European heart journal open最新文献

Aims: Heart failure (HF) with preserved ejection fraction disproportionately affects women. There are no validated sex-specific tools for HF diagnosis despite widely reported differences in cardiac structure. This study investigates whether sex, as assigned at birth, influences cardiac magnetic resonance (CMR) assessment of left ventricular filling pressure (LVFP), a hallmark of HF agnostic to ejection fraction.

Methods and results: A derivation cohort of patients with suspected pulmonary hypertension and HF from the Sheffield centre underwent invasive right heart catheterization and CMR within 24 h of each other. A sex-specific CMR model to estimate LVFP, measured as pulmonary capillary wedge pressure (PCWP), was developed using multivariable regression. A validation cohort of patients with confirmed HF from the Leeds centre was used to evaluate for the primary endpoints of HF hospitalization and major adverse cardiovascular events (MACEs). Comparison between generic and sex-specific CMR-derived PCWP was undertaken. A total of 835 (60% female) and 454 (36% female) patients were recruited into the derivation and validation cohorts respectively. A sex-specific model incorporating left atrial volume and left ventricular mass was created. The generic CMR PCWP showed significant differences between males and females (14.7 ± 4 vs. 13 ± 3.0 mmHg, P > 0.001), not present with the sex-specific CMR PCWP (14.1 ± 3 vs. 13.8 mmHg, P = 0.3). The sex-specific, but not the generic, CMR PCWP was associated with HF hospitalization (hazard ratio 3.9, P = 0.0002) and MACE (hazard ratio 2.5, P = 0.001) over a mean follow-up period of 2.4 ± 1.2 years.

Conclusion: Accounting for sex improves precision and prognostic performance of CMR biomarkers for HF.

Aims: APOC3, ANGPTL3, and ANGPTL4 are circulating proteins that are actively pursued as pharmacological targets to treat dyslipidaemia and reduce the risk of atherosclerotic cardiovascular disease. Here, we used human genetic data to compare the predicted therapeutic and adverse effects of APOC3, ANGPTL3, and ANGPTL4 inactivation.

Methods and results: We conducted drug-target Mendelian randomization analyses using variants in proximity to the genes associated with circulating protein levels to compare APOC3, ANGPTL3, and ANGPTL4 as drug targets. We obtained exposure and outcome data from large-scale genome-wide association studies and used generalized least squares to correct for linkage disequilibrium-related correlation. We evaluated five primary cardiometabolic endpoints and screened for potential side effects across 694 disease-related endpoints, 43 clinical laboratory tests, and 11 internal organ MRI measurements. Genetically lowering circulating ANGPTL4 levels reduced the odds of coronary artery disease (CAD) [odds ratio, 0.57 per s.d. protein (95% CI 0.47-0.70)] and Type 2 diabetes (T2D) [odds ratio, 0.73 per s.d. protein (95% CI 0.57-0.94)]. Genetically lowering circulating APOC3 levels also reduced the odds of CAD [odds ratio, 0.90 per s.d. protein (95% CI 0.82-0.99)]. Genetically lowered ANGPTL3 levels via common variants were not associated with CAD. However, meta-analysis of protein-truncating variants revealed that ANGPTL3 inactivation protected against CAD (odds ratio, 0.71 per allele [95%CI, 0.58-0.85]). Analysis of lowered ANGPTL3, ANGPTL4, and APOC3 levels did not identify important safety concerns.

Conclusion: Human genetic evidence suggests that therapies aimed at reducing circulating levels of ANGPTL3, ANGPTL4, and APOC3 reduce the risk of CAD. ANGPTL4 lowering may also reduce the risk of T2D.

Aims: This study aims to evaluate the distribution of extracellular volume fraction detected via computed tomography, clinical characteristics of high extracellular volume fraction detected via computed tomography, and the rate of incidental detection of cardiac amyloidosis in patients undergoing cardiac computed tomography for coronary artery evaluation.

Methods and results: This study included 874 consecutive patients (mean age, 74.4 ± 7.1 years; men, 65%), comprising men aged ≥60 years and women aged ≥70 years, who had undergone cardiac computed tomography between January 2020 and September 2022. The mean extracellular volume fraction detected via computed tomography was 29.7 ± 5.2%, and 108 patients (12.4%) had an extracellular volume fraction detected via computed tomography of ≥35%. Older age (75.9 ± 8.2 years vs. 74.2 ± 6.9 years; P = 0.042), male sex (75.9% vs. 63.0%; P = 0.007), impaired left ventricular ejection fraction, increased high-sensitivity cardiac troponin T and B-type natriuretic peptide levels, and increased left ventricular thickness showed significant associations with an extracellular volume fraction detected via computed tomography of ≥35%. Cardiac amyloidosis was diagnosed incidentally in 15 patients based on an increase in extracellular volume fraction detected via computed tomography. The prevalence of cardiac amyloidosis was 1.7% (15/874) and 14.3% (15/105) in the entire study population and in patients with an extracellular volume fraction detected via computed tomography of ≥35%, respectively. An increase in the extracellular volume fraction detected via computed tomography was suggestive of cardiac amyloidosis.

Conclusion: Elevated extracellular volume fraction detected via computed tomography, associated with elevated cardiac biomarker levels and myocardial structural changes, may lead to the incidental diagnosis of cardiac amyloidosis.

Aims: High lipoprotein(a) [Lp(a)] level has been demonstrated as an important risk factor for atherosclerotic cardiovascular diseases (ASCVD) amongst the older populations, whereas its effects in the younger population remain unclear. This study evaluated the associations between Lp(a) and the risk of premature ASCVD.

Method and results: PubMed and Embase were searched for related studies until 12 November 2023. Fifty-one studies including 100 540 participants were included. Mean age of patients ranged from 35.3 to 62.3 years. The proportion of male participants ranged from 0% to 100%. The mean follow-up was provided in five studies ranging from 1 year to 40 years. The definition of elevated Lp(a) varied among studies, such as >30 mg/dL, >50 mg/dL, the top tertiles, the top quartiles, the top quintiles, and so on. Higher Lp(a) was significantly associated with the composite ASCVD [odds ratio (OR): 2.15, 95% confidence interval (95% CI): 1.53-3.02, P < 0.001], especially for coronary artery disease (OR: 2.44, 95% CI: 2.06-2.90, P < 0.001) and peripheral arterial disease (OR: 2.56, 95% CI: 1.56-4.21, P < 0.001). This association remained significant in familial hypercholesterolaemia (FH) (OR: 3.11, 95% CI: 1.63-5.96, P < 0.001) and type 2 diabetes mellitus (T2DM) patients (OR: 2.23; 95% CI: 1.54-3.23, P < 0.001).Significant results were observed in South Asians (OR: 3.71, 95% CI: 2.31-5.96, P < 0.001), Caucasians (OR: 3.17, 95% CI: 2.22-4.52, P < 0.001), and patients with baseline low-density lipoprotein cholesterol (LDL-c) level ≥ 2.6 mmol/L.

Conclusion: Elevated Lp(a) predicts the risk of the composite or individual ASCVD in young, regardless of study design, gender, population characteristics (community or hospitalized), different premature definitions, and various Lp(a) measurement approaches. This association was important in South Asians, Caucasians, FH patients, T2DM patients, and patients with baseline LDL-c level ≥ 2.6 mmol/L.

Aims: To evaluate the effects of a multi-component intervention for smokers hospitalized for atherosclerotic cardiovascular disease (ASCVD) on the participation rate in community-based cessation programmes and the use of cessation drugs. Additionally, to explore the impact on the cessation rates at 6 months.

Methods and results: A randomized parallel-group study was conducted at a Norwegian secondary care hospital in 2021. The intervention group was: (i) counselled using motivational interviewing techniques during hospitalization; (ii) given an information leaflet, detailing the cessation programme; and (iii) referred to the community-based smoking cessation treatment including a post-discharge pro-active telephone invitation. The control group received usual care and the same information leaflet containing clear contact details for initiating participation. Data were collected at baseline, 1, 3, and 6 months. Among 99 smokers hospitalized with ASCVD, 40 were excluded. Of 59 randomized patients, 4 were lost to follow-up and 55 completed the study. The mean age was 65.1 (standard deviation 9.3) years, 35% were female, and 88% had smoked >20 years. Co-morbidity was prevalent (mean Charlson score 4.8). The intervention group was more likely to participate in the smoking cessation treatment {48 vs. 7%, difference: 41% [95% confidence interval (CI): 14%, 63%]} and used cessation drugs more frequently [59 vs. 21%, difference: 38% (95% CI: 17%, 59%)]. At the 6 months point prevalence, we observed notable between-group differences in self-reported cessation rate (48 vs. 25%).

Conclusion: The intervention significantly increased the participation rate at community-based smoking cessation programmes and the use of cessation drugs among multi-morbid smokers hospitalized for ASCVD.

Aims: The aim of this study was to investigate circulating ceramides involved in cardiovascular disease (CVD) in young adult childhood cancer survivors (CCS) and their correlations to previously reported adverse cardiovascular changes in this cohort.

Methods and results: Fifty-seven CCS and 53 healthy controls (age 20-30 years) were studied. Plasma long-chain ceramides, known to be cardiotoxic (C16:0, C18:0, C24:0, and C24:1), were analysed by mass spectrometry. The coronary event risk test 2 (CERT2) score was calculated from the ceramide data. Cardiac and carotid artery ultrasound data and lipid data available from previous studies of this cohort were used to study partial correlations with ceramide and CERT2 score data. All four analysed ceramides were elevated in CCS compared with controls (P ≤ 0.012). The greatest difference was noted for C18:0, which was 33% higher in CCS compared with controls adjusted for sex, age, and body mass index (BMI) (P < 0.001). The CERT2 score was higher in CCS compared with controls (P < 0.001). In the CCS group, 35% had a high to very high CERT2 score (7-12) when compared with 9% in the control group (P < 0.001). The CCS subgroup with a CERT2 score ≥ 7 had higher heart rate, systolic blood pressure, and higher levels of apolipoprotein B compared with CCS with a CERT2 score < 6 (P ≤ 0.011). When adjusted for age, sex, and BMI, CERT2 score was significantly correlated with arterial stiffness, growth hormone, and cranial radiotherapy (P < 0.044).

Conclusion: Ceramides could be important biomarkers in understanding the pathophysiology of CVD and in predicting CVD disease risk in young adult CCS.