Background: The serum biochemical indexes are classic detection in clinical practice. Methods: In this study, for avoiding the risks of serious complications, high-cost in diagnosis of suspected coronary heart disease (CHD), the common biochemical indexes were detected from 68 eligible patients with suspected CHD. Treadmill exercises test (TET)-electrocardiogram (ECG) was measured during TET, and invasive examination of coronary angiography (CAG, golden standard for CHD diagnosis) was also performed. Results: For CAG, 48 patients were positive and 20 were negative; while for TET 38 were positive, 14 were inconclusive, and 16 were negative, respectively. Among these biochemical indexes, the HbA1c (%) level in CAG positive patients was much higher than that in CAG negative patients ( P = 0.019). Furthermore, according to receiver operating characteristic (ROC) curve, HbA1c showed effective diagnosis for CHD and its best cutoff value was 5.85% and 29 of the patients were HbA1c positive and 30 were negative. Conclusions: It was found that HbA1c combined with TET obviously enhanced the sensitivity of examinations. All the patients who were negative in both HbA1c and TET tests turned out to be 90% CAG negative, which meant that the combination might stand invasive examination of CAG for CHD diagnosis. Further studies in multi-center investigation will be expected to validate the findings.
CHD has a close relationship with myocardial ischemic disease that threatens patients’ life. Various risk factors are associated with CHD, such as diabetes, severe hypertension and hypercholesterolemia. Diabetes is one of the major causes of CHD and nearly 70% type 2 diabetes die of cardiovascular causes, especially CHD. Moreover HbA1c was associated with a more obvious increase in diabetes [
Coronary angiography (CAG) is the “gold standard” for myocardial ischemia diagnosis. However, as CAG is only cost-effectively conducted in highly suspected patients, it has the risks of serious complications and might be impossible in some common hospitals and affect the diagnosis of CHD in some patients [
As the non-invasive detective way, ECG measured during TET (TET-ECG) is a more sensitive way of identifying CHD. TET can give extra load to heart so that oxygen consumption of myocardium increases, which can arouse ischemia in potential cases before inhibition of glyceryl trinitrate [
In this study, TET results and biochemical indexes of all the 68 patients were recruited for the inconclusive TET diagnosis. For all these examinations, CAG is the “gold standard” to make a definite CHD diagnosis, and TET combined with other indexes can improve the diagnostic effect of CHD.
68 patients with complaints of “chest pressure, chest pain, or chest discomfort” [
Biomarker were analysed by HITACHI-7600 automatic biochemistry analyzer (HITACHI, Japan); TET was analysed by GE Cardiosoft V6.51 system (Mortara Instrument, USA); CAG was conducted by GE innova 3100 X-ray machine (General Electric Company, USA).
TET adopted Bruce scheme, which the patients should reach 100% (maximal exercises) or 85% (submaximal exercise) of their maximal heart rate (220 age). After the Bruce protocol, the Duke Treadmill Score was calculated as following: exercise time (ET, min) − (5×maximal ST-segment depression [mm]) − (4 × angina index [no Angina, 0; Angina, 1; Angina as reason for stopping test 2]) [
The “positive” criteria were: ECG showed upsloping ST-segment depressions ≥ 1.5 mm or downsloping or horizontal depressions ≥ 1.0 mm in at least 2 leads and last for more than 2 min, with or without concomitant typical angina symptoms; while the “negative” criteria were: objective load achieved without ST-T changes [
All 68 patients were tested CAG that Seldinger technique was adopted to puncture and a cather was carefully moved to heart before dye injecting. Stenosis or any blokages in blood flow can be highlighted by dye moving through the artery. At least a stenosis ≥ 50% in the coronary artery was defined as CHD [
Data were presented as mean ± SEM. For baseline characteristics of between CAG positive and negative were tested by Chi-square test. For biochemical indexes mean comparisons between TET positive and negative were tested by independent samples t-test. Receiver operating characteristic (ROC) curve was used for general evaluation of biochemical indexes. Calculation and illustration were made by software SPSS 13.0. Statistical significance was established at P < 0.05.
The analysis also showed that positive CAG patients compared to negative CAG patients had higher evaluations in peak heart rate (Peak HR, bmp) (Independent t-test, P < 0.05), maximum peak heart rate achieved (MPHR achieved %) (Independent t-test, P < 0.05) and maximum RPP (Independent t-test, P < 0.05). Other baseline characteristics and exercise parameters had no significantly different between positive and negative CAG patients (P > 0.05).
As shown in
ROC curve was often used to determine the best cutoff value for a diagnostic test. The Test Variable was defined as new variable, and the State Variable was defined as the results of “golden diagnosis”, a series of sensitivity and specificity values can be calculated. The ROC curve was made with sensitivity (the true positive rate) as y-axis and 1-specificity (the false positive rate) as x-axis, to show the relationship between sensitivity and specificity. ROC curve which is shaped with convexity towards the upper-left quadrant, where the point most close to was chosen as the best cutoff value, of the reference frame was desirable [
All patients were executed TET and CAG. As for CAG, “positive” was defined as existing at least a stenosis ≥ 50% in the coronary artery. In
Taking CAG results as gold standard for CHD diagnosis, we compared four different detections for CHD diag-
All (n = 68) | Negative CAG (n = 20) | Positive CAG (n = 48) | p | |
---|---|---|---|---|
Male gender, n (%)# | 45 (66) | 11 (55) | 34 (71) | 0.214 |
Age (y) | 59 ± 1.1 | 59 ± 1.9 | 59 ± 1.3 | 0.979 |
Hypertension, n (%)# | 34 (50) | 6 (30) | 28 (58) | 0.034 |
Diabetes, n (%)# | 24 (35) | 3 (15) | 21 (44) | 0.024 |
Hyperlipoidemia, n (%)# | 19 (28) | 6 (30) | 13 (27) | 0.811 |
Smoking, n (%)# | 23 (34) | 8 (40) | 15 (31) | 0.494 |
Family History of CAD, n (%)# | 8 (12) | 3 (15) | 5 (10) | 0.599 |
pre-TET diagnosis | ||||
Asymptomatic (%)# | 28 (41) | 8 (40) | 20 (42) | 0.901 |
After PCI (%)@,# | 12 (18) | 1 (5) | 11 (23) | 0.08 |
Symptomatic (%)# | 29 (43) | 11 (55) | 18 (38) | 0.189 |
MET | 8.385 ± 0.191 | 8.650 ± 0.358 | 8.275 ± 0.226 | 0.375 |
UST (%)# | 44 (65) | 16 (80) | 28 (58) | 0.091 |
Terminal (%)# | 24 (35) | 4 (20) | 20 (42) | 0.091 |
No symptoms during test (%)# | 30 (44) | 12 (60) | 18 (37) | 0.091 |
Typical angina during test (%)# | 3 (4) | 0 (0) | 3 (100) | 0.259 |
Atypical angina during test (%#) | 21 (31) | 4 (20) | 17 (35) | 0.216 |
Dyspnea during test (%)# | 31 (46) | 8 (40) | 23 (48) | 0.557 |
Arrhythmia during test (%)# | 34 (50) | 8 (40) | 26 (54) | 0.294 |
MPHR, bpm | 161.088 ± 1.033 | 160.100 ± 1.799 | 161.500 ± 1.264 | 0.541 |
Exercise load | 2.838 ± 0.065 | 2.900 ± 0.124 | 2.813 ± 0.077 | 0.543 |
Peak HR, bpm | 151.397 ± 2.102 | 158.200 ± 3.911 | 148.563 ± 2.401 | 0.036 |
MPHR achieved, % | 93.441 ± 1.217 | 98.350 ± 2.240 | 91.396 ± 1.358 | 0.008 |
maximum RPP | 248.657 ± 8.871 | 278.700 ± 15.027 | 236.640 ± 9.775 | 0.027 |
Exercise time, min | 6.765 ± 0.185 | 6.969 ± 0.321 | 6.679 ± 0.227 | 0.478 |
Pre-TET Resting SBP, mm Hg | 131.735 ± 2.200 | 130.300 ± 3.220 | 132.333 ± 2.830 | 0.677 |
Pre-TET Resting DBP, mm Hg | 77.500 ± 1.384 | 78.500 ± 2.124 | 77.083 ± 1.755 | 0.644 |
Post-TET Resting SBP, mm Hg | 130.515 ± 1.816 | 131.900 ± 3.029 | 129.938 ± 2.257 | 0.626 |
Post-TET Resting DBP, mm Hg | 79.868 ± 1.282 | 79.400 ± 2.156 | 80.063 ± 1.590 | 0.816 |
Peak SBP, bpm | 184.838 ± 3.151 | 185.050 ± 5.783 | 184.750 ± 3.800 | 0.966 |
Peak DBP, bpm | 82.941 ± 1.692 | 85.450 ± 2.800 | 81.896 ± 2.094 | 0.342 |
Duke Treadmill Score# | ||||
Group 1 (≥5), n (%) | 12 (17.6) | 4 (33) | 8 (67) | <0.001 |
Group 2 (−10 to <5), n (%) | 48 (70.6) | 6 (12) | 42 (88) | <0.001 |
Group 3 (≤−11), n (%) | 8 (11.8) | 0 (0) | 8 (100) | <0.001 |
Statistical comparisons of repeated multiple comparisons were carried out with Independent samples t-test. @Patients after PCI who had T-wave changes. #Statistical comparisons of repeated multiple comparisons were carried out with Chi-square test. Values are n (%) or mean ± SEM. Typical angina individuals were with complaints of angina, exertional chest discomfort, after that it was substernal and relieved with rest or nitroglycerin.
CAG | TET (+, ±) | TET (−) | |
---|---|---|---|
BUN (mmol/L) | − | 347.692 ± 27.927 | 397.000 ± 38.142 |
+ | 381.081 ± 19.537 | 449.667 ± 48.257 | |
CHL (mmol/L) | − | 4.507 ± 0.303 | 4.646 ± 0.334 |
+ | 4.838 ± 0.228 | 4.083 ± 0.444 | |
CK (mmol/L) | − | 91.231 ± 11.184 | 124.571 ± 11.820 |
+ | 103.028 ± 6.930 | 222.429 ± 123.171 | |
CKMB (mmol/L) | − | 14.077 ± 1.059 | 17.429 ± 1.131 |
+ | 17.028 ± 1.799 | 24.000 ± 6.448 | |
HDL (mmol/L) | − | 1.290 ± 0.085 | 1.143 ± 0.133 |
+ | 1.272 ± 0.068 | 1.089 ± 0.061 | |
LDH1 (mmol/L) | − | 34.385 ± 2.168 | 33.571 ± 2.339 |
+ | 44.353 ± 9.767 | 74.000 ± 30.232 | |
LDL (mmol/L) | − | 2.278 ± 0.232 | 2.380 ± 0.404 |
+ | 2.935 ± 0.171 | 2.248 ± 0.272 | |
TP (mmol/L) | − | 70.125 ± 1.919 | 68.514 ± 2.862 |
+ | 68.216 ± 1.173 | 69.288 ± 2.002 | |
TG (mmol/L) | − | 1.651 ± 1.173 | 1.754 ± 0.221 |
+ | 1.417 ± 0.093 | 1.686 ± 0.309 | |
HbA1c (%) | − | 5.509 ± 0.109* | 5.450 ± 0.273 |
+ | 6.077 ± 0.147* | 6.078 ± 0.267 |
+: positive; −: negative; ±: inconclusive. *: significantly differences between CAG (−) and CAG (+) in TET (+, ±) group.
Results | CAG | TET | HbA 1c | |||
---|---|---|---|---|---|---|
n | % | n | % | n | % | |
+ | 48 | 0.705882353 | 38 | 0.558823529 | 29 | 0.426470588 |
− | 20 | 0.294117647 | 16 | 0.235294118 | 30 | 0.441176471 |
nosis, which were TET alone, HbA1c alone, and the combination of these two for either serial (TET × HbA 1c , both examinations positive could be presumed as positive) or parallel (TET + HbA 1c , defined as either HbA1c or TET was positive) tests. For HbA 1c , the best cutoff value used to estimate positive and negative patients was 5.85%. As shown in Figures 2(a)-(d), compared with the gold standard diagnosis of CAG by ROC curve, the sensitivity values of TET alone, HbA1c alone, TET × HbA1c and TET+HbA1c were 60%, 55%, 36% and 80%, respectively; and the specificity values of them were 60%, 67%, 89% and 31%, respectively (
This study was about the analyses of generally acknowledged serum biochemical indexes in the suspected CHD patients. For each of them, serum assays were performed. TET which was an examination could assist CHD diagnosis and might arouse myocardial ischemia to make us study the combination TET and results of those biochemical indexes [
After the biochemical indexes were compared between CAG positive and CAG negative groups in positive TET (+, ±) and negative TET (−) groups, one significant difference was found: HbA1c levels in CAG positive group were higher than those in CAG negative group. In other words, HbA1c were significantly different between CHD patients and non-CHD people, which made it a potential biomarker to help diagnose in suspected CHD. ROC curve was used to testify this hypothesis, which showed that HbA1c had effective diagnosis for CHD and the best cutoff value for identifying positive or negative was 5.85%.
Thus besides CAG, we had another four detective diagnosis for CHD, which were TET, HbA 1c , and combination of both as serial and parallel tests. As a result, we found that the parallel tests had higher sensitivity of CHD diagnosis (80%) than that of the TET examination (60%). This has important clinical meanings. Although CAG was a golden standard diagnosis of CHD, it was an invasive procedure. Since both TET and HbA1c are non-invasive, cheap, high sensitivities and accessible, they can be used as screen examinations in suspected CHD patients. Although the specificities of tests dropped down 29% for parallel tests, it was still acceptable fact that parallel tests were efficient methods to diagnose CHD. As long as the serious consequence of missed diagnosis for CHD, high sensitivity was more important than low specificity. However, the serial tests can be compensated for low specificity of parallel tests, for the specificity was as high as 89%.
In this study, we also found that all the persons with negative TET and HbA1c results were also 90% negative CAG, for this group of people, the non-invasive serial tests could stand CAG for ruling out CHD diagnosis, decreasing lots of unnecessary pains and risks.
To summarize, in our study, the HbA1c (%) of CHD patients were higher than those of non-CHD persons. By means of ROC curve, it was found to have diagnostic effect of CHD, and could obviously enhance the sensitivity of examinations in combination with TET as parallel tests. And because of the identical results, the latter strategy could potentially stand invasive CAG for the diagnosis of CHD. However, considering the number of patients in our study is relatively limited, and so far no other similar studies were reported, further researches and evidence are warranted to validate the findings in this paper.
We found that HbA1c combined with TET obviously enhanced the sensitivity of examinations. All the patients who were negative in both HbA1c and TET tests turned out to be 90% CAG negative, which meant that the combination might stand invasive examination of CAG for CHD diagnosis. Further studies in multi-center investigation will be expected to validate the findings.
We sincerely thank Zicheng Li and Jitian Xia for their generous assistance in manuscript preparation and clinical laboratory for the biochemical indexes in detection.
This work was supported by Grants from Science and Information Technology of Guangzhou (No. 40108003), the Fundamental Research Funds for Central Universities (No. 21611333). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The study received the First Affiliated Hospital of Jinan University Ethic Committee approval. Informed consent was obtained from all 68 patients.
The authors have declared that no competing interests exist.
Hongcheng Mai,Zhifeng Huang,Tao Zhang, (2016) Analysis of Serum Biochemical Indexes for the Diagnosis of Coronary Heart Disease in Suspected Patients. Open Access Library Journal,03,1-8. doi: 10.4236/oalib.1102389