Practical Echocardiographic Approach of the Regurgitant Mitral Valve Assessment.

Mitral regurgitation is the second-most frequent valvular heart disease in Europe after degenerative aortic stenosis. It is associated with significant morbidity and mortality, and its prevalence is expected to increase with population aging. Echocardiography is the first diagnostic approach to assess its severity, constituting a challenging process in which a multimodality evaluation, integrating quantitative, semiquantitative and qualitative methods, as well as a detailed evaluation of the morphology and function of both left ventricle and atria is the key. In this review, we would like to provide a practical diagnosis approach on the mitral valve regurgitation mechanism, severity quantification, and planning of future therapeutic options.

Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium.

BACKGROUND: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. METHODS: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). RESULTS: Kaplan-Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confidence interval (CI) 1.02-1.31, p = 0.02) for cardiovascular mortality, 1.13 (95% CI 1.03-1.24, p = 0.01) for CVD incidence, and 1.09 (95% CI 1.02-1.17, p = 0.01) for overall mortality was observed per 10 mmol/mol increase in HbA1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA1c levels (HR 1.12; 95% CI 1.01-1.25, p = 0.04) and HR 1.10; 95% CI 1.01-1.20, p = 0.02) respectively. HbA1c cut-off values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk. CONCLUSIONS: HbA1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA1c levels and outcomes. Elevated HbA1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA1c levels in the overall population.

Association of Circulating Metabolites With Risk of Coronary Heart Disease in a European Population: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

Relations of Sex to Diagnosis and Outcomes in Acute Coronary Syndrome.

BACKGROUND: The atypical presentation of women with acute coronary syndrome (ACS) has been related to delayed diagnosis and treatment, which may explain worse outcome compared with men. METHODS AND RESULTS: We analyzed pooled data of 2520 patients of 2 prospective cohorts in terms of differences in presentation and management of women and men suggestive of ACS. Using logistic regression, we established 2 diagnostic models and tested their diagnostic performance in both sexes separately. Sex-specific differences in management of patients with ACS were ascertained and a 2-year follow-up was performed. Women were older than men (median 67 versus 61 years, P=0.001), had more often dyspnea (22% versus 18%, P=0.024), nausea or vomiting (26% versus 16%, P=0.001) and radiating chest pain (47% versus 40%, P=0.001). Classical risk factors (smoking, diabetes mellitus, dyslipidemia or known coronary artery disease) were less frequent in women. Diagnostic models showed no significant sex-related differences in diagnostic performance in a "first contact" setting (medical history and symptoms) or after "complete triage" (including ECG and biomarkers). Women with ACS underwent coronary angiography (73.8% versus 84.3%, P<0.001) and revascularization (53.8% versus 70.1%, P<0.001) less frequently. Two-year incidence of myocardial infarction and death was similar in both sexes, but revascularization and cardiac rehospitalization were more frequent in men. CONCLUSIONS: In a large cohort of patients with suspected ACS, sex differences in clinical presentation did not impair diagnostic accuracy. Two-year outcomes were comparable. Our findings suggest a benefit of chest pain units to minimize sex differences in ACS management and prognosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02355457 (BACC), NCT03227159 (stenoCardia).

Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts: Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe).

BACKGROUND: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood. METHODS: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1-97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years. RESULTS: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12-1.23 in women versus 1.31; 95% CI 1.25-1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81-0.90 versus 0.92; 95% CI, 0.88-0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index. CONCLUSIONS: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies.

Assessment of microRNAs in patients with unstable angina pectoris.

AIMS: While cardiac troponin measurements have significantly improved the early diagnosis of myocardial infarction, the timely biomarker-based diagnosis of unstable angina pectoris (UAP) remains a major unmet clinical challenge. The aim of this study was to assess levels of circulating microRNAs (miRNAs) as possible novel biomarkers in patients with UAP. METHODS AND RESULTS: A three-phase approach was conducted, comprising (i) profiling of miRNAs in patients with UAP and controls groups; (ii) replication of significant miRNAs in an independent patient cohort, (iii) validation of a multi-miRNAs panel in a third cohort. Out of 25 miRNAs selected for replication, 8 miRNAs remained significantly associated with UAP. In a validation phase, a miRNA panel including miR-132, miR-150, and miR-186 showed the highest discriminatory power [area under the receiver-operating-characteristic curve (AUC): 0.91; CI: 0.84-0.98]. CONCLUSION: Using a profiling-replication-validation model, we identified eight miRNAs, which may facilitate the diagnosis of UAP.

Angiographic score assessment improves cardiovascular risk prediction: the clinical value of SYNTAX and Gensini application.

BACKGROUND: Severity of coronary artery disease (CAD) is related to cardiovascular outcome. We aimed to assess the long-term follow-up depending on Synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) and Gensini score for prognosis. Both scores increase with complexity and thus reflect risk of cardiovascular events. METHODS AND RESULTS: We determined complexity and extent of CAD by the SYNTAX and Gensini score in the AtheroGene cohort (N = 1,974, with 22.6 % women). The endpoint was non-fatal myocardial infarction (N = 132) and cardiovascular death (N = 159) over a median follow-up of 5.4 (Q1: 5.23/Q3: 5.57) years up to 8 years maximum (follow-up rate 99.4%). For SYNTAX score, the following distribution was used: low (≤22, N = 1,404), medium (23-32, N = 314), high score (>32, N = 256). Gensini score was split into thirds. Cox regression analysis showed a hazard ratio (HR) of 1.5 (95% confidence interval 1.16-1.95; p = 0.0024) for the log transformed SYNTAX score in a fully adjusted model and a HR of 1.41 (95% CI 1.13-1.77; p = 0.0025) for the Gensini score. The SYNTAX score alone had a C-index of 0.62, whereas adding clinical variables increased the C-index to 0.67. Similar results were obtained for the Gensini score. Regarding the SYNTAX score using net reclassification index, discrimination of events and non-events was enhanced by 37.2% in a model of clinical variables and biomarkers and by 31.8% for the Gensini score. CONCLUSION: The SYNTAX and Gensini score in combination with clinical variables could be used to predict the cardiovascular prognosis during a long-term follow-up of up to 8 years in CAD patients.