This is the first and largest observational retrospective study with electronic health data from all over Kazakhstan, shedding a light on the incidence of macrovascular complications and their impact on survival among diabetic patients and corroborating that the global un-meet need associated with macrovascular complications also affects the Kazakhstani diabetic patients.
According to the results, cumulative incidence of AMI, stroke, and LLA was 1.30%, 1.94%, and 2.94%, respectively. Those complications have a significant impact on survival of diabetic patients.
Ischemic heart disease and cerebrovascular disease represents the main causes of life lost to premature death in Kazakhstan . Cardio-metabolic factors related with DM and their vascular complications, as dietary risks, high systolic blood pressure and high body mass index were the highest ranked risk factors for disease burden in Kazakhstan. Despite of progress due to reform over the past few years resulting in improvements in prevention and management of non-communicable disorders in the country , those health problems still have a significant public health impact and call for continuing strengthening of the health system to respond to their significant burden, including the evaluation of those interventions . Along with increasing incidence and prevalence of DM in Kazakhstan, about 80% of diabetic patients are overweight or obese and uncontrolled elevated blood pressure is also highly prevalent, factors that contribute to the development of DM-related micro- and macrovascular complications [13–15].
The incidence of AMI found in this work is lower than has been reported in Africa, Americas, Europe and Eastern Mediterranean, but higher than in South-East Asia and Western Pacific; stroke was higher in Europe and Western Pacific, and lower in Africa, Americas, South-East Asia and Eastern Mediterranean. Studies from Spain and Israel with hospitalized diabetic patients reported a similar 2.0–3.0% incidence of AMI [16, 17].
LLA were significantly higher in Kazakhstan than in any of those regions . LLA has shown incidence ranging from 0.02–2.48% [19–21]. The higher observed incidence of LLA in our study could be associated with high prevalence of risk factors among diabetic patients in Kazakhstan , resembling the trends in low- and middle-income countries (LMICs), where the incidence is increasing, possibly due to poor control of vascular risk factors among diabetic patients.
We observed a higher incidence of AMI, stroke and LLA in men [19–26], while mortality was higher in women compared to men [26–28]. Although there is still a gap in explanation of this observation, previously it was found that diabetic women had a higher overall CVD risk at baseline , including higher body fat percentage and higher abdominal fat, a factor that is associated with insulin-resistance, but also were less likely to reach recommended levels of low-density lipoprotein (LDL) and cholesterol [30, 31]: men may be treated more intensively . But, there could be other socio-economic factors associated with sex-differences in mortality after macrovascular complications in diabetic patients . Regarding LLA, men could seek less foot care and have a greater risk for development of fool ulcers, which is associated with higher incidence of LLA .
The incidence of all macrovascular complications in our study increased with age: factors like a higher presence of comorbidities, obesity, low level of physical activity, hyperglycemia and a longer duration of the disease are risk factors positively associated with CVDs and LLA . Older age has been consistently associated with higher incidence of stroke and AMI . However, fewer studies reported the incidence stratified by age categories for AMI, stroke and LLA [17, 20, 28].
Mortality rates for these complications were almost similar: 29.03% for AMI, 25.16% for stroke and 29.80% for LLA during the follow-up. The 5-year mortality rate due to AMI and stroke in other studies varied between 13.9%-50% [36–40] having been reported to be 62% for LLA .
Mortality reflects an increased risk of post-hospitalization mortality [37, 38, 42–44]. Overall, diabetic patients suffering from AMI, stroke or LLA have a significantly higher risk of death during 6 year of follow up [4, 45]. Some differences observed in the estimates from other studies could be partially explained by the diversity of data sources and methodologies applied in each study, by the heterogeneity in the characteristics of study populations, but may also be associated with the variations in care for diabetic patients in different countries.
Strengths and limitations.
Overall, this observational retrospective study has certain strengths. First, we have investigated the incidence of macro-vascular complications using a large database that covered all hospitalization cases with DM from all regions of Kazakhstan. We assume that the findings reflected the real situation of incidence and mortality after those events. To our knowledge, this is the first study in Kazakhstan and Central Asia to utilize such a large database, therefore representing an important contribution to understand the epidemiology of DM-related macrovascular complications in Kazakhstan.
Inevitably, this research has several limitations. Even though this study utilized a representative sample of diabetic patients, some major variables were not available for the analysis, including the type of DM, duration of DM, treatments, laboratory measures or comorbidities, including obesity, or health behaviors such as smoking or alcohol consumption, or lifestyle factors, such as level of physical activity and eating behavior. It is possible that the hospitalized population might be at a more progressed stage of the disease and have been prescribed different medications, which might affect consequent complications. Secondly, we used a probabilistic approach for imputations of missing RpnID, thus, our estimates of incidence could be underestimated. Third, there could be potential misclassification bias as diagnosis of DM and DM-related complications were defined by ICD-9 and ICD-10 codes. Fourth, the mortality rates for AMI and stroke could be underestimated as some cases could be coded with codes for main hospitalization reasons which might not be related to them.