Pressure-wire assessment of coronary stenosis is considered the invasive reference standard for detection of ischaemia-generating lesions. Recently, methods to estimate the fractional flow reserve (FFR) from conventional angiography without the use of a pressure wire have been developed, and were shown to have an excellent diagnostic accuracy. The present systematic review and meta-analysis aimed at determining the diagnostic performance of angiography-derived FFR for the diagnosis of haemodynamically significant coronary artery disease. A systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived FFR systems were performed. The primary outcome of interest was pooled sensitivity and specificity. Thirteen studies comprising 1842 vessels were included in the final analysis. A Bayesian bivariate meta-analysis yielded a pooled sensitivity of 89% (95% credible interval 83-94%), specificity of 90% (95% credible interval 88-92%), positive likelihood ratio (+LR) of 9.3 (95% credible interval 7.3-11.7) and negative likelihood ratio (-LR) of 0.13 (95% credible interval 0.07-0.2). The summary area under the receiver-operating curve was 0.84 (95% credible interval 0.66-0.94). Meta-regression analysis did not find differences between the methods for pressure-drop calculation (computational fluid dynamics vs. mathematical formula), type of analysis (on-line vs. off-line) or software packages. The accuracy of angiography-derived FFR was good to detect haemodynamically significant lesions with pressure-wire measured FFR as a reference. Computational approaches and software packages did not influence the diagnostic accuracy of angiography-derived FFR. A diagnostic strategy trial with angiography-derived FFR evaluating clinical endpoints is warranted.

Exposure to diesel exhaust was recently identified as an important cardiovascular risk factor, but whether it impairs nitric oxide (NO)–mediated endothelial function and increases production of reactive oxygen species (ROS) in endothelial cells is not known. We tested these hypotheses in a randomized, controlled, crossover study in healthy male volunteers exposed to ambient and polluted air (n=12). The effects of skin microvascular hyperemic provocative tests, including local heating and iontophoresis of acetylcholine and sodium nitroprusside, were assessed using a laser Doppler imager. Before local heating, skin was pretreated by iontophoresis of either a specific NO–synthase inhibitor (L- N -arginine-methyl-ester) or a saline solution (Control). ROS production was measured by chemiluminescence using the lucigenin technique in human umbilical vein endothelial cells preincubated with serum from 5 of the subjects. Exposure to diesel exhaust reduced acetylcholine-induced vasodilation ( P <0.01) but did not affect vasodilation with sodium nitroprusside. Moreover, the acetylcholine/sodium nitroprusside vasodilation ratio decreased from 1.51±0.1 to 1.06±0.07 ( P <0.01) and was correlated to inhaled particulate matter 2.5 ( r =−0.55; P <0.01). NO–mediated skin thermal vasodilatation decreased from 466±264% to 29±123% ( P <0.05). ROS production was increased after polluted air exposure ( P <0.01) and was correlated with the total amount of inhaled particulate matter <2.5 μm (PM2.5). In healthy subjects, acute experimental exposure to diesel exhaust impaired NO–mediated endothelial vasomotor function and promoted ROS generation in endothelial cells. Increased PM2.5 inhalation enhances microvascular dysfunction and ROS production.

Environmental tobacco smoke (ETS) acutely affects peripheral and coronary vascular tone. Whether ETS exerts specific deleterious effects on aortic wave reflection through nicotine exposure, whether they persist after ETS cessation, and whether the smoke environment impairs microvascular function and increases asymmetrical dimethyl-arginine levels are not known. We tested these hypotheses in a randomized, crossover study design in 11 healthy male nonsmokers. The effects of 1 hour of exposure to ETS, as compared with a nontobacco smoke and normal air, on augmentation index corrected for heart rate and skin microvascular hyperemia to local heating were examined. Augmentation index increased both during ( P =0.01) and after ( P <0.01) the ETS session but remained unchanged in the nontobacco smoke session when compared with normal air. Nicotine levels after the exposure were related to the peak rise in augmentation index ( r =0.84; P <0.01), denoting a predominant role of nicotine in ETS vascular effects. This was confirmed in a second set of experiments (n=14), where the sublingual administration of nicotine was associated with an acute impairment in wave reflection as compared with placebo ( P =0.001). Both ETS and nontobacco smokes increased plasma asymmetrical dimethyl-arginine levels ( P <0.001), but only ETS reduced the late rise in skin blood flow in response to heating ( P =0.03). In conclusion, passive smoking specifically increases aortic wave reflection through a nicotine-dependent pathway and impairs microvascular function, even after the end of the exposure. However, both tobacco and nontobacco passive smoking inhalation increase plasma asymmetrical dimethyl-arginine levels.