The present invention provides compositions and methods based on genetic polymorphisms that are associated with coronary heart disease (particularly myocardial infarction), aneurysm/dissection, and/or response to drug treatment, particularly statin treatment. For example, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by these nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and variant proteins, and methods of using the nucleic acid molecules and proteins as well as methods of using reagents for their detection.

Systems and methods for detecting an intracranial aneurysm in a test subject are provided. Liquid biological samples are obtained from the test subject, each liquid biological sample comprising a plurality of protein analytes. Liquid biological samples are analyzed using an immunoassay, obtaining a test dataset comprising a plurality of abundance measures. Each abundance measure corresponds to a respective protein analyte in the plurality of protein analytes. The test dataset is inputted into a trained classifier, obtaining an indication from the trained classifier that the subject has an intracranial aneurysm, based at least in part on the plurality of abundance measures for the test subject in the test dataset.

This present disclosure relates to the use of one or more biomarkers for diagnosis, screening, or monitoring aortic aneurysm disease (e.g., ascending aortic aneurysm, descending thoracic aortic aneurysm, abdominal aortic aneurysm and Marfan syndrome) in a biological sample (e.g., a blood sample) of a subject. Accordingly, this disclosure provides methods and kits for determining the presence of one or more biomarkers for aortic aneurysm disease in a biological sample of a subject; methods for using the presence of such biomarkers to predict or diagnose aortic aneurysm disease in a subject; and methods to select or modify a therapeutic regimen (e.g., a beta-blocker treatment) for a subject based on the use of such biomarkers.

A method for detecting thoracic aortic aneurysm (TAA) or predisposition to TAA in a subject comprises measuring the amount of tetrahydrobiopterin (H.sub.4B) present in the test sample; and comparing a measured amount of HUB to a standard amount of H.sub.4B. A decreased amount of H.sub.4B present in the test sample compared to the standard is indicative of TAA or predisposition to TAA. The method can further comprise identifying a candidate for further testing or monitoring for TAA, such as by ultrasound or by repeated testing for H.sub.4B after one or more designated intervals. The method can also further comprise prescribing treatment for TAA to the subject, such as with folic acid therapy, and/or DHFR therapy, including gene therapy, and other therapies effective for recoupling eNOS and/or therapies targeting uncoupled eNOS. Methods are also described for monitoring the efficacy of treatment of TAA, and for evaluating the severity of TAA or risk of TAA.

Provided herein are methods of detecting biomarkers and/or candidate biomarkers for heart disorders and uses of the same.

The present invention provides compositions and methods based on genetic polymorphisms that are associated with coronary heart disease (particularly myocardial infarction), aneurysm/dissection, and/or response to drug treatment, particularly statin treatment. For example, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by these nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and variant proteins, and methods of using the nucleic acid molecules and proteins as well as methods of using reagents for their detection.

Thoracic aortic aneurysm is a common and lethal disease that requires regular imaging surveillance to determine timing of surgical repair and prevent major complications such as rupture. Current cross-sectional imaging surveillance techniques, largely based on computed tomography angiography (CTA) or magnetic resonance angiography (MRA), are focused on measurement of maximal aortic diameter, although this approach is limited to fixed anatomic positions and is prone to significant measurement error. The present techniques demonstrate novel approaches (generally termed herein Vascular Deformation Mapping (VDM)) for assessing changes in aortic dimensions. The present techniques quantify three-dimensional changes in the anatomic dimensions of a vessel through a process that involves non-rigid co-registration of serial imaging data and quantification of vascular deformation on a 3D surface model using some derivation of the spatial deformations resulting from the optimized spatial transform.

The present invention relates to a method for predicting the risk of having or developing Intracranial aneurysms (IA) in a subject, by identifying at least one mutation in an angiogenic protein, such as Angiopoietin-Like 6 (ANGPTL6). In particular, inventors identified one rare nonsense variant (c.1378A>T) in the last exon of the ANGPTL6 gene which encodes a 10 circulating pro-angiogenic factor mainly secreted from the liver shared by the 4 tested affected members of a large pedigree with multiple IA carriers. They GC showed a 50% reduction of ANGPTL6 serum concentration in heterozygous c.1378A>T carriers compared to non-carrier relatives, due to the non-secretion of the truncated protein produced by the c.1378A>T transcripts. They observed a higher rate of individuals with a history of high blood pressure 15 among affected versus healthy carriers of ANGPTL6 variants, suggesting that ANGPTL6 could trigger cerebrovascular lesions when combined with other risk factors such as hypertension.

The present invention provides compositions and methods based on genetic polymorphisms that are associated with coronary heart disease (particularly myocardial infarction), aneurysm/dissection, and/or response to drug treatment, particularly statin treatment. For example, the present invention relates to nucleic acid molecules containing the polymorphisms, variant proteins encoded by these nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and variant proteins, and methods of using the nucleic acid molecules and proteins as well as methods of using reagents for their detection.

Systems and methods are provided for monitoring mortality risk in children with congenital cyanotic heart condition such as Tetralogy of Fallot (ToF) including prioritizing ToF patients for medical treatment and determining that a ToF patient is eligible for urgent surgical correction. Some embodiments of the invention determine a prognosis in terms of a predicted survival probability within a timeframe wherein the pediatric subject awaits surgical correction, based on determining the amount of a marker, such as BNP (brain natriuretic peptide) in serial samples of blood plasma from the subject and determining a Tetralogy of Fallot Index (TOFI) score from the biomarker values. Some embodiments of the invention use the score to determine severity of the heart condition for one or more patients, which may be used for managing treatment, such as scheduling surgery, transfers to available treatment centers, managing medical resources, or predicting costs, including for settings where the resources to perform pediatric cardiac surgery are limited.