Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial.
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SUBMITTER: Liu Y
PROVIDER: S-EPMC5234728 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial.
Liu Yanhong Y Kong Xiangyi X Wang Wen W Fan Fangfang F Zhang Yan Y Zhao Min M Wang Yi Y Wang Yupeng Y Wang Yu Y Qin Xianhui X Tang Genfu G Wang Binyan B Xu Xiping X Hou Fan Fan FF Gao Wei W Sun Ningling N Li Jianping J Venners Scott A SA Jiang Shanqun S Huo Yong Y
Journal of lipid research 20161122 1
The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte ...[more]
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Project description:Our group recently identified a panel of ten genes whose RNA expression levels in whole blood have utility for detection of stroke. The purpose of this study was to determine the mechanisms by which these genes become differentially expressed during stroke pathology. First, we assessed the transcriptional distribution of the ten genes across the peripheral immune system by measuring their expression levels on isolated neutrophils, monocytes, B-lymphocytes, CD-4+ T-lymphocytes, CD-8+ T-lymphocytes, and NK-cells generated from the blood of healthy donors (n?=?3). Then, we examined the relationship between the whole-blood expression levels of the ten genes and white blood cell counts in a cohort of acute ischemic stroke patients (n?=?36) and acute stroke mimics (n?=?15) recruited at emergency department admission. All ten genes displayed strong patterns of lineage-specific expression in our analysis of isolated leukocytes, and their whole-blood expression levels were correlated with white blood cell differential across the total patient population, suggesting that many of them are likely differentially expressed in whole blood during stroke as an artifact of stroke-induced shifts in leukocyte counts. Specifically, factor analysis inferred that over 50% of the collective variance in their whole-blood expression levels across the patient population was driven by underlying variance in white blood cell counts alone. However, the cumulative expression levels of the ten genes displayed a superior ability to discriminate between stroke patients and stroke mimics relative to white blood cell differential, suggesting that additional less prominent factors influence their expression levels which add to their diagnostic utility. These findings not only provide insight regarding this particular panel of ten genes, but also into the results of prior stroke transcriptomics studies performed in whole blood.
| S-EPMC6141354 | biostudies-literature
Project description:BackgroundTotal leukocyte and differential Leukocyte counts are prognostic indictors in patients with coronary artery disease (CAD). However, there is no data available regarding their prognostic utility in very old patients with acute myocardial infarction (AMI). The aim of this study is to investigate the potential role of different leukocyte parameters in predicting the mortality among very old patients with AMI.MethodsA total of 523 patients aged over 80 years with AMI were consecutively enrolled into this study. Leukocyte and its subtypes were obtained at admission in each patient. The primary study endpoint was cardiovascular mortality. Patients were followed up for an average of 2.2 years and 153 patients died. The associations of leukocyte parameters with mortality were assessed using Cox regression analyses. The concordance index was calculated to test the model efficiency.ResultsIn multivariable regression analysis, neutrophils-plus-monocytes-to-lymphocytes ratio (NMLR) and neutrophils-to-lymphocytes ratio (NLR) were two most significant predictors of mortality among all the leukocyte parameters (HR = 3.21, 95% CI 1.75-5.35; HR = 2.79, 95% CI 1.59-4.88, respectively, all p < 0.001, adjusted for age, male gender, body mass index, family history of CAD, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, high sensitivity C-reactive protein, creatinine, left ventricular ejection fraction, troponin I, use of statin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and percutaneous coronary intervention). Furthermore, adding NMLR and NLR into the Cox model increased the C-statistic by 0.038 and 0.037 respectively, which were more significant than that of other leukocyte parameters. Besides, addition of NMLR and NLR to the Canada Acute Coronary Syndrome Risk Score model also increased the C-statistic by 0.079 and 0.077 respectively.ConclusionOur data firstly indicated that most leukocyte subtypes were independent markers for the mortality in very old patients with AMI, while NMLR and NLR appeared to be more effective.
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Project description:BackgroundNeuroinflammation plays an important role in the pathogenesis of acute ischemic stroke (AIS) and peripheral leukocyte counts have proved to be independent predictors of stroke severity and outcomes. Clinical significance of large vessel occlusion (LVO) in AIS is increasing, as these patients are potential candidates for endovascular thrombectomy and likely to have worse outcomes if not treated urgently. The aim of our study was to assess the relationship between on admission leukocyte counts and the presence of LVO in the early phase of AIS.MethodsWe have conducted a cross-sectional, observational study based on a registry of consecutive AIS patients admitted up to 4.5 h after stroke onset. Blood samples were taken at admission and leukocyte counts were measured immediately. The presence of LVO was verified based on the computed tomography angiography scan on admission.ResultsTotal white blood cell (WBC) and neutrophil counts were significantly higher in patients with LVO than those without LVO (P < 0.001 respectively). After adjustment for potential confounders total WBC counts (adjusted OR: 1.405 per 1 × 109/L increase, 95% CI: 1.209 to 1.632) and neutrophil counts (adjusted OR: 1.344 per 1 × 109/L increase, 95% CI: 1.155 to 1.564) were found to have the strongest associations with the presence of LVO. Total WBC and neutrophil counts had moderate ability to discriminate an LVO in AIS (AUC: 0.667 and 0.655 respectively). No differences were recorded in leukocyte counts according to the size of the occluded vessel and the status of collateral circulation in the anterior vascular territory. However, total WBC and neutrophil counts tended to be higher in patients with LVO in the posterior circulation (p = 0.005 and 0.010 respectively).ConclusionHigher admission total WBC and neutrophil counts are strongly associated with the presence of LVO and has moderate ability to discriminate an LVO in AIS. Detailed evaluation of stroke-evoked inflammatory mechanisms and changes according to the presence of LVO demands further investigation.
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Project description:BACKGROUND:The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood. OBJECTIVES:We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects. METHODS:The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 (TLR4), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term. RESULTS:There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×103/?L (95% CI: 0.070, 0.301×103/?L) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p=0.15). CONCLUSIONS:This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings. https://doi.org/10.1289/EHP661.
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Project description:Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn.
| S-EPMC5063275 | biostudies-literature
Project description:Growing evidence suggests that stroke alters the phenotype of the peripheral immune system; better characterization of this response could provide new insights into stroke pathophysiology. In this investigation, we employed a deconvolution approach to informatically infer the cellular composition of the circulating leukocyte pool at multiple timepoints following stroke onset based on whole blood mRNA expression. Microarray data generated from the peripheral blood of 23 cardiovascular disease controls and 23 ischemic stroke patients at 3, 5, and 24 hours post-symptom onset were obtained from a public repository. Transcriptomic deconvolution was used to estimate the relative counts of nine leukocyte populations based on the expression of cell-specific transcripts, and cell counts were compared between groups across timepoints. Inferred counts of lymphoid cell populations including B-cells, CD4+ T-cells, CD8+ T-cells, ?? T-cells, and NK-cells were significantly lower in stroke samples relative to control samples. With respect to myeloid cell populations, inferred counts of neutrophils and monocytes were significantly higher in stroke samples compared to control samples, however inferred counts of eosinophils and dendritic cells were significantly lower. These collective differences were most dramatic in samples collected at 5 and 24 hours post-symptom onset. Findings were subsequently confirmed in a second dataset generated from an independent population of 24 controls and 39 ischemic stroke patients. Collectively, these results offer a comprehensive picture of the early stroke-induced changes to the complexion of the circulating leukocyte pool, and provide some of the first evidence that stroke triggers an acute decrease in eosinophil counts.
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Project description:Background: Ischemic stroke patients show alterations in peripheral leukocyte counts that may result from the sterile inflammation response as well as the occurrence of early infections. We here aimed to determine whether alterations of circulating leukocytes in acute ischemic stroke are associated with long-term functional outcome and hemorrhagic complications, independently of the occurrence of infections. Methods: Blood laboratory values of patients with acute ischemic stroke, presenting within 4.5 h from symptom onset, were collected. Leukocyte subsets were analyzed in relation to 3-month functional outcome, mortality, and parenchymal hemorrhagic transformation (PH). A multivariable logistic regression analysis, considering the occurrence of early post-stroke infections, was performed for each outcome measure. Results: Five-hundred-ten patients were included in the study. Independently of infections, good functional outcome was associated with a lower neutrophil to lymphocyte ratio (NL-R, OR 0.906 [95% CI 0.822-0.998]), a higher lymphocyte count (OR 1.547 [95% CI 1.051-2.277]), a higher eosinophil count (OR 1.027 [95% CI 1.007-1.048]), and a higher eosinophil to leukocyte ratio (EoLeu-R, OR 1.240 [95% CI 1.071-1.436]) at admission. Death within 3 months was associated with higher NL-R (OR 1.103 [95% CI 1.032-1.179]) as well as with lower eosinophil counts (OR 0.909 [95% CI 0.827-0.999]). Patients developing parenchymal hemorrhagic transformation had higher neutrophil counts (OR 1.420 [95% CI 1.197-1.684]) as well as a higher NL-R (OR 1.192 [95% IC 1.088-1.305]). Conclusion: Leukocyte subtype profiles in the acute phase of ischemic stroke represent a predictor of outcome independently of infections. Stroke-evoked sterile inflammation is a pathophysiological relevant mechanism that deserves further investigation.
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Project description:ImportanceEmerging evidence implicates a role for neuroinflammation in Alzheimer disease (AD) pathogenesis, predominantly involving the innate immune system. Blood leukocyte counts are easily accessible markers of immune function; however, their association with the risk of AD is unknown.ObjectiveTo investigate the observational and genetic associations between types of blood leukocytes and risk of AD.Design, setting, and participantsIn a cohort study comprising observational and genetic analyses, the Copenhagen General Population Study prospective cohort (n = 101 582) was used for the observational analyses. For the genetic studies, nonlinearity was first evaluated for the association between leukocyte cell counts and AD risk using individual-level data from the UK Biobank (n = 365 913). Subsequently, a 2-sample mendelian randomization framework was applied using genetic instruments for blood leukocyte counts (n = 563 085); for AD, the European Alzheimer & Dementia Biobank was used, including 85 934 individuals with AD and 401 577 controls and the International Genomics of Alzheimer's Project, including 21 982 individuals with AD and 41 944 controls.ExposuresObservational and genetically determined types of blood leukocyte counts.Main outcomes and measuresHazard ratios (HRs) and 95% CIs for AD of cell count percentile groups in observational studies and odds ratios (ORs) and 95% CIs for AD per 1 SD genetically determined cell counts.ResultsThis cohort study included 101 582 participants (55 891 [55.0%] women) with a median age of 58 years (IQR, 48-67 years); of these, 1588 individuals developed AD. Multivariable-adjusted HRs for participants in the less than 5th vs the 25th to 75th (reference) percentile group were 1.24 (95% CI, 0.99-1.54) for blood monocytes and 1.25 for blood eosinophils (95% CI, 1.05-1.50). For participants in the greater than 95th vs the 25th to 75th percentile group, the HR was 1.30 (95% CI, 1.06-1.61) for blood neutrophils. Genetically, no evidence favored possible nonlinear associations. The ORs for AD per 1-SD decrease in genetically determined blood monocytes were 1.04 (95% CI, 1.00-1.10) in the European Alzheimer & Dementia Biobank consortium and 1.09 (95% CI, 1.01-1.17) in the International Genomics of Alzheimer's Project consortium. Using mendelian randomization, sensitivity analyses and multivariable analysis showed similar results.Conclusions and relevanceThe findings of this study suggest that low blood monocyte counts are associated with increased AD risk. These findings highlight a potential role of the innate immune system in AD pathogenesis.
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Project description:Background: The benefit of blood cholesterol reduction for secondary prevention of ischemic stroke remains undetermined in Chinese patients. The purpose of this meta-analysis was to determine whether lipid-lowering agents including statins, fibrates, nicotinic acid, and ezetimibe reduced the risk of recurrent stroke in ischemic stroke patients in China and whether such findings could inform treatment decisions for blood lipid-lowering treatment in China. Methods: The English electronic databases PubMed, EMBASE, Cochrane Library and Chinese databases CNKI, Sino-Med, Wan Fang, and VIP were searched for studies published between January 1990 and April 2020. This meta-analysis included published data from trials that randomly assigned patients to groups treated with either blood lipid-lowering regimens or placebo. Effect comparisons were made using fixed effects model in meta-analysis and linear and spline regression were performed to identify the relative risk of stroke recurrence. The primary outcome was the reduction of total ischemic stroke events, and relative risk values were obtained using a risk prediction equation developed from the control groups of the included trials. Results: Five studies including 4,999 individuals with available data met the inclusion criteria. Relative to the control groups, the pooled estimated odds ratio (OR) for recurrent stroke among those who received lipid-lowering therapy was 0.79 (95% confidence interval [CI]: 0.63-1.00). A 50% or greater reduction in low-density lipoprotein cholesterol (LDL-C) significantly reduced the risk of ischemic stroke recurrence (OR: 0.15 [95% CI: 0.11-0.20]). The overall beneficial effect of statin therapy was confirmed to prevent ischemic stroke with an OR of 0.51 (95% CI: 0.36-0.72). Conclusions: Effective lipid-lowering therapy could decrease the blood LDL-C level, which had a protective effect against stroke recurrence. These results support the use of predicted baseline cerebrovascular disease risk equations to inform decisions regarding blood lipid-lowering treatment in ischemic stroke patients in China.
| S-EPMC7717969 | biostudies-literature
Project description:High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes.Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45-73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22-1.53) for total leukocytes, 1.33 (1.19-1.49) for neutrophils and 1.29 (1.15-1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes.Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations may not be causal, although limitations in statistical power and balancing pleiotropic effects cannot be excluded.
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