Of the 1680 consecutive patients admitted to Mantua (Italy) Stroke Unit from January 1st
, 2006, to December 31st
, 2008, we analysed 781 (46.5%) cases living in the urban area within 10 km from one of the urban air pollution stations. The limit of 10 km is considered an appropriate distance from the recording site for quantifying the exposure of the population to outdoor pollution. Preliminary data of the study are presented elsewhere.15
We analyzed all consecutive patients hospitalized in Mantua Stroke Unit for a Transient Ischemic Attack (TIA) or stroke over three years (from January the 1st
, 2006 to December 31st
, 2008) and enrolled in the Lombardia Stroke Unit Network (SUN) registry. All patients, or relatives, gave written informed consent to the SUN epidemiological survey, that was previously approved by the local health care authorities (Regione Lombardia) as a permanent diseases registry.16,17
The hospital registry recorded all strokes and TIA among patients admitted in the Stroke Unit of Carlo Poma Hospital in Mantua, which is the only tertiary centre of the county for stroke admission. The arrival time from stroke onset in the Mantua Stroke Unit, according to the periodical monitoring, ranges between 2 to 25 hours. The majority of stroke patients (70%) in study period was admitted within 16 hours from onset.
The ischaemic or haemorrhagic subtype was identified by computed tomography (CT) scan or by magnetic resonance imaging (MRI) in more than 98% of the cases (87% CT scan, 13% DWI). We also collected data on risk factors for stroke such as gender, age, hypertension), ischaemic heart disease [history of angina pectoris or myocardial infarction or ischaemic features on electrocardiogram (ECG)], cardiac arrhythmia (history of atrial fibrillation, by electrocardiogram or diagnosed on ECG or Holter recording), diabetes mellitus (fasting plasma glucose level >7.8 mmol/L or patients who had been treated with insulin or oral hypoglycaemic drugs), dyslipidemia (total cholesterol level >6.0 mmol/L or treatment with lipid-lowering drugs) and smoking history (ex-smoker and current smoker). Two-dimensional echocardiography was performed to detect possible cardioembolic source. Carotid and vertebral ultrasonography were routinely performed. Diagnosis of the subtypes of stroke was always performed on clinical and cerebral imaging: ischaemic stroke from atheroma of large arteries; ischaemic stroke from small vessel disease, so called lacunar infarct; ischaemic stroke from cardiac embolism; primary cerebral haemorrhagic stroke; subarachnoid haemorrhagic stroke. All available data regarding the patients risk factors profile and hospital diagnostic procedures (e.g. vascular imaging, laboratory results etc.) were taken into account. When it was difficult to differentiate ischaemic stroke from atheroma of large arteries, lacunar infarct and cardiac embolism, consensus meetings were performed to classify the difficult cases in one of the three groups. A transient ischaemic attack was diagnosed when clinical symptoms disappeared within 24 hours without any infarct lesion on imaging.
Stroke subtypes were defined at discharge, according to the TOAST and OCSP criteria.13,14,18,19
Air pollution and meteorology data
The county of Mantua, which includes about 70 municipalities, is located in Lombardy, Northern Italy and has about 400,000 inhabitants with a population density of 172.6 people/Km2
. The city of Mantua has 47,649 inhabitants (December 2007) in an area of 63.9 km2
and a population density of 745 people per Km2
The major air pollution sources in the area originate from combustion (i.e.
automobile exhausts, heating systems) and other crustal erosion or mechanical processes (i.e.
wind, fire, industrial activity).21
Mantua has a 4-seasons climate and an annual temperature range of 2.1°C to 33.2°C. Data on 24-hours average temperature and relative humidity were obtained from the National Meteorological Office.
Air pollution data were provided by the Regional Environmental Protection Agency - ARPA - of Lombardy.
For all air pollutants, we considered the daily average values. In particular the data collected for the following meteorological parameters and the following environmental pollutants concern: temperature, humidity, barometric pressure, particles of diameter <10 micron (PM10), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), benzene, nitric oxide (NO) and ozone (O3).
Exposure measurements during the study period were taken from 7 monitoring sites (1. Gramsci; 2. S. Agnese; 3. Tridolino; 4. Ariosto; 5. Lunetta; 6. Porto Mantovano; 7. Bosco Fontana), which provide hourly measurements of total suspended particles (TSP; by x-ray absorption) and gaseous pollutants: sulfur dioxide (SO2; by ultraviolet fluorescence), nitrogen dioxide (NO2; by chemiluminescence), ozone (O3; by ultraviolet photometry), and carbon monoxide (CO; by non-dispersive infrared photometry).
We calculated the hourly mean value of each pollutant collected from the 7 monitoring stations and then computed their 24-hours average values. For ozone, a daytime 8-hours average interval instead of a 24-hours interval was used.
The case-crossover design was used to study the association between air pollution and hospital admission for CVD.22
According to this design, a variant of the case-control design, each subject serves as his/her own control; controls were selected to focus on times (e.g.
days) in which the event did not occur. Thus, all individual characteristics not varying during the given time are adjusted to fit the design. For this study, a bidirectional symmetric case-crossover design was used, selecting days 1, 3, 5, 7 before and after the event (admission for stroke) as control days.
To evaluate the effect of air pollution a multi-pollutant conditional logistic regression model was performed, considering the effect of all pollutants, controlling for barometric pressure, average temperature, weekdays, holidays, the day after a holiday and dividing the cases according to gender and stroke subtype.
The statistical analyses were performed by the statistical software package SPSS Statistics 18.0 (IBM SPSS, Chicago, IL, USA).