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Vascular disease of the heart, brain and limbs: new insights into a looming epidemic
Comment
Vascular disease of the heart, brain and limbs: new insights into a looming epidemic
www.thelancet.com Vol 366 November 19, 2005
overlapping sources of ascertainment, and capitalising on an extraordinarily high rate of patients’ consent and access to medical records, despite ever-increasing privacy and ethical barriers. The results, for stroke incidence at least, are validated by the highly similar results of other ideal community-based studies of stroke incidence in western populations.13 The accuracy of diagnoses and estimates of early prognoses are also likely to be valid given the use of present-day diagnostic criteria for major events, the remarkable notification and assessment of communitybased cases within a median 2 days of the onset of qualifying events, and the complete follow-up at 1 month. The estimates of incidence and outcome should be reasonably precise, given the large denominator (population: 91 106) and numerator (2024 vascular events in 1657 patients) ascertained over 3 years. The results of the OXVASC study have important implications for managing, and planning for, the health of our nations. If populations continue to age at current rates, and if the incidence and case fatality of vascular events cannot be reduced, a looming epidemic of death and disability due to vascular disease will emerge in the next 15 years (33% increase), 25 years (58% increase,) and 35 years (75% increase). Moreover, these estimates are likely to understate the future burden of vascular disease in the community because they do not include prevalent symptomatic vascular disease causing vascular cognitive impairment, stable angina, intermittent claudication, and rest pain. Because almost two-thirds of acute vascular events are first-ever incident events, effective primary
Published online November 16, 2005 DOI:10.1016/S0140-6736(05) 67703-3 See Articles page 1773
Rights were not granted to include this image in electronic media. Please refer to the printed journal Science Photo Library
Acute ischaemic events of the heart (acute coronary syndrome), brain and eye (transient ischaemic attack [TIA] and ischaemic stroke), and limbs and other organs are the leading cause of premature death and disability in the developed world.1 The usual culprit is atherosclerosis. Although a systemic disease, the clinical manifestations of atherosclerosis tend to be studied and managed as a focal disease by organ-oriented researchers and clinicians (eg, neurologists, cardiologists). Research evidence and clinical experience therefore tends to be biased toward different organ-based manifestations of atherosclerosis (eg, stroke or coronary deaths) and limited to different times and populations (eg, volunteers, hospital-referred patients, younger people aged 65 years).2–8 In today’s Lancet, Peter Rothwell and colleagues report the incidence and short-term outcome of all three major acute clinical manifestations of atherosclerosis (coronary, cerebral, and peripheral vascular) in 2002–05 in a large unselected entire population in Oxfordshire, UK.9 The Oxford Vascular Study (OXVASC) results are novel because they are comprehensive, comparative, current, and representative (of the Oxfordshire population, at least). Further, they challenge some of the prevailing dogma about cardiovascular disease that resonates from earlier highly regarded studies, whose methodological limitations are now exposed.2–8 The OXVASC data contradict the results of earlier studies confined to middleaged individuals,2–6 and suggest that acute cerebrovascular events are at least as, if not more, common than acute coronary events (relative incidence 1·19, 95% CI 1·06–1·33), despite a 40% reduction in the incidence of stroke in the past 20 years10 and a recent increase in rates of myocardial infarction due to the adoption of more sensitive diagnostic criteria.11 In addition, the OXVASC data suggest that most acute coronary syndromes do not occur in people younger than 65 years, and acute coronary syndrome is not substantially more common in men than women. The results of OXVASC are likely to be valid because the study design meets the criteria for an ideal study of incidence and short-term prognosis.12,13 Further, case ascertainment is likely to be all but complete because cases were detected by hot and cold pursuit, with multiple
1753
Comment
prevention of first-ever events is likely to have greater potential to reduce the burden of vascular disease than effective secondary prevention of recurrent events, although both strategies are clearly necessary, complementary, and not mutually exclusive. The elderly must not be dismissed, nor dismiss themselves, as being too old to participate in, or be the target of, effective prevention trials and strategies. Increasing age is a crucial determinant of the incidence of vascular disease, with more than half of all events occurring in the minority (6%) of the population aged 75 years or older. The implications of these findings for the provision of long-term care of elderly dependent survivors of vascular events are salutary because many of the enormous number of acute vascular events in older age groups are non-fatal yet disabling. If clinical and population benefits are to arise from the OXVASC data, research into cerebrovascular and peripheral vascular disease needs to be supported and funded at least in proportion to the burden it imposes, and is likely to impose, on the community.14 The external validity of OXVASC needs to be examined in similar studies of nonwhite populations in underdeveloped countries (who make up most of the world population) and white populations of lower socioeconomic class in developed countries. The long-term prognosis of the OXVASC population needs to be determined by continued follow-up of this large cohort. And the OXVASC study needs to be repeated at a later date in the same population to monitor trends in the incidence, outcome, and risk factors of vascular disease in Oxfordshire. This will be an important adjunct to routinely collected population statistics for monitoring the possible impact of prevention and treatment strategies. Already an offspring of the Oxfordshire Community Stroke Project in 1981–84, the OXVASC study of 2002–05 has highlighted the value of such follow-up studies, recently reporting that the 40% reduction in age-specific incidence of major stroke in Oxfordshire over the past 20 years occurred in association with
increased use of preventive treatments and major reductions in premorbid risk factors.10 Hopefully successors of OXVASC will report an even healthier population. Graeme J Hankey Department of Neurology, Royal Perth Hospital, Perth, Western Australia 6001, Australia [email protected] I declare that I have no conflict of interest. 1 2
3
4 5
6 7
8
9
10
11
12 13
14
Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease study. Lancet 1997; 349: 1269–76. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas A, Pajak A. Myocardial infarction and coronary deaths in the WHO MONICA Project: registration procedures, event rates and case fatality rates in 38 populations from 21 countries in four continents. Circulation 1994; 90: 583–612. Sarti C, Stegmayr B, Tolonen H, for the WHO MONICA Project. Are changes in mortality from stroke caused by changes in stroke events rates or case fatality? Results from the WHO MONICA Project. Stroke 2003; 34: 1833–41. Asplund K. What MONICA told us about stroke. Lancet Neurol 2005; 4: 64–68. Fox CS, Evans JC, Larson MG, Kannel WB, Levy D. Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: the Framingham Heart Study. Circulation 2004; 110: 522–27. The ARIC investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objective. Am J Epidemiol 1989; 129: 687–702. Steg PG, Goldberg RJ, Gore JM, et al. Baseline characteristics, management practices, and in-hospital outcomes of patients hospitalised with acute coronary syndromes in the Global Registry of Acute Coronary Events (GRACE). Am J Cardiol 2002; 90: 358–63. Blomkalns AL, Chen AY, Hochman JS, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol 2005; 45: 832–37. Rothwell PM, Coull AJ, Silver LE, for the Oxford Vascular Study. Populationbased study of event-rate, incidence, case fatality, mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 2005; 366: 1773–83. Rothwell PM, Coull AJ, Giles MF, for the Oxford Vascular Study. Change in stroke incidence, mortality, case-fatality, severity and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet 2004; 363: 1925–33. Ferguson JL, Beckett GJ, Stoddart M, et al. Myocardial infarction redefined: the new ACC/ESC definition, based on cardiac troponin, increases the apparent incidence of infarction. Heart 2002; 88: 343–47. Feigin V, Vander Hoorn S. How to study stroke incidence. Lancet 2004; 363: 1920–21. Feigin VL, Lawes CMM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2003; 2: 43–53. Pendlebury ST, Rothwell PM, Algra A, et al. Underfunding of stroke research: a Europe-wide problem. Stroke 2004; 35: 2368–71.
Fabry’s disease—an important risk factor for stroke Published online November 9, 2005 DOI:10.1016/S0140-6736(05) 67636-2 See Articles page 1794
1754
In today’s Lancet, Arndt Rolfs and colleagues describe the prevalence of Fabry’s disease (MIM 301500, -galactosidase A mutations) in a large cohort of patients with cryptogenic stroke.1 Fabry’s disease is an under-recognised single-gene defect caused by
-galactosidase A deficiency, which results in a failure to catabolise -D-galactosyl glycolipid moieties. Increased concentrations of glycolipid are a risk factor for cardiomyopathy, cardiac conduction abnormalities, valvular defects, coronary artery disease, renal failure, and stroke. www.thelancet.com Vol 366 November 19, 2005
Vascular disease of the heart, brain and limbs: new insights into a looming epidemic
www.thelancet.com Vol 366 November 19, 2005
overlapping sources of ascertainment, and capitalising on an extraordinarily high rate of patients’ consent and access to medical records, despite ever-increasing privacy and ethical barriers. The results, for stroke incidence at least, are validated by the highly similar results of other ideal community-based studies of stroke incidence in western populations.13 The accuracy of diagnoses and estimates of early prognoses are also likely to be valid given the use of present-day diagnostic criteria for major events, the remarkable notification and assessment of communitybased cases within a median 2 days of the onset of qualifying events, and the complete follow-up at 1 month. The estimates of incidence and outcome should be reasonably precise, given the large denominator (population: 91 106) and numerator (2024 vascular events in 1657 patients) ascertained over 3 years. The results of the OXVASC study have important implications for managing, and planning for, the health of our nations. If populations continue to age at current rates, and if the incidence and case fatality of vascular events cannot be reduced, a looming epidemic of death and disability due to vascular disease will emerge in the next 15 years (33% increase), 25 years (58% increase,) and 35 years (75% increase). Moreover, these estimates are likely to understate the future burden of vascular disease in the community because they do not include prevalent symptomatic vascular disease causing vascular cognitive impairment, stable angina, intermittent claudication, and rest pain. Because almost two-thirds of acute vascular events are first-ever incident events, effective primary
Published online November 16, 2005 DOI:10.1016/S0140-6736(05) 67703-3 See Articles page 1773
Rights were not granted to include this image in electronic media. Please refer to the printed journal Science Photo Library
Acute ischaemic events of the heart (acute coronary syndrome), brain and eye (transient ischaemic attack [TIA] and ischaemic stroke), and limbs and other organs are the leading cause of premature death and disability in the developed world.1 The usual culprit is atherosclerosis. Although a systemic disease, the clinical manifestations of atherosclerosis tend to be studied and managed as a focal disease by organ-oriented researchers and clinicians (eg, neurologists, cardiologists). Research evidence and clinical experience therefore tends to be biased toward different organ-based manifestations of atherosclerosis (eg, stroke or coronary deaths) and limited to different times and populations (eg, volunteers, hospital-referred patients, younger people aged 65 years).2–8 In today’s Lancet, Peter Rothwell and colleagues report the incidence and short-term outcome of all three major acute clinical manifestations of atherosclerosis (coronary, cerebral, and peripheral vascular) in 2002–05 in a large unselected entire population in Oxfordshire, UK.9 The Oxford Vascular Study (OXVASC) results are novel because they are comprehensive, comparative, current, and representative (of the Oxfordshire population, at least). Further, they challenge some of the prevailing dogma about cardiovascular disease that resonates from earlier highly regarded studies, whose methodological limitations are now exposed.2–8 The OXVASC data contradict the results of earlier studies confined to middleaged individuals,2–6 and suggest that acute cerebrovascular events are at least as, if not more, common than acute coronary events (relative incidence 1·19, 95% CI 1·06–1·33), despite a 40% reduction in the incidence of stroke in the past 20 years10 and a recent increase in rates of myocardial infarction due to the adoption of more sensitive diagnostic criteria.11 In addition, the OXVASC data suggest that most acute coronary syndromes do not occur in people younger than 65 years, and acute coronary syndrome is not substantially more common in men than women. The results of OXVASC are likely to be valid because the study design meets the criteria for an ideal study of incidence and short-term prognosis.12,13 Further, case ascertainment is likely to be all but complete because cases were detected by hot and cold pursuit, with multiple
1753
Comment
prevention of first-ever events is likely to have greater potential to reduce the burden of vascular disease than effective secondary prevention of recurrent events, although both strategies are clearly necessary, complementary, and not mutually exclusive. The elderly must not be dismissed, nor dismiss themselves, as being too old to participate in, or be the target of, effective prevention trials and strategies. Increasing age is a crucial determinant of the incidence of vascular disease, with more than half of all events occurring in the minority (6%) of the population aged 75 years or older. The implications of these findings for the provision of long-term care of elderly dependent survivors of vascular events are salutary because many of the enormous number of acute vascular events in older age groups are non-fatal yet disabling. If clinical and population benefits are to arise from the OXVASC data, research into cerebrovascular and peripheral vascular disease needs to be supported and funded at least in proportion to the burden it imposes, and is likely to impose, on the community.14 The external validity of OXVASC needs to be examined in similar studies of nonwhite populations in underdeveloped countries (who make up most of the world population) and white populations of lower socioeconomic class in developed countries. The long-term prognosis of the OXVASC population needs to be determined by continued follow-up of this large cohort. And the OXVASC study needs to be repeated at a later date in the same population to monitor trends in the incidence, outcome, and risk factors of vascular disease in Oxfordshire. This will be an important adjunct to routinely collected population statistics for monitoring the possible impact of prevention and treatment strategies. Already an offspring of the Oxfordshire Community Stroke Project in 1981–84, the OXVASC study of 2002–05 has highlighted the value of such follow-up studies, recently reporting that the 40% reduction in age-specific incidence of major stroke in Oxfordshire over the past 20 years occurred in association with
increased use of preventive treatments and major reductions in premorbid risk factors.10 Hopefully successors of OXVASC will report an even healthier population. Graeme J Hankey Department of Neurology, Royal Perth Hospital, Perth, Western Australia 6001, Australia [email protected] I declare that I have no conflict of interest. 1 2
3
4 5
6 7
8
9
10
11
12 13
14
Murray CJL, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease study. Lancet 1997; 349: 1269–76. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas A, Pajak A. Myocardial infarction and coronary deaths in the WHO MONICA Project: registration procedures, event rates and case fatality rates in 38 populations from 21 countries in four continents. Circulation 1994; 90: 583–612. Sarti C, Stegmayr B, Tolonen H, for the WHO MONICA Project. Are changes in mortality from stroke caused by changes in stroke events rates or case fatality? Results from the WHO MONICA Project. Stroke 2003; 34: 1833–41. Asplund K. What MONICA told us about stroke. Lancet Neurol 2005; 4: 64–68. Fox CS, Evans JC, Larson MG, Kannel WB, Levy D. Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: the Framingham Heart Study. Circulation 2004; 110: 522–27. The ARIC investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objective. Am J Epidemiol 1989; 129: 687–702. Steg PG, Goldberg RJ, Gore JM, et al. Baseline characteristics, management practices, and in-hospital outcomes of patients hospitalised with acute coronary syndromes in the Global Registry of Acute Coronary Events (GRACE). Am J Cardiol 2002; 90: 358–63. Blomkalns AL, Chen AY, Hochman JS, et al. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol 2005; 45: 832–37. Rothwell PM, Coull AJ, Silver LE, for the Oxford Vascular Study. Populationbased study of event-rate, incidence, case fatality, mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 2005; 366: 1773–83. Rothwell PM, Coull AJ, Giles MF, for the Oxford Vascular Study. Change in stroke incidence, mortality, case-fatality, severity and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet 2004; 363: 1925–33. Ferguson JL, Beckett GJ, Stoddart M, et al. Myocardial infarction redefined: the new ACC/ESC definition, based on cardiac troponin, increases the apparent incidence of infarction. Heart 2002; 88: 343–47. Feigin V, Vander Hoorn S. How to study stroke incidence. Lancet 2004; 363: 1920–21. Feigin VL, Lawes CMM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol 2003; 2: 43–53. Pendlebury ST, Rothwell PM, Algra A, et al. Underfunding of stroke research: a Europe-wide problem. Stroke 2004; 35: 2368–71.
Fabry’s disease—an important risk factor for stroke Published online November 9, 2005 DOI:10.1016/S0140-6736(05) 67636-2 See Articles page 1794
1754
In today’s Lancet, Arndt Rolfs and colleagues describe the prevalence of Fabry’s disease (MIM 301500, -galactosidase A mutations) in a large cohort of patients with cryptogenic stroke.1 Fabry’s disease is an under-recognised single-gene defect caused by
-galactosidase A deficiency, which results in a failure to catabolise -D-galactosyl glycolipid moieties. Increased concentrations of glycolipid are a risk factor for cardiomyopathy, cardiac conduction abnormalities, valvular defects, coronary artery disease, renal failure, and stroke. www.thelancet.com Vol 366 November 19, 2005