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AimA major feature of endothelial dysfunction is reduced endothelium‐dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both.MethodWe tested this hypothesis in 12 younger (age 18–38 years, six women) and 12 older healthy adults (age 55–73 years, six post‐menopausal women). Endothelium‐dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra‐arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 μg dl−1forearm tissue min−1) before and 90 min after inhibition of the enzyme cyclo‐oxygenase‐2 (COX‐2) with oral celecoxib (400 mg), followed by the addition of endothelialNOsynthase inhibition with intra‐arterialNG‐monomethyl‐l arginine acetate (L‐NMMA).ResultsAgeing was associated with a significantly reducedFVCresponse toACh(P= 0.009, age‐by‐dose interaction; highest doseFVC±SEMin ageing: 11.2 ± 1.4vs.younger: 17.7 ± 2.4 units,P= 0.02). Celecoxib did not reduce restingFVCor the responses toAChin any group.L‐NMMAsignificantly reduced restingFVCand the responses toAChin all groups, and absoluteFVCvalues followingL‐NMMAwere similar between groups.ConclusionIn healthy normotensive younger and older adults, there is minimal contribution of prostacyclin toACh‐mediated vasodilation, yet theNOcomponent of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e.COX‐2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use ofCOX‐2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors.

ObjectiveTo demonstrate that a distinct group of patients with Grade Ia diastolic dysfunction who do not conform to present ASE/ESE diastolic grading exists.Method and ResultsEchocardiographic and demographic data of the Grade Ia diastolic dysfunction were extracted and compared with that of Grades I and II in 515 patients. The mean of age of the cohort was 75 ± 9 years and body mass index did not differ significantly between the 3 groups (P = 0.45). Measurements of left atrial volume index (28.58 ± 7 mL/m2 in I, 33 ± 10 mL/m2 in Ia, and 39 ± 12 mL/m2 in II P < 0.001), isovolumic relaxation time (IVRT) (100 ± 17 msec in I, 103 ± 21 msec in Ia, and 79 ± 15 msec in II P < 0.001), deceleration time (248 ± 52 msec in I, 263 ± 58 msec in Ia, and 217 ± 57 msec in II P < 0.001), medial E/e′ (10 ± 3 in I, 18 ± 5.00 in Ia, and 22 ± 8 in II), and lateral E/e′ (8 ± 3 in I, 15 ± 6 in Ia, and 18 ± 9 in II P < 0.001) were significantly different in grade Ia compared with I and II. These findings remained significant even after adjusting for age, gender, diabetes, and smoking.ConclusionPatients with echocardiographic characteristics of relaxation abnormality (E/A ratio of <0.8) and elevated filling pressures (septal E/e′ ≥15, lateral E/e′ ≥12, average E/e′ ≥13) should be graded as a separate Grade Ia group.

Background— Current guidelines recommend coronary artery bypass graft surgery (CABG) when treating significant de novo left main coronary artery (LM) stenosis; however, percutaneous coronary intervention (PCI) has a class IIa indication for unprotected LM disease in selected patients. This analysis compares 5-year clinical outcomes in PCI- and CABG-treated LM patients in the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) trial, the largest trial in this group to date. Methods and Results— The SYNTAX trial randomly assigned 1800 patients with LM or 3-vessel disease to receive either PCI (with TAXUS Express paclitaxel-eluting stents) or CABG. The unprotected LM cohort (N=705) was predefined and powered. Major adverse cardiac and cerebrovascular event rates at 5 years was 36.9% in PCI patients and 31.0% in CABG patients (hazard ratio, 1.23 [95% confidence interval, 0.95–1.59]; P =0.12). Mortality rate was 12.8% and 14.6% in PCI and CABG patients, respectively (hazard ratio, 0.88 [95% confidence interval, 0.58–1.32]; P =0.53). Stroke was significantly increased in the CABG group (PCI 1.5% versus CABG 4.3%; hazard ratio, 0.33 [95% confidence interval, 0.12–0.92]; P =0.03) and repeat revascularization in the PCI arm (26.7% versus 15.5%; hazard ratio, 1.82 [95% confidence interval, 1.28–2.57]; P <0.01). Major adverse cardiac and cerebrovascular events were similar between arms in patients with low/intermediate SYNTAX scores but significantly increased in PCI patients with high scores (≥33). Conclusions— At 5 years, no difference in overall major adverse cardiac and cerebrovascular events was found between treatment groups. PCI-treated patients had a lower stroke but a higher revascularization rate versus CABG. These results suggest that both treatments are valid options for LM patients. The extent of disease should accounted for when choosing between surgery and PCI, because patients with high SYNTAX scores seem to benefit more from surgery compared with those in the lower tertiles. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00114972.

Background— Coronary collateral flow is an alternative source of myocardial perfusion in patients with totally occluded coronary arteries. Clinical evaluation of collateral flow has been limited by the need of invasive measurements. We investigated whether noninvasive coronary computed tomographic angiography can evaluate the angiographic extent of coronary collateral flow. Methods and Results— We enrolled 325 coronary computed tomographic angiography cases with angiographically confirmed chronic total occlusion (median age, 63 years; men 83%). Transluminal attenuation gradient (TAG), which reflects the kinetics of contrast media in coronary artery, of an entire artery as well as of a distal vessel was assessed to evaluate the flow in entire vessel and distal vessel. TAGs were validated against visually assessed angiographic collateral connection and Rentrop grading. TAG of an entire artery increased consistently according to the angiographic extent of collateral flow ( P <0.001). Well-developed collaterals, defined by highest collateral connection and Rentrop grades (n=103), could be predicted by TAG of an entire artery (cutoff, ≥−7.6 Hounsfield units/10 mm; c -statistics, 0.72; sensitivity, 65%; specificity, 73%; positive predictive value, 52%; negative predictive value, 82%). TAG of a distal vessel could discriminate the antegrade (n=143) and retrograde (n=182) flows in distal artery (cutoff, 0.0 Hounsfield unit/10 mm; c -statistics, 0.88; sensitivity, 78%; specificity, 85%; positive predictive value, 87%; negative predictive value, 75%). Conclusions— TAG, an intracoronary attenuation-based analysis of coronary computed tomographic angiography, moderately reflected the functional extent and direction of collateral flow.