Robert L. Nolan

Prevalence and Associations of Coronary Artery Calcification in Patients With Stages 3 to 5 CKD Without Cardiovascular Disease

BACKGROUND Patients with chronic kidney disease (CKD) have a high prevalence of coronary artery calcification, suggesting that CKD itself is a risk factor for its occurrence. Existing studies are confounded by the inclusion of patients who may not have CKD by means of diagnostic criteria and by failing to account for existing cardiovascular disease. STUDY DESIGN Cross-sectional study. PARTICIPANTS & SETTING 119 patients with CKD stages 3 to 5 (excluding dialysis) without known cardiovascular disease receiving care at a single center in Kingston, Ontario, Canada. PREDICTORS Glomerular filtration rate was estimated (eGFR) by using the 4-variable Modification of Diet in Renal Disease Study equation. Traditional and nontraditional coronary artery calcification risk factors were defined a priori. OUTCOMES Coronary artery calcification was measured by means of multislice computed tomographic scan. RESULTS Mean and median coronary artery calcification scores were 566.5 +/- 1,108 and 111 (interquartile range, 2 to 631.5), respectively. A total of 32.8% of patients showed little calcification (score, 0 to 10). Calcification correlated with age (r = 0.44; P < 0.001), body mass index (r = 0.28; P = 0.002), high-density lipoprotein cholesterol level (r = -0.23; P = 0.01), diabetes mellitus (r = 0.23; P = 0.01), and cardiovascular risk score (r = 0.35; P < 0.001). By means of multivariable linear regression controlling for eGFR and diabetes mellitus, age (beta = 0.05; 95% confidence interval, 0.03 to 0.06; P < 0.001), body mass index (beta = 0.04; 95% confidence interval, 0.02 to 0.07; P = 0.001), and serum calcium level (beta = 0.9; 95% confidence interval, 0.15 to 1.6; P = 0.02), were risk factors for coronary artery calcification. LIMITATIONS Inadequate sample size and uncontrolled confounding are possible limitations, but are unlikely to have changed the main study findings. CONCLUSIONS In this study, traditional cardiovascular disease risk factors and serum calcium level were associated with coronary artery calcification. No association was shown with eGFR. Studies exploring protective mechanisms against coronary artery calcification are needed.

Associations of epicardial fat with coronary calcification, insulin resistance, inflammation, and fibroblast growth factor-23 in stage 3-5 chronic kidney disease.

BackgroundEpicardial fat, quantified in a single multi-slice computed tomography (MSCT) slice, is a reliable estimate of total epicardial fat volume (EFV). We sought to determine risk factors for EFV detected in a single-slice MSCT measurement (ssEFV) in pre-dialysis chronic kidney disease (CKD) patients. Our primary objective was to determine the association between ssEFV and coronary artery calcification (CAC).Methods94 pre-dialysis stage 3–5 CKD patients underwent MSCT to measure ssEFV and CAC. ssEFV was quantified at the level of the left main coronary artery. Measures of inflammation, traditional and kidney-related cardiovascular disease risk factors were collected.ResultsMean age: 63.7 ± 14 years, 56% male, 39% had diabetes, and mean eGFR: 25.1 ± 11.9 mL/min/1.73 m2. Mean ssEFV was 5.03 ± 2.4 cm3. By univariate analysis, body mass index (BMI) (r = 0.53; P = <0.0001), abdominal obesity (r = 0.51; P < 0.0001), high density lipoprotein (HDL) cholesterol (r = − 0.39; P = <0.0001), insulin resistance (log homeostasis model assessment of insulin resistance (log HOMA-IR)) (r = 0.38, P = 0.001), log interleukin-6 (IL-6) (r = 0.34; P = 0.001), and log urinary albumin to creatinine ratio (UACR) (r = 0.30, P = 0.004) demonstrated the strongest associations with ssEFV. Log coronary artery calcification (log CAC score) (r = 0.28, P = 0.006), and log fibroblast growth factor-23 (log FGF-23) (r = 0.23, P = 0.03) were also correlated with ssEFV. By linear regression, log CAC score (beta =0.40; 95% confidence interval (CI), 0.01-0.80; P = 0.045), increasing levels of IL-6 (beta = 0.99; 95% CI, 0.38 – 1.61; P = 0.002), abdominal obesity (beta = 1.86; 95% CI, 0.94 - 2.8; P < 0.0001), lower HDL cholesterol (beta = −2.30; 95% CI, – 3.68 to −0.83; P = 0.002) and albuminuria (log UACR, beta = 0.81; 95% CI, 0.2 to 1.4; P = 0.01) were risk factors for increased ssEFV.ConclusionsIn stage 3–5 CKD, coronary calcification and IL-6 and were predictors of ssEFV. Further studies are needed to clarify the mechanism by which epicardial fat may contribute to the pathogenesis of coronary disease, particularly in the CKD population.

Evaluation of the Bullard, GlideScope, Viewmax, and Macintosh laryngoscopes using a cadaver model to simulate the difficult airway

STUDY OBJECTIVE To assess the performance and cervical (C)-spine movement associated with laryngoscopy using the Bullard laryngoscope (BL), GlideScope videolaryngoscope (GVL), Viewmax, and Macintosh laryngoscopes during conditions of a) unrestricted and b) restricted C-spine and temporomandibular joint (TMJ) mobility. DESIGN Prospective, controlled, randomized, crossover study. SETTING University teaching hospital. SUBJECTS 21 cadavers with intact C-spine anatomy. INTERVENTIONS Each cadaver underwent to total of 8 intubation attempts to complete the intubation protocol using all four devices under unrestricted and restricted C-spine and TMJ mobility. MEASUREMENTS Laryngoscopic view was graded using the modified Cormack-Lehane system. Time to best laryngoscopic view and total time to intubation were recorded. C-spine movement was measured between McGregors line and each vertebra from radiographs taken at baseline and at best laryngoscopic view. MAIN RESULTS During both intubating conditions, the BL achieved the highest number of modified Cormack-Lehane grade 1 and 2A laryngoscopic views as compared to the other three devices (P < 0.05) and had fewer intubation failures than the Viewmax or Macintosh laryngoscopes (P < 0.05). The GVL had superior laryngoscopic performance as compared to the Viewmax and Macintosh laryngoscopes (P < 0.05) and had fewer intubation failures than those two devices (P < 0.05). All devices except the Macintosh laryngoscope in restricted mobility achieved median times to intubation in less than 30 seconds. For both conditions, BL showed the least total absolute movement between Occiput/C1 and C3/C4 of all the devices (all P < 0.05). Most of the difference was seen at C1/C2. CONCLUSIONS In cadavers with unrestricted and restricted C-spine mobility, the BL provided superior laryngoscopic views, comparable intubating times, and less C-spine movement than the GVL, Viewmax, or Macintosh laryngoscopes.

Primary cardiac diffuse large B cell lymphoma presenting with superior vena cava syndrome

Primary cardiac lymphomas are rare extranodal lymphomas that should be distinguished from secondary cardiac involvement by disseminated non-Hodgkins lymphoma. Cardiac lymphomas often mimic other cardiac neoplasms, including myxomas and angiosarcomas, and often require multimodality cardiac imaging, in combination with endomyocardial biopsy, excisional biopsy or pericardial fluid cytology, to establish a definitive diagnosis. A 60-year-old immunocompetent man who presented with superior vena cava syndrome secondary to a right atrial, primary cardiac diffuse large B cell lymphoma (non-Hodgkins lymphoma) is described in the present article. The patient had no clinical evidence of disseminated lymphoma and was successfully treated with prompt surgical excision of his atrial mass, followed by anthracycline-based chemotherapy. The patient required multi-modality cardiac imaging to accurately identify and plan surgical excision of his cardiac lymphoma. The therapeutic management and clinical and radio-logical features of primary cardiac lymphoma are reviewed.

Insulin resistance is associated with Fibroblast Growth Factor-23 in stage 3-5 chronic kidney disease patients☆ , ☆☆

AIM To determine the associations between insulin resistance, fibroblast growth factor 23 (FGF-23), and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. INTRODUCTION FGF-23 is associated with atherosclerosis and cardiovascular disease, but its association with insulin resistance in CKD has not been explored. SUBJECTS Cross sectional study of 72 stage 3-5 CKD patients receiving care in Ontario, Canada. MATERIALS AND METHODS Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR), FGF-23 was measured by carboxyl terminal enzyme linked immunoassay (ctFGF-23) and CAC was measured by multi-slice computed tomography. RESULTS Median HOMA-IR was 2.19μU/ml (interquartile range 1.19 to 3.94). Patients with HOMA-IR>2.2 had greater ctFGF-23 (179.7 vs 109.6; P=0.03), and 40% higher log CAC scores (2.09±0.87 vs 1.58±1.26; P=0.049). Multivariable linear regression adjusted for 1,25 dihydroxyvitamin D, kidney function, and parathyroid hormone revealed insulin resistance was a risk factor for greater log ctFGF-23 levels (log HOMA IR β=0.37; 95% confidence interval 0.14 to 0.59; P=0.002). CONCLUSIONS Insulin resistant CKD patients demonstrated higher FGF-23 levels, and increased CAC, while PO4 levels remained normal, suggesting a potential link between insulin resistance and PO4 homeostasis in CKD.

Percutaneous endourologic approach for transitional cell carcinoma of the renal pelvis.

A small mass was detected in the renal pelvis during investigation for hypertension and diminished renal function. Its presence was confirmed by computed tomography. Since the patient was not a candidate for nephrectomy, interventional percutaneous techniques were used to confirm the diagnosis of transitional cell carcinoma and ultimately permit endourologic access for resection and cure.

Catamenial Hemoptysis and Pneumothoraces in a Patient with Cystic Fibrosis

Hemoptysis or pneumothorax that recurs with the onset of menses is strongly suggestive of thoracic endometriosis syndrome (TES). TES is a rare disorder, with relatively few cases reported in the literature. A 32-year-old woman with cystic fibrosis, who over a period of several months had experienced recurrent catamenial hemoptysis and pneumothoraces, including an episode of life-threatening hemoptysis that coincided with menstruation, is presented. Thoracic computed tomography and magnetic resonance imaging scans, as well as a bronchoscopic evaluation that demonstrated endobronchial lesions that disappeared after menses, support the diagnosis of TES in the present patient. The patient was treated empirically with danazol and subsequently underwent a successful double-lung transplantation. Danazol was discontinued postoperatively, and she was started on an oral contraceptive. Eighteen months post-transplant, she has not experienced a recurrence of her catamenial symptoms, despite having resumed a regular menstrual cycle.

Superior approach for radiofrequency ablation of atrio-ventricular nodal reentrant tachycardia in a patient with anomalous inferior vena cava and azygos continuation.

We present a 45-year-old woman with supraventricular tachycardia. During placement of diagnostic catheters, an interruption of the inferior vena cava was suspected. An MRI confirmed the interruption of the inferior vena cava above the level of the renal veins with azygos vein continuation up to the superior vena cava. Catheter ablation was performed using a superior approach via the left subclavian vein.

Sequence Variation in Vitamin K Epoxide Reductase Gene Is Associated With Survival and Progressive Coronary Calcification in Chronic Kidney Disease

Objective—Sequence variations in the gene(s) encoding vitamin K epoxide reductase complex subunit 1 (VKORC1), the enzyme target of warfarin, have been associated with increased cardiovascular disease in the general population. Coronary artery calcification (CAC) is a prevalent form of cardiovascular disease in chronic kidney disease. We tested the hypothesis that the VKORC1 rs8050894 CC genotype would be associated with mortality and progression of CAC ⩽4 years. Approach and Results—This study is an observational, prospective study of 167 individuals with stages 3 to 5 chronic kidney disease. Survival ⩽4 years was assessed in all participants, and CAC progression was measured in a subset of 86 patients. Participants with the CG/GG genotype of VKORC1 had higher baseline CAC scores (median score, 112 versus 299; P=0.036). Of those 86 patients who had a 4-year CAC score, those with the CG/GG genotype had an increased risk of progressive CAC (adjusted for age, diabetes mellitus, estimated glomerular filtration rate, and hypertension) compared with those with the CC genotype. Four-year mortality risk was 4 times higher for individuals with the CG/GG genotypes compared with individuals with the CC genotype (odds ratio, 3.8; 95% confidence interval, 1.2–12.5; P=0.02), adjusted for age, sex, diabetes mellitus, estimated glomerular filtration rate, baseline CAC, and hypertension. Conclusions—Patients with the CG/GG genotype of VKORC1 had a higher risk of CAC progression and a poorer survival. These data provide new perspectives on the potential extrahepatic role of VKORC1 in individuals with chronic kidney disease.

Body Mass Index, Coronary Artery Calcification, and Kidney Function Decline in Stage 3 to 5 Chronic Kidney Disease Patients

OBJECTIVE To determine whether body mass index (BMI) and coronary artery calcification (CAC) are risk factors for kidney function decline in predialysis chronic kidney disease (CKD) patients. DESIGN Prospective cohort study of 125 stage 3 to 5 predialysis CKD patients. SUBJECTS AND SETTING CKD patients receiving care in Kingston, Ontario, Canada. METHODS BMI, CAC, and kidney function were measured at baseline. CAC was measured by multislice computed tomography scan. Kidney function was determined by the 4-variable reexpressed Modification of Diet in Renal Disease Study equation. At study end, kidney function decline among patients was compared according to baseline BMI and CAC. MAIN OUTCOME Kidney function decline was defined as a 1-year decline in estimated glomerular filtration rate (eGFR) of ≥ 5%. RESULTS Individuals with a decline in eGFR of ≥ 5% at 1 year had higher baseline BMI (33.5 ± 8.3 vs. 28.4 ± 4.9 kg/m(2); P = .0001) and higher baseline median CAC scores (239 vs. 25 Agatston units; P = .01) compared with subjects without such a decline. BMI (r = 0.35; P < .0001) and logarithmically transformed CAC score (r = 0.22; P = .01) correlated with an eGFR decline of ≥ 5%. Both crude and adjusted logistic regression analyses showed escalating CAC (with CAC reported in quintiles and CAC score = 0 Agatston unit as the reference group) was associated with an increased risk of eGFR decline of ≥ 5%. CONCLUSIONS CAC and BMI were associated with kidney function decline over 1 year. The risk of kidney function decline was greater in those with increasing burden of CAC, which remained robust in the adjusted analysis accounting for the risk factors for CKD progression. Larger studies will be required for independent validation of the associations of BMI, CAC, and kidney function decline, and to investigate whether obesity and CAC treatment strategies are efficacious in attenuating kidney function decline in predialysis CKD patients.