| Background and ObjectionD-dimer (DD) units are generated by action of factor ⅩⅢa on fibrin monomers and polymers and when the endogenous fibrinolytic system degrades cross-linked fibrin present in the organism. Because of D-dimer stay stable and can resist active by vitro. It is the most widely used as clinical marker of activated blood coagulation, like pulmonary embolism and deep venous thrombosis, anticoagulant therapy, acute dissecting aortic dissection, the risk of cardiovascular diseases and the metastasis of cancer.In previous studies, plasma D-dimer level rose with age, plasma cholesterol level, triglyceride, creatinine, erythrocyte sedimentation rate, hemoglobin and body mass index, which are independently associated with the level of D-dimer. The level of D-dimer increased with age, partly because of pro-in-flammatory state, lip id abnormalities and obesity, which may explain the reasons of the specificity for embolism decrease, which makes the test less useful to exclude pulmonary embolism in older patients. Indeed, the test is able to rule out pulmonary embolism in60%of patients aged<40years, but in only5%of patients aged>80. Rene’e A Douma, et al. analyzed retrospective multicenter cohort studies, in order to conclude a age adjusted cut-off value for D-dimer test=(ageX10)μg/l (if age>50). This new cut-off value adjusted to age combined with clinical probability greatly increased the utility ofthe D-dimer test for the exclusion of pulmonary embolism among older patients without reducing safety. Haas F J et al found, for patients> or=60years, a threshold of750microg/L has the best results with negative predictive value of100%for all assays and specificity of48.5%(STA Liatest),60.6%(Tina-quant), and49.2%(Innovance).The study is to analyze the variation factors of plasma D-dimer levels in healthy people. In case of the influence factors of elderly persons, most studies observational indexes were mostly from subsequent views:substance metabolism, flammatory state and genetics. In this study, we will disscuss the reasons of high level of plasma D-dimer in elderly people from three parts:coagulation system, fibrinolytic system and vascular endothelial dysfunction. We made a cross-sectional study to analyze the influence factors of D-dimer increased with aging in elderly people.Methods and materialsOur study included by two parts. Part one The objects of study were164health examination persons in Navy general hospital from June2009to December2009. The inclusion criteria:①age>or=18years;②according to the protocol of SENIEUR on health adult. The exclusion criteria:①malignant tumor history;②with coagulation and embolism diseases;③with anticoagulant drugs;④with activated cardiovascular diseases and chronic congestive heart failure;⑤with surgery history;⑥with chronic obstructive pulmonary disease, acute or chronic infection and sepsis;⑦with hepatic diseases and nephropathy, including diabetic nephropathy;⑧pregnant women. There were164persons who met the inclusion criteria, age32-90y, male verse female=132:32. According to the definition of world health organization, the elderly is defined as the age>60y. Blood routine examination, hepatic and renal function, fibrinogen and D-dimer were given to each object. The levels of D-dimer were measured by turbidimetric quantitative immunoassay. The following stastics methods were used to analyze of data:One-way ANOVA, correlation and regression, polychotomous logistic regression, of which the first two methods were used to analyze the change of D-dimer, the last one was used to analyze the influence factors.Part two The objects of study were132health examination persons in Navy general hospital of China People Liberation Army from March2011to November2011. The inclusion criteria:①age≥60years;②According to the ’Chinese Medical Association’tenth recommendations in1995. The exclusion criteria:①with hepatic disease and nephropathy, including diabetic nephropathy;②with malignant tumor history;③with coagulation and embolism diseases, such as pulmonary embolism, deep venous embolism;④with acute or chronic infection, without sepsis;⑤with activated cardiovascular diseases;⑥with chronic obstructive pulmonary disease;⑦with anticoagulant drugs;④with chronic congestive heart failure;⑨with surgery history during the recently half year. There were132persons who met the inclusion criteria, age60-91y, male:female=68:64. The reference interval value of D-dimer is0-232ng/ml.Total of66subjects were included in experimental group, which D-dimer is higher than reference limits. The other66subject were in control group, which D-dimer levels are normal. The general information, such us name, sex, blood pressure, smoking, chronic disesases history, could be obtained through Information-based Doctor Worksation. The marker of fibrinolytic system-D-dimer, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor-1, the markers of coagulation system-fibrinogen, activated partial thro mbop last in time, prothrombin time, and the markers of vascular endothelial--won Willebrand factor, thrombomodulin were given to each subject. These results could be retrievaled through laboratory information management. The following stastics methods were used to analyze ofdata:correlation, regression and polychotomous logistic regression, of which the first two methods were used to analyze the change of D-dimer, the last one was used to analyze the influence factors. The enumeration data were analyzed with Chi-square test.ResultsPart one According to age group analysis D-dimer:the participants were divided into four groups according to age≤49y;50-59y;60-69y and≥70y. Oneway ANOVA were conducted between the four groups and have significance difference (P=0.001). D-dimer levels have no significant difference between≤49y and50-59y (P=1.000). D-dimer levels in60-69y and≥70y separately compared with other three groups, which analysis shown have significance difference(P<0.05). The analysis revealed that D-dimer levels were stable in less than60years group and increased with age in old group. D-dimer levels were significantly higher in aged group than that in the young group (P<0.05). The correlation and regression of D-dimer and age: the D-dimer was log transformed because it was not normally distributed. The logDD level correlated significantly with age (r=0.38, P=0.001), and the regression equation was1.38+0.01×age. According to Freddy Tita-Nwa et al study and our laboratory reference interval limit, total of164Participants were divided into three groups according to baseline D-dimer levels>232ng/ml;100-232ng/ml and<100ng/ml. Polychotomous logistic regression analysis illustrated that age, sex and fibrinogen were risk factors of D-dimer. For DD<100ng/ml group versus100-232ng/ml group, age (odds ratio:1.048,95%confidence interval:1.010-1.087, P=0.013), sex (OR:2.828,95%CI:1.095-7.304, P=0.032), fibrinogen (OR:2.367,95%CI:1.152-4.865, P=0.019). For DD<100ng/ml group versus>232ng/ml group, age (OR:1.142,95%CI:1.084-1.204, P<0.001), sex (OR:13.516,95%CI:1.229-148.701, P=0.033), fibrinogen (OR:3.082,95%CI:1.244-7.634, P=0.015). Part two Analysis of the level of fibrinogen, von Willebrand factor, thrombomodulin between the experimental group and ther control group:the levels of fibrinogen, von Willebrand factor antigen and thrombomodulin between experimental group and control group are different (P=0.001, P=0.0002and P=0.008), and higher levels were found in experimental group. There were no difference in sex, smoking, diastolic blood pressure, systolic blood pressure, weight, hypertension, coronary heart disease and diabetes (P>0.05). However, age was older in experimental group than control (P=0.0003). Controlling for aging, partial correlation analysis was conducted between D-dimer and fibrinogen, and fibrinogen was associated with elevated logD-dimer, correlation coefficient (r) was0.187(P=0.034), the correlation is significant, but the relevance is not apparent. Von Willebrand factor antigen was associated with logD-dimer, r=0.450(P=0.001), which means significant correlation and closely. Thrombomodulin was associated with logD-dimer, r=0.301(P=0.025), which means significant correlation, but not much closely. There were no difference in plasminogen, tissue plasminogen activator and plasminogen activator inhibitor-1(P>0.05).ConclusionsIn healthy people, plasma D-dimer rises with age, and the analysis reveals that D-dimer levels stay stable in less than60years people, while increased with age in elderly people. The D-dimer level is positive associated with aging using linear correlation analysis. According to the reference level of D-dimer<100ng/ml, D-dimer levels are influenced by age, sex and fibrinogen. Plasma D-dimer increases with age and fibrinogen and is slightly higher in women than in men.Further research was to analysis the relationship of the increased level of D-dimer and the influence factors. Including, the general condition (sex, weight, smoking, systolic pressure, diastolic pressure), the chronic diseases (hypertension, coronary heart disease, diabetes), fibrinolytic system (plasminogen, tissue plasminogen activator and plasminogen activator inhibitor-1), coagulation system (activated partial thromboplastin time, prothrombin time and fibrinogen), endothelial dysfunction (von Willebrand factor antigen and thrombomodulin). There were difference in age, fibrinogen, von Willebrand factor antigen and thrombomodulin between experimental group and normal control group in elderly people. Controlling for age, there were partial correlation respectively D-dimer and fibrinogen, D-dimer and von Willebrand factor antigen and D-dimer and endothelial dysfunction. And closely with von Willebrand factor antigen. It concludes that endothelial dysfunction is a reason of high level of D-dimer.The increased D-dimer in elderly is a important issue, which is a tough trouble in clinical diagnosis and therapy. Our study finds that plasma D-dimer increased with age, and the reason is related with endothelial dysfunction. The test of D-dimer is a predictor of endothelial dysfunction that is many diseases risk factors. Protecting endothelial medine may be a good choice when plasma D-dimer is high in elderly people. |
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