Научная статья на тему 'Obesity and physical activity in Health and diseaeses?'

Obesity and physical activity in Health and diseaeses? Текст научной статьи по специальности «Фундаментальная медицина»

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Ключевые слова
WEIGHT GAIN / FOODS / DIET / BRAIN FUNCTION / INSULIN RESISTANCE

Аннотация научной статьи по фундаментальной медицине, автор научной работы — Fedacko Jan, Moshiri Mahmood, Singh Ram B., Pella Daniel, Agarval Radzhesh K.

Background: Obesity is a major contributor to the global burden of chronic disease and disability. Physical inactivity is the major cause of obesity.Methods: Selected review based on internet search and discussion with experts.Results: In developing countries, obesity coexist with under-nutrition. It is a complex condition, with serious social and psychological dimensions, affecting virtually all ages and socioeconomic groups. Increased consumption of energy-dense foods with high levels of sugar and saturated fats, and deficient in micronutrients, in conjunction with physical inactivity, have led to obesity rates that have risen three-fold or more since 1980 in middle and higher income countries. The obesity epidemic is not restricted to industrialized societies; this increase is often faster in developing countries than in the developed world. Regular physical activity may be associated with a significant reduction of chronic noncommunicable diseases (NCDs) such as cardiovascular disease (CVD), obesity, cancer, osteoporosis, and diabetes mellitus most of which begin with obesity.Physical activity is also known to have beneficial effects on several biomarkers of noncommunicable diseases; inflammation, hyperlipidemia, oxidative stress, hyperglycemia, stress hormones as well as on brain function and psychological wellbeing.Conclusion: Obesity has become a major health problem in the world and may be responsible for NCDs. Increased physical activity can provide protection against adverseEffects of obesity resulting in to decreased burden of NCDs and may provide better quality oflife and well being.

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Текст научной работы на тему «Obesity and physical activity in Health and diseaeses?»

The Journal of scientific articles “Health & education millennium”

Журнал научных статей «Здоровье и образование в XXI веке» №1 2010 том 12

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OBESITY AND PHYSICAL ACTIVITY IN HEALTH AND DISEAESES?

Jan Fedacko, MD, Mahmood Moshiri, MD, Ram B Singh, MD, Daniel Pella, MD, Radzhesh K Agarval, PhD, Chibisov Sergei, MD; Trinity Medical Center, Richmond Hill, Canada Faculty of Medicine, PJ Safaric University, Kosice, Slovakia;

Tsim Tsoum Institute, Krakow, Poland.

CORRESPONDENCE.

Prof Dr M Moshiri,MD,FICN Trinity Medical Centre, Richmond Hill, Canada; email moshiri@canada. com

ABSTRACT:

Background: Obesity is a major contributor to the global burden of chronic disease and disability. Physical inactivity is the major cause of obesity.

Methods: Selected review based on internet search and discussion with experts.

Results: In developing countries, obesity coexist with under-nutrition. It is a complex condition, with serious social and psychological dimensions, affecting virtually all ages and socioeconomic groups. Increased consumption of energy-dense foods with high levels of sugar and saturated fats, and deficient in micronutrients, in conjunction with physical inactivity, have led to obesity rates that have risen three-fold or more since 1980 in middle and higher income countries. The obesity epidemic is not restricted to industrialized societies; this increase is often faster in developing countries than in the developed world. Regular physical activity may be associated with a significant reduction of chronic noncommunicable diseases (NCDs) such as cardiovascular disease (CVD), obesity, cancer, osteoporosis, and diabetes mellitus most of which begin with obesity.

Physical activity is also known to have beneficial effects on several biomarkers of non-communicable diseases; inflammation, hyperlipidemia, oxidative stress, hyperglycemia, stress hormones as well as on brain function and psychological wellbeing.

Conclusion: Obesity has become a major health problem in the world and may be responsible for NCDs. Increased physical activity can provide protection against adverse

Effects of obesity resulting in to decreased burden of NCDs and may provide better quality of life and well being.

Key words: Weight gain, foods, diet, brain function, insulin resistance.

INTRODUCTION.

Recent evidence indicate that there is epidemic of greater prevalence of overweight, obesity, and lack of wellbeing in conjunction with sedentary behaviour in the urban populations of developing countries as well as in the higher income countries (1-8). Further studies indicate that regular physical activity may be associated with a significant reduction of chronic noncommunicable diseases (NCDs) such as cardiovascular disease (CVD), obesity, cancer, osteoporosis, and diabetes mellitus, most of which begin with obesity (1-5). Obesity has reached epidemic proportions globally, with more than 1 billion adults overweight including 300 million of them having obesity. It is a major contributor to the global burden of chronic disease and disability. In developing countries, often coexist with under-nutrition. It is a complex condition, with serious social and psychological dimensions, affecting virtually all ages and socioeconomic groups. Increased consumption of more energy-dense, nutrient-poor foods with high levels of sugar and saturated fats, in conjunction with physical inactivity, have led to obesity rates that have risen three-fold or more since 1980 in some areas of North America, the United Kingdom, Eastern Europe, the Middle East, the Pacific Islands, Australasia and China. The obesity epidemic is not

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Журнал научных статей «Здоровье и образование в XXI веке» №1 2010 том 12

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restricted to industrialized societies; this increase is often faster in developing countries than in the

developed world. In this article we review the prevalence of overweight, obesity, and physical

inactivity and discusses the numerous physical and psychosocial consequences of overweight and

obesity; and present information regarding interventions that have been demonstrated to be

effective in preventing overweight and obesity and create a physical and psychological status of

wellbeing. In apparently healthy subjects as well as among patients, physical activity can create a

feeling of wellbeing and protect against psychological disorders. Increased physical activity can

cause significant reduction in the risk for serious diet-related chronic diseases, including type 2

diabetes, cardiovascular disease, hypertension and stroke, and certain forms of cancer. The health

consequences of greater physical activity range from decreased risk of premature death, to reduction

in all serious chronic conditions which increase the overall quality of life.

CURRENT ESTIMATES:

Current obesity levels range from below 5% in China, India, Japan and certain African nations, to over 75% in urban Samoa. But even in relatively low prevalence countries like India and China, rates are almost 20% in some cities. Childhood obesity is already epidemic in some areas and on the rise in others. An estimated 22 million children under five are estimated to be overweight worldwide. According to the US Surgeon General, in the USA the number of overweight children has doubled and the number of overweight adolescents has trebled since 1980. The prevalence of obese children aged 6-to-11 years has more than doubled since the 1960s. Obesity prevalence in youths aged 12-17 has increased dramatically from 5% to 13% in boys and from 5% to 9% in girls between 1966-70 and 1988-91 in the USA. The problem is global and increasingly extends into the developing world; for example, in Thailand the prevalence of obesity in 5-to-12 year olds children rose from12.2% to 15-6% in just two years. Obesity accounts for 2-6% of total health care costs in several developed countries; some estimates put the figure as high as 7%. The true costs are undoubtedly much greater as not all obesity-related conditions are included in the calculations. In developed countries, childhood and adolescent overweight and obesity are an epidemic problem. Studies show that approximately one third of youth are overweight or obese, representing a tripling since the 1960s and 1970s. The average male and female adult in the United States has gained 25 lbs and 24 lbs, respectively, since 1962. The body mass index of the average adult has increased from 25 to 28. Among youth, the average body mass index has increased from 21.3 to 24.1 since 1963. This increase in bodyweight among adults and youth is partially due to the decreased levels of physical activity.

In the Five City study, cross-sectional surveys were conducted in 6-12 urban streets in each of five cities in five different regions of India using a common study protocol and criteria of diagnosis to assess obesity, physical activity and lack of wellbeing (1). A total of 6940 subjects (3433 women and 3507men) aged 25 years and above were randomly selected from the cities of Moradabad (n=2002), Trivandrum (n=1602), Calcutta (n=900), Nagpur (n=894) and Bombay (n=1542). Evaluation and validation were performed by a physician and dietitian-administered questionnaire at Moradabad. After pooling of data, all subjects were divided into various age groups for men and women. Obesity (body mass index=30 = kg/m2) and overweight (BMI = 25-29.9kg/m2 and >23kg/m2) as well as waist-hip ratio (>0.85 in women and >088. in men, central obesity) were calculated and physical activity status and wellbeing were assessed by a validated questionnaire.

The overall prevalence of obesity was 6.8% (7.8 vs. 6.2%, P<0.05) and overweight 33.5% (35.0 vs. 32.0%,P<0.05) among women and men, respectively. The highest prevalence of obesity (7.8%) and overweight (36.9%) was found among subjects aged 35 to 44years in both sexes. The prevalence of obesity was significantly (P <0.05) greater in Trivandrum (8.5%), Calcutta (7.1%)

The Journal of scientific articles “Health & education millennium”

Журнал научных статей «Здоровье и образование в XXI веке» №1 2010 том 12

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and Bombay (8.3%) compared to Moradabad (6.2%) among women and in Trivandrum (7.4%) and

Bombay (7.2%), compared to Nagpur (5.0%) among men. There was a significant decreasing trend

in obesity (P <0.05) and overweight (P< 0.05) with increasing age above 35-44years in both sexes.

The overall prevalence of subjects obesity was 50.8% and central obesity 52.6%.The overall

prevalence of sedentary behaviour was 59.3% among women and 58.5% among men, which were

significantly associated with lack of wellbeing. Both sedentary behaviour and mild activity showed

a significant increasing trend in women after the age of 35-4488years. In men, such a trend was

observed above the age of 45 years. Sedentary behaviour was significantly (P <0.05) greater in

Trivandrum, Calcutta, and Bombay compared to Nagpur. Sedentary behaviour was significantly (P

<0.001) associated with obesity in both sexes, compared to non-obese men and women, indicating

lack of wellbeing in these subgroups. In brief, obesity, overweight and central obesity and sedentary

behaviour coexist with lack of wellbeing and have become a public health problem in all the five

cities of India. The prevalence of obesity and sedentary behaviour causing lack of wellbeing was

significantly greater in Trivandrum, Calcutta and Bombay compared to Moradabad and Nagpur.

Sedentary behaviour was significantly associated with obesity indicating poor wellbeing compared

to non-obese subjects in both sexes, which may be due to greater economic development in metro

cities.

ADVERSE EFFECTS OF OBESITY:

The economic and health consequences of this epidemic are enormous. Type 2 diabetes mellitus, a disease that was rare among youth 20 to 30 years ago, now represents as many as 45% of all cases of diabetes among youth. Cardiovascular risk factors are worsened in overweight and obese youth, and early evidence of atherosclerosis manifested by endothelial dysfunction and increased coronary artery calcium is present in a high percentage of overweight youth which predisposes to coronary artery disease (CAD). Numerous psychosocial problems also are increased among overweight and obese youth. However, there are numerous examples in the scientific literature of successful approaches to the prevention and management of overweight and obesity in the world population. Increased physical activity is a potential method to reduce obesity.

Overweight and obesity lead to adverse metabolic effects on hypertension, hypercholesterolemia, hypertriglyceridemia and insulin resistance. Some confusion of the consequences of obesity arise because researchers have used different BMI cut-offs, and because the presence of many medical conditions involved in the development of obesity may confuse the effects of obesity itself. The non-fatal, but debilitating health problems associated with obesity include respiratory difficulties, chronic musculoskeletal problems, skin problems and infertility. Complications of obesity are: CVD diseases; conditions associated with insulin resistance such as type 2 diabetes; certain types of cancers, especially the hormonally related and large-bowel cancers; and gallbladder disease. The risk of developing Type 2 diabetes and hypertension rises steeply with increase in obesity. Confined to older adults for most of the 20th century, this disease now affects obese children even before puberty. Approximately 85% of people with diabetes are type 2, and of these, 90% are obese or overweight. Obesity is increasingly becoming a problem in the developing world. In 1995, the Emerging Market Economies had the highest number of diabetics. If current trends continue, India and the Middle Eastern crescent will have taken over by 2025.Large increases would also be observed in China, Latin America and the Caribbean, and the rest of Asia. Increase in BMI also increases the risks of cancer of the breast, colon, prostate, endometrium, kidney and gallbladder. Chronic overweight and obesity contribute significantly to osteoarthritis, a major cause of disability in adults. Although obesity should be considered a disease in its own right, it is also one of the key risk factors for other chronic diseases together with smoking, high blood pressure

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and high blood cholesterol. In the analyses carried out for World Health Report 2002,

approximately 58% of diabetes and 21% of CAD and 8-42% of certain cancers globally were

attributable to a BMI above 21 kg/m2.

While overweight and obesity are important risk factors of death due to cardiovascular disease(CVD) and diabetes, underweight predisposes deaths due to infections. In a recent study, Vargova et al (3), examined the association of body mass index(BMI) with causes of deaths among urban decendents in India. For the period 1999-2001, the authors studied the randomly selected records of death of 2222 (1385 men and 837 women) decedents, aged 25-64 years, out of 3034 death records overall from the records at Municipal Corporation, Moradabad.(Tables 1,2). All the families of these decendents could be contacted individually to find out the causes of death, by scientist/doctor administered, informed consented, verbal autopsy questionnaire, completed with the help of the spouse and local treating doctor practicing in the appropriate health care region.Clinical data and causes of death were assessed by a questionnaire based on available hospital record and verbal autopsy questionnaire, suggested by WHO. Decendents were classified in to underweight, normal weight, overweight and obese based on new criteria of WHO and International College of Nutrition. The association of BMI with causes of death was calculated by Mantel-Haesnzel Chi square test. Majority of the decendents (n=792,35.6%) (men 31.1%,n=431; and women 43.1%,n=361) had normal BMI of 18.5-22.9Kg/m2.The prevalence of underweight victims was 14.2%(n=315), overweight 29.4%(n=654)and obese 20.8%(n=461).There was an overall increase in risk factors; diabetes mellitus, hypertension, and CAD among overweight and obese victims based on BMI criteria, and the trend was significant. However, tobacco intake showed nonsignificant trend, highest in the underweight victims, without significant differences in the other categories of BMI. BMI was positively associated with significant rising trend in the prevalence of circulatory causes of death, both among men and women. Infections and cancers as the cause of death were inversely associated with increase in BMI among both men and women. Injury and miscellaneous causes of death showed no association with BMI among men whereas among women, miscellaneous causes of death were positively and significantly associated with BMI. No such association was noted for injury with BMI among women. Among circulatory causes of death, 25.0%(n=108) of the victims had normal BMI (18.5-22.9Kg/m2), which was because of victims dying due to rheumatic heart diseases and heart failure, where lower BMI may be the result of these diseases. The conclusion was that overweight(>23Kg/m 2) and obesity(>25Kg/m 2) are important determinant of mortality due to circulatory diseases and underweight due to infections. Those decendents dying of heart failure, rheumatic heart disease and cancers, may have underweight during the deaths, similar to those dying of infections, as a result of the complication of the disease rather than cause of the deaths. Larger studies would be necessary to demonstrate the association of BMI with causes of death in India.

CAUSES OF OBESITY:

The rising epidemic reflects the profound changes in society and in behavioural patterns of communities over recent decades. While genes are important in determining a person's susceptibility to weight gain, energy balance is determined by calorie intake and physical activity. Thus societal changes and worldwide nutrition transition are driving the obesity epidemic. Economic growth, modernization, urbanization and globalization of food markets are just some of the forces thought to underlie the epidemic. As incomes rise and populations become more urban, diets high in complex carbohydrates give way to more varied diets with a higher proportion of fats, saturated fats and sugars. At the same time, large shifts towards less physically demanding work have been observed worldwide. Moves towards less physical activity are also found in the

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increasing use of automated transport, technology in the home, and more passive leisure pursuits.

The distribution of BMI is shifting upwards in many populations. And recent studies have shown

that people who were undernourished in early life and then become obese in adulthood, tend to

develop conditions such as high blood pressure, CAD and diabetes at an earlier age and in more

severe form than those who were never undernourished.

DEFINITIONS OF OBESITY:

The prevalence of overweight and obesity is commonly assessed by using body mass index (BMI), defined as the weight in kilograms divided by the square of the height in metres (kg/m2 ). A BMI over 25 kg/m2 is defined as overweight, and a BMI of over 30 kg/m2 as obese. These markers provide common benchmarks for assessment, but the risks of disease in all populations can increase progressively from lower BMI levels. Adult mean BMI levels of 22-23 kg/m2 are found in Africa and Asia, while levels of 25-27 kg/m2 are prevalent across North America, Europe, and in some Latin American, North African and Pacific Island countries. BMI increases amongst middle-aged elderly people, who are at the greatest risk of health complications. In countries undergoing nutrition transition, overnutrition often co-exists with undernutrition. People with a BMI below 18.5 kg/m2 tend to be underweight. In Asia, a BMI more than 23 may be considered to have overweight because majority of the subjects above this limit develop central obesity (1). The Indian Consensus Group made this advice in 1996 (11) and a similar consensus was suggested by an Asia Pacific Expert Group from WHO in 2000 (12) and now also by the International College of Cardiology and the The Tsim Tsoum Institute (17)

REGULAR PHYSICAL ACTIVITY, WELLBEING AND HEATH:

Recent studies indicate that the effects of physical activity on biomarkers of health and clinical outcome are as good as of low w-6/w-3 ratio diet (16-23). Moderate physical activity can influence all the biomarkers of health and provide protection from non-communicable diseases (2231). Sofi et al (22) performed a meta-analysis in 18 prospective cohort studies involving a total population 500,000 subjects who were evaluated for physical activity performed during leisure time. This study showed that physical activity of moderate intensity was significantly associated with a decrease of developing CAD by 22% which is of great interest. This beneficial effect has been observed after the exclusion of activity of categories of higher intensity that are found only among small number of subjects in the general population. In the Harvard Alumini study (24) by Paffenberger et al, risk of first CAD was found to be related inversely to energy expenditure reported by 16,936 male alumni, aged 35-74 years. Of these male alumini, 572 developed CAD in 117,680 person-years of follow-up. Stairs climbed, blocks walked, strenuous sports played, and a composite physical activity index all were beneficial against risk of CAD. Men with index below 2000 kilocalories per week were at 64% higher risk than classmates with higher index. Adult exercise was independent of other influences on CAD risk, and peak exertion as strenuous sports play enhanced the effect of total energy expenditure. Notably, alumni physical activity supplanted student athleticism assessed in college 16-50 years earlier. If it is postulated that varsity athlete status implies selective cardiovascular fitness, such selection alone is insufficient to explain lower CAD risk in later adult years. Ex-varsity athletes retained lower risk only if they maintained a high physical activity index as alumni.

Recently Singh et al (1) in a cross sectional survey among 6940 subjects from five Indian cities reported that physical activity was inversely associated with risk of central obesity.

The Journal of scientific articles “Health & education millennium”

Журнал научных статей «Здоровье и образование в XXI веке» №1 2010 том 12

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Oguma et al conducted a study (25) to review and quantify the dose-response relationship of

physical activity in initially healthy women on cardiovascular disease (CVD) outcomes, especially CAD and stroke, and to assess the minimum amount of activity to reduce CVD risk. Studies were included if they provided data on women; assessed activity (exposure) as either a continuous variable or a categorical variable with three or more levels, and CVD outcome; and provided information on relative risks and 95% confidence intervals. Studies were reviewed, abstracted, and rated for quality by each author. Thirty articles met the inclusion criteria. When studies were combined according to relative activity levels, the RRs showed a dose-response relationship for CAD (RR=1 [reference], 0.78, 0.53, 0.61, respectively; p for trend was <0.0001 for studies with four activity levels, n =5); for stroke (RR=1 [reference], 0.73, 0.68, p for trend was <0.0001 for studies with three activity levels, n =7); and for overall CVD (RR=1 [reference], 0.82, 0.78, p for trend was <0.0001 for studies with three PA levels, n =6). When studies were combined by absolute walking amount, even 1 hour/week walk was associated with reduced risk of CVD outcome. In brief, physical activity was associated with reduced risk of CVD among women in a dose-response fashion. Inactive women benefited by even slightly increasing their activity by walking one hour per week and even more from additional physical activity.

Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. The INTERHEART Study (26) established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15152 cases and 14820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction. This showed that the implementation of regular physical activity is able to give more than 40% protection with respect to acute myocardial infarction, independently of the country and of socio-environmental conditions.

Physical activity has been associated with reduced blood pressure in observational epidemiologic studies and individual clinical trials (27,28). This meta-analysis of randomized, controlled trials was conducted to determine the effect of aerobic exercise on blood pressure (27).

The Journal of scientific articles “Health & education millennium”

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Main sources were english-language articles published before September 2001. 54 randomized,

controlled trials (2419 participants) whose intervention and control groups differed only in aerobic

exercise. Using a standardized protocol and data extraction form, three of the investigators

independently abstracted data on study design, sample size, participant characteristics, type of

intervention, follow-up duration, and treatment outcomes. In a random-effects model, data from

each trial were pooled and weighted by the inverse of the total variance. Aerobic exercise was

associated with a significant reduction in mean systolic and diastolic blood pressure (-3.84 mm Hg

[95% CI, -4.97 to -2.72 mm Hg] and -2.58 mm Hg [CI, -3.35 to -1.81 mm Hg], respectively). A

reduction in blood pressure was associated with aerobic exercise in hypertensive participants and

normotensive participants and in overweight participants and normal-weight participants. Aerobic

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exercise reduces blood pressure in both hypertensive and normotensive persons. An increase in

aerobic physical activity should be considered an important component of lifestyle modification for

prevention and treatment of high blood pressure. In experimental studies, a moderate physical

activity not causing ventricular hypertrophy in patients with myocardial infarction may provide

protection against ischemic reperfusion. The gene expression profile indicated that they may be

responsible for beneficial effects in exercise trained rats.

In another study (21), Kelley et al used the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in adults 50 years of age and older. Twenty-eight outcomes representing 1427 subjects (806 exercise, 621 control) were available for pooling. Random-effects modeling yielded statistically significant improvements of 1.1%, 5.6%, 2.5%, and 7.1%, respectively, for total cholesterol (mean +/- SEM in mg/dL, -3.3+/-1.7; 95% confidence interval [CI], -6.5 to -0.02; p=0.05), high-density lipoprotein cholesterol (2.5+/-1.0; 95% CI, 0.74.4; p=0.01), low-density lipoprotein cholesterol (-3.9+/-1.9; 95% CI, -7.7 to -0.08; p=0.05), ratio of total cholesterol to high-density lipoprotein cholesterol (-0.8+/-0.2; 95% CI, -1.2 to -0.4; p<0.001), but not triglycerides (-7.0+/-3.6; 95% CI, -14.0 to 0.1; p=0.06). After conducting sensitivity analyses, only the improvements in high-density lipoprotein cholesterol and the ratio of total cholesterol to high-density lipoprotein cholesterol remained statistically significant (p<0.05 for both). It was concluded that aerobic exercise increases high-density lipoprotein cholesterol and decreases the ratio of total cholesterol to high-density lipoprotein cholesterol in older adults, within 3 months of follow up. Majority of the studies indicate that moderate physical activity can cause significant decline in CVD risk factors, apart from deaths, stoke and reinfarction rates.

In a randomized, single blind trial, 621 high risk patients were assigned either a Indo-Mediterranean style diet (n=310) or control diet (n=311) similar to National Cholesterol Education Program step 1 diet (29, 30). After 12 weeks of follow up intervention group received 400-500g per day of fruits, vegetables and nuts and whole grains with high w-3 fatty acids, antioxidants, amino acids, vitamins and minerals compared to control group receiving almost half of these foods and nutrients (29). There was a significant reduction in the blood pressures, blood glucose and blood lipoproteins after 12 week of treatment. Intervention group also did increased physical and yogic exercises compared to control group after 12 weeks on Mediterranean style diet (30). The overall score of diet and exercise after 24 week was significantly greater in the intervention group than control group. There was a significant decline in total cholesterol (13.3%), LDL cholesterol (16.9%) and triglycerides (19.2%), fasting blood glucose (19.9%) and blood pressures (11.5/6.2 mm Hg) in the intervention group compared to baseline and changes in the control group. The effect of exercise on the decrease in risk factors was additive to dietary changes. Within group A, overall score for diet and exercise was greater in one subset of 116 patients in the intervention group which had maximum lifestyle changes. A separate analysis of data in this sub-group revealed a greater decline

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i n risk factors including in biomarkers compared to risk factor changes in the remaining 194

patients with lower overall score as well as changes in the control group.

Although preventive drug therapy is a priority after acute coronary syndrome (ACS), less is known about adherence to behavioral recommendations; diet and lifestyle changes after ACS on risk of future outcome (31). The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio,

0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise. In the JUPITER study (32, 33), the substantial reductions in LDL and hsCRP were not translated into significant reduction in cardiovascular deaths in the intervention group compared to placebo group( 12 vs 12 deaths). The case fatality rate due to MI was greater in the rosuastatin group compared to placebo group( 29.0% vs 8.8%), n= 9 vs 6) after 1.9 years of treatment which indicated that this statin might increase rate of infarction and deaths if given for longer follow up.It is possible that in the JUPITER study (32,33), diet and lifestyle changes were not advised or not followed by the patients resulting in to no benefit in hard end points. However, the authors reported that participants who achieved an LDL cholesterol level of below 1.8 mmol/l (70 mg/dl) had a 55% reduction in CVD events and those who achieved a hsCRP reduction of below 2 mg/l, a 62% reduction, which is slightly greater benefit compared to LDL reduction. In patients who achieved the more stringent target of a LDL cholesterol level of below 1.8 m mol/l (70 mg/dl) and a hsCRP reduction of below 1 mg/l had a 79% reduction in CVD events. However, the beneficial effect was only on soft end points with no reduction in cardiovascular deaths and hence the conclusions made by the authors may be just to oblige the industry (32,33). It seems that we have forgotten the simple principle of clinical medicine that it is the cause of the disease which should be treated, rather than a hypothetical biomarker; LDL-cholesterol or hsCRP.

EFFECT OF PHYSICAL ACTIVITY ON BIOMARKERS:

Physical activity can reduce circulating levels of C-reactive protein, IL-6, TNF-alpha, hyperglycemia, hyperuricemia, hyperinsulinemia, parameters of oxidative stress, total and low density lipoprotein cholesterol, triglycerides, very low density lipoprotein cholesterol as well as mobilization of endothelial progenitor cells. Physical activity also reduces proinflammatory cytokines and transcription factors and increases anti-inflammatory cytokines. Kirwan et al conducted a study in elderly subjects above 65 years, to evaluate the effect of vigorous endurance exercise training; approximately 80 % of maximal heart rate, glucose stimulated insulin response and glucose disposal rate using the hyperglycemic clamp procedure with normal glucose tolerance (34). The result indicated that VO2 max increased approximately 23% and plasma insulin level during hyperglycemia at 180mg/dl was significantly lower after the exercise program compared to

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baseline level (26 vs 36uU/ml). Similar beneficial effects of exercise have been observed among

postmenopausal women (35), nonobese type 2 diabetes mellitus, obese men, healthy young and

middle aged men with insulin resistance(36-39) and in coronary patients (40).

CAN EXERCISE DECREASE INFLAMMATION?

Spare time physical activity or exercise has anti-inflammatory effects (41). The relation between exercise and inflammation and the relevance of low-grade systemic inflammation in CAD, hypertension, type 2 diabetes mellitus, obesity and other non-communicable diseases appears to be important. It is known from 6th decade that men who are physically active have a lower incidence of CAD in middle age than men who are physically inactive. It was also emphasized that if the CAD occurs in those who are physically active, it tends to be relatively less severe or relatively benign (42). Since CAD is increasingly seen as an inflammatory process, it is reasonable to hypothesize that physical activity reduces risk of CAD by reducing or preventing inflammation. The Third National Health and Nutrition Examination Survey, included 3,638 apparently healthy US men and woman, 40 years and older. This study showed that more frequent physical activity was associated with lower C-reactive protein (CRP), white blood cell count, and fibrinogen levels (43). It is possible that more frequent physical activity is independently associated with lower odds of having elevated inflammation levels among apparently healthy US adults 40 years and older, indicating that the association between physical activity and CAD risk may be mediated by anti-inflammatory effects of regular physical activity. Regular exercise also improved endothelial vasodilator function and left ventricular diastolic function as well as reduced total and abdominal fat (44). The benefit in body composition may mediate improvements in insulin sensitivity and blood pressure and may improve endothelial vasodilator function, indicaing that the benefits of exercise training go beyond the recognized benefits of glycemic control and blood pressure reduction.

In chronic heart failure, an abnormal expression of cellular adhesion molecules and cytokines and endothelial dysfunction are indicators of inflammation which may impaire exercise capacity seen among these patients. In patients with stable chronic heart failure (ischemic heart failure, dilated cardiomyopathy,( New York Heart Association class II and III, ejection fraction: 24+=2% ) before and after a 12-week program of physical training performed in a randomized crossover design fashion showed a significant reduction in serum GM-CSF (28+_2 versus 21+_ 2pg/mL ,P<0.001), MCP-1(192+_ 5 versus 174 +_ 6pg/mL, P < 0.001), sICAM-1 (367+_ 31versus 314+_ 29 ng/mL, P< 0.001), and sVCAM -1 (1,247+_ 103 versus 1,095 +_ 100 ng/mL, P < 0.01), as well as a significant increase in peak oxygen consumption (14.6+_ 0.5 versus 16.5+_ 0.5mL/kg -1/min-1, P < 0.005) (45). In addition, a significant correlation was found between the training -induced improvement in peak oxygen consumption and the percentage reduction in soluble adhesion molecules sICAM-1 (r = -0.72, P < 0.01) and sVCAM -1 (r = -0.67, P < 0.02). It seems that physical training suppresses peripheral inflammation and cross-talk leading to improvement in exercise tolerance in chronic heart failure possibly due to the ability of exercise to attenuate the inflammatory process. In a further study, Troseid et al (46), performed an unmasked randomized 2 into 2 factorial trial of 12 week duration on the effects of exercise and the HMG-CoA reductase inhibitor pravastatin on peripheral markers of inflammation in subjects with metabolic syndrome. There was a significant reduction in monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in the combined exercise groups as compared to the combined non-exercise groups. Change in MCP-1 were significantly correlated to changes in visceral fat (r = 0.41, P = 0.02). It is possible that the beneficial effects of exercise are due to its ability to suppress the inflammatory process. Since inflammation plays a crucial role in the atherosclerotic and thrombotic process, and MCP-1 and IL-8 participate in the pathogenesis of atherosclerosis, these results also suggest that

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atherosclerosis is an inflammatory process and that exercise by virtue of its anti-inflammatory effect

can prevent athero-thrombosis.

Panagiotakos et al. (47) randomly recruited 1,524 adult men and 1,.518 woman in the ATTICA study, without any evidence of cardiovascular disease, stratified by age and gender. Multivariate statistical analysis after adjustment for gender, age, smoking habits, body mass index, total cholesterol, blood glucose, and systolic and diastolic blood pressure levels showed that participants devoted to high physical activity (>7 kcal/min expended ) had 29% lower levels of C-reactive protein, 19% lower levels of white blood cell counts, 22% lower concentrations of amyloid-A, 20% lower levels of TNF-a, 32% lower levels of interleukin-6, and 11% lower levels of fibrinogen (all P < 0.05) as compared to those who were devoted to sedentary life. These results reinforce the idea that the adoption of a physically active lifestyle suppresses the inflammation process in healthy individuals. Kondo et al. (48) recruited 50 subjects who did not have diabetes mellitus and made them perform a multistep treadmill exercise test to obtain the maximum oxygen uptake when assessed by computerized breath-by-breath analysis. They also measured the homeostasis modal insulin resistance index (HOMA-R; Fasting glucose + fasting insulin/405) as on index of insulin resistance. The subjects’ body weight , body mass index, subcutaneous fat thickness, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels were noted. Multivariate analysis revealed that hs-CRP was significantly correlated with HDL-cholesterol, uric acid, gamma-glutamyl transpeptidase, and maximum oxygen uptake, suggesting that the development of exercise habits increased the maximum oxygen uptake and that an elevated maximum oxygen uptake decreased HOMA-R and reduced the inflammatory marker CRP. These results led to the suggestion that the exercise habits plays an important role in suppressing inflammatory events and in the primary prevention of CAD.

While strenuous exercise can be responsible for a short-term inflammatory response and increase in hs-CRP level, but exercise training and regular physical activity are anti-inflammatory, homeostatic, and reduce hs-CRP levels, improving endothelial function. There is reduced risk of atherosclerosis in the various vascular beds: coronary, cerebral, peripheral vascular, pulmonary, and renal (49-52). Regular exercise reduces overweight and obesity, especially abdominal obesity as well as improved back pain in automotive workers (53). It also has a direct reducing effect on elevated blood pressure (54); reduces activation of leukocytes and platelets (55, 56), partly by enhancing L-arginine-ntric oxide metabolism; and suppresses tumor growth in both experimental animals and humans( 57-61). Further studies demonstrated that exercise decreased the levels of pro-inflammatory cytokines CRP, IL-6, and TNF-alpha as well as simultaneously enhanced the concentrations of anti-inflammatory cytokines IL-4, IL-10, and tumor growth factor-B (TGF-B) compared to controls. IL-4, IL-10, and TGF-B are anti-inflammatory as well as suppress the production of pro-inflammatory cytokines IL-1, IL-2, and TNF-alpha (62,63). The increase in Mm-SOD activity in response to exercise-induced free radical generation, suggest that under certain circumstances free radicals may have beneficial actions, especially when they are produced in response to physiological stimulus such as exercise. Pro-inflammatory cytokines can also enhance free radical generation as natural mechanism of adaptation. However, administration of antibodies to TNF-alpha and IL-1 abolished the cardioprotective action of exercise and activation of Mn-SOD. This suggests that exercise-induced increase in the production of pro-inflammatory cytokines augments the production of free radicals that, in turn, enhance Mn-SOD activity. The enhanced Mn-SOD activity could be ultimately responsible for the cardioprotective action of exercise. The circulating levels of extracellular SOD may be lower in subjects with CAD. SOD also enhances the half-life of nitric oxide (NO), a potent vasodilator, platelet antiaggregator, and antiatherosclerotic

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molecule. Supplementation of antioxidant vitamin E counteract the beneficial effects of exercise,

suggesting that stimulation of endogenous antioxidants such as Mn-SOD is more critical to the

beneficial actions of the exercise and this benefit can not be initiated by exogenous therapy with

antioxidants. It seems that regular physical activity ensures adequate expression of endogenous

antioxidants as well as anti-inflammatory cytokines and provide cardioprotective actions (57-62).

There is evidence that low grade systemic inflammation can predispose metabolic syndrome indicating that lack of exercise causing this syndrome may be mediated by inflammation. Exercise is also provides benefit in patients with hypertension, type 2 diabetes, obesity, insulin resistance and CAD because there is low grade systemic inflammation in all these conditions. The protective effects of exercise may be related to a reduction in hyperglycemia, hyperuricemia, IL-

6,CRP and TNF-alpha resulting into improvement in endothelial dysfunction and insulin resistance. The anti-inflammatory activity of exercise can prolong the survival of beta cells of pancreas and enhances their activity for insulin release for prolonged periods. Exercise can also modulate leucocyte and platelet activation and involvement of the transcriptional coactivator PGC1 alpha that is known to regulate multiple aspects of muscle function and dysfunction.

EFFECT OF EXERCISE ON BRAIN FUNCTION AND PSYCHOLOGICAL WELLBEING.

While limited research is available, evidence indicates that physical and mental activity influence the aging process. Human data show that executive functions of the type associated with frontal lobe and hippocampal regions of the brain may be selectively maintained or enhanced in humans with higher levels of fitness (64-67). Similarly enhanced performance is observed in aged animals exposed to elevated physical and mental demand and it appears that the vascular component of the brain response may be driven by physical activity whereas the neuronal component may reflect learning. Recent results have implicated neurogenesis, at least in the hippocampus, as a component of the brain response to exercise, with learning enhancing survival of these neurons (64-69). Non-neuronal tissues also respond to experience in the mature brain, indicating that the brain reflects both its recent and its longer history of experience. Preliminary measures of brain function hold promise of increased interaction between human and animal researchers and a better understanding of the substrates of experience effects on behavioral performance in aging.Van Praag et al in 2009 (64), also emphasized that exercise has profound benefits for brain function. Physical activity improves learning and memory in humans and animals. Moreover, an active lifestyle might prevent or delay loss of cognitive function with aging or neurodegenerative disease. Recent research indicates that the effects of exercise on the brain can be enhanced by concurrent consumption of natural products such as omega fatty acids or plant polyphenols. The potential synergy between diet and exercise could involve common cellular pathways important for neurogenesis, cell survival, synaptic plasticity and vascular function. Optimal maintenance of brain health might depend on exercise and intake of natural products.

Cotman et al in 2007 (65), indicated that exercise targets many aspects of brain function and has broad effects on overall brain health. The benefits of exercise have been best defined for learning and memory, protection from neurodegeneration and alleviation of depression, particularly in elderly populations. Exercise increases synaptic plasticity by directly affecting synaptic structure and potentiating synaptic strength, and by strengthening the underlying systems that support plasticity including neurogenesis, metabolism and vascular function. Such exercise-induced structural and functional change has been documented in various brain regions but has been best-studied in the hippocampus -the focus of this review. A key mechanism mediating these broad benefits of exercise on the brain is induction of central and peripheral growth factors and growth

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factor cascades, which instruct downstream structural and functional change. In addition, exercise

reduces peripheral risk factors such as diabetes, hypertension and cardiovascular disease, which

converge to cause brain dysfunction and neurodegeneration. A common mechanism underlying the

central and peripheral effects of exercise might be related to inflammation, which can impair

growth factor signaling both systemically and in the brain. Thus, through regulation of growth

factors and reduction of peripheral and central risk factors, exercise modulates brain function.

Chronic swimming training and phytotherapeutic supplementation are assumed to alleviate oxidative damage, and support cell survival in the brain. Toldy et al studied ( 66 )he effect of forced, chronic swimming training, and enriched lab chow containing 1% (w/w) dried nettle (Urtica dioica) leaf were investigated for oxidative stress, inflammation and neurotrophic markers in Wistar rat brains.

The rats were divided into groups subjected to swimming training (6 weeks) or to nettle supplementation (8 weeks) or to a combination of these two treatments. The level of oxidative stress was measured by electron spin resonance (EPR), and by the concentration of carbonylated proteins. Nettle supplementation resulted in a decreased concentration of free radicals in both cerebellum and frontal lobe. Swimming, however, did not influence significantly the oxidative damage nor was it reflected in the carbonyl content. The protein content of nerve growth factor (NGF), and brain-derived neurotrophic factors (BDNF) was evaluated by E-Max ImmunoAssay in the cerebellum. No changes occurred either with exercise or nettle diet treatments. On the other hand, nuclear factor kappa B (NF-kB) binding activity to DNA increased with the combined effect of swimming training and nettle diet, while the activator protein1 (AP-1) DNA binding activity showed a more profound elevation in the nettle treated animals. The amount of c-Jun decreased by swimming training. In conclusion, the results suggest that both exercise and nettle influenced physiological brain functions. Nettle supplementation reduces the free radical concentration and increases the DNA binding of AP-1 in the brain. Nettle was found to be an effective anti oxidant and possible antiapoptotic supplement promoting cell survival in the brain. Exercise, as a downregulator of c-Jun and in combined group as an upregulator of NF-kB, may play also a role in antiapoptotic processes, which is important after brain injury. Radak et al (67) tested how swimming training (T) (8 week, 5 times/week, 2 h/day), and detraining affects brain functions and oxidative stress markers in rat brain. The free radical concentration, measured by electron paramagnetic resonance, decreased in brain of T and DT rats compared to controls (C). The level of brain-derived neurotrophic factor (BDNF) increased as a result of training, but decreased below the control level after 6 weeks of detraining. In addition, the concentration of nerve growth factor (NGF) also declined with detraining. The passive avoidance test was used to assess the memory of rats, and training-induced improvement was observed but the enhancement disappeared with detraining. When the content of mitochondrial electron transport complexes, as a potent free radical generator, was evaluated by the blue native gel method, no significant alterations were observed. The repair of nuclear and mitochondrial 8-oxodeoxyguanosine, as measured by the activity of OGG1, showed no significant difference. Therefore, the results suggest that regular exercise training improves memory, decreases the level of reactive oxygen species, and increase the production of BDNF and NGF. On the other hand, it appears that the beneficial effects of training are reversible in the brain, since detraining down-regulates the neurotrophin level, and memory. It is suggested that exercise training is more likely to beneficially effect the production of reactive oxygen species and the related oxidative damage.

While it is well established that exercise can improve cognitive performance, it is unclear how long these benefits endure after exercise has ended (68,69). Accordingly, the effects of

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voluntary exercise on cognitive function and brain-derived neurotrophic factor (BDNF) protein

levels, a major player in the mechanisms governing the dynamics of memory formation and storage,

were assessed immediately after a 3-week running period, or after a 1-week or 2-week delay

following the exercise period. All exercised mice showed improved performance on the radial arm

water maze relative to sedentary animals. Unexpectedly, fastest acquisition (fewest errors and

shortest latency) occurred in animals trained following a 1-week delay, while best memory

performance in the probe trial was observed in those trained immediately after the exercise period.

Assessment of the time course of hippocampal BDNF availability following exercise revealed

significant elevations of BDNF immediately after the exercise period (186% of sedentary levels)

and at 1 and 2 weeks after exercise ended, with levels returning to baseline by 3-4 weeks. BDNF

protein levels showed a positive correlation with cognitive improvement in radial water maze

training and with memory performance on day 4, supporting the idea that BDNF availability

contributes to the time-dependent cognitive benefits of exercise revealed in this study. Overall, this

novel approach assessing the temporal endurance of cognitive and biochemical effects of exercise

unveils new concepts in the exercise-learning field, and reveals that beneficial effects of exercise on

brain plasticity continue to evolve even after exercise has ended.

In brief, long-term strategis are necessary for the effective weight management for individuals and groups at risk of developing obesity. These include prevention, weight maintenance, management of co-morbidities and weight loss. They should be part of an integrated, multi-sectoral, population-based approach, which includes environmental support for healthy diets and regular physical activity. Encouragement and regulation of increased physical activity at work place and home and promotion of sports in the schools are important to create awareness about usefulness of this approach. There is a need to create supportive population-based environments through public policies that promote the availability and accessibility of a variety of low-fat, high-fibre foods, and that provide opportunities for physical activity. Promoting healthy behaviours to encourage, motivate and enable individuals to lose weight by: - eating more fruit and vegetables, as well as nuts and whole grains; engaging in daily moderate physical activity for at least 30-45 minutes; cutting the amount of fatty, sugary foods in the diet; moving from saturated animal-based fats to unsaturated vegetable-oil based fats rich in w-3 and monounsaturated fatty acids are important. Mounting a clinical response to the existing burden of obesity and associated conditions through clinical program and staff training to ensure effective support for those affected to lose weight or avoid further weight gain.

Acknowledgements are due to International College of Nutrition and International College of Cardiology for support to prepare this article.

There is no conflict of interest by any of the authors.

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Table 1:Risk factors in relation to body mass index. (modified from reference 3)

Body Mass Index n Diabetes Hypertension CAD Tobacco

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(Kg/m2) mellitus >140/90 mmHg intake

Men

BMI <18.5 207 6 (2.9) 4 (1.9) - 110 (53.1)

BMI 18.5-22.9 431 31 (7.2) 66 (15.3) 9 (2.1) 187 (43.4)

BMI 23-24.9 470 42 (8.9) 202 (42.9) 51 (10.8) 200 (42.5)

BMI 25-29.9 266 28 (10.5) 180 (67.6) 69 (25.9) 125 (46.9)

BMI >=30 11 3 (27.2) 6 (54.5) 3 (27.2) 1 (9.0)

Total 1385 110 (7.9) 458(33.1) 132 (9.5) 623 (45.0)

Mantel-Haenszel X2 13.3 21.8 12.2 8.1

P Value <0.001 <0.001 <0.02 >0.05

Women

BMI <18.5 108 - 2 (1.8) - 22 (20.3)

BMI 18.5-22.9 361 9 (2.5) 43 (11.9) 2 (0.5) 56 (15.5)

BMI 23-24.9 184 20 (10.8) 95 (51.6) 12 (6.5) 26 (14.1)

BMI 25-29.9 174 26 (14.9) 105 (60.3) 26 (14.9) 20 (11.5)

BMI >=30 10 3 (30.0) 6 (60.0) 2 (20.0) 1 (10.0)

Total 837 58 (6.9) 251 (30.0) 42 (5.0) 125 (14.9)

Mantel-Haenszel X2 16.6 22.8 10.9 7.5

P Value <0.001 <0.001 <0.05 >0.05

Values are number and %,BMI=body mass index,CAD=Coronary artery disease.

Table 2: Causes of death in relation to body mass index.(modified from Vargova et al Ref

3).

Body Mass Index (Kg/m2) Infections Circulatory Malignant Injury Miscellaneous

Men(%)

BMI (<18.5) (n=207) 180 (86.9) 2 (0.9) 14 (6.7) 6 (2.9) 5 (2.4)

BMI (18.5-22.9) (n=431) 248 (57.5) 108 (25.0) 28 (6.5) 25 (5.8) 22 (5.1)

BMI (23-24.9) (n=470) 146 (31.0) 135 (28.7) 25 (5.3) 114 (24.2) 50 (10.6)

BMI (25-29.9) (n=266) 35 (13.1) 155 (58.3) 10 (3.7) 52 (19.5) 14 (5.2)

BMI (<30) (n=11) - 6 (54.5) - 2 (1.8) 3 (27.2)

Total (n=1385) Mantel-Haenszel X 2 P value 609(43.9) 23.7 <0.001 406(29.3) 18.8 <0.001 77(5.5) 8.7 <0.05 199(14.3) 7.6 <0.05 94(6.8) 6.1 >0.05

Women(%)

BMI (<18.5) (n=108) 75 (69.4) 5 (4.6) 16 (14.8) 10 (9.2) 2 (1.8)

The Journal of scientific articles “Health & education millennium”

Журнал научных статей «Здоровье и образование в XXI веке» №1 2010 том 12 ________________________— —_______________________________________________________

BMI (18.5-22.9) (n=361) 180(49.8) 64 (17.7) 27 (7.5) 58 (16.0) 32 (8.8)

BMI (23-24.9) (n=184) 40 (21.7) 70 (38.0) 10 (5.4) 24 (13.0) 40 (21.7)

BMI (25-29.9) (n=174) 11 (6.3) 97 (55.7) 1 (0.6) 18 (10.3) 47 (27.0)

BMI (>30) (n=10) - 4 (40.0) - 4 (40.0) 2 (20.0)

Total (n=837) 306(36.5) 240(28.6) 54(6.4) 114(13.6) 123(14.7)

Mantel-Haenszel X2 22.5 18.5 8.8 6.2 9.2

P value <0.001 <0.001 <0.05 >0.05 <0.05

Values are number (%). BM I=body mass index

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