Factors that showed a predominant association with ischaemic stroke or myocardial infarction (RRR>1+SE and RRR<1-SE).

<p>(¹) Normalised ratios for LA-screen and LA-confirm coagulation times. The positivity for lupus anticoagulant was considered when the ratio was 1.15 or higher, on the basis of the 99th percentile of the value recorded for 40 healthy volunteers. More details can be found in the original publication.</p><p>(*) Prothrombotic factors with an RRR greater than 1+2SE. No prothrombotic factor had an RRR less than 1-2SE.</p><p>Factors that showed a predominant association with ischaemic stroke or myocardial infarction (RRR>1+SE and RRR<1-SE).</p

Flow chart of the steps of data collection.

<p>The figure shows the three steps in the data collection: (1) identification of publications which report on the effect of measures of hypercoagulability and the risk of myocardial infarction (MI) or ischaemic stroke (IS) (2) identification of study populations (3) identification of publications with comparable data. Comparable data can be found in the same publication or in two different publications.</p

Prothrombotic risk factors and their effect on myocardial infarction and ischemic stroke.

<p>Each point depicts the log odds ratio as a measure of effect of a particular risk factor on the risk of myocardial infarction (x-axis) as well as the effect on the risk of ischaemic stroke (y-axis). The red dashed lines indicate the null effect for either myocardial infarction (vertical line) or ischaemic stroke (horizontal line). The blue diagonal line represents the theoretical line along which all points would cluster when the role of thrombotic factors is similar in the aetiology of myocardial infarction and ischaemic stroke. <i>As an explicative example red dots represent</i>: <i>#312</i>: <i>KAL-C1-INH (RR</i>_<i>IS</i><i>5</i>.<i>14 e RR</i>_<i>MI</i><i>2</i>.<i>12)</i>. <i>#281</i>: <i>FXIIIA SNP rs3024462 allele (RR</i>_<i>IS</i><i>1</i>.<i>82 e RR</i>_<i>MI</i><i>0</i>.<i>49)</i>.</p

Distribution of RRRs greater than 1+1SE and smaller than 1-1SE for different subgroups of population.

<p>(¹) Young age at onset is defined as younger than 50 years old for women and 55 for men.</p><p>(²) Low risk for arterial thrombosis is defined as a risk comparable with the general population. High risk for arterial thrombosis is given to populations affected by one or more diseases with a high impact on cardiovascular risk (such as atrial fibrillation, end stage renal disease, previous cardiovascular event).</p><p>Distribution of RRRs greater than 1+1SE and smaller than 1-1SE for different subgroups of population.</p

Prothrombotic risk factors with RRR either >1+SE and <1-SE (left) and either > 1+SE and <1-SE (right).

<p>Each point depicts the log odds ratio as a measure of effect of a particular risk factor on the risk of myocardial infarction (x-axis) as well as the effect on the risk of ischaemic stroke (y-axis). The red dashed lines indicate the null effect for either myocardial infarction (vertical line) or ischaemic stroke (horizontal line). The blue diagonal line represents the theoretical line along which all points would cluster when the role of thrombotic factors is similar in the aetiology of myocardial infarction and ischaemic stroke. On the left are depicted RRR>1+SE and RRR<1-SE. on the right RRR>1+2SE. No factors had RRR<1-2SE. Numbers represent the ID of the corresponding marker in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133523#pone.0133523.t001" target="_blank">Table 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133523#pone.0133523.s005" target="_blank">S2</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133523#pone.0133523.s006" target="_blank">S3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133523#pone.0133523.s007" target="_blank">S4</a> Tables.</p

Baseline characteristics.

<p>* Patients were excluded because of quality concerns</p><p>Baseline characteristics.</p

Cox proportional hazard models and AUC-ROC.

<p>Table displays univariable analyses of risk factors for vascular disease for different endpoints. The bold numbers are accounted in the multivariable model with and without genetic risk scores. AUC-ROC = Area Under Curve of the Receiver Operating Characteristics Curve. M1 = primary outcome. M2 = secondary outcome, ischemic stroke</p><p>Cox proportional hazard models and AUC-ROC.</p

ROC curves for the primary outcome.

<p>(a) based on classical risk factors only; (b) based on classical risk factors plus the genetic risk score.</p

Multivariable hazard ratio’s for risk factors for intracerebral hemorrhage in general, lobar and non-lobar hemorrhage.

<p>The number of patients included in the analyses varied from 8,453 to 11,643 in the combined cohort and from 7,232 to 8,953 in the SMART cohort. Abbreviations: SMART, Second Manifestations of ARTerial disease study; ESPRIT, European/Australasian Stroke Prevention in Reversible Ischaemia Trial; ICH, intracerebral hemorrhage; aHR, adjusted Hazard Ratio; SBP, systolic blood pressure; eGFR, estimated glomerular filtration rate; I, index event; A, age; P, antiplatelet medication; C, anticoagulant medication; G, sex; S, systolic blood pressure.</p><p>Multivariable hazard ratio’s for risk factors for intracerebral hemorrhage in general, lobar and non-lobar hemorrhage.</p

Baseline characteristics of patients.

<p>For the combined cohort, data were missing in 0.2% of patients or less, except for hyperlipidemia (1.4%). For the SMART cohort data were missing for impaired renal function (0.8%), hyperhomocysteinemia (7.1%), alcohol use (0.7%) and statins in 27.2% of patients. Abbreviations: SMART, Second Manifestations of ARTerial disease study; ESPRIT, European/Australasian Stroke Prevention in Reversible Ischaemia Trial; SD, standard deviation; HDL, high density lipoprotein; LDL, low density lipoprotein; eGFR, estimated glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein.</p><p>Baseline characteristics of patients.</p