In this study, we investigated the relationship between baseline elevation of cTn-I in asymptomatic hemodialysis patients and the angiographic CAD burden when they present with symptomatic elevation in serum cTn-I above baseline levels. For such a presentation, our findings demonstrated that in hemodialysis patients with no known prior CAD, 59% had severe angiographic CAD, and only 17% had normal coronary angiography. Moreover, baseline elevation of cTn-I in asymptomatic hemodialysis patients was significantly correlated with the angiographic CAD burden, and with the increased baseline cTn-I levels, the specificity of this cardiac biomarker increases to predict more advanced angiographic CAD.
The assessment of CAD in ESRD is challenging [8]. We included patients with or without baseline elevation of cTn-I and excluded patients with known underlying CAD. Our study's most important finding is that despite baseline elevation in asymptomatic hemodialysis patients, cTn-I is still reliably associated with the presence and severity of coronary stenosis. Baseline cTn-I was elevated in 84% and above the 99th percentile URL in 20% of the study population, similar to the previously reported elevation of cTn-I in asymptomatic hemodialysis patients [9]. Baseline cTn-I in asymptomatic hemodialysis patients predicted severe CAD with a specificity of 0.95 and an overall accuracy of 0.72. The specificity increased dramatically with increased baseline cTn-I. Therefore, the higher the baseline cTn-I values, the more likely the presentation is due to more advanced CAD. This was in line with previous studies showing that patients presenting with altered cTn are at high risk of coronary stenosis [10], and baseline cTn-I are rarely elevated without evidence of CAD in hemodialysis patients [11]. Moreover, a previous study showed that not only a negative cTn-I identifies patients at low risk of MI and 30-day cardiac mortality, but also those with cTn-I levels at or above the 99th percentile had a 2-fold increased risk of MI and cardiac death at one year [12]. In our study, patients with baseline cTn-I above the 99th percentile had a high test accuracy to indicate more advanced CAD. Therefore, earlier cardiac workup and more strict risk management might be suggested, given that hemodialysis patients with MI suffer dismal long-term survival [13, 14].
Our study adds to the growing literature demonstrating the diagnostic power of cTn-I cardiac for predicting the severity of CAD in hemodialysis patients. Our findings should help clarify the challenging clinical problem of interpreting the significance of the symptomatic rise of cTn-I when there is an existing elevation of cTn-I in hemodialysis patients. We show a low false-positive elevation of cTn-I to predict advanced CAD. Various risk stratification models that are routinely used in clinical practice have been shown to improve clinical outcomes and reduce the financial burden on the healthcare system. Improving our ability to forecast risk, especially in a high-risk population like hemodialysis patients, has tangible benefits. Therefore, our results suggest the potential value of including baseline cTn measurements to the existing scoring systems for risk stratification of patients hospitalized for suspected acute coronary syndrome (ACS).
The pathophysiology behind cTn-I elevations in hemodialysis patients is not fully understood [15, 16]. The elevation of cardiac biomarkers is predictive of all-cause and cardiovascular mortality, suggesting true underlying cardiac pathology [5, 7, 17]. Several studies have implicated epicardial CAD as a potentially major cause of increased cTn-I in hemodialysis patients[17, 18]. Other cardiac pathologies like microvascular dysfunction, diffuse CAD, vascular calcification, and arteriosclerosis can potentially explain the chronic enzyme elevation [8, 19]. Results from our study support this evidence by showing that the severity of coronary stenosis is associated with higher baseline cTn-I.
Concerning CAD risk factors, we noted, unsurprisingly, a higher prevalence of diabetes mellitus, hyperlipidemia, and peripheral artery diseases in hemodialysis patients with severe CAD. Hypertension was present in most hemodialysis patients (91%) regardless of their CAD status. This was similar to previous reports documenting hypertension as high as 86% in chronic hemodialysis patients.[20, 21] Likewise, smoking prevalence was equally high in all groups. We demonstrate that more CAD risk factors are associated with an increased risk of obstructive CAD in hemodialysis patients. Therefore, optimal medical management for CAD risk factors in hemodialysis patients is essential. Very few clinical trials have investigated outcomes of conservative strategy compared to invasive strategy in coronary disease in patients with advanced kidney disease [22, 23]. However, none of these studies have differentiated the outcomes in hemodialysis patients with or without cTn-I elevation.
We recognize some limitations in our study. The retrospective design, the majority of the study population, consisted of African Americans, who share a disproportionately higher prevalence of ESRD and are overall understudied; this can affect the generalizability of the results. There may be selection bias as hemodialysis patients with no measured baseline cTn-I level were automatically excluded, and the study was limited to hospitalized patients. Also, there were no cardiac structural and functional correlations with the baseline elevation of cTn-I, focusing only on the association with the angiographic CAD burden. Lastly, the study was not designed to evaluate the prognostic value of elevated baseline cTn-I.