Welcome to the EAS 2022 Interactive Program
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Extracellular vesicles in CVD
Systems biology to estimate cardiovascular risk
HIGH LIPOPROTEIN(A) AND SYSTEMIC INFLAMMATION JOINTLY CONFER ADDITIVE HIGH RISK OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE AND AORTIC VALVE STENOSIS
Abstract
Background and Aims
Lipoprotein(a) and low-grade systemic inflammation are both risk factors for atherosclerotic cardiovascular disease (ASCVD) but recent evidence has indicated that the lipoprotein(a)-associated ASCVD risk is observed only in individuals with low-grade systemic inflammation. We hypothesized that high lipoprotein(a) and low-grade systemic inflammation, measured as high sensitive C-reactive protein (hsCRP), jointly influence the risk of ASCVD and aortic valve stenosis (AVS).
Methods
We included 56,625 individuals from the Copenhagen General Population Study, a contemporary prospective cohort study of randomly selected individuals from the general Danish population. During a median of 7.4 years of follow-up, 2,952 developed ASCVD and 681 developed AVS.
Results
For individuals with hsCRP <2 mg/L, the multivariable adjusted hazard ratio for ASCVD and AVS for individuals in the 90th-100th percentiles of lipoprotein(a) levels (≥69 mg/dL, ≥145 nM) were 1.7 (95% confidence interval: 1.5-2.0) and 2.4 (1.7-3.3) compared to individuals in the 1st-24th percentiles (≤4 mg/dL, ≤4 nM) of lipoprotein(a). The corresponding hazard ratios for individuals with hsCRP≥2 mg/L were 1.7 (1.4-2.1) and 1.7 (1.2-2.5), respectively. We found no evidence of interaction of lipoprotein(a) and hsCRP on risk of ASCVD (P for interaction=0.58) or AVS (P for interaction=0.56). The highest absolute 10-year risk of ASCVD and AVS was found in individuals with concomitant high lipoprotein(a) and hsCRP (Figure 1). For men aged 70-79 with lipoprotein(a) levels in the 90th-100th percentiles and hsCRP ≥2 mg/L, absolute 10-year risks of ASCVD and AVS were 30% and 11%, respectively.
Conclusions
High lipoprotein(a) and systemic inflammation jointly confer additive high risk of ASCVD and AVS.
MATERNAL INHERITANCE OF A GENETIC MUTATION FOR FAMILIAL HYPERCHOLESTEROLEMIA PREDISPOSE TO CORONARY ATHEROSCLEROSIS IN ADULTHOOD
Abstract
Background and Aims
Animal studies have demonstrated that the fetal exposition to high maternal cholesterol levels during pregnancy predispose their offspring to aortic atheroma. In human, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease (ASCVD) later in life.
Methods
We included 1350 patients followed in the French register of Familial Hypercholesterolemia (FH), with a genetic diagnosis and data on parental inheritance of the mutation. We used a propensity score to match 556 patients who had a coronary atheroma evaluation assessed by a coronary artery calcium (CAC) score. We performed multivariate analysis to assess proper effect of each variable on CAC score.
Results
Before matching, patients with maternal inheritance were 2 years older [RG1] than those with paternal inheritance (46.9±16.8 vs 44.7±15.9 years old, p=0.02), and had less family history of premature ASCVD (27.7% vs 45%, p<0.0001). In multivariate analysis realized on the age and sex matched groups, maternal inheritance was significantly associated with a raised CAC score by 95 Agatston units (95% CI 23-166, p=0.01), a 1.77-fold risk to have a CAC score above 100 (95% CI 1.03–3.06, p=0.04) and a 2.71-fold risk to have a CAC score above 400 (95% CI 1.38–5.48, p=0.004), compared to paternal inheritance. There was no differences on the prevalence of ASCVD between the two groups.
Conclusions
Maternal inheritance of the FH mutation was associated with more severe infra-clinic coronary atheroma assessed by CAC score, and may be considered as a supplemental CV risk factor in the offspring of women FH patients.
PREDICTION OF CORONARY ARTERY DISEASE AND MAJOR ADVERSE CARDIOVASCULAR EVENTS USING CLINICAL AND GENETIC RISK SCORES FOR CARDIOVASCULAR RISK FACTORS
Abstract
Background and Aims
Risk stratification of coronary artery disease (CAD) and major adverse cardiovascular events (MACE) remains suboptimal. CAD genetic risk scores (GRSs) predict risk independently from the QRISK3 score. We assessed the added value of GRSs for cardiovascular traits (CV GRSs).
Methods
We used data from 379,581 participants in the UK Biobank without known cardiovascular conditions (follow-up 11.3 years, 3.3% CAD cases, 5.2% MACE cases). In a training subset (50%) we built (1) QRISK3; (2) QRISK3 and an established CAD GRS; and (3) QRISK3, the CAD GRS and the CV GRSs. In an independent subset (50%), we evaluated their performance using the area under the curve (AUC) and odds ratio (ORs). We, then, repeated the analyses with (4) CAD GRS; and (5) CAD GRS and CV GRSs.
Results
For CAD, the combination of QRISK3 and the CAD GRS had a better performance than QRISK3 alone (AUC of 0.767 versus 0.756, P = 3.0x10-7, OR of 5.47 versus 4.82). Adding the CV GRSs did not significantly improve risk stratification. When only looking at genetic information, the combination of CV GRSs and the CAD GRS had a better performance than the CAD GRS alone (AUC of 0.635 versus 0.624, P = 1.4x10-13, OR of 2.17 versus 2.07). Similar results were obtained for MACE.
Conclusions
The inclusion of CV GRSs to QRISK3 and an established CAD GRS does not improve CAD or MACE risk stratification. However, their combination only with the CAD GRS increases prediction performance indicating potential use before the advanced development of conventional CV risk factors.
VASCULAR TISSUE SPECIFIC MIRNA PROFILES REVEAL NOVEL CORRELATIONS WITH RISK FACTORS IN CORONARY ARTERY DISEASE
Abstract
Background and Aims
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors.
Methods
Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis.
Results
We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701–significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction.
Conclusions
We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD.
COMPARISON OF CARDIOVASCULAR PROGNOSIS BETWEEN TRIGLYCERIDE VARIABILITY AND EXPOSURE ESTIMATE IN DIABETIC PATIENTS
Abstract
Background and Aims
Serum triglyceride levels are an important lipid profile for dyslipidemia in diabetic patients. Recently, visit-to-visit variability of lipid profile has been suggested as a residual risk factor for cardiovascular disease. This study compared the impact on cardiovascular prognosis between the visit-to-visit variability and the cumulative exposure estimates of serum triglyceride in diabetic patients.
Methods
A total of 13,414 patients, whose the 1st lipid profile measurement was taken between 2002 and 2007, measured 3 or more times, not prescribed for fibrate and omega-3 were selected from three tertiary hospitals. After excluding the patients with the prior myocardial infarction, stroke and malignancy history, 5,657 patients were finally analyzed. They were grouped based on their median values for the coefficient of variation (CV) and cumulative exposure estimate (CEE) of serum triglyceride levels during the 8-year modeling period. Incidence of major adverse cerebrocardiovascular event (MACCE), a composite of death, myocardial infarction (MI) and stroke, during the following 5 years were compared between groups after the propensity score matching.
Results
The mean age was 65 years. High CEE group and high CV group showed younger, less hypertension and chronic kidney disease. Nevertheless, after the propensity score matching, the incidence of MACCE was higher in the high CV group compared to low CV group (9.26% vs 11.62%, log-rank p=0.02, Figure 1). On the other hand, it was similar between the high CEE group and low CEE group.
Conclusions
Visit-to-visit variability of triglyceride rather than their cumulative exposure is more strongly related to the incidence of MACCE in diabetic patients.