*Medical Faculty of the Mustafa Kemal University, Antakya, Assistant Professor of Internal Medicine, M.D.
**Medical Faculty of the Mustafa Kemal University, Antakya, Associated Professor of Internal Medicine, M.D.
***Medical Faculty of the Mustafa Kemal University, Antakya, Assistant Professor of Family Medicine, M.D.

Correspondence
Mehmet Rami Helvaci, M.D.
Hospital of the Mustafa Kemal University
31100, Antakya, Turkey
e-mail: mramihelvaci@hotmail.com
Tel: +903262140649
Fax: +903262148214

INTRODUCTION

Aging alone may be one of the major disorders of human beings since it comes with many associated disorders. First of all, it has been reported in many studies that aging is strongly associated with weight excess (1,2). Secondly, chronic inflammation is frequently observed with aging, and is considered as a major risk factor for age-related chronic disorders such as atherosclerosis, hypertension (HT), type 2 diabetes mellitus (DM), and cancers (3-5). The chronic inflammatory status is characterized by increased circulatory levels of inflammatory parameters, such as tumor necrosis factor-alpha, interleukin-6, and C-reactive protein, and there is a close relationship between these inflammatory parameters and insulin sensitivity, so prevalence of glucose intolerance increases with age (6). The insulin resistance may also be involved in age-related muscular loss since its anabolic action is essential for protein gain. For example, insulin deficiency as in type 1 DM is associated with a rapid and major muscular loss (7). Beside that many structural and functional modifications occur in skeletal muscle during aging, and these defects lead to the impairment in muscular strength, contractile capacity, and performance (8,9). Similarly, the human heart undergoes many functional changes with advancing age, including increased prevalence of rhythmic abnormalities, decreases in myocyte numbers, accumulation of collagen and fibrosis, and decreases in stress-induced cardiac function, all of which cause an age-related increase in the risk of coronary heart disease (CHD) and other cardiac pathologies (10). We tried to understand here of there are or not some breaking points of aging for excess weight, DM, HT, dyslipidemia, and CHD-like major health problems.

MATERIAL and METHODS

The study was performed in the Internal Medicine Polyclinic of the Dumlupinar and Mustafa Kemal Universities on routine check up patients between August 2006 and September 2007. Consecutive patients at and above the age of 20 years were taken into the study to permit growth of weight in youngers. Their medical histories including smoking habits, HT, DM, dyslipidemia, and already used medications were learnt, and a routine check up procedure including fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and an electrocardiography was performed. Current daily smokers, at least for a period of last 12 months, and cases with a history of at least five packs/years smoked, were included as smokers. Patients with devastating illnesses, including type 1 DM, malignancies, acute or chronic renal failure, chronic liver diseases, hyper- or hypothyroidism, and heart failure were excluded to avoid their possible effects on weight. Body mass index (BMI) of each case was calculated by the measurements of the same physician in stead of verbal expressions. Weight in kilograms is divided by height in meters squared, and underweight is defined as a BMI of lower than 18.5, normal weight as 18.5-24.9, overweight as 25.0-29.9, and obesity as a BMI of 30.0 kg/m(2) or greater (11). Cases with an overnight FPG level of 126 mg/dL or greater on two occasions or already taking anti-diabetic medications were defined as diabetics (11). An oral glucose tolerance test with 75-gram glucose was performed in cases with a FPG level between 110 and 126 mg/dL, and diagnosis of cases with a 2-hour plasma glucose level 200 mg/dL or higher is DM (1). Additionally patients with dyslipidemia were detected, and we used the National Cholesterol Education Program Expert Panel's recommendations for defining dyslipidemic subgroups (11). Dyslipidemia is diagnosed when LDL-C is 160 or higher and/or TG is 200 or higher and/or HDL-C is lower than 40 mg/dL. Office blood pressure was checked after a 5 minute rest in seated position with a mercury sphygmomanometer on three visits, and no smoking was permitted during the previous 2-hours. A 10-day twice daily measurement of blood pressure at home (HBP) was obtained in all cases, even in normotensives in the office due to the risk of masked HT after 10-minutes of education about proper BP measurement techniques (12). The education included recommendation of upper arm while discouraging wrist and finger devices, using a standard adult cuff with bladder sizes of 12 x 26 cm for arm circumferences up to 33 cm in length and a large adult cuff with bladder sizes of 12 x 40 cm for arm circumferences up to 50 cm in length, and taking a rest at least for a period of 5-minute in the seated position before measurement. An additional 24-hour ambulatory blood pressure monitoring (ABP) was not required due to the equal efficacy of the method with HBP measurement to diagnose HT (13). Eventually, HT is defined as a BP of 135/85 mmHg or greater on HBP measurements (12). A stress electrocardiography was performed in suspected cases, and a coronary angiography was obtained only for the stress electrocardiography positive cases. Eventually, number of cases in each decade was detected, and prevalence of smoking, excess weight, hyperbetalipoproteinemia, hypertriglyceridemia, dyslipidemia, DM, HT, and CHD were compared between the decades. Comparison of proportions was used as the method of statistical analysis.

RESULTS

The study included 1068 cases (628 females and 440 males) totally. Due to the small number of cases in the ninth decade, 20 cases only, they were not included for statistical comparison. There were only 19 (1.7%) cases with underweight and 307 (28.7%) with normal weight, and a very high prevalence 69.4% (742) of cases at and above the age of 20 years had excess weight. When we looked at the prevalence of the above disorders, prevalence of excess weight, hyperbetalipoproteinemia, hypertriglyceridemia, and dyslipidemia showed their most significant progressions in the fourth decade of life (p<0.001 for all). One decade later, DM showed its most significant progression (p<0.001), and two decades later, HT and CHD showed their greatest progressions (p<0.001). So there was a stepwise progression initiating from dyslipidemia and excess weight and terminating with HT and CHD. Interestingly, although all of the disorders continuously increased in prevalence by decades, the prevalence of excess weight decreased in the eighth decade of life, parallel to the decreasing prevalence of hyperbetalipoproteinemia, hypertriglyceridemia, and dyslipidemia, significantly (p<0.05 for all). Another interesting finding of our study, was that prevalence of smoking increased significantly (p<0.001) in the fourth decade parallel to the significantly increasing prevalence of excess weight again, and it remained nearly stable in the rest of life (Table 1).

Table 1: Associated disorders of the study cases

*p<0.05 **p<0.01 ***p<0.001 †Nonsignificant (p>0.05)

DISCUSSION

Although aging alone may be a major disorder of human beings, all of the above disorders cannot solely be explained by aging, and probably excess weight is a major contributing factor of it. Excess weight leads to structural and functional abnormalities of body, and recent studies have revealed that adipose tissue produces biologically active leptin, tumor necrosis factor-alpha, plasminogen activator inhibitor-1, and adiponectin, which are closely related to the development of complications (14). For example, numerous epidemiological studies have indicated that inflammation plays an important role in the pathogenesis of atherosclerosis and thrombosis in the cardiovascular system (15,16), and adipose tissue is involved in the regulation of these cytokines (17). Additionally, individuals with excess weight have an increased circulating blood volume as well as an increased volume of cardiac output, thought to be the result of increased oxygen demand of the extra body tissue. The prolonged increase in circulating blood volume can lead to myocardial hypertrophy and decreased compliance, in addition to the common comorbidity of HT (18). In addition to the HT, the prevalences of high FPG, high serum total cholesterol, and low HDL-C, and their clustering were all raised with increases in BMI (19). Combination of these cardiovascular risk factors eventually leads to the increase in left ventricular stroke with a higher risk of arrhythmias, cardiac failure, and even sudden cardiac death. So the above prospective cohort study showed that elevated BMI is one of the independent risk factors for stroke and CHD (19). Similarly, the incidences of CHD and stroke, especially ischemic stroke, have increased with an elevated BMI in other studies (20). Eventually, the risk of death from all causes including cancers increases throughout the range of moderate and severe weight excess both for men and women in all age groups (21), so it is important in medical terms to specify the excess weight not only as a risk factor but as an obesity disease. As similar results of our study, prevalence of excess weight was 63.6% even in the fourth and it was 87.0% in the seventh decades of life. On the other hand, prevalence of excess weight showed its most significant progression in the fourth decade, parallel to the most significant progressions of hyperbetalipoproteinemia, hypertriglyceridemia, and dyslipidemia in the same decade (p<0.001 for all). Just one decade later, DM showed its most significant progression (p<0.001), and two decades later, HT and CHD showed their greatest progressions (p<0.001). So there was a stepwise progression initiating from dyslipidemia and excess weight and terminating with HT and CHD.

Although excess weight may be a major contributoing factor for the above disorders, it cannot be the sole reason for all of them. As already shown in this study, the decreased prevalences of excess weight in the eighth decade, the prevalences of DM, HT, and CHD continued to increase, and their prevalence reached up to 26.1%, 38.3%, and 24.2% in the eighth decade of life. But as an interesting result of our study, although all the disorders increased in prevalence by decades, the prevalence of excess weight decreased in the eighth decade parallel to the decreasing prevalences of hyperbetalipoproteinemia, hypertriglyceridemia, and dyslipidemia, significantly (p<0.05 for all), indicating the pioneer sign of dyslipidemia for excess weight.

It was shown in some previous studies that smoking cessation usually leads to weight gain and changes in adipose cell metabolism, in particular increases in adipose tissue lipoprotein lipase activity (22,23). This increase in lipoprotein lipase activity may contribute to the increase in body weight associated with smoking cessation. Also, this trend may be due to the inhibitory effect of smoking on appetite. Similar findings were seen in some other studies, (24,25). Whereas in our study, prevalence of smoking increased significantly (p<0.001) in the fourth decade, parallel to the significantly increasing prevalence of excess weight, and it nearly remained stable, and did not decrease by the decreasing prevalence of excess weight in the eighth decade of life. As a similar result to ours, smokers in India constitute a greater percentage of the obese group (26). So further studies are required about smoking and body weight.

As a conclusion, aging may be one of the major disorders of human beings, particularly in the presence of excess weight, and probably there are some breaking points of life for dyslipidemia, excess weight, DM, HT, and CHD with this order, and dyslipidemia may be a pioneer sign of excess weight.

References