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Detecting diastolic heart failure by protease and protease inhibitor plasma profiling

A heart failure, diastolic technology, applied in the direction of biochemical equipment and methods, microbial determination/examination, etc.

Inactive Publication Date: 2009-07-22
MUSC FOUND FOR RES DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A specific problem in identifying patients at risk of developing hypertensive heart failure is the lack of a rapid screening test to identify patients with intrinsic changes in the myocardium secondary to hypertension

Method used

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  • Detecting diastolic heart failure by protease and protease inhibitor plasma profiling
  • Detecting diastolic heart failure by protease and protease inhibitor plasma profiling
  • Detecting diastolic heart failure by protease and protease inhibitor plasma profiling

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0217] 1. Example 1: Tissue Inhibitors of Matrix Metalloproteinases / Metalloproteinases: Changes in Proteolytic Factors of Matrix Components and the Relationship Between Structure, Function and Clinical Manifestations of Hypertensive Cardiac Diseases

[0218]Brief description of methods and results: 103 subjects were divided into 4 groups as follows: a) reference subjects (CTL) without evidence of cardiovascular disease; b) hypertensive (HTN), controlled blood pressure and no LV hypertrophy ; c) Hypertension, blood pressure controlled and LV hypertrophy (HTN&LVH), but no CHF; d) Hypertension, blood pressure controlled, LVH and CHF (HTN&LVH&CHF), plasma MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, and Doppler echocardiography. All MMPs or TIMPs were not significantly altered in HTN patients compared with CTL. In HTN&LVH patients, MMP-9 and MMP-13 decreased, while MMP-9 increased. TIMP-1 was only elevated in HTN&LVH&CHF patients. TIMP-1>1200ng / mL predicted CHF.

[0219] Conclusi...

Embodiment 2

[0260] 2. Example 2: Matrix metalloproteinases / tissue inhibitors of metalloproteinases: the relationship between changes in the proteolytic factors of matrix components and the structure, function and clinical manifestations of hypertensive heart disease

[0261] method

[0262] Study Access: Table 6 shows the study access. Exclusion criteria were history of myocardial infarction, cardiomyopathy, abnormal valve or ventricular wall motion, arrhythmia, invasive heart disease, EF140 or DBP>90) or affecting MMP / TIMP plasma spectrum of systemic disease. Inclusion criteria for controls and HTN controls were men and women aged 18-90 years without evidence of structural cardiovascular disease. The entry criteria for LVH and LVH with CHF were echocardiographically confirmed LV hypertrophy (wall thickness >1.2 cm or LV mass index >125 g / m 2 ), men and women aged 18-90.

[0263] Table 6: Study Access

[0264]

[0265] Echocardiographic measurements: Dimensional echocardiographi...

Embodiment 4

[0272] 3. Example 4: Criteria for distinguishing, predicting and diagnosing heart failure in hypertensive patients

[0273] A definitive list of normal values ​​for human subjects within the stated age ranges and across genders is provided in Table 7. A compiled list of normal reference values ​​for MMP / TIMP as encompassed by the present invention has not been provided before, and since age-matched subjects without cardiovascular disease were included, Table 7 also provides normal reference ranges. Furthermore, new stoichiometric ratios of the MMP / TIMP profile are provided, demonstrating that this profile covers important diagnostic and prognostic information as detailed in the table below. These data were collected and analyzed from more than 100 subjects.

[0274] Table 7: Normal Human* Reference Ranges

[0275]

[0276] *Normal adult age is 25-70 years old

[0277] Table 8 presents the absolute values ​​of MMP and TIMP, the absolute value of the MMP / TIMP ratio, and th...

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Abstract

The invention discloses methods of detecting and predicting diastolic heart failure and predicting congestive heart failure comprising protease and protease inhibitor profiling.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 60 / 798,953, filed May 9, 2006, and U.S. Provisional Application No. 60 / 893,781, filed March 8, 2007, which are hereby incorporated by reference in their entirety Apply. [0003] Statement on Federally Sponsored Research [0004] This application was awarded under Contract No. VA of the Merit Review (Spinale 0001) Research Service of the Department of Veterans Affairs and the National Heart, Lung, and Blood Institute Completed with government funding under contracts PO1-HL48788, RO1-HL-59165 and MO1-RR-01070-251. Background technique [0005] Despite strides in the availability of hypertensive (high blood pressure) medications and the recognition that high blood pressure is a major risk factor for developing heart failure, the disease remains the leading cardiovascular disease in the United States. A specific problem in identifying patients at risk...

Claims

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Application Information

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IPC IPC(8): C12Q1/37
Inventor F·G·斯皮纳尔R·E·斯特劳德M·R·齐利
Owner MUSC FOUND FOR RES DEV
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