, and one-way ANOVA testing was used to compare PCAT
MA
in different kV groups.
Results
The overall mean ± standard deviation (SD) PCAT
MA
was − 90.3 ± 11.1 HU. PCAT
MA
in men was higher than that in women: − 88.5 ± 10.5 HU versus − 91.5 ± 11.3 HU (
p
= 0.001). PCAT
MA
of LAD, LCX, and RCA was − 92.4 ± 11.6 HU, − 88.4 ± 9.9 HU, and − 90.2 ± 11.4 HU, respectively. Pairwise comparison of the arteries showed significant difference in PCAT
MA
: LAD and LCX (
p
< 0.001), LAD and RCA (
p
= 0.009), LCX and RCA (
p
= 0.033). PCAT
MA
of the 70 kV, 80 kV, 90 kV, 100 kV, and 120 kV groups was − 95.6 ± 9.6 HU, − 90.2 ± 11.5 HU, − 87.3 ± 9.9 HU, − 82.7 ± 6.2 HU, and − 79.3 ± 6.8 HU, respectively (
p
< 0.001).
Conclusions
In patients without plaque on cCTA, PCAT
MA
varied by tube voltage, with minor differences in PCAT
MA
between coronary arteries (LAD, LCX, RCA). PCAT
MA
values need to be interpreted taking into account tube voltage setting.
Key Points
• In patients without plaque on cCTA, PCAT
MA
differs slightly by coronary artery (LAD, LCX, RCA).
• Tube voltage of cCTA affects PCAT
MA
measurement, with mean PCAT
MA
increasing linearly with increasing kV.
• For longitudinal cCTA analysis of PCAT
MA
, the use of equal kV setting is strongly recommended.
There is ongoing debate on the association between eosinophil count and diseases, as previous studies were inconsistent. We studied the relationship of eosinophil count with 22 complex metabolic, ...cardiac, and pulmonary traits and diseases. From the population-based LifeLines Cohort Study (N = 167,729), 13,301 individuals were included. We focused on relationship of eosinophil count with three classes of metabolic (7 traits, 2 diseases), cardiac (6 traits, 2 diseases), and pulmonary (2 traits, 2 diseases) outcomes. Regression analyses were applied in overall, women and men, while adjusted for age, sex, BMI and smoking. A p-value of <0.00076 was considered statistically significant. 58.2% of population were women (mean±SD 51.3±11.1 years old). In overall, one-SD higher of ln-eosinophil count was associated with a 0.04 (±SE ±0.002;p = 6.0×10-6) SD higher levels in ln-BMI, 0.06 (±0.007;p = 3.1×10-12) SD in ln-TG, 0.04 (±0.003;p = 7.0×10-6) SD in TC, 0.04 (±0.004;p = 6.3×10-7) SD in LDL, 0.04 (±0.006;p = 6.0×10-6) SD in HbA1c; and with a 0.05 (±0.004;p = 1.7×10-8) SD lower levels in HDL, 0.05 (±0.007;p = 3.4×10-23) SD in FEV1, and 0.09 (±0.001;p = 6.6×10-28) SD in FEV1/FVC. A higher ln-eosinophil count was associated with 1.18 (95%CI 1.09-1.28;p = 2.0×10-5) odds ratio of obesity, 1.29 (1.19-1.39;p = 1.1×10-10) of metabolic syndrome, 1.40 (1.25-1.56;p = 2.7×10-9) of COPD and 1.81 (1.61-2.03;p = 1.0×10-23) of asthma. Similar results were found in women. We found no association between ln-eosinophil count either with blood pressure indices in overall, women and men; or with BMI, LDL, HbA1c and obesity in men. In a large population based cohort, we confirmed eosinophil count as a potential factor implicated in metabolic and pulmonary outcomes.
Background
Incomplete atrial lesions resulting in pulmonary vein‐left atrium reconnection after pulmonary vein antrum isolation (PVAI), are related to atrial fibrillation (AF) recurrence. ...Unfortunately, during the PVAI procedure, fluoroscopy and electroanatomic mapping cannot accurately determine the location and size of the ablation lesions in the atrial wall and this can result in incomplete PVAI lesions (PVAI‐L) after radiofrequency catheter ablation (RFCA).
Aim
We seek to evaluate whether cardiac magnetic resonance (CMR), immediately after RFCA of AF, can identify PVAI‐L by characterizing the left atrial tissue.
Methods
Ten patients (63.1 ± 5.7 years old, 80% male) receiving a RFCA for paroxysmal AF underwent a CMR before (<1 week) and after (<1 h) the PVAI. Two‐dimensional dark‐blood T2‐weighted short tau inversion recovery (DB‐STIR), Three‐dimensional inversion‐recovery prepared long inversion time (3D‐TWILITE) and three‐dimensional late gadolinium enhancement (3D‐LGE) images were performed to visualize PVAI‐L.
Results
The PVAI‐L was visible in 10 patients (100%) using 3D‐TWILITE and 3D‐LGE. Conversely, On DB‐STIR, the ablation core of the PAVI‐L could not be identified because of a diffuse high signal of the atrial wall post‐PVAI. Microvascular obstruction was identified in 7 (70%) patients using 3D‐LGE.
Conclusion
CMR can visualize PVAI‐L immediately after the RFCA of AF even without the use of contrast agents. Future studies are needed to understand if the use of CMR for PVAI‐L detection after RFCA can improve the results of ablation procedures.
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