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Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.

ABSTRACT: Background Individual blood cell count abnormalities have been associated with cardiovascular disease and increased mortality. In this study, we defined a "cytopenia phenotype," reflecting bone marrow hypoproliferation, to determine if peripheral blood cytopenia is associated with increased cardiovascular disease and mortality risk. Methods and Results Study participants were derived from a biracial observational cohort study, REGARDS (Reasons for Geographic and Racial Differences in Stroke), that enrolled 30 239 Black and White participants aged ≥45 years between 2003 and 2007. Median follow up was ≈9 years. The current study included 19 864 participants from REGARDS study (37.9% men, 40% Black participants) who have complete blood count available at study enrollment. We defined a cytopenia phenotype based on age-, sex-, and race-adjusted lowest fifth percentile of blood counts. Multivariable Cox proportional hazards models estimated the hazard ratios (HR) and 95% CI of cytopenia for mortality and incident cardiovascular disease in adjusted models. Mean age of the study participants was 64 years (SD:9.7). The prevalence of cytopenia was 1.9% (n=378). Cytopenia was associated with increased risk of all-cause mortality (HR, 1.73; 95% CI, 1.34-2.22) and cardiovascular disease mortality (HR, 1.56; 95% CI, 1.11-2.29). Cytopenia was associated with stroke risk in Black but not White participants (HR, 1.96 versus 0.86; P-interaction for race=0.08) and was not associated with coronary heart disease risk. Conclusions We defined a cytopenia phenotype with clinical implications for mortality and stroke risk in a large biracial and geographically diverse population. Whether generated through somatic mutations or decreased organ function, cytopenia was associated with mortality risk and was a race-specific risk factor for stroke.

SUBMITTER: Gangaraju R

PROVIDER: S-EPMC8649504 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.

Gangaraju Radhika R Koh Insu I Irvin Marguerite R MR Lange Leslie L Houghton Damon E DE Herrera Diego Adrianzen DA Safford Monika M Cushman Mary M Bhatia Smita S Zakai Neil A NA

Journal of the American Heart Association 20210913 18

Background Individual blood cell count abnormalities have been associated with cardiovascular disease and increased mortality. In this study, we defined a "cytopenia phenotype," reflecting bone marrow hypoproliferation, to determine if peripheral blood cytopenia is associated with increased cardiovascular disease and mortality risk. Methods and Results Study participants were derived from a biracial observational cohort study, REGARDS (Reasons for Geographic and Racial Differences in Stroke), th ...[more]

PMID: 34514816

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Project description:Peripheral blood cytopenias may precede the development of hematological malignancies and frequently pose clinical challenges in the older population. The natural course of (mild) cytopenias during aging and their association with hematological disorders in community-dwelling individuals are not well studied. Within the population-based Lifelines cohort (n = 167729), we studied changes in peripheral blood counts, occurrence of cytopenias, and associated hematological outcomes in the context of aging. Development of hematological malignancies and (cause-specific) mortality were evaluated by linkage to nationwide registries. Anemia and thrombocytopenia emerged with older age, in line with a general age-related decline in these blood counts. For neutropenia, no increase in prevalence with older age was observed. Using standard reference limits to define cytopenias, anemia (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.59-2.12), thrombocytopenia (HR, 1.58; 95% CI, 1.32-1.89), and, especially the concomitant presence of anemia and thrombocytopenia (HR, 4.75; 95% CI, 2.98-7.55) were associated with inferior overall survival. Only a minor proportion of deaths was explained by diagnosed hematological malignancies, with the majority attributable to other causes. Neutropenia, either isolated (HR, 0.88; 95% CI, 0.73-1.06) or combined with another cytopenia, did not affect overall survival. For individuals aged ≥60 years, 5-year cumulative incidence of hematological malignancies was 0.60% (95% CI, 0.50-0.70), with higher incidences among those with anemia (P < .001) or thrombocytopenia (P < .001) but not neutropenia (P = .201). Highest cumulative incidences of diagnoses and mortality from hematological malignancies were observed in individuals with >1 cytopenia. We conclude that anemia and thrombocytopenia, but not neutropenia, are associated with inferior overall survival of community-dwelling individuals. Hematological malignancies develop in a small fraction of these cases.

Project description:BackgroundProspective cohort studies suggest that frailty is associated with an increased risk of incident cardiovascular disease (CVD) morbidity and mortality, but their mechanistic and developmental relations are not fully understood. We investigated whether frailty predicted an increased risk of incident nonfatal and fatal CVD among community-dwelling older adults.MethodsA population cohort of 5015 participants aged 55 years and above free of CVD at baseline was followed for up to 10 years. Pre-frailty and frailty were defined as the presence of 1-2 and 3-5 modified Fried criteria (unintentional weight loss, weakness, slow gait speed, exhaustion, and low physical activity), incident CVD events as newly diagnosed registered cases of myocardial infarction (MI), stroke, and CVD-related mortality (ICD 9: 390 to 459 or ICD-10: I00 to I99). Covariate measures included traditional cardio-metabolic and vascular risk factors, medication therapies, Geriatric Depression Scale (GDS), Mini-Mental State Exam (MMSE), and blood biomarkers (haemoglobin, albumin, white blood cell counts and creatinine).ResultsPre-frailty and frailty were significantly associated with elevated HR = 1.26 (95%CI: 1.02-1.56) and HR = 1.54 (95%CI:1.00-2.35) of overall CVD, adjusted for cardio-metabolic and vascular risk factors and medication therapies, but not after adjustment for GDS depression and MMSE cognitive impairment. The HR of association between frailty status and both CVD mortality and overall mortality, however, remained significantly elevated after full adjustment for depression, cognitive and blood biomarkers.ConclusionFrailty was associated with increased risk of CVD morbidity and especially mortality, mediated in parts by traditional cardio-metabolic and vascular risk factors, and co-morbid depression and associated cognitive impairment and chronic inflammation. Given that pre-frailty and frailty are reversible by multi-domain lifestyle and health interventions, there is potential benefits in reducing cardiovascular diseases burden and mortality from interventions targeting pre-frailty and early frailty population.

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Project description:BackgroundDNA methylation patterns associated with habitual diet have not been well studied.MethodsDiet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality.ResultsWe identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10-6).ConclusionsHabitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

Project description:ImportanceClinical trials have documented that lowering blood pressure reduces cardiovascular disease and premature deaths. However, the optimal target for reduction of systolic blood pressure (SBP) is uncertain.ObjectiveTo assess the association of mean achieved SBP levels with the risk of cardiovascular disease and all-cause mortality in adults with hypertension treated with antihypertensive therapy.Data sourcesMEDLINE and EMBASE were searched from inception to December 15, 2015, supplemented by manual searches of the bibliographies of retrieved articles.Study selectionStudies included were clinical trials with random allocation to an antihypertensive medication, control, or treatment target. Studies had to have reported a difference in mean achieved SBP of 5 mm Hg or more between comparison groups.Data extraction and synthesisData were extracted from each study independently and in duplicate by at least 2 investigators according to a standardized protocol. Network meta-analysis was used to obtain pooled randomized results comparing the association of each 5-mm Hg SBP category with clinical outcomes after adjusting for baseline risk.Main outcomes and measuresCardiovascular disease and all-cause mortality.ResultsForty-two trials, including 144 220 patients, met the eligibility criteria. In general, there were linear associations between mean achieved SBP and risk of cardiovascular disease and mortality, with the lowest risk at 120 to 124 mm Hg. Randomized groups with a mean achieved SBP of 120 to 124 mm Hg had a hazard ratio (HR) for major cardiovascular disease of 0.71 (95% CI, 0.60-0.83) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.58 (95% CI, 0.48-0.72) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.46 (95% CI, 0.34-0.63) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.36 (95% CI, 0.26-0.51) compared with those with a mean achieved SBP of 160 mm Hg or more. Likewise, randomized groups with a mean achieved SBP of 120 to 124 mm Hg had an HR for all-cause mortality of 0.73 (95% CI, 0.58-0.93) compared with randomized groups with a mean achieved SBP of 130 to 134 mm Hg, an HR of 0.59 (95% CI, 0.45-0.77) compared with those with a mean achieved SBP of 140 to 144 mm Hg, an HR of 0.51 (95% CI, 0.36-0.71) compared with those with a mean achieved SBP of 150 to 154 mm Hg, and an HR of 0.47 (95% CI, 0.32-0.67) compared with those with a mean achieved SBP of 160 mm Hg or more.Conclusions and relevanceThis study suggests that reducing SBP to levels below currently recommended targets significantly reduces the risk of cardiovascular disease and all-cause mortality. These findings support more intensive control of SBP among adults with hypertension.

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Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.

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Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.

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