02859nas a2200397 4500008004100000022001400041245014100055210006900196260001300265300001200278490000600290520171800296653001002014653000902024653001502033653003002048653002502078653001802103653001602121653001102137653004302148653001102191653000902202653001602211653003202227653002402259653001702283653001302300653001802313653002702331100001702358700001702375700001802392700001502410856003602425 2009 eng d a1538-783600aPeak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study.0 aPeak thrombin generation and subsequent venous thromboembolism t c2009 Oct a1639-480 v73 a

BACKGROUND: Thrombin is an enzyme that is essential for the acceleration of the coagulation cascade and the conversion of fibrinogen to clottable fibrin.

OBJECTIVES: We evaluated the relationship of basal peak thrombin generation with the risk of future venous thromboembolism (VTE), and determined whether associations were independent of other coagulation markers.

METHODS: The Longitudinal Investigation of Thromboembolism Etiology (LITE) study investigated VTE in two prospective population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS). Peak thrombin generation was measured on stored plasma in a nested case-control sample (434 cases and 1004 controls). Logistic regression was used to estimate the relationship of peak thrombin generation with VTE, adjusted for age, sex, race, center, and body mass index. Mediation was evaluated by additionally adjusting for factor VIII and D-dimer.

RESULTS: Relative to the first quartile of peak thrombin generation, the odds ratio (OR) of VTE for those above the median was 1.74 [95% confidence interval (CI) 1.28-2.37]. The association was modestly attenuated by adjustment for FVIII and D-dimer (OR 1.47, 95% CI 1.05-2.05). Associations appeared to be stronger for idiopathic than for secondary VTE. Elevated peak thrombin generation more than added to the VTE risk associated with FV Leiden or low activated partial thromboplastin time.

CONCLUSIONS: In this prospective study of two independent cohorts, elevated basal peak thrombin generation was associated with subsequent risk of VTE, independently of established VTE risk factors.

10aAdult10aAged10aBiomarkers10aBlood Coagulation Factors10aCase-Control Studies10aEthnic Groups10aFactor VIII10aFemale10aFibrin Fibrinogen Degradation Products10aHumans10aMale10aMiddle Aged10aPartial Thromboplastin Time10aProspective Studies10aRisk Factors10aThrombin10aUnited States10aVenous Thromboembolism1 aLutsey, P, L1 aFolsom, A, R1 aHeckbert, S R1 aCushman, M uhttps://chs-nhlbi.org/node/111902476nas a2200253 4500008004100000022001400041245010400055210006900159260001600228520173900244100001801983700001702001700001702018700001702035700001202052700002002064700001702084700002002101700001802121700001502139700001502154700001702169856003602186 2017 eng d a1538-783600aTaller height as a risk factor for venous thromboembolism: a Mendelian randomization meta-analysis.0 aTaller height as a risk factor for venous thromboembolism a Mend c2017 Apr 263 a

BACKGROUND: Taller height is associated with greater risk of venous thromboembolism (VTE).

OBJECTIVES: We used instrumental variable (IV) techniques (Mendelian randomization) to further explore this relationship METHODS: Participants of European ancestry were included from two cohort studies [Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS)] and one case-control study [Mayo Clinic VTE Study (Mayo)]. We created two weighted genetic risk scores (GRS) for height; the full GRS included 668 single nucleotide polymorphisms (SNPs) from a previously published meta-analysis and the restricted GRS included a subset of 362 SNPs not associated with weight independently of height. Standard logistic regression and IV models were used to estimate odds ratios (ORs) for VTE per 10 cm increment in height. ORs were pooled across the three studies using inverse variance weighted random effects meta-analysis RESULTS: Among 9143 ARIC and 3180 CHS participants free of VTE at baseline, there were 367 and 109 incident VTE events. There were 1143 VTE cases and 1292 controls included from Mayo. The pooled ORs from non-IV models and models using the full and restricted GRSs as IVs were 1.27 (95% CI: 1.11, 1.46), 1.34 (95% CI: 1.04, 1.73), and 1.45 (95% CI: 1.04, 2.01) per 10 cm greater height, respectively CONCLUSIONS: Taller height is associated with an increased risk of VTE in adults of European ancestry. Possible explanations for this association, including that taller people may have greater venous surface area, greater number of venous valves, or greater hydrostatic pressure, need to be explored further. This article is protected by copyright. All rights reserved.

1 aRoetker, N, S1 aArmasu, S, M1 aPankow, J, S1 aLutsey, P, L1 aTang, W1 aRosenberg, M, A1 aPalmer, T, M1 aMacLehose, R, F1 aHeckbert, S R1 aCushman, M1 aAndrade, M1 aFolsom, A, R uhttps://chs-nhlbi.org/node/7359