To the best of our knowledge, this is the first study conducted in the Middle East region reporting the population attributable fraction for stroke events. Results from this study suggest that most stroke events in Iranian populations can be attributed to modifiable risk factors of hypertension, CKD and diabetes. There was no difference between CKD, hypertension and diabetes, with regard to the prediction of total as well as ischemic stroke events.
The INTERSTROKE study was the first large case–control study aimed at ascertaining risk factors for stroke, in which low and middle income countries like Iran were included
. The study showed that five established risk factors (reported hypertension, smoking status, waist to hip ratio, diet risk score and physical activity) account for 80% cases of stroke events. With addition of five other risk factors (diabetes, alcohol intake, psychosocial factors, cardiac causes and ApoA1), the population-attributable risks for stroke reached 90%, a finding which indicated that there are some other risk factors that need to be considered beyond these potential risk factors, bearing in mind that usually the sum of PAFs goes beyond than 100%
Since, CKD and CVD often shared the same pathophysiological mechanism
 and most of those who had CKD died because of their CVD problems not progression to end stage renal failure, much attention is being paid to the magnitude of relationship between CKD and stroke
. In our dataset, we demonstrated the importance of CKD as the second strongest predictor of stroke. CKD, independent of age, gender, smoking, hypertension and diabetes, was associated with ischemic stroke and accounts for 30% of all stroke patients. Importantly, we found the same risk for CKD vs. other independent risk factors in prediction of incident stroke; obviously, the higher PAF of hypertension compared with CKD was related more to higher prevalence of the former than to the latter in our population. Recently in a meta-analysis of 21 articles, Lee et al
 showed that patient with baseline eGFR < 60 ml/min/1.73 m2 had 43% higher chance of developing stroke events than those with baseline eGFR > 90 ml/min/1.73 m2; however, they did not find significant increase risk of stroke among patients with eGFR of 60-90 ml/min/1.73 m2. They also demonstrated that the effect of reduced eGFR was more profound on risk of fatal stroke than all other types of stroke, which is in line with the fact that kidney disease even with mild severity is independently associated with poor prognosis in patients with stroke disease resulting in higher risk of death
. It has been also measured that those with low GFR had smaller brain volume, smaller deep white matter volume and more white matter layer and these associations were independent of cardiovascular risk factors
Hypertension is known to be the single most important risk factor for all kinds of stroke. In an overview of reviews, Lawes et al documented a continuous steep and log linear association between blood pressure and stroke
; they also highlighted a 10 mmHg lower SBP or 5 mmHg lower DBP to be associated with 30-40% lower risk of stroke. In the current study, among modifiable and non-modifiable risk factors, hypertension showed the greatest PAF for total as well as ischemic stroke events.
Consistent with previous studies, in our population, diabetes independently increased the risk of stroke event. The PAF of 24% of diabetes for ischemic stroke in the current study was in the range of 5–27% reported in Goldstein et al study
. Despite the significant risk of diabetes for stroke events, no strong benefit in stroke reduction with tight glycemic control has been shown
. However, control of blood pressure in patients with type 2 diabetes as part of a complete cardiovascular risk-reduction program and treatment of adults with diabetes with a statin, especially those with additional risk factors, is recommended to lower risk of a first stroke
In the current study, smoking showed 73% risk for incident ischemic stroke, which was marginally significant and leading to PAF of 14% for incident stroke. Similarly, Goldstein et al recently reported that among risk factors for incident stroke, smoking showed a PAF of 12 to 14%
. A meta-analysis of 32 studies reported the relative risk for ischemic stroke to be 1.9 (95% CI, 1.7 to 2.2) for smokers compared with nonsmokers
In this study, we failed to detect any relationship between high TG, low HDL and hypercholesterolemia with stroke events. There are still ongoing debates about the role of lipid components in the risk of stroke event and epidemiologic findings are not consistent
. Recently, a meta-analysis of 61 prospective studies, showed a weak association between lipid profiles and stroke events
. They found that the association between serum cholesterol and stroke mortality was modified by age and blood pressure levels, whereas no association was observed between serum cholesterol and stroke, except in individuals aged 40-59y and in participants with normal or high normal blood pressure. Also, most but not all the epidemiologic studies have found a reverse association between hemorrhagic stroke and level of blood cholesterol
An important strength of our study was that, we used a population based cohort study to determine the risk factors of stroke and reached a model with good fitness in our analysis, indicating that we had considered the main risk factors in our models with acceptable low residuals; some of our limitations however, merit mentioning; first due to the limited number of our stroke events, we were unable to separately analyze and assess the risk factors for hemorrhagic stroke. Wu et al
 had concluded that the risk factors of stroke subtypes differ as they had have different etiopathologies. Second, in the current study, also as reported from other studies in Iran
[3, 9], we might fail to detect all cerebrovascular events in district 13 of Tehran because there are different types of public and private healthcare systems in Iran, and the public hospitals are not completely free of charge; hence some of people who do not have any type of healthcare insurance might being managed in outpatient clinics and not be admitted to hospital. Furthermore, despite a referral healthcare structure in Iran, there may be situations where people bypass a primary care contact and self-refer to private specialists
[3, 9]. Third, we analyzed the associations between risk factors and stroke events from a single measurement at baseline, which may have misclassified the risk factor profiles of some individuals; contributing to the attenuation between the risk factors and incident stroke.