Дијагноза и прогноза на коронарна артериска болест кај асимптоматски пациенти со умерен и висок кардиоваскуларен ризик: улога на биомаркери и техники на миокардна визуелизација

Abstract

Coronary artery disease (CAD) is a leading cause for morbidity and mortality in the modern world, with the tendency for further increase, especially in the developing countries, which includes R. Macedonia. Having in mind the big economic and health burden of treating patients with CAD and its complications and the limitations for health care resources from other side, there is an actual need for early CAD diagnosis and sophisticated risk stratification, which would improve patient’s management. This approach is expected also to improve cardiovascular prevention measures and complications of lately established diagnosis. Modern techniques for myocardial and vascular imaging like myocardial perfusion scintigraphy (MPS), new echocardiography techniques, computed tomography of coronary arteries and high sensitive C reactive protein (hs-CRP) enables the improved prediction of cardiac events risk in the subclinical phase of the disease, which was a motivation for this research. The study includes 110 asymptomatic patient’s (50 with moderate and 60 with high CV risk), without previously known or established CAD. The patients were ambulatory examined at the University Cardiology Clinic. In all patients standard laboratory analyses were performed, microalbuminuria in patients with hypertension and diabetes type 2, hs-CRP and carotid ultrasound. In patients with moderate CV risk we have assessed coronary arteries calcium score (CAC) for detection of coronary atherosclerosis. Selected patients with CAC>400AE and all patients with high CV risk were referred for MPS for detection of myocardial ischemia in the frames of routine examination in collaboration with Institute for Pathophysiology and Nuclear Medicine. Patients were clinically followed mean 20+/4 months for the hard events (cardiac death and acute coronary syndromes – unstable angina, non ST and ST elevation myocardial infarction) and soft events (revascularization and heart failure). Our study results showed high prevalence of silence myocardial ischemia in 16 patients (48,1%). Independent predictors fo myocardial ischemia were diabetes type 2 induration over 5 years, LDL holesterol, smoking and reduced global longitudinal left ventricual function. Subclinical atherosclerosis was found in 26 patients (52%) and it correlates with the severity of myocardial ischemia. We found significant association of MPS parameters, especially perfusion variables and myocardial ischemia with cardiac events. Patients with moderate ischemia (10-15% od left ventricle) had 9,45 times increased risk for cardiac events in comparition with patients without ischemia. The impact of moderate ischemia was significant (95%CI: 1,45-11,21; p=0,001). Patients with severe ischemia (>15% of left ventricle) had 12,32 times higher risk for cardiac events comparing to the patients without ischemia. The impact of severe ischemia was significant (95%CI: 1,23-17,67; p=0,000). Significant independent predictors for all cardiac events were coronary atherosclerosis and myocardial ischemia, with marginal significance of the presence of abnormal MPS scan result (SSS>0). We did not found significant differences in the values of c-IMT with increase of the myocardial ischemia severity, contrary c-IMT increases with the increase of CAC. The presence of carotid plaques increases with the increase of the severity of myocardial ischemia. Reduced global longitudinal left ventricular function was found in 23 high risk patients (38,3%). From all included parameters from non invasive imaging techniques, only reduced global left ventricular longitudinal function at rest was significant independent predictor for the presence of myocardial ischemia. The evaluated biomarker high sensitivity C reactive protein (hs-CRP), was independent predictor for myocardial ischemia in the univariate regression analysis, however it was not predictor for cardiac events. We confirmed that MPS in a noninvasive imaging method which enables clear, precise and simple prediction of the risk for cardiac events in asymptomatic patients with moderate and high CV risk. Comparative analysis of clinical data, hs-CRP, CAC, global left ventricular longitudinal function and MPS variables have shown that in the prediction of different risks for cardiac events, MPS perfusion parameters have the most significant clinical value. The most important predictor was severity and extensity of myocardial ischemia expressed though summed differential MPS score (SDS). Normal MPS has high negative predictive value for future cardiac events in the follow up period. The study showed that noninvasive myocardial and vascular imaging techniques improve risk stratification in patients with moderate cardiovascular risk in comparison with traditional risk factors and improved shorter and intermediate term prognosis in high risk patients.