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 loge 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 loge 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 loge 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-017-0277-4) contains supplementary material, which is available to authorized users.

Oxidized low‐density lipoprotein in inflammation‐driven thrombosis

“…The recent conclusion of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) showing a significant benefit of the anti-interleukin (IL)-1b antibody canakinumab in the secondary prevention of atherothrombotic events has clearly demonstrated the causal involvement of inflammation in this disease process [10]. On the other hand, only a modest association between C-reactive protein (CRP) levelsas markers of inflammationand venous thromboembolism (VTE) risk has been found, as demonstrated in a recent meta-analysis [11]. Nevertheless, increasing clinical evidence shows a close link between inflammation and venous thrombosis.…”

Inverse association between serum albumin and future risk of venous thromboembolism: interrelationship with high sensitivity C-reactive protein

“…We selected these risk markers based on their potential as confounders as a result of their known associations with VTE outcomes and observed associations with serum albumin using the available data (28) or evidence from previous research, as discussed in previous studies. (17) We evaluated if the association was modified by pre-specified clinically relevant characteristics including…”

“…(16) There were however some drawbacks of this study which included (i) inability to evaluate if inflammation might explain the findings, as there were no available measurements of C-reactive protein (CRP) in the study cohorts. Though a subject of debate, CRP -the major inflammatory marker -has been implicated in the aetiopathogenesis of VTE; (5,6,17) (ii) also, the study cohorts had no information on liver enzymes and hence it is uncertain if the association could be attributed to liver disease; (iii) a formal assessment of the shape of the relationship between serum albumin and VTE risk was not undertaken; hence it is uncertain if there is a dose-response relationship to the association; and (iv) finally, whether the association is A c c e p t e d M a n u s c r i p t modified by relevant clinical characteristics is not certain, as no interaction analysis was conducted in this study. In this context, our main objective was to assess the shape, nature, magnitude, and consistency of the prospective association between serum albumin and risk of VTE in one comprehensive investigation using a population-based cohort of 2,176 men with no previous history of VTE from eastern Finland.…”

Different predictive value for short-term all-cause mortality with commonly used biomarkers regarding the cause of pulmonary embolism

“…Pulmonary embolism (PE) is a huge global health problem and life-threatening condition associated with significant morbidity and all-cause mortality [1][2][3][4][5]. PE is considered to be provoked in the presence of permanent or temporary risk factors or unprovoked in the absence thereof [6,7]. Different states and diseases, sometimes very clearly and sometimes completely hidden, very often underlie PE and their presence is often crucial for the management and prognosis of patients with PE.…”