A Population Study of Acute Vascular Events

Abstract & Commentary

By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.

Synopsis: The high rates of acute vascular events outside the coronary arterial territory and the steep rise in event rates with age in all territories have implications for prevention strategies, clinical trial design, and the targeting of funds for service provision and research.

Source: Rothwell PM, et al. Population-Based Study of Event-Rate, Incidence, Case Fatality, and Mortality for All Acute Vascular Events In All Arterial Territories (Oxford Vascular Study). Lancet. 2005;366:1773-1783.

A very large epidemiologic survey of vascular disease in almost 100,000 individuals from Oxfordshire, England (UK), suggests that there has been an overemphasis on the prevalence of acute events in coronary artery disease (CAD) morbidity and mortality when compared to peripheral vascular disease and stroke. In OXVASC (Oxford Vascular Study), rates of events in 3 different arterial territories were prospectively assessed to include incidence, 30-day case fatality, and mortality rates for all acute symptomatic arterial vascular events. Ninety-one thousand individuals, all cared for by general medical physicians, were enrolled. The population was dominantly Caucasian (94%), and the population was less deprived, indicating an average income above the UK norm. A large variety of data collection approaches were employed, including daily searches of emergency department admissions, visits to hospitals to document acute vascular admissions, and comprehensive ascertainment of deaths. Research nurses followed surviving subjects for 2 years after any index event. Standard definitions of vascular deaths, TIA, and stroke were utilized; high rates of autopsy substantiated the cause of death. Troponin testing was used for assessment of STEMI and NSTEMI. Events were classified as first ever (incident) or recurrent. Age and sex specific rates per 1000 population per year were calculated for all types of events, as was case fatality and mortality. The OXVASC study began in April of 2002; this report includes all events through June 2005. Rothwell and colleagues emphasize that the age and gender characteristics of the OXVASC population "closely resemble that of the entire population of the UK."

Results: A total of over 2000 acute vascular events occurred in 1600 individuals during the study, of which 90% were considered definite, 8% probable, and 2% unclassifiable. The major finding of the study was that 45% of all events were cerebrovascular (618 strokes and 300 TIAs) and 42% of all events were coronary (159 STEMI and 316 NSTEMI), including unstable angina and sudden cardiac death. Least common were peripheral vascular events, including aortic and peripheral vascular ischemia, and emboli, representing 9% of all events. In the events classified as TIAs, 50% were ultimately reclassified as not likely. During the study period, 12% of subjects had 2 vascular events and 4% had more than 2, either in the same or different vascular territories. The relative rates for acute cerebrovascular events vs coronary events were 1.07 overall, 0.97 if TIA and unstable angina were excluded. Overall, 63% of events were incident or first time. The relative incidence of all cerebrovascular vs coronary events was 1.19 (NS). Event rates and incidence rates rose steeply with age. The mean age for all acute events was 73, and for first ever events. There were no differences among the 3 arterial territories for age at the time of event. Rates of acute coronary events were higher in men, particularly at age < 65 (risk ratio of 4) vs 1.65 risk ratio for > 65. Of note, the gender event difference in subjects < 65 years was largest for STEMI, decreasing with higher age; in older women reaching age 85, there was no longer any gender differential. There were more cardioembolic strokes in older women and "an excess of strokes in men associated with 50% or more symptomatic carotid stenosis." Major aortic events were much higher in men than women. Overall, age-event and age incidence for stroke and coronary events were similar at all ages in men, but stroke rates were higher in women > 75. Fatal rates for TIA and unstable angina were low. Fatal and incident event rates rose steeply with age for all arterial territories, age after 65 (P < 0.0001). There were very high rates of non-fatal stroke in the older age groups. Calculation of total burden of acute vascular events revealed a yearly overall rate of 0.37% at age 45-54, 0.94% at 55-64, rising to 2.4% at 65-74 years, 5% at 75-84, and 8.8% at 85 years or greater. The large majority of all events occurred in 14% of the study population aged 65 or more; more than half of all events in various territories occurred in the 6% of the population of age 75 or older.

Commentary

Projections of the total burden of vascular disease for the next 40 years predict a major increase of events in the older population. Rothwell et al stress that the OXVASC data are unique in that its population base is different from almost all other published epidemiologic studies, most of which do not assess individuals over the age of 65. In addition, few studies equal the assiduous manner with which the data were collected. These results make it clear that there are high rates of acute vascular events that occur outside the coronary circulation, and they highlight the steep rise in event rates with age in all territories. This study suggests that acute cerebrovascular events are at least as frequent as acute coronary events, and that the wide spread assumption that coronary events occur at a younger ages appears to be incorrect. They note that previous epidemiologic studies have not included overage populations, even for coronary artery disease. Thus, "probably exaggerated in sex difference in rates, particularly in rates for STEMI." The latter "occurs about 20 years earlier in men than in women, but that rates in women do eventually catch up." Half of STEMIs in men occurred in men younger than 65 compared to 16% of women. Rothwell et al stress the implications of excess vascular disease in the elderly population. "The very high rates emphasize the need for primary and secondary prevention in older age groups." Most events in older age groups were non-fatal, and presumably more disabling than in the younger populations, suggesting an increase in prevalence of disability in the aging population. They predict that increases in numbers of non-fatal events in individuals > 85 years of age will importantly impact the medical care system. Rothwell et al emphasize that OXVASC is different than many of the mortality reports in the literature suggesting that CAD is the leading cause of death. The rates of acute cerebral vascular events "are in fact higher than those for acute coronary events." The data indicate that "event rates and incidence of stroke alone were similar to those of myocardial infarction and sudden cardiac death combined at all ages in men, and higher in women." Rothwell et al believe that OXVASC stroke incidence rates ". . . are highly consistent with those reported in other comparable studies. . . "but that no comparable recent data have been available for coronary events. They conclude that their study indicates that cerebrovascular events are the most frequent acute manifestation of vascular disease, and that age event curves are similarly steep in all arterial territories, with half of all events occurring in people age 75 or older. They stress that their findings have "important implications for prevention strategies, clinical trial design, and targeting of funds.

For American physicians, it appears that the most significant findings in this study are the substantially higher cerebrovascular event rates than we appear to see in our daily practice, and that aging is clearly associated with marked increases in all types of vascular events. While these are not really new findings, the outstanding design and follow-up in OXVASC provides a warning that more emphases must be made in preventing and/or slowing the rates of vascular events in individuals over 65. Very few studies in the cardiology literature have emphasized evidence-based therapies or clinical trial data in these age groups. Furthermore, elderly patients in general exist below the radar screen of prevention and/or intervention. Whether or not the OXVASC data will be similar to a large population in the United States or Canada is moot; the meticulous data collection in this study clearly tells us that these data should be generalizable to a US population. While African Americans and other non-white groups are not assessed in the OXVASC population, it is unlikely that there are major differences in the age and gender phenomena.

What does this mean for the practicing physician? Identification of risk factors and treatment in patients over 65 must be upgraded. Many of our older patients are not treated because of a lack of data and perhaps a belief that one cannot substantially affect the course of vascular disease once an individual reaches the age of 65-70. These data, while not providing therapeutic guidelines, fly in the face of the nihilistic approach to the elderly. The remarkable statin story of the last decade is a case in point. There has been a steady lowering of target LDL for individuals with and without vascular disease over the past decade. Hypertension RCT have indicated that effective therapies have demonstrated improvement in vascular events, and target levels for blood pressure have been progressively lowered. The elderly represent an often overlooked target for hypertension therapy; the emphasis on the treatment of systolic blood pressure elevation data of the last few years is to be applauded, but needs to be more widely acknowledged. It would appear that vascular risk is a continuum, and that it is now time to turn our sights on older populations. This is particularly true in that randomized trials enroll mostly middle aged individuals, typically less than 65-70, and have, perhaps, been sending a message that older age does not matter. One wonders if the event rates in OXVASC individuals over the age of 65 could have been modified by treatment of hypertension, diabetes, and hyperlipidemia, with the widespread use of aspirin, antihypertensive drugs, and statins.