We identified a number of specific predictors separating the risk of SCD from incident CHD in a cohort of men and women initially free of CHD who were enrolled in two of the largest community-based studies in the USA: ARIC and CHS. These predictors included race/ethnicity, hypertension, BMI, heart rate, QTc, abnormally inverted T wave in any ECG lead group and level of ST elevation (STJ and ST60) in V2. Elevated STJ amplitude in leads V3, II and aVF was ‘protective’ from SCD but was not associated with incident CHD and, hence, can be used as a ‘favourable’ marker for less risk of SCD. As expected and given that the SCD cases in our study are mostly atherosclerotic, we also showed that many demographic, clinical and ECG predictors/risk factors are shared between SCD and incident CHD and, subsequently, could not separate between these two outcomes.
The previously reported association between high resting heart rate and marker of ventricular arrhythmogenesis independently from myocardial ischaemia22
as well as being predictive of SCD in post-MI patients and in the general population23–25
may explain why heart rate was more predictive of SCD in our study. Similarly, prolonged QTc has been frequently linked to SCD,26
and minor T wave abnormalities have been linked to fatal CHD but not non-fatal MI, suggesting that T wave abnormalities are harbingers of arrhythmic sudden death.27
On the other hand, there is no clear explanation why race/ethnicity, hypertension and BMI were more predictive of SCD than incident CHD. Genetic predisposition (for race/ethnicity) or indirect effect on the electrophysiology of the heart (hypertension and BMI) may be part of the explanation—a hypothesis that requires further investigation.
ST segment elevation has been reported in many conditions and disease states including acute coronary syndrome, acute pericarditis, early repolarization and Brugada syndrome. The latter two conditions have been looked at as two extreme examples of conditions associated with non-atherosclerotic ST elevation. Early repolarization has always been considered benign, while Brugada syndrome has been associated with sudden death. Nevertheless, recent reports showed that early repolarization (albeit with an idiosyncratic definition of early repolarization) could also be associated with sudden death.28
In our study, ST elevation (STJ and ST60) was mostly protective from SCD. This accords with what is always believed as a benign nature of early repolarization, in which ST elevation is a key feature. Differences in the outcomes associated with ST elevation (or early repolarization) could be explained by differences in the pathophysiological basis of SCD (non-atherosclerotic vs. atherosclerotic as in our study) or differences in the populations studied (patient-based vs community-based).
Although presence of STelevation (STJ or ST60) was generally protective
from SCD, it was predictive
of high incident CHD risk. This may explain the recently reported increased cardiovascular and all-cause mortality associated with early repolarization as defined mainly on the basis of STelevation.29, 30
The mechanism by which ST elevation could be predictive of high CHD risk is unclear.
Our results should be interpreted in the context of some limitations. We have conducted many statistical tests without adjusting for multiple comparisons. Thus, some of the positive results could be due to chance. However, since this analysis is the first attempt to get a general idea on what could be potentially SCD-specific predictors, adjusting for multiple comparisons and using a more stringent p value may lead to missing some potentially important predictors. This is the same reason for using most of the predictor variables in our analysis as continuous variables in the statistical models (ie, reporting HRs per 1 SD increase) rather than using arbitrary cut points that can miss important associations which may exist with other cut points. For example, using ST elevation, whether in any lead group or separately, as a categorical variable (defined by Minnesota Code) was not predictive of either SCD or CHD (results not shown), but using ST elevation (STJ and ST60) as a continuous variable highlighted the potential importance of ST elevation in V2. Noteworthy, STJ and ST60 in the same lead or in different leads in the same lead group are correlated to some degree, and subsequently, the tests may not be fully independent. However, we preferred to test STJ and ST60 in individual leads because different ion channels may be active at these times or clearly manifested in some leads compared to others. Validation of the SCD distinguishing predictors which we identified and searching for the optimal cut points for these predictors are needed. Another limitation of our study is that we depended solely on resting standard 12-lead ECG without utilisation of other recent prognostically important ECG predictors of SCD such as heart rate turbulence, T wave alternans, late potentials detected by signal-averaged ECG, etc. Nevertheless, lack of widespread availability of these new ECG predictors would be an obstacle to make practical use of them even if they proved useful in distinguishing between SCD from CHD.
The strengths of this study are the very large size of the cohort studied and that our classification of SCD is much more precise and rigorous than that of other investigations. Also, most of the previous studies on predictors of SCD have ignored the competitive risk of CHD, which does not provide meaningful risk stratification of patients if definitive preventive strategies are to be implemented.
In conclusion, SCD and incident CHD have many risk factors in common. However, we identified specific predictors that have the potential to separate between the risks of SCD and CHD. These predictors include race/ethnicity, hypertension, BMI, heart rate, QTc, abnormally inverted T wave in any ECG lead group and level of ST elevation in V2. These results need to be validated in another cohort.