Predictors of 10-Year Stent-Related Adverse Outcomes after Coronary Drug-Eluting Stent Implantation: The Importance of Stent Size.

INTRODUCTION: The predictors of stent treatment failure and their importance 10 years after treatment with drug-eluting stents (DESs) have not been reported in detail. METHODS: Data were retrieved from the SORT-OUT II database encompassing 2,849 non-left main coronary lesions in 2,073 unselected all-comer patients treated with first-generation DES and followed clinically for 10 years. Stent treatment failure (STF) was defined as definite or probable stent thrombosis, target lesion revascularization (TLR), or >70% restenosis left untreated. Target lesion failure (TLF) was defined as cardiac death, target vessel myocardial infarction, or TLR. Characteristics predicting higher hazard ratios (HRs) were identified by the multivariate Cox regression analysis. RESULTS: A stent diameter ≤2.5 versus ≥3.5 mm had STF 23.3 versus 11.8% and TLF 27.9 versus 18.8%. Stent length <20 versus >40 mm had STF 13.0 versus 29.0% and TLF 18.7 versus 34.6%. In multivariate analysis, decreasing stent diameter (HR: 1.24 [3.0 mm] to 2.12 [2.25 mm], reference ≥3.5 mm) and increasing stent length (HR: 1.15 [20-30 mm] to 2.07 [>40 mm], reference <20 mm) predicted STF together with diabetes (HR: 1.31), previous revascularization (HR: 1.31), restenotic (HR: 2.25), bifurcation (HR: 1.45), and chronically occluded lesions (HR: 1.54). A predictive score (PS) was calculated for each lesion from the HRs for the predictors present. The 10-year rates of STF were 10% in lesions with a PS ≤ 1.5 and 37% in those with PS ≥ 3.5. CONCLUSIONS: Ten-year outcomes show large variations depending on the stent size and a few patient and lesion characteristics. The calculation of a PS from these unambiguous variables may be used to improve the risk estimate in individual lesions and patients.

Office blood pressure or ambulatory blood pressure for the prediction of cardiovascular events.

AIMS: To determine the added value of (i) 24-h ambulatory blood pressure relative to office blood pressure and (ii) night-time ambulatory blood pressure relative to daytime ambulatory blood pressure for 10-year person-specific absolute risks of fatal and non-fatal cardiovascular events. METHODS AND RESULTS: A total of 7927 participants were included from the International Database on Ambulatory blood pressure monitoring in relation to Cardiovascular Outcomes. We used cause-specific Cox regression to predict 10-year person-specific absolute risks of fatal and non-fatal cardiovascular events. Discrimination of 10-year outcomes was assessed by time-dependent area under the receiver operating characteristic curve (AUC). No differences in predicted risks were observed when comparing office blood pressure and ambulatory blood pressure. The median difference in 10-year risks (1st; 3rd quartile) was -0.01% (-0.3%; 0.1%) for cardiovascular mortality and -0.1% (-1.1%; 0.5%) for cardiovascular events. The difference in AUC (95% confidence interval) was 0.65% (0.22-1.08%) for cardiovascular mortality and 1.33% (0.83-1.84%) for cardiovascular events. Comparing daytime and night-time blood pressure, the median difference in 10-year risks was 0.002% (-0.1%; 0.1%) for cardiovascular mortality and -0.01% (-0.5%; 0.2%) for cardiovascular events. The difference in AUC was 0.10% (-0.08 to 0.29%) for cardiovascular mortality and 0.15% (-0.06 to 0.35%) for cardiovascular events. CONCLUSION: Ten-year predictions obtained from ambulatory blood pressure are similar to predictions from office blood pressure. Night-time blood pressure does not improve 10-year predictions obtained from daytime measurements. For an otherwise healthy population sufficient prognostic accuracy of cardiovascular risks can be achieved with office blood pressure.

Prediction of cardiovascular events from systolic or diastolic blood pressure.

Over time, a focus on blood pressure has transferred from diastolic pressure to systolic pressure. Formal analyses of differences in predictive value are scarce. Our goal of the study was whether office SBP adds prognostic information to office DBP and whether both 24-h ambulatory SBP and 24-h ambulatory DBP is specifically important. The authors examined 2097 participants from a population cohort recruited in Copenhagen, Denmark. Cause-specific Cox regression was performed to predict 10-year person-specific absolute risks of fatal and non-fatal cardiovascular (CV) events. Also, the time-dependent area under the receiver operator curve (AUC) was utilized to evaluate discriminative ability. The calibration plots of the models (Hosmer-May test) were calculated as well as the Brier score which combines (discrimination and calibration). Adding both 24-h ambulatory SBP and 24-h ambulatory diastolic blood pressure did not significantly increase AUC for CV mortality and CV events. Moreover, adding both office SBP and office DBP did not significantly improve AUC for both CV mortality and CV events. The difference in AUC (95% confidence interval; p-value) was .26% (-.2% to .73%; .27) for 10-year CV mortality and .69% (-.09% to 1.46%; .082) for 10-year risk of CV events. The difference in AUC was .12% (-.2% to .44%; .46) for 10-year CV mortality and .04% (-.35 to .42%; .85) for 10-year risk of CV events. Moreover, for both CV mortality and CV events, office SBP did not improve prognostic information to office DBP. In addition, the Brier scores of office BP in both CV mortality and CV events were .078 and .077, respectively. Furthermore, the Brier scores were .077 and .078 in CV mortality and CV events of 24-h ambulatory. For the average population as those participating in a population survey, the 10-year discriminative ability for long-term predictions of CV death and CV events is not improved by adding systolic to diastolic blood pressure. This finding is found for ambulatory as well as office blood pressure.

Vasomotor dysfunction in human subcutaneous arteries exposed ex vivo to food-grade titanium dioxide.

Animal studies have shown that titanium dioxide (TiO2) exposure affects arterial vasomotor function, whereas little is known about the effects in arteries from humans. This study investigated vasomotor responses after direct exposure of human subcutaneous arteries to food-grade TiO2 (E171) (14 or 140 µg/ml) for 30 min and 18 h. Vasomotor responses to bradykinin, 5-hydroxytryptamine (5-HT), sarafotoxin 6c (S6c) and nitroglycerin were recorded in wire-myographs. Vasoconstrictor responses to 5-HT were increased in arteries exposed to E171 for 18 h (P < 0.05). Furthermore, an increase in S6c responses was seen in low concentration E171 exposed arteries (30 min exposure; P < 0.05). The vasorelaxation response to nitroglycerin was increased in low concentration E171 exposed arteries (30 min exposure; P < 0.05). Vasorelaxation responses to bradykinin were unaffected after treatment with E171. There was no difference in gene expression levels of intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, 5-hydroxytryptamine receptor 1B, 5-hydroxytryptamine receptor 2A, endothelin receptor A and endothelin receptor B in E171 exposed arteries after exposure to TiO2 for 30 min or 18 h. In conclusion, this study shows that the same type of vasomotor dysfunction is found in artery segments of rats and humans following ex vivo exposure to E171.

Vascular and molecular pharmacology of the metabolically stable CGRP analogue, SAX.

The main purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and a recently discovered metabolically stable CGRP analogue, SAX, in isolated rat and human artery segments. In rat, CGRP and SAX induced similar vasodilatory responses in isolated mesenteric artery with the potency of SAX being lower than that of CGRP (vasodilatory pEC50 8.2 ±â€¯0.12 and 9.0 ±â€¯0.11, respectively). A corresponding difference in receptor binding affinity of SAX and CGRP was determined in rat cerebral membranes (pKi 8.3 ±â€¯0.19 and 9.3 ±â€¯0.14, respectively). CGRP and SAX-induced vasodilation was antagonised with similar potencies by the CGRP receptor antagonist BIBN4096BS supporting a uniform receptor population for the agonists. In human tissue, SAX and CGRP induced similar pharmacological responses with different potencies in subcutaneous artery (vasodilatory pEC50 8.8 ±â€¯0.18 and 9.5 ±â€¯0.13, respectively) and human recombinant receptors (cAMP signalling pEC50 9.1 ±â€¯0.16 and 10.2 ±â€¯0.19). Like in the rat mesenteric artery, both SAX and CGRP-responses were inhibited by the CGRP receptor antagonist BIBN4096BS with similar antagonistic potencies. In conclusion, all pharmacological characteristics of SAX and CGRP in human and rat sources points towards action via a uniform BIBN4096BS sensitive receptor population with the potency of SAX being 5-10 fold lower than that of CGRP.

[Two cases of takotsubo cardiomyopathy in patients treated with high doses of inhaled beta-2-agonists].

Takotsubo cardiomyopathy (TCM) is characterised by reversible left ventricular dysfunction in patients presenting with acute coronary syndrome (ACS). TCM is considered multifactorial, and the repetitive exposure to inhaled beta-2-agonists has been suspected to induce TCM in predisposed individuals. We report two cases of TCM in female patients presenting with ACS both exposed to inhaled beta-2-agonists. Eccocardiography revealed apical ballooning and reduced left ventricular function. Coronary angiography was with no significant stenosis. Both patients recovered by anticongestive treatment.