Table 1.
Summary of population-based studies assessing the relationship between circulating CRP levels and VTE.
| Author, year of publication | Type of study & participant numbers | Patient group | Timing of CRP measurement | Risk association to first or recurrent VTE | Association (yes/no) |
|---|---|---|---|---|---|
| Ridker et al., 1997 (34) | Nested case control study; 101 VTE and 543 controls. | Male physicians | Baseline CRP, prospectively followed to subsequent VTE development. | Non-significantly higher CRP (1.26 vs 1.13 mg/L, p=0.34) in cases compared to controls. | No |
| Kamphuisen et al., 1999 (51)LETS study | Case control study; 474 VTE and 474 controls. | Age <70 years Excluded malignancy | CRP measured at least 6 months after VTE episode. | CRP higher in VTE cases (1.49 mg/L, 95% CI 1.32-1.68), compared to controls (1.12 mg/L, 95% CI 1.0-1.25). | Yes |
| Tsai et al., 2002 (52)LITE study (combined CHS and ARIC studies) | Cohort / nested case control study;21680 participants. | Middle aged and elderly.Excluded prior VTE or cancer. | Baseline CRP, prospective follow up (median 7.8 years). | No association between baseline CRP and subsequent VTE. | No |
| Vormittag et al., 2005 (53) | Case control study;214 VTE and 104 controls. | Unprovoked VTE Excluded malignancy, diabetes, IBD, HRT or rheumatic disease. | CRP measured after VTE episode (at least 3 months after diagnosis). | Non-significant adjusted OR for VTE of 1.7 (95% CI 0.7-4.5) per 1 mg/L increment in CRP. Unadjusted OR 2.8 (1.1-6.8). | No |
| Folsom et al., 2009 (54).ARIC study | Cohort study; 10505 participants. | Caucasian and African American aged 45-64 years.Excluded prior VTE or CRP >20 mg/L. | CRP at baseline, 8.3 years of prospective follow up. | HR for VTE 2.07 for those with CRP above 10th percentile (>8.55 mg/L) compared to lowest 90%. | Yes |
| Luxembourg et al., 2009 (55)MAISTHRO registry | Case control study;101 unprovoked VTE, 101 provoked VTE and 202 healthy controls. | Age 18-69 years Excluded those with VTE <3 months or >5.5 years prior and >1 prior VTE; malignancy, pregnancy, autoimmune disease in prior 3 months. | CRP taken after VTE episode. | Higher CRP in those with unprovoked VTE compared to provoked VTE and healthy controls. | Yes |
| Zacho et al., 2010 (44)CCHS and CGPS | 2 cohorts:1. Prospective study, 10135 participants;2. Cross-sectional study, 36616 participants. | Danishgeneral population, no exclusions. | CCHS: Baseline CRP; 16 year prospective follow up.CGPS: VTE may have occurred before or after CRP measurement. | 2.3x increased risk VTE if CRP >3 mg/L compared to <1 mg/L.No association between genetically increased CRP and VTE risk. | Yes |
| Quist-Paulsen et al., 2010 (56)HUNT-2 study | Nested case control study;515 cases and 1505 controls. | Mean age 65 years Excluded prior VTE. | CRP at baseline. | OR 1.6 (95% CI 1.2-2.2) for CRP in highest quintile compared to lowest quintile. Highest risk if the VTE occurred within a year of blood sampling. | Yes |
| Hald et al., 2011 (57)Tromso study | Cohort study; 6426 participants. | 25-84 years Excluded prior VTE and if CRP >10 mg/L. | CRP at baseline, prospective follow up. | HR 1.08 per 1 SD increase in hsCRP (95% CI 0.95-1.23).No increased risk of VTE across quartiles of hsCRP (p=0.6) | No |
| Olson et al., 2014 (58)REGARDS | Cohort study; 30239 participants. | Caucasian and African American aged>45 years. | CRP at baseline, prospective follow up. | HR for VTE 1.25 per SD increase in log-CRP (CI 1.09-1.43) | Yes |
| Kunutsor et al., 2017 (59) | Cohort study;2420 participants. | Men aged 42-61 years | Baseline CRP, prospective follow up. | HR for VTE 1.17per 1 SD increase in log-CRP (CI 0.98-1.4) | Yes |
| Grimnes et al., 2018 (50)Tromso study | Case-crossover study;707 patients with VTE. | >25 years Excluded CRP levels taken within 2 days of VTE episode. | CRP in 90 days prior to VTE (“hazard period”) compared to CRP in four preceding 90-day “control periods”. | Median CRP58% higher in hazard period compared to control period.1 unit increase in log-transformed CRP OR 1.79 (95% CI 1.48-2.16). | Yes |
VTE, venous thromboembolism; CRP, C-reactive protein; CI, confidence interval; IBD, inflammatory bowel disease; HRT, hormone replacement therapy; OR, odds ratio; HR, hazard ratio; SD, standard deviation; hsCRP, high sensitivity CRP; LETS, Leiden Thrombophilia Study; LITE, Longitudinal Investigation of Thromboembolism Etiology; CHS, Cardiovascular Healthy Study; ARIC, Atherosclerosis Risk in Communities; MAISTHRO, Main-ISar-THROmbosis; CCHS, Copenhagen City Heart Study; CGPS, Copenhagen General Population Study; HUNT-2, Nord-Trondelag Health Study 1995-1997; REGARDS, Reasons for Geographic and Racial Differences in Stroke.