Impact of Parathyroid Hormone Level on Intracoronary Calcification and Short- and Long-Term Outcomes in Dialysis Patients Undergoing Percutaneous Coronary Intervention

Abstract

Background: Dialysis patients have strong intracoronary calcification, accelerated by secondary hyperparathyroidism as well as atherosclerosis. We evaluated the association of intact parathyroid hormone (iPTH) level with intracoronary calcification evaluated by intravascular ultrasound (IVUS), and its impact on both stent expansion after percutaneous coronary intervention (PCI) and long-term clinical outcomes, in dialysis patients with coronary artery disease (CAD).

Methods and Results: A total of 116 patients on dialysis, who underwent PCI with IVUS guidance between March 2012 and December 2020, were enrolled. Patients were divided into 2 groups based on their median iPTH level. The degree of intracoronary calcification was evaluated by calcification score using grayscale IVUS in the target lesions. Preprocedural calcification scores were significantly higher in the high iPTH group compared with the low iPTH group (2.9±1.1 vs. 2.1±0.7, P<0.001). After PCI, the high iPTH group had a significantly lower stent expansion index (0.6±0.2 vs. 0.7±0.1, P<0.001) and stent symmetry index (0.5±0.1 vs. 0.7±0.1, P<0.001) compared with the low iPTH group. The incidence of major adverse cardiac or cerebrovascular events within 3 years was significantly higher in the high iPTH group (log-rank P<0.05).

Conclusions: High iPTH level is likely to increase intracoronary calcification, and cause inadequate stent expansion, which may be associated with increased risk of future adverse events in dialysis patients with CAD requiring PCI.

Patients with chronic kidney disease (CKD), especially those with endstage renal disease (ESRD) in need of renal replacement therapy, are prone to developing atherosclerotic cardiovascular disease and have a significantly higher mortality rate compared with the general population.^1–4 Patients with ESRD on dialysis frequently have intracoronary calcification to a much greater extent that in patients without ESRD.⁵ In general, it is well known that ectopic calcification, including in the coronary arteries, is accelerated by secondary hyperparathyroidism, in addition to atherosclerosis, in dialysis patients.^6,7 Evaluation of secondary hyperparathyroidism is usually by measuring the intact parathyroid hormone (iPTH) level, and previous studies have reported that higher iPTH levels are associated with progression of coronary calcification.⁷ Coronary calcification is reportedly connected to increased cardiovascular events and death.^8,9 Moreover, the iPTH level is also associated with all-cause and cardiovascular death in dialysis patients. However, there is limited information regarding the relationship between iPTH and prognosis in dialysis patients with severe coronary artery disease (CAD) requiring coronary revascularization.

Although percutaneous coronary intervention (PCI) is widely performed in dialysis patients with CAD, intracoronary calcification is one of the important obstacles for successful device delivery and adequate stent expansion, which affects both the short- and long-term outcomes.^10,11 Although intracoronary imaging, such as intravascular ultrasound (IVUS) and optical coherence tomography, are useful to assess intracoronary calcification during the PCI procedure, there are few studies investigating the association of iPTH level with intracoronary calcification at the culprit lesion, as well as on stent expansion after PCI. Integrated backscatter-intravascular ultrasound (IB-IVUS) can identify coronary plaque components, such as calcification, using radiofrequency data analysis as well as conventional grayscale imaging assessment.¹² Thus, the aim of this study was to evaluate the association of iPTH level with intracoronary calcification using IB-IVUS, as well as its effect on stent expansion and long-term clinical outcomes after PCI in CAD patients with ESRD on dialysis.

Methods

Study Design and Patient Population

Patients with ESRD on dialysis who underwent PCI for CAD with IB-IVUS guidance at Chiba University Hospital between March 2012 and December 2020 were enrolled. The major criteria for exclusion were no stent implantation (e.g., drug-coated balloon), in-stent restenosis, and severe calcification in the culprit vessel precluding IVUS imaging before or after stent placement. The patients were divided into 2 groups according to the median iPTH level. Patients’ laboratory data, including iPTH level, were collected immediately before dialysis. In patients who underwent PCI for multiple lesions, the lesion with greatest intracoronary calcification based on the calcification score, as described later, was included for this analysis.

Grayscale IVUS Analysis

IVUS imaging was performed in the target lesion before any intervention or after predilatation with a small balloon if needed. The images were acquired with a commercially available IVUS imaging system (VISICUBE, Terumo, Tokyo, Japan) using a 60-MHz mechanically rotating IVUS catheter (AltaView, Terumo) with motorized transducer pullback speed of 3 mm/s. All IVUS measurements were performed by an experienced investigator who was blinded to the patient’s clinical characteristics, as recommended by consensus documents.^13,14 Offline analysis including the IB-IVUS images was performed using a computerized system (VISIATLAS, Terumo). IVUS measurements were performed in the target lesion, which was defined as the segment in the pre-stent images where stents would be deployed, identified by comparing any markers such as side branches and calcification with the post-stent images. In the grayscale IVUS analysis of the target lesion, cross-sectional areas of the lumen and external elastic membrane (vessel) were manually measured for each 1.0 mm of axial length. Volumetric IVUS data were presented as total volume per lesion length (mm³/mm) for correcting the differences of lesion length. The minimum lumen area, lumen volume index, vessel volume index, and plaque volume index were calculated in the target lesion. In the semiquantitative analysis, the degree of intracoronary calcification was scored by grading the measured angles as 0–4 for 0°, <90°, 90–180°, 180–270° and >270° at 1-mm intervals along the entire target lesion. The calcification score was the total score along the entire target lesion divided by the number of analyzed cross-sections. Calcified nodules were defined as irregular and protruding calcification with a convex luminal surface. To compare the degree of stent expansion after PCI, minimum stent area, acute lumen area gain, stent expansion index, and stent symmetry index were calculated in the stented segment as previously described.^13,14 The acute lumen area gain was defined as the minimum stent area minus the minimum lumen area in the pre-stent images. The stent expansion index (%) was defined as the minimum stent area divided by the average of the proximal and distal reference lumen areas multiplied by 100. The stent symmetry index was calculated by dividing the minimum stent diameter by the maximal stent diameter at a cross-section with minimum stent area.

IB-IVUS Analysis

IB-IVUS analysis was performed to compare the plaque composition of the target lesion between the high and low iPTH groups. Using a computerized system (VISIATLAS), tissue components of the target lesion were automatically classified into 4 categories: calcification (red), dense fibrosis (yellow), fibrosis (green), and lipid pool (blue + purple), according to signal level. Next the percentage volume of each component (each component volume/plaque volume ×100) was calculated.

Clinical Outcomes

Long-term outcomes were evaluated by comparing the incidence of major adverse cardiac or cerebrovascular events (MACCE), all-cause death, cardiovascular death, non-fatal myocardial infarction (MI), and target lesion revascularization (TLR) within 3 years after PCI between the high and low iPTH groups. MACCE was defined as a composite of cardiovascular death, non-fatal MI, non-fatal cerebrovascular accident, and all revascularizations. TLR was defined as clinically indicated percutaneous or surgical revascularization of the target lesion during follow-up.

Statistical Analysis

Continuous variables are presented as mean±standard deviation, and categorical variables are presented as percentages. Statistical analysis was performed with R statistical software package version R version 4.0.3 (Foundation for Statistical Computing, Vienna, Austria). Continuous variables were compared using analysis of the Mann-Whitney test. Categorical variables were compared with chi-square statistics or Fisher’s exact test. A value of P<0.05 was considered significant. Clinical outcomes were illustrated by Kaplan-Meier curves, and a comparative study was performed by log-rank quantification. Hazard ratio was calculated by analyzing the frequency of MACCE occurrence for each parameter. Univariate and multivariate Cox-proportional regression analyses were performed to determine the predictors of MACCE. Variables with a P value of <0.05 in the univariate Cox-proportional hazard model were examined in the multivariate model. Receiver operating characteristic (ROC) curve was used to determine the best cutoff value of iPTH level and the area under the curve (AUC) for predicting MACCE.

Results

Baseline Clinical Characteristics

The total number of patients who underwent PCI for CAD at Chiba University Hospital between March 2012 and December 2020 was 2,954. Of them, 184 (6.2%) were dialysis patients, and 176 (95.7%) had undergone IB-IVUS and 8 (4.3%) had undergone OCT during the PCI procedure. Of the 176 patients who underwent PCI with IB-IVUS imaging, 60 met the exclusion criteria. Consequently, 116 patients were included this study (Figure 1). The median iPTH level was 132 pg/mL, which was the basis for subdividing the study population into 2 groups: low iPTH group (<132 pg/mL, n=59) and high iPTH group (≥132 pg/mL, n=57). The characteristics of the 2 groups are shown in Table 1. There were no significant differences between groups in clinical characteristics, including dialysis period, serum calcium level, or phosphorus level and diagnosis that led to PCI. PCI procedural data are shown in Table 2 and there were no significant differences between groups.

Figure 1.

Flowchart of patients included in the present analysis. CAD, coronary artery disease; ESRD, endstage renal disease; IB-IVUS, integrated backscatter intravascular ultrasound; iPTH, intact parathyroid hormone; OCT, optical coherence tomography; PCI, percutaneous coronary intervention.

Table 1. Baseline Clinical Characteristics of the 2 Groups of Patients Based on Median iPTH Level

	Low iPTH (n=59)	High iPTH (n=57)	P value
Age (years)	67.3±10.0	67.0±11.4	0.96
Male (%)	46 (80.0)	49 (86.0)	0.81
Body mass index (kg/m2)	22.3±3.7	23.7±4.4	0.054
Hypertension (%)	50 (84.7)	51 (89.4)	1.0
Dyslipidemia (%)	36 (61.0)	34 (59.6)	0.68
Diabetes (%)	39 (66.1)	37 (64.9)	0.65
Current smoker (%)	24 (40.7)	18 (31.6)	0.27
Dialysis period (months)	76.6±81.4	67.3±69.1	0.51
Creatinine (mg/dL)	7.2±2.6	8.1±3.1	0.092
Total cholesterol (mg/dL)	155.1±40.4	162.1±43.8	0.37
LDL cholesterol (mg/dL)	87.1±32.2	93.9±35.9	0.28
HDL cholesterol (mg/dL)	49.5±15.1	46.7±15.2	0.32
Triglycerides (mg/dL)	106.3±52.8	136.6±82.4	0.021
Serum calcium (mg/dL)	8.4±0.6	8.5±0.8	0.34
Serum phosphorus (mg/dL)	5.1±1.5	5.5±1.8	0.13
Serum albumin (g/dL)	3.2±0.6	3.3±0.5	0.51
Prior PCI (%)	28 (47.5)	29 (50.9)	1.0
Prior CABG (%)	2 (3.4)	11 (19.3)	0.022
Prior myocardial infarction (%)	7 (11.9)	12 (21.1)	0.36
ACS (%)	23 (39.0)	22 (38.6)	0.85
STEMI (%)	9 (15.3)	6 (10.5)
NSTE-ACS (%)	14 (23.7)	16 (28.1)	0.70
Stable CAD (%)	36 (61.0)	35 (61.4)
Statin administration (%)	40 (67.8)	37 (64.9)	0.51
Phosphate binder administration (%)	26 (44.1)	33 (57.9)	0.35

ACS, acute coronary syndrome; CABG, coronary artery bypass graft; HDL, high-density lipoprotein; iPTH, intact parathyroid hormone; LDL, low-density lipoprotein; NSTE-ACS, non-ST-elevation ACS; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.

Table 2. PCI Procedural Information for the 2 Groups of Patients Based on Median iPTH Level

	Low iPTH (n=59)	High iPTH (n=57)	P value
Target vessel
Left anterior descending (%)	31 (52.5)	28 (49.1)
Left circumflex (%)	8 (13.6)	14 (24.6)	0.29
Right coronary artery (%)	20 (33.9)	15 (26.3)
Drug-eluting stent (%)	59 (100)	57 (100)	n/a
X-EES (%)	49 (83.1)	43 (75.4)
U-SES (%)	3 (5.1)	4 (7.0)
R-ZES (%)	2 (3.4)	4 (7.0)	0.38
S-EES (%)	3 (5.1)	6 (10.5)
P-EES (%)	2 (3.4)	0
Total stent length (mm)	37.2±18.7	37.4±20.0	0.93
Stent profile diameter (mm)	3.2±0.5	3.1±0.5	0.25
Debulking device use (%)	5 (8.5)	6 (10.5)	0.75
Maximal device diameter (mm)	3.4±0.5	3.3±0.6	0.37
Maximal inflation pressure (atm)	18.5±4.2	18.9±4.0	0.57

P-EES, Promus^® everolimus-eluting stent; R-ZES, Resolute^® zotarolimus-eluting stent; S-EES, Synergy^® everolimus-eluting stent; U-EES, Ultimaster^® sirolimus-eluting stent; X-EES, Xience^® everolimus-eluting stent. Other abbreviations as in Table 1.

Grayscale IVUS Analysis

The results of grayscale IVUS analysis are given in Table 3. The average target lesion length was comparable between groups (P=0.93). The high iPTH group had a significantly smaller minimum lumen area (P<0.001), smaller lumen volume index (P<0.05), smaller vessel volume index (P<0.05), higher calcification score (P<0.001), and higher frequency of calcified nodules (P<0.05) compared with the low iPTH group. In the analysis of the stented segment, the high iPTH group showed a significantly smaller minimum stent area (P<0.05), lower stent symmetry index (P<0.001), lower stent expansion index (P<0.001), and lower acute lumen area gain (P<0.05) compared with the low iPTH group.

Table 3. Grayscale IVUS Analysis in the 2 Groups of Patients Based on Median iPTH Level

	Low iPTH (n=59)	High iPTH (n=57)	P value
Target lesion
Lesion length (mm)	37.4±18.2	37.2±20.6	0.98
Minimum lumen area (mm2)	2.4±0.6	2.1±0.8	<0.05
Lumen volume index (mm3/mm)	5.4±1.9	4.4±1.7	<0.05
Vessel volume index (mm3/mm)	12.8±4.5	10.7±4.1	<0.05
Plaque volume index (mm3/mm)	7.6±3.0	6.4±2.7	<0.05
Calcification score	2.1±0.7	2.9±1.1	<0.001
Calcified nodule (%)	22 (38.6)	38 (64.4)	<0.05
Stented segment
Minimum stent area (mm2)	6.0±1.9	5.4±2.2	<0.05
Stent symmetry index	0.7±0.1	0.5±0.1	<0.001
Stent expansion index	0.7±0.1	0.6±0.2	<0.001
Acute area gain (mm2)	3.7±1.8	3.2±2.1	<0.05

IVUS, intravascular ultrasound. Other abbreviations as in Table 1.

IB-IVUS Analysis

In the IB-IVUS analysis, the high iPTH group had significantly higher percentage of calcification (%calcification) and percentage of fibrosis (P<0.001, respectively), and that of lipid pool was significantly lower (P<0.05) compared with the low iPTH group (Figure 2). Representative images are shown in Figure 3.

Figure 2.

Comparison of plaque composition evaluated by IB-IVUS in the target lesion between the low and high iPTH groups. IB-IVUS, integrated backscatter-intravascular ultrasound; iPTH, intact parathyroid hormone.

Figure 3.

Representative images of plaque composition evaluated by IB-IVUS in the target lesion and stent expansion after stent placement in a comparison between patients with low and high iPTH levels. (A–C) Representative IB-IVUS images in a patient with low iPTH level: (A) grayscale image at the MLA site; (B) IB-IVUS analysis at the MLA site: %dense calcium was 2.42% (red area); (C) after stent placement at the corresponding site of MLA. (D–F) Representative IB-IVUS images in a patient with high iPTH level: (D) grayscale image at the MLA site; (E) IB-IVUS analysis at the MLA site: %dense calcium was 7.30% (red area); (F) after stent placement at the corresponding site of MLA. IB-IVUS, integrated backscatter-intravascular ultrasound; iPTH, intact parathyroid hormone; MLA, minimal lumen area.

Clinical Outcomes

Clinical outcomes during the follow-up period of 3 years were compared. The incidence of MACCE within 3 years was 33.9% in the low iPTH group and 60.7% in the high iPTH group (P<0.05). The incidence of all-cause death within 3 years was 32.2% and 54.4% (P<0.05), cardiovascular death was 16.9% and 42.1% (P<0.05), non-fatal MI was 13.6% and 21.1% (P=0.32), and TLR was 13.6% and 22.8% (P=0.23) in the low iPTH and high iPTH groups, respectively. Kaplan-Meier curves revealed that MACCE-, all-cause death-, cardiovascular death-, and TLR-free survival rates were significantly lower (log-rank P<0.05 for each), and the non-fatal MI-free survival rate tended to be lower (P=0.067) in the high iPTH group compared with the low iPTH group (Figure 4). The 3-year follow-up rates for all-cause death were 78.0% and 75.4%, the 2-year follow-up rates were 81.4% and 77.2%, and the 1-year follow-up rates were 89.8% and 89.4% in the low iPTH and high iPTH groups, respectively. Furthermore, the 3-year follow-up rates for MACCE were 72.9% and 70.2%, the 2-year follow-up rates were 74.6% and 71.9%, and the 1-year follow-up rates were 84.7% and 80.7% in the low iPTH and high iPTH groups, respectively. The results of Cox-proportional hazard regression analysis adjusted for the covariates are shown in Table 4. Multivariate analysis determined lower serum albumin and higher iPTH levels as independent predictors for MACCE. Finally, ROC curve analysis was performed to evaluate the predictive value of iPTH level for the onset of 3-year MACCE, and the AUC was 0.644 (95% confidence interval 0.542–0.746) and the best cutoff value was 127 pg/mL.

Figure 4.

Kaplan-Meier curves show that the MACCE-, all-cause death-, cardiovascular death-, and TLR-free survival rates were significantly lower, and the non-fatal myocardial infarction-free survival rate tended to be lower in the high iPTH group compared with the low iPTH group. iPTH, intact parathyroid hormone; MACCE, major adverse cardiac or cerebrovascular events; TLR, target lesion revascularization.

Table 4. Cox-Proportional Hazard Regression Model Depicting MACCE Risk

Value	Univariable analysis			Multivariable analysis
	HR	95% CI	P value	HR	95% CI	P value
Age	1.039	1.001–1.079	<0.05	1.022	0.981–1.065	0.30
Male	0.959	0.462–1.994	0.91
Body mass index	0.977	0.907–1.053	0.55
Hypertension	1.136	0.481–2.685	0.77
Dyslipidemia	0.597	0.332–1.071	0.083
Diabetes	0.934	0.511–1.706	0.82
Current smoker	0.995	0.547–1.809	0.99
Dialysis period	1.004	1.000–1.007	<0.05	1.003	0.995–1.007	0.090
Serum creatinine	0.940	0.850–1.040	0.23
Serum calcium	0.802	0.558–1.156	0.24
Serum phosphorus	1.073	0.876–1.314	0.50
Serum albumin	0.532	0.299–0.946	<0.05	0.496	0.251–0.980	<0.05
iPTH	1.002	1.001–1.004	<0.05	1.002	1.000–1.004	<0.05
LDL cholesterol	0.998	0.991–1.005	0.51
Triglycerides	0.997	0.992–1.002	0.19
Prior PCI	1.847	1.003–3.400	<0.05	1.779	0.916–3.458	0.090
Prior CABG	1.868	0.832–4.193	0.13
Statin administration	0.680	0.377–1.227	0.20
Phosphate binder administration	0.987	0.536–1.819	0.97

MACCE, major adverse cardiac or cerebrovascular events. Other abbreviations as in Table 1.

Discussion

The main findings of this study were: (1) higher iPTH level was significantly associated with a greater degree of calcification in the target lesion; (2) higher iPTH level resulted in unfavorable stent expansion and symmetricity after stent implantation; and (3) higher iPTH level was related to increased risk of MACCE and TLR in dialysis patients with CAD undergoing PCI.

Correlation Between iPTH and Intracoronary Calcification

To the best of our knowledge, no-one has investigated the correlation between iPTH level and intracoronary calcification using intracoronary imaging, although there has been a similar examination using the coronary calcium score evaluated by coronary computed tomography.⁷ In addition, it has been reported that higher serum calcification propensity is associated with greater coronary calcification score in patients with CKD stages 2–4.¹⁵ Our grayscale IVUS analysis demonstrated that the high iPTH group had a significantly higher calcification score, which is a semiquantitative grading method representing the extent of intracoronary calcification. It is conceivable that high levels of iPTH directly affect bone metabolism and cause ectopic calcification, including the coronary arteries, whereas the serum calcium level can be substantially maintained by the levels of iPTH and vitamin D level, as well as the absorption, excretion, and administration of phosphate binder.

There is also no report of the appropriate cutoff iPTH level for predicting clinical outcomes. We divided patients into 2 groups according to the median iPTH level (132 pg/mL), and a significant difference in the incidence of MACCE for 3 years was observed between groups. ROC curve analysis of iPTH level revealed the best cutoff value to predict MACCE was 127 pg/mL. Therefore, an iPTH level around 130 pg/mL might be useful for estimating future clinical outcomes.

Evaluation of Intracoronary Calcification Using IVUS

Any evaluation using IVUS has limitations on assessing the degree of calcification, and precise volumetric analysis cannot be done by IVUS because the ultrasound signal is almost entirely reflected on the surface of calcification. Although the calcification score is a useful semiquantitative parameter to assess the degree of calcification, it is based on subjective judgment of hyperechoic plaque that is brighter than the reference adventitia. Virtual histology-IVUS (VH-IVUS) is an IVUS-based imaging modality utilizing the radiofrequency data of reflected ultrasound signals in a frequency domain analysis, and it determines 4 tissue components: fibrous, fibrofatty, necrotic core, and calcification.¹⁶ Although VH-IVUS has been used to assess intracoronary calcification in previous studies, there are limitations to evaluating calcification due to the characteristics of IVUS.^17,18 IB-IVUS is another tool for evaluating the tissue characteristics of human coronary arterial plaques in vivo.¹⁹ A previous study reported that the accuracy of IB-IVUS for detecting fibrocalcific plaques is 96%.²⁰ On the other hand, there have been no studies examining intracoronary calcification using IB-IVUS. Based on the aforementioned limitations of IVUS, it should be taken into consideration that %calcification calculated by IB-IVUS is a conceptual, semiquantitative value that can only estimate the extent of calcification, and accurate quantitative evaluation of intracoronary calcification cannot be performed by IB-IVUS. However, because %calcification is an objective measure obtained by radiofrequency data of ultrasound signals using the dedicated algorithm, it might be a supplementary parameter of the degree of calcification without subjective aspects like calcification score.

Intracoronary Calcification and Stent Expansion

In the present study, iPTH level was associated with stent expansion and symmetricity after PCI, which might be affected by the intermediary of intracoronary calcification. Poor stent dilation is reported to increase the risk of TLR, in-stent thrombosis and cardiovascular death in the entire population.^21,22 That was also apparent in the results of this study. There are 2 main forms of arterial calcification: intimal and medial.^23,24 The former is observed as superficial, and the latter as deep calcification, distinguished by their location within the plaque. Because IVUS is limited to assessing tissue behind the calcification,²³ superficial and deep calcifications were not distinguished in the present study. In general, secondary hyperparathyroidism promotes medial calcification in dialysis patients,^25–27 which leads to an increase in arterial stiffness. In addition, we found that high iPTH levels were associated with a high frequency of intracoronary calcified nodules. Thus, it is possible that both medial and intimal calcification, as well as calcified nodule formation, in dialysis patients with high iPTH levels result in suboptimal stent expansion.

Relationship Between iPTH Level and Long-Term Outcomes

Previous studies have revealed that the frequency of advanced atherosclerotic lesions with calcification gradually increases as estimated glomerular filtration rate (eGFR) decreases.²⁸ It has also been reported that there is a graded association between reduced eGFR and the risk of death and cardiovascular events.²⁹ The iPTH level is considered one of the important factors involved in prognosis in dialysis patients, and is reportedly associated with all-cause and cardiovascular death,³⁰ which is consistent with the results of the present study. We assumed that the poorer stent expansion after PCI in the high iPTH group was associated with increased risk of TLR in the present study. A previous study reported that arterial media calcification is a strong prognostic marker of all-cause and cardiovascular death in dialysis patients.²⁵ Severe, advanced arterial calcification, especially in the media of the arteries, which is promoted by high iPTH level, may be associated with not only TLR, but also long-term death. High iPTH level is associated with accelerated intracoronary calcification, resulting in inadequate stent expansion after PCI. Furthermore, patients with high iPTH level have increased risk of MACCE, death, and TLR. The serum iPTH level can be a surrogate marker of short- and long-term clinical outcomes of dialysis patients with CAD undergoing PCI. The strict management of secondary hyperparathyroidism, including phosphate binders, vitamin D derivatives, calcimimetics, and parathyroidectomy, may be necessary to improve prognosis in dialysis patients with CAD requiring PCI.

Study Limitations

First, the number of patients was relatively small. Second, of 176 patients on dialysis, 47 (27%) were excluded due to very severe calcification precluding IVUS assessment. Third, because of the inherent characteristics of IVUS, the degree of calcification in the target lesion calculated by IB-IVUS is a conceptual, semiquantitative value, and accurate quantitative evaluation cannot be performed by IB-IVUS. Fourth, IVUS could not be performed in patients with extremely severe intracoronary calcification because of inherent limitations in catheter-based intravascular imaging.

Conclusions

High iPTH level is likely to increase intracoronary calcification and cause inadequate stent expansion, which may be associated with increased risk of future revascularization and death in dialysis patients with CAD requiring PCI.

Acknowledgment

We thank Heidi N. Bonneau, RN, MS, CCA for her editorial review of the manuscript.

Disclosures

Y.K. is a member of Circulation Journal’s Editorial Team. This research received no payment/grant from any funding agency for manuscript preparation.

IRB Information

This study was approved by the Ethics Committee, Chiba University, Chiba, Japan (ID: 3964).

Data Availability

1. Will the individual deidentified participant data (including data dictionaries) be shared?

- Yes.

2. What data in particular will be shared?

- All of it.

3. Will any additional, related documents be available? If so, what is it? (e.g., study protocol, statistical analysis plan, etc.)

- No.

4. When will the data become available and for how long?

- Immediately following publication. No end date.

5. By what access criteria will the data be shared (including with whom)?

- The data that support the findings of this study are available from the corresponding author, [Hideki Kitahara], upon reasonable request.

6. For what types of analyses, and by what mechanism will the data be available?

- The data can be applied to any kind of analysis. The data will be shared as Excel or csv files via E-mail.

References

• 1.   Cheung AK, Sarnak NF, Yan G. Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int 2000; 58: 353–362.
• 2.   Parfrey PS, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol 1999; 10: 1606–1615.
• 3.   Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Lmbers HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention. Lancet 2013; 382: 339–352.
• 4.   Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C. Chronic kidney disease and the risk of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–1305.
• 5.   Sugiyama T, Kimura S, Ohtani H, Yamakami Y, Kojima K, Sagawa Y, et al. Impact of chronic kidney disease stages on atherosclerotic plaque components on optical coherence tomography in patients with coronary artery disease. Cardiovasc Interv Ther 2017; 32: 216–224.
• 6.   Hernandes FR, Barreto FC, Rocha LA, Draibe SA, Canziani MEF, Carvalho AB. Evaluation of the role of severe hyperparathyroidism on coronary artery calcification in dialysis patients. Clin Nephrol 2007; 67: 89–95.
• 7.   Coen G, Manni M, Mantella D, Pierantozzi A, Balducci A, Condò S, et al. Are PTH serum levels predictive of coronary calcifications in haemodialysis patients? Nephrol Dial Transplant 2007; 22: 3262–3267.
• 8.   Kälsch H, Lehmann N, Berg MH, Mahabadi AA, Mergen P, Möhlenkamp S, et al. Coronary artery calcification outperforms thoracic aortic calcification for the prediction of myocardial infarction and all-cause mortality: The Heinz Nixdorf Recall Study. Eur J Prev Cardiol 2014; 21: 1163–1170.
• 9.   Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: The Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008; 52: 519–530.
• 10.   Sugawara Y, Ueda T, Soeda T, Watanabe M, Okura H, Saito Y. Plaque modification of severely calcified coronary lesions by scoring balloon angioplasty using Lacrosse non-slip element: Insights from an optical coherence tomography evaluation. Cardiovasc Interv Ther 2019; 34: 242–248.
• 11.   Aoki J, Nakazawa G, Ando K, Nakamura S, Tobaru T, Sakurada M, et al; ELEGANT investigators. Impact of hemodialysis on clinical and angiographic outcomes in in-stent restenotic lesions following optical coherence tomography-guided drug-coated balloon treatment. Cardiovasc Interv Ther 2021; 36: 429–435.
• 12.   Sharma SK, Vengrenyuk Y, Kini AS. IVUS, OCT, and coronary artery calcification: Is there a bone of contention? JACC Cardiovasc Imaging 2017; 10: 880–882.
• 13.   Mintz CS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, et al. American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS): A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2001; 37: 1478–1492.
• 14.   Saito Y, Kobayashi Y, Fujii K, Sonoda S, Tsujita K, Hibi K, et al. Clinical expert consensus document on standards for measurements and assessment of intravascular ultrasound from the Japanese Association of Cardiovascular Intervention and Therapeutics. Cardiovasc Interv Ther 2020; 35: 1–12.
• 15.   Bundy JD, Cai X, Scialla JJ, Dobre MA, Chen J, Hsu C, et al. Serum calcification propensity and coronary artery calcification among patients with CKD: The CRIC (Chronic Renal Insufficiency Cohort) Study. Am J Kidney Dis 2019; 73: 806–814.
• 16.   Kitahara S, Kataoka Y, Sugane H, Otuka F, Asaumi Y, Noguchi T, et al. In vivo imaging of vulnerable plaque with intravascular modalities: Its advantages and limitations. Cardiovasc Diagn Ther 2020; 10: 1461–1479.
• 17.   Amano H, Ikeda T, Toda M, Okubo R, Yabe T, Koike M, et al. Assessment of angiographic coronary calcification and plaque composition in virtual histology intravascular ultrasound. J interv Cardiol 2015; 28: 205–214.
• 18.   Andrews J, Psaltis PJ, Di Bartolo BA, Nicholls SJ, Puri R. Coronary arterial calcification: A review of mechanisms, promoters and imaging. Trends Cardiovasc Med 2018; 28: 491–501.
• 19.   Kawasaki M, Takatsu H, Noda T, Sano K, Ito Y, Hayakawa K, et al. In vivo quantitative tissue characterization of human coronary arterial plaques by use of integrated backscatter intravascular ultrasound and comparison with angioscopic findings. Circulation 2002; 21: 2487–2492.
• 20.   Okubo M, Kawasaki M, Ishihara Y, Takeyama U, Kubota T, Yamaki T, et al. Development of integrated backscatter intravascular ultrasound for tissue characterization of coronary plaques. Ultrasound Med Biol 2008; 34: 655–663.
• 21.   Fujimura T, Matsumura M, Witzenbichler B, Metzger DC, Rinaldi MJ, Duffy PL. Stent expansion indexes to predict clinical outcomes: An IVUS substudy from ADAPT-DES. JACC Cardiovasc Interv 2021; 14: 1639–1650.
• 22.   Nakamura D, Wijns W, Price MJ, Jones MR, Barbato E, Akasaka T. New volumetric analysis method for stent expansion and its correlation with final fractional flow reserve and clinical outcome: An ILUMIEN I substudy. JACC Cardiovasc Interv 2018; 11: 1467–1478.
• 23.   Stary HC. Natural history of calcium deposits in atherosclerosis progression and regression. Z Kardiol 2000; 89: 28–35.
• 24.   Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Chuang YC, et al. Patterns of calcification in coronary artery disease: A statistical analysis of intravascular ultrasound and coronary angiography in 1155 lesions. Circulation 1995; 1: 1959–1965.
• 25.   Abedin M, Titut Y, Demer LL. Vascular calcification: Mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol 2004; 24: 1161–1170.
• 26.   London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: Impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18: 1731–1740.
• 27.   Shroff RC, McNair R, Figg N, Skepper JN, Schurgers L, Gupta A, et al. Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation 2008; 118: 1748–1757.
• 28.   Nakano T, Ninomiya T, Sumiyoshi S, Fujii H, Doi Y, Hirakata H, et al. Association of kidney function with coronary atherosclerosis and calcification in autopsy samples from Japanese elders: The Hisayama study. Am J Kidney Dis 2010; 55: 21–30.
• 29.   Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–1305.
• 30.   Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: The Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008; 52: 519–530.