Aortic calcification index predicts mortality and cardiovascular events in operatively treated patients with peripheral artery disease: A prospective PURE ASO cohort follow-up study.

OBJECTIVE: The present study evaluates the association of aortic calcification with mortality and major adverse cardiovascular and leg events (MACEs and MALEs) in patients with peripheral artery disease (PAD). The risk for mortality and MACEs and MALEs is considered in clinical decision-making. METHODS: This cohort found in 2012-2013 consists of 226 patients with symptomatic PAD referred to Turku University Hospital for invasive treatment. Follow-up data about mortality and survival without MACEs and MALEs were collected up to 5 years from the inclusion date, and aortic calcification index (ACI) was measured from patients with available imaging studies (164 of 226). ACIs' association with events and mortality was evaluated in Cox regression, Kaplan-Meier, and classification and regression tree analysis. RESULTS: All-cause mortality at 1, 3, and 5 years was 13.7% (31), 26.1% (59), and 46.9% (106), respectively. In multivariable Cox regression analysis, ACI and ACI > 43 were independent risk factors for all-cause mortality (hazard ratio [HR]: 1.13 per 10 units, 95% confidence interval [CI]: 1.00-1.22 and HR: 1.83, 95% CI: 1.01-3.32, respectively) and for MACEs (HR: 1.10 per 10 units, 95% CI: 1.00-1.22 and HR: 3.14, 95% CI: 1.67-5.91, respectively), but not for MALEs. Classification and regression tree analysis showed that ACI = 43 best divides cohort in relation to mortality. Kaplan-Meier analyses showed that ACI > 43 is associated with greater mortality and occurrence of MACEs compared with those who have ACI ≤ 43 (log-rank P value .005 and .0012, respectively). CONCLUSIONS: Risk for mortality and MACEs is associated with high ACI. ACI can expose the risk in patients with PAD for further cardiovascular events and mortality.

The combined prognostic significance of alkaline phosphatase and vascular calcification in patients with end-stage kidney disease.

BACKGROUND AND AIMS: Little is known about the interaction between serum alkaline phosphatase (ALP) and vascular calcification (VC) affecting cardiovascular events (CVE) and mortality in end-stage kidney disease (ESKD) patients. This study investigated the combined effect of ALP and VC on prognosis in ESKD patients starting dialysis. METHODS AND RESULTS: Data from 587 ESKD patients treated at a single center between January 2006 and July 2017 were retrospectively evaluated. VC was assessed by the aortic calcification index (ACI) using abdominal computed tomography. Patients were stratified into four groups according to the median ACI (17.18) and serum ALP value (108.0 U/L) as low ACI-low ALP, low ACI-high ALP, high ACI-low ALP, or high ACI-high ALP. The association between ALP and VC and the composite of CVE and death was analyzed. During a median follow-up of 3.1 years (range, 1.5-5.6 years), 140 patients (23.8%) developed CVE and 130 deaths (22.1%) occurred. In the stratified analysis, patients with high ACI-low ALP had a greater risk of the composite endpoint than patients with low ACI-low ALP (adjusted hazard ratio, 2.09; 95% confidence interval, 1.58-2.60; P = 0.004). Patients with high ACI-high ALP had the greatest risk (adjusted hazard ratio, 2.25; 95% confidence interval, 1.77-2.72; P = 0.001). The interaction between ACI and ALP on CVE and mortality was statistically significant (P < 0.05). CONCLUSIONS: The combined effect of VC and higher ALP was associated with a greater risk of CVE and death, and high serum ALP amplified the risk associated with VC in ESKD patients starting dialysis.

Predictive value of abdominal aortic calcification index for mid-term cardiovascular events in patients with acute coronary syndrome.

The utility of abdominal aortic calcification (AAC) for prediction of cardiovascular events (CVEs) in patients with acute coronary syndrome (ACS) remains to be determined. The aim of this prospective study was to determine the predictive value of the abdominal aortic calcification index (ACI), a semi-quantitative measure of AAC, for CVEs in patients with ACS. We evaluated 314 patients with ACS. All patients underwent successful percutaneous coronary intervention to the culprit coronary vessel without in-hospital adverse events. ACI was calculated on non-contrast computed tomography images. CVEs were defined as a composite of cardiovascular death, ACS recurrence, and stroke. During a median follow-up period of 19.1 months, CVEs occurred in 29 patients (9.2%). Multivariable regression analysis after adjustment for age and gender showed a significantly higher baseline ACI in patients with CVEs than in those without [median (interquartile ranges), 42.1 (25.9-60.2) vs. 20.8 (8.8-38.6) %; P = 0.021]. The cutoff value of ACI for prediction of CVEs, estimated by receiver-operating characteristic analysis, was 29.2%, with sensitivity of 76% and specificity of 64% (area under the curve, 0.69). After adjustment for conventional cardiovascular risk factors, Cox analysis showed high ACI (≥29.2%) to be significantly associated with increased risk of CVEs (P = 0.011; hazard ratio, 1.82). Multivariate analysis identified high ACI as an independent predictor of CVEs (P = 0.012; hazard ratio, 1.80). Stepwise forward selection procedure also showed that high ACI was a significant independent determinant of CVEs (P = 0.004; R2, 0.089). Both net reclassification improvement (0.64; P = 0.001) and integrated discrimination improvement (0.04; P < 0.001) improved significantly after the addition of high ACI to conventional risk factors. Evaluation of ACI using CT seems to provide valuable clinical information for proper assessment of mid-term CVEs in patients with ACS after percutaneous coronary intervention.

Radial augmentation index may be an effective predictor of vascular calcification in patients on peritoneal dialysis.

Vascular calcification (VC) is an important promoter of cardiovascular disease (CVD) in patients undergoing peritoneal dialysis (PD). Several indices can be used to evaluate VC, including the abdominal aortic calcification index (AACI) and carotid artery intima-media thickness (IMT); however, simpler and lesser expensive predictors, such as the radial augmentation index (RAI), should be investigated. A total of 101 patients undergoing PD were recruited to measure RAI, AACI, and carotid artery IMT and perform echocardiography. Fifty healthy controls (HCs) were recruited to undergo RAI measurement. RAI in patients undergoing PD was significantly higher than the RAI in HCs (86.25%±8.39% vs. 76.05%±9.81%, p < 0.05). Patients undergoing PD and who suffer with diabetic mellitus, hypertension, and CVD had more severe VC than those without the abovementioned diseases. In patients with PD, RAI was positively correlated with AACI (r = 0.671, p < 0.05) and carotid artery IMT (r = 0.596, p < 0.05). RAI was positively correlated with left ventricular end-diastolic dimensions (LVDd; r = 0.678, p < 0.05), left ventricular mass index (r = 0.595, p < 0.05), and negatively correlated with early-diastolic mitral inflow velocity/late-diastolic mitral inflow velocity (r = -0.342, p < 0.05) and left ventricular ejection fraction (r= -0.497, p < 0.05). Multiple linear regression analysis showed that RAI was associated with AACI, LVDd, age, and serum phosphate (p < 0.05). RAI might be an effective predictor of VC and cardiac structural/functional abnormalities in patients undergoing PD.

Relationship between abdominal aortic and coronary artery calcification as detected by computed tomography in chronic kidney disease patients.

The purpose of this study was to investigate the relationship between abdominal aortic calcification (AAC) and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. We evaluated 126 asymptomatic CKD patients (mean estimated glomerular filtration rate: 36.1 ± 14.1 mL/min/1.73 m(2), mean age 70.3 ± 10.1 years). A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) and CAC score, and this relationship was investigated. Among the subjects, AAC was present in 109 patients (86.5 %) as defined by ACI >0 and median ACI was 11.7 %. ACI increased in accordance with advances in CAC score grades (3.0, 5.2, 17.2, and 32.8 % for CAC score 0, 1-100, 101-400, and 401 or more, respectively, p < 0.001). Even after multivariate adjustment, ACI was independently associated with severe CAC score as defined by CAC score >400 [odds ratio 1.08, 95 % confidence interval (CI) 1.04-1.12, p < 0.001]. Receiver-operating curve analysis showed that the ACI optimal cut-off value predicting severe CAC score was 16.5 % (area under the curve = 0.79, 95 % CI 0.69-0.90, p < 0.001). The C statics for predicting CAC score was significantly increased by adding ACI values to the model including other risk factors (0.853 versus 0.737, p = 0.023). In conclusion, the ACI value of 16.5 % allows us to predict the presence of severe CAC in CKD patients, and that the addition of ACI to the model with traditional risk factors significantly improves the predictive ability of severe CAC score. These data reinforce the utility of ACI as a screening tool in clinical practice.

Vitamin K antagonists and cardiovascular calcification: A systematic review and meta-analysis.

Background: Many patients treated with Vitamin K antagonists (VKA) for anticoagulation have concomitant vascular or valvular calcification. This meta-analysis aimed to evaluate a hypothesis that vascular and valvular calcification is a side-effect of VKA treatment. Methods: We conducted a systematic literature search to identify studies that reported vascular or valvular calcification in patients treated with VKA. The associations between VKA use and calcification were analyzed with random-effects inverse variance models and reported as odds ratios (OR) and 95% confidence intervals (95% CI). In addition, univariate meta-regression analyses were utilized to identify any effect moderators. Results: Thirty-five studies were included (45,757 patients; 6,251 VKA users). The median follow-up was 2.3 years [interquartile range (IQR) of 1.2-4.0]; age 66.2 ± 3.6 years (mean ± SD); the majority of participants were males [77% (IQR: 72-95%)]. VKA use was associated with an increased OR for coronary artery calcification [1.21 (1.08, 1.36), p = 0.001], moderated by the duration of treatment [meta-regression coefficient B of 0.08 (0.03, 0.13), p = 0.0005]. Extra-coronary calcification affecting the aorta, carotid artery, breast artery, and arteries of lower extremities, was also increased in VKA treated patients [1.86 (1.43, 2.42), p < 0.00001] and moderated by the author-reported statistical adjustments of the effect estimates [B: -0.63 (-1.19, -0.08), p = 0.016]. The effect of VKA on the aortic valve calcification was significant [3.07 (1.90, 4.96), p < 0.00001]; however, these studies suffered from a high risk of publication bias. Conclusion: Vascular and valvular calcification are potential side effects of VKA. The clinical significance of these side effects on cardiovascular outcomes deserves further investigation.

HbA1c and Aortic Calcification Index as Noninvasive Predictors of Pre-Existing Histopathological Damages in Living Donor Kidney Transplantation.

We previously reported that allografts from living donors may have pre-existing histopathological damages, defined as the combination of interstitial fibrosis (ci), tubular atrophy (ct), and arteriolar hyalinosis (ah) scores of ≧1, according to the Banff classification. We examined preoperative characteristics to identify whether the degree of these damages was related to metabolic syndrome-related factors of donors. We conducted a single-center cross-sectional analysis including 183 living kidney donors. Donors were divided into two groups: chronic change (ci + ct ≧ 1 ∩ ah ≧ 1, n = 27) and control (n = 156). Preoperative characteristics, including age, sex, blood pressure, hemoglobin A1c (HbA1c), aortic calcification index (ACI), and psoas muscle index (PMI), were analyzed. Comparing the groups, the baseline estimated glomerular filtration rate was not significantly different; however, we observed a significant difference for ACI (p = 0.009). HbA1c (p = 0.016) and ACI (p = 0.006) were independent risk factors to predict pre-existing histopathological damages, whereas PMI was not. HbA1c correlated with ct scores (p = 0.035), and ACI correlated with ci (p = 0.005), ct (p = 0.021), and ah (p = 0.017). HbA1c and ACI may serve as preoperative markers for identifying pre-existing damages on the kidneys of living donors.

Impact of Renal Functional/Morphological Dynamics on the Calcification of Coronary and Abdominal Arteries in Patients with Chronic Kidney Disease.

AIM: Fast-progressing vascular calcification (VC) is accompanied by renal atrophy and functional deterioration along with atherosclerosis in patients with chronic kidney disease (CKD). However, the relationship between VC progression and renal functional and/or morphological changes remains unclear. METHODS: We included 70 asymptomatic patients with CKD without hemodialysis in our study. To identify temporal variations, the coronary artery calcification score (CACS), abdominal aortic calcification index (ACI), and renal parenchymal volume index (RPVI) were determined via spiral computed tomography scans taken during the study. We investigated significant factors related to annualized variations of CACS (ΔCACS/y) and ACI (ΔACI/y). RESULTS: During the follow-up period (4.6 years), median values of CACS [in Agatston units (AU)] and ACI increased from 40.2 to 113.3 AU (p=0.053) and from 13.2 to 21.7% (p=0.036), respectively. Multivariate analysis revealed that CACS at baseline (p＜0.001) and diabetes mellitus (DM) status (p=0.037) for ΔCACS/y and ACI at baseline (p=0.017) and hypertension (HT) status (p= 0.046) for ΔACI/y were significant independent predictors. Furthermore, annualized RPVI variation was significantly related to both ΔCACS/y and ΔACI/y (R=-0.565, p＜0.001, and R=-0.289, p=0.015, respectively). On the other hand, independent contributions of the estimated glomerular filtration rate (eGFR) and annualized eGFR variation to VC progression were not confirmed. CONCLUSION: The degree of VC at baseline, DM, HT, and changes in renal volume, but not eGFR, had a strong impact on VC progression in patients with CKD.

Predictors of abdominal aortic calcification progression in patients with chronic kidney disease without hemodialysis.

BACKGROUND AND AIMS: Abdominal aortic calcification (AAC) is an important predictor of cardiovascular mortality in patients with chronic kidney disease (CKD). However, little is known regarding AAC progression in these patients. This study aimed to identify risk factors associated with AAC progression in patients with CKD without hemodialysis. METHODS: We recruited 141 asymptomatic patients with CKD without hemodialysis [median estimated glomerular filtration rate (eGFR), 40.3 mL/min/1.73 m2] and evaluated the progression of the abdominal aortic calcification index (ACI) over 3 years. To identify risk factors contributing to the rate of ACI progression, the associations between baseline clinical characteristics and annual change in ACI for each CKD category were analyzed. The annual change of ACI (ΔACI/year) was calculated as follows: (second ACI - first ACI)/duration between the two evaluations. RESULTS: Median ΔACI/year values significantly increased in advanced CKD stages (0.73%, 0.87%, and 2.24%/year for CKD stages G1-2, G3, and G4-5, respectively; p for trend = 0.041). The only independent risk factor for AAC progression in mild to moderate CKD (G1-3, eGFR ≥ 30 mL/min/1.73 m2) was pulse pressure level (ß = 0.258, p = 0.012). In contrast, parathyroid hormone (PTH) level was significantly correlated with ΔACI/year (ß = 0.426, p = 0.007) among patients with advanced CKD (G4-5, eGFR < 30 mL/min/1.73 m2). CONCLUSIONS: This study suggests that the AAC progression rate was significantly accelerated in patients with advanced CKD. In addition, measuring PTH is useful to evaluate both bone turnover and AAC progression in patients with advanced CKD.

Impact of abdominal aortic calcification on long-term cardiovascular outcomes in patients with chronic kidney disease.

BACKGROUND: The presence of abdominal aortic calcification (AAC) can predict cardiovascular (CV) outcomes in hemodialysis patients. However, little is known about the predictive value of AAC for CV outcomes in chronic kidney disease (CKD) patients without hemodialysis. The aim of this study was to investigate the prevalence and the predictive value of AAC in asymptomatic CKD patients. METHODS: We prospectively evaluated 347 asymptomatic CKD patients without hemodialysis [median estimated glomerular filtration rate (eGFR): 43.2 mL/min/1.73 m(2)]. A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) as a semi-quantitative measure of AAC. The patients were divided into three groups according to the tertiles of ACI. RESULTS: Among the subjects, AAC was found (ACI > 0) in 296 patients (86.3%), and the median ACI was 11.4%. During the median follow-up of 41.5 months, a total of 33 CV events were observed. Patients with the highest tertile of ACI had the highest risk of CV outcomes compared with the other two groups (96.5%, 93.0%, and 74.3%, respectively; p < 0.001). The Cox proportional hazard models showed that ACI was an independent predictor of CV outcomes (hazard ratio 1.36, 95% confidence interval 1.17-1.60, p < 0.001). The C-index was also significantly increased by adding eGFR and ACI values to the model along with the other conventional risk factors (0.79 versus 0.66, p = 0.043). CONCLUSION: Evaluation of the AAC provides useful information for predicting adverse clinical outcomes among asymptomatic CKD patients without hemodialysis.