Jonaz Ripsweden

Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification

Sclerostin, an osteocyte-derived inhibitor of bone formation, is linked to mineral bone disorder. In order to validate its potential as a predictor of vascular calcification, we explored associations of circulating sclerostin with measures of calcification in 89 epigastric artery biopsies from patients with end-stage renal disease. Significantly higher sclerostin levels were found in the serum of patients with epigastric and coronary artery calcification (calcification score 100 or more). In Spearmans rank correlations, sclerostin levels significantly associated with age, intact parathyroid hormone, bone-specific alkaline phosphatase, and percent calcification. Multivariable regression showed that age, male gender, and sclerostin each significantly associated with the presence of medial vascular calcification. Receiver operating characteristic curve analysis showed that sclerostin (AUC 0.68) predicted vascular calcification. Vascular sclerostin mRNA and protein expressions were low or absent, and did not differ between calcified and non-calcified vessels, suggesting that the vasculature is not a major contributor to circulating levels. Thus, high serum sclerostin levels associate with the extent of vascular calcification as evaluated both by coronary artery CT and scoring of epigastric artery calcification. Among circulating biomarkers of mineral bone disorder, only sclerostin predicted vascular calcification.

Nonthyroidal illness: a risk factor for coronary calcification and arterial stiffness in patients undergoing peritoneal dialysis?

Low triiodothyronine levels, as part of the nonthyroidal illness syndrome, are common in dialysis patients and have repeatedly been shown to be associated with increased (cardiovascular) mortality rates. We hypothesized that increased vascular calcification may mediate this relationship.

Impact on image quality and radiation exposure in coronary CT angiography: 100 kVp versus 120 kVp

Background: The risk of radiation-induced cancer has become a major concern with the increasing use of computed tomography (CT). Purpose: To compare image quality and radiation doses when decreasing X-ray tube peak kilovoltage (kVp) from 120 to 100 kVp in patients undergoing coronary CT angiography (CCTA). Material and Methods: Patients referred for evaluation of suspected coronary artery disease (CAD) underwent 64-channel detector CCTA using a tube voltage of either 120 kVp (n = 46) or 100 kVp (n = 82). The individual volume CT dose index (CTDIvol) and dose length product (DLP) were recorded and effective radiation dose was estimated on the basis of DLP. Subjective image quality was assessed by two radiologists on per-patient based consensus. Vascular density and image noise were quantified in the left main coronary artery (LMCA) and proximal ascending aorta (AA). Mean density in the adjacent perivascular tissue was also quantified. Contrast-to-noise ratio (CNR) was calculated. Corresponding invasive coronary angiography (ICA) was performed, which constituted the gold standard. Results: Mean values in the 100/120 kVp cohorts regarding CNR in the LMCA were 12.7/16.0 (P<0.0001)) and in the AA 13.2/17.2 (P<0.0001), CTDIvol 34.4/57.4 mGy (a 40% reduction, P<0.0001), DLP 578/1125 mGy × cm (P<0.0001), and estimated effective dose 9.6/20.2 mSv (P<0.0001). There was no statistically significant difference in subjective image quality between the two cohorts. The sensitivity to detect significant coronary stenoses was 88% (120 kVp) and 84% (100 kVp) and the specificity was 71% (120 kVp) and 74% (100 kVp), respectively. Conclusion: By reduction of tube voltage from 120 to 100 kVp at CCTA, while keeping all other scanning parameters unchanged, the radiation dose to the patient can be almost halved while keeping the diagnostic image quality at a clinically acceptable level.

Heart rate variability and heat sensation during CT coronary angiography: Low-osmolar versus iso-osmolar contrast media

Background: During computed tomography coronary angiography (CTCA) unexpected changes in heart rate while scanning may affect image quality. Purpose: To evaluate whether an iso-osmolar contrast medium (IOCM, iodixanol) and a low-osmolar contrast medium (LOCM, iomeprol) affect heart rate and experienced heat sensation differently. Material and Methods: One hundred patients scheduled for CTCA were randomized to receive either iodixanol 320 mgI/ml or iomeprol 400 mgI/ml. Depending on their heart rate, the patients were assigned to one of five scanning protocols, each optimized for different heart rate ranges. During scanning the time between each heart beat (hb) was recorded, and the corresponding heart rate was calculated. For each contrast medium (CM) the average heart rate, the variation in heart rate from individual mean heart rate, and the mean deviation from the predefined scanning protocol were calculated. Experience of heat was obtained immediately after scanning by using a visual analog scale (VAS). Examination quality was rated by two radiologists on a three-point scale. Results: The mean variation in heart rate after IOCM was 1.4 hb/min and after LOCM it was 4.4 hb/min (NS). The mean deviations in heart rate from that in the predefined scanning protocol were 2.0 hb/min and 4.7 hb/min, respectively (NS). A greater number of arrhythmic hb were observed after LOCM compared with IOCM (P<0.001). There was no statistically significant difference in image quality. The LOCM group reported a stronger heat sensation after CM injection than the IOCM group (VAS =36 mm and 18 mm, P<0.05). Conclusion: At clinically used concentrations the IOCM, iodixanol 320 mgI/ml, does not increase the heart rate during CTCA and causes less heart arrhythmia and less heat sensation than the LOCM, iomeprol 400 mgI/ml.

Does statins promote vascular calcification in chronic kidney disease

In end‐stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD.

Coronary Plaque Burden, as Determined by Cardiac Computed Tomography, in Patients with Myocardial Infarction and Angiographically Normal Coronary Arteries Compared to Healthy Volunteers: A Prospective Multicenter Observational Study

Objectives Patients presenting with acute myocardial infarction and angiographically normal coronary arteries (MINCA) represent a diagnostic and a therapeutic challenge. Cardiac computed tomography (CT) allows detection of coronary artery disease (CAD) even in the absence of significant stenosis. We aimed to investigate whether patients suffering from MINCA had a greater coronary plaque burden, as determined by cardiac CT, than a matched group of healthy volunteers. Methods Consecutive patients, aged 45 to 70, with MINCA were enrolled in the Stockholm metropolitan area. Patients with myocarditis were excluded using cardiovascular magnetic resonance imaging. Remaining patients underwent cardiac CT, as did a reference group of healthy volunteers matched by age and gender, with no known cardiovascular disease. Plaque burden was evaluated semi-quantitatively on a per patient and a per segment level. Results Despite a higher prevalence of smoking and hypertension, patients with MINCA did not have more CAD than healthy volunteers. Among 57 MINCA patients and 58 volunteers no signs of CAD were found in 24 (42%) and 25 (43%) respectively. On a per segment level, MINCA patients had less segments with stenosis ≥20% (2% vs. 5%, p<0.01), as well as a smaller proportion of large (2% vs. 4%, p<0.05) and mixed type plaques (1% vs. 4%, p<0.01). The median coronary calcium score did not differ between MINCA patients and healthy volunteers (6 vs. 8, ns). Conclusions MINCA patients with no or minimal angiographic stenosis do not have more coronary atherosclerosis than healthy volunteers, and a large proportion of these patients do not have any signs of CAD, as determined by cardiac CT. The MINCA patient group is probably heterogeneous, with a variety of different underlying mechanisms. Non-obstructive CAD is most likely not the most prevalent cause of myocardial infarction in this patient group.

Vertebral bone density associates with coronary artery calcification and is an independent predictor of poor outcome in end-stage renal disease patients

OBJECTIVE Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major complication of end-stage renal disease (ESRD). Reduced bone mineral density (BMD) is associated with vascular calcification. Here we investigated associations between vertebral bone density (VBD) and coronary artery calcification (CAC), quantified by cardiac computed tomography (CT), and BMD quantified by dual-energy X-ray absorptiometry (DXA), and their relations with mortality. METHODS In 231 ESRD patients (median age 56years, 63% males) comprising incident dialysis patients, prevalent peritoneal dialysis patients and recipients of living donor kidney transplant, VBD (Hounsfield units, HUs) and CAC scores (Agatston units, AUs) were quantified by cardiac CT, and, in 143 of the patients, BMD was measured by DXA of total body. Metabolic and inflammation biomarkers potentially linked to CKD-MBD were also analysed. RESULTS Patients with low tertile of VBD were older and had more often cardiovascular disease (CVD), and higher HbA1c (non-diabetics), interleukin-6 and CAC score. Low VBD was independently associated with higher CAC score (>100 AUs) after adjustment for age, gender, diabetes, CVD, inflammation and cohorts. In Cox proportional hazards analysis, low VBD was independently associated with all-cause mortality after adjustment for age, gender, diabetes, CVD, inflammation and subjective global assessment (SGA). The root mean-squared error of prediction (RMSE) showed a good degree of association between VBD and BMD evaluated from DXA. In receiver-operator characteristics curve (ROC) analysis, lower VBD was more strongly associated with higher CAC score and all-cause mortality than BMD evaluated from DXA. CONCLUSIONS While assessments of BMD by DXA and CT showed good degree of agreement, associations of high CAC, and mortality, with low VBD were stronger than those based on low BMD by DXA. The strong independent associations of low VBD with high CAC score and increased mortality risk suggest that VBD may serve as an important prognosticator in ESRD patients.

Associations between Thyroid Hormones, Calcification Inhibitor Levels and Vascular Calcification in End-Stage Renal Disease

Introduction Vascular calcification is a common, serious and elusive complication of end-stage renal disease (ESRD). As a pro-calcifying risk factor, non-thyroidal illness may promote vascular calcification through a systemic lowering of vascular calcification inhibitors such as matrix-gla protein (MGP) and Klotho. Methods and Material In 97 ESRD patients eligible for living donor kidney transplantation, blood levels of thyroid hormones (fT3, fT4 and TSH), total uncarboxylated MGP (t-ucMGP), desphospho-uncarboxylated MGP (dp-ucMGP), descarboxyprothrombin (PIVKA-II), and soluble Klotho (sKlotho) were measured. The degree of coronary calcification and arterial stiffness were assessed by means of cardiac CT-scans and applanation tonometry, respectively. Results fT3 levels were inversely associated with coronary artery calcification (CAC) scores and measures of arterial stiffness, and positively with dp-ucMGP and sKlotho concentrations. Subfractions of MGP, PIVKA-II and sKlotho did not associate with CAC scores and arterial stiffness. fT4 and TSH levels were both inversely associated with CAC scores, but not with arterial stiffness. Discussion The positive associations between fT3 and dp-ucMGP and sKlotho suggest that synthesis of MGP and Klotho is influenced by thyroid hormones, and supports a link between non-thyroidal illness and alterations in calcification inhibitor levels. However, the absence of an association between serum calcification inhibitor levels and coronary calcification/arterial stiffness and the fact that MGP and Klotho undergo post-translational modifications underscore the complexity of this association. Further studies, measuring total levels of MGP and membrane bound Klotho, should examine this proposed pathway in further detail.

Is training essential for interpreting cardiac computed tomography

Background: Cardiac computed tomography (CT) has gained increasing acceptance for diagnosing obstructive coronary artery disease (CAD). Several guidelines have been published on required education for proficiency in the interpretation of these examinations. Purpose: To describe the learning-curve effect of the interpretation of 100 consecutive cardiac CT examinations aimed at diagnosing CAD. The diagnostic accuracy of radiologists and radiographers was also compared. Material and Methods: Two radiologists and two radiographers, all with no prior experience in evaluation of cardiac CT, independently underwent a dedicated training program of 100 examinations randomized into 10 blocks (sessions), with 10 cases in each. They independently evaluated the coronary arteries regarding significant obstructive CAD. After every session, individual feedback on diagnostic accuracy and comparison with the corresponding invasive coronary angiography (currently regarded as the gold standard to detect coronary lesions) was given. The time required for interpretation was recorded. Results: The mean review time decreased (P<0.0001) successively during the 10 sessions for all the observers together. The first session had a mean review time of 32 min, and the last session 16 min. No significant improvement in sensitivity, specificity, or negative predictive value (NPV) was observed. For positive predictive value (PPV), there was an improvement for the radiologists (P<0.05), but not for the radiographers. The radiographers had a higher total specificity compared to the radiologists (P<0.01). Conclusion: The review time for novices in cardiac CT was approximately halved during the first 100 cases, with maintained accuracy. There was a learning-curve effect in PPV for the radiologists. The diagnostic accuracy of dedicated radiographers indicates that they might be considered to be included as part of the evaluation team.

Assessment of left ventricular volumes using simplified 3-D echocardiography and computed tomography - a phantom and clinical study.

ObjectivesTo compare the accuracy of simplified 3-dimensional (3-D) echocardiography vs. multi-slice computed tomography (MSCT) software for the quantification of left ventricular (LV) volumes.DesignThree-D echocardiography (3-planes approach) and MSCT-CardIQ software were calibrated by measuring known volumes of 10 phantoms designed to closely mimic blood-endocardium interface. Subsequently, LV volumes were measured with both the methods in 9 patients referred routinely for coronary angiography and the agreement between the measurements was evaluated.ResultsSimplified 3D-echocardiography provided higher degree of agreement between the measured and true phantom volumes (mean difference 0 ± 1 ml, variation range +4 to -4 ml) than MSCT software (mean difference 6 ± 5 ml; variation range +22 to -10 ml). The agreement between LV measurements in the patients was considerably poorer, with significantly larger volumes produced by MSCT (mean difference -23 ± 40 ml, variation between +93 and -138 ml).ConclusionSimplified 3-D echocardiography provides more accurate assessment of phantom volumes than MSCT-CardIQ software. The discrepancy between the results of LV measurements with the two methods is even greater and does not warrant their interchangeable diagnostic use.