RESULTS Weight loss was associated with a decline in CRP level .
Our results suggest that weight loss may be an effective nonpharmacologic strategy for lowering CRP level
BACKGROUND Several studies suggest that weight loss reduces C-reactive protein ( CRP ) level ; however , the consistency and magnitude of this effect has not been well characterized .
Our objective was to test the hypothesis that weight loss is directly related to a decline in CRP level .
Effects of Aerobic Physical Exercise on Inflammation and Atherosclerosis in Men: The DNASCO Study
Context Few data address whether exercise slows progression of atherosclerosis . Contribution In this 6-year trial , middle-aged Finnish men were r and omly assigned to progressive aerobic exercise or usual activity . Progressive exercise targeted 45- to 60-minute sessions 5 times weekly of activities such as walking , jogging , or cycling . Exercisers improved their ventilatory aerobic threshold and decreased their resting heart rate . However , intimamedia thickness of the carotid artery measured by ultrasonography did not differ between groups , except in a subgroup of men not taking statins . Implication s Aerobic exercise did not slow progression of atherosclerosis in middle-aged men , except for those not taking statins . The Editors Observational studies suggest that physical inactivity and low cardiorespiratory fitness predict atherosclerotic cardiovascular disease ( CVD ) ( 1 - 6 ) and that an increase in habitual physical activity ( 7 ) and cardiorespiratory fitness ( 8) are associated with decreased mortality . These findings are the basis for a general public health message recommending a minimum of 30 minutes of regular moderate exercise per day ( 9 ) . While exercise training at a weekly energy expenditure of 1500 kcal or more attenuates the progression of angiographically established coronary atherosclerosis ( 10 ) , there are no data from r and omized , controlled trials on the antiatherosclerotic effects of regular physical exercise in a general population . Moreover , studies using CVD mortality as an end point would require enormous sample sizes , and ethical issues limit the use of intracoronary arteriography in asymptomatic persons . Ultrasonographically assessed intimamedia thickness of the carotid arteries allows noninvasive investigation of pre clinical stages of atherosclerosis in unselected human population s ( 11 ) . Intimamedia thickness has been used as a surrogate end point for clinical coronary events ( 12 ) and in clinical trials ( 13 ) . We previously reported an inverse association of cardiorespiratory fitness to carotid artery intimamedia thickness ( 14 ) and its progression rate ( 15 ) . Clinical trials have revealed several plausible antiatherogenic mechanisms of exercise , such as favorable changes in plasma lipid levels , blood pressure , body adiposity , plasma glucose levels , insulin levels , and hemostatic factors ( 9 ) . However , these effects only partially explain the inverse association between physical activity and CVD . Inflammation plays a major role in the pathogenesis of atherosclerosis ( 16 ) . High-sensitivity C-reactive protein ( CRP ) levels are a marker of inflammation , and even slightly elevated serum levels of CRP predict clinical manifestations of atherosclerotic CVD ( 17 ) . Short-term uncontrolled studies suggest that physical activity has a beneficial impact on the inflammatory reaction ( 18 ) . In the DNASCO ( DNA Polymorphism and Carotid Atherosclerosis ) Study , a 6-year r and omized , controlled trial in a population -based sample of middle-aged men , we investigated the effect of regular long-term physical exercise on chronic low- grade inflammation and the progression of atherosclerosis , as assessed by noninvasive repeated measurements of carotid artery intimamedia thickness . Methods Study Design The primary end point was progression of the mean intimamedia thickness of the carotid artery in a 6-year r and omized , controlled trial of an exercise intervention . The Research Ethics Committee of the Kuopio University Hospital approved the protocol . Figure 1 shows the flow of patients through the study during recruitment , intervention allocation , and follow-up to data analysis . Participants were a r and om sample obtained from the population registry . Men were sent a letter inviting them to participate , and all participants provided signed informed consent . Forty-eight men did not respond to the invitation , and another 40 men did not present to the laboratory for the baseline examinations ; no data are available on the characteristics of these 88 men . Figure 1 . Flow of participants through the study . In 1994 to 1995 , 140 men were r and omly assigned to the exercise group ( n= 70 ) or the control group ( n= 70 ) by selecting a sealed , opaque envelope that contained the group assignment . The envelopes appeared identical , and an equal number was reserved for both study groups . Exclusion criteria were diseases or physical conditions restricting participation in regular exercise and malignant diseases or mental states restricting cooperation . During the 6-year intervention , 20 men ( 9 in the exercise group and 11 in the  control group ) dropped out because of death ( 2 in the exercise group and 4 in the control group ) , severe diseases ( 4 in the control group ) , relocation ( 1 in the exercise group ) , or loss of motivation ( 6 in the exercise group and 3 in the control group ) . For statistical analyses , multiple imputation methods were applied to replace missing end-point values . The first dropouts , all due to death , did not take place until the third year . Table 1 shows the number of patients with common chronic diseases as well as the number of patients who received drug treatment during the intervention . Table 1 . Patients with Chronic Diseases and Those Who Received Drug Treatment during the Intervention Primary End Point Carotid artery atherosclerosis was measured ultrasonographically as the mean intimamedia thickness . The same certified sonographer performed all biannual scannings during the 6 years , and we report results from 6 study visits ( at baseline and at years 2 through 6 ) . An ultrasound device with a high-resolution 10-MHz transducer was used , following a st and ardized and pretested protocol , and the scannings were recorded on super VHS videotape . The calibration of the ultrasound unit was routinely checked . Another certified sonographer measured intimamedia thickness of the far wall of the right carotid artery . Both sonographers were blinded to the r and omization status of the study participants . The measurement of intimamedia thickness extended to the longest wall region where the lumenintimal and mediaadventitial boundaries could be clearly identified by an automated edge-detection program on the basis of active contour ( 19 ) . The mean intimamedia thickness of the traced region was used for the statistical analysis . Cardiorespiratory Performance , Exercise Electrocardiography , and Blood Pressure To allow assessment of changes in cardiorespiratory fitness and to monitor exercise habits more objective ly , all participants annually performed a bicycle ergospirometry test . The patients ' electrocardiograms were continuously monitored and recorded every minute during the test and up to 7 minutes after exercise . An exercise physiologist visually defined ventilatory aerobic threshold as the first nonlinear increase of ventilation in the ergospirometry test . A trained nurse measured blood pressure annually . After the men had been lying on an examination bed for 45 minutes , blood pressure was measured by a r and om-zero mercury sphygmomanometer , according to the MONICA ( MONItoring CArdiovascular disease ) protocol ( 20 ) . Exercise Intervention The men in the exercise group were prescribed walking , jogging , cross-country skiing , swimming , and cycling as the main methods of aerobic exercise . The program was progressive : During the first 3 months , the men were advised to exercise 3 times per week for 30 to 45 minutes per session . Thereafter , they were asked to exercise 5 times per week for 45 to 60 minutes per session . Exercise intensity was determined individually , and modified when necessary , to correspond to ventilatory threshold level , that is , 40 % to 60 % of maximal oxygen uptake . The men in the exercise group were given heart rate monitors to help them adhere to the prescribed training heart rate . The participants performed the program on their own and were asked to report each exercise session in a diary , which was checked in a face-to-face meeting with an exercise physiologist at 6-month intervals . In accordance with the regulations of the Ethics Committee , men in the control group were allowed to choose whether to engage in physical exercise , but no efforts were made to change their habitual activity . Accordingly , the participants in the  control group were not asked to report their exercise habits in a diary . Biochemical Analyses Blood sampling and serum assays for fasting cholesterol and its subfractions have been described elsewhere ( 21 ) . Serum high-sensitivity CRP levels were measured by a commercial immunoassay ( IMMULITE 2000 High-Sensitivity CRP , Diagnostic Products Corp. , Los Angeles , California ) using the IMMULITE 2000 Analyzer ( Diagnostic Products Corp. ) . Other Methods Participants were asked about smoking habits and were classified as smokers or nonsmokers on the basis of current smoking status . Dietary energy and fat intake were assessed annually with 4-day food records ( 3 weekdays and Sunday ) . Portion sizes were estimated by using a picture booklet or household measurement units . Records were analyzed by using MicroNutrica software ( The Social Insurance Institution , Turku , Finl and ) , based on nutrient files from Finnish food analyses ( 22 ) . Statistical Analysis An estimate of the sample size ( 2n= 114 ) was based on assumptions about the reduction ( 25 % ) in the rate of progression of intimamedia thickness between the exercise and control groups , the duration of the trial ( 6 years ) , the number of equally spaced end-point measurements ( 7 ) , variability due to participants and measurement error ( 0.4 mm ) , and dropout rate ( 25 % ) . The significance level was 5 % , with a power of 90 % ( 23 ) . Statistical analyses were based primarily on an intention-to-treat approach with 140 participants . For secondary analyses , patients treated with cholesterol synthesis inhibitors , which are known to have a powerful antiatherosclerotic effect ( 24 ) , were excluded ( 6 in the exercise group and 9 in the control group ) ( Figure 1 ) . Multiple imputation methods available in
RESULTS Weight loss was associated with a decline in CRP level .
Our results suggest that weight loss may be an effective nonpharmacologic strategy for lowering CRP level
BACKGROUND Several studies suggest that weight loss reduces C-reactive protein ( CRP ) level ; however , the consistency and magnitude of this effect has not been well characterized .
Our objective was to test the hypothesis that weight loss is directly related to a decline in CRP level .