Essentials
Chronic kidney disease (CKD) is associated with procoagulant and inflammatory biomarkers.
We studied the association of CKD and venous thromboembolism (VTE) in a case‐cohort study.
Factor ...VIII, D‐dimer and C‐reactive protein appeared to explain the association of CKD and VTE.
Statin use was protective against VTE in those with and without CKD.
Summary
Background
Chronic kidney disease (CKD) is associated with venous thromboembolism (VTE) risk via unknown mechanisms. Whether factors associated with reduced VTE risk in the general population might also be associated with reduced VTE risk in CKD patients is unknown.
Objectives
To determine whether thrombosis biomarkers attenuate VTE risk, and whether factors associated with reduced VTE risk are similarly effective in CKD patients.
Methods
Baseline biomarkers were measured in a cohort (294 VTE cases; 939 non‐cases) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a nationwide prospective cohort study of 30 239 persons aged ≥45 years with 4.3 years of follow‐up. The hazard ratio (HR) of VTE per 10 mL min−1 1.73 m−2 decrease in estimated glomerular filtration rate (eGFR), and the percentage attenuation of this HR by each biomarker, were calculated. Associations of protective factors (physical activity, lower body mass index BMI, and aspirin, warfarin and statin use) with VTE were estimated in those with and without CKD.
Results
The HR for VTE with lower eGFR was 1.13 (95% confidence interval CI 1.02–1.25), and VTE risk was attenuated by 23% (95% CI 5–100) by D‐dimer, by 100% (95% CI 50–100) by factor VIII, and by 15% (95% CI 2–84) by C‐reactive protein. Normal BMI was associated with lower VTE risk in those without CKD (HR 0.47, 95% CI 0.32–0.70), but not in those with CKD (HR 1.07, 95% CI 0.51–2.22). Statin use, physical activity and warfarin use were associated with lower VTE risk in both groups.
Conclusions
Procoagulant and inflammatory biomarkers mediated the association of eGFR with VTE. Higher physical activity, statin use and warfarin use mitigated VTE risk in those with CKD and those without CKD, but normal BMI did not mitigate VTE risk in CKD patients.
It has been suggested that inflammation is important in the aetiology of hypertension and that this may be most relevant among obese persons. To study this, we examined the independent relationships ...between obesity, inflammation-related proteins (interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen) and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA). Hypertension status, defined as a blood pressure ≥140/90 mm Hg or a history of hypertension and use of blood pressure medications, was determined at baseline and two subsequent exams over 5 years. Among 3543 non-hypertensives at baseline, 714 individuals developed incident hypertension by Exam 3. Cox proportional hazard models were used to determine the relationship between baseline levels of IL-6, CRP and fibrinogen and future risk of hypertension. One s.d. difference in baseline concentration of IL-6, CRP or fibrinogen was associated with 20-40% greater risk of incident hypertension. This risk was attenuated after accounting for other hypertension risk factors (hazard ratio (HR) IL-6: 1.13 (95% CI: 1.04-1.23); CRP: 1.11 (95% CI: 1.02-1.21); fibrinogen 1.0 (95% CI: 0.92-1.08)). Conversely, obesity was an independent risk factor for hypertension risk, minimally impacted by other covariates, including IL-6 and CRP (HR 1.72 (95% CI: 1.36-2.16)). IL-6 and CRP did not modify the relationship between obesity and hypertension, though an adjusted twofold greater risk was observed for obese individuals with a CRP >3 mg l⁻¹ compared with CRP <1 mg l⁻¹. The relationship between inflammation-related proteins and hypertension risk was predominantly explained by other hypertension risk factors. Obesity, independent of inflammation, remained a potent risk factor for future hypertension.
Background: Protein C is an important plasma natural anticoagulant. Although protein C deficiency increases risk of venous thrombosis, it remains uncertain whether low protein C increases risk of ...atherothrombosis. Objective: To examine whether low protein C may be a risk factor for ischemic stroke or coronary events in a prospective population‐based study. Patients/Methods: The Atherosclerosis Risk in Communities Study assessed protein C antigen by ELISA at baseline in 1987–89 and followed participants (n = 13 879) for incident ischemic stroke or coronary events through 2005. Results: Over a median of 16.9 years of follow‐up, 613 ischemic strokes and 1257 coronary heart disease events occurred. Protein C was inversely associated with incidence of ischemic stroke. Adjusted for multiple risk factors, the rate ratios (95% CIs) from highest to lowest quintiles were 1.0, 1.16 (0.90–1.50), 1.22 (0.94–1.58), 1.18 (0.90–1.55) and 1.52 (1.17–1.98). This inverse association was stronger for non‐lacunar and cardioembolic stroke than for lacunar stroke. In contrast, there was a positive association between protein C and coronary heart disease in incompletely adjusted models, but no association after adjustment for plasma lipids. Conclusions: In this cohort study, low protein C was a risk factor for incident ischemic stroke but not coronary heart disease. Levels of protein C associated with stroke risk were not restricted to the traditional ‘deficient’ range for protein C (< 0.5 percentile), suggesting that other etiologies for a lower protein C, or genetic variants associated with more subtle changes in protein C, are playing a role in disease pathogenesis.
Objective To determine the effect of sex on the risk of recurrent venous thromboembolism in all patients and in patients with venous thromboembolism that was unprovoked or provoked (by non-hormonal ...factors).Data source Comprehensive search of electronic databases (Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials) until July 2010, supplemented by review of conference abstracts and contact with content experts.Study selection Seven prospective studies investigating an association between D-dimer, measured after anticoagulation was stopped, and disease recurrence in patients with venous thromboembolism.Data extraction Patient level databases were obtained, transferred to a central database, checked, and completed with further information provided by authors.Data synthesis 2554 patients with a first venous thromboembolism had follow-up for a mean of 27.1 (SD 19.6) months. The one year incidence of recurrent venous thromboembolism was 5.3% (95% confidence interval 4.1% to 6.7%) in women and 9.5% (7.9% to 11.4%) in men, and the three year incidence of recurrence was 9.1% (7.3% to 11.3%) in women and 19.7% (16.5% to 23.4%) in men. Among patients with unprovoked venous thromboembolism, men had a higher risk of recurrence than did women (hazard ratio 2.2, 95% confidence interval 1.7 to 2.8). After adjustment for women with hormone associated initial venous thromboembolism, the risk of recurrence remained higher in men (hazard ratio 1.8, 1.4 to 2.5). In patients with provoked venous thromboembolism, occurring after exposure to a major risk factor, recurrence of disease did not differ between men and women (hazard ratio 1.2, 0.6 to 2.4). In women with hormone associated venous thromboembolism and no other risk factors, recurrence was lower than that in women with unprovoked venous thromboembolism and no previous hormone use (hazard ratio 0.5, 0.3 to 0.8).Conclusion In patients with a first unprovoked venous thromboembolism, men have a 2.2-fold higher risk of recurrent venous thromboembolism than do women, which remained 1.8-fold higher in men after adjustment for previous hormone associated venous thromboembolism in women. In patients with a first provoked venous thromboembolism, risk of recurrence does not differ between men and women with or without hormone associated venous thromboembolism. Indefinite anticoagulation may be given greater consideration in men than in women after a first venous thromboembolism.
Minimal literature is available on the diagnosis and treatment of proximal plantaris tendinopathy. Calf pain is a common complaint in runners, ranging from myofascial pain to acute strains. Rarely, ...the plantaris tendon can be involved in mid-calf pain. This case highlights a 23-year-old female elite runner with a case of symptomatic proximal plantaris tendinopathy. Insidious mid-calf pain and/or tightness with tenderness to palpation was noted, and ultrasonographic examination provided an accurate diagnosis. An ultrasound-guided corticosteroid injection was performed, providing complete pain relief without recurrence, even 1 year after the initial injection. The patient was able to return to full activity. Successful treatment of this rare condition with ultrasound-guided corticosteroid injection should be considered once a proper diagnosis is made.
Aim: Our aim was to examine the association between platelet count and the incidence of myocardial infarction, ischemic stroke, hemorrhagic stroke, venous thrombosis, and mortality. Methods and ...results: Platelet count was measured at baseline in 1989–1990 and at 3 years follow‐up, or at baseline (for a newly recruited group) in 1992–1993 in 5766 community‐dwelling individuals aged 65 years and older (mean age at baseline, 73 years). During 12–15 years of follow‐up, there were 821 incident myocardial infarctions, 807 ischemic strokes, 161 hemorrhagic strokes, 159 venous thrombotic events, and 3413 participants died. Platelet count was not associated with the occurrence of myocardial infarction, ischemic or hemorrhagic stroke, venous thrombosis, or cardiovascular mortality. Non‐cardiovascular mortality was higher among both participants with low and with high platelet count. Adjusted non‐cardiovascular mortality rates for platelet counts below 100, 100–199, 300–399, and above 400 × 109 L−1 relative to the reference mortality rate in participants with platelet count values between 200 and 299 × 109 L−1 were 1.89 (1.21–2.96), 1.08 (0.98–1.20), 1.20 (1.06–1.37), and 1.47 (1.14–1.90), respectively. Conclusion: Platelet counts were not associated with vascular outcomes but low and high platelet counts were associated with non‐cardiovascular mortality, including cancer mortality.
Summary
Background
HMG‐CoA reductase inhibitors (statins) reduce the risk of venous thromboembolism (VTE) in healthy people. Statins reduce levels of inflammation biomarkers; however, the mechanism ...for the reduction in VTE risk is unknown.
Aim
In a large cohort of healthy people, we studied associations of statin use with plasma hemostatic factors related to VTE risk.
Methods
Cross‐sectional analyses were performed in the Multi‐Ethnic Study of Atherosclerosis (MESA), a cohort study of 6814 healthy men and women aged 45–84 years, free of clinical cardiovascular disease at baseline; 1001 were using statins at baseline. Twenty‐three warfarin users were excluded. Age, race and sex‐adjusted mean hemostatic factor levels were compared between statin users and non‐users, and multivariable linear regression models were used to assess associations of statin use with hemostatic factors, adjusted for age, race/ethnicity, education, income, aspirin use, hormone replacement therapy (in women), and major cardiovascular risk factors.
Results
Participants using statins had lower adjusted levels of D‐dimer (− 9%), C‐reactive protein (− 21%) and factor VIII (− 3%) than non‐users (P < 0.05). Homocysteine and von Willebrand factor levels were non‐significantly lower with statin use. Higher fibrinogen (2%) and plasminogen activator inhibitor‐1 (22%) levels were observed among statin users than among non‐users (P < 0.05). Further adjustment for LDL and triglyceride levels did not attenuate the observed differences in these factors with statin use.
Conclusions
Findings of lower D‐dimer, FVIII and C‐reactive protein levels with statin use suggest hypotheses for mechanisms whereby statins might lower VTE risk. A prospective study or clinical trial linking these biochemical differences to VTE outcomes in statin users and non‐users is warranted.
Essentials
Inflammatory and cardiac diseases are associated with increased venous thromboembolism (VTE) risk.
Our prospective study assessed rise in inflammatory or cardiac biomarkers and VTE risk.
A ...greater 6‐year rise in N‐terminal natriuretic peptide is associated with increased VTE incidence.
Volume overload or impending cardiac disease may contribute to VTE occurrence.
Summary
Background
We previously showed that participants in the population‐based Atherosclerosis Risk in Communities (ARIC) cohort with elevated levels of blood biomarkers of inflammation or cardiac disease were at increased risk of venous thromboembolism (VTE).
Objective
We hypothesized that ARIC participants with larger 6‐year increases in the levels of three biomarkers – C‐reactive protein (CRP), N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), and troponin T – would also have an increased subsequent risk of VTE.
Methods
We measured changes in the levels of these biomarkers in 9844 participants from 1990–1992 to 1996–1998, and then identified VTEs through 2015.
Results
A greater 6‐year rise in the level of NT‐proBNP, but not in that of CRP or troponin T, was significantly associated with increased VTE incidence over a median of 17.6 years of follow‐up. After adjustment for other VTE risk factors, those whose NT‐proBNP level rose from < 100 pg mL−1 to ≥ 100 pg mL−1 had a hazard ratio for VTE of 1.44 (95% confidence interval CI 1.15–1.80), as compared with the reference group with an NT‐proBNP level of < 100 pg mL−1 at both times. This hazard ratio was slightly higher (1.66, 95% CI 1.19–2.31) during the first 10 years of follow‐up, but was attenuated (1.24, 95% CI 0.99–1.56) after adjustment for prevalent and incident coronary heart disease, heart failure, and atrial fibrillation.
Conclusions
The two most likely explanations for our results are that: (i) an increasing NT‐proBNP level reflects increasing subclinical volume overload and potentially increased venous stasis or subclinical PE that had gone unrecognized over time; or (ii) an increasing NT‐proBNP level is a risk marker for impending cardiac disease that places patients at risk of VTE.
Background: Whether atherosclerotic disease predisposes to venous thrombosis is uncertain. Objective: To determine whether subclinical atherosclerosis, manifested as increased carotid intima‐media ...thickness (IMT) or presence of carotid plaque, is associated with increased incidence of venous thromboembolism (VTE). Patients and methods: The Atherosclerosis Risk in Communities study is a prospective cohort of adults aged 45–64 years, examined at baseline (1987–89) and followed for cardiovascular events. Bilateral carotid ultrasound for IMT measurements was done at baseline for portions of the common and internal carotid arteries, and carotid bifurcation and also to detect the presence of carotid plaque. Exclusion criteria included baseline anticoagulant use, history of coronary heart disease, stroke, or VTE, and incomplete data. First VTE during follow‐up was validated using ed medical records. Results: Among 13 081 individuals followed for a mean of 12.5 years, 225 first VTE events were identified. Unadjusted hazard ratios (HR) (95% CI) of VTE across quartiles of baseline IMT were 1.0, 1.16 (0.77–1.75), 1.64 (1.12–2.40), and 1.52 (1.03–2.25). However, this association disappeared after adjustment for age, sex, and ethnicity (HRs: 1.0, 1.06, 1.40, and 1.18). Further adjustment for body mass index and diabetes weakened the relative risks even further. Presence of carotid plaque at baseline also was not associated with VTE occurrence; adjusted HR = 0.97, 95% CI = 0.72–1.29. Conclusion: Increased carotid IMT or presence of carotid plaque was not associated with an increased incidence of VTE in this middle‐aged cohort, suggesting subclinical atherosclerosis itself is not a VTE risk factor.
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