1. Baseline characteristics
A total of 2,786 patients were enrolled; 555 patients (20.0%) were defined as the AS group and 2,231 (80.0%) were defined as the non-AS group. Among the patients in the AS group, 193 patients (6.9%) were classified into the severe AS group. Table 1 shows the baseline characteristics of the patients. The median ages of the AS, severe AS, and non-AS groups were 75, 77, and 68 years, respectively. The median hemodialysis duration of the AS, severe AS, and non-AS groups were 8.0, 7.4, and 6.2 years, respectively. The prevalence rates of diabetes mellitus in the AS, severe AS, and non-AS groups were 36.0%, 39.9%, and 46.0%, respectively. There was no significant difference in the average serum phosphorus and serum-corrected calcium levels among the three groups. For the TTE results, the aortic valve calcification rates in the AS and severe AS groups were 80.7% and 83.8%, respectively, which were higher than the 53.3% in the non-AS group.
Table 1
Baseline characteristics of the non-AS, AS, and severe AS groups
| Non-AS Group | AS Group | p value | Severe AS Group | p value |
| | | (vs Non-AS) | | (vs Non-AS) |
Basic Characteristics | | | | | |
Male, % | 67.0 | 63.6 | 0.13 | 59.6 | 0.04 |
Age, years | 68 (59-75) | 75 (68-82) | <0.001 | 77 (70-83) | <0.001 |
Dialysis duration, years | 6.2 (3.1-12.4) | 8.0 (3.8-15.1) | <0.001 | 7.4 (4.0-14.8) | 0.005 |
Primary Disease | | | | | |
Nephrosclerosis, % | 11.9 | 17.3 | 0.001 | 16.6 | 0.07 |
Diabetic nephropathy, % | 39.8 | 29.5 | <0.001 | 31.6 | 0.03 |
Chronic glomerulonephritis, % | 19.5 | 23.8 | 0.03 | 23.8 | 0.16 |
Comorbidity | | | | | |
Diabetes mellitus, % | 46.0 | 36.0 | <0.001 | 39.9 | 0.11 |
Admission due to HF < 1 year, % | 2.0 | 5.2 | <0.001 | 8.3 | <0.001 |
Percutaneous coronary intervention, % | 10.8 | 15.5 | 0.003 | 16.1 | 0.03 |
Coronary artery bypass grafting, % | 4.7 | 6.7 | 0.07 | 9.3 | 0.01 |
Aortic disease, % | 4.8 | 10.8 | <0.001 | 14.0 | <0.001 |
Usage rate of medicine related to MBD | | | | | |
Vitamin D receptor activators, % | 81.3 | 79.6 | 0.40 | 78.2 | 0.29 |
Calcimimetics, % | 34.9 | 35.5 | 0.80 | 38.3 | 0.35 |
Phosphate binders, % | 84.7 | 78.6 | <0.001 | 77.2 | 0.01 |
Blood Test | | | | | |
Corrected Calcium, mg/dl | 9.1±0.6 | 9.1±0.6 | 0.16 | 9.1±0.7 | 0.55 |
Phosphorus, mg/dl | 5.3±1.3 | 5.2±1.2 | 0.76 | 5.2±1.2 | 0.59 |
Intact PTH, pg/ml | 132 (80-193) | 122 (76-185) | 0.05 | 118 (76-162) | 0.04 |
Albumin, g/dl | 3.6±0.4 | 3.5±0.4 | <0.001 | 3.4±0.37 | <0.001 |
C-reactive protein, mg/dl | 0.12 (0.05-0.37) | 0.12 (0.06-0.43) | 0.15 | 0.11 (0.06-0.55) | 0.15 |
Hemoglobin, g/dl | 11.1±1.1 | 10.9±1.2 | <0.001 | 10.8±1.1 | 0.002 |
Chest X-ray | | | | | |
Cardiothoracic ratio, % | 50.2±5.1 | 52.2±5.0 | <0.001 | 53.0±5.0 | <0.001 |
Aortic calcification, % | 57.0 | 70.4 | <0.001 | 73.3 | <0.001 |
Electrocardiogram | | | | | |
Atrial fibrillation, % | 5.7 | 9.6 | 0.002 | 12.0 | 0.002 |
Heart rate, /min | 74±13 | 74±13 | 0.91 | 75±13 | 0.63 |
Transthoracic Echocardiography | | | | | |
Left atrial diameter, mm | 36.6±6.5 | 38.5±6.4 | <0.001 | 39.1±5.9 | <0.001 |
LVDd, mm | 46.9±6.8 | 46.9±6.1 | 0.63 | 46.2±6.4 | 0.26 |
LVDs, mm | 30.6±6.4 | 30.5±6.0 | 0.96 | 30.1±6.6 | 0.17 |
Left ventricular ejection fraction, % | 63.4±9.7 | 63.5±10.0 | 0.52 | 63.5±11.3 | 0.37 |
Aortic valve calcification, % | 53.3 | 80.7 | <0.001 | 83.8 | <0.001 |
Mean pressure gradient, mmHg | 5.1±2.7 | 15.5±9.6 | <0.001 | 23.3±11.8 | <0.001 |
Aortic valve area, cm2 | 2.51±0.77 | 1.56±0.62 | <0.001 | 1.08±0.46 | <0.001 |
Velocity max, m/s | 1.43±0.28 | 2.52±0.62 | <0.001 | 2.96±0.87 | <0.001 |
Data are presented as the mean ± standard deviation or percentages. Age, dialysis duration, intact PTH, and C-reactive protein are expressed as the median (interquartile range). Abbreviations: Admission due to HF < 1 year, admission due to heart failure within 1 year before echocardiography; LVDd, left ventricular end-diastolic diameter; LVDs, left ventricular end-systolic diameter. |
2. Multivariate analysis for AS
We included the aforementioned 14 items, which we predicted to be related to AS, as the multivariable adjusted model’s factors. We performed a multivariate analysis comparing the AS and severe AS groups with the non-AS group (Table 2). In a comparison between the AS and non-AS groups, it was revealed that aging, long-term dialysis, and elevated serum phosphorus levels were associated with AS (multivariate-adjusted odds ratio [MOR], 1.93; 95% confidence interval [CI], 1.71–2.19; p < 0.001, MOR, 1.41; 95% CI, 1.21–1.64; p < 0.001, MOR, 1.16; 95% CI, 1.06–1.28; p = 0.001, respectively). Regarding these three factors, similar tendencies were observed for the severe AS group against the non-AS group (MOR, 2.51; 95% CI, 2.02–3.12; p < 0.001, MOR, 1.35; 95% CI, 1.06–1.71; p = 0.01, MOR, 1.24; 95% CI, 1.07–1.44; p = 0.005, respectively). On the other hand, nephrosclerosis as the cause of CKD was not associated with AS. Having diabetic mellitus had a significantly lower risk of AS in the AS group than the non-AS group (MOR, 0.74; 95% CI, 0.58–0.95; p = 0.02); however, no significant difference was found between the severe AS and non-AS group (MOR, 0.95; 95% CI 0.64–1.40, p = 0.79).
Table 2
Odds ratio for aortic valve stenosis by multivariate Cox regression
| AS group | Severe AS group |
| OR (95% CI) | p value | OR (95% CI) | p value |
Male | 1.02 (0.81-1.29) | 0.86 | 0.94 (0.65-1.37) | 0.75 |
Age (per 10 years) | 1.93 (1.71-2.19) | <0.001 | 2.51 (2.02-3.12) | <0.001 |
Dialysis duration (per 10 years) | 1.41 (1.21-1.64) | <0.001 | 1.35 (1.06-1.71) | 0.01 |
Nephrosclerosis as the primary disease of CKD | 0.94 (0.67-1.32) | 0.72 | 0.88 (0.52-1.50) | 0.65 |
Diabetes complications | 0.74 (0.58-0.95) | 0.02 | 0.95 (0.64-1.40) | 0.79 |
Use of calcimimetics | 1.16 (0.91-1.48) | 0.24 | 1.59 (1.07-2.34) | 0.02 |
Use of VDRA | 0.94 (0.70-1.25) | 0.66 | 0.91 (0.58-1.44) | 0.69 |
Use of phosphate binders | 0.87 (0.65-1.17) | 0.35 | 0.86 (0.55-1.35) | 0.52 |
Corrected Calcium (per 1 mg/dl) | 1.27 (1.04-1.54) | 0.02 | 1.17 (0.86-1.59) | 0.31 |
Phosphorus (per 1 mg/dl) | 1.16 (1.06-1.28) | 0.001 | 1.24 (1.07-1.44) | 0.005 |
Intact PTH (per 10 pg/ml) | 1.00 (0.99-1.01) | 0.41 | 1.00 (0.98-1.02) | 0.91 |
Albumin (per 1 g/dl) | 1.51 (1.05-2.17) | 0.03 | 1.04 (0.58-1.84) | 0.91 |
C-reactive protein (per 1 mg/dl) | 0.98 (0.89-1.08) | 0.67 | 1.02 (0.91-1.14) | 0.77 |
Hemoglobin (per 1 g/dl) | 0.85 (0.76-0.95) | 0.003 | 0.86 (0.72-1.03) | 0.10 |
Analyses were performed using the multivariable adjusted model. Abbreviations: OR, odd ratio; CI, confidence interval, CKD, chronic kidney disease; VDRA, Vitamin D receptor activator. |
In addition, we divided the patients into two groups (with and without aortic valve calcification) and performed multivariate analysis (Table 3). The results showed that aortic valve calcification was associated with aging, long-term dialysis, diabetes mellitus, Vitamin D receptor activators (VDRA) administration, elevated serum calcium level, and anemia, but not with elevated serum phosphorus level.
Table 3
Odds ratio for aortic valve calcification by multivariable Cox regression
| Aortic valve calcification |
| OR (95% CI) | p value |
Male | 0.93 (0.75-1.16) | 0.53 |
Age (per 10 years) | 1.70 (1.54-1.88) | <0.001 |
Dialysis duration (per 10 years) | 1.42 (1.22-1.64) | <0.001 |
Nephrosclerosis as the primary disease of CKD | 0.88 (0.69-1.06) | 0.43 |
Diabetes comorbidity | 1.53 (1.23-1.90) | <0.001 |
Use of calcimimetics | 0.86 (0.69-1.06) | 0.16 |
Use of VDRA | 0.70 (0.54-0.91) | 0.007 |
Use of phosphate binders | 0.92 (0.69-1.23) | 0.57 |
Corrected Calcium (per 1 mg/dl) | 1.30 (1.09-1.54) | 0.004 |
Phosphorus (per 1 mg/dl) | 1.03 (0.95-1.12) | 0.46 |
Intact PTH (per 10 pg/ml) | 1.00 (0.99-1.01) | 0.56 |
Albumin (per 1 g/dl) | 1.19 (0.87-1.63) | 0.28 |
C-reactive protein (per 1 mg/dl) | 0.98 (0.90-1.07) | 0.65 |
Hemoglobin (per 1 g/dl) | 0.89 (0.81-0.98) | 0.02 |
3. Comparison of AS parameters with and without aortic valve calcification
The mean PG, AVA, and Vmax as measured using TTE were compared between the patients with and without aortic valve calcification (Table 4). The results significantly showed that those with aortic valve calcification had characteristics of AS in all parameters.
Table 4
Comparison of AS parameters with and without aortic valve calcification
| With aortic valve calcification | Without aortic valve calcification | p value |
Velocity max, m/s | 1.78±0.64 | 1.51±0.50 | <0.001 |
Mean pressure gradient, mmHg | 8.3±7.9 | 6.3±4.8 | <0.001 |
Aortic valve area, cm2 | 2.19±0.79 | 2.50±0.90 | <0.001 |
Analyses were performed using Mann-Whitney U test. |
4. Stratified multivariate analysis for AS
We determined the MOR for AS between the categories of age, duration of dialysis, and serum phosphorus level (Figures 2A, 2B, and 2C). The MOR in both the AS and the severe AS groups significantly increased with age. Regarding the duration of dialysis, the MOR in the AS group tended to increase as the duration of dialysis increased. It was found that in the severe AS group, the MOR of >15 years of dialysis was 1.86 fold greater (95% CI, 1.06–3.24; p = 0.03) compared to that of <5 years. Regarding the serum phosphorus level, the MOR tended to increase as the serum phosphorus level increased. The MORs of the categories of serum phosphorus levels of 5.0–5.9 and >6.0 mg/dL were 1.52 and 1.83 fold and 2.24 and 2.66 fold greater in the AS group and severe AS group, respectively, compared to that of a serum phosphorus level <4.0 mg/dL.