Lipoprotein(a), polymorphisms in the LPA gene, and incident venous thromboembolism among 21483 women.
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ABSTRACT:
SUBMITTER: Danik JS
PROVIDER: S-EPMC3557784 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
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Lipoprotein(a), polymorphisms in the LPA gene, and incident venous thromboembolism among 21483 women.
Danik J S JS Buring J E JE Chasman D I DI Zee R Y L RY Ridker P M PM Glynn R J RJ
Journal of thrombosis and haemostasis : JTH 20130101 1
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Project description:Elevated lipoprotein(a) [Lp(a)] is a risk factor for coronary heart disease (CHD), but there are few studies on the prediction of future cardiovascular events by Lp(a) and its LPA single nucleotide polymorphisms (SNPs). The aim of this study was to investigate whether elevated Lp(a) and its SNPs can predict cardiovascular events. We evaluated whether Lp(a) and LPA SNPs rs6415084 and rs12194138 were associated with the incidence rate and severity of CHD. All participants were followed up for 5 years. Elevated Lp(a) is an independent risk factor for the risk and severity of CHD (CHD group vs. control group: OR = 1.793, 95% CI: 1.053-2.882, p = 0.043; multiple-vessel disease group vs. single-vessel disease group: OR = 1.941, 95% CI: 1.113-3.242, p = 0.027; high GS group vs. low GS group: OR = 2.641, 95% CI: 1.102-7.436, p = 0.040). Both LPA SNPs were risk factors for CHD, and were positively associated with the severity of CHD (LPA SNPs rs6415084: CHD group vs. control group: OR = 1.577, 95% CI: 1.105-1.989, p = 0.004; multiple-vessel disease group vs. single-vessel disease group: OR = 1.613, 95% CI: 1.076-2.641, p = 0.030; high GS group vs. low GS group: OR = 1.580, 95% CI: 1.088-2.429, p = 0.024; LPA SNPs rs12194138: CHD group vs. control group: OR = 1.475, 95% CI: 1.040-3.002, p = 0.035; multiple-vessel disease group vs. single-vessel disease group: OR = 2.274, 95% CI: 1.060-5.148, p = 0.038; high GS group vs. low GS group: OR = 2.067, 95% CI: 1.101-4.647, p = 0.021). After 5 years of follow-up, elevated Lp(a) and LPA SNPs rs6415084 and rs12194138 can independently predict cardiovascular events. The increase of serum Lp(a) and LPA SNPs rs6415084 and rs12194138 are associated with increased prevalence and severity of CHD, and can independently predict cardiovascular events.
| S-EPMC8897417 | biostudies-literature
Project description:Venous thromboembolism (VTE) is the third most common cardiovascular disease. Low amount of mitochondrial DNA copy number (mtDNA-CN) has been associated with arterial cardiovascular disease (CVD) and reflects mitochondrial dysfunctions. However, whether mtDNA-CN is associated with VTE has not been determined. To examine the association between mtDNA-CN and incident VTE among middle-aged women. 6917 women aged 50-64 years, followed for 20 years in the Women's Health In the Lund Area (WHILA) study. DNA samples for mtDNA quantification were available from 2521 women. Quantification of mtDNA-CN was performed using a well-optimized droplet digital PCR method. After exclusions of women with anticoagulant treatment, women living in nursing homes, and women who were diagnosed with cancer, stroke, VTE, or coronary heart disease at baseline, a cohort of 2117 women remained for analysis. Cox regression was used to analyze the relationship between mtDNA-CN and time to VTE (hazard ratio = HR). In total, 87 women were diagnosed with VTE during follow-up, corresponding to an incidence rate of 2.8 per 1000 person-years. Neither crude nor adjusted HR for mtDNA-CN were significantly associated with incident VTE. A sensitivity analysis with inclusion of excluded women did not change the results. MtDNA-CN was not significantly associated with VTE. The present study suggests that mtDNA-CN, reflecting mitochondrial dysfunction, should not be considered a biomarker that plays a major role for developing VTE. However, due to limited study size we may not exclude minor associations.
| S-EPMC8282550 | biostudies-literature
Project description:Background and aimsThrombosis is a major driver of adverse outcome and mortality in patients with Coronavirus disease 2019 (COVID-19). Hypercoagulability may be related to the cytokine storm associated with COVID-19, which is mainly driven by interleukin (IL)-6. Plasma lipoprotein(a) [Lp(a)] levels increase following IL-6 upregulation and Lp(a) has anti-fibrinolytic properties. This study investigated whether Lp(a) elevation may contribute to the pro-thrombotic state hallmarking COVID-19 patients.MethodsLp(a), IL-6 and C-reactive protein (CRP) levels were measured in 219 hospitalized patients with COVID-19 and analyzed with linear mixed effects model. The baseline biomarkers and increases during admission were related to venous thromboembolism (VTE) incidence and clinical outcomes in a Kaplan-Meier and logistic regression analysis.ResultsLp(a) levels increased significantly by a mean of 16.9 mg/dl in patients with COVID-19 during the first 21 days after admission. Serial Lp(a) measurements were available in 146 patients. In the top tertile of Lp(a) increase, 56.2% of COVID-19 patients experienced a VTE event compared to 18.4% in the lowest tertile (RR 3.06, 95% CI 1.61-5.81; p < 0.001). This association remained significant after adjusting for age, sex, IL-6 and CRP increase and number of measurements. Increases in IL-6 and CRP were not associated with VTE. Increase in Lp(a) was strongly correlated with increase in IL-6 (r = 0.44, 95% CI 0.30-0.56, p < 0.001).ConclusionsIncreases in Lp(a) levels during the acute phase of COVID-19 were strongly associated with VTE incidence. The acute increase in anti-fibrinolytic Lp(a) may tilt the balance to VTE in patients hospitalized for COVID-19.
| S-EPMC8690577 | biostudies-literature
Project description:BackgroundUnderstanding venous thromboembolism (VTE) recurrence risk is central to determining the appropriate treatment course. Whether this risk varies after discontinuing anticoagulation or overall by type of incident event (pulmonary embolism [PE] vs deep vein thrombosis [DVT]) and by the detailed location of the DVT needs further clarification.MethodsIn this population-based inception cohort of incident VTE cases with follow-up by electronic health record review, incident DVT was categorized as distal, popliteal, or iliofemoral. We used the Fine-Gray regression model to describe the predictive association of the thrombus location with the risk of recurrence before death.ResultsAmong 2766 participants with an incident event from 2002 to 2010, 1713 (62%) ceased anticoagulation and were followed for recurrent events; 301 events were observed during the 4.5 years of follow-up. Relative to participants with an incident thrombus in an iliofemoral location and no PE, those with a thrombus in a popliteal location and no PE had a similar risk of recurrence (adjusted subdistribution hazard ratio [aSHR], 0.82 [95% confidence interval (CI), 0.57-1.19]), while those with a thrombus in a distal location and no PE and those with a thrombus that included a PE had lower risk of recurrence: aSHR, 0.34 (95% CI, 0.20-0.57); and aSHR, 0.58 (95% CI 0.45-0.76), respectively.ConclusionsThe findings of this population-based inception cohort confirm that the risk of recurrent VTE after discontinuing anticoagulants is similar after iliofemoral and popliteal DVT but is lower after distal DVT. Recurrence may be lower after PE than proximal DVT.
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Project description:BackgroundHeart failure (HF) hospitalization places patients at increased short-term risk for venous thromboembolism (VTE). Long-term risk for VTE associated with incident HF, HF subtypes, or structural heart disease is unknown.ObjectivesIn the ARIC (Atherosclerosis Risk In Communities) cohort, VTE risk associated with incident HF, HF subtypes, and abnormal echocardiographic measures in the absence of clinical HF was assessed.MethodsDuring follow-up, ARIC identified incident HF and subcategorized HF with preserved ejection fraction or reduced ejection fraction. At the fifth clinical examination, echocardiography was performed. Physicians adjudicated incident VTE using hospital records. Adjusted Cox proportional hazards models were used to evaluate the association between HF or echocardiographic exposures and VTE.ResultsOver a mean of 22 years in 13,728 subjects, of whom 2,696 (20%) developed incident HF, 729 subsequent VTE events were identified. HF was associated with increased long-term risk for VTE (adjusted hazard ratio: 3.13; 95% confidence interval: 2.58 to 3.80). In 7,588 subjects followed for a mean of 10 years, the risk for VTE was similar for HF with preserved ejection fraction (adjusted hazard ratio: 4.71; 95% CI: 2.94 to 7.52) and HF with reduced ejection fraction (adjusted hazard ratio: 5.53; 95% confidence interval: 3.42 to 8.94). In 5,438 subjects without HF followed for a mean of 3.5 years, left ventricular relative wall thickness and mean left ventricular wall thickness were independent predictors of VTE.ConclusionsIn this prospective population-based study, incident hospitalized HF (including both heart failure with preserved ejection fraction and reduced ejection fraction), as well as echocardiographic indicators of left ventricular remodeling, were associated with greatly increased risk for VTE, which persisted through long-term follow-up. Evidence-based strategies to prevent long-term VTE in patients with HF, beyond time of hospitalization, are needed.
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Project description:Venous thromboembolism (VTE) involves the formation of a blood clot, typically in the deep veins of the leg or arm (deep vein thrombosis), which then travels via the circulatory system and ultimately lodges in the lungs, resulting in pulmonary embolism. A number of microRNAs (miRNAs) are well-known regulators of thrombosis and thrombolysis, and mutations in miRNA biogenesis genes, such as DICER1, DROSHA have been implicated in miRNA synthesis and function. We investigated the genetic association between polymorphisms in four miRNA biogenesis genes, DICER1 rs3742330A > G, DROSHA rs10719T > C, RAN rs14035C > T and XPO5 rs11077A > C, and VTE in 503 Koreans: 300 controls and 203 patients. Genotyping was assessed with polymerase chain reaction-restriction fragment length polymorphism assays. We detected associations between polymorphisms in RAN and XPO5 and VTE prevalence (RAN rs14035CC + CT versus TT: p = 0.018; XPO5 rs11077AA + AC versus CC: p < 0.001). Analysis of allele combinations of all four polymorphisms (DICER1, DROSHA, RAN, XPO5) revealed that A-T-T-A was associated with decreased VTE prevalence (p = 0.0002), and A-T-C-C was associated with increased VTE prevalence (p = 0.027). Moreover, in subjects with provoked VTE, the DROSHA rs10719T > C, polymorphism was associated with increased disease prevalence (TT versus TC + CC: p < 0.039). Our study demonstrates that RAN and XPO5 polymorphisms are associated with risk for VTE in Korean subjects.
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Project description:BackgroundVenous thromboembolism (VTE) is the third most common cause of cardiovascular death worldwide, following coronary heart disease and stroke, and many risk factors for VTE are not yet clear. Our study investigated the association between multiple inflammatory gene polymorphisms and VTE prognosis, aiming to find a new predictor of VTE prognosis.MethodsBased on our previous studies, we detected the plasma levels of serum amyloid A protein (SAA), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) and their 8 gene polymorphisms by ELISA and a multiplex ligation detection reaction (iMLDR) method in 284 patients with VTE. All subjects were followed up for 5 years.ResultsThe 5-year follow-up results of this study showed that 62 of the 284 patients (21.83%) had reached the endpoint (all-cause death). Kaplan-Meier survival analyses revealed that the mortality rate of VTE patients with a high Simplified Pulmonary Embolism Severity Index (SPESI) score and carrying IL-1 rs1800587 mutation genotypes was significantly increased (log-rank p=0.000 and 0.034 respectively). The multifactor Cox regression results confirmed that the mortality rate of patients who carrying IL-1 rs1800587 mutation genotypes was significantly increased (HR=2.982; 95% CI: 1.681-5.100). The mortality rate of those carrying IL-1 rs1143634 mutation genotypes was significantly decreased (HR=0.294; 95% CI: 0.132-0.652). There were no significant differences in mortality rates between wild-type and mutant genotypes of IL-1 rs1143634, IL-1 rs2234650, SAA rs11603089, and TNF-α rs1800629 (P>0.05).ConclusionA high SPESI score and the presence of the IL-1 rs1800587 mutant genotype predict shorter survival in patients with VTE, whereas the IL-1 rs1143634 genotype is associated with a lower mortality rate. Screening for mutations in inflammation-related genes has prognostic value in the clinical management of VTE.
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Project description:IntroductionAssociation between arterial vascular dysfunction and risk of venous thromboembolism (VTE) is uncertain. We determined the associations between comprehensive measures of arterial vascular function and risk of incident VTE in a community-based cohort study with robust longitudinal follow-up.Materials and methodsIn the Framingham Heart Study Original, Offspring, Third Generation, and Omni cohorts, we measured carotid-femoral pulse wave velocity and central pulse pressure (n = 8261, age 51.5 ± 15.5 years, 54% women), flow-mediated dilation and hyperemic velocity (n = 6540, age 47.9 ± 14.1 years, 54% women), and peripheral arterial tonometry ratio (n = 4998, age 54.3 ± 16.0 years, 52% women). Deep venous thrombosis and pulmonary embolism were diagnosed with imaging studies and adjudicated by three Framingham Heart Study physicians.Results and conclusionsThe rate of incident VTE was 1.6-2.1 per 1000 person-years during mean follow-up of 8.5-11.2 years. In age- and sex-adjusted Cox proportional hazards regression models, carotid-femoral pulse wave velocity was associated with increased risk of VTE (HR 1.32, 95% CI 1.05-1.66, p = 0.02), however the association was no longer statistically significant after multivariable adjustment (HR 1.24, 95% CI 0.96-1.61, p = 0.10). None of the other vascular variables were associated with the risk of VTE in any of the models. In our comprehensive examination of arterial vascular function and risk of VTE, we did not observe any association between select arterial function measures and risk of VTE after multivariable adjustment.
| S-EPMC8297907 | biostudies-literature
Project description:BackgroundObesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established.ObjectivesTo examine whether adipokines are associated with increased risk of incident VTE.MethodsWe studied 1888 participants of the Multi-Ethnic Study of Atherosclerosis cohort who were initially free of VTE and had adipokine (adiponectin, leptin, and resistin) levels measured at either examination 2 or 3 (2002-2004 or 2004-2005, respectively). During follow-ups, VTE was ascertained through hospitalization records and death certificates by using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE.ResultsThe mean ± SD age was 64.7 ± 9.6 years, and 49.8% of participants were women. Medians (interquartile range) of adiponectin, leptin, and resistin were 17.3 (11.8-26.2) mcg/mL, 13.5 (5.6-28.2) ng/mL, and 15.0 (11.9-19.0) ng/mL, respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0-12.4) years of follow-up. After adjusting for sociodemographics, smoking, and physical activity, the hazard ratios (95% CIs) per 1 SD increment of adiponectin, leptin, and resistin were 1.14 (0.90-1.44), 1.29 (1.00-1.66), and 1.38 (1.09-1.74), respectively. The association for resistin persisted after further adjustments for body mass index and computed tomography-derived total visceral adipose tissue area.ConclusionHigher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.
| S-EPMC10152466 | biostudies-literature
Project description:IntroductionEpidemiological studies generally have not found plasma total fibrinogen to be a risk factor for venous thromboembolism (VTE), but several have reported associations between variants in the fibrinogen gamma gene (FGG) and VTE. A case-control study in whites suggested plasma γ' fibrinogen concentration may be associated inversely with VTE, but this was not replicated in African Americans.ObjectiveTo examine the prospective association between γ' fibrinogen concentrations and occurrence of VTE.MethodsWe used the Longitudinal Investigation of Thromboembolism Etiology (LITE), involving two pooled population-based cohorts in the United States including 16,234 participants. The cohorts comprised white and African American men and women, aged 50years and older at study onset in the early 1990s. We identified VTEs during follow-up and documented they met standardized diagnostic criteria.ResultsDuring two decades of follow-up, neither γ' fibrinogen nor total fibrinogen nor their ratio was associated with VTE overall (n=521 VTEs), in subgroups defined by race, or in other subgroups. In both race groups, the minor allele of FGG rs2066865 was associated with lower γ' fibrinogen concentrations, but this allele was not associated with VTE.ConclusionsA lower plasma concentration of γ' fibrinogen in healthy adults does not appear to increase VTE risk.
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