FINCAVAS is aimed at characterising individuals with a high risk of cardiovascular diseases and death. By the end of 2004, data had been gathered on more than 2,200 patients. The recruitment period will continue until the end of 2007, and the final number of patients is estimated to reach 5,000. All of the participants will go through detailed interviews and a clinical exercise test. Moreover, approximately 20% of the patients will be examined with coronary angiography, and 5–10% will perform another exercise test during the study period. The high number of exercise tests combined with other related data is one of the particular strengths of this study. To our knowledge, this is the first large-scale database with digitally recorded high resolution ECG data covering the entire duration of the exercise test.
Traditional ECG parameters for CHD diagnosis during exercise test – such as the amount and type of depression of the ST segment as well as T wave changes – are reasonably accurate in patients with an intermediate pre-test likelihood for having disease [36
]. However, the test lacks sensitivity and specificity for many patient groups, particularly among women [38
]. A central objective of FINCAVAS is to enhance the accuracy of exercise ECG in diagnosing CHD by combining some of the existing markers and by creating completely new algorithms. The digital high-resolution exercise ECG of the patients undergoing a coronary angiography is a valuable and fundamental resource for this purpose.
Several studies have demonstrated exercise capacity as an independent predictor of cardiac events and mortality in healthy persons and those with cardiac diseases [2
]. The HR profile during exercise and recovery is a predictor of death [5
]. Furthermore, the changes in blood pressure during and after exercise have been shown to predict cardiovascular events and mortality [4
]. However, the importance of various combinations of the predictive parameters is poorly known. When it comes to ECG parameters, ST depression [2
] and ST/HR analysis [3
] during exercise have been connected to survival, but no studies thus far have revealed whether the values of and changes in T wave alternans, ST/HR hysteresis [34
], HR variability and many other ECG parameters during exercise are linked with mortality. Our research team has made extensive and persistent efforts in studying the sophisticated CHD diagnostics based on ECG parameters and ECG leads [34
]. The present continuous ECG at 500 Hz during the entire exercise test provides a solid foundation for testing the relevance of both existing prognostic parameters and those developed during the project.
The importance of classical risk factors for atherosclerosis has been evaluated in detail. In recent years, many genetic polymorphisms have been associated with atherosclerosis [45
]. However, the majority of these new risk factors provide limited contribution to the total risk of cardiovascular morbidity and mortality. Therefore, defining and measuring specific and precise phenotypes is of crucial value when the quantitative importance of these risk factors and markers are assessed.
Some of the phenotype data included in FINCAVAS, such as angiographic findings and ECG parameters, can be considered particularly accurate. Blood pressure and breathing parameters during the exercise test are also accurate, while medical history may constitute the data most vulnerable to imprecision. Knowledge of the pharmaceuticals used and prior diseases are collected with care, but the process inherently bears some level of uncertainty. Many middle-aged and elderly individuals are suffering from considerable atherosclerosis and CHD although they may remain undiagnosed. Even MI, the most serious complication of CHD, is often silent and diagnosed only when a routine ECG is recorded. The level of uncertainty for each phenotype needs to be taken into account when the results of analyses and classifications using these parameters are interpreted.
Many polymorphisms are most likely not disease-causing genes, but rather risk modifiers, and might thus also influence the progression of cardiovascular diseases. Although certain polymorphisms do not induce marked effects on cardiovascular parameters, they may still have linkage effects with some functionally more important polymorphisms. In the course of FINCAVAS, the independent and combined effects of many genotypic variations on cardiovascular morbidity and mortality will be assessed prospectively with a long-term follow-up. The purpose of this strategy is not only to study the effects of polymorphisms on known risk factors, but also to find new mechanisms and factors contributing to the aetiology of cardiovascular diseases directly in the arterial wall. To achieve this goal, we will exploit and use high throughput techniques for expression analysis and genotyping to find genes affecting the expression, synthesis and function of proteins associated with cell signal transduction, regulation of inflammation, apoptosis and lipid metabolism directly in the cells of the arterial wall. Better understanding of the function of the genes in these cells during the progression of cardiovascular disease could serve as a new tool in both research and therapeutic applications.
FINCAVAS is subject to certain limitations. We include all patients scheduled for a clinical exercise test at a university setting, which is both a strength and a weakness of the study. The present study population consists of patients with a wide spectrum of ages, life styles, histories and status of cardiac diseases. It is probable that the importance of many genotypes, responses to exercise and ECG markers vary from one patient group to another. Therefore, the study enables the assessment of risks for many patient groups, but, on the other hand, these groups need to be adequately recognised before analyses. In some cases, the subgroups may still be relatively small in spite of the high total number of patients.
In conclusion, FINCAVAS is compiling an extensive set of data on patient history, genetic variation, cardiovascular parameters and ECG markers prior to, during and after an exercise test. Furthermore, approximately 20% of the patients are being examined with coronary angiography. As the follow-up progresses, this data will enable us to estimate the importance of different diagnostic and prognostic markers for many distinct patient groups.