title: Effect of weight loss on inflammatory and endothelial markers and FMD using two low-fat diets Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. Weight Loss Reduces C-Reactive Protein Levels in Obese Postmenopausal Women Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. Effects of diet and/or exercise on the adipocytokine and inflammatory cytokine levels of postmenopausal women with type 2 diabetes. Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men. A substitution model of dietary manipulation is an effective means of optimising lipid profile, reducing C-reactive protein and increasing insulin-like growth factor-1. Markers of chronic inflammation and obesity: a prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention Effect of an energy-restricted, high-protein, low-fat diet relative to a conventional high-carbohydrate, low-fat diet on weight loss, body composition, nutritional status, and markers of cardiovascular health in obese women. Effects of a low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss. Serum levels of C-reactive protein are associated with obesity, weight gain, and hormone replacement therapy in healthy postmenopausal women. Differentiation Between Obesity and Insulin Resistance in the Association With C-Reactive Protein Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study. The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia. Long-term effects of advice to consume a high-protein, low-fat diet, rather than a conventional weight-loss diet, in obese adults with Type 2 diabetes: one-year follow-up of a randomised trial Effects of exercise training on 5 inflammatory markers associated with cardiovascular risk. Use of portion-controlled entrees enhances weight loss in women. Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response? Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women. Effect of physical activity on serum C-reactive protein. Attenuation of inflammation with short-term dietary intervention is associated with a reduction of arterial stiffness in subjects with hypercholesterolaemia Exercise training is not associated with improved levels of C-reactive protein or adiponectin. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. Association between physical activity and markers of inflammation in a healthy elderly population. Diet-induced weight loss is associated with decreases in plasma serum amyloid a and C-reactive protein independent of dietary macronutrient composition in obese subjects. Effects of Aerobic Physical Exercise on Inflammation and Atherosclerosis in Men: The DNASCO Study
abstract: OBJECTIVE : Cardiovascular disease is strongly associated with obesity and there is evidence that weight loss has positive effects on cardiovascular disease risk . The aims of this study were to compare meal replacements ( MR ) with a conventional low-fat diet as weight loss strategies and to examine the effect of weight loss on flow-mediated dilatation ( FMD ) and other markers of endothelial function in overweight Australians with raised triglycerides ( TG ) ( > 2 mmol/l ) . RESEARCH METHODS : Subjects matched for age , gender , fasting plasma TG and body mass index were r and omized to two low- fat high- carbohydrate weight loss strategies ( both < 6000 kJ ) , one using MR and the other a structured eating plan , control ( C ) . Subjects followed both diets for 3 months . In total , 55 subjects completed the study .  FMD , pulse wave velocity and blood pressure ( BP ) were measured at baseline and at 3 months , as were fasting blood sample s for lipids , glucose , insulin , C reactive protein ( CRP ) and endothelium-derived factors . RESULTS : Mean weight loss was 6.3±3.7 kg ( 6.0±4.2 vs 6.63±3.35 kg , MR vs C ) with no difference between diet groups . TG , insulin , CRP , plasminogen activator inhibitor 1 ( PAI-1 ) and soluble intracellular adhesion molecule-1 ( sICAM1 ) fell after weight loss , but FMD did not change . Systolic BP fell by 8 mmHg and pulse wave velocity improved . DISCUSSION : In subjects with elevated TG , weight loss result ed in significant improvements in cardiovascular risk markers , particularly endothelium-derived factors ( PAI-1 and sICAM1 ) . However , FMD did not improve with weight loss CONTEXT To enhance the effectiveness of diet in lowering cholesterol , recommendations of the Adult Treatment Panel III of the National Cholesterol Education Program emphasize diets low in saturated fat together with plant sterols and viscous fibers , and the American Heart Association supports the use of soy protein and nuts . OBJECTIVE To determine whether a diet containing all of these recommended food components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . DESIGN R and omized controlled trial conducted between October and December 2002 . SETTING AND PARTICIPANTS Forty-six healthy , hyperlipidemic adults ( 25 men and 21 postmenopausal women ) with a mean ( SE ) age of 59 ( 1 ) years and body mass index of 27.6 ( 0.5 ) , recruited from a Canadian hospital-affiliated nutrition research center and the community . INTERVENTIONS Participants were r and omly assigned to undergo 1 of 3 interventions on an outpatient basis for 1 month : a diet very low in saturated fat , based on milled whole-wheat cereals and low-fat dairy foods ( n = 16 ; control ) ; the same diet plus lovastatin , 20 mg/d ( n = 14 ) ; or a diet high in plant sterols ( 1.0 g/1000 kcal ) , soy protein ( 21.4 g/1000 kcal ) , viscous fibers ( 9.8 g/1000 kcal ) , and almonds ( 14 g/1000 kcal ) ( n = 16 ; dietary portfolio ) . MAIN OUTCOME MEASURES Lipid and C-reactive protein levels , obtained from fasting blood sample s ; blood pressure ; and body weight ; measured at weeks 0 , 2 , and 4 and compared among the 3 treatment groups . RESULTS The control , statin , and dietary portfolio groups had mean ( SE ) decreases in low-density lipoprotein cholesterol of 8.0 % ( 2.1 % ) ( P = .002 ) , 30.9 % ( 3.6 % ) ( P<.001 ) , and 28.6 % ( 3.2 % ) ( P<.001 ) , respectively . Respective reductions in C-reactive protein were 10.0 % ( 8.6 % ) ( P = .27 ) , 33.3 % ( 8.3 % ) ( P = .002 ) , and 28.2 % ( 10.8 % ) ( P = .02 ) . The significant reductions in the statin and dietary portfolio  groups were all significantly different from changes in the control group . There were no significant differences in efficacy between the statin and dietary portfolio treatments . CONCLUSION In this study , diversifying cholesterol-lowering components in the same dietary portfolio increased the effectiveness of diet as a treatment of hypercholesterolemia Background —C-reactive protein ( CRP ) has been proposed as an independent risk factor for cardiovascular disease and has been positively associated with body weight and body fatness . We examined the hypothesis that weight loss would reduce plasma CRP levels in obese postmenopausal women . Methods and Results —In a sample of 61 obese ( body mass index , 35.6±5.0 kg/m2 ) , postmenopausal women ( age , 56.4±5.2 years ) , we found that plasma CRP levels were positively associated with dual x-ray absorptiometry – measured total body fatness ( r = 0.36 , P < 0.005 ) and CT-measured intra-abdominal body fat area ( r = 0.30 , P < 0.02 ) . Significant correlations were also found between plasma CRP and triglyceride levels ( r = 0.33 , P < 0.009 ) and glucose disposal measured by the hyperinsulinemic-euglycemic clamp technique ( r = −0.29 , P < 0.03 ) . Twenty-five of the 61 women tested at baseline completed a weight loss protocol .  The average weight loss was 14.5±6.2 kg ( −15.6 % , P < 0.0001 ) , with losses of 10.4±5.4 kg fat mass ( −25.0 % , P < 0.0001 ) and 2.8±1.4 kg fat-free mass ( −6.0 % , P < 0.0001 ) . Visceral and subcutaneous fat areas were reduced by −36.4 % and −23.7 % , respectively ( P < 0.0001 ) . Plasma CRP levels were significantly reduced by weight loss : average −32.3 % , from 3.06 ( + 0.69 , −1.29 ) to 1.63 ( + 0.70 , −0.75 ) & mgr;g/mL ( P < 0.0001 , medians and interquartile differences ) . Changes in body weight and in total body fat mass were both positively associated with plasma CRP level reductions . Conclusions —Adiposity was a significant predictor of plasma CRP in postmenopausal women on a cross-sectional basis . Moreover , caloric restriction – induced weight loss decreased plasma CRP levels . Weight loss may represent an important intervention to reduce CRP levels , which may mediate part of its cardioprotective effects in obese postmenopausal women CONTEXT There are few data directly comparing the effects of physical activity and body weight on cardiovascular biomarkers . OBJECTIVE To examine the association of physical activity  and body mass index ( BMI , defined as weight in kilograms divided by the square of height in meters ) alone and in combination with cardiovascular biomarkers . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional analysis of 27,158 apparently healthy US women ( mean age , 54.7 years ) at the time of enrollment ( 1992 - 1995 ) in the Women 's Health Study , a r and omized , double-blind , placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer . MAIN OUTCOME MEASURES The association of physical activity and BMI with high-sensitivity C-reactive protein ( CRP ) , fibrinogen , soluble intracellular adhesion molecule 1 ( ICAM-1 ) , homocysteine , low- and high-density lipoprotein ( LDL and HDL ) cholesterol , total cholesterol , apolipoprotein A-1 and B100 , lipoprotein(a ) , and creatinine . RESULTS Lower levels of physical activity and higher levels of BMI were independently associated ( P for trend < .001 ) with adverse levels of nearly all lipid and inflammatory biomarkers . High BMI showed stronger associations with these biomarkers than physical inactivity . For example , using the reference group of physically active , normal weight women ( energy expenditure > or = 1000 kcal/week ; BMI , 18.5 - 24.9 ) and adjusting for age , race , smoking , blood pressure , diabetes , menopausal status , and hormone use , the odds ratios ( 95 % confidence intervals [ CIs ] ) for having CRP > 3 mg/L were : for inactive , normal weight women 1.26 ( 1.15 - 1.37 ) ; active , overweight 2.68 ( 2.41 - 2.98 ) ; inactive , overweight 3.11 ( 2.84 - 3.41 ) ; active , obese 8.25 ( 7.15 - 9.51 ) ; and inactive , obese 9.86 ( 8.84 - 10.99 ) . In similar analyses , the odds ratios ( 95 % CIs ) for having HDL cholesterol < 50 mg/dL were 1.20 ( 1.11 - 1.30 ) ; 2.25 ( 2.04 - 2.49 ) ; 2.62 ( 2.41 - 2.85 ) ; 4.21 ( 3.68 - 4.81 ) ; and 5.27 ( 4.77 - 5.84 ) , respectively , and for having apolipoprotein B100 > 120 mg/dL they were 1.21 ( 1.11 - 1.33 ) ; 1.86 ( 1.66 - 2.08 ) ; 2.06 ( 1.88 - 2.67 ) ; 2.35 ( 2.04 - 2.70 ) ; and 2.33 ( 2.09 - 2.59 ) . Fibrinogen , ICAM-1 , apolipoprotein A1 , total cholesterol , and LDL cholesterol showed similar associations . By contrast , homocysteine , lipoprotein ( a ) , and creatinine showed weak or nonsignificant associations . CONCLUSIONS High BMI was more strongly related to adverse cardiovascular biomarker levels than physical inactivity . However , within BMI categories , physical activity was generally associated with more favorable cardiovascular biomarker levels than inactivity BACKGROUND When substituted for carbohydrate in an energy-reduced diet , dietary protein enhances fat loss in women . It is unknown whether the effect is due to increased protein or reduced carbohydrate . OBJECTIVE We compared the effects of 2 isocaloric diets that differed in protein and fat content on weight loss , lipids , appetite regulation , and energy expenditure after test meals . DESIGN This was a parallel , r and omized study in which subjects received either a low-fat , high-protein ( LF-HP ) diet ( 29 + /- 1 % fat , 34 + /- 0.8 % protein ) or a high-fat , st and ard-protein ( HF-SP ) diet ( 45 + /- 0.6 % fat , 18 + /- 0.3 % protein ) during 12 wk of energy restriction ( 6 + /- 0.1 MJ/d ) and 4 wk of energy balance ( 7.4 + /- 0.3 MJ/d ) . Fifty-seven overweight and obese [ mean body mass index ( in kg/m(2 ) ) : 33.8 + /- 0.9 ] volunteers with insulin concentrations > 12 mU/L completed the study . RESULTS Weight loss ( LF-HP group , 9.7 + /- 1.1 kg ; HF-SP group , 10.2 + /- 1.4 kg ; P = 0.78 ) and fat loss were not significantly different between diet groups even though the subjects desired less to eat after the LF-HP meal ( P = 0.02 ) . The decrease in resting energy expenditure was not significantly different between diet groups ( LF-HP , -342 + /- 185 kJ/d ; HF-SP , -349 + /- 220 kJ/d ) . The decrease in the thermic effect of feeding with weight loss was smaller in the LF-HP group than in the HF-SP group ( -0.3 + /- 1.0 % compared with -3.6 + /- 0.7 % ; P = 0.014 ) . Glucose and insulin responses to test meals improved after weight loss ( P < 0.001 ) with no significant diet effect . Bone turnover , inflammation , and calcium excretion did not change significantly . CONCLUSION The magnitude of weight loss and the improvements in insulin resistance and cardiovascular disease risk factors did not differ significantly between the 2 diets , and neither diet had any detrimental effects on bone turnover or renal function BACKGROUND Persistent , low- grade inflammation is an independent predictor of several chronic diseases and all-cause mortality . OBJECTIVE The intention of this study was to determine the independent and combined effects of diet-induced weight loss and exercise on markers of chronic inflammation . DESIGN Three hundred sixteen community-dwelling , older ( > or = 60 y ) , overweight or obese [ body mass index ( in kg/m2 ) > or = 28 ] , sedentary men and women with radiographic evidence of knee osteoarthritis were r and omly assigned to four 18-mo treatments : healthy lifestyle control , diet-induced weight loss , exercise , and diet plus exercise . The exercise intervention consisted of combined weight training and walking for 1 h 3 times/wk . The weight-loss intervention consisted of a weekly session with a registered dietitian to provide education and support for lowering energy intake . RESULTS The diet-induced weight-loss intervention result ed in significantly greater reductions in concentrations of C-reactive protein ( P = 0.01 ) , interleukin 6 ( P = 0.009 ) , and soluble tumor necrosis factor alpha receptor 1 ( P = 0.007 ) than did no weight-loss treatment . Changes in soluble tumor necrosis factor alpha receptor 1 but not in C-reactive protein or interleukin 6 correlated with changes in body weight .  Exercise training did not have a significant effect on these inflammatory biomarkers , and there was no significant interaction between weight loss and exercise training . CONCLUSIONS These findings provide evidence from a r and omized controlled trial that a dietary intervention design ed to elicit weight loss reduces overall inflammation in older , obese persons . Additional studies are needed to assess the effects of different modes and intensities of exercise on inflammation The aim of this study was to investigate the potential role of adipose cytokines in the obesity-associated insulin resistance . To that end , we compared : 1 ) serum concentrations of interleukin 6 ( IL-6 ) , tumor necrosis factor alpha ( TNFalpha ) , and leptin in eight healthy lean control females and in and roid obese female without ( n = 14 ) and with ( n = 7 ) type 2 diabetes ; and 2 ) the levels of these cytokines both in serum and in sc adipose tissue in the 14 obese nondiabetic women before and after 3 weeks of a very low-calorie diet ( VLCD ) .  As compared with lean controls , obese nondiabetic and diabetic patients were more insulin resistant and presented increased values for leptin , IL-6 , TNFalpha , and C-reactive protein . In the whole group , IL-6 values were more closely related to the parameters evaluating insulin resistance than leptin or TNFalpha values .  VLCD result ed in weight loss and decreased body fat mass ( approximately 3 kg ) . Insulin sensitivity was improved with no significant change in both serum and adipose tissue TNFalpha levels . In contrast , VLCD induced significant decreases in IL-6 and leptin levels in both adipose tissue and serum . These results suggest that , as for leptin , circulating IL-6 concentrations reflect , at least in part , adipose tissue production . The reduced production and serum concentrations after weight loss could play a role in the improved sensitivity to insulin observed in these patients This study examined the independent and combined effects of diet and exercise on adipocytokine and inflammatory cytokines in postmenopausal women with type 2 diabetes . Using a r and omized , controlled design , 33 women ( age , 50 - 70 years ) were assigned to diet alone ( D ) , exercise alone ( EX ) , or diet + exercise ( D + E ) for 14 weeks . Before and after the interventions , blood sample s for adipocytokines and inflammatory markers were drawn , a meal test was performed , and abdominal fat distribution was measured by magnetic resonance imaging ( MRI ) . Body weight decreased approximately 4.5 + /- 0.6 kg ( P < .05 ) after the D and D + E interventions , whereas only small changes in body weight were found with the exercise-alone intervention . Plasma C-reactive protein levels were decreased by approximately 15 % with all 3 interventions , whereas leptin levels were reduced with the D and D + E intervention ( D : pre = 48.7 + /- 6.0 , post = 38.9 + /- 5.0 ng/mL ; D + E : pre = 38.5 + /- 6.0 , post = 22.9 + /- 5.0 ng/mL ; P < .05 ) with no differences between groups . There was a trend for leptin levels to decrease in the EX group ( P = .06 ) . Plasma resistin levels were not altered by the 3 interventions from pre- to posttreatment ( D : pre = 6.9 + /- 0.6 , post = 6.2 + /- 0.4 ng/mL ; D + E : pre = 5.6 + /- 0.6 , post = 5.7 + /- 0.4 ng/mL ; E : pre = 6.2 + /- 0.6 , post = 5.9 + /- 0.6 ng/mL , P > .05 ) , and no differences in adiponectin and tumor necrosis factor alpha ( TNF- alpha ) levels were found . Visceral adipose tissue and tumor necrosis factor alpha were the only predictors of calculated insulin resistance ( P < .05 ) , explaining 43 % of the variability . A typically prescribed weight loss program with lifestyle changes result ed in few changes in adipocytokines and inflammatory cytokines in older women with type 2 diabetes , suggesting that dramatic weight loss or clinical interventions are needed Several prospect i ve studies have demonstrated a direct association between C-reactive protein ( CRP ) levels and the risks of developing cardiovascular disease . Few studies , however , have explored the interrelations between CRP levels and other risk factors for cardiovascular disease . We evaluated the relation of CRP with several cardiovascular risk factors in a cross-sectional survey of 1,172 apparently healthy men . There were significant positive associations between  CRP levels and age , number of cigarettes smoked per day , body mass index , systolic and diastolic blood pressure , total cholesterol , triglycerides , lipoprotein(a ) , apolipoprotein B , tissue-type plasminogen activator antigen ,  D-dimers  , total homocysteine , and fibrinogen ( all p values < 0.05 ) . Significant inverse associations were observed for exercise frequency , high-density lipoprotein cholesterol , and apolipoprotein A-I and A-II ( all p values < 0.02 ) . In multivariate analysis , age , smoking status , and serum levels of tissue-type plasminogen activator antigen , fibrinogen , lipoprotein(a ) , and total homocysteine were independent correlates of CRP levels . Finally , in an analysis controlled either for all the independent correlates or for several usual risk factors , we observed progressive increases in levels of CRP with increasing prevalence of risk factors ( p for trend < 0.001 for independent correlates and < 0.01 for usual risk factors ) . In conclusion , in a large cohort of apparently healthy men ,  CRP levels were associated with several cardiovascular risk factors . These data are compatible with the hypothesis that  CRP levels may be a marker for pre clinical cardiovascular disease There are two key methods in which fat intake may be manipulated ; the ' substitution model ' and the ' reduction model ' . However insufficient information is known about the mechanisms of dietary fat reduction in individuals who have successfully reduced their fat intake , to be clear as to which strategy offers the greatest chance of success . Our objective was to ascertain the most effective dietary intervention for improving cardiovascular risk profile .  Eighty female volunteers ( high fat consumers ) were recruited . Each subject was r and omly allocated into one of the following groups . Substitution of high-fat foods was made with reduced-fat products , by the reduction of high-fat foods , by a combination of substitution and reduction strategies , or no advice was given . Each intervention lasted 3 months . Anthropometric measures and fasting blood sample s were taken at baseline and follow-up . The substitution intervention result ed in weight loss ( mean -1.4 ( 95 % CI -2.4 , -0.2 ) kg ) and reduced percentage body fat ( mean -1.3 ( 95 % CI -2.0 , -0.5)% ) . There was no significant weight change with the other interventions . Fasting triacylglycerols ( -0.2 ( SEM 0.07 ) mm ; P=0.04 ) , cholesterol and C-reactive protein ( CRP ) levels ( 0.8 ( SEM 0.2 ) mg/l ; P=0.04 ) fell with the substitution intervention , but not with the other interventions . Insulin-like growth factor-1 increased with both substitution and reduction ( P=0.02 ) . There was no significant change in fasting insulin or glucose with any intervention . The substitution model of dietary intervention is effective even over a relatively short interval of time in reducing fasting total cholesterol , triacylglycerols and CRP . Although the group size for the present study was small and involved females only , it has significant implication s for population intervention strategies Background : Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity . Hypothesis : To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures .Subjects and Methods : Twenty morbidly obese women participated in this prospect i ve study . Subjects were examined for fat mass , high-sensitive C-reactive protein ( hs-CRP ) , interleukin 6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-α ) before and 1 y after Swedish adjustable gastric b and ing . Results : Anthropometric measures displayed a significant reduction of the body mass index ( BMI ) from 41.6±5.4 to 30.8±6.1 kg/m2 and the fat mass from 53.9±10.3 to 29.8±12.1 kg ( mean±s.d . ) . Hs-CRP levels decreased significantly from 1.33±1.21 mg/dl in pre-gastric b and ing subjects to 0.40±0.61 mg/dl in post-gastric b and ing subjects , respectively . IL-6 and TNF-α levels did not differ significantly between pre- and post-gastric b and ing subjects . Conclusions : We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-α BACKGROUND Limited evidence suggests that a higher ratio of protein to carbohydrate during weight loss has metabolic advantages . OBJECTIVE The objective was to evaluate the effects of a diet with a high ratio of protein to carbohydrate during weight loss on body composition , cardiovascular disease risk , nutritional status , and markers of bone turnover and renal function in overweight women . DESIGN The subjects were r and omly assigned to 1 of 2 isocaloric 5600-kJ dietary interventions for 12 wk according to a parallel design : a high-protein ( HP ) or a high-carbohydrate ( HC ) diet . RESULTS One hundred women with a mean ( + /-SD ) body mass index ( in kg/m(2 ) ) of 32 + /- 6 and age of 49 + /- 9 y completed the study .  Weight loss was 7.3 + /- 0.3 kg with both diets . Subjects with high serum triacylglycerol ( > 1.5 mmol/L ) lost more fat mass with the HP than with the HC diet ( x + /- SEM : 6.4 + /- 0.7 and 3.4 + /- 0.7 kg , respectively ; P = 0.035 ) and had a greater decrease in triacylglycerol concentrations with the HP ( -0.59 + /- 0.19 mmol/L ) than with the HC ( -0.03 + /- 0.04 mmol/L ) diet ( P = 0.023 for diet x triacylglycerol interaction ) . Triacylglycerol concentrations decreased more with the HP ( 0.30 + /- 0.10 mmol/L ) than with the HC ( 0.10 + /- 0.06 mmol/L ) diet ( P = 0.007 ) . Fasting LDL-cholesterol , HDL-cholesterol , glucose , insulin , free fatty acid , and C-reactive protein concentrations decreased with weight loss . Serum vitamin B-12 increased 9 % with the HP diet and decreased 13 % with the HC diet ( P < 0.0001 between diets ) . Folate and vitamin B-6 increased with both diets ; homocysteine did not change significantly . Bone turnover markers increased 8 - 12 % and calcium excretion decreased by 0.8 mmol/d ( P < 0.01 ) . Creatinine clearance decreased from 82 + /- 3.3 to 75 + /- 3.0 mL/min ( P = 0.002 ) . CONCLUSION An energy-restricted , high-protein , low-fat diet provides nutritional and metabolic benefits that are equal to and sometimes greater than those observed with a high-carbohydrate diet CONTEXT Weight loss elicits physiological adaptations relating to energy intake and expenditure that antagonize ongoing weight loss . OBJECTIVE To test whether dietary composition affects the physiological adaptations to weight loss , as assessed by resting energy expenditure . DESIGN , STUDY , AND PARTICIPANTS : A r and omized parallel- design study of 39 overweight or obese young adults aged 18 to 40 years who received an energy-restricted diet , either low-glycemic load or low-fat .  Participants were studied in the General Clinical Research Centers of the Brigham and Women 's Hospital and the Children 's Hospital , Boston , Mass , before and after 10 % weight loss . The study was conducted from January 4 , 2001 , to May 6 , 2003 . MAIN OUTCOME MEASURES Resting energy expenditure measured in the fasting state by indirect calorimetry , body composition by dual-energy x-ray absorptiometry , cardiovascular disease risk factors , and self-reported hunger . RESULTS Resting energy expenditure decreased less with the low-glycemic load diet than with the low-fat diet , expressed in absolute terms ( mean [ SE ] , 96 [ 24 ] vs 176 [ 27 ] kcal/d ; P = .04 ) or as a proportion ( 5.9 % [ 1.5 % ] vs 10.6 % [ 1.7 % ] ; P = .05 ) . Participants receiving the low-glycemic load diet reported less hunger than those receiving the low-fat diet ( P = .04 ) . Insulin resistance ( P = .01 ) , serum triglycerides ( P = .01 ) , C-reactive protein ( P = .03 ) , and blood pressure ( P = .07 for both systolic and diastolic ) improved more with the low-glycemic load diet . Changes in body composition ( fat and lean mass ) in both groups were very similar ( P = .85 and P = .45 , respectively ) . CONCLUSIONS Changes in dietary composition within prevailing norms can affect physiological adaptations that defend body weight . Reduction in glycemic load may aid in the prevention or treatment of obesity , cardiovascular disease , and diabetes mellitus The authors evaluated the cross-sectional and prospect i ve associations between the serum concentration of C-reactive protein and measures of obesity and fat distribution , hormone replacement therapy ( HRT ) use , and serum sex hormones in postmenopausal women from the Healthy Women Study ( Allegheny County , Pennsylvania , 1998 ) . The authors tested the hypothesis that C-reactive protein levels would be higher among  HRT users and among women with greater body mass index , waist circumference , or visceral fat . There were 207 women in the study who were > or = 8 years postmenopausal ( 101 HRT users and 106 HRT nonusers ) . The median levels of C-reactive protein were 3.01 mg/liter in HRT users compared with 1.74 mg/liter in nonusers ( p = 0.002 ) . C-reactive protein levels were strongly positively correlated with measures of body size , fatness , fat distribution , and weight gain among HRT users and nonusers . C-reactive protein was also positively correlated with serum estrone levels ( r(s ) = 0.38 ) among HRT nonusers . The highest level of C-reactive protein was found among HRT users in the highest quartile of visceral fat ( 4.29 mg/liter ) compared with women not on HRT and in the lowest quartile of visceral fat ( 0.96 mg/liter ) . The use of HRT and measures of overall body fatness are important correlates of C-reactive protein among postmenopausal women Background —Plasma C-reactive protein ( CRP ) concentrations are increased in obese and /or hyperinsulinemic individuals . The goal of this study was to determine if the relation between insulin resistance and CRP was independent of obesity . Methods and Results —Plasma CRP concentrations were measured before and after 3 months of calorie restriction in 38 healthy , obese women .  Steady-state plasma glucose ( SSPG )  concentration during a 180-minute infusion of octreotide , glucose , and insulin was used to stratify participants into insulin-resistant ( IR , n=20 ) or insulin-sensitive ( n=18 ) groups , similar in terms of mean age ( 46±2 versus 44±2 years ) , body mass index ( 32.0±0.4 versus 31.4±0.3 kg/m2 ) , and waist circumference ( 96±2 versus 95±2 cm ) . Mean CRP ( 0.39±0.08 versus 0.12±0.03 mg/dL , P = 0.003 ) concentrations were higher in the IR group , as were day-long plasma glucose and insulin responses ( P < 0.001 ) . There was a significant correlation at baseline between CRP and day-long plasma integrated insulin response ( r = 0.47 , P = 0.001 ) but not between CRP and body mass index ( r = 0.14 ) or waist circumference ( r = 0.10 ) . Weight loss was similar in the two groups ( 8.7±0.9 versus 8.4±0.8 kg ) but was associated with significant ( P < 0.001 ) decreases in SSPG and CRP concentrations in the IR group only . Regression analysis showed that SSPG and day-long plasma insulin response were the only significant predictors of CRP concentration . Conclusions —CRP concentrations are elevated predominantly in obese individuals who are also insulin resistant and fall in parallel with weight loss – associated improvements in insulin resistance . The relation between CRP concentrations and insulin resistance is independent of obesity BACKGROUND Chronic hyperglycemia has been hypothesized to contribute to coronary heart disease ( CHD ) , but the extent to which hemoglobin A(1c ) ( HbA(1c ) ) level , a marker of long-term glycemic control , is independently related to CHD risk is uncertain . METHODS We conducted a prospect i ve case-cohort study of 1321 adults without diabetes and a cohort study of 1626 adults with diabetes from the Atherosclerosis Risk in Communities Study . Using proportional hazards models , we assessed the relation between HbA(1c ) level and incident CHD during 8 to 10 years of follow-up . RESULTS In adults with diabetes , the relative risk ( RR ) of CHD was 2.37 ( 95 % confidence interval [ CI ] , 1.50 - 3.72 ) for the highest quintile of HbA(1c ) level compared with the lowest after adjustment for CHD risk factors . In persons without diabetes , the adjusted RR of CHD in the highest quintile of HbA(1c ) level was 1.41 ( 95 % CI , 0.90 - 2.30 ) ; however , there was evidence of a nonlinear relationship in this group . In nondiabetic adults , HbA(1c ) level was not related to CHD risk below a level of 4.6 % but was significantly related to risk above that level ( P<.001 ) . In diabetic adults , the risk of CHD increased throughout the range of HbA(1c ) levels . In the adjusted model , the RR of CHD for a 1-percentage point increase in HbA(1c ) level was 2.36 ( 95 % CI , 1.43 - 3.90 ) in persons without diabetes but with an HbA(1c ) level greater than 4.6 % . In diabetic adults , the RR was 1.14 ( 95 % CI , 1.07 - 1.21 ) per 1-percentage point increase in HbA(1c ) across the full range of HbA(1c ) values . CONCLUSION Elevated HbA(1c ) level is an independent risk factor for CHD in persons with and without diabetes Reductions in low-density lipoprotein-cholesterol ( LDL-C ) result from diets containing almonds , or diets that are either low in saturated fat or high in viscous fibers , soy proteins , or plant sterols . We have therefore combined all of these interventions in a single diet ( portfolio diet ) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events . Twenty-five hyperlipidemic subjects consumed either a portfolio diet ( n=13 ) , very low in saturated fat and high in plant sterols ( 1.2 g/1,000 kcal ) , soy protein ( 16.2 g/1,000 kcal ) , viscous fibers ( 8.3 g/1,000 kcal ) , and almonds ( 16.6 g/1,000 kcal ) , or a low-saturated fat diet ( n=12 ) based on whole-wheat cereals and low-fat dairy foods .  Fasting blood , blood pressure , and body weight were obtained at weeks 0 , 2 , and 4 of each phase . LDL-C was reduced by 12.1 % + /- 2.4 % ( P<.001 ) on the low-fat diet and by 35.0 % + /- 3.1 % ( P<.001 ) on the portfolio diet , which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol ( HDL-C ) significantly ( 30.0 % + /- 3.5 % ; P<.001 ) . The reductions in LDL-C and the LDL : HDL-C ratio were both significantly lower on the portfolio diet than on the control diet ( P<.001 and P<.001 , respectively ) . Mean weight loss was similar on test and control diets ( 1.0 kg and 0.9 kg , respectively ) . No difference was seen in blood pressure , HDL-C , serum triglycerides , lipoprotein(a ) [ Lp(a ) ] , or homocysteine concentrations between diets . Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy Aims /hypothesisThis study compared the long-term weight loss and health outcomes at 1-year follow-up , after a 12-week intensive intervention consisting of two low-fat , weight-loss diets , which differed in protein content . Methods We r and omly assigned 66 obese patients ( BMI : 27–40 kg/m2 ) with Type 2 diabetes to either a low-protein ( 15 % protein , 55 % carbohydrate ) or high-protein diet ( 30 % protein , 40 % carbohydrate ) for 8 weeks of energy restriction ( ~6.7 MJ/day ) and 4 weeks of energy balance . Subjects were asked to maintain the same dietary pattern for a further 12 months of follow-up . Results The study was completed by 38 of the subjects , with equal dropouts in each group . At Week 64 , weight reductions against baseline were −2.2±1.1 kg ( low protein ) and −3.7±1.0 kg ( high protein ) , p<0.01 , with no diet effect . Fat mass was not different from baseline in either group . At Week 12 , both diets reduced systolic and diastolic blood pressure by 6 and 3 mm Hg respectively , but blood pressure increased more with weight regain during follow-up in the low-protein group ( p≤0.04 ) . At Week 64 , both diets significantly increased HDL cholesterol and lowered C-reactive protein concentrations . There was no difference in the urinary urea : creatinine ratio at baseline between the two groups , but this ratio increased at Week 12 ( in the high-protein group only , p<0.001 , diet effect ) , remaining stable during follow-up in both diets . Conclusions /interpretationA high-protein weight-reduction diet may in the long term have a more favourable cardiovascular risk profile than a low-protein diet with similar weight reduction in people with Type 2 diabetes BACKGROUND Cross-sectional studies suggest that regular exercise has anti-inflammatory effects , leading to lower levels of several proatherogenic inflammatory markers . However , this has yet to be confirmed by r and omized prospect i ve trials . We performed a r and omized controlled trial to assess whether exercise training decreases levels of 5 inflammatory markers linked to future cardiovascular risk : white blood cell count , fibrinogen , C-reactive protein , soluble intercellular adhesion molecule 1 , and soluble CD40 lig and . METHODS One hundred fifty-two healthy female smokers were r and omized to either 12 weeks of exercise training or health education as part of a smoking cessation program . Smoking was held steady for the first 6 weeks , and thereafter , smoking cessation was actively attempted . One hundred four participants completed 6 weeks , and 88 completed 12 weeks . Fitness and circulating inflammatory marker levels were measured at baseline , 6 weeks , and 12 weeks . To avoid potential confounding from changes in smoking exposure during the second 6 weeks of the trial , the primary end point was change in inflammatory marker levels from baseline to 6 weeks . Change in inflammatory markers from baseline to 12 weeks was a secondary end point . RESULTS At baseline , greater physical fitness was associated with lower white blood cell , fibrinogen , and C-reactive protein levels , but these associations were not statistically significant after adjusting for body mass index ( P > .1 for all ) . Fitness improved significantly in the exercise group at both 6 and 12 weeks . However , there were no differences in levels of any inflammatory marker between the exercise and control groups at either 6 weeks ( primary end point ) or 12 weeks ( secondary end point ) ( P > .05 for all comparisons ) . CONCLUSION In female smokers , baseline associations between fitness and inflammatory markers were largely attributable to differences in body fat ; regular exercise did not reduce levels of any of the inflammatory markers studied despite a significant improvement in fitness at both 6 and 12 weeks OBJECTIVE To determine the efficacy of a weight-loss diet using packaged portion-controlled entrees compared with a self-selected diet based on the U.S. Department of Agriculture Food Guide Pyramid ( FGP ) ( United States Department of Agriculture , Center for Nutrition Policy and Promotion , Washington , DC ; 1996 ) . RESEARCH METHODS AND PROCEDURES Sixty healthy women ( BMI 26 to 40 kg/m(2 ) ; 24 to 60 years old ) were r and omized into two intervention groups for an 8-week parallel arm study . The portion-controlled group consumed two frozen entrees daily , plus additional food servings from the FGP . The self-selected diet group consumed a recommended number of servings from the FGP . Diets were design ed to be the same in composition ( 55 % carbohydrate , 25 % protein , 20 % fat ) and energy level ( 1365 kcal ) . Each group met weekly to monitor compliance and take measures . Outcomes included weight , body composition by DXA , hip and waist circumference , blood pressure , fasting blood lipids , glucose , insulin , and C-reactive protein . Significant differences were assessed using repeated measures ANOVA . RESULTS The portion-controlled group ( n = 26 ) experienced greater decreases in weight ( 5.6 + /- 2.2 kg or 6.5 % vs. 3.6 + /- 2.5 kg or 4.2 % ) , fat mass ( 3.6 + /- 1.8 vs. 2.3 + /- 1.4 kg ) , total cholesterol ( 24.4 + /- 21.5 mg/dL or 12.4 % vs. 13.0 + /- 13.9 mg/dL or 6.7 % ) , and fasting insulin ( -1.8 + /- 3.7 vs.+0.3 + /- 3.8 micro U/mL ) than the self-selected diet group ( n = 27 ) ( p < 0.05 ) . DISCUSSION Consumption of portion-controlled entrees result ed in greater losses of weight and fat , thereby reducing cardiovascular disease risk . Accurate portion control is an important factor in weight loss success , and use of packaged entrees is an effective method of achieving this OBJECTIVES To identify a stable biochemical marker of disease severity in patients with intermittent claudication and to use these findings to assess the effect of therapeutic exercise training . DESIGN Case-control study : prospect i ve r and omised-controlled trial of exercise training . MATERIAL S AND METHODS Plasma fibrinogen , serum amyloid A protein ( SAA ) , C-reactive protein ( CRP ) and urinary albumin-creatinine ratio ( ACR ) were measured in 67 claudicants and 15 controls . Twenty-two patients were r and omised to supervised exercise training and 17 r and omised to observation .  Subjects were review ed at 3 , 6 and 12 months . RESULTS The median ( interquartile range ) baseline fibrinogen was 3.7 g/l ( 3.3 - 4.25 ) in claudicants and 3.5 g/l ( 2.9 - 3.95 ) in controls ( p = 0.045 ) ; CRP was 4.7 mg/l ( 2.2 - 9.0 ) and 2.1 mg/l ( 1.0 - 2.8 ) , respectively ( p < 0.0001 ) ; SAA was 72 mg/l ( 35 - 132 ) and 30 mg/l ( 20 - 89 ) ( p = 0.0009 ) . Claudicants showed an increased urinary ACR following treadmill exercise ( Wilcoxon , p < 0.0001 ) with no change in controls . Exercise training reduced SAA at 6 months , CRP at 3 months and progressively attenuated the post-exercise increase in ACR . No similar changes were found in controls . CONCLUSIONS Repetitive low- grade inflammatory events in claudicants lead to elevation of serum acute-phase proteins .  Exercise training is associated with symptomatic improvement and reduction inflammatory markers . The concern that exercise has adverse systemic effects therefore seems to be unjustified The purpose of this study was to determine whether a hypocaloric diet with and without exercise training is effective in reducing plasma C-reactive protein , IL-6 , TNFalpha , and their soluble receptors ( sIL-6R , sTNFR1 , and sTNFR2 ) , and whether changes in these inflammatory markers are related to changes in regional lipolysis in obese ( body mass index , 32.78 + /- 4.73 ) postmenopausal women ( diet alone , n = 17 ; diet plus exercise , n = 17 ) . All inflammatory markers were measured by an ELISA method . In vitro lipolysis was evaluated by measuring glycerol release using a one-step enzymatic fluorometric technique . Six months of diet and diet plus exercise decreased total and abdominal fat to a similar degree . Diet plus exercise , but not diet alone , decreased plasma levels of C-reactive protein , IL-6 , sIL-6R , and sTNFR1 and increased basal and postreceptor stimulated lipolysis in both abdominal and gluteal regions . Changes in abdominal stimulated lipolysis correlated significantly with changes in plasma IL-6 ( r = -0.39 ) and TNFR1 ( r = -047 ) . Thus , diet plus exercise training , but not diet alone , is effective in reducing chronic inflammation in obese postmenopausal women . In addition , modification of chronic inflammation is associated with changes in local adipose tissue metabolism in response to diet and exercise This study examines the association between physical activity and C-reactive protein levels , indicating that high levels of strenuous aerobic activity are associated with lower C-reactive protein levels among men Background Increased arterial stiffness has been found in patients with chronic high- grade inflammatory diseases . Whether mitigation of low- grade systemic inflammation , through a low-cholesterol/low-saturated fat diet , may have a role in improving arterial stiffness is still untested . Design We investigated whether variations in blood lipids and plasma C-reactive protein induced by low-cholesterol/low-saturated fat diet are associated with variations in large-artery stiffness in hypercholesterolemia . Methods Thirty-five patients with primary hypercholesterolemia and 15 normal control subjects were recruited for the study . Hypercholesterolaemic patients followed an 8-week low-cholesterol/low-saturated fat diet ( 30 % total fat , 5 % saturated fat , cholesterol < 200mg/daily ) . Anthropometric characteristics , blood lipids , plasma C-reactive protein and arterial stiffness were measured at baseline and after the diet . Results Arterial stiffness and C-reactive protein levels were higher in hypercholesterolaemic patients than in controls . Significant reductions in body weight ( 2 kg , 3 % ) , plasma total cholesterol ( 13.4mg/dl , 5.3 % ) , low-density lipoprotein cholesterol ( 11.2 mg/dl , 6.4 % ) , C-reactive protein ( 0.7 mg/l , 39 % ) and arterial stiffness ( from 8.9 ± 2.0 to 8.1 ± 1.9 m/s , 11 % ) were achieved among hypercholesterolaemic patients after the 8-week diet ( P < 0.05 for all ) . Bivariate correlations and multivariate analysis showed reduction in arterial stiffness after short-term diet to be associated with reduction of plasma C-reactive protein levels ( r = 0.59 , β = 0.38 , P<0.05 for both ) The purpose of this study was to determine the effect of exercise training on the levels of C-reactive protein ( CRP ) and adiponectin , and to assess whether exercise-induced changes in insulin resistance could be explained in part by changes in these inflammation markers . Study participants included 51 middle-aged ( 45.3+/-8.3 years ; mean+/-SD ) , overweight ( 33.7+/-4.8 BMI ) , insulin-resistant , nondiabetic individuals . Subjects had their insulin sensitivity , body fat , CRP , and adiponectin levels measured , and their predicted maximal fitness calculated before and after 16 weeks of moderate , intense , or no exercise training . Modest improvements in fitness , body composition , and insulin sensitivity were observed , but these changes were not associated with decreased CRP or increased adiponectin levels , even when subjects were stratified by their change in fitness or obesity . Regression analysis demonstrated that the change in percentage of body fat was significantly related to changes in insulin sensitivity , whereas changes in VO2 MAX , CRP , and adiponectin were not . Participation in moderate to intense exercise was not associated with improved measures of chronic inflammation markers , as measured by CRP and adiponectin . Moreover , improvements in insulin sensitivity result ing from exercise or modest weight loss did not appear to be related to changes in these markers CONTEXT Obesity is an independent risk factor for cardiovascular disease , which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue . OBJECTIVE To determine the effect of a program of changes in lifestyle design ed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance . DESIGN AND SETTING R and omized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy . PATIENTS One hundred twenty premenopausal obese women ( body mass index > or = 30 ) aged 20 to 46 years without diabetes , hypertension , or hyperlipidemia . INTERVENTIONS The 60 women r and omly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10 % or more through a low-energy Mediterranean-style diet and increased physical activity . The control group ( n = 60 ) was given general information about healthy food choices and exercise . MAIN OUTCOME MEASURES Lipid and glucose intake ; blood pressure ; homeostatic model assessment of insulin sensitivity ; and circulating levels of interleukin 6 ( IL-6 ) , interleukin 18 ( IL-18 ) , C-reactive protein ( CRP ) , and adiponectin . RESULTS After 2 years , women in the intervention group consumed more foods rich in complex carbohydrates ( 9 % corrected difference ; P<.001 ) , monounsaturated fat ( 2 % ; P = .009 ) , and fiber ( 7 g/d ; P<.001 ) ; had a lower ratio of omega-6 to omega-3 fatty acids ( -5 ; P<.001 ) ; and had lower energy ( -310 kcal/d ; P<.001 ) , saturated fat ( -3.5 % ; P = .007 ) , and cholesterol intake ( -92 mg/d ; P<.001 ) than controls . Body mass index decreased more in the intervention group than in controls ( -4.2 ; P<.001 ) , as did serum concentrations of IL-6 ( -1.1 pg/mL ; P = .009 ) , IL-18 ( -57 pg/mL ; P = .02 ) , and CRP ( -1.6 mg/L ; P = .008 ) , while adiponectin levels increased significantly ( 2.2 microg/mL ; P = .01 ) . In multivariate analyses , changes in free fatty acids ( P = .008 ) , IL-6 ( P = .02 ) , and adiponectin ( P = .007 ) levels were independently associated with changes in insulin sensitivity . CONCLUSION In this study , a multidisciplinary program aim ed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance Higher levels of physical activity are associated with lower risk of cardiovascular disease . There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation . In this study , the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population . Data obtained in 1989 - 1990 and 1992 - 1993 from the Cardiovascular Health Study , a cohort of 5,888 men and women aged > /=65 years , were analyzed . Concentrations of the inflammation markers-C-reactive protein , fibrinogen , Factor VIII activity , white blood cells , and albumin-were compared cross-sectionally by quartile of self-reported physical activity . Compared with persons in the lowest quartile , those in the highest quartile of physical activity had 19 % , 6 % , 4 % , and 3 % lower concentrations of C-reactive protein , white blood cells , fibrinogen , and Factor VIII activity , respectively , after adjustment for gender , the presence of cardiovascular disease , age , race , smoking , body mass index , diabetes , and hypertension . Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose . There was no association between physical activity and albumin . Higher levels of  physical activity  were associated with lower concentrations of four out of five inflammation markers in this elderly cohort . These data suggest that increased exercise is associated with reduced inflammation . Prospect i ve studies will be required for verification of these findings Elevated levels of serum amyloid A ( SAA ) and C-reactive protein ( CRP ) have been associated with increased cardiovascular risk . Although levels of CRP decrease with weight loss , it is not known whether SAA decreases with weight loss or whether dietary macronutrient composition affects levels of either SAA or CRP . SAA and CRP levels were measured retrospectively on baseline and 3-month plasma sample s from 41 obese ( mean body mass index 33.63 + /- 1.86 kg/m2 ) women completing a r and omized trial comparing a low-fat diet ( n = 19 ) and a very low-carbohydrate diet ( n = 22 ) . For the 41 participants , there were significant decreases from baseline to 3 months in both LogSAA ( P = 0.049 ) and LogCRP ( P = 0.035 ) . The very low-carbohydrate dieters had a significantly greater decrease in LogSAA ( P = 0.04 ) , but their weight loss also was significantly greater ( -7.6 + /- 3.2 vs. -4.3 + /- 3.5 kg , P < 0.01 ) . In this study , the decreases in inflammatory markers correlated significantly with weight loss ( r = 0.44 , P = 0.004 vs. LogSAA and r = 0.35 , P = 0.03 vs. LogCRP ) . Also , change in LogSAA correlated with change in insulin resistance ( r = 0.35 , P = 0.03 ) . Thus , in otherwise healthy , obese women , weight loss was associated with significant decreases in both SAA and CRP . These effects were proportional to the amount of weight lost but independent of dietary macronutrient composition 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
target: 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: 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 .