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Epidemiological studies have identified several risk factors for coronary heart disease (CHD), many of which are present in young people. [For the purpose of this review, the phrase "young people" embraces both children and adolescents.] One such risk factor is hypertension. In adults, exercise is thought to have a positive effect on blood pressure levels; however, findings are inconclusive for young people. Despite its association with CHD, obesity is on the increase in Western society's young population; prevention and intervention during early years is needed. An active lifestyle is considered to have a beneficial effect on body fatness. Lipoprotein profiles are directly associated with CHD status. In adults, there is some evidence that physical activity and/or fitness have a favourable effect on lipoprotein levels. Although information regarding the younger population is more ambiguous, it tends to concur with these findings. High levels of lipoprotein(a), are considered an independent risk factor for CHD. Relatively little has been written on young people, although some studies have postulated a favourable relationship with physical activity. An inverse relationship between aerobic fitness and CHD has been confirmed in adults; an association is not as easily verified for young people. Physical activity is similarly deemed to have a beneficial effect on health status. A high-fat diet has been linked to CHD in adults, and evidence to date reports similar findings for young people. Smoking increases the risk of CHD and even moderate smoking during youth could have damaging long-term consequences. There is some evidence that smoking is related to physical activity and fitness levels in young people. In adults, high levels of homocyst(e)ine have been associated with CHD. As yet, little has been written on the relationship between physical activity or physical fitness and homocysteine status in young people. High levels of plasma fibrinogen have been linked to CHD. Several studies have explored the relationship between plasma fibrinogen and physical activity and/or fitness in adults, but findings are inconclusive; for young people, the ambiguity is even greater. C-reactive protein is a molecular marker for CHD but, to date, little attention has been given to this aspect, especially amongst young people. The link between high levels of plasminogen activator inhibitor-1 and CHD has been confirmed, although the essence of this relationship is not established. There is a paucity of data on the younger population and the relevance of collating such information is questionable. For the younger population, most research is limited to the established CHD risk factors and further investigations of recently identified CHD risk factors are needed.
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PMID:Established and recently identified coronary heart disease risk factors in young people: the influence of physical activity and physical fitness. 1284 88

C-reactive protein (CRP) is an acute-phase reactant whose levels increase in response to a variety of inflammatory stimuli. Elevated levels in serum are observed after trauma, tissue necrosis, infection, surgery, and myocardial infarction and are associated with an increased risk of cardiovascular disease. CRP levels are also elevated in noninflammatory states, such as obesity, sleep disturbances, depression, chronic fatigue, aging, and physical inactivity. In this study, the performance of a highly sensitive CRP enzyme immunoassay was evaluated, along with common laboratory variables (specimen type, processing time, and storage conditions) that may influence measured blood concentrations of CRP. The measurement range of the assay was from 0.4 to 50 microg/liter. Total imprecision (coefficient of variation) ranged from 8.1 to 11.4%. CRP levels obtained with the enzyme immunoassay were highly correlated with those obtained with an automated immunonephelometric assay. Comparable results were obtained for plasma (heparin and EDTA treated) and serum samples, and levels were unaffected by delays in sample processing and storage temperature. CRP levels were also unaffected by up to seven freeze-thaw cycles. The median CRP concentration in healthy adults was determined to be 0.94 mg/liter, with a 95% working reference interval of 0 to 6.9 mg/liter. In view of these data, we recommend that serial serum or plasma samples for CRP should be stored at 4 degrees C for short periods of time or at -70 degrees C for longer periods and tested within the same run to minimize interassay variability.
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PMID:Analytical performance of a highly sensitive C-reactive protein-based immunoassay and the effects of laboratory variables on levels of protein in blood. 1285

Certain markers of systemic inflammation are powerful predictors of cardiovascular events. Fibrinogen, C-reactive protein (CRP), and cytokines are among the inflammatory markers associated with various cardiovascular end points. Fibrinogen and CRP both have been associated with coronary artery disease (CAD) mortality in patients with stable angina. High-sensitivity CRP (hs-CRP) and fibrinogen also have prognostic value in patients with unstable angina. In addition to prognostic implications, several cardiovascular risk factors (eg, smoking, obesity, diabetes) are associated with high levels of fibrinogen and hs-CRP. Benefits from aspirin are more likely in patients whose hs-CRP levels are very high. Some fibrates decrease fibrinogen levels and hs-CRP. Statin therapy either reduces the CAD risk associated with system inflammation or lowers circulating levels of hs-CRP.
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PMID:Utility of inflammatory markers in the management of coronary artery disease. 1286 50

The recent focus on emerging cardiovascular risk factors, such as C-reactive protein, homocysteine, and small, dense low-density lipoprotein (LDL), may give the false impression that the current approach to the assessment of cardiovascular disease risk fails to identify a large section of the high-risk population. On the contrary, the new guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) propose classifying an enormous number of individuals, including people with any form of atherosclerotic disease, diabetes, and a combination of major risk factors, into the category of high risk (>20% likelihood of a major coronary event or stroke in 10 years). Considering the widespread prevalence of the metabolic syndrome-a high-risk condition characterized by mild hypertension, mild dyslipidemia, hyperglycemia, and visceral obesity-we may be faced with the challenge of implementing aggressive risk reduction therapies in as much as 30% of the adult US population. From the point of view of risk assessment, a practical approach is to follow the NCEP guidelines (ie, place patients with diabetes and those with atherosclerotic complications in the highest risk category), apply the Framingham calculation to determine risk in people with common risk factors, and initiate early intervention in people who have familial hypercholesterolemia (LDL cholesterol >200 mg/dL) or a family history of early cardiovascular disease. The emerging risk factors may be useful for further stratifying risk in individuals with intermediate risk and the presence of risk factors not included in the Framingham calculation.
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PMID:A practical approach to risk assessment to prevent coronary artery disease and its complications. 1286 51

Acute-phase biomarkers such as C-reactive protein (CRP) and IL-6 have emerged as predictors of incident type 2 diabetes mellitus, implicating chronic subclinical inflammation as a factor in the pathophysiology of diabetes. Gestational diabetes (GDM) identifies a population of women at high risk of subsequent type 2 diabetes mellitus, representing an early stage in the natural history of the disease. In this context, we performed a cross-sectional study to determine whether markers of subclinical inflammation are elevated in patients with GDM. We studied 180 healthy pregnant women undergoing oral glucose tolerance testing in the late second or early third trimester. Based on oral glucose tolerance testing and prepregnancy body mass index (BMI), participants were stratified into four groups: 1) normal glucose tolerance (NGT) lean (BMI, <25 kg/m(2)) (n = 65); 2) NGT overweight (n = 28); 3) impaired glucose tolerance (n = 39); and 4) GDM (n = 48). Median CRP level was highest in overweight NGT subjects (8.8 mg/liter), followed by GDM (5.5 mg/liter), impaired glucose tolerance (4.4 mg/liter), and lean NGT (4.4 mg/liter) (overall P = 0.0297). CRP was significantly correlated with prepregnancy BMI (r = 0.38, P < 0.0001), followed by fasting insulin (r = 0.27, P = 0.0002) and fasting blood glucose (r = 0.18, P = 0.016). In multivariate linear regression analysis, prepregnancy BMI emerged as the most important determinant of CRP concentration, whereas glycemic tolerance status was not a significant factor. Furthermore, the observed stepwise increase in CRP per tertile of prepregnancy BMI was not significantly attenuated by glycemic tolerance status or factors known to be associated with GDM. In summary, we demonstrate that maternal serum levels of CRP are not related to GDM but rather correlate significantly with prepregnancy obesity. An independent contribution of CRP to risk of GDM could not be confirmed. These data suggest a model in which obesity mediates a systemic inflammatory response, with possible downstream metabolic sequelae, including insulin resistance and glucose dysregulation.
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PMID:C-reactive protein and gestational diabetes: the central role of maternal obesity. 1291 26

Consecutive cancer referrals to a palliative medicine program were evaluated to assess nutritional status using a standard protocol. The study included 352 patients (180 men, 172 women; median age 61 years, range 22-94 years). The most common diagnosis was lung cancer. All had metastatic disease, 139 with gastrointestinal involvement. The most common gastrointestinal symptoms were weight loss ( n=307), anorexia ( n=285), and early satiety ( n=243). Of those with any weight loss, 71% had lost >or0% of their pre-illness weight. The most common factor identified which might have contributed to weight loss was hypophagia ( n=275/307). Men had lost weight more often and to a greater extent than women. Triceps skinfold (TSF) was measured in 337: 51% had values that suggested severe fat deficiency. Upper mid-arm muscle area (AMA) was measured in 349: 30% had evidence of significant muscle mass reduction. The body mass index (BMI) was normal or increased in most patients. Calculated resting energy expenditure (REE) ( n=324) was high in 41%. C-reactive protein was elevated in 74% of those measured ( n=50). We conclude that: (1).most of this group of cancer patients referred to palliative medicine had severe weight loss; (2).there was a gender difference in the severity and type of weight loss; (3).males lost more weight overall and more muscle than females; (4).males with any degree of weight loss had a higher REE than females; (5).a significant correlation existed between the time from diagnosis to death and the severity of weight loss in the prior month; (6).BMI was normal in most patients, suggesting precancer diagnosis obesity; and (7).both TSF and AMA correlated well with body composition of both fat and protein as determined by bioelectrical impedance.
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PMID:Evaluation of nutritional status in advanced metastatic cancer. 1292 Jun 23

This study aimed to reveal the relationships among C-reactive protein (CRP), obesity, blood pressure (BP), and serum lipids in children. Eighty-six obese and 58 non-obese boys aged an average of 11.2 years were examined. Serum CRP levels were measured by high sensitivity latex turbidimetric immunoassay and subjects with CRP levels below 0.3 mg/dl were adopted. Comparisons of serum CRP levels, BP, and serum lipids levels between age-matched obese and non-obese groups were performed. A comparison of serum CRP levels among the percentage of relative weight quartiles and the relationships among percentage of relative weight, BP, and serum lipids in CRP quartiles were analyzed. The relationships between CRP and other parameters were analyzed by simple and stepwise multiple regressions. Obese children had significantly higher high-sensitivity CRP (hs-CRP) levels than their non-obese counterparts. The mean hs-CRP level was 5.5-fold higher in the top quartile of the percentage of relative weight than in the bottom quartile. In the top quartile of CRP, the percentage of relative weight, systolic BP, diastolic BP, pulse pressure, and low density/high density lipoprotein-cholesterol (LDL-C/HDL-C) were significantly higher than in the bottom quartile. The percentage of relative weight, BP, LDL-C, and apolipoprotein B (ApoB) showed positive correlations and HDL-C showed a negative correlation with log CRP by simple regression. Stepwise multiple regression analysis indicated that only the percentage of relative weight was strongly related to CRP. In conclusion, this study revealed a significant relationship between CRP and obesity in children. Obese children tended to have high CRP levels, BP elevation, and slight dyslipidemia. These results support the findings that CRP is one of the useful indices of childhood obesity that would affect the progression to future atherosclerotic disease. We consider that a strategy of preventing obesity from childhood would contribute to a drop in the future incidence of metabolic syndromes.
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PMID:Elevation of serum C-reactive protein levels is associated with obesity in boys. 1292 21

Inflammatory processes, marked in part by the acute phase reactant C-reactive protein (CRP) and insulin resistance are implicated in atherogenesis. Low insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) concentrations are closely associated with insulin resistance. We examined CRP in ethnic groups with differing risk for cardiovascular disease and type 2 diabetes and its relationship with insulin sensitivity (Homeostasis model assessment (HOMA)-S) and the IGF system. European (n=155), Pakistani (n=108) and African-Caribbean (African Caribbean) (n=177) origin participants were randomly sampled from population registers. All underwent basic anthropometry, glucose tolerance testing and measurement of insulin sensitivity, CRP and other metabolic variables. CRP was significantly lower in African Caribbean men and women than in other ethnic groups. Across all groups CRP correlated negatively with (HOMA-S) (rho=-0.29, P<0.001). Regression analysis which included ethnicity and body mass index (BMI) showed that low HOMA-S (beta=-0.17, P<0.001) and low IGFBP-1 (beta=-0.14, P<0.001) were independently and inversely associated with CRP, but the effect was modified by obesity. In obese subjects insulin sensitivity was not associated with CRP. However, for the whole population, a 2.7 mg/l increase in CRP was associated with a 50% (95% confidence interval (CI) 10-210%) greater risk of WHO defined metabolic syndrome, independent of IGF-I (odds ratio (OR) 0.46 (95% CI 0.22-0.96)), IGFBP-1 (OR 0.58 (0.44-0.76)), female sex (OR 0.43 (0.22-0.84)), NEFA (OR 1.06 (1.03-1.09)) and Pakistani ethnicity. High CRP (as a measure of chronic subclinical inflammation), low IGF-I and low IGFBP-1 are independently associated with the presence of the metabolic syndrome and with insulin resistance. In obese subjects insulin sensitivity is not associated with changes in CRP whilst in non-obese subjects CRP independently contributes to variation in HOMA-S.
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PMID:C-reactive protein and the insulin-like growth factor (IGF)-system in relation to risk of cardiovascular disease in different ethnic groups. 1295 85

Obesity is a risk factor for venous and arterial thrombosis. We examined relationships between body mass index (BMI) and a number of haemostatic and inflammatory variables in a community-based study of 150 adults (73 male, 77 female; age range, 23-80 years). Associations with BMI were sought after adjustment for age, smoking and diurnal variation. There were significant interactions of gender on the associations of BMI with fibrinogen (P = 0.002) and C-reactive protein (P = 0.02). In women, there were strong positive associations of BMI with fibrinogen (r = 0.57, P < 0.0001) and C-reactive protein (r = 0.40, P = 0.001). In men, these associations were non-significantly inverse. For all other variables there were no sex differences, so results for men and women were combined. Significant positive associations with BMI were seen for factor VIIc, activated factor XII, antithrombin activity, protein C activity and plasminogen activator inhibitor-1 activity. Inverse associations with BMI were seen for tissue plasminogen activator activity and activated protein C ratio. Increasing BMI is associated with elevation of certain coagulation factors, inhibitors of fibrinolysis, and inhibitors of coagulation, the latter potentially reflecting a compensatory response. Gender influences the association of certain inflammatory variables with BMI so the sexes should be considered separately in studies of inflammation and obesity.
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PMID:Associations of haemostatic variables with body mass index: a community-based study. 1296 Jun 11

Traditional risk factors for atherosclerosis are well known and their control decreases importantly the appearance of the disease. These factors are the genetic charge, dyslipidemia, smoking, systemic arterial hypertension, diabetes, obesity, gender, age, stress, estrogen levels in women, and life style. However, in the last decade, new risk factors have been identified especially for coronary and cerebrovascular atherosclerosis. Among these factors, the inflammatory process has been pointed out in which acute stage reactants participate, such as C-reactive protein, leukocyte count, globular sedimentation, multiple cytokines, alpha tumor necrosis factor, vascular and cellular adhesion molecules, some metalloproteinases, pregnancy-associated plasma protein A, lipoprotein-associated phospholipase A2, angiotensin II, and very probably infection. This article discusses the mechanism by which these markers participate in the atherosclerotic process and their value as predictors of future coronary events, as well as to what extent current therapeutics can contribute to decrease these events and to improve patient care.
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PMID:[Inflammation in atherosclerosis]. 1296 66


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