Dominic P.J. Howard

Population-Based Study of Incidence and Outcome of Acute Aortic Dissection and Premorbid Risk Factor Control 10-Year Results From the Oxford Vascular Study

Background— Acute aortic dissection is a preventable life-threatening condition. However, there have been no prospective population-based studies of incidence or outcome to inform an understanding of risk factors, strategies for prevention, or projections for future clinical service provision. Methods and Results— We prospectively determined incidence and outcomes of all acute aortic dissections in a population of 92 728 in Oxfordshire, United Kingdom, from 2002 to 2012. Among 155 patients with 174 acute aortic events, 54 patients had 59 thoracoabdominal aortic dissections (52 incident events: 6/100 000, 95% confidence interval, 4–7; 37 Stanford type A, 15 Stanford type B; 31 men, mean age=72.0 years). Among patients with type A incident events, 18 (48.6%) died before hospital assessment (61.1% women). The 30-day fatality rate was 47.4% for patients with type A dissections who survived to hospital admission and 13.3% for patients with type B dissections, although subsequent 5-year survival rates were high (85.7% for type A; 83.3% for type B). Even though 67.3% of patients were on antihypertensive drugs, 46.0% of all patients had at least 1 systolic BP ≥180 mm Hg in their primary care records over the preceding 5 years, and the proportion of blood pressures in the hypertensive range (>140/90 mm Hg) averaged 56.0%. Premorbid blood pressure was higher in patients with type A dissections that were immediately fatal than in those who survived to admission (mean/standard deviation pre-event systolic blood pressure=151.2/19.3 versus 137.9/17.9; P<0.001). Conclusions— Uncontrolled hypertension remains the most significant treatable risk factor for acute aortic dissection. Prospective population-based ascertainment showed that hospital-based registries will underestimate not only incidence and case fatality, but also the association with premorbid hypertension.

Symptomatic Carotid Atherosclerotic Disease Correlations Between Plaque Composition and Ipsilateral Stroke Risk

Background and Purpose— For symptomatic patients with carotid artery stenosis, the risk benefit for surgical intervention may vary among patient groups. Various modalities of plaque imaging have been promoted as potential tools for additional risk stratification, particularly in patients with moderate stenosis. However, it remains uncertain to what extent carotid plaque components predict risk of future ipsilateral ischemic stroke. Methods— In 2 large atherosclerotic carotid plaque biobank studies, we related histological characteristics of 1640 carotid plaques with a validated risk model for the prediction of individual 1- and 5-year stroke risk. Results— No significant heterogeneity between the studies was found. Predicted 5-year stroke risk (top versus bottom quartile) was related to plaque thrombus (odds ratio, 1.42; 95% confidence interval, 1.11–1.89; P=0.02), fibrous content (0.65; 0.49–0.87; P=0.004), macrophage infiltration (1.41; 1.05–1.90; P=0.02), high microvessel density (1.49; 1.05–2.11; P=0.03), and overall plaque instability (1.40; 1.05–1.87; P=0.02). This association was not observed for cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration. Plaques removed within 30 days of most recent symptomatic event were most strongly correlated with predicted stroke risk. Conclusions— Features of the vulnerable carotid plaque, including plaque thrombus, low fibrous content, macrophage infiltration, and microvessel density, correlate with predicted stroke risk. This study provides a basis for plaque imaging studies focused on stroke risk stratification.

Population-Based Study of Incidence, Risk Factors, Outcome, and Prognosis of Ischemic Peripheral Arterial Events Implications for Prevention

Background— There are few published data on the incidence and long-term outcomes of critical limb ischemia, acute limb ischemia, or acute visceral ischemia with which to inform health service planning, to monitor prevention, and to enable risk prediction. Methods and Results— In a prospective population-based study (Oxfordshire, UK; 2002–2012), we determined the incidence and outcome of all acute peripheral arterial events in a population of 92 728. Risk factors were assessed by comparison with the underlying population. A total of 510 acute events occurred in 386 patients requiring 803 interventions. Two hundred twenty-one patients (59.3%) were ≥75 years of age, and 98 (26.3%) were ≥85 years old. Two hundred thirty patients (62.3%) were independent before the event, but 270 (73.4%) were dead or dependent at the 6-month follow-up, and 328 (88.9%) were dead or dependent at 5 years. The 30-day survival was lowest for patients with acute visceral ischemia (28.2%) compared with acute limb ischemia (75.3%) and critical limb ischemia (92.6%; P<0.001). Risk factors (all P<0.001) were hypertension (age- and sex-adjusted risk ratio, 2.75; 95% confidence interval, 1.95–3.90), smoking (adjusted risk ratio, 2.14; 95% confidence interval, 1.37–3.34), and diabetes mellitus (adjusted risk ratio, 3.01; 95% confidence interval, 1.69–5.35), particularly for critical limb ischemia (adjusted risk ratio, 5.96; 95% confidence interval, 3.15–11.26). Two hundred eighty-eight patients (77.2%) had known previous cardiovascular disease, and 361 (96.8%) had vascular risk factors, but only 203 (54.4%) were on an antiplatelet and only 166 (44.5%) were on a statin. Although 260 patients (69.7%) were taking antihypertensives, 42.9% of all blood pressures recorded during the 5 years before the event were >140/90 mm Hg. Of 88 patients (23.6%) with incident cardioembolic events, 62 had known atrial fibrillation (diagnosed before the event), of whom only 14.5% were anticoagulated despite 82.3% having a CHA2DS2VASC score ≥2 without contraindications. Conclusions— The clinical burden of peripheral arterial events is substantial. Although the vast majority of patients have known vascular disease in other territories and multiple treatable risk factors, premorbid control is poor.

Age-Specific Incidence, Outcome, Cost, and Projected Future Burden of Atrial Fibrillation–Related Embolic Vascular Events

Background— Prevalence of atrial fibrillation (AF) is >10% at age ≥80 years, but the impact of population aging on rates of AF-related ischemic events is uncertain. Methods and Results— We studied age-specific incidence, outcome, and cost of all AF-related incident strokes and systemic emboli from 2002 to 2012 in the Oxford Vascular Study (OXVASC). We determined time trends in incidence of AF-related stroke in comparison with a sister study in 1981 to 1986, extrapolated numbers to the UK population and projected future numbers. Of 3096 acute cerebral or peripheral vascular events in the 92 728 study population, 383 incident ischemic strokes and 71 systemic emboli were related to AF, of which 272 (59.9%) occurred at ≥80 years. Of 597 fatal or disabling incident ischemic strokes, 262 (43.9%) were AF-related. Numbers of AF-related ischemic strokes at age ≥80 years increased nearly 3-fold from 1981–1986 to 2002–2012 (extrapolated to the United Kingdom: 6621 to 18 176 per year), due partly to increased age-specific incidence (relative rate 1.52, 95% confidence interval 1.31-1.77, P=0.001), with potentially preventable AF-related events at age ≥80 years costing the United Kingdom £374 million per year. At current incidence rates, numbers of AF-related embolic events at age ≥80 years will treble again by 2050 (72 974/year), with 83.5% of all events occurring in this age group. Conclusions— Numbers of AF-related incident ischemic strokes at age ≥80 years have trebled over the last 25 years, despite the introduction of anticoagulants, and are projected to treble again by 2050, along with the numbers of systemic emboli. Improved prevention in older people with AF should be a major public health priority.

Histological Features of Carotid Plaque in Patients With Ocular Ischemia Versus Cerebral Events

Background and Purpose— Patients with carotid artery stenosis and ocular ischemic events have a much lower risk of future ipsilateral ischemic stroke on medical treatment and lower procedural risks for endarterectomy and stenting than patients with cerebral ischemic events, and are closer in risk to patients with asymptomatic stenosis. The reasons for this difference in prognosis are not fully understood, but may reflect differences in carotid plaque pathology. Methods— In consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis (Oxford Plaque Study, Athero-Express Study), we compared carotid plaque histology (using validated semiquantitative scales) in those who had cerebral events within the last 6 months (n=1317) versus those with ocular events only (n=323). Results— Compared with plaques from patients with ocular events only, those from patients with cerebral events had significantly more large lipid core (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.05–1.82; P=0.02), inflammation (OR, 1.32; 95% CI, 1.02–1.72; P=0.04) and overall plaque instability (OR, 1.37; 95% CI, 1.05–1.80; P=0.02), and less fibrous content (OR, 0.71; 95% CI, 0.54–0.92; P=0.01), and calcification (OR, 0.70; 95% CI, 0.54–0.91; P=0.008). The overall number of histological features known to be associated with vulnerable plaque was greater in patients with cerebral events than in those with ocular events (P=0.002). Conclusions— Carotid plaques from patients undergoing endarterectomy for previous ocular ischemic events have fewer vulnerable plaque features than those from patients with recent cerebral ischemic events, possibly explaining some of the differences in risk of stroke between these groups.

Age-specific incidence, risk factors and outcome of acute abdominal aortic aneurysms in a defined population.

Contemporary population‐based data on age‐specific incidence and outcome from acute abdominal aortic aneurysm (AAA) events are needed to understand the impact of risk factor modification and demographic change, and to inform AAA screening policy.

Surgical site infection rate is lower in laparoscopic than open colorectal surgery

Objective  Few studies have investigated whether surgical site infection (SSI) incidence differs between laparoscopic colorectal surgery (LCS) and open colorectal surgery (OCS). This study investigated the SSI incidence using the validated UK SSI Surveillance Service (SSISS) criteria for diagnosing wound infections.

A simple effective clean practice protocol significantly improves hand decontamination and infection control measures in the acute surgical setting.

Background:The Hand Hygiene Liaison Group and Epic Projects (Pratt et al., J Hosp Infect 47[Suppl A], 2001) have asked specifically for further trials of educational interventions to improve hand decontamination compliance and infection control in the hospital setting. This study investigates the efficacy of a ‘clean practice protocol’ (CPP), derived from international guidelines, to improve compliance of infection-control practices by surgical teams in a large UK teaching hospital.Methods:The key infection-control activities were summated to form the CPP presented here. An undisclosed infection-control audit of consultant-led ward-rounds from breast, gastrointestinal, vascular, urological, and intensivecare departments was performed. The audit results were presented to the surgical teams, after which an education/awareness program was implemented. A repeat undisclosed audit was performed 3 months later. In both audits, infection-control activities were recorded together with consultation time and any patient infective complications.Results:The surgical teams performed as follows in the initial audit: hand decontamination (28% of consultations), correct use of gloves (2%), instrument cleaning (0%), garment contamination (49%), and notes contamination (34%). Introduction of the CPP education program significantly improved hand decontamination to 87% (p < 0.0001), the correct use of gloves/aprons to 50% (p < 0.0001), and overall infection-control practice from 63% to 89% (p < 0.05).Conclusions:The introduction of the CPP significantly improved compliance of hand decontamination, correct usage of gloves and aprons, and overall infection-control in a large teaching hospital. The CPP is a highly effective auditing and educational tool that can be readily adapted for use in hospitals globally to monitor and improve infection-control practices.

Incidence, risk factors, outcome and projected future burden of acute aortic dissection.

Acute aortic dissection has a high mortality rate, despite well-established treatment guidelines (1). Data on risk factors, incidence and outcome of aortic dissection are limited, largely due to a lack of contemporary population-based studies of this condition. Existing hospital-based studies, often from specialist centers or studies of retrospective registry data such as the International Registry of Acute Aortic Dissection (IRAD), may underestimate incidence and case fatality by incomplete inclusion of deaths prior to hospital admission, which might also bias assessment of risk factors and predictors of outcome. This research highlight outlines the findings of our recent population-based research of acute aortic dissection, which is the first-ever prospective epidemiological study of this condition (2). We studied event rates, incidence, risk factors, early case fatality, and long-term outcome of all acute aortic events occurring in a population of 92,728 in Oxfordshire, UK, during 2002-2012, as part of the Oxford Vascular Study (OXVASC). Using current incidence data and Office of National Statistics (ONS) population projections (3), we went on to predict UK incidence event rates for acute aortic dissection over the next 40 years.

l-Arginine Effects on Na+ Transport in M-1 Mouse Cortical Collecting Duct Cells—A Cationic Amino Acid Absorbing Epithelium

Abstract. The effect of l-arginine on transepithelial ion transport was examined in cultured M-1 mouse renal cortical collecting duct (CCD) cells using continuous short circuit current (ISC) measurements in HCO3−/CO2 buffered solution. Steady state ISC averaged 73.8 ± 3.2 μA/cm2 (n= 126) and was reduced by 94 ± 0.6% (n= 16) by the apical addition of 100 μm amiloride. This confirms that the predominant electrogenic ion transport in M-1 cells is Na+ absorption via the epithelial sodium channel (ENaC). Experiments using the cationic amino acid l-lysine (radiolabeled) as a stable arginine analogue show that the combined activity of an apical system y+ and a basal amino acid transport system y+L are responsible for most cationic amino acid transport across M-1 cells. Together they generate net absorptive cationic amino acid flux. Application of l-arginine (10 mm) either apically or basolaterally induced a transient peak increase in ISC averaging 36.6 ± 5.4 μA/cm2 (n= 19) and 32.0 ± 7.2 μA/cm2 (n= 8), respectively. The response was preserved in the absence of bath Cl− (n= 4), but was abolished either in the absence of apical Na+ (n= 4) or by apical addition of 100 μm amiloride (n= 6). l-lysine, which cannot serve as a precursor of NO, caused a response similar to that of l-arginine (n= 4); neither L-NMMA (100 μm; n= 3) nor L-NAME (1 mm; n= 4) (both NO-synthase inhibitors) affected the ISC response to l-arginine. The effects of arginine or lysine were replicated by alkalinization that mimicked the transient alkalinization of the bath solution upon addition of these amino acids. We conclude that in M-1 cells l-arginine stimulates Na+ absorption via a pH-dependent, but NO-independent mechanism. The observed net cationic amino acid absorption will counteract passive cationic amino acid leak into the CCD in the presence of electrogenic Na+ transport, consistent with reports of stimulated expression of Na+ and cationic amino acid transporters by aldosterone.