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Serum C-reactive protein increases the risk of venous thromboembolism: a prospective study and meta-analysis of published prospective evidence.

ABSTRACT: Evolving debate suggests that C-reactive protein (CRP) might be associated with the development of venous thromboembolism (VTE); however, the evidence is conflicting. We aimed to assess the prospective association of CRP with VTE risk. C-reactive protein was measured in serum samples at baseline from 2420 men aged 42-61 years, from the Kuopio Ischemic Heart Disease study. Within-person variability in CRP levels was corrected for using repeat measurements of CRP taken 11 years after baseline. Incident VTE events (n = 119) were recorded during a median follow-up of 24.7 years. The age-adjusted regression dilution ratio for log_e CRP was 0.57 [95% confidence interval (CIs): 0.51-0.64]. In age-adjusted Cox regression analysis, the hazard ratio (95% CIs) for VTE per 1 standard deviation (SD) increase in log_e baseline CRP was 1.17 (0.98-1.40). Further adjustment for several established and emerging risk factors did not alter the association. In a meta-analysis of nine population-based studies (including the current study) comprising 81,625 participants and 2225 VTE cases, the fully-adjusted risk estimate for VTE was 1.14 (1.08-1.19) per SD increase in log_e baseline CRP. In a pooled dose-response analysis, a linear association between CRP and VTE risk was suggested (P for nonlinearity = 0.272). The pooled risk estimate for VTE per 5 mg/l increment in CRP levels was 1.23 (1.09-1.38). C-reactive protein was only modestly associated with VTE risk in the primary analysis. Pooled evidence, however, suggests that elevated CRP is associated with greater VTE risk, consistent with a linear dose-response relationship.

SUBMITTER: Kunutsor SK

PROVIDER: S-EPMC5591345 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Serum C-reactive protein increases the risk of venous thromboembolism: a prospective study and meta-analysis of published prospective evidence.

Kunutsor Setor K SK Seidu Samuel S Blom Ashley W AW Khunti Kamlesh K Laukkanen Jari A JA

European journal of epidemiology 20170717 8

Evolving debate suggests that C-reactive protein (CRP) might be associated with the development of venous thromboembolism (VTE); however, the evidence is conflicting. We aimed to assess the prospective association of CRP with VTE risk. C-reactive protein was measured in serum samples at baseline from 2420 men aged 42-61 years, from the Kuopio Ischemic Heart Disease study. Within-person variability in CRP levels was corrected for using repeat measurements of CRP taken 11 years after baseline. Inc ...[more]

PMID: 28718029

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Project description:Rationale: Metabolic syndrome (MetS), the clinical clustering of hypertension, dyslipidemia, insulin resistance, and abdominal obesity, has been associated with a prothrombotic and hypofibrinolytic state, although data linking MetS with venous thromboembolism (VTE) remain limited.Objectives: The aim of this study was to measure the prevalence of MetS in patients with pulmonary embolism (PE) across a large population and to examine its impact on VTE recurrence.Methods: This was a retrospective, population-based analysis using deidentified information from a large statewide database, the Indiana Network for Patient Care. All patients with an International Classification of Diseases-defined diagnosis of PE from 2004 to 2017 were included. We measured the frequency with which patients with PE carried a comorbid diagnosis of each MetS component. Multiple logistic regression analysis was performed with VTE recurrence as the dependent variable to test the independent effect of MetS diagnosis, with a statistical model using a directed acyclic graph to account for potential confounders and mediators. Kaplan-Meier curves were constructed to compare rates of VTE recurrence over time based on the presence or absence of MetS and its individual components.Results: A total of 72,936 patients were included in this analysis. The most common MetS component was hypertension with a prevalence of 59%, followed by hyperlipidemia (41%), diabetes mellitus (24%), and obesity (22%). Of these patients, 69% had at least one comorbid component of MetS. The overall incidence of VTE recurrence was 17%, increasing stepwise with each additional MetS component and ranging from 6% in patients with zero components to 37% in those with all four. Logistic regression analysis yielded an adjusted odds ratio of 3.03 (95% CI, 2.90-3.16) for the effect of composite diagnosis requiring at least three of the four components of MetS diagnosis on VTE recurrence.Conclusions: The presence of comorbid MetS in patients with PE is associated with significantly higher rates of VTE recurrence, supporting the importance of recognizing these risk factors and initiating appropriate therapies to reduce recurrence risk.

Project description:BACKGROUND:Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE). METHODS:We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis. RESULTS:The studies included 244?865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm?Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively. CONCLUSIONS:Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.

Dataset Information

Serum C-reactive protein increases the risk of venous thromboembolism: a prospective study and meta-analysis of published prospective evidence.

Publications

Serum C-reactive protein increases the risk of venous thromboembolism: a prospective study and meta-analysis of published prospective evidence.

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