Ian R. Hall

Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia

OBJECTIVES The goal of this study was to investigate the relation between serum cholesterol, arterial stiffness and central blood pressure. BACKGROUND Arterial stiffness and pulse pressure are important determinants of cardiovascular risk. However, the effect of hypercholesterolemia on arterial stiffness is controversial, and central pulse pressure has not been previously investigated. METHODS Pressure waveforms were recorded from the radial artery in 68 subjects with hypercholesterolemia and 68 controls, and corresponding central waveforms were generated using pulse wave analysis. Central pressure, augmentation index (AIx) (a measure of systemic stiffness) and aortic pulse wave velocity were determined. RESULTS There was no significant difference in peripheral blood pressure between the two groups, but central pulse pressure was significantly higher in the group with hypercholesterolemia (37 +/- 11 mm Hg vs. 33 +/- 10 mm Hg [means +/- SD]; p = 0.028). Augmentation index was also significantly higher in the patients with hypercholesterolemia group (24.8 +/- 11.3% vs. 15.6 +/- 12.1%; p < 0.001), as was the estimated aortic pulse wave velocity. In a multiple regression model, age, short stature, peripheral mean arterial pressure, smoking and low-density lipoprotein cholesterol correlated positively with AIx, and there was an inverse correlation with heart rate and male gender. CONCLUSIONS Patients with hypercholesterolemia have a higher central pulse pressure and stiffer blood vessels than matched controls, despite similar peripheral blood pressures. These hemodynamic changes may contribute to the increased risk of cardiovascular disease associated with hypercholesterolemia, and assessment may improve risk stratification.

Heart rate dependency of pulse pressure amplification and arterial stiffness.

BACKGROUND Pulse pressure and aortic pulse wave velocity, measures of arterial stiffness, are both important determinants of cardiovascular risk. However, assessment of peripheral pulse pressure does not always provide a reliable measure of changes in central pulse pressure or arterial stiffness. The aim of the present study was to assess the effect of acute changes in heart rate on arterial stiffness and on peripheral and central pulse pressure in healthy subjects. METHODS Twenty subjects (age range, 20 to 72 years) were studied at cardiac catheterization. Pulse wave analysis was used to determine central pressure, augmentation index (AIx), a measure of systemic arterial stiffness, and aortic pulse wave velocity (PWV) during right atrial pacing (80 to 120 beats/min). RESULTS Pulse pressure amplification increased during pacing due to a reduction in central pressure augmentation. AIx was significantly and inversely related to heart rate (r = -0.70, P < .001) due to an alteration in the relative timing of the reflected pressure wave, rather than a reduction in arterial stiffness, as PWV did not change. CONCLUSIONS These data suggest that peripheral pulse pressure does not provide an accurate assessment of changes in central hemodynamics in relation to changes in heart rate, and that aortic stiffness is not affected by acute changes in heart rate.

Comparison of P2Y12 inhibitors for mortality and stent thrombosis in patients with acute coronary syndromes: Single center study of 10 793 consecutive ‘real-world’ patients

Abstract Three oral platelet P2Y12 inhibitors, clopidogrel, prasugrel, and ticagrelor, are available for reducing the risk of cardiovascular death and stent thrombosis in patients with acute coronary syndromes (ACS). We sought to compare the efficacy of these antiplatelet drugs in contemporary practice. Data were collected for 10 793 consecutive ACS patients undergoing coronary angiography at Sheffield, UK (2009–2015). Since prasugrel use was mostly restricted to the STEMI subgroup, clopidogrel and ticagrelor were compared for all ACS patients, and all three agents were compared in the STEMI subgroup. Differences in outcomes were evaluated at 12 months by KM curves and log-rank test after adjustment for independent risk factors. Of 10 793 patients with ACS (36% STEMI), 43% (4653) received clopidogrel, 11% (1223) prasugrel and 46% (4917) ticagrelor, with aspirin for all. In the overall group, ticagrelor was associated with lower all-cause mortality compared with clopidogrel (adjusted hazard ratio (adjHR) 0.82, 95% confidence intervals (CI) 0.71–0.96, p = 0.01). In the STEMI subgroup, both prasugrel and ticagrelor were associated with a lower mortality compared with clopidogrel (prasugrel vs. clopidogrel: adjHR 0.65, CI 0.48–0.89, p = 0.007; ticagrelor vs. clopidogrel: adjHR 0.70, CI 0.61–0.99, p = 0.05). Of the 7595 patients who underwent PCI, 78 (1.0%) had definite stent thrombosis by 12 months. Patients treated with ticagrelor had a lower incidence of definite stent thrombosis compared with clopidogrel (0.6% vs. 1.1%; adjHR 0.51, CI 0.29–0.89, p = 0.03). In the STEMI subgroup, there was no significant difference between the three groups (ticagrelor 1.0%, clopidogrel = 1.5%, prasugrel = 1.6%; p = 0.29). In conclusion, ticagrelor was superior to clopidogrel for reduction in both mortality and stent thrombosis in unselected invasively managed ACS patients. In STEMI patients, both ticagrelor and prasugrel were associated with lower mortality compared with clopidogrel, but there was no significant difference in the incidence of stent thrombosis.

The Coalition and the UK Housing Market

With its origins in the collapse of the US sub-prime market, the global financial crisis might more accurately be termed a global housing crisis. Over the last decade, most developed countries experienced house price inflation; however few matched the UK, whose boom started earlier and was more sustained. A taxpayer-led recovery stopped a UK price correction in its tracks; however it will be argued that these measures only delayed momentum towards a reduced housing market under the Con–Lib Dem coalition.

Percutaneous brachial artery access for coronary artery procedures: Feasible and safe in the current era

BACKGROUND Percutaneous vascular access for coronary intervention is currently achieved predominately via the radial route, the femoral route acting as a backup. Percutaneous trans-brachial access is no longer commonly used due to concerns about vascular complications. This study aimed to investigate the safety and feasibility of percutaneous brachial access when femoral and radial access was not possible. METHODS This is a retrospective data analysis of patients who attended a single tertiary cardiology centre in the UK between 2005 and 2014 and had a coronary intervention (coronary angiogram or PCI) via the brachial route. The primary endpoints were procedural success and the occurrence of vascular complications. RESULTS During the study period 26602 patients had a procedure (15655 underwent PCI and 10947 diagnostic angiography). Of these, 117 (0.44% of total) had their procedure performed via the brachial route. The procedure was successful in 96% (112/117) of cases. 13 (11%) patients experienced post procedural complications, of which 2 (1.7%) were serious. There were no deaths. CONCLUSION Percutaneous trans-brachial arterial access is feasible with a high success rate and without evidence of high complication rate in a rare group of patients in whom femoral or sometimes radial attempts have failed.

Hypertensive Emergency and Type 2 Myocardial Infarction Resulting From Pheochromocytoma and Concurrent Capnocytophaga Canimorsus Infection

A diagnosis of myocardial infarction is made using a combination of clinical presentation, electrocardiogram and cardiac biomarkers. However, myocardial infarction can be caused by factors other than coronary artery plaque rupture and thrombosis. We describe an interesting case presenting with hypertensive emergency and type 2 myocardial infarction resulting from Pheochromocytoma associated with Capnocytophaga canimorsus infection from a dog bite. We also review current literature on the management of hypertensive emergency and Pheochromocytoma.

Pharmacodynamic Effects of a 6-Hour Regimen of Enoxaparin in Patients Undergoing Primary Percutaneous Coronary Intervention (PENNY PCI Study)

Delayed onset of action of oral P2Y 12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2–3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y 12 inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y 12 inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y 12 inhibition.

Study of Two Dose Regimens of Ticagrelor Compared with Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention for Stable Coronary Artery Disease (STEEL-PCI)

Background: Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndromes but has not been assessed in patients undergoing percutaneous coronary intervention for stable coronary artery disease. We compared the pharmacodynamic effects of ticagrelor and clopidogrel in this stable population. Methods: One hundred eighty aspirin-treated stable coronary artery disease patients, who were planned to undergo elective percutaneous coronary intervention in a single center, were randomized 1:1:1 to either a standard clopidogrel regimen or 1 of 2 regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180 mg loading dose. Cellular adenosine uptake was assessed, at the time of the procedure and pre- and postdose at 1 month, by adding adenosine 1 µmol/L to aliquots of anticoagulated whole blood and mixing with a stop solution at 0, 15, 30, and 60 seconds, then measuring residual plasma adenosine concentration by high-performance liquid chromatography. Systemic plasma adenosine concentration and platelet reactivity were assessed at the same timepoints. High-sensitivity troponin T was measured pre- and 18 to 24 hours postpercutaneous coronary intervention. Results: One hundred seventy-four patients underwent an invasive procedure, of whom 162 received percutaneous coronary intervention (mean age 65 years, 18% female, 21% with diabetes mellitus). No effect on in vitro adenosine uptake was seen postdose at 1 month for either ticagrelor dose compared with clopidogrel (residual adenosine at 15 seconds, mean±SD: clopidogrel 0.274±0.101 µmol/L; T90 0.278±0.134 µmol/L; T60 0.288±0.149 µmol/L; P=0.37). Similarly, no effect of ticagrelor on in vitro adenosine uptake was seen at other timepoints, nor was plasma adenosine concentration affected (all P>0.1). Both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition than clopidogrel (VerifyNow P2Y12 reaction units, 1 month, mean±SD: predose, T60: 62±47, T90: 40±38, clopidogrel 181±44; postdose, T60: 34±30, T90: 24±21, clopidogrel 159±57; all P<0.0001 for ticagrelor versus clopidogrel). High platelet reactivity was markedly less with both T60 and T90 compared with clopidogrel (VerifyNow P2Y12 reaction units>208, 1 month postdose: 0%, 0%, and 21%, respectively). Median (interquartile range) high-sensitivity troponin T increased 16.9 (6.5–46.9) ng/L for clopidogrel, 22.4 (5.5–53.8) ng/L for T60, and 17.7 (8.1–43.5) ng/L for T90 (P=0.95). There was a trend toward less dyspnea with T60 versus T90 (7.1% versus 19.0%; P=0.09). Conclusions: Maintenance therapy with T60 or T90 had no detectable effect on cellular adenosine uptake at 1 month, nor was there any effect on systemic plasma adenosine levels. Both regimens of ticagrelor achieved greater and more consistent platelet inhibition than clopidogrel but did not appear to affect troponin release after percutaneous coronary intervention. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02327624.

COMPARISON OF P2Y12 INHIBITORS FOR MORTALITY AND STENT THROMBOSIS IN PATIENTS WITH ACUTE CORONARY SYNDROMES: SINGLE CENTRE STUDY OF 10,793 CONSECUTIVE ‘REAL-WORLD’ PATIENTS

Background: We compared clopidogrel, prasugrel and ticagrelor, for mortality and stent thrombosis (ST) in patients with acute coronary syndromes (ACS). Methods: Data were collected for 10,793 consecutive ACS patients undergoing coronary angiography at Sheffield, UK (2009–2015). Clopidogrel and

27 Impact of Culprit Versus Non-Culprit Angiography Strategy on Primary PCI Door to Balloon Times

Background Guidelines for ST-segment elevation myocardial infarction (STEMI) recommend primary percutaneous coronary intervention (PPCI) within 90 min of arrival in a PCI-capable hospital. Some PCI operators perform diagnostic angiography of the non-culprit artery prior to intervention (‘non-culprit’ strategy) while others proceed directly to the presumed culprit vessel (‘culprit’ strategy) reserving imaging of the non-culprit vessel until after the PCI. We evaluated the ‘time cost’ of each approach and their impact upon door to balloon times (D2B). Methods All consecutive patients presenting with STEMI to a regional heart attack centre between April 2014 and March 2015 (n = 630) were included. The time from the first angiogram acquisition (culprit or non-culprit vessel) to device use (thrombectomy catheter, balloon or stent) was recorded for each strategy. Overall D2B times were analysed. Results A culprit strategy was followed in 69/630 and a non-culprit approach in 561/630. The mean time from first image to device use was 15 mins 41s for non-culprit strategy and 8 mins 9s for culprit strategy. The non-culprit strategy therefore incurred a delay of 7 mins 32s (p < 0.01). The mean D2B time was 52 mins and 66 mins for the culprit and non-culprit strategies respectively (p < 0.05). The percentage meeting D2B time <90mins was 86% for culprit and 78% for non-culprit strategies. Percentage meeting D2B time <60 mins (which may have additional mortality benefit) was 71% and 58% for the culprit and non-culprit strategies respectively. In our cohort, mortality was significantly lower in patients with D2B <90 mins at 2.0%, versus 4.6% in those whose D2B was >90mins (p = 0.02). Conclusion A ‘culprit’ PPCI strategy results in significantly shorter D2B times, facilitating institutional attainment of national guideline targets, which may translate into improved patient outcomes.