Panagiotis Antiochos

Association between parental history and genetic risk scores for coronary heart disease prediction: The population-based CoLaus study

BACKGROUND AND AIMS Parental history (PH) and genetic risk scores (GRSs) are separately associated with coronary heart disease (CHD), but evidence regarding their combined effects is lacking. We aimed to evaluate the joint associations and predictive ability of PH and GRSs for incident CHD. METHODS Data for 4283 Caucasians were obtained from the population-based CoLaus Study, over median follow-up time of 5.6 years. CHD was defined as incident myocardial infarction, angina, percutaneous coronary revascularization or bypass grafting. Single nucleotide polymorphisms for CHD identified by genome-wide association studies were used to construct unweighted and weighted versions of three GRSs, comprising of 38, 53 and 153 SNPs respectively. RESULTS PH was associated with higher values of all weighted GRSs. After adjustment for age, sex, smoking, diabetes, systolic blood pressure, low and high density lipoprotein cholesterol, PH was significantly associated with CHD [HR 2.61, 95% CI (1.47-4.66)] and further adjustment for GRSs did not change this estimate. Similarly, one standard deviation change of the weighted 153-SNPs GRS was significantly associated with CHD [HR 1.50, 95% CI (1.26-1.80)] and remained so, after further adjustment for PH. The weighted, 153-SNPs GRS, but not PH, modestly improved discrimination [(C-index improvement, 0.016), p = 0.048] and reclassification [(NRI improvement, 8.6%), p = 0.027] beyond cardiovascular risk factors. After including both the GRS and PH, model performance improved further [(C-index improvement, 0.022), p = 0.006]. CONCLUSION After adjustment for cardiovascular risk factors, PH and a weighted, polygenic GRS were jointly associated with CHD and provided additive information for coronary events prediction.

Association between anti-apolipoprotein A-1 antibodies and cardiovascular disease in the general population. Results from the CoLaus study

We aimed to determine the association between autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) and prevalent cardiovascular (CV) disease (CVD) as well as markers of CV risk in the general population. Cross-sectional data were obtained from 6649 subjects (age 52.6 ± 10.7 years, 47.4 % male) of the population-based CoLaus study. CVD was defined as myocardial infarction, angina pectoris, percutaneous revascularisation or bypass grafting for ischaemic heart disease stroke or transient ischaemic attack, and was assessed according to standardised medical records. Anti-apoA-1 IgG and biological markers were measured by ELISA and conventional automated techniques, respectively. Prevalence of high anti-apoA-1 IgG levels in the general population was 19.9 %. Presence of anti-apoA-1 IgG was significantly associated with CVD [odds ratio 1.34, 95 % confidence interval (1.05-1.70), p=0.018], independently of established CV risk factors (CVRFs) including age, sex, hypertension, smoking, diabetes, low and high-density lipoprotein cholesterol levels. The n=455 (6.8 %) study participants with a history of CVD (secondary prevention subgroup) presented higher median anti-ApoA-1 IgG values compared with subjects without CVD (p=0.029). Among patients in the secondary prevention subgroup, those with positive anti-apoA-1 IgG levels had lower HDL (p=0.002) and magnesium (p=0.001) levels, but increased uric acid and high-sensitivity C-reactive protein levels (p=0.022, and p<0.001, respectively) compared to patients with negative anti-apoA-1 IgG levels. In conclusion, anti-apoA-1 IgG levels are independently associated with CVD in the general population and also related to CV biomarkers in secondary prevention. These findings indicate that anti-apoA-1 IgG may represent a novel CVRF and need further study in prospective cohorts.

Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

Background Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) have emerged as an independent biomarker for cardiovascular disease and mortality. However, their association with all-cause mortality in the community, as well as their genetic determinants, have not been studied. Objective To determine whether anti-apoA-1 IgG: (a) predict all-cause mortality in the general population and (b) are associated with single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS). Methods Clinical, biological, and genetic data were obtained from the population-based, prospective CoLaus study, including 5,220 participants (mean age 52.6 years, 47.3% men) followed over a median duration of 5.6 years. The primary study outcome was all-cause mortality. Results After multivariate adjustment, anti-apoA-1 IgG positivity independently predicted all-cause mortality: hazard ratio (HR) = 1.54, 95% confidence interval (95% CI): 1.11–2.13, P = 0.01. A dose–effect relationship was also observed, each SD of logarithmically transformed anti-apoA-1 IgG being associated with a 15% increase in mortality risk: HR = 1.15, 95% CI: 1.02–1.28, P = 0.028. The GWAS yielded nine SNPs belonging to the Fc receptor-like 3 (FCRL3) gene, which were significantly associated with anti-apoA-1 IgG levels, with the lead SNP (rs6427397, P = 1.54 × 10−9) explaining 0.67% of anti-apoA-1 IgG level variation. Conclusion Anti-apoA-1 IgG levels (a) independently predict all-cause mortality in the general population and (b) are linked to FCRL3, a susceptibility gene for numerous autoimmune diseases. Our findings indicate that preclinical autoimmunity to anti-apoA-1 IgG may represent a novel mortality risk factor.

Impact of CD14 Polymorphisms on Anti-Apolipoprotein A-1 IgG-Related Coronary Artery Disease Prediction in the General PopulationHighlights

Objective— We aimed to determine whether autoantibodies against apoA-1 (apolipoprotein A-1; anti-apoA-1 IgG) predict incident coronary artery disease (CAD), defined as adjudicated incident myocardial infarction, angina, percutaneous coronary revascularization, or bypass grafting, in the general population. We further investigated whether this association is modulated by a functional CD14 receptor single nucleotide polymorphism. Approach and Results— In a prospectively studied, population-based cohort of 5220 subjects (mean age 52.6±10.7 years, 47.4% males), followed over a median period of 5.6 years, subjects positive versus negative for anti-apoA-1 IgG presented a total CAD rate of 3.9% versus 2.8% (P=0.077) and a nonfatal CAD rate of 3.6% versus 2.3% (P=0.018), respectively. After multivariate adjustment for established cardiovascular risk factors, the hazard ratios of anti-apoA-1 IgG for total and nonfatal CAD were: hazard ratio=1.36 (95% confidence interval, 0.94–1.97; P=0.105) and hazard ratio=1.53 (95% confidence interval, 1.03–2.26; P=0.034), respectively. In subjects with available genetic data for the C260T rs2569190 single nucleotide polymorphism in the CD14 receptor gene (n=4247), we observed a significant interaction between anti-apoA-1 IgG and rs2569190 allele status with regards to CAD risk, with anti-apoA-1 IgG conferring the highest risk for total and nonfatal CAD in non-TT carriers, whereas being associated with the lowest risk for total and nonfatal CAD in TT homozygotes (P for interaction =0.011 and P for interaction =0.033, respectively). Conclusions— Anti-apoA-1 IgG are independent predictors of nonfatal incident CAD in the general population. The strength of this association is dependent on a functional polymorphism of the CD14 receptor gene, a finding suggesting a gene–autoantibody interaction for the development of CAD.

Using light microscopy for diagnosing the cause of a case of acute stroke

A 60-year-old febrile man was transferred to the emergency department after being found alone and unconscious in a park. No medical history was available. Brain CT revealed a hyperdense lesion in the basilar artery (figure, A) suggesting a thromboembolic occlusion, which was subsequently thromboaspirated (figure, B and C). The fresh thrombus was retrieved (figure, D) and urgently analyzed using light microscopy, which revealed colonies of gram-positive bacilli (figure, E). A cardiac echogram showed severe mitral valve insufficiency and vegetations on its anterior leaflet (figure, F). After mitral valve repair and a long course of antibiotic therapy, the patients symptoms improved.

Prognostic value of pulse pressure after an acute coronary syndrome

BACKGROUND AND AIMS Pulse pressure (PP) is a surrogate of aortic stiffness (AS) easily obtainable. The link between AS and cardio-vascular disease is documented, however, data regarding acute coronary syndrome (ACS) patients are scarce and contradictory. We aimed to assess the prognostic value of PP measured at admission, with regard to major adverse outcomes (all-cause mortality, recurrence of MI, and stroke), during the first year following an acute coronary syndrome (ACS). METHODS The SPUM-ACS project is a prospective cohort study of patients with ACS conducted in 4 Swiss University hospitals. Patients with no PP at admission or with severe clinical heart failure or cardiogenic shock were excluded. Cox regression analyses were performed to determine associations between PP and outcomes (all-cause mortality, recurrence of myocardial infarction (MI), and stroke). Three multivariate Cox regression models were adjusted for hemodynamic, cardiovascular, and non-cardiovascular confounders, added successively. RESULTS Of 5635 eligible patients, 5070 met the inclusion criteria. Mean patient age was 63 years (range: 54-72), 79.6% were male, and mean blood pressure and PP were 93.9 ± 15.6 and 54 ± 17 mmHg, respectively. Multivariate analyses confirmed the prognostic significance of PP for each 10-mmHg increase for the composite endpoint, hazard ratio (HR) 1.126 [1.051-1.206], p = 0.001; all-cause mortality, HR1.129 [1.013-1.260], p = 0.029; and recurrence of MI, HR1.206 [1.102-1.320], p < 0.001; but not for stroke, HR1.014[0.853-1.205]. CONCLUSIONS PP measured at admission is a strong, independent prognostic marker predicting mortality and recurrence of MI after ACS. PP should be considered for the management of secondary prevention.

Endovascular management of heavily calcified abdominal aorta dissection during transcatheter aortic valve implantation.

Figure 1. A. Before transcatheter aortic valve implantation (TAVI): abdominal aorta with extensive circumferential calcifications; B, C. After TAVI: fracture and vertical displacement of abdominal aorta wall with bilateral dissection traces; D, E. Transfemoral implantation of a covered metal stent across the fracture site and successful restoration of the aortic trajectory, without signs of residual dissection; F. Post-procedural computed tomography showing TAV-in-TAV implantation, transjugular temporary pacemaker lead and stent into the abdominal aorta. (TAVI). The first aortic prosthesis (Corevalve 29 mm, Medtronic, MN, USA) was implanted too high above the native aortic annulus, resulting in severe paravalvular regurgitation. TAV-in-TAV