This study is the first long-term observational study to explore the prevalence and clinical impact of ECG abnormality on cerebrocardiovascular prognosis in Asian CKD patients. We found several clinical perspectives on ECG with respect to cerebrocardiovascular prognosis in CKD patients. First, the prevalence of major ECG abnormalities increases as CKD stage increases. In CKD patients, the most common ECG diagnosis corresponding to major ECG abnormalities was prolonged QT interval (7%). CKD patients with major ECG abnormalities had poor cerebrocardiovascular prognosis, in particular a higher incidence of MI.
Several surrogate markers, such as albumin-creatinine ratio (ACR), pulse wave velocity, and carotid ultrasound, have been proposed in predicting CVD in CKD patients(21). Of note, depending on the race, there are differences in the association of some surrogate markers with CVD, and their decision criteria are accordingly different. For example, ACR levels are higher and have a stronger association with CVD in Asians compared to Europeans(22). Previously, several studies demonstrated that ECG abnormalities are associated with poor cardiovascular prognosis in CKD patients(9, 10, 23). Although almost all these studies have been conducted in CKD patients in Caucasian and black people, our study expands these associations in Asian CKD patients.
Previous studies included patients taking medications that affect ECG results. For example, the use of 𝛽-blockers capable of increasing PR intervals was at least 15% up to 65% in the previous studies. The prevalence of CVD and psychotic disease also rises as renal function decreases in CKD patients, and since many drugs for CVD and psychotic disease affect the ECG results, it is difficult to confirm the prevalence of ECG abnormalities when excluding this confounding factor. Our study excluded those patients taking almost all medications affecting ECG results such as 𝛽-blockers, non-dihydropyridine calcium channel blockers, digoxin, ivabradine, type IA/IC/III antiarrhythmics, antipsychotics, antidepressants, antihistamines, macrolides and chloroquines. Our study confirmed the solid independent association of major ECG abnormalities with CKD patients and their cerebrocardiovascular prognosis.
Interestingly, Cox regression analysis of MACCE in our study suggested major ECG abnormality as an independent risk predictor, but not CKD stage. This suggests that ECG results are more important than CKD stage for the occurrence of MACCE. Among various ECG diagnoses, prolonged QT interval was the most common major ECG abnormality and was associated with CKD stage and CVD prognosis. This is consistent with previous reports that QT interval is associated with cardiovascular events and deaths(9, 23–26). QT interval reflects both conduction and repolarization of the heart and is affected by electrolyte imbalance as well as myocardial ischemic condition. Therefore, QT interval is likely to be associated with the occurrence of MI and sudden death, and prolonged QT interval is frequently observed in patients with sudden death and MI(27), further suggesting it as a risk predictor for obstructive coronary artery disease(28).
There are several limitations in our study. First, there is selection bias. We excluded CKD patients taking medications that can affect the ECG results. As mentioned earlier, CKD patients often have other comorbidities, so many of them take drugs that affect ECG. In our study, 20% of patients were excluded because of use of these drugs. Therefore, our results cannot be extended to CKD patients taking these drugs. Second, since different ECG abnormality criteria can be used for each study, we should be careful when comparing or applying our study to other studies. Some previous studies adopted different criteria for major and minor ECG abnormality(29–31). Although the Minnesota code classification, which was adopted in our study, cannot be considered the only standard for classification of ECG abnormalities, we applied the latest version of the Minnesota code classification. This is the first study to use the updated version. Third, only 280 (21.6%) patients with advanced CKD under eGFR 30 mL/min/1.73m² were included in our study. Similarly, the proportion of severe CKD patients was about 5–20% in previous studies(9, 10, 23),. In addition, considering that cardiovascular comorbidities become more common in severe CKD patients, the rate of drug use that affects ECG results will also be higher. Since these patients were excluded in this study, the number of severe CKD patients in this study was smaller. Therefore, it is limited in inferring the clinical impact of ECG abnormalities in patients with severe CKD.
In conclusion, major ECG abnormalities in Asian CKD patients increase the risk of cerebrocardiovascular events, especially MI. Further research is needed on more precise cerebrocardiovascular risk assessment and appropriate intervention strategies using ECG in the future.