European journal of preventive cardiology最新文献

Aims: Inclisiran, an siRNA-targeting hepatic PCSK9 mRNA, reduces low-density lipoprotein cholesterol (LDL-C), but its effect on major adverse cardiovascular event (MACE) remains unconfirmed. The SIRIUS in-silico modelling program aimed to predict the efficacy of inclisiran on MACE in virtual patients with atherosclerotic cardiovascular disease (ASCVD).

Methods: The SIRIUS simulation (NCT05974345) used a validated mechanistic model of ASCVD and lipid-lowering therapy (LLT) effects in a virtual population with established ASCVD and LDL-C ≥70 mg/dL. Each virtual patient served as their own control to compare inclisiran versus placebo as an adjunct to high-intensity statin therapy, alone or with ezetimibe over 5 years. The model did not account for non-adherence, recurrent events, or adverse effects.

Results: Among 204 691 virtual patients, inclisiran was predicted to reduce LDL-C by 49.7% versus placebo (from 91.1 to 48.3 mg/dL). Relative to placebo, inclisiran was predicted to lower 5 years risk of 3-point MACE by 25.2% (11.3% vs. 14.9%), myocardial infarction by 34.8% (5.7% vs. 8.6%; HR 0.65), ischaemic stroke by 26% (2.6% vs. 3.4%; HR 0.74), and major adverse limb event by 34.1% (0.5% vs. 0.8%; HR 0.66). A 7.1% relative reduction of cardiovascular death was predicted (4.2% vs. 4.5%; HR 0.93).

Conclusions: SIRIUS is the first in-silico simulation using a knowledge-based mechanistic model to predict the efficacy of LLT on cardiovascular outcomes in ASCVD. These findings offer early model-based prediction of inclisiran's potential cardiovascular benefit ahead of phase 3 outcome trials.

Aims: To assess independent impacts of air and noise pollution and residential green exposure on non-invasively derived coronary obstruction and myocardial ischaemia.

Methods and results: Consecutive patients screened by coronary computed tomography angiography (CCTA) for stable chest pain between 1 January 2019 and 31 December 2020 were included in a registry. Exposure associations between residential PM2.5 (particulate matter <2.5 μm), NO2 (nitric dioxide), major road distance, airport distance, normalized difference vegetation index, obstructive coronary artery disease (OCAD, stenosis ≥50%), and abnormal fractional flow reserve (FFRCT ≤80%) measurements were assessed by propensity score (PS)-adjusted logistic regression. A subgroup analysis was performed according to Framingham low (<10%) and high (>20%) 10-year coronary heart disease risk categories. A total of 2620 patients were enrolled, including 420 (16%) FFRCT analyses. OCAD was reported in 518 (20%) patients and abnormal FFRCT in 276 (11%). People with OCAD lived closer to the airport [10.841 (7.869-19.022) km vs. 12.297 (8.691-22.843) km, P < 0.001). People living closer to the airport had more cardiovascular (CV) and socio-economic risk factors. Distance to airport decreased OCAD risk (OR 0.983, 95% CI 0.974-0.992, per 1 km) in univariable analysis. After PS adjustment, environmental stressors were not significantly associated with OCAD, regardless of risk categories. Only distance to major road decreased abnormal FFRCT risk (OR 0.634, 95% CI 0.421-0.926, per 1 km) in high-risk patients after PS adjustment.

Conclusion: We found no clear environmental associations with CT-derived coronary obstruction or ischaemia. However, airport proximity was linked to OCAD risk via CV and socio-economic factors, while major road proximity was independently associated with myocardial ischaemia in high-CV-risk patients, warranting further investigation.

Aims: This study aimed to explore the associations of exposure to residential green space and natural environment with incident heart failure (HF) risk and to investigate the role of PM2.5 and physical activity in these associations.

Methods and results: We conducted a prospective study using data from the UK Biobank cohort, which included 437 656 participants. Cox proportional hazards regression models were employed to assess the association between residential exposure and HF risk, adjusting for multiple potential confounding factors. Casual mediation analysis was used to determine the mediation effect of PM2.5 and physical activity. Over a median follow-up of 13.5 years, 16 209 cases with HF were recorded. In the fully adjusted models, participants with green space coverage and natural environment coverage at the 300 m buffer in the highest tertiles had 13% [hazard ratio (HR) = 0.87, 95% confidence interval (CI): 0.84-0.91] and 12% (HR = 0.88, 95% CI: 0.84-0.91) lower risks of incident HF, respectively. Similar protective associations were observed for green space (HR = 0.87, 95% CI: 0.84-0.91) and the natural environment (HR = 0.85, 95% CI: 0.81-0.88) at the 1000 m buffer. PM2.5 and physical activity partially mediated these relationships between residential exposure and HF risk.

Conclusion: Increased residential green space and natural environment levels were associated with decreased risk of incident HF, and these associations may be partially mediated by PM2.5 and physical activity.