Biomarkers in cardiovascular disease. Felix J. Rogers, DO, FACOI April 29, 2018

Size: px

Start display at page:

Download "Biomarkers in cardiovascular disease. Felix J. Rogers, DO, FACOI April 29, 2018"

Austen Gilmore
5 years ago
Views:

1 Biomarkers in cardiovascular disease Felix J. Rogers, DO, FACOI April 29, 2018

2 Biomarkers NIH: A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.

3 Biomarkers NIH: A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Intended uses: screening diagnostic prognostic

4 Cardiac biomarkers in HF Markers of inflammation Markers of fibrosis, extracellular matrix remodeling Markers of biochemical strain Markers of neurohormonal activation Markers of cardiomyocyte injury

5 Cardiac biomarkers in HF Markers of inflammation C-reactive protein Markers of fibrosis, extracellular matrix remodeling Markers of biochemical strain Natriuretic peptides Markers of neurohormonal activation Markers of cardiomyocyte injury Cardiac troponins

6 Cardiac biomarkers in HF Markers of inflammation C-reactive protein Markers of fibrosis, extracellular matrix remodeling Markers of biochemical strain Natriuretic peptides Markers of neurohormonal activation Markers of cardiomyocyte injury Cardiac troponins

7 Markers of Inflammation Heart failure Hemodynamic hypothesis Cytokine hypothesis

8 The cytokine hypothesis Braunwald, NEJM, 2008, from Seta and Anker & von Haehling

9 Deleterious effects of biomarkers of inflammation

10 C-reactive protein CRP is known to be involved in the immune response, as a mediator of inflammation as well as a marker of the presence of of an inflammatory process.

11 C-reactive protein CRP is known to be involved in the immune response, as a mediator of inflammation as well as a marker of the presence of of an inflammatory process. Elevated levels of CRP predict future vascular events, even out to 20 years

12 C-reactive protein CRP is known to be involved in the immune response, as a mediator of inflammation as well as a marker of the presence of of an inflammatory process. Elevated levels of CRP predict future vascular events, even out to 20 years However, CRP elevation is not independent of other markers, is not uniformly prognostic and it does not respond to treatment, except for statins, which has not resulted in improved outcomes

13 Natriuretic peptides Natriuretic peptides (BNP and ANP) are neurohormones which affect body fluid homeostasis via natriuresis and diuresis. They decrease vasoconstriction by decreasing angiotensin II and norepinephrine synthesis BNP is synthesized as a prohormone and is released in response to volume overload and wall stress Breathing Not Properly study BNP more accurate than any history or physical exam finding in identifying patients with heart failure in a group of patients with dyspnea presenting to the emergency room

14 Markers of cardiomyocyte injury cardiac troponins Troponin is elevated in myocardial injury and is an essential component of diagnosis of MI. Troponin is also elevated in the setting of heart failure Prevalence of ctn elevation corresponds to stage of heart failure

15 Prevalence of ctn in HF

16 Markers of cardiomyocyte injury cardiac troponins Troponin is elevated in myocardial injury and is an essential component of diagnosis of MI. Troponin is also elevated in the setting of heart failure Prevalence of ctn elevation corresponds to stage of heart failure Hazard ratios of hospitalization for HF, all-cause mortality and incident ischemic cardiovascular events (mostly heart failure)

17 Hazard ratio of new HF with ctn ARIC study, Circ 2011; 123:

18 Markers of cardiomyocyte injury cardiac troponins Troponin is elevated in myocardial injury and is an essential component of diagnosis of MI. Troponin is also elevated in the setting of heart failure Prevalence of ctn elevation corresponds to stage of heart failure Hazard ratios of hospitalization for HF, all-cause mortality and incident ischemic cardiovascular events (mostly heart failure) This latter point suggests that the mechanism for ctn release is not small asymptomatic MI, but other mechanisms for myocyte cell death

19 Troponin I & T 2016 BioFactors, 42(2): , 2016

20 Troponin elevation 1. Necrosis 2. Apoptosis 3. Normal myocyte cell turnover 4. Release of proteolytic troponin degradation products 5. Increased cell-membrane permeability due to integrinmediated stretch mechanisms 6. Formation and release of membrane blebs

21 Let s try a case

22 Patient No. 1 This 29 year old woman had a C-Section complicated by severe bleeding. She had emergency hysterectomy. This was complicated by pneumonia, shock and severe anemia. Additional medical issues: BMI 45.3, smoker

23 Patient No. 1 This 29 year old woman had a C-Section complicated by severe bleeding. She had emergency hysterectomy. This was complicated by pneumonia, shock and severe anemia. Additional medical issues: BMI 45.3, smoker From the cardiology consult: No chest pain BNP 468, trop 0.52 Hb at 11:32 PM g/dl Echocardiogram normal Conclusion: Elevated troponin due to Type 2 MI ECG - normal

24 What s wrong with this picture?

25 What s wrong with this picture?

26 Patient No. 1 This 29 year old woman had a C-Section complicated by severe bleeding. She had emergency hysterectomy. This was complicated by pneumonia, shock and severe anemia. Additional medical issues: BMI 45.3, smoker From the cardiology consult: No chest pain BNP 468, trop 0.52 Hb at 11:32 PM g/dl Echocardiogram normal Conclusion: Elevated troponin due to Type 2 MI ECG - normal

27 Universal Definition of Myocardial Infarction

28 Universal Definition of Myocardial Infarction Simplified version Symptoms of ischemia (chest pain) New or presumed new ST-T changes, or new LBBB New Q waves on the ECG (except in lead 3) Evidence on imaging study of new loss of viable myocardium, or of new wall motion abnormality Identification of intra coronary thrombus on cath or at autopsy

29 Universal Classification of MI

30 Universal Classification of MI Simplified version Type 2 MI Myocardial necrosis caused by a condition other than CAD when a mismatch between myocardial oxygen supply and demand occurs, e.g. when there is excessive tachycardia, hypoxemia, hypotension, hypertension (with or without LVH)

31 Proper diagnosis Non-MI troponin elevation

Biomarkers in Heart Disease. Felix J. Rogers, DO, FACOI April 29, 2018

Biomarkers in Heart Disease. Felix J. Rogers, DO, FACOI April 29, 2018 Biomarkers in Heart Disease Felix J. Rogers, DO, FACOI April 29, 2018 Biomarkers NIH: A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes,