Jack F. Fairhead

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.

Underinvestigation and undertreatment of carotid disease in elderly patients with transient ischaemic attack and stroke: comparative population based study

Abstract Objective To identify any underinvestigation of older patients with transient ischaemic attack (TIA) and stroke. Design Comparative population based studies. Setting Routine clinical practice in all secondary care services in Oxfordshire and a nested population based study of incidence of transient ischaemic attack and stroke (the Oxford vascular study—OXVASC). Participants/population All patients undergoing carotid imaging for ischaemic retinal or cerebral transient ischaemic attack or stroke from 1 April 2002 to 31 March 2005 in the Oxford vascular study (n = 91 105) and from 1 April 2002 to 31 March 2003 in routine clinical practice (n = 589 899). Main outcome measures Age specific rates of carotid imaging, diagnosed ≥ 50% symptomatic carotid stenosis, and subsequent endarterectomy, in patients with recent transient ischaemic attack or stroke. Results Of patients with recent carotid territory transient ischaemic attack or ischaemic stroke, 575 in routine clinical practice and 402 in the Oxford vascular study had carotid imaging, with similar rates up to the age of 80. The incidence of ≥ 50% symptomatic stenosis increased steeply with age, particularly in those aged ≥ 80. Compared with investigations in patients in the Oxford vascular study, the rates of carotid imaging (relative rate 0.36, 95% confidence interval 0.28 to 0.46, P < 0.0001), diagnosis of ≥ 50% symptomatic stenosis (0.33, 0.16 to 0.69, P = 0.004), and carotid endarterectomy (0.19, 0.06 to 0.63, P = 0.007) in this age group in routine clinical practice were all substantially lower. Conclusions Incidence of symptomatic carotid stenosis increases steeply with age, but, despite good evidence of major benefit from endarterectomy in elderly patients and a willingness to have surgery, there is substantial underinvestigation in routine clinical practice in patients aged ≥ 80 with transient ischaemic attack or ischaemic stroke.

The Need for Urgency in Identification and Treatment of Symptomatic Carotid Stenosis Is Already Established

gency carotid endarterectomy in patients with unstable neurological syndromes remains unacceptably high at about 20% (updated from Bond et al. [3] by addition of 4 new studies [2, 4–6] ). However, there is no evidence that early surgery after stroke in patients who are neurologically stable is associated with an increased operative risk. Table 2 shows operative risks in neurologically stable patients undergoing endarterectomy after stroke by time since the event (updated from Bond et al. [3] by addition of 4 new studies [7, 8–10] ). Data on the risks of surgery within 1 week of the event are relatively few, but table 2 certainly does not support a delay of 6 weeks. The danger of delaying investigation and treatment after a TIA or minor stroke was underestimated until recently because data on prognosis were derived from studies that did not recruit patients until several weeks after the event [11] . Any patients who had had a major stroke during this period were excluded. Recent data from population-based studies have shown that the true risk of stroke from the time of a TIA or minor stroke is about 10% at 7 days, close to 20% at 1 month, and falls rapidly thereafter [12, 13] . Moreover, the subgroup of patients with carotid stenosis is at highest risk of early recurrence and account for the largest proportion of recurrent strokes Signifi cant carotid stenosis is found in 10–20% of patients with TIA or stroke. Randomised controlled trials (RCTs) have shown that endarterectomy reduces the risk of stroke in patients with 6 50% symptomatic carotid stenosis [1] . However, there has previously been uncertainty about how soon after the presenting event surgery should be performed. Welsh et al. [2] now propose an RCT of emergency endarterectomy within 48 h of presentation after a stroke versus delayed surgery 6 weeks after the event. However, such a trial is unethical because both options have already been shown to be clinically inappropriate as emergency endarterectomy within hours of a stroke or TIA has been shown to carry an unacceptably high operative risk and, although endarterectomy can be performed safely within a few days of a stroke, a delay to surgery of 6 weeks would be associated with a substantial reduction in benefi t and a very high risk of otherwise preventable recurrent stroke in the interim. Early studies showed that carotid endarterectomy performed within hours or days after a large cerebral infarction carried a high risk, particularly of intracranial haemorrhage. Although endarterectomy is no longer performed for such severe strokes, table 1 shows that the operative risk of stroke or death in more recent studies of emerPublished online: April 15, 2005

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, 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.

Lower Rates of Intervention for Symptomatic Carotid Stenosis in Women Than in Men Reflect Differences in Disease Incidence A Population-Based Study

Background and Purpose— Although there is little sex difference in the age-specific incidence of transient ischemic attack (TIA) and stroke, substantially more men than women undergo endarterectomy/stenting for symptomatic carotid stenosis. Sexism in referral for investigation or intervention has been proposed as an explanation; however, a lower incidence of carotid disease in women or reluctance to undergo intervention might also be responsible. Methods— We determined the sex-specific incidence of symptomatic carotid stenosis and subsequent endarterectomy/stenting from 2002 to 2009 in consecutive patients with TIA or nondisabling ischemic stroke in the Oxford Vascular Study. We studied equivalent data from routine clinical practices in the wider Oxfordshire population. Results— There was no sex difference in age-specific referral rates for carotid imaging in the Oxford Vascular Study (n=616; age-adjusted relative rate [RR] for males vs females=1.08; 95% CI, 0.79 to 1.46; P=0.64). However, rates of 50% to 99% symptomatic carotid stenosis were higher in men (RR=1.89; 95% CI, 1.31 to 2.71; P=0.0005). The same was seen in imaged patients (n=575) in the wider Oxfordshire population (RR=1.82; 95% CI, 1.31 to 2.53; P=0.003) and in pooled data (RR=1.87; 95% CI, 1.32 to 2.64; P=0.0003). Rates of symptomatic carotid occlusion were also higher in men in both populations (RR=3.19; 95% CI, 1.95 to 5.23; P<0.0001). Consequently, although men were more likely to undergo carotid intervention (RR=1.98; 95% CI, 1.43 to 2.75; P<0.0001), the proportion of patients with 50% to 99% symptomatic carotid stenosis who received intervention was similar for men and women (odds ratio=1.13; 95% CI, 0.57 to 2.25; P=0.72). Conclusion— Lower rates of intervention for 50% to 99% symptomatic carotid stenosis in women can be explained by sex differences in population-based incidence. We found no evidence of any investigation or intervention bias.

Population-Based Study of Incidence of Acute Abdominal Aortic Aneurysms With Projected Impact of Screening Strategy.

Background Current abdominal aortic aneurysm (AAA) screening in men age 65 might have limited impact on overall AAA death rates if incidence is moving to older ages. Up-to-date population-based studies of age-specific incidence, risk factors, and outcome of acute AAA are needed to inform screening policy. Methods and Results In a prospective, population-based study (Oxfordshire, UK, 2002–2014), the incidence and outcome of acute AAA events were determined. Based on population projections and current incidence trends, the impact of screening strategies in the UK was estimated. Over the 12-year period, 103 incident acute AAA events occurred in the study population of 92 728. Incidence/100 000/year was 55 in men ages 65 to 74 years, but increased to 112 at 75 to 85 and 298 at ≥85, with 66.0% of all events occurring at age ≥75 years. Incidence at ages 65 to 74 was highest in male smokers (274), with 96.4% of events in men <75 years occurring in ever-smokers. Extrapolating rates to the UK population, using trial evidence of screening efficacy, the current UK screening program would prevent 5.6% of aneurysm-related deaths (315 200 scans/year: 1426/death prevented, 121/year-of-life saved). Screening only male smokers age 65 and then all men at age 75 would prevent 21.1% of deaths (247 900 scans/year; 297/death prevented, 34/year-of-life saved). By 2030, 91.0% of deaths will occur at age ≥75, 61.6% at ≥85, and 28.6% in women. Conclusions Given that two thirds of acute AAA occurred at ≥75 years of age, screening older age groups should be considered. Screening nonsmokers at age 65 is likely to have very little impact on AAA event rates.

Population-Based Study of Incidence and Outcome of Acute Aortic Dissection and Premorbid Risk Factor Control

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.

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

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.

Population-Based Study of Incidence, Risk Factors, Outcome, and Prognosis of Ischemic Peripheral Arterial EventsCLINICAL PERSPECTIVE: 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.