Aims Conventional fractional flow reserve (FFR) is measured invasively using a coronary guidewire equipped with a pressure sensor. A non-invasive derived FFR would eliminate risk of coronary injury, minimize technical limitations, and potentially increase adoption. We aimed to evaluate the diagnostic performance of a computational pressure-flow dynamics derived FFR (caFFR), applied to coronary angiography, compared to invasive FFR. Methods and results The FLASH FFR study was a prospective, multicentre, single-arm study conducted at six centres in China. Eligible patients had native coronary artery target lesions with visually estimated diameter stenosis of 30–90% and diagnosis of stable or unstable angina pectoris. Using computational pressure-fluid dynamics, in conjunction with thrombolysis in myocardial infarction (TIMI) frame count, applied to coronary angiography, caFFR was measured online in real-time and compared blind to conventional invasive FFR by an independent core laboratory. The primary endpoint was the agreement between caFFR and FFR, with a pre-specified performance goal of 84%. Between June and December 2018, matched caFFR and FFR measurements were performed in 328 coronary arteries. Total operational time for caFFR was 4.54 ± 1.48 min. caFFR was highly correlated to FFR (R = 0.89, P = 0.76) with a mean bias of −0.002 ± 0.049 (95% limits of agreement −0.098 to 0.093). The diagnostic performance of caFFR vs. FFR was diagnostic accuracy 95.7%, sensitivity 90.4%, specificity 98.6%, positive predictive value 97.2%, negative predictive value 95.0%, and area under the receiver operating characteristic curve of 0.979. Conclusions Using wire-based FFR as the reference, caFFR has high accuracy, sensitivity, and specificity. caFFR could eliminate the need of a pressure wire, technical error and potentially increase adoption of physiological assessment of coronary artery stenosis severity. Clinical Trial Registration URL: http://www.chictr.org.cn Unique Identifier: ChiCTR1800019522.

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Objective— We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results— In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 μm were 62.9 µg/m 3 (8.1–331.0 µg/m 3 ). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, −4.3 to −0.3) to 5.0% (95% CI, −7.6 to −2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 μm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant’s clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein. Conclusions— Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.

Rationale: The pathophysiologic mechanisms of air pollution–associated exacerbation of cardiovascular events remain incompletely understood. Objective: To assess whether ambient air pollution can be a trigger of the vulnerable plaque and heightened thrombogenicity through systemic inflammatory pathways. Methods and Results: In Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunctions in Healthy Adults Living in Beijing), 73 healthy adults (mean±SD, 23.3±5.4 years) were followed up in 2014 to 2016. We estimated associations between air pollutants and biomarkers relevant to atherosclerotic plaque vulnerability, thrombogenicity, and inflammation using linear mixed-effects models and elucidated the biological pathways involved using mediation analyses. Receiver operating characteristic analyses were conducted to assess the ability of each biomarker to predict ambient air pollution exposures. High average concentrations of particulate matter in diameter <2.5 μm (91.8±63.8 µg/m 3 ) were observed during the study period. Significant increases in circulating biomarkers of plaque vulnerability, namely MMPs (matrix metalloproteinases; MMP-1, 2, 3, 7, 8, and 9), of 8.6% (95% CI, 0.1–17.8) to 141.4% (95% CI, 111.8–171.0) were associated with interquartile range increases in moving averages of particulate matter in diameter <2.5 μm, number concentrations of particles in sizes of 5 to 560 nm and black carbon, during the last 1 to 7 days before each participant’s clinic visit. Higher air pollutant levels were also significantly associated with decreases in TIMP (tissue inhibitors of MMPs; TIMP-1 and 2), heightened thrombogenicity (shortened prothrombin time and increases in sCD40L [soluble CD40 ligand], sCD62P [soluble P-selectin], and fibrinogen/fibrin degradation products), and elevations in systemic inflammation (IL-1β [interleukin-1β], CRP [C-reactive protein], MIP-1α/β [macrophage inflammatory protein-1α/β], sRAGE [soluble receptor for advanced glycation end products], and IGFBP [insulin-like growth factor–binding protein]-1 and 3). Receiver operating characteristic curves showed that several biomarkers can serve as robust pollutant-specific predictors with high versus low black carbon exposure (area under the receiver operating characteristic curve of 0.974 [95% CI, 0.955–0.992] for MMP-8 and 0.962 [95% CI, 0.935–0.988] for sRAGE). Mediation analysis further showed that systemic inflammation can mediate ≤46% of the changes in MMPs and thrombogenicity associated with interquartile range increases in air pollutants. Conclusions: Our results suggest that air pollution may prompt cardiovascular events by triggering vulnerable plaque along with heightened thrombogenicity possibly through systemic inflammatory pathways.