Synergistic effects of depressed mood and obesity on long-term cardiovascular risks in 1510 obese men and women: results from the MONICA-KORA Augsburg Cohort Study 1984-1998

OBJECTIVE: To examine the contribution of depressed mood in obese subjects on the prediction of a future coronary heart disease event (CHD). DESIGN: A prospective population-based cohort study of three independent cross-sectional surveys with 6239 subjects, 45-74 years of age and free of diagnosed CHD, stroke and cancer. During a mean follow-up of 7 years, 179 CHD events occurred among men and 50 events among women. SUBJECTS: A total of 737 (23%) male and 773 (26%) female subjects suffering from obesity (BMI >or=30 kg/m2). MEASUREMENTS: Body weight determined by trained medical staff following a standardized protocol; standardized questionnaires to assess subsyndromal depressive mood and other psychosocial features. RESULTS: The main effect of obesity to predict a future CHD (hazard ratio, HR=1.38, 95% CI 1.03-1.84; P=0.031) and the interaction term of obesity by depression (HR=1.73, 95% CI 0.98-3.05; P=0.060) were borderline significant, both covariate adjusted for multiple risk factors. Relative to the male subgroup with normal body weight and no depression, the male obese group with no depression was not at significantly increased risk for CHD events (HR=1.17, 95% CI 0.76-1.80; P=0.473) whereas CHD risk in males with both obesity and depressed mood was substantially increased (HR=2.32, 95% CI 1.45-3.72, P>0.0001). The findings for women were similar, however, not significant probably owing to lack of power associated with low event rates. Combining obesity and depressed mood resulted in a relative risk to suffer from a future CHD event of HR 1.84 (95% CI 0.79-4.26; P=0.158). CONCLUSIONS: Depressed mood substantially amplifies the CHD risk of middle-aged obese, but otherwise apparently healthy men. The impact of depression on the obesity risk in women is less pronounced.     

C反应蛋白与冠心病的相关性研究

目的：探讨C反应蛋白（CRP）与冠心病发生、发展的关系及其对预后的预测价值。方法：采用免疫透射比浊法测定136例入选对象CRP的含量。其中冠心病106例,包括稳定型心绞痛（SAP）组38例。不稳定型心绞痛（USAP）组39例、急性心肌梗死（AMI）组29例;正常对照组30例。结果：（1）冠心病患中CRP异常升高率为67．9％;（2）SAP组CRP有所升高,但无统计学意义;USAP和AMI组较正常对照组CRP明显升高（P均＜0．01）;（3）AMI的CRP水平较USAP组更高（P＜0．05）。结论：CRP升高是冠心病发生、发展的危险因素之一,它与冠心病严重程度呈正相关,对预后有一定的预测价值。     

C反应蛋白与不同类型冠心病相关性的临床研究

目的:通过炎症反应标志物C反应蛋白(CRP)探讨炎症与急性冠状动脉综合征(ACS)、稳定型心绞痛(SAP)的关系,及其在急性心肌梗死(AMI)中发生心脏事件的特点。方法:受试者共 141 例,ACS组 71 例,其中AMI组31例,不稳定型心绞痛(UAP)组40例;SAP组32例;对照组38例。CRP含量测定采用免疫比浊法。结果:①ACS组CRP显著高于对照组。②AMI组 CRP显著高于 UAP组、SAP组、对照组。③UAP组与 SAP组及对照组相比CRP增高,均差异有统计学意义。④SAP组与对照组相比 ,CRP升高差异无统计学意义。⑤AMI组中CRP在发病后48 h达到峰值。⑥AMI组中发生心脏事件亚组的 CRP明显高于其中未发生心脏事件亚组。结论:发生ACS时CRP显著升高,表明ACS过程中存在炎症反应,并在一定程度上反映心肌损伤及坏死的严重程度。AMI中 CRP显著升高时,可较好地预测AMI心脏事件的发生。     

Macrophage migration inhibitory factor (MIF) and risk for coronary heart disease: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002

Objective

Macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity, has been reported to contribute to the development of cardiovascular disease. MIF is expressed in atherosclerotic lesions in humans, and gene deletion and antibody inhibition studies in animal models indicated that MIF may be cause rather than consequence of atherosclerosis. We sought to assess the triangular association between MIF genotypes, circulating MIF levels and risk for incident coronary heart disease (CHD) in the large, prospective, population-based MONICA/KORA case-cohort study (Augsburg, Southern Germany).

Methods

MIF genotypes, haplotypes and serum concentrations were determined in 363 individuals with incident CHD and 1908 individuals without CHD during follow-up (mean follow-up time 10.3 years).

Results

Circulating MIF concentrations were not associated with the risk for CHD. In women, carriers of the minor alleles rs755622C and rs2070766G had a higher risk for incident CHD, and a haplotype that contained these two minor alleles was significantly associated with increased risk for CHD (HR 2.44, 95%CI 1.30–4.59).

Conclusion

The lack of association between serum levels and incident CHD indicates that MIF may not be a novel biomarker for CHD risk. However, the association of a haplotype containing the rs755622C allele, which has been reported before to increase the susceptibility for various other proinflammatory conditions, with CHD points towards a role for MIF in local vascular inflammation and atherogenesis.     

C-reactive protein and coronary heart disease: diagnostic and therapeutic implications for primary prevention

Coronary heart disease (CHD) is the leading cause of death in the industrialized world. Recent laboratory and clinical studies have shown that inflammation plays a pivotal role in the inception, progression, and destabilization of atheromas. The acute-phase reactant C-reactive protein (CRP) has been shown to reflect systemic and, perhaps, vascular inflammation and to predict future cardiovascular events in asymptomatic individuals. The relative risk associated with CRP is independent of other cardiovascular disease risk factors. High-sensitivity assays (hs-CRP) are needed for the measurement of CRP concentration for the purpose of predicting the risk of future coronary events. Available assays must be standardized because patients' results will be interpreted using population-based cutpoints. An algorithm for risk stratification incorporating hs-CRP and total cholesterol to high-density lipoprotein cholesterol ratio has been developed. Statin class drugs and aspirin appear to modulate CHD risk in those with increased hs-CRP concentration. Several prospective studies are now underway to specifically develop novel clinical utilities and therapeutic strategies for hs-CRP.     

C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992

BACKGROUND: Inflammatory reactions in coronary plaques play an important role in the pathogenesis of acute atherothrombotic events; inflammation elsewhere is also associated with both atherogenesis generally and its thrombotic complications. Recent studies indicate that systemic markers of inflammation can identify subjects at high risk of coronary events. METHODS AND RESULTS: We used a sensitive immunoradiometric assay to examine the association of serum C-reactive protein (CRP) with the incidence of first major coronary heart disease (CHD) event in 936 men 45 to 64 years of age. The subjects, who were sampled at random from the general population, participated in the first MONICA Augsburg survey (1984 to 1985) and were followed for 8 years. There was a positive and statistically significant unadjusted relationship, which was linear on the log-hazards scale, between CRP values and the incidence of CHD events (n=53). The hazard rate ratio (HRR) of CHD events associated with a 1-SD increase in log-CRP level was 1.67 (95% CI, 1.29 to 2. 17). After adjustment for age, the HRR was 1.60 (95% CI, 1.23 to 2. 08). Adjusting further for smoking behavior, the only variable selected from a variety of potential confounders by a forward stepping process with a 5% change in the relative risk of CRP as the selection criterion, yielded an HRR of 1.50 (95% CI, 1.14 to 1.97). CONCLUSIONS: These results confirm the prognostic relevance of CRP, a sensitive systemic marker of inflammation, to the risk of CHD in a large, randomly selected cohort of initially healthy middle-aged men. They suggest that low-grade inflammation is involved in pathogenesis of atherosclerosis, especially its thrombo-occlusive complications.     

C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984-1998

BACKGROUND: Previous studies have suggested that low-grade systemic inflammation is involved in the pathogenesis of type 2 diabetes mellitus. OBJECTIVE: To investigate the association between C-reactive protein (CRP), the classic acute-phase protein, and incident type 2 diabetes mellitus among middle-aged men. METHODS: A total of 2052 initially nondiabetic men aged 45 to 74 years who participated in 1 of the 3 MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg surveys between 1984 and 1995 were followed up for an average of 7.2 years. Incidence of diabetes was assessed by questionnaire mailed to participants in 1998. High-sensitive CRP was measured by an immunoradiometric assay. RESULTS: A total of 101 cases of incident diabetes occurred during the follow-up period. The age-standardized incidence rate was 6.9 per 1000 person-years. Men with CRP levels in the highest quartile (CRP > or = 2.91 mg/L) had a 2.7 times higher risk of developing diabetes (95% confidence interval, 1.4-5.2) compared with men in the lowest quartile (CRP < or = 0.67 mg/L) in a Cox proportional hazards model adjusted for age and survey. After further adjustment for body mass index, smoking, and systolic blood pressure, the observed association was significantly reduced and became nonsignificant. CONCLUSIONS: Low-grade systemic inflammation is associated with an increased risk of type 2 diabetes mellitus in middle-aged men. Inflammation could be one mechanism by which known risk factors for diabetes mellitus, such as obesity, smoking, and hypertension, promote the development of diabetes mellitus.     

C-reactive protein gene haplotypes and risk of coronary heart disease: the Rotterdam Study.

AIMS: C-reactive protein is associated with risk of cardiovascular disease. However, whether C-reactive protein is a marker of severity of cardiovascular disease or actually is involved in its pathogenesis remains unknown. We investigated the relation between C-reactive protein haplotypes, representing the comprehensive variation of the C-reactive protein gene, and coronary heart disease. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based study among men and women aged 55 years and older. C-reactive protein was associated with risk of coronary heart disease, with a multivariable adjusted hazard ratio of 1.9 (95% CI 1.5-2.4) for the highest vs. the lowest quartile. Four C-reactive protein haplotypes were present with overall frequencies of 32.8, 31.7, 29.5, and 5.9%. C-reactive protein serum levels were significantly different according to C-reactive protein haplotypes. C-reactive protein haplotypes were not associated with coronary heart disease. CONCLUSION: Steady-state C-reactive protein serum level is influenced by C-reactive protein gene haplotypes. Although elevated C-reactive protein level has lately been found to be a consistent and relatively strong risk factor for cardiovascular disease, our study does not support that the common variation in the C-reactive protein gene has a large effect on the occurrence of coronary heart disease.     

C反应蛋白与冠心病病变程度相关的研究

目的 :探讨血浆 C反应蛋白 （CRP）与冠心病 （CHD）病变程度之间的关系。方法 :测定经选择性冠状动脉造影（CAG）证实为 CHD患者 （n=86 ）的血浆 CRP浓度 ,并与 CAG结果正常组 （n=80 ）的血浆 CRP浓度相比较 ,分析两组之间以及 CHD组中 ,冠状动脉 （冠脉 ）病变支数与相应 CRP浓度的关系。结果 :CRP浓度在对照组、稳定型心绞痛组、不稳定型心绞痛组依次增高 ,分别为 2 2 93± 198,5 12 6± 5 0 8和 12 96 9± 10 76 μg/ L。在 CHD组中 ,单支病变组、双支病变组以及三支病变组 ,其 CRP浓度也依次增高 ,分别为 5 131± 5 13,70 2 4± 6 89,11970± 2 0 75 μg/ L。结论 :CRP浓度与冠脉病变程度关联密切     

冠心病患者血清视黄醇结合蛋白4与高敏C反应蛋白的相关性分析

目的 测定冠心病患者血清视黄醇结合蛋白4（RBP4）和高敏C反应蛋白（hs-CRP）水平,分析两者与冠心病的相关性.方法 将90例冠心病患者分为急性心肌梗死组30例,不稳定性心绞痛组30例,稳定性心绞痛组30例,另选择30例冠状动脉造影结果正常者为对照组.采用酶联免疫吸附法测定受试者血清RBP4水平,采用增强免疫透射比浊法测定血清hs-CRP水平.结果 急性心肌梗死和不稳定性心绞痛组患者血清RBP4、hs-CRP水平高于稳定性心绞痛组和对照组,差异具有统计学意义（P〈0.05）,稳定性心绞痛组血清hs-CRP水平与对照组比较,差异有统计学意义（P〈0.05）,而稳定性心绞痛组患者血清RBP4水平与对照组比较差异尤统计学意义.单支、双支、三支病变组患者血清RBP4、hs-cRP水平均高于对照组（P〈0.05）,但单支、双支与三支病变组之间比较差异均无统计学意义.经Pearson＇s相关分析,冠心病患者血清RBP4与hs-CRP的浓度呈显著正相关（r=0.469,P〈0.01）.结论 血清RBP4、hs-CRP与冠心病存在一定的相关性,可能与斑块稳定性有关,可作为预测斑块稳定性的血清标志物,但其并不能反映冠状动脉狭窄程度及范围.     

C-reactive protein and heart failure after myocardial infarction in the community

Background

There is a paucity of data on the prognostic role of C-reactive protein (CRP) measured after myocardial infarction. We prospectively examined the association of CRP with heart failure and death among patients with myocardial infarction in the community.

Methods and Results

All Olmsted County residents who had a myocardial infarction meeting standardized criteria were prospectively enrolled to measure CRP on admission and followed for heart failure and death. A total of 329 consecutive patients (mean age 69 ± 16 years, 52% men) were enrolled. At 1 year, 28% of patients experienced heart failure and 20% died. There was a strong positive graded association between CRP and the risk of developing heart failure, as well as dying over the period of follow-up (P < .001). Compared with patients in the first tertile, patients in the third tertile of the CRP distribution had a markedly increased risk of heart failure and death independently of age, sex, troponin T, Q wave, comorbidity, previous myocardial infarction, and recurrent ischemic events (adjusted hazard ratio 2.47 [95% confidence interval, 1.27-4.82] for heart failure and 3.96 [95% confidence interval, 1.78-8.83] for death).

Conclusions

These prospective data indicate that among contemporary community subjects with myocardial infarction, heart failure and death remain frequent complications. CRP is associated with a large increase in the risk of heart failure and death, independently of age, sex, myocardial infarction severity, comorbidity, previous myocardial infarction, and recurrent ischemic events. These data suggest that inflammatory processes may play a role in the development of heart failure and death after myocardial infarction independently of other conventional prognostic indicators.     

超敏C反应蛋白、血清载脂蛋白与冠心病的关系

目的 观察冠心病患者血清载脂蛋白B（ApoB）、超敏C反应蛋白（hs-CRP）的变化及临床意义.方法 测定50例不同类型的冠心病患者的ApoB和hs-CRP水平,并且与42名健康者比较.结果 与健康对照组相比,冠心病组的血ApoB和hs-CRP水平明显增高（P＜0.05）.随着病变程度的加重,ApoB、hs-CRP水平明显升高,hs-CRP浓度与病变积分呈正相关（r＝0.832）,ApoB浓度与病变积分呈正相关（r＝0.697） P＜0.05）.结论 ApoB和hs-CRP同冠心病关系密切,是冠心病的危险因素.     

冠心病患者血清C反应蛋白水平的变化及其临床意义

目的 :探讨冠心病 （CHD）患者血清C反应蛋白 （CRP）水平的变化规律及其临床意义。方法 :采用速率散射比浊度法定量动态检测 10 0例不同类型的CHD患者血清的CRP水平 ,同期检测 30例健康志愿者血清的CRP水平做对照 ,并结合临床资料分析。结果 :CHD组CRP含量明显高于正常对照组 （P <0 .0 1） ;不同类型的CHD患者中CRP浓度 ,急性心肌梗死 （AMI）组 >不稳定型心绞痛组 （UAP） >稳定型心绞痛 （SAP） ,差异有显著性 （均P <0 .0 1）。其动态变化规律是SAP患者CRP呈轻度升高 ,心肌酶谱各指标无显著变化 ;UAP组发病早期CRP升高显著、稳定期下降迅速 ,心肌酶谱各指标轻度升高 ;AMI组持续升高 ,心肌酶谱显著升高。结论 :CRP同CHD关系密切 ,可作为判断CHD危险度的一个有用指标。     

C反应蛋白水平与冠心病的相关性研究

目的:探讨C反应蛋白(CRP)水平与冠心病的相关性。方法:所有对象均经选择性冠状动脉造影(CAG)证实,其中稳定性心绞痛组24例,不稳定性心绞痛组42例,正常对照组30例,分析两组之间以及冠心病组患者冠脉病变程度与相应CRP水平的关系。结果:CRP水平在对照组、稳定性心绞痛、不稳定性心绞痛组依次增高,不稳定性心绞痛组CRP水平显著高于对照组、稳定性心绞痛组(P均<0.01)。在冠心病组中,单支病变组、双支病变组以及三支病变组中CRP水平也依次增高(P<0.01)。结论:CRP水平与冠脉病变程度密切相关,对冠心病的病变程度具有预测价值。     

C-reactive protein, cardiovascular risk factors and the association with myocardial infarction in men

OBJECTIVES: This study had three objectives: first, to investigate the association of C-reactive protein levels and myocardial infarction amongst men; secondly, to study the associations of C-reactive protein levels with cardiovascular risk factors; and thirdly, to adjust the risk of myocardial infarction for such factors. DESIGN AND SUBJECTS: A case-control study including 560 patients with a first myocardial infarction who had survived at least 6 months, plus 646 control subjects. RESULTS: Patients had significantly higher levels of C-reactive protein (mean 2.2 mg L-1) than control subjects (mean 1.7 mg L-1; P < 0.001). Persons in the highest quintile of C-reactive protein had an unadjusted 1.9-fold increased risk of myocardial infarction compared with persons in the lowest quintile (odds ratio 1.9, 95% CI: 1.3-2.7). C-reactive protein was, in addition to smoking, associated with several cardiovascular risk factors: age, obesity, diabetes, blood pressure, triglycerides and inversely associated to HDL cholesterol. Adjustment for these variables, especially for total cholesterol, HDL cholesterol and triglycerides, substantially decreased the risk of myocardial infarction for persons in the highest quintile of C-reactive protein, compared to those in the lowest quintile, to 1.3 (95% CI: 0.9-1.9). CONCLUSIONS: Our findings confirm previous reports that C-reactive protein predicts the risk of myocardial infarction. However, this association does not appear to be causal, since the increase in risk can to a large extent be explained by the presence of other cardiovascular risk factors.     

高敏C反应蛋白、肌红蛋白、心肌肌钙蛋白和肌酸激酶同工酶联合检测在急性心肌梗死诊断中的应用

目的探究高敏C反应蛋白(hs-CRP)、肌红蛋白(Myo)、心肌肌钙蛋白T(cTnT)和肌酸激酶MB同工酶(CK-MB)联合检测对急性心肌梗死(AMI)诊断中的应用。方法随机选取并回顾性分析2011年6月至2012年66月于我院诊断为急性心肌梗死患者70例及同时期进行体检的健康人群70例。研究组为急性心梗患者,发病均在6h内;对照组为签署知情同意书的体检健康人群。采用化学发光法测定两组研究对象hs-CRP、MYO、cTnT、CK-MB四项指标的阳性率及研究组发病3h、6h、12h、24h内的指标变化。结果观察两组患者高敏C反应蛋白(hs-CRP)、肌红蛋白(Myo)、心肌肌钙蛋白T(cTnT)和肌酸激酶同工酶(CK-MB)检测值,研究组检测值明显高于对照组,差异存在统计学差异(P0.05);hs-CRP最高峰出现在发病后12-24h之间,Myo最高峰出现在发病后6-12h内,cTnT最高峰出现在发病后6-12h,CK-MB最高峰出现在发病后12-24h内。结论 AMI患者血清内Myo、hs-CRP、CK-MB和cTnT值均在AMI发病2h后不同程度的升高,四项联合检测对AMI的诊断中有较大参考价值,可作为AMI发生早期有效实验室指标。     

Serum C-reactive protein and infarct size in myocardial infarct patients with a closed versus an open infarct-related coronary artery after thrombolytic therapy

Serum C-reactive protein rises in acute myocardial infarction,correlating positively with infarct size if thrombolytic treatmentis not given. This correlation disappears if thrombolytic treatmentis given, although the serum C-reactive protein concentrationis still associated with the clinical outcome of the patient. We studied the effect of early coronary recanalization inducedby thrombolytic treatment alone or combined with coronary angioplastyon the infarct related rise in serum C-reactive protein concentration. The C-reactive protein response caused by the myocardial infarctwas lower in patients with an open infarct-related coronaryartery than in patients with a closed infarct-related coronaryartery, or in control patients who did not receive thrombolytictherapy. In control patients we found the expected strong positivecorrelation between infarct size and serum C-reactive protein(r = 0.58; P <0.001, n = 48), which was similar to that inpatients with a closed infarct-related coronary artery (r =0.62; P <0.001, n = 17). In patients with an open infarct-relatedcoronary artery the correlation between infarct size and serumC-reactive protein was much weaker (r = 30; P < 0.00l, n=91).Consequently infarct size explained approximately 35% of thevariation in serum C-reactive protein values in the controlpatients and 36% in the patients with a closed infarct-relatedcoronary artery, but only 9% of the variation in the patientswith an open infarct-related artery. Ejection fraction correlatednegatively with serum C-reactive protein in both control andrecanalized patients. The association was again much strongerin the control patients. Ejection fraction explained 27% (28%if only first infarctions were considered) of the variationin serum C-reactive protein in the control patients and 8% (6%)in the recanalized patients. The present results show that coronary recanalization variablyreduces the infarct-associated rise in serum C-reactive protein.This explains the weaker association between serum C-reactiveprotein and infarct size in the patients receiving thrombolytictreatment when compared to those treated without thrombolyticdrugs and may have clinical implications.     

N-terminal probrain natriuretic peptide and C-reactive protein in stable coronary heart disease

Purpose

C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) provide prognostic information in patients with stable coronary heart disease. The aim of the study was to investigate whether combined use of NT-proBNP and CRP improves risk stratification in these patients.

Methods

This cohort study included 989 patients with stable coronary heart disease who underwent coronary stenting. CRP and NT-proBNP were measured before angiography. The primary end point of the study was all-cause mortality. Using median values of NT-proBNP (279.9 ng/L) and CRP (1.2 mg/L), patients were divided into 4 groups: low NT-proBNP-low CRP group (305 patients with NT-proBNP<median and CRP<median); low NT-proBNP-high CRP group (190 patients with NT-proBNP<median and CRP≥median; high NT-proBNP-low CRP group (237 patients with NT-proBNP≥median and CRP<median); and high NT-proBNP-high CRP group (257 patients with NT-proBNP≥median and CRP≥median).

Results

During a median follow-up of 3.6 years (interquartile range 3.3 to 4.5 years), there were 85 deaths: 6 deaths in the low NT-proBNP-low CRP group, 11 deaths in the low NT-proBNP-high CRP group, 20 deaths in the high NT-proBNP-low CRP group, and 48 deaths in the high NT-proBNP-high CRP group with Kaplan-Meier mortality estimates of 2.7%, 8.9%, 12.1% and 35.6%, respectively (P <.001). Cox proportional hazards model showed that combination NT-proBNP-CRP was the strongest independent correlate of mortality (hazard ratio [HR] 4.3, 95% confidence interval [CI], 2.0-9.3; P <.001 for high NT-proBNP-high CRP vs low NT-proBNP-low CRP).

Conclusion

Combined use of NT-proBNP and CRP improves long-term risk prediction of mortality in patients with stable coronary heart disease.