Danuta Ryglewicz

RISK FACTORS FOR ISCHAEMIC AND INTRACEREBRAL HAEMORRHAGIC STROKE IN 22 COUNTRIES (THE INTERSTROKE STUDY): A CASE-CONTROL STUDY

BACKGROUNDnThe contribution of various risk factors to the burden of stroke worldwide is unknown, particularly in countries of low and middle income. We aimed to establish the association of known and emerging risk factors with stroke and its primary subtypes, assess the contribution of these risk factors to the burden of stroke, and explore the differences between risk factors for stroke and myocardial infarction.nnnMETHODSnWe undertook a standardised case-control study in 22 countries worldwide between March 1, 2007, and April 23, 2010. Cases were patients with acute first stroke (within 5 days of symptoms onset and 72 h of hospital admission). Controls had no history of stroke, and were matched with cases for age and sex. All participants completed a structured questionnaire and a physical examination, and most provided blood and urine samples. We calculated odds ratios (ORs) and population-attributable risks (PARs) for the association of all stroke, ischaemic stroke, and intracerebral haemorrhagic stroke with selected risk factors.nnnFINDINGSnIn the first 3000 cases (n=2337, 78%, with ischaemic stroke; n=663, 22%, with intracerebral haemorrhagic stroke) and 3000 controls, significant risk factors for all stroke were: history of hypertension (OR 2.64, 99% CI 2.26-3.08; PAR 34.6%, 99% CI 30.4-39.1); current smoking (2.09, 1.75-2.51; 18.9%, 15.3-23.1); waist-to-hip ratio (1.65, 1.36-1.99 for highest vs lowest tertile; 26.5%, 18.8-36.0); diet risk score (1.35, 1.11-1.64 for highest vs lowest tertile; 18.8%, 11.2-29.7); regular physical activity (0.69, 0.53-0.90; 28.5%, 14.5-48.5); diabetes mellitus (1.36, 1.10-1.68; 5.0%, 2.6-9.5); alcohol intake (1.51, 1.18-1.92 for more than 30 drinks per month or binge drinking; 3.8%, 0.9-14.4); psychosocial stress (1.30, 1.06-1.60; 4.6%, 2.1-9.6) and depression (1.35, 1.10-1.66; 5.2%, 2.7-9.8); cardiac causes (2.38, 1.77-3.20; 6.7%, 4.8-9.1); and ratio of apolipoproteins B to A1 (1.89, 1.49-2.40 for highest vs lowest tertile; 24.9%, 15.7-37.1). Collectively, these risk factors accounted for 88.1% (99% CI 82.3-92.2) of the PAR for all stroke. When an alternate definition of hypertension was used (history of hypertension or blood pressure >160/90 mm Hg), the combined PAR was 90.3% (85.3-93.7) for all stroke. These risk factors were all significant for ischaemic stroke, whereas hypertension, smoking, waist-to-hip ratio, diet, and alcohol intake were significant risk factors for intracerebral haemorrhagic stroke.nnnINTERPRETATIONnOur findings suggest that ten risk factors are associated with 90% of the risk of stroke. Targeted interventions that reduce blood pressure and smoking, and promote physical activity and a healthy diet, could substantially reduce the burden of stroke.nnnFUNDINGnCanadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Pfizer Cardiovascular Award, Merck, AstraZeneca, and Boehringer Ingelheim.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study

BACKGROUNDnStroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke.nnnMETHODSnWe completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals.nnnFINDINGSnBetween Jan 11, 2007, and Aug 8, 2015, 26u2008919 participants were recruited from 32 countries (13u2008447 cases [10u2008388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13u2008472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001).nnnINTERPRETATIONnTen potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke.nnnFUNDINGnCanadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

Incidence of Stroke in Europe at the Beginning of the 21st Century: The European Registers of Stroke (EROS) Investigators

BACKGROUND AND PURPOSEnComparable data on stroke incidence across European countries are lacking because previous studies have used different methods of case ascertainment, different periods of observation, and different age restrictions.nnnMETHODSnPopulation-based stroke registers were established in 6 European countries: France (Dijon); Italy (Sesto Fiorentino); Lithuania (Kaunas); the United Kingdom (London); Spain (Menorca); and Poland (Warsaw). Standardized criteria were used among these register including overlapping sources of notification. Overall, a source population of 1087048 inhabitants was observed, ranging from 47236 in Sesto Fiorentino to 365191 in Kaunas. All patients with first-ever stroke of all age groups from the source populations were included. Data collection took part between 2004 and 2006; 4 centers collected data for a 24-month and 2 for a 12-month time period. Crude annual incidence rates were age-adjusted to the European population.nnnRESULTSnA total of 2129 patients with first stroke were registered. Median age was 73 years and 51% were female. Annual stroke incidence adjusted to the European population was found in men to be higher in Kaunas and lower in Sesto Fiorentino and Menorca and in women to be higher in Kaunas and Warsaw and lower in Sesto Fiorentino and Menorca compared with mean incidence rates. Total stroke incidence ranged in men from 101.2 per 100000 (95% CI, 82.5 to 123.0) in Sesto Fiorentino to 239.3 per 100000 (95% CI, 209.9 to 271.6) in Kaunas and in women from 63.0 per 100000 (95% CI, 48.5 to 80.7) in Sesto Fiorentino to 158.7 per 100000 (95% CI, 135.0 to 185.4) in Kaunas. Differences in prior-to-stroke risk factors were found among the populations with prevalence of hypertension highest in Warsaw and Kaunas (76% and 67%, respectively) and lowest in Menorca and Sesto Fiorentino (54% and 62%, respectively).nnnCONCLUSIONSnThe risk of stroke among European populations in our study varied more than 2-fold in men and women. On average, higher rates of stroke were observed in eastern and lower rates in southern European countries.

A prospective community-based study of stroke in Warsaw, Poland.

Background and Purpose Poland is a country with high morbidity and mortality rates from cardiovascular diseases. No recent studies have evaluated the contribution of cerebrovascular diseases to this morbidity and mortality. Our aim was to accurately determine stroke incidence rates in Warsaw, Poland. Methods A 2-year prospective and population-based stroke registry was maintained for health care units 2 and 3 in Warsaw, Poland (population, 182 285). Case subjects were ascertained by surveying hospital admissions, outpatient visits, and death certificates. Results During the 2 years of the study (1991 to 1992), 633 cases of first-event strokes were registered, 462 of which were first ever in a lifetime. Computed tomography or necropsy was performed in 72% of first-ever stroke cases. The crude annual incidence rate for first-ever stroke was 127/100 000 (95% confidence intervals, 111 to 145); the rate standardized to the European population was 111 (95% confidence intervals, 96 to 128). Our incidence rates for first-event strokes were found to be in the middle of the range among other first-event studies. When comparing our first-ever stroke incidence rates with those of comparable studies performed throughout Europe, they were found to be similar for groups aged younger than 65 years but lower in the older age groups. The distribution of ischemic and hemorrhagic stroke subtypes was similar to that of other countries. Conclusions This first population-based prospective stroke registry in Poland showed that incidence rates were not high compared with other studies throughout Europe and the world. These stroke incidence rates are not a large contributing factor to high cardiovascular morbidity rates in Poland.

Three-month stroke outcome: The European Registers of Stroke (EROS) Investigators

Background: Contemporaneous data on variations in outcome after first-ever-lifetime stroke between European populations are lacking. We compared differences in case fatality rates, functional outcome, and living conditions 3 months after stroke within the European Registers of Stroke Collaboration. Methods: Population-based stroke registers were established in France (Dijon), Italy (Sesto Fiorentino), Lithuania (Kaunas), the United Kingdom (London), Spain (Menorca), and Poland (Warsaw). All patients with first-ever-lifetime stroke of all age groups from the source population (1,087,048 inhabitants) were included. Data collection took part between 2004 and 2006. The study investigated population variations in outcome at 3 months (death, institutionalization due to stroke, or Barthel Index below 12 points) using multivariable logistic regression analyses adjusted for age, sex, stroke severity, stroke subtype, and comorbidities. Results: A total of 2,034 patients with first-ever-lifetime stroke were included. Median age was 73 years, 52% were female. The mean weighted cumulative risk of death was 21.8% (95% confidence interval 20.0 to 23.6) with a 3-fold variation across populations. The weighted proportion of poor outcome was 41.3% (95% confidence interval 39.0 to 43.7) with a 2-fold variation across populations. Conclusion: More than 40% of patients had a poor outcome, defined as being dead, dependent, or institutionalized 3 months after stroke. Substantial outcome variations were found between populations that were explained by case mix variables in this analysis, yet a trend toward a higher risk of poor outcome was present in Kaunas.

Elevated Levels of Anti-Heat Shock Protein Antibodies in Patients with Cerebral Ischemia

One of the important mechanisms involved in the development of vascular lesions leading to ischemic stroke could be an immune response to heat shock proteins (hsp). For carotid atherosclerosis and myocardial infarction, an association with an increase in anti-hsp 65 antibodies has been demonstrated. The aim of our study was (1) to investigate whether ischemic stroke is associated with a humoral immune response to hsp; (2) to study the connection between anti-hsp antibodies and other stroke risk factors; (3) to estimate if the elevated levels of anti-hsp antibodies could be an independent risk factor for stroke. We examined 180 patients (in the first 48 h after stroke onset) and 64 age-matched healthy controls. The levels of IgG and IgM antibodies to hsp 65 and 70 were measured by ELISA. Ischemic stroke was connected with a significant elevation of anti-hsp 65 and anti-hsp 70 antibody levels (IgG and IgM) compared with controls (p < 0.0001). The multifactorial logistic regression analysis showed that increased levels of anti-hsp 65 and anti-hsp 70 IgG antibodies are independent risk factors for stroke. Our results suggest that humoral immunity to hsp is common in stroke patients and that elevated levels of anti-hsp antibodies could be triggering factors for stroke.

Rationale and Design of INTERSTROKE: A Global Case-Control Study of Risk Factors for Stroke

Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 countries (29,972 participants), identified nine modifiable risk factors that accounted for >90% of population-attributable risk. However, traditional risk factors (e.g. hypertension, cholesterol) appear to exert contrasting risks for stroke compared with coronary heart disease, and the etiology of stroke is far more heterogeneous. In addition, our knowledge of risk factors for stroke in low-income countries is inadequate, where a very large burden of stroke occurs. Accordingly, a similar epidemiological study is required for stroke, to inform effective population-based strategies to reduce the risk of stroke. Methods: INTERSTROKE is an international, multicenter case-control study. Cases are patients with a first stroke within 72 h of hospital presentation in whom CT or MRI is performed. Proxy respondents are used for cases unable to communicate. Etiological and topographical stroke subtype is documented for all cases. Controls are hospital- and community-based, matched for gender, ethnicity and age (±5 years). A questionnaire (cases and controls) is used to acquire information on known and proposed risk factors for stroke. Cardiovascular (e.g. blood pressure) and anthropometric (e.g. waist-to-hip ratio) measurements are obtained at the time of interview. Nonfasting blood samples and random urine samples are obtained from cases and controls. Study Significance: An effective global strategy to reduce the risk of stroke mandates systematic measurement of the contribution of the major vascular risk factors within defined ethnic groups and geographical locations.

Anticardiolipin antibodies are an independent risk factor for ischemic stroke

Our aim was to determine if anticardiolipin antibodies are an independent risk factor for ischemic stroke and to determine their influence on stroke type and clinical outcome. We prospectively studied 194 consecutive patients with ischemic stroke admitted within 48 h of stroke. A control group consisted of 100, age and sex matched, healthy individuals. Neurological and functional status was assessed on admission, at 30 days, and at 1 year. IgG anticardiolipin antibodies were significantly more frequent in stroke patients (25.3%) than controls (6%, p < 0.05). A multivariate analysis suggested that anticardiolipin antibodies are an independent risk factor for ischemic stroke in addition to hypertension and atrial fibrillation (RR = 2.94, p < 0.05). Elevated IgG anticardiolipin antibodies were associated with cognitive impairment as measured by the Mini Mental State Examination at 30 days and at 1 year. IgG anticardiolipin antibodies did not correlate with stroke recurrence, or mortality at 30 days or 1 year.

Stroke Mortality Rates in Poland Did Not Decline Between 1984 and 1992

BACKGROUND AND PURPOSEnStroke mortality has decreased in most industrialized countries in recent decades. In Poland, as in other eastern European countries, mortality rates for stroke remain high.nnnMETHODSnThe Warsaw Stroke Registry (WSR) registered patients in the Mokotów district of Warsaw from 1991 through 1992. The Warsaw Pol-MONICA study registered stroke patients in the North and South Praga regions of Warsaw from 1984 through 1992. Stroke incidence rates, case-fatality rates, and stroke mortality rates were computed based on both studies and compared with published mortality rates based on death certificates. Eight-year trends of stroke incidence, case-fatality rate, and mortality were derived from the Warsaw Pol-MONICA study.nnnRESULTSnThe WSR and Warsaw Pol-MONICA studies showed similar incidence rates, mortality rates, and 28-day case-fatality rates for stroke. Mortality rates from the WSR and the Warsaw Pol-MONICA study were similar to rates from death certificate data. Mortality rates in the group aged 35 to 64 years were higher in men (47.5 to 50/100000 per year) than in women (30/100000 per year).nnnCONCLUSIONSnTwo different population-based studies suggest that stroke mortality is high in Poland because of high 28-day case-fatality rates. Stroke mortality failed to decline in Poland in the period 1984 through 1992 because neither case fatality nor stroke incidence declined in this period.

Acute Ischemic Stroke Care and Outcome in Centers Participating in the Polish National Stroke Prevention and Treatment Registry

Background and Purpose— Significant intercenter variability in quality of care and stroke outcomes was found in many countries. The aim of the study was to compare the acute ischemic stroke care and outcomes in centers participating in the Polish National Stroke Prevention and Treatment Registry. Methods— The World Health Organization Stepwise Approach to Stroke Surveillance–based questionnaire was used to collect data on patients admitted to participating centers between December 1, 2001, and July 31, 2002. To ensure data quality, only centers reporting representative sample of patients were analyzed. Ischemic stroke patient characteristics, in-hospital care, and early outcomes (adjusted for case mix) were compared for participating centers. Results— There were 26 of 48 centers that met inclusion criteria, with a total of 8736 patients (52% women; mean age 71 years, with a range among institutions from 68 to 75 years). Significant differences between centers were observed for distribution of risk factors and in-hospital care. The rates for death and poor outcome (defined as a Rankin score ≥3 or death) ranged from 8.0% to 31.8% and from 44.2% to 74.7%, respectively. After adjusting for case mix, the death or poor outcome prognoses remained significantly different between centers. Conclusions— The observed significant differences between Polish stroke centers indicate the need for improvement of patient education, effective stroke risk factor control, and standardized in-hospital care.