Influence of lifestyle modification on atherosclerotic progression determined by ultrasonographic change in the common carotid intima-media thickness. High-Sensitivity C-Reactive Protein Is Not Associated With Carotid Intima-Media Progression: The Carotid Atherosclerosis Progression Study Endothelial dysfunction in PCOS: role of obesity and adipose hormones. A dietary and exercise intervention slows menopause-associated progression of subclinical atherosclerosis as measured by intima-media thickness of the carotid arteries. The evaluation of endothelial function with flow-mediated dilatation and carotid intima media thickness in young nonobese polycystic ovary syndrome patients; existence of insulin resistance alone may not represent an adequate condition for deterioration of endothelial function. Carotid Intima-Media Thickening Indicates a Higher Vascular Risk Across a Wide Age Range: Prospective Data From the Carotid Atherosclerosis Progression Study (CAPS) Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. Plasma interleukin-18 levels are increased in the polycystic ovary syndrome: relationship of carotid intima-media wall thickness and cardiovascular risk factors. Results of the primary outcome measure and clinical events from the Asymptomatic Carotid Artery Progression Study. Serum aldosterone concentration and cardiovascular risk in women with polycystic ovarian syndrome. Evaluation of endothelial function in women with polycystic ovary syndrome. Correlates of increased lean muscle mass in women with polycystic ovary syndrome.
The Monitored Atherosclerosis Regression Study ( MARS ) was a r and omized , double-blind , placebo-controlled angiographic trial of lipid-lowering therapy in subjects with coronary artery disease . Subjects were counseled to follow a low-fat , low-cholesterol diet . At every clinic visit , data were obtained on body weight , dietary intake , alcohol consumption , and tobacco use . Semiannual determinations of early preintrusive atherosclerosis were made with high-resolution B-mode ultrasonography of the carotid artery intima-media thickness ( IMT ) . We evaluated the effects of lifestyle modification ( diet , alcohol , smoking , and weight loss ) on the rate of carotid artery IMT progression on the 94 subjects r and omly assigned to the placebo group .  Dietary cholesterol , insoluble fiber , body mass index , and smoking were significant predictors of the annual rate of carotid artery IMT progression ( P < 0.05 ) . For subjects experiencing IMT progression , increased intakes of monounsaturated fat relative to saturated fat and stearic acid ( 18:0 ) consumption were significant predictors of a reduction in the annual rate of carotid artery IMT progression ; for subjects experiencing IMT regression , male sex was a significant predictor of a reduction in the annual rate of carotid artery IMT regression . Modifications reducing body mass index by 5 kg/m2 , quitting a 10 cigarette/d smoking habit , and reducing dietary cholesterol intake by 100 mg/d on average would reduce the annual rate of carotid wall IMT progression by 0.13 mm/y , which is equivalent to the maximum rate of IMT progression observed in the MARS placebo group . Progression of early preintrusive atherosclerosis can be reduced and overall regression can occur with dietary and lifestyle modification Background and Purpose — It is unclear whether elevated serum C-reactive protein ( CRP ) is causal to the initiation and progression of atherosclerosis . We undertook a prospect i ve longitudinal cohort study to address this question . Methods — In a population -based sample of 3122 subjects , we measured  carotid intima media thickness ( IMT ) at baseline and after 3 years and surveyed clinical events . Associations between baseline high-sensitivity CRP ( hs-CRP ) and baseline IMT , and IMT progression were determined before and after controlling for vascular risk factors . The relationship between baseline IMT and clinical events during follow up was determined . Results — All vascular risk factors were significantly associated with hs-CRP ( P<0.001 ) . Hs-CRP was significantly associated with baseline IMT in all carotid segments ( P<0.001 ) , but this association was no longer significant after controlling for age , gender , and cardiovascular risk factors . Hs-CRP was not related to individual IMT progression . Interactions between hs-CRP and body mass index , HbA1c , or blood pressure showed no association with IMT progression . Baseline hs-CRP was related to the risk of clinical events ( myocardial infa rct ion or stroke or death , hazard ratio of 1.22 per mg/L hs-CRP increase , 95 % CI : 1.07 to 1.39 , P=0.004 , adjusted for age and gender ) , but this association was not significant after controlling for age , gender , and cardiovascular risk factors ( 1.59 , 95 % CI : 0.96 to 2.64 , P=0.072 ) . Conclusions — Our results suggest that hs-CRP is not an independent causal factor for the initiation and progression of early atherosclerotic changes of the carotid arteries . Univariate associations between  hs-CRP and IMT were largely explained by confounding by age , gender , and cardiovascular risk factors PURPOSE Polycystic ovary syndrome ( PCOS ) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk and altered endothelial function have been found . This study was design ed to determine if abnormal carotid intima-media thickness ( IMT ) and brachial flow-mediated dilation ( FMD ) in young women with PCOS may be explained by insulin resistance and elevated adipocytokines . METHODS A prospect i ve study in 50 young women with PCOS ( age : 25.2 + /- 1 years ; body mass index [ BMI ] : 28.7 + /- 0.8 ) and 50 matched ovulatory controls ( age : 25.1 + /- 0.7 years ; BMI : 28.5 + /- 0.5 ) was performed . Carotid IMT , brachial FMD , and blood for fasting glucose , insulin , leptin , adiponectin and resistin  were measured . RESULTS PCOS , IMT was increased ( P < .01 ) , FMD was decreased ( P < .01 ) , fasting insulin was increased ( P < .01 ) , QUICKI ( a marker of insulin resistance ) was decreased ( P < .01 ) , and adiponectin was lower ( P < .05 ) , whereas leptin and resistin were not different compared with matched controls . Whereas BMI or waist/hip ratios did not correlate with IMT or FMD , insulin and QUICKI correlated positively and negatively with IMT ( P < .01 ) . There was a significant negative correlation between adiponectin and IMT ( P < .05 ) . These correlations were unchanged when adjusting for BMI and the correlation between IMT and adiponectin was unaffected by insulin resistance parameters . CONCLUSIONS These data suggest that young women with PCOS have evidence for altered endothelial function . Adverse endothelial parameters were correlated with insulin resistance and lower adiponectin . Both insulin resistance and adiponectin appear to be important parameters . It is hypothesized that the type of fat distribution may influence these factors OBJECTIVES The object of this study was to assess the effects of menopause and a diet/exercise intervention on sub clinical atherosclerosis progression . BACKGROUND Sub clinical atherosclerosis has been linked to higher coronary heart disease and stroke rates and is greater among postmenopausal women according to cross-sectional analyses . Whether menopause is associated with an accelerated progression of sub clinical disease is unknown , as is the extent to which lifestyle intervention can alter the course of progression . METHODS Intima-media thickness ( IMT ) measures of the common carotid artery ( CCA ) , internal carotid artery ( ICA ) , and bulb segments of the carotid arteries were measured twice during the course of 4 years in 353 women from the Women 's Healthy Lifestyle Project , a dietary and exercise clinical trial design ed to prevent adverse risk factor changes through the menopause . A third measure was obtained 2.5 years later for 113 women . RESULTS The progression of IMT was observed for the average of all segments ( AVG ) , the CCA , and the bulb ( 0.007 mm/year , 0.008 mm/year , and 0.012 mm/year ; p < 0.01 for all ) , but not for the ICA . Among controls , menopause was associated with accelerated IMT progression ( 0.003 mm/year for premenopausal women vs. 0.008 mm/year for perimenopausal/postmenopausal women for AVG IMT ; p = 0.049 ) . Additionally , among the 160 perimenopausal/postmenopausal women , the intervention slowed IMT progression ( 0.008 mm/year for the control group vs. 0.004 mm/year for the intervention group for AVG IMT ; p = 0.02 ) . Similar results were found for the CCA and bulb segments . CONCLUSIONS These data demonstrate that the menopause transition is associated with accelerated sub clinical atherosclerosis progression and that a diet/exercise intervention slows menopause-related atherosclerosis progression OBJECTIVE To evaluate endothelial function with flow-mediated dilatation ( FMD ) and carotid intima media thickness ( IMT ) in young nonobese polycystic ovary syndrome ( PCOS ) patients . DESIGN Prospect i ve case-control study . SETTING Healthy volunteers and nonobese young PCOS patients in clinical research . PATIENT(S ) Thirty-nine PCOS patients with mean age of 22.82 + /- 5.53 years and 30 body mass index- and age-matched healthy controls were evaluated . INTERVENTION(S ) Insulin resistance was calculated with area under the curve , quantitative insulin sensitivity check , and the Matsuda index .  Endothelial function was assessed with FMD and carotid IMT by ultrasonography . MAIN OUTCOME MEASURE(S ) Antropometric , hormonal , biochemical ( insulin and glucose , tumor necrosis factor-alpha , hs-c-reactive protein , and homocysteine levels , and so forth ) , FMD , and IMT were measured . RESULT ( S ) There was a significant insulin resistance in PCOS patients . Serum FSH , total and free testosterone , cortisol , and rostenedione , and DHEA-S levels of PCOS patients were also higher than control subjects , but we could not find any significant difference in terms of endothelial function determined with FMD . CONCLUSION ( S ) Existence of insulin resistance alone may not be an adequate factor for deterioration of endothelial function and carotid IMT in young , nonobese patients with PCOS . Other factors such as duration of insulin resistance , older age , presence of obesity , and inflammatory markers may play an important role in this process Background and Purpose — Carotid intima-media thickness ( IMT ) is an independent predictor of  vascular events in age groups > 45 years . However , there is little information about the predictive value of IMT in younger individuals . Methods — In the Carotid Atherosclerosis Progression Study ( CAPS ; n=5056 ; age range 19 to 90 years ; mean age 50.1 years ) , common carotid artery ( CCA ) IMT , bifurcation IMT , internal carotid artery IMT and vascular risk factors were evaluated at baseline . The incidence of stroke , myocardial infa rct ion ( MI ) , and death was determined prospect ively . Data for younger ( < 50 years ; n=2436 ) and older subjects ( ≥50 years ; n=2620 ) were analyzed separately using Cox proportional hazard regression models . Results — During a mean follow-up period of 4.2 years , there were 228 cases of MI , 107 strokes , and 50 deaths . IMT at all carotid segments was highly predictive of all end points ( eg , hazard rate ratios [ HRRs ] per 1 SD CCA-IMT increase were 1.43 [ 95 % CI : 1.35 to 1.51 ] for MI , 1.47 [ 1.35 to 1.60 ] for stroke , and 1.45 [ 1.38 to 1.52 ] for MI , stroke or death ; all P<0.0001 ) . Even after adjustment for age , sex , and vascular risk factors , the predictive value of CCA-IMT and bifurcation IMT remained significant for MI and the combined end point . For the latter , the HRRs were considerably higher in the younger than in the older age group ( eg , HRR per 0.1 mm CCA-IMT was 1.34 [ 1.16 to 1.55 ] vis-à-vis 1.10 [ 1.05 to 1.15 ] ; P=0.011 for age-IMT interaction ) . Conclusions — Carotid IMT independently predicts future vascular events . Its predictive value is at least as high in younger subjects as in older subjects CONTEXT Polycystic ovary syndrome ( PCOS ) is associated with comorbidities that may contribute to increased risk of cardiovascular disease . PCOS is associated with increased risk of metabolic syndrome , dyslipidemia , and diabetes , but it remains unclear whether traditional cardiovascular ( CV ) risk factors can help predict coronary artery disease in this population . OBJECTIVE The objectives of the study were to detect early-onset sub clinical coronary atherosclerosis ( using coronary artery calcium as a marker ) in young women with PCOS , compared with age- and body mass index-matched controls , and to compare traditional CV risk factors and inflammatory markers in the two groups . DESIGN This was a prospect i ve case-control study . SETTING The study was conducted at a university hospital . SUBJECTS Twenty-four obese ( body mass index > or= 30 kg/m2 ) PCOS subjects and 24 obese controls participated . OUTCOME MEASURES Coronary artery calcium , inflammatory markers ( high-sensitivity C-reactive protein , IL-6 , TNFalpha , adiponectin , leptin ) , fasting blood tests ( glucose , lipids , insulin ) , and dual-energy x-ray absorptiometry scan for body fat distribution were measured . RESULTS Coronary artery calcium was detected in eight of 24 PCOS subjects ( 33 % ) and two of 24 controls ( 8 % ) ( odds ratio 5.5 , 95 % confidence interval 1.03 , 29.45 , P < 0.03 ) . Traditional CV risk factors did not differ significantly between the two groups , nor did markers of inflammation or adiposity , body fat distribution , or metabolic parameters with the exception of significantly lower quantitative insulin sensitivity check index ( marker for insulin resistance ) in the PCOS group ( P < 0.05 ) . CONCLUSIONS Young , obese women with PCOS have a high prevalence of early asymptomatic coronary atherosclerosis , compared with obese controls . This increased risk is independent of traditional CV risk factors and novel markers of inflammation . These findings underscore the need to screen and aggressively counsel and treat these women to prevent symptomatic CV disease OBJECTIVE To determine serum interleukin (IL)-18 levels and to find out whether IL-18 is associated with carotid intima-media wall thickness ( IMT ) and various cardiovascular risk factors in women with polycystic ovary syndrome ( PCOS ) . DESIGN A prospect i ve , controlled study . SETTING University hospital . PATIENT(S ) Sixty women with PCOS and 60 healthy women were included this study . INTERVENTION(S )  Serum levels IL-18 , homocysteine ( Hcy ) , C-reactive protein ( CRP ) , IL-6 , malonyldialdehyde ( MDA ) , lipid and hormone profiles were measured .  Carotid IMT  was evaluated for both common carotid arteries . MAIN OUTCOME MEASURE(S ) Serum IL-18 , carotid IMT , Hcy , CRP , IL-6 , MDA , and homeostasis model assessment of insulin resistance . RESULT ( S ) The evaluation , which was made without the obesity influence taken into consideration , revealed that patients with PCOS have increased serum IL-18 levels than that of the control group ( 214 + /- 102 vs. 170 + /- 78 pg/mL ) . The interaction between PCOS and obesity was seen to have statistical significance ( F = 67.8 ) . Body mass index ( BMI ) , waist to-hip ratio , Hcy , and homeostasis model assessment of insulin resistance are independent determinants of plasma IL-18 in patients with PCOS .  Elevated serum IL-18 levels were positively and significantly correlated with a greater carotid IMT . For Hcy and carotid IMT , the interaction between PCOS and obesity was found in a two-way ANOVA variation analysis ( F = 48.5 and F = 81.5 , respectively ) . CONCLUSION ( S ) Elevated serum IL-18 levels were associated with cardiovascular risk factors and carotid IMT in patients with PCOS The 3-hydroxy-3-methylglutaryl coenzyme A ( HMG-CoA ) reductase inhibitors have proven to be more effective in reducing levels of low density lipoprotein ( LDL ) cholesterol and to be better tolerated than other lipid-lowering compounds . Most of the trials evaluating the effects of these new agents on progression of atherosclerosis have not included individuals asymptomatic for cardiovascular disease and who have LDL cholesterol levels at or below the limits established by the National Cholesterol Education Program for initiating treatment . The Asymptomatic Carotid Artery Progression Study ( ACAPS ) tested the effect of the HMG-CoA reductase inhibitor , lovastatin , on early-stage carotid atherosclerosis ( as detected by B-mode ultrasonography ) in 919 asymptomatic men and women , 40 - 79 years of age , who had LDL cholesterol levels between the 60th and 90th percentiles . Participants r and omized into this double-blind , placebo-controlled , factorially design ed study received lovastatin ( 20 - 40 mg/day ) or lovastatin-placebo and warfarin ( 1 mg/day ) , or warfarin-placebo over a 3-year period . The progression of the mean maximum intimal-medial thickness ( IMT ) over 12 walls of both carotid arteries represented the primary outcome . Lovastatin treatment was associated with a reduction in progression of mean maximum IMT ( p < 0.001 ) . Levels of LDL cholesterol were reduced by 28 % ( 43.5 mg/dl [ 11.25 mmol/liter ] ) in the lovastatin group within 6 months ( p < 0.0001 ) and remained stable throughout the follow-up period , whereas these levels remained essentially unchanged in the lovastatin-placebo group . The difference in incidence of major cardiovascular events for patients in the lovastatin-placebo group was significant : 5 versus 14 , respectively ( p < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT Polycystic ovary syndrome ( PCOS ) is associated with early impairment of vascular structure and a low- grade chronic inflammation . Aldosterone is a well-recognized cardiovascular risk ( CVR ) factor and is related to inflammatory processes . OBJECTIVE Our objective was to investigate serum aldosterone levels in PCOS and correlate them to some CVR factors and early atherosclerotic markers . DESIGN AND SETTING A prospect i ve baseline-controlled clinical study was conducted at the University " Federico II " of Naples School of Medicine ( Naples , Italy ) . PATIENTS Fifty PCOS women age- and body mass index-matched with 50 healthy women were enrolled . MEAN OUTCOME MEASURES Anthropometric , hormonal , and metabolic patterns , including plasma aldosterone , renin , and C-reactive protein , were measured in each subject . Intima-media thickness was also evaluated in each patient and control . RESULTS Aldosterone levels were significantly increased ( P < 0.001 ) in PCOS compared with healthy women ( 10.5 + /- 3.2 vs. 5.7 + /- 2.5 ng/dl ) . In PCOS , a significant ( P < 0.001 ) direct correlation between plasma aldosterone and homeostasis model assessment , C-reactive protein , intima-media thickness , and mean blood pressure was found . On the other h and , high-density lipoprotein cholesterol and potassium were inversely ( P < 0.001 ) related to serum aldosterone . Multiple linear regression analysis showed that the area under the curve for insulin and homeostasis model assessment was linearly related to aldosterone in PCOS . CONCLUSION PCOS women show an insulin resistance related increase in serum aldosterone levels OBJECTIVES Previous studies have suggested that vascular reactivity may be altered in women with polycystic ovary syndrome ( PCOS ) . We sought to evaluate the vascular reactivity specifically the endothelial function ( EF ) in women with PCOS and to study the effect of metformin on their EF . STUDY DESIGN Thirty-one women diagnosed with PCOS and 33 healthy controls underwent evaluation of EF using a post-ischemia reactive hyperemia technique ( Endo-PAT ) . EF was quantitatively determined as the ratio between the arterial pulse wave amplitude following a 5min arterial occlusion in the forearm to the pre-occlusion value . Oral metformin 850 mg bid was administered to PCOS patients . After 3 months of treatment EF was reassessed using the same technique . RESULTS The average endothelial function was 1.48+/-0.32 in the PCOS group versus 2.00+/-0.51 in the controls ( P<0.001 ) . There were no significant changes in the EF among the 18 patients who were treated with metformin  , EF index pre- and post-treatment was 1.42 versus 1.43 , respectively . CONCLUSIONS Endothelial dysfunction is more likely to occur among PCOS patients than in healthy controls . These preliminary results suggest that metformin treatment for 3 months in PCOS patients does not improve endothelial function OBJECTIVE Muscle mass plays an important role in determining cardiovascular and metabolic risks in polycystic ovary syndrome ( PCOS ) . In addition , whether lean mass influences carotid intima-media thickness ( IMT ) in PCOS has not been assessed . DESIGN Prospect i ve investigation . METHODS Ninety-five women with PCOS were age- and weight-matched to 90 ovulatory controls . All women had dual X-ray absorptiometry for lean , fat and bone mass  , and bone mass density ( BMD )  . Serum testosterone , sex hormone-binding globulin , insulin , and glucose and carotid IMT  were determined . Free and rogen index ( FAI ) and insulin resistance ( by QUICKI ) were calculated . RESULTS In PCOS , waist circumference and insulin were higher and QUICKI lower than in controls ( P<0.01 ) . Trunk fat mass , % trunk fat , and lean mass were higher in PCOS compared to controls ( P<0.01 ) , while total bone mass and BMD were similar . IMT was increased in PCOS ( P<0.01 ) but only 15 % of PCOS patients had abnormal ( > or = 0.9 mm ) values . Lean mass correlated with fat parameters , insulin , QUICKI , and FAI , but not with total testosterone ; and after adjustments for insulin and QUICKI , lean mass still correlated with fat mass ( P<0.01 ) but not FAI . Lean mass correlated with IMT ( P<0.01 ) , but this was dependent on insulin . However , excluding those patients with abnormal IMT values , IMT correlated with lean mass independently of insulin . Bone mass correlated with lean and fat mass , but not with insulin or and rogen . PCOS patients with ' pathological ' IMT values had higher % trunk fat , lean mass , and insulin , lower QUICKI , and higher testosterone and FAI compared with those with normal IMT . CONCLUSION Lean mass is increased in PCOS , while bone mass is similar to that of matched controls . The major correlates of lean mass are fat mass and insulin but not and rogen . Lean mass also correlated with IMT , and although influenced by insulin , small changes in IMT may partially reflect changes in muscle mass , while clearly abnormal values relate to more severe abnormalities of PCOS
BACKGROUND Polycystic ovary syndrome ( PCOS ) is a common reproductive endocrine disorder associated with cardiovascular disease ( CVD ) risk factors and metabolic disturbances .
This systematic review and meta- analysis was conducted to determine whether carotid intima-media thickness ( CIMT ) , a marker of sub clinical atherosclerosis , is higher in women with PCOS compared with women without PCOS .