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1.
Ridker PM  Stampfer MJ  Rifai N 《JAMA》2001,285(19):2481-2485
CONTEXT: Several novel risk factors for atherosclerosis have recently been proposed, but few comparative data exist to guide clinical use of these emerging biomarkers. OBJECTIVE: To compare the predictive value of 11 lipid and nonlipid biomarkers as risk factors for development of symptomatic peripheral arterial disease (PAD). DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study using plasma samples collected at baseline from a prospective cohort of 14 916 initially healthy US male physicians aged 40 to 84 years, of whom 140 subsequently developed symptomatic PAD (cases); 140 age- and smoking status-matched men who remained free of vascular disease during an average 9-year follow-up period were randomly selected as controls. MAIN OUTCOME MEASURE: Incident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100. RESULTS: In univariate analyses, plasma levels of total cholesterol (P<.001), LDL-C (P =.001), triglycerides (P =.001), apo B-100 (P =.001), fibrinogen (P =.02), CRP (P =.006), and the total cholesterol-HDL-C ratio (P<.001) were all significantly higher at baseline among men who subsequently developed PAD compared with those who did not, while levels of HDL-C (P =.009) and apo A-I (P =.05) were lower. Nonsignificant baseline elevations of lipoprotein(a) (P =.40) and homocysteine (P =.90) were observed. In multivariable analyses, the total cholesterol-HDL-C ratio was the strongest lipid predictor of risk (relative risk [RR] for those in the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6), while CRP was the strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8; 95% CI, 1.3-5.9). In assessing joint effects, addition of CRP to standard lipid screening significantly improved risk prediction models based on lipid screening alone (P<.001). CONCLUSIONS: Of 11 atherothrombotic biomarkers assessed at baseline, the total cholesterol-HDL-C ratio and CRP were the strongest independent predictors of development of peripheral arterial disease. C-reactive protein provided additive prognostic information over standard lipid measures.  相似文献   

2.
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 designed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance. DESIGN AND SETTING: Randomized 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 randomly 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 aimed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance.  相似文献   

3.
Context  Postmenopausal hormone replacement therapy (HRT) has been shown to elevate C-reactive protein (CRP) levels. Several inflammatory biomarkers, including CRP, are associated with increased cardiovascular risk. However, whether the effect of HRT on CRP represents a clinical hazard is unknown. Objectives  To assess the association between baseline levels of CRP and interleukin 6 (IL-6) and incident coronary heart disease (CHD) and to examine the relationship between baseline use of HRT, CRP, and IL-6 levels as they relate to subsequent vascular risk. Design, Setting, and Participants  Prospective, nested case-control study of postmenopausal women, forming part of the Women's Health Initiative, a large, nationwide, observational study. Among 75 343 women with no history of cardiovascular disease or cancer, 304 women who developed incident CHD were defined as cases and matched by age, smoking status, ethnicity, and follow-up time with 304 study participants who remained event free during a median observation period of 2.9 years. Main Outcome Measure  Incidence of first myocardial infarction or death from CHD. Results  Median baseline levels of CRP (0.33 vs 0.25 mg/dL; interquartile range [IQR], 0.14-0.71 vs 0.10-0.47; P<.001) and IL-6 (1.81 vs 1.47 pg/mL; IQR, 1.30-2.75 vs 1.05-2.15; P<.001) were significantly higher among cases compared with controls. In matched analyses, the odds ratio (OR) for incident CHD in the highest vs lowest quartile was 2.3 for CRP (95% confidence interval [CI], 1.4-3.7; P for trend = .002) and 3.3 for IL-6 (95% CI, 2.0-5.5; P for trend <.001). After additional adjustment for lipid and nonlipid risk factors, both inflammatory markers were significantly associated with a 2-fold increase in odds for CHD events. As anticipated, current use of HRT was associated with significantly elevated median CRP levels. However, there was no association between HRT and IL-6. In analyses comparing individuals with comparable baseline levels of either CRP or IL-6, those taking or not taking HRT had similar CHD ORs. In analyses stratified by HRT, we observed a positively graded relationship between plasma CRP levels and the OR for CHD among both users and nonusers of HRT across the full spectrum of baseline CRP. Conclusions  These prospective findings indicate that CRP and IL-6 independently predict vascular events among apparently healthy postmenopausal women and that HRT increases CRP. However, use or nonuse of HRT had less importance as a predictor of cardiovascular risk than did baseline levels of either CRP or IL-6.   相似文献   

4.
目的 探讨痰涂片联合C反应蛋白(CRP)、降钙素原(PCT)及白细胞介素-6(IL-6)水平检测对老年细菌性肺炎的诊断价值。方法 选取2019年6月—2022年6月四川省第二中医医院100例老年细菌性肺炎患者作为细菌性肺炎组,另取同期60例老年病毒性肺炎患者作为病毒性肺炎组。两组均接受痰涂片及CRP、PCT及IL-6水平检测,对比两组检测结果,绘制受试者工作特征(ROC)曲线分析痰涂片联合CRP、PCT及IL-6水平检测对老年细菌性肺炎的诊断价值。结果 细菌性肺炎组痰涂片阳性率较病毒性肺炎组高(P <0.05)。细菌性肺炎组WBC、CRP、PCT、IL-6较病毒性肺炎组高(P <0.05)。经点二列相关性分析结果显示,WBC、CRP、PCT、IL-6水平与细菌性肺炎呈正相关(r =0.626、0.618、0.676和0.586,均P <0.05)。ROC曲线结果显示:痰涂片诊断细菌性肺炎的敏感性为0.870(95% CI:0.811,0.931)、特异性为0.867(95% CI:0.806,0.922),CRP敏感性为0.800(95% CI:0.789,0.902)、特异性为0.883(95% CI:0.824,0.953),PCT敏感性为0.850(95% CI:0.802,0.925)、特异性为0.917(95% CI:0.889,0.988),IL-6敏感性为0.790(95% CI:0.725,0.865)、特异性为0.767(95% CI:0.712,0.864),四者联合检测的敏感性为0.950(95% CI:0.845,0.978)、特异性为0.769(95% CI:0.713,0.878)。结论 痰涂片、CRP、PCT、IL-6水平可有效鉴别老年细菌性肺炎与病毒性肺炎,联合检测可进一步提高诊断效能,为后续治疗方案的制订提供参考依据。  相似文献   

5.
CONTEXT: Persons with impaired glucose tolerance (IGT) are known to have an elevated risk of developing diabetes mellitus. Less is known about diabetes risk among persons with impaired fasting glucose (IFG) or with normal glucose levels. OBJECTIVE: To determine the incidence of diabetes in relation to baseline fasting and postload glucose levels and other risk factors. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study conducted from October 1989 to February 1992 among 1342 nondiabetic white residents of Hoorn, the Netherlands, aged 50 to 75 years at baseline, in whom fasting plasma glucose (FPG) levels and glucose levels 2 hours after a 75-g oral glucose tolerance test were measured at baseline and at follow-up in 1996-1998. MAIN OUTCOME MEASURES: Cumulative incidence of diabetes, defined according to the diagnostic criteria of the World Health Organization (WHO-1985 and WHO-1999) and the American Diabetes Association (ADA-1997), during a mean follow-up of 6.4 years, compared among participants with IFG, IGT, and normal glucose levels at baseline. RESULTS: The cumulative incidence of diabetes was 6.1%, 8.3%, and 9.9% according to the WHO-1985, ADA, and WHO-1999 criteria, respectively. The cumulative incidence of diabetes (WHO-1999 criteria) for participants with both IFG and IGT was 64.5% compared with 4.5% for those with normal glucose levels at baseline. The odds ratios for diabetes (WHO-1999 criteria), adjusted for age, sex, and follow-up duration, were 10.0 (95% confidence interval [CI], 6.1-16.5), 10.9 (95% CI, 6.0-19.9), and 39.5 (95% CI, 17.0-92.1), respectively, for those having isolated IFG, isolated IGT, and both IFG and IGT. In addition to FPG and 2-hour postload glucose levels (P<.001 for both), the waist-hip ratio also was an important risk factor for developing diabetes (P =.002). CONCLUSION: In this study, the cumulative incidence of diabetes was strongly related to both IFG and IGT at baseline and, in particular, to the combined presence of IFG and IGT.  相似文献   

6.
CONTEXT: Although oligomenorrhea has been associated cross-sectionally with insulin resistance and glucose intolerance, it is not known whether oligomenorrhea is a marker for increased future risk of type 2 diabetes mellitus (DM). OBJECTIVE: To prospectively assess risk of type 2 DM in women with a history of long or highly irregular menstrual cycles. DESIGN AND SETTING: The Nurses' Health Study II, a prospective observational cohort study. PARTICIPANTS: A total of 101 073 women who had no prior history of DM and who reported their usual menstrual cycle pattern at age 18 to 22 years on the baseline (1989) questionnaire. MAIN OUTCOME MEASURE: Incident reports of DM, with follow-up through 1997, compared among women categorized by menstrual cycle length (5 categories). RESULTS: During 564 333 person-years of follow-up, there were 507 cases of type 2 DM. Compared with women with a usual cycle length of 26 to 31 days (referent category) at age 18 to 22 years, the relative risk (RR) of type 2 DM among women with a menstrual cycle length that was 40 days or more or was too irregular to estimate was 2.08 (95% confidence interval [CI], 1.62-2.66), adjusting for body mass index at age 18 years and several other potential confounding variables. The RR of type 2 DM associated with long or highly irregular menstrual cycles was greater in obese women, but was also increased in nonobese women (at body mass indexes at age 18 years of <25, 25-29, and >/=30 kg/m, RRs were 1.67 [95% CI, 1.14-2.45], 1.74 [95% CI, 1.07-2.82], and 3.86 [95% CI, 2.33-6.38], respectively). CONCLUSION: Women with long or highly irregular menstrual cycles have a significantly increased risk for developing type 2 DM that is not completely explained by obesity.  相似文献   

7.
CONTEXT: Microalbuminuria is a risk factor for cardiovascular (CV) events. The relationship between the degree of albuminuria and CV risk is unclear. OBJECTIVES: To estimate the risk of CV events in high-risk individuals with diabetes mellitus (DM) and without DM who have microalbuminuria and to determine whether levels of albuminuria below the microalbuminuria threshold increase CV risk. DESIGN: The Heart Outcomes Prevention Evaluation study, a cohort study conducted between 1994 and 1999 with a median 4.5 years of follow-up. SETTING: Community and academic practices in North and South America and Europe. PARTICIPANTS: Individuals aged 55 years or more with a history of CV disease (n = 5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine albumin/creatinine ratio (ACR) measurement. MAIN OUTCOME MEASURES: Cardiovascular events (myocardial infarction, stroke, or CV death); all-cause death; and hospitalization for congestive heart failure. RESULTS: Microalbuminuria was detected in 1140 (32.6%) of those with DM and 823 (14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI], 1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were seen for participants with or without DM, even after adjusting for other CV risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97 [95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those without DM).Compared with the lowest quartile of ACR (<0.22 mg/mmol), the RRs of the primary aggregate end point in the second quartile (ie, ACR range, 0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third quartile, 1.38 (95% CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth quartile, 1.97 (95% CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend <.001, even after excluding those with microalbuminuria). For every 0.4-mg/mmol increase in ACR level, the adjusted hazard of major CV events increased by 5.9% (95% CI, 4.9%-7.0%). CONCLUSIONS: Our results indicate that any degree of albuminuria is a risk factor for CV events in individuals with or without DM; the risk increases with the ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria identifies people at high risk for CV events.  相似文献   

8.
Lee IM  Rexrode KM  Cook NR  Manson JE  Buring JE 《JAMA》2001,285(11):1447-1454
CONTEXT: Physically active women have lower coronary heart disease (CHD) rates than inactive women. However, whether the association differs by intensity of activity or in women at high risk for CHD is unclear. OBJECTIVE: To examine the relation between physical activity, specifically investigating walking (a light-to-moderate activity depending on pace), and CHD among women, including those at high risk for CHD. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 39 372 healthy female health professionals aged 45 years or older, enrolled throughout the United States between September 1992 and May 1995, with follow-up to March 1999. Recreational activities, including walking and stair climbing, were reported at study entry. MAIN OUTCOME MEASURE: Correlation of CHD with energy expended on all activities, vigorous activities, and walking. RESULTS: A total of 244 cases of CHD occurred. Adjusting for potential confounders, the relative risks (RRs) of CHD for less than 200, 200-599, 600-1499, and 1500 or more kcal/wk expended on all activities were 1.00 (referent), 0.79 (95% confidence interval [CI], 0.56-1.12), 0.55 (95% CI, 0.37-0.82), and 0.75 (95% CI, 0.50-1.12), respectively (P for linear trend =.03). Vigorous activities were associated with lower risk (RR, 0.63; 95% CI, 0.38-1.04 comparing highest and lowest categories). Walking also predicted lower risk among women without vigorous activities. Among these women, the multivariate RRs for walking 1 to 59 min/wk, 1.0 to 1.5 h/wk, and 2 or more h/wk, compared with no regular walking, were 0.86 (95% CI, 0.57-1.29), 0.49 (95% CI, 0.28-0.86), and 0.48 (95% CI, 0.29-0.78), respectively. For walking paces of less than 3.2 km/h (2.0 mph), 3.2 to 4.7 km/h (2.0-2.9 mph), and 4.8 km/h (3.0 mph) or more, compared with no regular walking, RRs were 0.56 (95% CI, 0.32-0.97), 0.71 (95% CI, 0.47-1.05), and 0.52 (95% CI, 0.30-0.90), respectively. When analyzed simultaneously, time spent walking (P for linear trend =.01) but not walking pace (P for linear trend =.55) predicted lower risk. The inverse association between physical activity and CHD risk did not differ by weight or cholesterol levels (P for interaction =.95 and.71, respectively), but there were significant interactions by smoking and hypertension status. Physical activity was inversely related to risk in current smokers but not hypertensive women (P for interaction =.01 and.001, respectively). CONCLUSIONS: These data indicate that even light-to-moderate activity is associated with lower CHD rates in women. At least 1 hour of walking per week predicted lower risk. The inverse association with physical activity was also present in women at high risk for CHD, including those who were overweight, had increased cholesterol levels, or were smokers.  相似文献   

9.
CONTEXT: Microvascular processes have been hypothesized to play a role in the pathogenesis of type 2 diabetes mellitus, but prospective clinical data regarding this hypothesis are unavailable. OBJECTIVE: To examine the relation of retinal arteriolar narrowing, a marker of microvascular damage from aging, hypertension, and inflammation, to incident diabetes in healthy middle-aged persons. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities Study, an ongoing population-based, prospective cohort study in 4 US communities that began in 1987-1989. Included in this analysis were 7993 persons aged 49 to 73 years without diabetes, of whom retinal photographs were taken during the third examination (1993-1995). MAIN OUTCOME MEASURES: Incident diabetes (defined as fasting glucose levels of > or =126 mg/dL [7.0 mmol/L], casual levels of > or =200 mg/dL [11.1 mmol/L], diabetic medications use, or physician diagnosis of diabetes at the fourth examination) by quartile of retinal arteriole-to-venule ratio (AVR). RESULTS: After a median follow-up of 3.5 years, 291 persons (3.6%) had incident diabetes. The incidence of diabetes was higher in persons with lower AVR at baseline (2.4%, 3.1%, 4.0%, and 5.2%, from highest to lowest AVR quartile; P for trend < .001). After controlling for fasting glucose and insulin levels, family history of diabetes, adiposity, physical activity, blood pressure, and other factors, persons in the lowest quartile of AVR were 71% more likely to develop diabetes than those in the highest quartile (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.13-2.57; P for trend =.002). This association persisted with different diagnostic criteria (OR, 1.92; 95% CI, 1.10-3.36; P for trend =.01, using a fasting glucose level of > or =141 mg/dL [7.8 mmol/L] as a cutoff), and was seen even in people at lower risk of diabetes, including those without a family history of diabetes, without impaired fasting glucose, and with lower measures of adiposity. CONCLUSIONS: Retinal arteriolar narrowing is independently associated with risk of diabetes, supporting a microvascular role in the development of clinical diabetes.  相似文献   

10.
E Lindmark  E Diderholm  L Wallentin  A Siegbahn 《JAMA》2001,286(17):2107-2113
CONTEXT: Inflammatory activity is associated with high rates of long-term mortality in unstable coronary artery disease (CAD). Interleukin 6 (IL-6) induces C-reactive protein and fibrinogen, systemic markers of inflammation. OBJECTIVES: To determine whether plasma levels of IL-6 are predictive of mortality and to evaluate the interaction of IL-6 levels with the effects of invasive vs noninvasive treatment strategies in unstable CAD patients. DESIGN, SETTING, AND PATIENTS: The prospective, randomized Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease II trial, conducted among 3489 patients, 3269 of whom had plasma samples analyzed for IL-6 levels, with diagnosed unstable CAD (67% male; median age, 67 years) at 58 Scandinavian hospitals between June 1996 and August 1998. INTERVENTIONS: Patients were randomly assigned to receive either an early invasive (n = 1222) or a noninvasive treatment strategy (n = 1235). The latter group, as well as 666 patients with contraindications to invasive therapy, were further randomized to 90-day treatment with low-molecular-weight heparin (dalteparin, 5000-7500 IU twice per day; n = 1140) or placebo (n = 1127). MAIN OUTCOME MEASURE: Mortality at 6 and 12 months in the medically and interventionally randomized cohorts, respectively, in relation to IL-6 levels, measured at randomization. RESULTS: Plasma levels of IL-6 that were at least 5 ng/L compared with levels lower than 5 ng/L were associated with greatly increased mortality in the noninvasive group (7.9% vs 2.3%; relative risk [RR], 3.47; 95% confidence interval [CI], 1.94-6.21) and in the placebo-treated group (7.9% vs 2.5%; RR, 3.19; 95% CI, 1.77-5.74). The association remained significant after adjustment for most established risk indicators. An early invasive treatment strategy strongly reduced 12-month mortality among those with elevated IL-6 levels (5.1% absolute reduction; P =.004) whereas mortality was not reduced among patients without elevated IL-6 concentrations. Those taking dalteparin with elevated IL-6 levels experienced lower 6-month mortality than those who did not take dalteparin (3.5% absolute reduction; P =.08). CONCLUSIONS: Circulating IL-6 is a strong independent marker of increased mortality in unstable CAD and identifies patients who benefit most from a strategy of early invasive management.  相似文献   

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