ELEVATED LEVEL OF C-REACTIVE PROTEIN ASSOCIATES WITH PRONOUNCED AUTONOMIC IMBALANCE AFTER  MYOCARDIAL INFARCTION.

T. Ristimäe, A. Kaasik, R. Teesalu
    Department of Cardiology, University of Tartu, Tartu, Estonia

Abstract: This study was performed to assess associations between heart rate variability (HRV) and C-reactive protein (CRP) in patients the first acute myocardial infarction (AMI).

Methods: In 40 male patients with Q-wave AMI, indices of HRV and CRP were obtained within 72 hour after the event.

Results: In the group II with significantly elevated CRP, HRV was significantly decreased when compared to the group I with normal CRP values. Also, CRP correlated inversely with the selected HRV data (-0.50 for total HRV, and –0,55 for SDNN, the standard deviation of all RR intervals )(p<0.05).

Conclusions: Elevated CRP might possibly contribute to the development of more pronounced autonomic imbalance after AMI, potentially harmful and prognostically unfavourable.

INTRODUCTION

Sympathovagal imbalance following AMI has been reported to carry prognostic information in risk stratification as expressed with indices of HRV (1). Decreased indices of  HRV have been suggested to identify  patients with AMI at greater risk for mortality (2). Whether CRP is unique among the acute-phase proteins as a cardiovascular risk factor cannot be definitely answered the moment. Traditionally, CRP has been used as an acute phase marker of tissue injury, infection, and inflammation, but the use of high sensitivity assays has recently shown that increased C reactive protein values predict future cardiovascular disease (3).

This study was performed to assess associations between HRV and CRP in patients the first AMI.

METHODS

Fourty male patients with Q-wave AMI were studied within 72 hour after the event (mean age 58.2 ± 12.1 years).  All patients were in sinus rhythm, and had culprit lesion(s) on coronary angiography performed during their stay in the hospital. All patients were taking aspirin, beta-blockers, and  angiotensin-converting inhibitors. The following HRV indices were obtained from 24-hour recordings (SpaceLabs Medical model FT2000ä /FT3000ä): (1) SDNN - the standard deviation of all RR intervals; (2) high frequency power (HF, 0.15-0.4 Hz); (3) low frequency power (LF, 0.04-0.15 Hz); (5) total spectral power (0.0037-0.5 Hz) (4). Assays for CRP were performed by a latex particle–enhanced immunoturbidimetric assay. Patients were subdivided according to their values of CRP: group I (with mean CRP values of 2.1 ±1.9 mg/l), and group II (mean CRP 20.8 ± 6.7 mg/l). For inclusion in the group II, elevations of CRP ³10 mg/l, detectable ³1 measurements were required.

RESULTS

TABLE 1. Demographic data and HRV parameters in the study groups.

Variable	Group I (N=17)	Group II (N=23)
Age (years)	56.4 ±9.8	57.6±10.0
AMI (anterior/inferior)	10/7	14/9
LVEF (ml)	55.3±13.9	52.1±15.2
Smokers	11	15
Mean R-R interval (msec)	945.3 ± 255.6	746.6±116.7 *
SDNN(msec)	104.6±32.4	85.2±21.0 *
LF(msec2)	509.8±359.9	264.4±210.6 *
HF(msec2)	189.2±179.8	89.5±78.2
Total power (msec2)	2153.7±1155.3	1293.9±750.0 *

LVEF, left ventricular ejection fraction. Other abbreviations as in text. Data are presented as mean ± SD. * p<0.05 for differences between groups. CRP correlated significantly with SDNN (-0.55), and total power (-0.50) (p<0.05 for both).

DISCUSSION

Increased levels of CRP-complement complexes in infarcted tissues from patients dying of AMI and in plasma of patients with AMI have been found (5). Presently, there is strong evidence that CRP increases ischaemic myocardial damage. CRP production increases in all patients with myocardial infarction, peaking at about 50 hours, and high values are associated with a poor short term and long term prognosis. It has now been confirmed that human CRP, via its capacity to activate complement, greatly increases infarct size after experimental coronary artery ligation, (3) and this presumably also happens in patients.

Prior studies have shown that elevated CRP levels are associated with a profound impairment in systemic endothelial vascular reactivity in patients with coronary artery disease (6). The endothelium exerts potent antithrombotic and vasodilator effects on the vascular wall. The exposure of endothelial cells to proinflammatory cytokines induces procoagulant activity, leads to the expression of cell surface adhesion molecules, and impairs endothelium-dependent vascular relaxation. The blunted systemic endothelial vasodilator function related to elevated plasma CRP levels is independent of classic risk factors for coronary artery disease (6). Impaired endothelium-dependent relaxation may be associated with alterations of other endothelial functions, such as adhesion of leukocytes or altered balance of profibrinolytic to prothrombotic activity (7). It has been demonstrated that the impairment in systemic endothelial vasodilator function associated with elevated CRP levels is superimposed on the effects of atherosclerosis itself and its risk factors (6). Moreover, endothelial vasodilator dysfunction clearly appears to be associated with a marker of systemic inflammation and not secondary to the presence of acute coronary syndromes (6).

Experimental and some clinical studies indicate that impaired endothelium-dependent relaxation is, at least to a large extent, related to impaired availability of NO (7). Importantly, prior studies indicate that systemic inhibition of NO synthase has sympathoexcitatory effects in humans (8). Thus,  NO is also involved in the central regulation of sympathetic outflow, which suggests that both neuronal and endothelial NO synthesis may contribute to the regulation of vasomotor tone (7).

AMI is known to result in remarkable imbalance in autonomic input, with parasympathetic withdrawal and increased sympathetic input, readily assessable with markers of HRV. One may propose that in AMI which is  characterized by an marked sympathovagal imbalance and endothelial dysfunction, the latter could possibly expose to sustained sympathetic activation. Elevated CRP levels, an exquisitely sensitive objective marker of inflammation which partly reflect underlying endothelial impairement, may contribute to more pronounced autonomic imbalance after AMI, potentially harmful and prognostically unfavourable.

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