European journal of preventive cardiology最新文献

Aims: Most polygenic risk scores (PRSs) for coronary heart disease (CHD) are derived from European ancestry populations. This paper evaluates the performance of CHD PRSs in a Mexican population.

Methods and results: 133 207 participants aged 35-79 years from the Mexico City Prospective Study were included. Eight PRSs (comprising 44-6 472 620 polymorphisms) were selected for prediction of CHD (defined as self-reported prior heart attack or angina, or CHD death before age 80 years). Logistic regression was adjusted for age, sex, and the first seven genetic principal components, before and after adjustment for other cardiovascular risk factors. The area under the receiving operating characteristic curve ('C-statistic') was also estimated. Of the included participants, 67% were women, the mean (±SD) age was 51 ± 12 years, and Indigenous American ancestry averaged 67%. CHD was documented for 5163 participants (3.9%), including 1901 prevalent and 3479 fatal cases. All eight PRSs were positively and log-linearly associated with CHD, with odds ratios (ORs) per 1 SD PRS increase ranging from 1.05 (95% CI, 1.03-1.08) to 1.29 (95% CI, 1.25-1.33). Associations were consistent across strata of age and ancestry and were independent of other vascular risk factors. For six PRSs, however, associations were substantially stronger in men than women. Multi-ancestry PRSs outperformed Eurocentric-ancestry PRSs. Despite remaining predictive of risk independently of established non-genetic risk factors, inclusion of a PRS into a risk model did not increase the C-statistic noticeably.

Conclusion: In this Mexican population, existing PRSs predicted CHD independently of established vascular risk factors, particularly for men. PRSs better capturing genetic variation in Latin American people may further enhance risk prediction in such populations.

Aims: The study aimed to assess the effectiveness of three clinical diagnostic criteria [Simon Broome (SB), MEDPED (MP), and guideline-derived (GL-EAS)] in identifying children with familial hypercholesterolaemia (FH) compared with genetic testing. The evaluation involved 1337 children with elevated LDL cholesterol (LDL-C) levels, focusing on the sensitivity and specificity of these clinical scores in detecting genetically confirmed FH cases.

Methods and results: Clinical data were gathered by a self-reporting questionnaire. Clinical FH was defined in accordance with the tested FH score. Genetically confirmed heterozygous FH (HeFH) was defined by a (likely) pathogenic variant. Of the 1337 children undergoing genetic analysis, 211 showed a pathogenic FH mutation. Applying SB, MP, and GL-EAS criteria resulted in 210/1337, 125/1337, and 112/835 children being categorized to have FH clinically. The sensitivity of the clinical scores ranged from 0.44 to 0.54 with a positive predictive value (PPV) of 0.51-0.79. The specificity was 0.91-0.97 with a negative predictive value (NPV) of 0.89-0.91. Similar results were observed for the three clinical scores regarding sensitivity, specificity, PPV, and NPV in subgroup analyses defined by gender, age (<10 years vs. ≥10 years), or weight [≥90th BMI (body mass index) percentile vs. <90th BMI percentile].

Conclusion: Clinical FH scores offer a high degree of specificity for FH diagnosis in children, but at the expense of low sensitivity. Specifically, half of the mutation-positive children in this study would have been missed for early diagnosis and preventive treatment. Given the widespread availability of affordable genetic testing, such analysis should be performed at a lower threshold than that indicated by these clinical scores.

Aims: Iron levels imbalances are linked to cardiovascular outcomes. We aimed to assess the association between genetically predicted lifelong higher iron levels and cardiovascular outcomes, employing a two-sample Mendelian randomization (MR) approach to account for confounding biases.

Methods and results: We used a study involving 257 953 subjects across six cohort studies that identified genetic variants consistently associated with iron biomarkers, including ferritin, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT). The UK Biobank study was used to investigate the association between the same genetic variants and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), left ventricular mass (LVM), and left ventricular mass-to-end-diastolic volume ratio (LVMVR). Two-sample MR approach was used in our main analysis. Heterogeneity, pleiotropy, bidirectional MR, MR-Egger, weighted median, and weighted mode were explored in the sensitivity analysis. One standard deviation (SD) increase in genetically predicted serum iron levels was associated with lower LVEDV (beta (95%CI): -0.11, (-0.19, -0.03), P-value = 0.006) and lower LVESV (-0.11 (-0.19, -0.03), P-value = 0.007). Moreover, one SD increase in genetically predicted TSAT was associated with higher LVMVR (0.09, (0.03, 0.15), P-value = 0.005). Heterogeneity, pleiotropy, and bidirectional effects were not observed. The identified associations were explained by HFE, TMPRSS6, TF, and TFR2 genes. No other associations were identified between iron biomarkers and cardiovascular outcomes.

Conclusion: Our study provides MR evidence that iron status may alter cardiovascular function and structure. HFE, TMPRSS6, TF and TFR2 genes play a crucial role in the identified associations.

Aims: Available data on economic consequences of carrying an inherited familial hypercholesterolaemia (FH) genetic variant are sparse. This study aims to explore the hospital and pharmaceutical resource use and costs associated with cardiovascular disease (CVD) in patients with genetically verified FH compared with age- and sex-matched controls during the period 2010 through 2019.

Methods and results: We included 5585 individuals with genetically verified FH from the Norwegian Unit for Cardiac and Cardiovascular Genetics registry and 111 483 age- and sex-matched controls from the general Norwegian population. Resource use and costs associated with CVD were collected from the Norwegian Patient Registry, the Cause of Death Registry, and the Norwegian Prescription Database. We estimated costs in European euros (EUR, €) based on diagnosis-related group (DRG) cost weights and pharmaceutical drug prices (Norwegian kroner 1 = EUR 0.1015). During 2010-19, patients with FH had CVD-related costs of €3911 per person for hospital care and €6119 for pharmaceuticals compared with €1498 and €514 among controls, respectively. The 10-year costs per person of percutaneous coronary interventions were €561 for FH and €140 for controls. The costs of CVD prescription drugs doubled in the FH population during 2010-19, largely due to the introduction of proprotein convertase subtilisin/kexin Type 9 inhibitors. Costs for prescription drugs increased in both the FH and control populations (P = 0.002 for FH and P = 0.005 for controls), while costs decreased for hospital care (P = 0. 0069 for FH and P = 0. 0943 for controls).

Conclusion: Familial hypercholesterolaemia patients had about three times higher CVD-related hospital costs and more than 10 times higher pharmaceutical costs than age- and sex-matched controls during a 10-year follow-up. During the 10 years, costs for pharmaceuticals increased and costs for hospital decreased.