Stroke Incidence and Mortality Rates 1987 to 2006 Related to Secular Trends of Cardiovascular Risk Factors in Gothenburg, Sweden

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1 ; Stroke Incidence and Mortality Rates 1987 to 2006 Related to Secular Trends of Cardiovascular Risk Factors in Gothenburg, Sweden Per Harmsen, MD; Lars Wilhelmsen, MD, PhD; Anders Jacobsson, BSc Background and Purpose Stroke incidence rates were unchanged whereas fatality rates declined during the period 1971 to 1987 in Gothenburg (Göteborg), Sweden. For the period 1987 to 2006, we now report on trends in stroke incidence and mortality with concurrent risk factor trends in the same population. Since 1976 the incidence of myocardial infarction decreased by 50%. Methods Through the National Hospital Discharge Register linked with the Cause of Death Register, males and females with first strokes were detected for the period 1987 to Cardiovascular risk factor data were available for random population samples of men and women aged 50 years from 1963 to Results Incidence and mortality rates for all-stroke were unchanged. Rates for subarachnoid hemorrhage declined for the age group 45 to 54 in men, but not significantly in any other age group of men or women. Mortality rates of intracerebral hemorrhage declined for women aged 65 to 74, with no significant changes in any other age group. Ischemic stroke incidence did not change, but mortality increased for men and women aged 75 and older, whereas mortality declined for the age group 20 to 44 for men. In the general population there were significant reductions in smoking, total cholesterol, and blood pressure levels in both men and women, whereas diabetes prevalence, body weight, and BMI increased among both sexes, and triglycerides increased in men. Conclusion Contrary to myocardial infarction, stroke incidence and mortality did not change. Monitoring of cardiovascular risk factors in the community is important. (Stroke. 2009;40: ) Key Words: brain infarction epidemiology registry mortality rates myocardial infarction risk factors subarachnoid hemorrhage incidence rates time trends A decrease in stroke incidence and mortality in some high-income countries during the 1960s and 1970s leveled out during the 1980s. Since the 1990s mortality has continued to decrease, but several studies have reported either no change 1 or an increase in stroke incidence. 2,3 In a recent survey, data for Europe regarding stroke were considered to be very limited, 4 and such data are of great importance for health care planning. In contrast with a recent report from the United Kingdom of a 40% decrease in major stroke in Oxfordshire over the past 20 years, 5 studies from Sweden report on increasing stroke incidence in recent years 6 8 or no change. 9 In an earlier study from the stroke register in Gothenburg, we reported no change in stroke incidence but a decline in fatality rates during the period 1971 to Continued stroke recordings for the years 1984 to 1994 from the MONICA center in Gothenburg showed no definite trends. 11 It was recently shown that coronary heart disease incidence as well as mortality decreased markedly in Gothenburg from 1975 to 1979 and 2000 to It was also shown that the level of risk factors for coronary heart disease declined correspondingly. 12 In recent years, national registers have been used for epidemiological descriptive purposes in Finland, 13 in England, 14 and in Canada. 15,16 In this article we present data for Gothenburg on stroke incidence and mortality based on the Swedish Hospital Discharge Register linked and matched with the Swedish Cause of Death Register covering the period 1987 to Further, we relate to concurrent time trends for cardiovascular risk factors in the Gothenburg population. Subjects and Methods Data on stroke for the Gothenburg population were collected from the Hospital Discharge Register, which has operated on a nationwide base since 1987 and is kept by the Swedish National Board of Health and Welfare. The coverage of the register was at least 98% for somatic short-term care; 17 this includes care of stroke patients in the acute phase, during which rehabilitation also is initiated. The city of Received February 23, 2009; final revision received April 3, 2009; accepted May 1, From Institute of Clinical Neuroscience (P.H.), Department of Internal Medicine (L.W.), Sahlgrenska University Hospital, Gothenburg, Sweden; Sahlgren s Academy (A.J.), University of Gothenburg, Gothenburg, Sweden, and Centre for Epidemiology, the National Board of Health and Welfare, Stockholm, Sweden. Correspondence to Professor Lars Wilhelmsen, Fregattgatan 16, SE V Frölunda, Sweden. lars.wilhelmsen@gu.se 2009 American Heart Association, Inc. Stroke is available at DOI: /STROKEAHA

2 2692 Stroke August 2009 Table 1. Person-Years at Risk and Age-Specific All-Stroke, Intracerebral Hemorrhage, and Ischemic Stroke Incidence Rates Per Persons in Gothenburg N at Risk Incidence Rate N at Risk Incidence Rate N at Risk Incidence Rate AS IH Isc AS IH Isc AS IH Isc AS indicates all-stroke; IH, intracerebral hemorrhage; Isc, ischemic stroke; NS, not significant. ICD 10 I60 I64, I61 I62, and I63 I64, respectively. Gothenburg has 1 university hospital located in 3 sites with identical procedures for acute care of stroke patients. Traditionally, every acute stroke patient is taken to hospital, and during recent years this practice has been further strengthened with the introduction of modern therapy and by the guiding principles laid out by the National Board of Health and Welfare. The Swedish Cause of Death Register has been operating since 1961 and has been found to miss only single events. An ongoing validation study of population coverage of stroke incidence derived from the Hospital Discharge Register and the Cause of Death Register finds that positive predicted value and sensitivity of the 2 are close to 90%, (unpublished data 2009). 18 In the present study, the records of the 2 registers were linked based on personal identification codes. For any person, only the first episode of hospitalization since 1987 for stroke was Table 2. Person-Years At Risk and Age-Specific All-Stroke, Intracerebral Hemorrhage, and Ischemic Stroke, Mortality Rates Per Persons in Gothenburg N at Risk Mortality Rate Mortality Rate AS IH Isc N at Risk AS IH Isc ICD 10 I60 I64, I61 I62, and I63 I64 respectively.

3 Harmsen et al Stroke Incidence and Mortality Rates 2693 Table 1. Continued N at Risk Incidence Rate N at Risk Incidence Rate P for Trend AS IH Isc AS IH Isc AS IH Isc NS NS NS NS 0.07 NS NS NS NS NS NS 0.09: NS NS NS NS NS NS NS NS NS NS 0.14 NS NS NS NS included to obtain first incidence rates. An event (nonfatal or fatal) that occurred within 28 days was considered to be the same event and was counted as 1 event. In 1987 the International Classification of Diseases (ICD) was changed from the 8 th to the 9 th revision, and in 1997 there was a change to ICD-10. For the present analyses the following principal or contributory diagnoses at hospitalization or death were used: stroke, nonfatal and fatal, Table 2. N at Risk Continued ICD-9 codes , 436, and ICD-10 codes I60, I61, I62, I63, and I64. Risk Factor Analyses Cardiovascular risk factors in the population of Gothenburg were analyzed in representative population samples of 50-year-old men examined every tenth year from 1963 to 2003, 12 in 45- to 54-year-old Mortality Rate Mortality Rate Mortality Rate P for Trend AS IH Isc N at Risk AS IH Isc N at Risk AS IH Isc AS IH Isc NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS

4 2694 Stroke August 2009 Table 3. Incidence of All-Stroke (I60 I64) by Sex and 5-Year Time Groups, Adjusted to the European Population Year N N at Risk Crude Adjust 95% CI Table 4. Mortality of All-Stroke (I60 I64) by Sex and 5-Year Time Groups, Adjusted to the European Population Year N N at Risk Crude Adjust 95% CI women in 1968 to 1969, and in 50-year-old women in ,20 Data on smoking and treatment for hypertension were assessed via questionnaires, diabetes at examination, and through blood analyses, body variables, and blood pressure measured at examination; all laboratory tests were performed at the same accredited hospital laboratory. Statistical Methods Incidence and mortality rates were calculated with the mid-year Gothenburg population in the respective age groups as denominator. Ages were categorized in 10-year age groups. Differences over time in incidence and mortality were tested with the 2 trend test (EpiInfo). Differences between discrete variables and differences between continuous variables were tested with 2 analyses and the t test, respectively. Two-sided tests with P 0.05 were considered significant. Stroke incidence and mortality were age-adjusted to the standard European population. 21 Results The number of patients aged 20 years and older who were hospitalized for a first stroke in 1987 to 2006 were men and women in a population of men and women aged 20 years and older in Incidence and mortality rates per of the population for all strokes (ICD-10, I60 I64), with intracerebral hemorrhage (I61 I62), and ischemic stroke (I63 I63) are shown in Tables 1 and 2. There were no significant trends over time for any age group of men or women. The incidence rates and mortality rates for subarachnoid hemorrhage declined for the age group 45 to 54 among men, whereas declining trends in some other age groups were not statistically significant, and are not shown in the Tables. The incidence and mortality rates of intracerebral hemorrhage did not change over time, except for women aged 65 to 74, among whom mortality decreased significantly. Incidence and mortality rates for ischemic stroke increased for men aged 75 and older, whereas mortality declined in the age group 20 to 44, and mortality declined in the oldest age group of women. The 28-day fatality rate among hospitalized cases for all-stroke (I60 I64) as well as for ischemic stroke decreased significantly for the age groups 65 to 74 and 75 and older for both men and women (data not shown). Stroke incidence and mortality rates age-standardized to the European population for all-stroke (I60 I64) are shown in Tables 3 and 4. It should be emphasized that rates also include stroke as a secondary diagnosis in people cared for under other primary diagnoses. We have previously reported on stroke risk factors in the Gothenburg population 22 and have documented some differences in risk factors between stroke and myocardial infarction. 23 The secular changes in cardiovascular risk factors were investigated in successive cross-sectional population samples of 50-year-old men every 10 years in Gothenburg from 1963 to 2003, 12 and in 50-year-old women from 1968 to 1969 until 2003, 19,20 as shown in Table 5. It appears that important risk factors decreased (smoking, blood pressure, and total serum cholesterol), others did not change (physical activity, mental stress, and triglycerides in women), and some increased (diabetes prevalence, body weight, BMI, as well as serum triglycerides in men). Discussion The incidence of stroke, with few exceptions such as subarachnoid hemorrhage and ischemic stroke among the oldest men, did not decrease significantly during the period 1987 to Stroke mortality was also rather stable, with the exception of a single age group of women aged 65 to 74 years with intracerebral hemorrhage. Mortality increased for the oldest age group of both men and women with ischemic stroke, perhaps because a larger proportion of persons of older age made up this rather broad age group (75 years and older). In general, the incidence is influenced by the level of risk factors and preventive treatment of especially high blood pressure, whereas fatality rates among hospitalized stroke patients depend on the severity of the stroke and treatment in hospital. The primary aim of this report is to analyze incidence rates. In our previous report covering the period 1971 to 1987, stroke incidence rates were unchanged, whereas fatality rates decreased. Data were based on the Gothenburg Stroke Register, which was continued until The rates in that report were slightly lower than those of the present series. These

5 Harmsen et al Stroke Incidence and Mortality Rates 2695 Table 5. Cardiovascular Risk Factor Changes Among 50-Year-Old During the Years 1963 and and Among From and ,20 SD SD P for Trend Year of examination N examined Never and ex-smokers, % Smokers, % Diabetes % BMI, kg/m Waist circumference, cm Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Drugs for hypertension, % Serum cholesterol, mmol/l Serum triglycerides, mmol/l SD SD P for Trend Year of examination N examined Never and ex-smokers, % Smokers, % Diabetes % BMI, kg/m Systolic blood pressure, mm Hg Diastolic blood pressure, mm Hg Drugs for hypertension, % Serum cholesterol mmol/l Serum triglycerides, mmol/l NS differences are slight and probably do not indicate any true increase. In the present series there was some decrease in fatality rates for ischemic stroke in the older age groups (65 to 74 years and 75 years and older) for both men and women, but this did not correspond to significant decreases in total stroke mortality for the same groups, or for any other group. Mortality did not decline during this period. Use of the national registers might incur more uncertain identification of stroke cases than the use of stroke registration, as we encountered previously with a community-based, prospective registry. 10 However, the procedure of reporting to the national register is well-established, and a population coverage of 90% is being validated by Koster and Stegmayr. 18 With increasing awareness of early, prompt hospitalization of patients with stroke, the number not admitted will be negligible. Our comparisons are kept within the period 1987 to 2006, using identical methodology. The increasing incidence rates reported from the southern parts of Sweden 6,7,24 were followed by a report that incidence rates had leveled out since the turn of the century in southern Sweden. 25 The rates seem to be of the same order of magnitude as our rates from Gothenburg in western Sweden. The decline in incidence or mortality reported from England, 5,14 Finland, 13 and from the north of Sweden 26 are at variance with our results. Smoking rates and total cholesterol values decreased significantly during the period 1963 to Blood pressure decreased during these years, partly because slightly more people were being treated with drugs, but there was also a decline that could not be explained by more intensive drug treatment. 12 According to a multivariable risk function based on the 3 risk factors, high blood pressure, smoking, and total serum cholesterol, the risk of myocardial infarction was estimated to have decreased to 45% of its value in men in The incidence of myocardial infarction decreased by almost 50% in men and decreased somewhat less in women. We have previously reported 23 that there were differences in risk factors for stroke and myocardial infarction, with serum total cholesterol being a strong risk factor for myocardial infarction but not for stroke, whereas blood pressure and BMI were stronger risk factors for stroke. Diabetes was of equal strength. Even though the mean blood pressure levels declined (only partly because of increased antihypertensive treatment), there was still a considerable number of both men and women who had blood pressures above the

6 2696 Stroke August 2009 recommended limits 140/90 mm Hg (46% of 50-year-old men and 36% of the women). 20 This is probably the main reason for the unchanged stroke incidence and mortality. The increased diabetes prevalence and higher BMI and serum triglycerides (in men), despite declining smoking habits, may be additional reasons. We have previously found that diabetes is a strong risk factor for stroke. 22 It has also been shown that high serum triglycerides is a risk factor for stroke in both sexes, and high BMI has been shown to be a risk factor in men 30 and in women Fibrinogen levels 35 (not assessed during all of the study period) might also have contributed to the unchanged stroke incidence. The declining incidence rate of myocardial infarction was, however, unaffected. Stroke mortality also remained unchanged despite the improved knowledge of stroke care. The city of Gothenburg had insufficient coverage of specialized stroke units during part of the period studied. Contrary to these findings, there was a marked decline in mortality rate after a myocardial infarction. 11 In this study we included cases of stroke as a secondary diagnosis. This may be 1 reason for the high rates recorded here compared to the recent study from 6 European countries. 36 In other studies, premorbid risk factor prevalence is often given for the stroke patients; we emphasize that we present risk factor prevalence in the general population here. We are aware of no population studies (since the MONICA study 37 ) of trends in cardiovascular risk factor prevalence covering the same population as the reporting of stroke incidence other than the Gothenburg population studies presented here. In conclusion, there has been no change in stroke incidence and mortality over the past 20 years in Gothenburg. At the same time there has been a major reduction in the incidence of myocardial infarction. Simultaneously, some risk factors for stroke have increased or have decreased only slightly. These findings stress the importance of continued monitoring of individual cardiovascular diseases and their risk factors in the community. None. Disclosures References 1. Bejot Y, Osseby G, Aboa-éboulé C, Durier J, Cottin Y, Moreau T, Giroud M. Dijon s vanishing lead with regard to low incidence of stroke. Eur J Neurol. 2009;16: Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and casefatality in the late 20th century. Lancet Neurol. 2003;2: Kleindorfer D, Broderick J, Khoury J, Flaherty M, Woo D, Alwell K, Moomaw CJ, Schneider A, Miller R, Shukla R, Kissela B. The Unchanging Incidence and Case-Fatality of Stroke in the 1990s: A Population-Based Study. Stroke. 2006;37: Truelsen T, Piechowski-Jozwiak B, Bonita R, Mathers C, Bogousslavsky J, Boysen G. Stroke incidence and prevalence in Europe: a review of available data. Eur J Neurol. 2006;13: Rothwell PM, Coull AJ, Giles MF, Howard SC, Silver LE, Bull LM, Gutnikov SA, Edwards P, Mant D, Sackley CM, Farmer A, Sandercock PA, Dennis MS, Warlow CP, Bamford JM, Anslow P. Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study). Lancet. 2004;363: Johansson B, Norrving B, Lindgren A. Increased Stroke Incidence in Lund-Orup, Sweden, Between 1983 to 1985 and 1993 to Stroke. 2000;31: Medin J, Nordlund A, Ekberg K. Increasing stroke incidence in Sweden between 1989 and 2000 among persons aged 30 to 65 years: evidence from the Swedish Hospital Discharge Register. Stroke. 2004;35: Appelros P, Nydevik I, Seiger A, Terent A. High incidence rates of stroke in Orebro, Sweden: further support for regional incidence differences within Scandinavia. Cerebrovasc Dis. 2002;14: Terent A. Trends in stroke incidence and 10-year survival in Soderhamn, Sweden, Stroke. 2003;34: Harmsen P, Tsipogianni A, Wilhelmsen L. Stroke incidence rates were unchanged, while fatality rates declined, during in Goteborg, Sweden. Stroke. 1992;23: Thorvaldsen P, Kuulasmaa K, Rajakangas AM, Rastenyte D, Sarti C, Wilhelmsen L. Stroke trends in the WHO MONICA project. Stroke. 1997;28: Wilhelmsen L, Welin L, Svardsudd K, Wedel H, Eriksson H, Hansson PO, Rosengren A. Secular changes in cardiovascular risk factors and attack rate of myocardial infarction among men aged 50 in Gothenburg, Sweden Accurate prediction using risk models. J Intern Med. 2008;263: Pajunen P, Paakkonen R, Hamalainen H, Keskimaki I, Laatikainen T, Niemi M, Rintanen H, Salomaa V. Trends in fatal and nonfatal strokes among persons aged 35 to 85 years during in Finland. Stroke. 2005;36: Goldacre MJ, Duncan M, Griffith M, Rothwell PM. Mortality rates for stroke in England from 1979 to 2004: trends, diagnostic precision, and artifacts. Stroke. 2008;39: Saposnik G, Baibergenova A, Bayer N, Hachinski V. Weekends: a dangerous time for having a stroke? Stroke. 2007;38: Campbell NRC, Brant R, Johansen H, Walker RL, Wielgosz A, Onysko J, Gao RN, Sambell C, Phillips S, McAlister FA, for the Canadian Hypertension Education Program Outcomes Research Task Force. Increases in antihypertensive prescriptions and reductions in cardiovascular events in Canada. Hypertension. 2009;53: Spetz CL. In-patient diseases in Sweden Stockholm, Sweden: The National Board of Health and Welfare, Centre for Epidemiology; Koster M, Stegmayr B. Validation of stroke incidence derived from the Swedish Hospital Discharge Register and the Cause of Death Register. 2009:Personal communication. 19. Bengtsson C. Ischaemic heart disease in women. A study based on a randomized population sample of women and women with myocardial infarction in Goteborg, Sweden. Acta Med Scand Suppl. 1973;549: Welin L, Adlerberth A, Caidahl K, Eriksson H, Hansson PO, Johansson S, Rosengren A, Svardsudd K, Welin C, Wilhelmsen L. Prevalence of cardiovascular risk factors and the metabolic syndrome in middle-aged men and women in Gothenburg, Sweden. BMC Public Health. 2008; 8: Waterhouse J, Muir C, Correo P, Powell J. Cancer Incidence in Five Continents. Lyon, France: International Agency for Research on Cancer; Harmsen P, Rosengren A, Tsipogianni A, Wilhelmsen L. Risk factors for stroke in middle-aged men in Goteborg, Sweden. Stroke. 1990;21: Wilhelmsen L, Koster M, Harmsen P, Lappas G. Differences between coronary disease and stroke in incidence, case fatality, and risk factors, but few differences in risk factors for fatal and non-fatal events. Eur Heart J. 2005;26: Pessah-Rasmussen H, Engstrom G, Jerntorp I, Janzon L. Increasing stroke incidence and decreasing case fatality, A study from the stroke register in Malmo, Sweden. Stroke. 2003; Hallstrom B, Jonsson AC, Nerbrand C, Norrving B, Lindgren A. Stroke incidence and survival in the beginning of the 21st century in southern Sweden: comparisons with the late 20th century and projections into the future. Stroke. 2008;39: Rautio A, Eliasson M, Stegmayr B. Favorable Trends in the Incidence and Outcome in Stroke in Nondiabetic and Diabetic Subjects: Findings From the Northern Sweden MONICA Stroke Registry in 1985 to Stroke. 2008;39:

7 Harmsen et al Stroke Incidence and Mortality Rates Lindenstrom E, Boysen G, Nyboe J. Influence of total cholesterol, high density lipoprotein cholesterol, and triglycerides on risk of cerebrovascular disease: the Copenhagen City Heart Study. BMJ. 1994;309: Njolstad I, Arnesen E, Lund-Larsen PG. Body height, cardiovascular risk factors, and risk of stroke in middle-aged men and women. A 14-year follow-up of the Finnmark Study. Circulation. 1996;94: Freiberg JJ, Tybjaerg-Hansen A, Jensen JS, Nordestgaard BG. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA. 2008;300: Harmsen P, Lappas G, Rosengren A, Wilhelmsen L. Long-term risk factors for stroke. Twenty-eight years of follow-up of 7457 middle-aged men in Goteborg, Sweden. Stroke. 2006;37: Rosengren A, Wilhelmsen L, Lappas G, Johansson S. Body mass index, coronary heart disease and stroke in Swedish women. A prospective 19-year follow-up in the BEDA study. J Cardiovasc Risk. 2003;10: Rexrode KM, Hennekens CH, Willett WC, Colditz GA, Stampfer MJ, Rich-Edwards JW, Speizer FE, Manson JE. A prospective study of body mass index, weight change, and risk of stroke in women. JAMA. 1997; 277: Tanko LB, Bagger YZ, Qin G, Alexandersen P, Larsen PJ, Christiansen C. Enlarged waist combined with elevated triglycerides is a strong predictor of accelerated atherogenesis and related cardiovascular mortality in postmenopausal women. Circulation. 2005;111: Zia E, Pessah-Rasmussen H, Khan FA, Norrving B, Janzon L, Berglund G, Engstrom G. Risk factors for primary intracerebral hemorrhage. A population-based nested case-control study. Cerebrovasc Dis. 2005;21: Fibrinogen Studies Collaboration. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294: The European Registers of Stroke (EROS) Investigators. Incidence of Stroke in Europe at the Beginning of the 21st Century. Stroke. 2009;40: Tolonen H, Mahonen M, Asplund K, Rastenyte D, Kuulasmaa K, Vanuzzo D, Tuomilehto J. Do trends in population levels of blood pressure and other cardiovascular risk factors explain trends in stroke event Rates? Comparisons of 15 populations in 9 countries within the WHO MONICA Stroke Project. Stroke. 2002;33:

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