Coronary Care Cardiology 1992;80:65-70

Richard C. Becker Jeanne M. Corrao Robert Lew James Bradley James Queenan

Relationship between Serum Total Cholesterol, Infarct Size, and Early Clinical Outcome following Acute Myocardial Infarction

KeyWords

Abstract

Myocardial infarction Serum total cholesterol Thrombosis

Strategies designed to decrease coronary heart disease (CHD) associated morbidity and mortality have focused primarily on established risk fac­ tors, including hypercholesterolemia, systemic hypertension, and cigarette smoking. Indeed, primary and secondary intervention trials have pro­ vided evidence for cholesterol lowering as an efficient method of CHD risk reduction. To test the hypothesis that serum total cholesterol influences the clinical outcome following acute myocardial infarction, infarct size, left ventricular ejection fraction, infarct-related vessel paten­ cy, and in-hospital cardiac events were determined in 106 consecutive patients given thrombolytic therapy within 5 h of symptom onset. Cumu­ lative 48-hour creatine kinase (CK) release, peak CK, and calculated infarct size did not differ significantly between patients with an admitting serum total cholesterol level < 200 mg/dl (group 1) and those with a cho­ lesterol level > 250 mg/dl (group 2). Total cholesterol did not correlate with either cumulative CK release, peak CK, infarct size, vessel patency, or left ventricular ejection fraction. The vessel patency correlated in­ versely with cumulative CK release (r = -0.27; p = 0.03) and directly with left ventricular ejection fraction (r = 0.24; p = 0.03). The incidence of inhospital cardiac events including recurrent infarction, congestive heart failure, and death was 6.9, 13.9, and 2.6%, respectively, and did not differ significantly between patient groups. Thus, although serum total choles­ terol has been shown to influence CHD incidence, morbidity, and overall mortality, the findings of our study suggest that it does not impact directly on infarct size, left ventricular function, or in-hospital clinical outcome among patients sustaining acute myocardial infarction.

Received: July 24. 1991 Accepted after revision: August 8, 1991

Richard C. Becker. MD. Thrombosis Research Center, Division of Cardiology University of Massachusetts Medical Center Worcester, MA 01655 (USA)

© 1992 S. Kargcr AG. Basel 0008-6312/92/ 0801 -0066S2.75/0

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Thrombosis Research Center. Division of Cardiology, Departments of Medicine and Pharmacology, University of Massachusetts Medical Center. Worcester, Mass., USA

Patients and Methods

A dramatic and progressive decline in cor­ onary heart disease (CHD) mortality has oc­ curred in the United States over the past three decades [1-6]. Nevertheless, CHD remains the leading cause of death in this country, accounting for 590.000 deaths annually. Information obtained from large, popula­ tion-based epidemiologic studies provides strong, supportive evidence that the decline in CHD mortality reflects (1) a decreased inci­ dence of disease and (2) an improvement in overall patient survival [7-9], The relative contributions of each are yet to be deter­ mined; however, a clear decline in the inci­ dence of myocardial infarction (MI) has been observed, concomitant with marked reduc­ tions in both short-term case fatality rates and out-of-hospital CHD-related deaths [8-10], An elevated serum total cholesterol con­ centration has been identified as a major risk factor for the development and subsequent progression of CHD [11-13]. Moreover, there is convincing evidence that cholesterol reduc­ tion is associated with reduced CHD mortal­ ity [14], While the beneficial effects of choles­ terol reduction may be attributable to one or more mechanisms, including a decreased inci­ dence of CHD. a significant reduction in the severity of existing coronary disease [15], and a decreased incidence of postinfarction recur­ rent cardiac events [16, 17], the possibility that serum total cholesterol may impact di­ rectly on in-hospital prognosis following MI has not been considered. Accordingly, this study was performed to explore potential rela­ tionships between serum total cholesterol, in­ farct size, and short-term clinical outcome among patients with CHD complicated by MI.

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Patients Patients presenting to the University of Massachu­ setts Medical Center between July 1. 1988. and July I. 1990. with clinical and electrocardiographic ev idence of acute myocardial ischemia were considered for study inclusion. As per an institutional protocol, all patients with a suspected Ml in evolution, in whom absolute contraindications were not present, received intravenously recombinant tissue-type plasminogen activator (rt-PA; Genentech. San Francisco. Calif., USA) as a 3-hour infusion. Intravenous heparin was given as a 5.000-unit bolus followed by a continuous infusion at 1.000 U/h. All patients received daily oral aspirin (325 mg) as well. The use of (3-blockers, cal­ cium channel antagonists, intravenous lidocainc, and nitrate preparations was left to the discretion of the attending physician. All patients were carefully monitored in the coro­ nary care unit for 48-72 h. Serial creatine kinase deter­ minations were performed every' 4 h for the first 24 h and every 6 h thereafter for a total of 48 h. Serum total cholesterol was determined within 24 h of symptom onset (18], Following discharge, the patients were carefully monitored in a step-down (telemetry) unit. Informa­ tion on each patient w'as obtained prospectively and entered into the University of Massachusetts Medical Center’s Thrombolysis Data Bank. Methods Cardiac Catheterization. Coronary arteriography was performed within 48 h of rt-PA administration. Restoration of arterial patency was determined using a standard T1MI grading scale. The left ventricular ejec­ tion fraction was determined utilizing the length-area method of Sheehan et al. [ 19], Patient Selection. Following a retrospective review of consecutive cases contained within the Thromboly­ sis Data Bank, patients with a validated MI (defined as typical evolutionary electrocardiographic changes and a serial rise in serum creatine kinase levels with an increased MB fraction) were selected for study entry. Patient characteristics, demographic variables, and clinical features were retrieved directly from the data bank files and when unavailable were obtained from medical records. Serum Total Cholesterol. The total cholesterol was measured directly in serum by an automated system (Paramax System: Baxter Health Care. Santa Ana. Cal­ if.). The automated system is calibrated frequently using a Center of Disease Control national standard.

Becker/Corrao/Lew/Bradley/Queenan

Serum Total Cholesterol

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Introduction

Table 1. Baseline characteri­ stics and in-hospital events for the overall patient population (n = 106)

Mean Age, years Weight, kg Males, % Time to treatment, min Cumulative creatine kinase, 1U-M Infarct size (CPKr-g-k) LV ejection fraction, % Total cholesterol, mg/dl Infarct vessel. % RCA LAD LCX Not identified Patency. % Recurrent ML % Congestive heart failure. % Death, %

59.4 81.0 78.3 215 14.952 16.7 52 223 48.6 33.3 16.2 1.9 74.5 6.9 13.9 2.6

Standard deviation 33.7 16.3 -

76 9.767 5.3 11 103 -

LV = Left ventricle: RCA = right coronary artery'; LAD = left anterior descending coronary artery. LCX = Left circumflex coronary' artery.

Serum cholesterol values in the University of Massa­ chusetts Medical Center are ± 2% of reference values. Creatine Kinase Activity. Quantitative serum total creatine kinase was determined using a reagent formu­ lation based on Rosalki’s [20] modification of the pro­ cedure of Oliver [21] (Paramax: Baxter Health Care). Statistical Analysis. The initial data analysis had two major portions: ( I) calculation of myocardial in­ farct size and (2) statistical analysis of potential asso­ ciations. The ten measurements of creatine kinase formed the data for a nonlinear curve-fitting problem. We fit the difference of exponential functions to a sys­ tem in which the blood flow into a compartment and out of a compartment determined the concentration. C. at time T. The calculation was carried out using the nonLIN84 computational package [22] to find the flow rates KI (into) and K2 (out of) in the equation:

heart up to time, t, when C(t) has fallen to near zero. This follows the definition previously provided by Sobcl et al. [23]. The infarct size equals CPKr-body weight-K. The value of K is a constant for the cardio­ vascular blood flow system in man. The explicit value of K is derived from the work of Sobel et al. [23]. We tested whether the infarct size correlated with other factors, so that K could be omitted from the analysis, given that the correlation coefficient is invariant under changes in scale. Because the nonlinear estimaton of the parameters for the equation for C(t) can produce unrealistic values (outliers), a variety of simple criteria for outliers and logarithmic transforms were used to confirm primary tests of hypotheses.

Results

The constant depends on Kl and K2: it is propor­ tionate to K1/(K2-K1) where K2 > KL The area under the curve defined by C(t) corresponds to the cumulative activity of creatine kinase released by the

The patient characteristics are shown in table 1. One hundred and six patients with a validated MI were identified and included in the final analysis. Serum total cholesterol

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C(t) = constant - [cxp(—Kl •t) - ext(-K2-t)]

2, 500 -, 7_

2,000 -

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Relationship between serum total cholesterol, infarct size, and early clinical outcome following acute myocardial infarction.

Strategies designed to decrease coronary heart disease (CHD) associated morbidity and mortality have focused primarily on established risk factors, in...
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