Diagnosis of cardiovascular disease
This invention relates to methods for the detection of cardiovascular disease, e.g., acute coronary syndrome, heart failure and/or pulmonary embolism, in high body mass index (BMI) individuals, e.g., with a BMI of 25-29, or 30 or above, and those with impaired renal function.
1. A method of diagnosing heart failure in a subject who has one or both of a body mass index (BMI) of greater than or equal to 25, and impaired renal function, and treating the subject, the method comprising:
(a) one or both of:
(i) determining the subject's BMI, and if the subject's BMI is equal to or greater than 25, selecting the subject; and
(ii) evaluating the subject's renal function, and if the subject has impaired renal function, selecting the subject;
(b) performing an immunoassay to determine a level of brain natriuretic peptide (BNP) and a level of soluble ST2 in a biological sample from the selected subject;
(c) identifying a selected subject having a BNP level of between 100 pg/mL and 500 pg/mL, and an elevated level of soluble ST2 as compared to a reference level of soluble ST2 as having heart failure; and
(d) administering a pharmaceutical treatment for heart failure to the identified subject.
2. The method of claim 1 , wherein the biological sample comprises blood, plasma, or serum.
3. The method of claim 1 , wherein the reference level of soluble ST2 represents a level of soluble ST2 in a subject who does not have heart failure.
4. The method of claim 2 , wherein the reference level of soluble ST2 is about 0.2 ng/mL of serum, and values above that level indicate, in part, the presence of heart failure.
5. The method of claim 1 , further comprising performing an assay to determine a level of one or more other biomarkers in the subject.
6. The method of claim 5 , wherein the one or more other biomarkers are selected from the group consisting of atrial natriuretic peptide (ANP), N-terminal-proANP, troponin, C-reactive protein, creatinine, Blood Urea Nitrogen, liver function enzymes, and albumin.
7. The method of claim 1 , wherein determining whether the subject has impaired renal function comprises determining glomerular filtration rate (GFR) and/or serum creatinine level, and determining that the subject has impaired renal function if they have a GFR or serum creatinine level as shown in the following table:
Serum
GFR
Creatinine
Grade
(ml/minute)
(μmol/liter)
mild
20-50
150-300
moderate
10-20
300-700
severe
<10
>700.
8. The method of claim 1 , wherein the subject has a BMI of greater than or equal to 30.
9. The method of claim 1 , wherein the subject has a BMI of 25 to 29.
10. The method of claim 1 , wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA).
11. A method of diagnosing heart failure in a subject who has impaired renal function, and treating the subject, the method comprising:
(a) evaluating the subject's renal function, and if the subject has impaired renal function, selecting the subject;
(b) performing an immunoassay to determine a level of soluble ST2 in a biological sample from the selected subject;
(c) identifying a selected subject having an elevated level of soluble ST2 as compared to a reference level of soluble ST2 as having heart failure; and
(d) administering to the identified subject a pharmaceutical treatment for heart failure.
12. The method of claim 11 , wherein the reference level of soluble ST2 represents a level in a subject who does not have heart failure.
13. The method of claim 11 , wherein the reference level of soluble ST2 is about 0.2 ng/mL of serum, and values above that level indicate that the subject has heart failure.
14. The method of claim 11 , wherein the biological sample comprises blood, plasma, or serum.
15. The method of claim 11 , further comprising performing an assay to determine a level of one or more other biomarkers in the subject.
16. The method of claim 15 , wherein the one or more other biomarkers are selected from the group consisting of: brain natriuretic peptide, D-Dimer, atrial natriuretic peptide (ANP), N-terminal-proANP, troponin, C-reactive protein, creatinine, Blood Urea Nitrogen, liver function enzymes, and albumin.
17. The method of claim 11 , wherein determining whether the subject has impaired renal function comprises determining glomerular filtration rate (GFR) and/or serum creatinine level, and determining that the subject has impaired renal function if they have a GFR or serum creatinine level as shown in the following table:
Serum
GFR
Creatinine
Grade
(ml/minute)
(μmol/liter)
mild
20-50
150-300
moderate
10-20
300-700
severe
<10
>700.
18. The method of claim 11 , wherein the immunoassay is an enzyme-linked immunosorbent assay (ELISA).