Study design
This is an ecological analysis of the geographical distribution of stroke using hospital admissions as a proxy for incidence and stroke mortality in Ecuador from 2001 to 2017. The analysis included all the stroke cases and fatalities reported in every city (cantons) of Ecuador as the unit of analysis with a yearly resolution. Stroke cases included all the hospital admissions and deaths according to the patient’s place of residence reported to the National Institute of Census and Statistics (INEC) including the following ICD-10 diagnoses: I60 subarachnoid haemorrhage (SAH), I61 intracerebral haemorrhage (ICH), I63 ischaemic stroke (IS) and I64 as not specified stroke.
Sample and setting
A country-wide comparison of the total number of strokes from the 24 provinces and the 221 cantons in Ecuador was performed from 2001-2017. Ecuador with an area of more than 283,000 Km2 is the smallest country in the Andean mountainous region in South America. The country is divided into 4 geographical regions, the coast, the highlands, the Amazon region and the Galapagos Islands. The political division encloses 24 provinces, 10 from the highlands, 7 from the coast, 6 from the Amazon region and 1 from the insular region of Galapagos. Every province has several political divisions called cantons and they are comparable to cities elsewhere.
Population
According to the 2017 National Institute of Census and Statistics (INEC) data projections, Ecuador has a population of 17,082,730, 51% women and 49% men. In terms of ethnicity, most of people are Mestizo (79.3%), followed by Afro-Ecuadorians (7.2%), indigenous (7.1%), white or Caucasians descendants (6.1%) and other groups (0.4%)[24].
Exposure
The association between altitude exposure and stroke incidence and mortality was analysed. The classification of low altitude < 2,500 m and high-altitude >2,500 m was used as a cut-off point for elevation exposure, while the classification offered by the International Society of Mountain Medicine (low altitude (<1,500 m), moderate altitude (1,500 to 2,500 m), high-altitude (2,500 to 3,500 m) and very high-altitude (3,500 to 5,500 m) was used to assess prevalence odds ratios by different elevations.
Outcome
Stroke age-sex and altitude adjusted incidence and mortality rates were calculated using the total number of stroke hospital admissions and all the stroke-related deaths in Ecuador.
Data source
Data was retrieved from the National Institute of Census and Statistics (INEC) using the general hospital admission and the mortality databases for the last 17 years of available data on discharges and death certificates according to the patient’s place of residence within the public and private health system in Ecuador. The databases included the latest International Classification of Diseases 10th Revision (ICD-10) coding system and the information concerning stroke was retrieved from the INEC public domain at https://www.ecuadorencifras.gob.ec/.
Inclusion criteria
Using the International Classification of Diseases 10th Revision (ICD-10) the following subtypes of stroke cases and deaths were included: I60 subarachnoid haemorrhage (SAH), I61 intracerebral haemorrhage (ICH), I63 ischaemic stroke, I64 Stroke not specified and the combination of all of them in a new variable called “all strokes”.
Exclusion criteria
Patient without an ICD-10 diagnosis of stroke were not included[25]. The following ICD-10 codes including transient ischemic attack (TIA) were excluded: I65 Occlusion and stenosis of precerebral arteries, not resulting in cerebral infarction, I66 Occlusion and stenosis of cerebral arteries, not resulting in cerebral infarction, I67 Other cerebrovascular diseases, I68 Cerebrovascular disorders in diseases classified elsewhere and I69 Sequelae of cerebrovascular disease.
Statistical analysis
Incidence and mortality crude and age-sex adjusted rates were calculated using the population at risk for every altitude location. The 2010 Ecuadorian census data was used as the standard population for the direct standardization[26]. Measurements of frequency (counts, absolute and relative percentages), central tendency (mean and median) and dispersion (range and standard deviation) as well as absolute differences were performed for age, sex and the canton’s elevation.
To reduce the impact of age-sex population distribution’s differences at different altitudes, a direct standardization method was applied to calculate incidence and mortality. A Poisson regression was used to find the altitude effect on incidence / mortality after adjusting for age and sex. For association, we obtained OR for the total number of expected cases by the population at risk in all the groups to obtain the likelihood of death due to stroke hospital admissions. Poisson regression models were used to quantify the association between sex, altitude, age and the risk of stroke. Relative risks were obtained from the exponents of the coefficients of the corresponding models.
The analysis if the data was performed using the SPSS statistics software for Mac (IBM Corp. 2014, version 24.0. Armonk, NY, USA) and the Poisson analysis was done in R version 3.6.2. Figures and graphs were performed in Prism 8 GraphPad Software version 8.2.0 (2365 Northside Dr. Suite 560, San Diego, CA 92108). The basic cartography maps were generated using QGIS Development Team 2.8 (Creative Commons Attribution-ShareAlike 3.0 licence CC BY-SA).
Ethical consideration
This secondary data analysis of publicly available, anonymized data received ethical approval from the University of Southampton with the Faculty of Medicine Ethics Committee ERGO 51422.R3 number.