High-Sensitivity C-Reactive Protein as an Independent Predictor of Progressive Myocardial Functional
High-Sensitivity C-Reactive Protein as an Independent Predictor of Progressive Myocardial Functional Deterioration
Background Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure.
Methods Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc.
Results During the follow-up period, participants (n = 785) with elevated CRP experienced a decrease in strain, independent of age, gender, and ethnicity (B = 0.081, ΔEcc change per 1 mg/L CRP change, 95% CI 0.036–0.126, P < .001, model 1) and, additionally, beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication, and glomerular filtration rate (B = 0.099, 0.052–0.145, P < .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events (B = 0.098, 0.049–0.147, P < .001, model 3).
Conclusion Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease.
Systemic inflammation has been shown to be related to hospitalization and mortality in patients with heart failure (HF). High-sensitivity C-reactive protein (CRP) is a biomarker of inflammation that has been associated with the development of symptomatic HF in large-scale population studies. Indeed, several prior reports have demonstrated a clear link between elevated levels of CRP and the development of HF, even among asymptomatic individuals. Among potential mechanisms, myocardial infarction caused by coronary arterial plaque rupture due to the local activation of proinflammatory cytokines is a well-known determinant of incident HF. However, the greater incidence of HF among patients with elevated CRP has been observed to be, in large part, independent of interim myocardial infarction in previous population studies including the Multi-Ethnic Study on Atherosclerosis (MESA). Therefore, the mechanisms by which higher systemic inflammatory markers contribute to the development of HF have not been fully elucidated. Basic research suggests that direct myocardial functional depression may be induced by inflammatory cytokines. In this regard, recent population studies have shown that CRP levels are independently related to regional myocardial dysfunction, although causation could not be ascertained in such cross-sectional analyses. Until now, there have been no large-scale longitudinal follow-up studies designed to evaluate the effects of systemic inflammation on progression of regional myocardial dysfunction in community-based populations.
Myocardial circumferential strain (Ecc), defined as proportional myocardial deformation during the cardiac cycle, can be accurately measured regionally by tagged magnetic resonance imaging (MRI) and has been validated and used as a reference index of regional myocardial function. Therefore, in this MESA ancillary study, we used serial cardiac MRI tagging examinations to determine whether elevated CRP can predict progressive regional myocardial functional deterioration independent of interim cardiovascular events, in a multiethnic population without clinically apparent cardiovascular disease at baseline.
Abstract and Introduction
Abstract
Background Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure.
Methods Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc.
Results During the follow-up period, participants (n = 785) with elevated CRP experienced a decrease in strain, independent of age, gender, and ethnicity (B = 0.081, ΔEcc change per 1 mg/L CRP change, 95% CI 0.036–0.126, P < .001, model 1) and, additionally, beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication, and glomerular filtration rate (B = 0.099, 0.052–0.145, P < .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events (B = 0.098, 0.049–0.147, P < .001, model 3).
Conclusion Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease.
Introduction
Systemic inflammation has been shown to be related to hospitalization and mortality in patients with heart failure (HF). High-sensitivity C-reactive protein (CRP) is a biomarker of inflammation that has been associated with the development of symptomatic HF in large-scale population studies. Indeed, several prior reports have demonstrated a clear link between elevated levels of CRP and the development of HF, even among asymptomatic individuals. Among potential mechanisms, myocardial infarction caused by coronary arterial plaque rupture due to the local activation of proinflammatory cytokines is a well-known determinant of incident HF. However, the greater incidence of HF among patients with elevated CRP has been observed to be, in large part, independent of interim myocardial infarction in previous population studies including the Multi-Ethnic Study on Atherosclerosis (MESA). Therefore, the mechanisms by which higher systemic inflammatory markers contribute to the development of HF have not been fully elucidated. Basic research suggests that direct myocardial functional depression may be induced by inflammatory cytokines. In this regard, recent population studies have shown that CRP levels are independently related to regional myocardial dysfunction, although causation could not be ascertained in such cross-sectional analyses. Until now, there have been no large-scale longitudinal follow-up studies designed to evaluate the effects of systemic inflammation on progression of regional myocardial dysfunction in community-based populations.
Myocardial circumferential strain (Ecc), defined as proportional myocardial deformation during the cardiac cycle, can be accurately measured regionally by tagged magnetic resonance imaging (MRI) and has been validated and used as a reference index of regional myocardial function. Therefore, in this MESA ancillary study, we used serial cardiac MRI tagging examinations to determine whether elevated CRP can predict progressive regional myocardial functional deterioration independent of interim cardiovascular events, in a multiethnic population without clinically apparent cardiovascular disease at baseline.