Validation of the SCORE2 risk prediction algorithm in a Portuguese population: A new model to estimate 10-year cardiovascular disease incidence in Europe.

INTRODUCTION AND OBJECTIVES: Subjects without cardiovascular (CV) disease (CVD) may suffer from subclinical atherosclerosis, and are at increased risk for atherosclerotic CV events (ASCVE). The ESC/EAS risk SCORE was updated by SCORE2, which estimates 10-year risk of fatal and non-fatal CVD in European populations aged 40-69 years without established CVD or diabetes. Our aim was to compare the two ESC/EAS risk scores and to validate SCORE2 in our population. METHODS: A total of 1071 individuals (age 57.2±6.1 years; 75.2% male) without CVD or diabetes, from GENEMACOR study controls, were analyzed over 5.4±3.9 years. The population was stratified into risk categories according to the two scores, and the area under the ROC curve (AUC) and Harrell's C-index assessed the scores' performance. Calibration was performed using the goodness-of-fit test, and occurrence of the first event assessed by Cox regression. Kaplan-Meier analysis estimated SCORE2 survival. RESULTS: SCORE stratified subjects into four risk categories: low (7.4%), moderate (46.5%), high (25.3%) and very high (20.8%), and SCORE2 into three: low-to-moderate (24.7%), high (59.0%) and very high (16.2%). SCORE presented good discrimination for CV mortality (AUC=0.838; C-index=0.834, 95% CI: 0.728-0.940), as did SCORE2 for total CV events (AUC=0.744; C-index=0.728, 95% CI: 0.648-0.808). Calibration did not show a disparity between observed and expected ASCVE. The probability of ASCVE was eight times higher in very-high-risk SCORE2 (p=0.001), and three times in the high-risk group (p=0.049). Event-free survival was 99%, 90% and 72% in the low-to-moderate, high and very-high-risk categories, respectively (p<0.0001). CONCLUSIONS: SCORE2 improved population stratification by identifying higher-risk patients, enabling early preventive measures. It showed good discriminative ability for all ASCVE.

Epicardial Adipose Tissue: The Genetics Behind an Emerging Cardiovascular Risk Marker.

Evidence points epicardial adipose tissue (EAT) as an emerging cardiovascular risk marker. Whether genetic polymorphisms linked with atherosclerosis are associated with higher EAT is still unknown. We aim to assess the role of genetic burden of atherosclerosis and its association to EAT in a cohort of asymptomatic individuals without coronary disease. A total of 996 participants were prospectively enrolled in a single Portuguese center. EAT volume was measured by Cardiac Computed Tomography and participants were distributed into 2 groups, above and below median EAT. SNPs were genotyped and linked to their respective pathophysiological axes. A multiplicative genetic risk score (mGRS) was constructed, representing the genetic burden of the studied SNPs. To evaluate the association between genetics and EAT, we compared both groups by global mGRS, mGRS by functional axes, and SNPs individually. Individuals above-median EAT were older, had a higher body mass index (BMI) and higher prevalence of hypertension, metabolic syndrome, diabetes, and dyslipidemia. They presented higher GRS, that remained an independent predictor of higher EAT volumes. The group with more EAT consistently presented higher polymorphic burden across numerous pathways. After adjustment, age, BMI, and mGRS of each functional axis emerged as independently related to higher EAT volumes. Amongst the 33 SNPs, MTHFR677 polymorphism emerged as the only significant and independent predictor of higher EAT volumes. Patients with higher polymorphism burden for atherosclerosis present higher EAT volumes. We present the first study in a Portuguese population, evaluating the genetic profile of EAT through GWAS and GRS, casting further insight into this complicated matter.

Good agreement between echocardiography and impedance cardiography in the assessment of left ventricular performance in hypertensive patients.

BACKGROUND: Impedance cardiography (ICG) is a noninvasive hemodynamic monitoring tool which can define hypertensive patients' hemodynamic profiles and help to tailor antihypertensive therapy. This study assesses the concordance between ICG-derived indexes used to evaluate left ventricular performance and transthoracic echocardiography (TTE) in hypertensive patients. METHODS: In this IMPEDDANS post-hoc analysis, the ICG-derived indexes are compared with TTE by Bland-Altman method. Statistical significance of the relationship between the values obtained was assessed by generalized linear mixed-effects models. RESULTS: In supine position, Bland-Altman analysis showed good concordance for cardiac output (CO) (mean difference of 0.006 mL/min [-0.120; 0.133]), cardiac index (CI) (mean difference of 0.016 mL/min/m2 [-0.471; 0.504]), pre-ejection period (PEP) (mean difference of -0.216 ms [-4.510; 4.077]), left ventricular ejection time (LVET) (mean difference of -0.140 ms [-6.573; 6.293]), and systolic time ratio (STR) (mean difference of -0.00004 [-0.008; 0.008]). In orthostatic position, good concordance was found for CO (mean difference 0.028 mL/min [-2.036; 1.980]), CI (mean difference -0.012 mL/min/m2 [-1.063; 1.039]), and STR (mean difference -0.101 [0.296; 0.094]). No significant difference between methods was identified by the linear mixed-effects models. CONCLUSION: The ICG-derived indexes CO, CI, PEP, LVET, and STR in supine position have good agreement with TTE. Therefore, ICG can be used to accurately evaluate left ventricular performance.

Systolic time ratio measured by impedance cardiography accurately screens left ventricular diastolic dysfunction in patients with arterial hypertension.

BACKGROUND: The use of impedance cardiography (ICG) may play a role in the assessment of cardiac effects of hypertension (HT), especially its hemodynamic features. Hypertensive heart disease involves structural changes and alterations in left ventricular geometry that end up causing systolic and/or diastolic dysfunction. The IMPEDDANS study aims to assess the usefulness of ICG for the screening of left ventricular diastolic dysfunction (LVDD) in patients with HT. METHODS: Patients with HT were assessed by echocardiography and ICG. Receiver-operating characteristic curve and the area under the curve were used to assess the discriminative ability of the parameters obtained by ICG to identify LVDD, as diagnosed by echocardiography. RESULTS: ICG derived pre-ejection period (PEP), left ventricle ejection time (LVET), systolic time ratio (STR) and D wave were associated (p < 0.001) with LVDD diagnosis, with good discriminative ability: PEP (AUC 0.81; 95% CI 0.74-0.89), LVET (AUC 0.82; 95% CI 0.75-0.88), STR (AUC 0.97; 95% CI 0.94-1.00) and presence of D wave (AUC = 0.87; 95% CI 0.82-0.93). STR ≥ 0.30 outperformed the other parameters (sensitivity of 98.0%, specificity of 90.2%, positive predictive value of 95.2%, and negative predictive value of 96.1%). CONCLUSION: The ICG derived value of STR allows the accurate screening of LVDD in patients with HT. It might as well be used for follow up assessment. TRIAL REGISTRATION: The study protocol was retrospectively registered as IMPEDDANS on ClinicalTrials.gov (ID: NCT03209141) on July 6, 2017.