To examine left ventricular (LV) function in patients after acute myocardial infarction (AMI) and assess its relation to C-reactive protein (CRP) as a measure of the early inflammatory response. We measured the CRP levels early after AMI and correlated them with the early structural and functional cardiac alterations. From November 2002 to December 2007, we prospectively enrolled community subjects who had experienced an AMI, as defined by standardized criteria, measured the CRP level, and obtained an echocardiogram. The study consisted of 514 patients (mean age 67 ± 15 years, 59% men). CRP was measured early after symptom onset (median 6.1 hours; twenty-fifth to seventy-fifth percentile 2.2 to 11.1). The median CRP level was 4.8 mg/L (twenty-fifth to seventy-fifth percentile 1.8 to 24). The echocardiograms were obtained at a median of 1 day after AMI. The wall motion score index, LV ejection fraction, and LV diameter were similar across the CRP tertiles (all p >0.05). Greater CRP levels were associated with the presence of moderate or severe diastolic dysfunction (p = 0.002) and moderate or severe mitral regurgitation (p <0.001). The association with moderate or severe mitral regurgitation was independent of the clinical characteristics and ST-segment elevation status. In conclusion, at the initial phase of AMI, CRP elevation was associated with the presence and severity of mitral regurgitation and diastolic dysfunction. This suggests that inflammation is related to the ventricular remodeling processes, independently of LV systolic function.
In the community, heart failure (HF) remains frequent after acute myocardial infarction (AMI) even in the current therapeutic era. HF occurs early at the acme of tissue necrosis and inflammation. Conceivably, ischemic injury promotes myocardial inflammation, and pro-inflammatory cytokines stimulate C-reactive protein (CRP), leading to cardiac remodeling, with HF as its clinical manifestation. However, the mechanisms of HF after AMI remain poorly understood. Although CRP is a marker of inflammation activated early after AMI and is associated with HF, the link between CRP and structural and functional cardiac alterations after AMI has not been delineated. Studying the association between CRP and cardiac alterations after AMI is complex. It requires the early diagnosis of AMI, measurement of CRP, and echocardiograms. To optimize its relevance to all patients with AMI, the study should be conducted in the community. Our ongoing prospective study of the epidemiology of AMI (R01 HL 59205, PI VL Roger) meets these requirements by enrolling prospectively subjects with AMI in the community and recording echocardiography and biomarkers. Hence, we examined left ventricular (LV) function and its relation to CRP as a measure of inflammation to test the hypothesis that CRP was associated with worse LV function after AMI.
Methods
In Olmsted County, medical care is delivered by a few providers, including the Mayo Clinic and its affiliated hospitals, Olmsted Medical Center and its affiliated community hospital, local nursing homes, and a few private practitioners. Each provider uses a medical record in which the patient care data, regardless of setting, are available. The records are easily retrievable because the indexes are maintained through the Rochester Epidemiology Project and extended to the records of all providers in the county, resulting in the linkage of all records from all sources of care. Olmsted County residents hospitalized from November 2002 to May 2006 who had presented with troponin T values ≥0.03 ng/ml (upper limit of normal for the assay defined as the value at which the coefficient of variation for the assay was <10%) were prospectively identified within 12 hours of their initial blood sample through the Department of Laboratory Medicine. All patients had troponin measured as a part of clinical practice. Up to 3 electrocardiograms per episode were coded using the “Minnesota Code Modular ECG [electrocardiographic] Analysis System.” Myocardial infarctions were classified using the European Society of Cardiology/American College of Cardiology guidelines. Only patients with incident myocardial infarction were included to ensure that the findings reflected the first infarction.
The clinical data included Killip class and co-morbidities. Clinical diagnoses were used to ascertain hypertension, diabetes mellitus, hyperlipidemia, and smoking.
High-sensitivity CRP was measured in the serum from the first sample drawn after symptom onset using a latex-enhanced immunoturbidimetric assay on a Hitachi 912 automated analyzer (Roche, Basel, Switzerland) and reagents from DiaSorin (Saluggia, Vercelli, Italy). CRP was measured in the laboratories of the Department of Laboratory Medicine and Pathology, which has been certified by the Clinical Laboratory Improvement Act of 1988 and the College of American Pathologists (Northfield, Illinois).
The data from the echocardiogram during the index hospitalization were retrieved. The parameters of LV systolic function included the ejection fraction and wall motion score index. The ejection fraction was measured by validated methods using the quantitative bi-dimensional biplane volumetric Simpson method, the Quinones formula, or the bi-dimensional estimate method from multiple echocardiographic views, a method comparable to other assessments of ejection fraction. The values were averaged when multiple measurements were performed. The LV wall motion score index was calculated. The LV end-diastolic diameter, ventricular septal thickness, and posterior wall thickness were measured by M-mode or bi-dimensional echocardiography from the parasternal views at end-diastole as recommended by the American Society of Echocardiography and used to calculate the LV mass, indexed to the body surface area. The end-systolic diameter was measured at end-systole by M-mode or 2-dimensional echocardiography. Diastolic function was assessed by integrating measurements of the mitral inflow and Doppler tissue imaging of the mitral annulus using the medial annulus velocity and classified into 4 categories: normal diastolic function, mild diastolic dysfunction (impaired relaxation without evidence of increased filling pressures), moderate dysfunction (impaired relaxation or pseudonormal with moderate elevation of filling pressures), and severe dysfunction (advanced reduction in compliance). The severity of mitral regurgitation (MR) was evaluated semiquantitatively from the area of the regurgitant jet observed by color Doppler and classified as absent or trivial, mild, and moderate or severe.
The trends in baseline characteristics across CRP tertiles were tested using the Mantel-Haenszel chi-square test for categorical variables and linear regression analysis for continuous variables. The associations between CRP and the echocardiographic variables were tested using linear regression analysis for the continuous echocardiographic variables and logistic regression analysis for the categorical variables. The CRP, wall motion score index, and LV mass index values were log-transformed in the regression models. The institutional review board approved the study.
Results
From November 2002 through December 2007, 514 patients with incident AMI had their CRP level measured and underwent echocardiography during hospitalization. The mean patient age was 67 ± 15 years, and 59% were men. CRP was measured at a median of 6.1 hours after symptom onset (twenty-fifth to seventy-fifth percentile 2.2 to 11.1). The median CRP level was 4.8 mg/L (twenty-fifth to seventy-fifth percentile 1.8 to 24). Echocardiograms were performed at a median of 1 day (twenty-fifth to seventy-fifth percentile 1 to 2) after symptom onset.
The baseline patient characteristics by CRP tertile are listed in Table 1 . The cutpoints for the CRP tertiles were <2.7, 2.7 to 10, and >10 mg/L. Patients with greater CRP levels were older, more likely to be women, more likely to have hypertension, diabetes mellitus, and more co-morbidities, and more likely to present with a greater Killip class. Patients with greater CRP values were less likely to present with ST-segment elevation AMI and had lower peak troponin, and lower peak creatine kinase-MB levels. The interval from the onset of symptoms to blood sampling for measurement of CRP was similar across all tertiles, as were all other baseline characteristics.
| Variable | Tertile 1 (<2.7 mg/L; n = 172) | Tertile 2 (2.7–10 mg/L; n = 169) | Tertile 3 (>10 mg/L; n = 173) | p Value |
|---|---|---|---|---|
| Age (years) | 65 ± 14 | 65 ± 15 | 71 ± 17 | <0.001 |
| Women | 62 (36%) | 65 (38%) | 86 (50%) | 0.023 |
| Body mass index (kg/m 2 ) | 28 ± 5 | 30 ± 7 | 28 ± 7 | 0.539 |
| Hypertension | 108 (63%) | 107 (63%) | 129 (75%) | 0.029 |
| Hyperlipidemia | 112 (65%) | 103 (61%) | 107 (62%) | 0.702 |
| Current smoker | 35 (20%) | 47 (28%) | 31 (18%) | 0.584 |
| Diabetes mellitus | 20 (12%) | 44 (26%) | 54 (31%) | <0.001 |
| Killip class 2, 3, or 4 | 31 (18%) | 42 (25%) | 67 (39%) | <0.001 |
| Infection within previous 2 weeks | 7 (4%) | 18 (11%) | 77 (45%) | <0.001 |
| Co-morbidity index | <0.001 | |||
| 0 | 88 (51%) | 42 (35%) | 26 (15%) | |
| 1–2 | 57 (33%) | 65 (38%) | 62 (36%) | |
| ≥3 | 27 (16%) | 44 (26%) | 85 (49%) | |
| Electrocardiographic findings | ||||
| Inferior location | 64 (38%) | 60 (37%) | 59 (36%) | 0.629 |
| Presence of Q waves | 88 (56%) | 85 (57%) | 90 (59%) | 0.579 |
| ST-segment elevation myocardial infarction | 49 (29%) | 45 (28%) | 32 (19%) | 0.039 |
| Biomarker findings | ||||
| Interval from symptoms to C-reactive protein measurement | 6.3 (3.1–10.5) | 6.9 (2.8–12.2) | 4.0 (0.7–10.7) | 0.091 |
| Peak troponin | 1.08 (0.31–3.57) | 0.94 (0.30–3.93) | 0.52 (0.18–1.52) | 0.001 |
| Peak creatine kinase-MB | 42 (11–135) | 31 (11–113) | 14 (7–30) | <0.001 |
The echocardiographic parameters by CRP tertile are reported in Table 2 . The presence of moderate or severe LV diastolic dysfunction and the presence of moderate or severe MR were associated with greater levels of CRP.
| Variable | Tertile 1 (<2.7 mg/L; n = 172) | Tertile 2 (2.7–10 mg/L; n = 169) | Tertile 3 (>10 mg/L; n = 173) | p Value ⁎ |
|---|---|---|---|---|
| Wall motion score index | 1.28 (1.00–1.63) | 1.31 (1.13–1.69) | 1.25 (1.00–1.82) | 0.122 |
| Ejection fraction | 57 (48–63) | 55 (47–62) | 57 (45–64) | 0.077 |
| Left ventricular end-diastolic diameter (mm) | 48 (46–52) | 50 (46–53) | 50 (44–53) | 0.781 |
| Left ventricular end-systolic diameter (mm) | 33 (29–36) | 33 (29–38) | 33 (28–39) | 0.124 |
| Left ventricular mass index (g/m 2 ) | 99 (82–118) | 95 (80–115) | 103 (83–125) | 0.459 |
| Diastolic dysfunction (moderate/severe) | 85 (49) | 81 (48) | 107 (62) | 0.002 |
| Mitral regurgitation | <0.001 | |||
| None/mild | 158 (94) | 149 (90) | 133 (81) | |
| Moderate/severe | 9 (5) | 17 (10) | 31 (19) |
⁎ From regression models including the logarithm of C-reactive protein.
After adjustment for age and gender and additional adjustment for co-morbidities and Killip class, the associations between greater CRP levels and moderate or severe diastolic dysfunction and moderate or severe MR remained. Table 3 quantifies the strength of these associations by expressing them as odds ratios. After additional adjustment for infection within 2 weeks before the AMI, the association between CRP and diastolic dysfunction was no longer significant; however, the association between CRP and MR remained. The association between CRP and MR was also independent of diastolic dysfunction and was not materially affected by the addition of ST-segment elevation status in the models (for the association between CRP and MR after adjustment for diastolic dysfunction and after adjustment for ST-segment elevation status, p = 0.035 and p = 0.088, respectively).
| Variable | Unadjusted | Adjusted for Age, Gender | Adjusted for Age, Gender, Co-morbidity, and Killip Class | Adjusted for Age, Gender, Co-morbidity, Killip Class, and Infection |
|---|---|---|---|---|
| Moderate or severe diastolic dysfunction | ||||
| C-reactive protein tertile 2 | 0.94 (0.62–1.44) | 0.93 (0.60–1.43) | 0.94 (0.61–1.46) | 0.92 (0.60–1.43) |
| C-reactive protein tertile 3 | 1.66 (1.08–2.55) | 1.43 (0.92–2.22) | 1.53 (0.96–2.44) | 1.35 (0.82–2.23) |
| p Value ⁎ | 0.002 | 0.028 | 0.021 | 0.10 |
| Moderate or severe mitral regurgitation | ||||
| C-reactive protein tertile 2 | 2.00 (0.87–4.63) | 2.01 (0.86–4.72) | 2.00 (0.85–4.72) | 1.92 (0.83–4.61) |
| C-reactive protein tertile 3 | 4.09 (1.88–8.90) | 3.13 (1.41–6.95) | 2.60 (1.14–5.89) | 2.32 (0.98–5.50) |
| p Value ⁎ | <0.001 | 0.002 | 0.009 | 0.030 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
