The burden of disease preventable by risk factor reduction in Serbia

Background/Aim. Reliable and comparable analysis of health risks is an important component of evidence-based and preventive programs. The aim of this study was to analyze the impact of the most relevant avoidable risk factors on the burden of the selected conditions in Serbia. Methods. Attributable fractions were calculated from the survey information on the prevalence of a risk factor and the relative risk of dying if exposed to a risk factor. The population-attributable risks were applied to deaths, years of life lost due to premature mortality (YLL), years of life with disability (YLD) and disability adjusted life years (DALY). Results. More than 40% of all deaths and of the total YLL are attributable to cigarette smoking, overweight, physical inactivity, inadequate intake of fruit and vegetables, hypertension and high blood cholesterol. Alcohol consumption has in total a beneficial effect. According to the percent of DALY for the selected conditions attributable to the observed risk factors, their most harmful effects are as follows: alcohol consumption on road traffic accidents; cigarette smoking on lung cancer; physical inactivity on cerebrovascular disease (CVD), ischemic heart disease (IHD) and colorectal cancer; overweight on type 2 diabetes; hypertension on renal failure and CVD; inadequate intake of fruit and vegetables on IHD and CVD, and high blood cholesterol on IHD. Conclusions. This study shows that a high percentage of disease and injury burden in Serbia is attributable to avoidable risk factors, which emphasizes the need for improvement of relevant preventive strategies and programs at both individual and population levels. Social preferences should be determined for a comprehensive set of conditions and cost effectiveness analyses of potential interventions should be carried out. Furthermore, positive measures, derived from health, disability and quality of life surveys, should be included.


Introduction
Reliable and comparable analysis of risks to health is an important component of evidence-based policies and preventive programs 1 .Understanding the distribution of risk-factor burden is important for targeting specific interventions and programs, and increasing cost-effectiveness 2 .In many studies the major effects from risk factors have been found to be among those at moderately elevated levels, motivating interventions beyond those intended for clinical hypertension 3,4 .
During the last decade of the 20th century, the health status of population in Serbia was harmfully influenced by numerous factors, but especially by the general situation in the country, i.e. the long-lasting economic crisis, the consequences of war in the neighboring countries, a wide range of political and economic sanctions 5,6 .
The aim of this study was to analyze the impact of the most relevant risk factors (cigarette smoking, alcohol, physical inactivity, overweight/obesity, inadequate intake of fruit and vegetables, hypertension, high blood cholesterol) on the burden of the 10 selected conditions as defined by the Ucodes in the Global Burden of Disease (GBD) study 7 [lung cancer, cervix uteri cancer, breast cancer, colorectal cancer, ischemic heart disease (IHD), cerebrovascular disease (CVD), type 2 diabetes mellitus, renal failure, road traffic accidents and self-inflicted injuries] in Serbia without Kosovo and Metohia and to determine the relative position of the Serbian Burden of Disease in comparison to the international reference.The main argument for this selection of risk factors was the proportion of related diseases and their public health importance according to Atanaskovi -Markovi et al. 8 .

Methods
The data presented in this paper are a part of the Serbian Burden of Disease Study (SBDS) 8 , which was conducted in Serbia proper between October 2002 and September 2003.This project was funded by the European Agency for Reconstruction.The SBDS was based on the methods developed for GBD study 7 .
Disability adjusted life years (DALY) was used to estimate the burden of disease in population 7,9,10 .This indicator is the aggregation of years of life lost because of premature death (YLL) and years of life with disability YLD at the population level.YLL, YLD and DALY were calculated according to standard procedures 7,11 .
The mortality data for the selected conditions for 2000 were used from the Serbian Office of Statistics mortality database.For most conditions the incidence was available directly from disease registers, routine data bases or epidemiology studies [12][13][14][15] .The prevalence was used only for diabetes mellitus.When reliable data were not available to run the model (as for injuries), the incidence estimates in other studies were used 16 .
YLL was determined by average life expectancy at the age of death while discounting future years by 3%.The life expectancy at birth was fixed at 82.5 years for women and 80.0 years for men 17 .YLL was calculated for all diseases and injuries and YLD was calculated only for the 10 selected diseases and injuries.
In the absence of Serbian specific disability weights, the SBDS adopted GBD 1990/2000 health state evaluation results expressed in the form of disability weights 7,18 .The GBD study weighted a year of healthy life lived at young ages and older ages lower than for other ages 7 .This approach was used in the SBDS study in order to make possible comparison with other studies.
The population-attributable risk (PAR) has been applied to estimate YLL and YLD, as well as the summary metric of DALYs.The burden of disease and injuries attributable to various health risks can be estimated if the prevalence of exposure to the risk factor in the population and the relative risk of dying if exposed to the risk factor are known 19 .The PAR was calculated using the formula: Population attributable fraction = P (RR -1) P (RR -1) + 1 P -prevalence of the risk; RR -relative risk of death comparing exposed to non-exposed.
For risk factors with different categories of exposure the next formula was used: ) + 1 i = 0 i -baseline category of risk; P i -prevalence of the risk factor level; RR i -corresponding relative risk Seven risk factors were chosen for the analysis 8 .For the six of them: cigarette smoking, alcohol consumption, physical inactivity, low vegetable and fruit intake, high blood pressure and overweight, the definition of borderlines and the corresponding prevalence data were derived from the 2000 Population Health Survey, which comprised 9,921 persons, aged 20 and more years 20 .The health survey collected self-reported information from the participants for the last seven days.Since there were no recent data on blood cholesterol level in Serbia proper, data from the Population Health Survey Study in the Republic of Srpska, Bosnia & Herzegovina 21 as the most equivalent if not identical neighbouring population were used to estimate the prevalence of that risk factor in Serbia.
Data on cigarette smoking refer only to current smoking.The prevalence of each level of alcohol intake (low, hazardous, harmful) was estimated from weekly consumption by the age group and gender, after conversion to standard drinks per day (10 mL of alcohol equal 7.9 g of alcohol).The consumption of 0-0.25 standard drinks per day was considered as abstinence 20 .The analyzed levels of inactivity were sedentary and low levels defined by estimation based on the frequency and duration of physical activity.More than one serving of fruit and vegetables per day was considered as adequate consumption.High blood pressure was defined as systolic blood pressure 160 mmHg and/or diastolic blood pressure 95 mm Hg 8 ."Hypertension" was used as a term referred to those with high blood pressure and/or receiving treatment for high blood pressure.
The body mass index (BMI) (kg/m 2 ) of 25-29.9 was defined as overweight and BMI > 30 as obesity.A blood cholesterol level > 5.5 mmol/L was defined as elevated 21 .
The relative risks associated with the exposure to these seven factors were accepted from the following studies as the best equivalents regarding populations, definitions and borderlines: For cigarette smoking, the age adjusted relative risk estimated for persons 35 years and over from the 2nd wave of the American Cancer Society ' s Cancer Prevention Study 22 ; For alcohol consumption, physical inactivity, hypertension, overweight and high blood cholesterol the relative risk from the Australian Burden of Disease Study [23][24][25] ; For inadequate fruit and vegetables intake, the relative risk estimated by the New Zealand Ministry of Health 26 .
As the prevalence data on risk factors were detailed enough 20 , it was possible to make the same category cutpoints for the risk factors as those categories used in studies from which the relative risks were accepted.The only exception was fruit and vegetables consumption.Instead of 3-5 servings of fruit and vegetables per day 26 , in SBDS more than 1 serving per day was considered as adequate consumption because it better corresponds to the Serbian population diet.For the attribution of the disability burden to risk factors, it was assumed that relative risks apply equally to mortality and morbidity.The relative risks were not fully adjusted to important covariates, and the univariate population attributable risks calculated did not allow for clustering and interaction of risk factors.

Results
In SBDS, the estimations of mortality burden attributable to alcohol harm indicate that 2.5% of total death and 3.4% of total YLL were attributed to alcohol consumption (Table 1).But alcohol benefit to mortality burden indicates that 4.3% of total deaths and 3.3% of total YLL were attributed to alcohol consumption.The most harmful effect of alcohol consumption was on road traffic accidents.The bene-ficial effect of alcohol on IHD was higher for males (-10.6% of total DALY) than for females (-8.7% of total DALY).Alcohol intake had a harmful effect on CVD in males (10.9% of total DALY) and beneficial effect in females (-19.4% of total DALY).
Cigarette smoking is responsible for 9.8% of total death and 13.7% of total YLL (Table 1).The harmful effect of cigarette smoking was greatest on lung cancer (82.8% of total lung cancer DALY in males and 90.2% in females were attributable to cigarette smoking) (Table 2 and Table 3).The estimated burden of IHD, CVD and cervical cancer attributable to cigarette smoking is higher for males than for females.
Physical inactivity is responsible for 12.0% of total death and 9.8% of total YLL (Table 1).Physical inactivity was most important for IHD and CVD, 22.2% of total IHD DALY in males and 15.1% in females, and 24.7% of total CVD DALY in males and 31.0% in females were attributable to physical inactivity (Tables 2 and 3).The estimated burden of IHD, CVD, colorectal cancer, breast cancer and type 2 diabetes attributable to physical inactivity was higher in females than in males.
Overweight is responsible for 5.4% of total death and 6.1% of total YLL (Table 1).The harmful effect of overweight was greatest for diabetes type 2, 47.3% of total diabetes type 2 DALY in males and 60.2% in females were attributable to overweight (Table 2 and Table 3).The burden of diabetes type 2, IHD, CVD, colorectal cancer and breast cancer attributable to overweight is higher in females than in males.
Hypertension is responsible for 13.3% of all death and 12.0% of YLL (Table 1).The harmful effect of hypertension is greatest on renal failure and CVD, 49.6% of total renal failure DALY in males and 58.9% in females, and 48.7% of total CVD DALY in males and 40.5% in females are attributable to hypertension (Table 2 and Table 3).Hypertension is also an important risk factor for IHD, 19.2% of total IHD DALY in males and 24.7% in females are attributable to hypertension.Burden of IHD, CVD and renal failure attributable to hypertension are higher in females than in males.
High blood cholesterol is responsible for 0.92% of all deaths and 0.99% of all YLL (Table 1).A part of total IHD burden is attributable to high blood cholesterol, 7.0% of total IHD DALY in males and 5.4% in females (Table 2 and Table 3).Inadequate intake of fruit and vegetables is responsible for 2.3% of total deaths and 3.2% of total YLL (Table 1).The disease burden attributable to inadequate intake of fruit and vegetables are calculated only for IHD and CVD (Table 2 and Table 3).Total deaths, YLL and DALY attributable to inadequate intake of fruit and vegetables for IHD and CVD are higher for males than females.

Discussion
Our study can be compared well to the Global and the Australian Burden of Disease (BD) studies 7,23 .Therefore, some of our key results are discussed in the following section with reference to these two main studies.
Alcohol consumption is a serious public health problem not only in Serbia but worldwide, as it is causally related to more than 60 types of diseases and injuries 27,28 .On the other hand, it is also protective against some diseases especially as regards to IHD 29 .Whereas in our study the balance is slightly positive, according to the majority of the literature the health impact of alcohol consumption on the whole is negative.It is estimated that 4% of the global burden of disease is attributable to alcohol 1 , more than half of it (2.8%) is related to high-risk drinking 30 , especially among young males.In 2001, the proportion of DALYs attributable to high-risk alcohol consumption was the highest in Europe and Central Asia (8.3%), and the lowest in South Asia (0.9%) and Sub-Saharan Africa (1.3%) 1,31,32 .In Serbia the mortality burden attributable to alcohol is 1.6 times higher than the average of the world population 7 .Also like in other East European countries, e.g. in Russia or Lithuania, there is a high alcohol-attributable mortality due to intentional and unintentional injuries, especially for men 28,33 .
Cigarette smoking is the risk factor associated with the greatest health problems and is responsible for 13.7% of the total YLL in Serbia, similar to the results of the BD study in Australia (13.1%) 23 , the greatest proportion of disease burden being associated with lung cancer.According to the World Health Report 2002, active cigarette smoking is after high blood pressure the second leading cause of premature mortality 1 .Cigarette smoking is a causal factor for more than 50 different diseases and causes for example 45% of acute myocardial deaths, 25% of deaths due to CVD and 85% of deaths from chronic obstructive pulmonary disease 34 .
In Serbia, 12% of all deaths and 9.8% of total YLL are attributable to physical inactivity, again most similar to the Australian BD study with 10.1% of all deaths and 9.0% of total YLL attributable to physical inactivity 23 .Murray and Lopez 35 estimated that the DALY attributable to physical inactivity are 1% worldwide, 4.8% in established market economies.
Overweight has been acknowledged recently as a key health problem.Worldwide 1.1 billion adults are overweight 36 .In the present study overweight is responsible for 6.1% of total YLL which is higher than in the BD study in Australia (4.6% of all YLL) 23 and with regard to DALYs also considerably higher than the European average 1 .Overweight is one of the strongest lifestyle-related factors for developing type 2 diabetes 1, 37 and associated with IHD, CVD, osteoarthritis, and breast, colorectal, prostate, endometrial, kidney and gallbladder cancer 38 .WHO 1 has estimated that approximately 58% of diabetes mellitus globally and 21% of IHD are attributable to a BMI above 25 kg/m 2 .
High blood pressure is the leading cause of global burden of disease, especially also in the developing world 39 .In Serbia, hypertension is responsible for 12.0% of all deaths and 13.3% of total YLLs, more in females than in males.In the Australian BD study 11.2% of total deaths and 8.2% of all YLL were attributable to hypertension, considerably less than in Serbia 23 .Globally, approximately two-thirds of CVD and one-half of IHD were attributable to non-optimal blood pressure, with little variation by sex 1,39 .It is surprising that the controlled fraction of this key risk factor is usually smaller than a quarter of those with hypertension 40 .
Because of differences in the definition of inadequate intake of fruits and vegetables our results are not completely comparable, although they are similar to the results of the Australian BD Study 23 .It has been estimated that globally 2.7 million (4.9%) deaths and 26.7 million (1.8%) DALYs in 2000 were attributable to low fruit and vegetable intake 41 .Ideally to protect against CVD and certain cancers, the WHO recommends an intake of 400 g/day 42 .In the global study, low intake of fruit and vegetables is estimated to cause about 31% of IHD, 19% of ischemic CVD, 20% of esophageal cancer and 19% of gastric cancer worldwide 43 .
High cholesterol in the present study is responsible for 7.0% of total DALYs in males and for 5.4% of total DALYs in females.Worldwide approximately 56% of IHD mortality and disease burden is attributable to cholesterol levels of more than 3.8 mmol/L, which correspond to 3.6 million deaths in the year 2000 44 .Overall, 4.4 million deaths (about 7.9% of the total) and 40.4 million DALYs (2.8% of total) worldwide were estimated to be due to non-optimal cholesterol levels.

Conclusion
More than 40% of all deaths and of the total YLL are attributable to cigarette smoking, overweight, physical inactivity, inadequate intake of fruit and vegetables, hypertension and high blood cholesterol, whereas alcohol consumption in Serbia had overall a slightly positive effect.According to the percent of DALY for the selected conditions attributable to the observed risk factors, their most harmful effects are as follows: alcohol consumption on road traffic accidents; cigarette smoking on lung cancer; physical inactivity on CVD, IHD and colorectal cancer; overweight on type 2 diabetes; hypertension on renal failure and CVD; inadequate intake of fruit and vegetables on IHD and CVD, and high blood cholesterol on IHD.A high percentage of disease and injury burden in Serbia is attributable to avoidable risk factors, which emphasizes the need for improvement of relevant preventive strategies and programs at both individual and population levels.Social preferences should be determined for a comprehensive set of conditions prevalent in Serbia and the burden of disease analysis be linked to marginal costeffectiveness analysis of potential interventions, e.g.Bjego- vic et al. 45 .Also in the future the burden of disease assessment could be supplemented by positive measures of health expectancy or health adjusted life expectancy, derived from national health, disability and quality of life surveys.

*
Inadequate intake of fruits and vegetables; † Risk factor dependant DALYs as percent of all DALYs generated by the specific disease in question; YLL -years of life because of premature death; YLD -years of life with disability; DALY -disability adjusted life years; CVD -cerebravascular disease; IHD -ischemic heart disease.

Table 2 Number of deaths, YLL, YLD and DALY attributable to the selected risk factors for 10 conditions in the male population of Serbia proper, 2002
*Inadequate