Activation of Hemostasis and Decline in Cognitive Function in Older People

Stott, David J.; Robertson, Michele; Rumley, Ann; Welsh, Paul; Sattar, Naveed; Packard, Christopher J.; Shepherd, James; Trompet, Stella; Westendorp, Rudi G. J.; Craen, Anton J. M. de; Jukema, J. Wouter; Buckley, Brendan M.; Ford, Ian; Lowe, G. D. O.

doi:10.1161/atvbaha.109.199448

Cited by 40 publications

(37 citation statements)

References 26 publications

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“…17,18 CRP was measured at baseline with an automated particle-enhanced immunoturbidimetric assay (Roche UK). 17 Heart failure hospitalization and cardiovascular mortality…”

Section: Inflammation and Endothelial Dysfunction Markersmentioning

confidence: 99%

Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study

Nanchen

Stott

Gussekloo

et al. 2013

European J of Heart Fail

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AimsResting heart rate is a promising modifiable cardiovascular risk marker in older adults, but the mechanisms linking heart rate to cardiovascular disease are not fully understood. We aimed to assess the association between resting heart rate and incident heart failure (HF) and cardiovascular mortality, and to examine whether these associations might be attributable to systemic inflammation and endothelial dysfunction. Methods and resultsWe studied 4084 older adults aged 70-82 years with known cardiovascular risk factors or previous cardiovascular disease, without pre-existing HF or beta-blockers in the PROSPER study. Over a 3.2-year follow-up period, we examined incident HF hospitalization and cardiovascular mortality according to resting heart rate, along with C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), and von Willebrand factor (vWf). Mean heart rate was 67 b.p.m. for men and 70 b.p.m. for women. CRP, IL-6, tPA, and vWf levels were all positively correlated with heart rate. After multivariate adjustment, heart rate was associated with HF hospitalization [hazard ratio (HR) 1.78 for highest vs. lowest distribution third, 95% confidence interval (CI) 1.21-2.63, P ¼ 0.003] and cardiovascular mortality (HR 1.74, 95% CI 1.23-2.47, P ¼ 0.002). Further adjustment for both IL-6 and vWf levels decreased HR to 1.60 (95% CI 1.08-2.38, P ¼ 0.020) for HF and to 1.50 (95% CI 1.04-2.15, P ¼ 0.028) for cardiovascular mortality. ConclusionIncreased heart rate is associated with increased systemic inflammation and endothelial dysfunction. These factors are likely to contribute to, but do not fully explain, the risk of HF and cardiovascular death associated with increased heart rate in older age.--

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“…17,18 CRP was measured at baseline with an automated particle-enhanced immunoturbidimetric assay (Roche UK). 17 Heart failure hospitalization and cardiovascular mortality…”

Section: Inflammation and Endothelial Dysfunction Markersmentioning

confidence: 99%

Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study

Nanchen

Stott

Gussekloo

et al. 2013

European J of Heart Fail

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“…The central finding was that increased levels of D-dimer and prothrombin fragment 1ϩ2 (ie, markers of thrombin generation) were associated independently with increased rates of cognitive decline and deterioration in activities of daily living (Table). 12 Interestingly, markers of endothelial dysfunction (eg, tissue plasminogen activator and von Willebrand factor) were not associated with cognitive decline.…”

Section: See Accompanying Articles On Pages 599 and 605mentioning

confidence: 98%

“…Oral anticoagulation with warfarin might be attractive because it reduces prothrombin fragment 1ϩ2, thrombin-antithrombin complexes, and D-dimer 12 ; safety concerns exist about its use in patients with leukoaraiosis 16 (ie, the group in whom it might be useful). Information from completed and ongoing trials of oral direct thrombin inhibitors, in which data on cognition were collected, will further illuminate this issue.…”

Section: See Accompanying Articles On Pages 599 and 605mentioning

confidence: 99%

Hemostasis and Vascular Dementia

Bath

Anderton

Ankolekar

2010

ATVB

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V ascular dementia (VaD) comprises a group of syndromes caused by vascular lesions in the brain. Cognitive impairment may follow a single cortical or lacunar infarct in a strategic area of the brain, multiple infarcts, small-vessel disease (leukoaraiosis), intracerebral hemorrhage, or any of these conditions coexisting with Alzheimer dementia (so-called mixed dementia). Depending on case mix and the type of observational study, 10% of patients already have dementia before their first stroke, 10% develop it soon after their first stroke, and more than 33% have dementia after a recurrent stroke. 1 Typically, dementia develops at a rate of 3% per year after stroke, and it is the stroke, rather than its underlying risk factors, that appears to be the dominant cause of subsequent dementia. 1 See accompanying articles on pages 599 and 605Although VaD, including poststroke dementia, is associated with conventional risk factors, such as hypertension and hypercholesterolemia, 2,3 their relationship with hemostatic factors is less clear. This contrasts with the relationship between hemostatic factors and stroke, which is well established and involves both soluble (eg, fibrinogen 4 ) and cellular (eg, mean platelet volume 5 ) biomarkers. Several hemostatic factors, including fibrinogen and fibrin D-dimer levels, are associated with subsequent cognitive impairment and dementia in observational studies (Table). 6 -10 This issue of Arteriosclerosis, Thrombosis, and Vascular Biology expands on this relationship between "sticky blood" and cognition. 11 Two new studies are described.First, Stott and colleagues 12 report observational data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), which examined lipid lowering 13 : 5699 people (average age, 75 years) not taking warfarin had measurements of hemostatic factors at baseline and annual assessments of cognition over 3.2 years of follow-up. Cognitive measures included speed of information processing (Letter Digit Coding Test and Stroop test) and verbal memory (picture-word naming). The central finding was that increased levels of D-dimer and prothrombin fragment 1ϩ2 (ie, markers of thrombin generation) were associated independently with increased rates of cognitive decline and deterioration in activities of daily living (Table). 12 Interestingly, markers of endothelial dysfunction (eg, tissue plasminogen activator and von Willebrand factor) were not associated with cognitive decline.Second, Gallacher and colleagues 14 present data on 865 men free of vascular disease, with biomarker measurements, who were observed in the Caerphilly community cohort. Hemostasis factors were measured at the age of 45 to 59 years, and cognition and dementia were determined up to the age of 65 to 84 years. During 17 years of follow-up, 59 of the men developed dementia and 112 developed cognitive impairment/no dementia. Increased fibrinogen, factor VIII, and plasminogen activator inhibitor-1 levels were associated independently with VaD (Table). 14 In contrast, increased lev...

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“…Various cohort and case-control-based studies have described an apparent association between higher levels of blood markers of thrombosis and haemostasis and incident dementia or cognitive decline (Bots et al 1998;Gallacher et al 2010;Stott et al 2010). Recent systematic review and meta-analysis have confirmed this link with blood markers; observed associations were strongest for Bvascular^dementia but also apparent for Ballcause^(undifferentiated) dementias (Quinn et al 2011).…”

Section: Introductionmentioning

confidence: 97%

Association between cognition and gene polymorphisms involved in thrombosis and haemostasis

Quinn

Alghamdi

Padmanabhan

et al. 2015

AGE

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An association between blood markers of thrombosis and haemostasis and cognitive decline has been described. These results may be confounded by lifestyle and environmental factors. We used a Mendelian randomisation approach to describe the association between thrombosis/haemostasis genotypes and cognition. We studied the genetic variants (single nucleotide polymorphisms) of circulating markers of thrombosis and haemostasis. Our chosen blood factors and associated polymorphisms were D-dimer [rs12029080], fibrinogen [rs1800789], plasminogen activator inhibitor [rs2227631], and von Willebrand factor [rs1063857]. We described association with multidomain cognitive test scores using data from the Scottish Family Health Study. Cognitive data were analysed for individual tests and combined to give a general cognitive factor. In 20,288 subjects, we found no evidence of association between cognitive function (individual tests and combined scores) and any of the above-mentioned single nucleotide polymorphisms. Lower scores on cognitive measures were associated with increasing age, socioeconomic deprivation, blood pressure, waist-hip ratio, smoking, and vascular comorbidity (all p < 0.001). In a post hoc sensitivity analysis restricted to those aged over 50 years, there was still no signal of association. Our data add to our understanding of determinants of cognition but are not definitive; the variation in blood levels explained by SNPs was modest and our sample size may have been insufficient to detect a modest association.

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Activation of Hemostasis and Decline in Cognitive Function in Older People

Cited by 40 publications

References 26 publications

Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study

Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study

Hemostasis and Vascular Dementia

Association between cognition and gene polymorphisms involved in thrombosis and haemostasis

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