Circulating Serum Copper Is Associated with Atherosclerotic Cardiovascular Disease, but Not Venous Thromboembolism: A Prospective Cohort Study.
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ABSTRACT: Background and objective
Serum copper has been linked to the risk of atherosclerotic cardiovascular disease (CVD). However, the potential association between serum copper and venous thromboembolism (VTE) is not known. The principal aim was to evaluate the potential prospective association between serum copper and VTE risk. A secondary aim was to confirm or refute previously reported associations between serum copper and atherosclerotic CVD.Methods
Serum copper was measured at baseline using atomic absorption spectrometry in 2,492 men aged 42-61 years without a history of VTE in the Kuopio Ischemic Heart Disease prospective cohort study. Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence interval (CI) for VTE.Results
During a median follow-up of 27.0 years, 166 VTE events occurred. The risk of VTE per 1 standard deviation increase in serum copper in age-adjusted analysis was HR: 1.02; 95% CI: 0.88-1.20, which was attenuated to HR: 0.99; 95% CI: 0.82-1.19, following further adjustment for several established and emerging risk factors. Comparing the top versus bottom tertiles of serum copper, the corresponding adjusted HRs were 1.16 (95% CI: 0.80-1.66) and 1.11 (95% CI: 0.74-1.68), respectively. In 1,901 men without a history of coronary heart disease (CHD), the multivariable-adjusted HR for CHD was 1.32 (95% CI: 1.10-1.59) comparing extreme tertiles of serum copper.Conclusion
In middle-aged Finnish men, we confirmed previously reported associations between high serum copper levels and increased risk of atherosclerotic CVD, but serum copper was not associated with future VTE risk. Other large-scale prospective studies conducted in women, other age-groups, and other populations are needed to confirm or refute these findings.
SUBMITTER: Kunutsor SK
PROVIDER: S-EPMC8739646 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: COVID-19 is associated with high rates of venous thromboembolism (VTE). The impact of common inherited thrombophilias on the development of COVID-19-associated VTE (COVID-19 VTE) is not well understood. Objective: To determine if the presence of inherited thrombophilias modifies the risk of COVID-19 VTE or COVID-19 mortality. Methods: Prospective population-based cohort study evaluating adult participants of the UK Biobank diagnosed with COVID-19 between November 2019 and May 2021. Individuals were of European descent and aged between 45 and 69 at recruitment to UK Biobank. We evaluated six single nucleotide polymorphisms including rs6025 (Factor V Leiden mutation) and rs1799963 (Prothrombin mutation) in addition to two polygenic risk scores (PRS-VTE and PRS-ABO). A genome-wide association study was performed for associations with COVID-19 VTE. COVID-19 VTE was defined using International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for VTE following COVID-19 diagnosis. COVID-19 mortality was defined using ICD-10 codes for COVID-19 on the death certificate. Results: Demographic and clinical characteristics are shown in Table 1. Of the 13 712 COVID-19 positive individuals included in the analysis, the median age was 54 years and 52.5% were female. There were 197 (1.4%) cases of COVID-19 VTE and 890 (6.5%) died due to COVID-19. The rs6025 variant, synonymous with FVL, was associated with a 1.8-fold risk of COVID-19 VTE (95% CI 1.040-2.931) (Table 2). The risk of COVID-VTE was also increased with rs2066865 (OR 1.345; 95% CI 1.074-1.675) and the PRS-VTE (OR 1.262; 95% CI 1.081-1.468) (Table 2). COVID-19 VTE was associated with increased COVID-19 mortality (OR 2.731; 95% CI 1.885-3.901) but this study found no association between the studied inherited thrombophilias and COVID-19 mortality (Table 2). On genome-wide analysis, two novel SNPs, rs4975019 and rs2875853, located on chromosomes 4 and 16 respectively, were associated with an increased occurrence of COVID-19 VTE. Conclusions: These data demonstrate that several inherited thrombophilias increase the risk of COVID-19 VTE and suggest that two novel SNPs are associated with COVID-19 VTE. These results suggest that certain inherited thrombophilias may assist in characterising a subgroup of COVID-19 patients at higher risk of thrombotic events who require individualised antithrombotic therapy. Future prospective studies are required to evaluate inherited thrombophilias in this patient cohort. Figure 1 Disclosures No relevant conflicts of interest to declare.
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Project description:BackgroundWhether obesity is associated with recurrent venous thromboembolism (VTE) in elderly patients is unknown.ObjectivesTo examine the association between two obesity measures, the body mass index (BMI) and the waist circumference (WC), and recurrent VTE in elderly patients.Patients/methodsWe studied 986 patients aged ?65 years with an acute VTE from a prospective multicenter cohort study (09/2009-12/2013). The BMI was determined and categorized as <25, 25 to <30, or ?30 kg/m2. The WC was categorized as <80 cm in women (w)/<94 cm in men (m), 80 to <88 cm (w)/94 to <102 cm (m), or ?88 cm (w)/?102 cm (m). We examined the association between the BMI and the WC and the time to a first symptomatic recurrent VTE using competing risk regression, adjusting for known risk factors of VTE recurrence and periods of anticoagulation.ResultsThe mean follow-up was 28 months. The 3-year cumulative incidence of recurrent VTE did not vary by BMI and was 17.6% for a BMI <25 kg/m2, 11.5% for a BMI 25 to <30 kg/m2, and 16.9% for a BMI ?30 kg/m2 (P = 0.09). The 3-year cumulative incidence of recurrent VTE did not vary by WC. After adjustment, neither the BMI (sub-hazard ratio [SHR] 1.02, 95% confidence interval [CI 0.98-1.05]) nor the WC (SHR 1.01, 95% CI 0.99-1.02) was associated with recurrent VTE.ConclusionsMeasures of body weight were not associated with recurrent VTE in our cohort. Obesity does not appear to be a predictor of recurrent VTE in the elderly.
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Project description:BACKGROUND:The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE:To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN:Prospective cohort study. SETTING:Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS:The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS:Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS:Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION:Limited sample size. CONCLUSION:The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE:University Medical Center Hamburg-Eppendorf.
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