Looking for a good review of the Concept2 Rower Model D? Read this.
The Concept2 Rower: Model D is one of the best-selling machines in its category.
Why? It's suitable for all athletes, no matter how advanced their training levels are.
Some of the features include a backlit performance monitor full of excellent programs and games. There's also a system for tracking calories, distance, and pace. And that information can be transferred via USD to another device. There are also awesome wireless capabilities to monitor heart rate and even race a friend on a separate machine.
I don't know about you, but when I read about gamified fitness machines, I get excited. Maybe it's my competitive streak. I am an Aries, after all.
Performance Monitor: The Concept2 backlit screen includes workouts, games, and session results. You can transfer the data wirelessly to other devices.
Air Resistance: The airflow changes in response to the effort you exert. The more forcefully you row, the more difficult it becomes.
Ergonomic Handles: The rower handles are poised at 10-degrees to support a comfortable rowing position.
Adjustable Footrests: No matter your shoe size, you should be able to fit it into the footrest.
Optional Slide: If you still long for the sensation of going out on the water, you can attach slides to the machine with bungee cables. These slides can be used to connect more than one rower for team training.
Transport Wheels: You can move this rowing machine wherever you need to.
Easy Storage: You can separate this rower device into two pieces.
One of the main differences between the Concept2 Indoor Rower and other machines is the advanced PM5 monitor. The backlit screen provides visibility, while the adjustable arm allows you to position it wherever you like. To keep costs low, the adjustable arm on the Concept2 is plastic.
The Concept2 comes equipped with a flywheel and damper to allow you to control your resistance. The spiral damper allows you to control airflow to your preference. The design also minimizes noise during workouts. I know my husband would be thankful for that!
While the rower has a pretty big footprint, it's not terribly tall. The machine is only 14" above the ground, so you may even be able to keep it concealed behind the sofa when guests come over.
In the middle of the machine, there is a quick-release frame lock mechanism to separate the two parts. You can then use the wheels underneath to roll it into your closet. You might not have to do any heavy lifting to put it away.
The machine has a nickel-plated chain that requires oil to move smoothly. So, take special care with this.
Altogether, this rower machine does not require especially tedious assembly. It's even simpler than Ikea instructions. You just have to install the front legs with a total of eight screws. I have a feeling you can handle that, right?
Lastly, when you buy this rowing machine, you have an option of a Concept2 slide. This can add the floating water sensation some buyers are looking for, as well as allowing you to connect multiple machines for team training.
Has a sturdy frame, this rower easy to assemble. The seat is at the height of only 14-inches. The frame lock makes it easy to take the machine apart. The wheels make it easy to move and store.
Has a larger footprint than other Concept2 models.
This machine is one of the more affordable rowers on the market. No wonder it is one of the best-selling in the world.
Could you even ask for cooler features than the ones this machines already has? The PM5 monitor makes this a smart buy.
No lifetime warranty on this machine.
In this video, Caitlin Steel from CrossFit Hershey provides an excellent product overview of the Concept2 Model D Rower. Now you can see it in action!
Click here to see some of the top rowing machines suggested by Home Fitness Life.


*Retain all heightened abilities even in human form.
*Reacts positively AND negatively to emotions.
*Must shift into werewolf form every full moon and upon every extreme outburst of rage, anger, and the smell of blood (in large volumes).


TOM HUDDLESTONE was last night in talks with Fulham over a £5million deadline-day switch to Craven Cottage.
Fulham made the offer to Tottenham for the midfielder yesterday and manager Martin Jol is hoping to get the deal done by the transfer deadline tonight in order to include Huddlestone in the side for Saturday's visit of Manchester United.
Fulham have completed the signing on loan until the end of the season of AC Milan's 26-year-old Dutch midfielder Urby Emanuelson.


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IMR Press / RCM / Volume 23 / Issue 12 / DOI: 10.31083/j.rcm2312386
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Open Access Original Research
Divergent Occurrence of Carotid Intima-Media Thickness and Carotid Arteries Plaques in Stable Kidney Transplant Recipients
Aureliusz Kolonko1,*, Rafał Ficek1, Beata Styrc1, Michał Sobolewski1, Roksana Stankowska1, Jerzy Chudek2, Andrzej Więcek1
1 Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice, 40-027 Katowice, Poland
2 Department of Internal Medicine and Oncological Chemotherapy, Medical University of Silesia in Katowice, 40-027 Katowice, Poland
*Correspondence: uryniusz@wp.pl (Aureliusz Kolonko)
Academic Editor: Jerome L. Fleg
Rev. Cardiovasc. Med. 2022, 23(12), 386; https://doi.org/10.31083/j.rcm2312386
Submitted: 26 July 2022 | Revised: 19 September 2022 | Accepted: 20 September 2022 | Published: 28 November 2022
(This article belongs to the Special Issue Vascular Injury: Basic, Translational and Clinical Insights and Therapeutic Implications)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Brower Figures
Background: Carotid atherosclerosis is one of the main cerebrovascular complications in kidney transplant recipients (KTRs). We analyzed the relationships between carotid intima-media thickness (IMT) and the occurrence and characteristics of carotid plaques in a cohort of KTRs. Methods: In 500 KTRs (aged 49.9 ± 12.0 years), IMT was measured and carotid plaques were semi-qualitatively assessed. Concomitantly, biochemical and hormonal inflammatory, vascular and calcium-phosphate metabolism parameters were also assessed. Results: In 10.2% of patients, a side-to-side IMT difference >0.1 mm was observed, whereas 26.8% of patients with no plaques in one carotid artery had at least one contralateral calcified plaque. Multivariate logistic regression analysis revealed that age (rpartial = 0.409; p < 0.001), male sex (rpartial = 0.199; p < 0.001), and coronary artery disease (rpartial = 0.139; p < 0.01) independently increased IMT (R2 = 0.25). For the occurrence of calcified carotid plaques, age (rpartial = 0.544; p < 0.001), male gender (rpartial = 0.127; p < 0.05), and the duration of renal insufficiency prior to transplantation (rpartial = 0.235; p < 0.001) were confirmed as independent variables. Conclusions: Substantial side-to-side differences in IMT values and carotid plaques distribution are present in a large percentage of stable KTRs. In addition, there are different clinical risk factors profiles associated with IMT and the presence of calcified plaques. Vascular and calcium-phosphate metabolism biomarkers were not associated with any carotid atherosclerosis characteristics.
calcified plaques
Carotid atherosclerosis is one of the major cardiovascular (CV) risk factors for the occurrence of an ischemic stroke [1, 2]. Traditional risk factors associated with atherosclerosis are age, male gender, smoking, dyslipidemia, hypertension, and diabetes mellitus [3]. In addition, chronic kidney disease (CKD) has also been shown to be associated with greater carotid intima-media thickness (IMT) and the occurrence of symptomatic ischemic stroke [4, 5] as well as with increased carotid artery stiffness and the presence of calcified plaques [6]. As a consequence, CV mortality is the major cause of death in CKD patients [7]. After successful kidney transplantation, despite the reduction of some risk factors (left ventricular hypertrophy, hypertension), CV disease remains a leading cause of death despite a functioning graft [8].
Quantitative evaluation of atherosclerosis with B-mode ultrasound involves the measurement of carotid intima-media thickness (IMT) and the assessment of carotid plaques. Both these measurements are biologically distinct entities and represent different phenotypes of atherosclerosis [9]. IMT is mainly reflective of hypertensive medial hypertrophy and is only weakly associated with traditional coronary risk factors whereas plaques are more strongly associated with traditional risk factors [10]. In patients with end-stage renal disease, the adverse CV consequences of hyperphosphatemia are most likely mediated via its ability to enhance the development of vascular calcifications [11]. CKD also significantly affects plaque composition [12]. Moreover, in CKD patients the rate of atherosclerotic plaque formation is a strong, independent predictor of CV events [13].
In clinical practice, we observed a significant asymmetry of carotid plaques and a substantial discrepancy between IMT values and the plaque burden in some stable kidney transplant recipients (KTRs). In our previous investigations, several clinical measures and biochemical markers were assessed in three different KTRs cohorts [14, 15, 16]. Based on our prospective kidney transplant database, we retrospectively analyzed IMT and the presence of plaques as markers of carotid atherosclerosis, as well as numerous biochemical and hormonal parameters.
2.1 Study Participants
This study enrolled 500 KTRs who attended our out-patient clinic from 2013 to 2017, in whom carotid artery ultrasound with IMT measurement and carotid plaque assessment were performed. Those examinations were part of the protocols of our previous clinical studies [14, 15, 16], and were approved by the Bioethics Committee of the Medical University of Silesia. All participants gave their written informed consent. The study was conducted in accordance with the Declaration of Helsinki. In addition to data retrieved from the prospective transplant center patient registry, carotid ultrasound, including the assessment of IMT and carotid plaques were performed.
Patients were identified as active smokers, when they were currently smoking or they declared the period of non-smoking as being shorter than 5 years.
2.2 Clinical and Anthropometric Measurements
Body weight and height were measured following standard procedures, and BMI was calculated in kg/m2.
Office arterial blood pressure (OBP) was measured three times in the sitting position in the arm without vascular access during the physical examination. Patients whose OBP was equal or above 140/90 mmHg or those who received antihypertensive medication were diagnosed as hypertensives.
Diabetes was diagnosed in accordance with the American Diabetes Association criteria [17].
The duration of renal function insufficiency was estimated, based on the data collected at the time of kidney transplantation (the period of time since the first elevated serum creatinine concentration to the kidney transplantation procedure).
2.3 Laboratory Measurements
Routine laboratory measurements were performed in the hospital laboratory (Synchron Cx-9, Beckmann Coulter Inc., Fullerton, CA, US). Plasma high-sensitivity C-reactive protein (CRP) concentration was measured by nephelometry (Siemens Healthcare Diagnostics, Deerfield, IL, US) with a limit of quantification (LoQ) of 0.02 mg/L. Intact plasma parathormon (iPTH) concentration was measured using the immunoassay method (Abbott Diagnostics, Abbott Park, IL, US) with a LoQ <3 pg/mL, intra-assay variation <6/1% and inter-assay variation <6.4%, whereas plasma concentrations of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA (R&D System, Minnesota, MN, US) with a LoQ 0.7 pg/mL and 6.23 pg/mL, intra-assay variation <4.2% and 3.0%, and inter-assay variation <6.4% and 8.4%, respectively. Plasma concentrations of osteoprotegerin (OPG) were measured with the use of an immunoassay (Microvue Bone Health; Biovendor Laboratory Medicine, Modrice, Czech Republic) with a LoQ 0.03 pmol/L, intra-assay variation <3.5% and inter-assay variation <5.8%. Plasma concentrations of asymmetric dimethylarginine (ADMA) and oxidized LDL (ox-LDL) were measured using ELISA (Immundiagnostik, AG, Bensheim, Germany), with a LoQ of 0.16 μmol/L and 0.0205 U/mL, intra-assay variation <7.6% and <6.9% and inter-assay variation <4% and <14.4%, respectively. Plasma concentrations of endothelin-1 (ET-1) were measured using ELISA (USCN Life Sciences, Wuhan, People's Republic of China), with a LoQ of 2.71 pg/mL, intra-assay variation <10%, inter-assay variation <12%.
2.4 Carotid Sonography
Carotid ultrasound was performed using a Siemens machine (Sonoline Antares, Mountain View, CA, USA), equipped with a 4.0–9.0 MHz linear transducer. Carotid arteries were examined with the patient in the supine position with the neck extended. The evaluation included the common, internal, and external carotid arteries, and the carotid bifurcation on each side. The common carotid artery intima-media thickness (IMT) was measured manually within 2 cm proximal to the carotid bulb, omitting any visible plaques. At longitudinal scans, the distal lines representing lamina intima and media were sharply visualized and the electronic calipers were placed to perform the exact IMT measurement. The accuracy of the single measurement was 0.5 mm and 3 consecutive measurements were made on each side, then the results were averaged. The highest value on both sides values was reported as the maximal IMT value. At each location, the carotid bulb and preceding common carotid artery were carefully evaluated in terms of the presence of plaques, which was classified based on the simplified scale: 0—no lesions, 1—non-calcified lesions, 2—at least one calcified lesion, 3—few calcified lesions, 4—carotid bulb heavily covered by calcified lesions. A final plaque score was equal to the highest score from both sides. All carotid sonographic examinations were performed by single investigator (AK).
2.5 Data and Statistical Analysis
Post-transplant major adverse cardio- or cerebrovascular events (MACE) were defined as the incidence of myocardial infarct, stroke, or cardiac artery stenting/surgical revascularization.
Kidney graft function was measured by the estimated glomerular filtration rate (eGFR) calculated according to the Modification of Diet in Renal Disease (MDRD) formula.
Statistical analyses were performed using the STATISTICA 13.3 PL for Windows software package (Tibco Inc., Palo Alto, CA, USA) and MedCalc 18.6 (MedCalc Software, Ostend, Belgium). Values are presented as means and 95% confidence intervals or medians with Q1–Q3 values, as appropriate, or frequencies. Comparisons were performed between 2 groups based on the mean value of maximal carotid IMT and between 3 groups, defined by the presence and type of carotid plaques. Based on the presence and type of carotid artery plaques, all study participants were assigned to the subgroup 1 (no plaques), subgroup 2 (only non-calcified plaque/plaques) or subgroup 3 (one or more calcified plaque). For these comparisons, the Student t test and the analysis of variance test (for quantitative variables) or the χ2 test (for qualitative variables) were used accordingly. For variables with non-parametric distribution, the Mann-Whitney U test or the Kruskal-Wallis test was used. Receiver operator characteristics (ROC) analysis was applied to determine the cut-off values for age and the duration of renal insufficiency, associated with the presence of calcified carotid lesions. Calculation of correlations were done using the Spearman coefficient.
Multivariate backward regression analysis was performed for the variability of IMT value, including potential explanatory variables: age, sex, the presence of coronary artery disease, smoking status, hemoglobin level and the presence of calcified carotid plaques. Multivariate models included variables selected on the basis of group comparison and univariate logistic regression analyses. The stepwise selection method was used.
Multivariate backward regression analysis was also performed for the presence of calcified plaques as dependent variable, including potential explanatory variables: age, sex, BMI, the presence of hypertension, pulse pressure, IMT, coronary artery disease or MACE, smoking status, serum glucose or the presence of hyperuricemia. Another multivariate backward regression analysis was performed for the presence of calcified lesions in a subset of 319 and 146 patients, respectively, i.e., in a cohort of patients with available results of relevant biochemical markers, and included age, the number of antihypertensive drugs, CRP, OPG and sclerostin levels as potential independent variables. In all the statistical tests, the 'p' values below 0.05 were considered statistically significant.
3.1 Study Group
The study group consist of 500 stable KTRs, whose clinical characteristics are presented in Table 1. Mean age at the time of the study was 49.9 ± 12.0 years. Median time after kidney transplantation was 86 (Q1–Q3, 65–117) months. The causes of end-stage renal disease were: glomerulonephritis (48%), diabetes mellitus (13.6%), pyelonephritis (11.6%), autosomal dominant polycystic kidney disease (8.4%), hypertensive nephropathy (5.6%), other and unknown (12.8%). 97.4% of patients received their organ from a deceased donor. Most of the patients received immunosuppression therapy with cyclosporine A or tacrolimus, anti-metabolic drugs (mainly mycophenolate mofetil or mycophenolate acid), and steroids.
Clinical characteristics of study group.
Age at the time of the study [years] 49.9 (48.8–51.0)
Gender [M/F] 284/216
BMI [kg/m2] 26.3 (25.9–26.7)
Dialysis vintage [months]* 25.0 (14.0–42.0)
Time after transplantation [months]* 86.0 (65.0–117.0)
Retransplant [n (%)] 42 (8.4)
Hypertension [n (%)] 445 (89)
MAP [mmHg] 100.5 (99.5–101.4)
Pulse pressure [mmHg]* 50.0 (40–60)
Number of antihypertensive drugs [n]* 2 (1–3)
Structure of hypertensive treatment [n (%)]
ACE-I/ARB 143 (28.6)
Beta-blocker 348 (69.6)
Ca-blocker 207 (41.4)
Diuretics 142 (28.4)
Diabetes [n (%)] 137 (27.4)
Coronary artery disease [n (%)] 63 (12.6)
Previous MACE [n (%)] 54 (10.8)
Smoking status [%] 89 (17.8)
eGFR [mL/min/1.73 m2]* 49.4 (36.4–68.0)
Proteinuria ≥1 g/24 h [n (%)] 35 (7.0)
Glucose [mmol/L]* 5.0 (4.7–5.7)
Calcium [mmol/L]* 2.4 (2.3–2.5)
Phosphate [mmol/L]* 1.0 (0.9–1.2)
iPTH [pg/mL]* 107 (69–174)
Cholesterol [mmol/L] 5.3 (5.2–5.4)
Triglycerides [mmol/L]* 1.5 (1.0–2.1)
Hyperlipidemia [n (%)] 265 (53)
Hyperuricemia [n (%)] 286 (57.1)
Hemoglobin [g%] 13.5 (13.3–13.7)
Main medications [n (%)]
Statins/fibrates 135 (27)
Calcineurin inhibitors [CyA/Tc] 238 (48)/246 (49)
Glucocorticoids 305 (61)
Calcium carbonate 74 (14.8)
Vitamin D 94 (18.8)
Data presented as means and 95% Confidence Intervals or frequencies, except * medians and Q1–Q3 values. BMI, body mass index; MAP, mean arterial pressure; ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; MACE, major adverse cardio- and cerebrovascular event; eGFR, estimated glomerular filtration rate; iPTH, intact parathormon; CyA, cyclosporine A; Tc, tacrolimus.
3.2 Intima-Media Thickness
In the entire study group, the mean value of carotid IMT, measured with omitting the visible plaques, was 0.66 (95%: 0.64–0.67) mm, with a range 0.4–1.3 mm. The median IMT value was 0.6 (Q1–Q3: 0.6–0.7) mm. The maximum intrapatient IMT difference was 0.6 mm and was observed in 1 study participant. Generally, the degree of carotid atherosclerosis was similar in both arteries, but in 51 (10.2%) patients a the side-to-side IMT difference >0.1 mm was noted. Patients in this specific subgroup were older [55.6 (51.9–59.3) vs. 49.2 (48.1–50.4) years; p < 0.001] and were more frequently men (72.6 vs. 55.0%; p < 0.05); however, there were no differences in BMI, pulse pressure, smoking status, the cause of CKD or the duration of the period of renal insufficiency. This "asymmetric" subgroup was characterized by a significantly greater presence of carotid plaques (72.6 vs. 53.2%; χ2 = 6.91, p < 0.01), including calcified lesions (62.8 vs. 44.5%; χ2 = 7.15, p < 0.05).
All study participants were divided by using the mean value of maximal carotid IMT, i.e., 0.66 mm. Table 2 shows the comparison of patients assigned to both groups. The structure of the primary cause of CKD was similar in both groups. IMT values were strongly associated with age (R = 0.498; p < 0.001). There were also positive correlations with BMI (R = 0.125; p < 0.01), pulse pressure (R = 0.220; p < 0.001) and the duration of renal insufficiency (R = 0.167; p < 0.001). Among the laboratory parameters, IMT was positively associated with blood hemoglobin level (R = 0.153; p < 0.001), OPG (R = 0.203; p < 0.001), IL-6 (R = 0.146; p < 0.01), serum sclerostin concentration (R = 0.198; p < 0.05) and negatively associated with serum Klotho concentration (R = –0.181; p < 0.05), but not with iPTH level.
The clinical characteristics of study subgroups based on the occurrence and type of atherosclerotic plaques visualized in both carotid arteries.
Parameter Study group according to the mean IMT value p Study groups according to the carotid plaque occurrence p
IMT max IMT max No plaques Non-calcified Calcified
<0.66 mm ≥0.66 mm N = 224 N = 44 N = 232
N = 280 N = 220
Age [years] 45.3 (43.9–46.6) 55.8 (54.3–57.3) <0.001 42.7 (41.3–44.1) 49.3 (45.9–52.8)∧∧∧ 57.0 (55.7–58.3) ###∧∧∧ <0.001
Gender [M/F] 138/142 146/74 <0.001 111/113 24/20 149/83## <0.01
BMI [kg/m2] 25.8 (25.2–26.4) 26.5 (25.9–27.1) 0.12 25.8 (25.1–26.5) 25.1 (23.8–26.4) 27.0 (26.4–27.6)#∧ <0.05
Dialysis vintage [months]* 23 (14–42) 25 (14–41) 0.61 22 (13–40) 26 (16–38) 27 (15–45) 0.19**
Time after transplant [months]* 85 (52–115) 87 (70–119) 0.20 87 (57–116) 79 (25–104) 86 (70–120) 0.44**
Retransplant [n (%)] 21 (7.5) 21 (9.6) 0.40 19 (8.5) 3 (6.8) 20 (8.6) 0.92
Duration of renal insufficiency [years]* 10 (7–15) 12 (10–17) <0.001 9.0 (7.0–12.0) 10.0 (7.5–15.5) 14.0 (10.0–18.0) <0.001
Hypertension [n (%)] 240 (85.7) 200 (90.9) 0.08 190 (84.8) 37 (84.1) 218 (94.0)##∧ <0.01
MAP [mmHg] 101 (100–103) 99 (98–101) <0.05 100.0 (98–101) 100 (96–103) 101 (100–103) 0.35
Pulse pressure [mmHg]* 50 (45–60) 50 (40–59) <0.001 50 (40–59) 50 (45–60) 50 (45–60)### <0.05**
Number of antihypertensive drugs [n]* 2 (1–3) 2 (1–3) 0.06 2 (1–2) 2 (1–3) 2 (1–3)### <0.001**
Diabetes [n (%)] 80 (28.5) 83 (37.8) 0.03 49 (21.9) 9 (20.4) 79 (34.1)## <0.01
Coronary artery disease [n (%)] 21 (7.5) 49 (22.2) <0.001 11 (4.9) 3 (6.8) 49 (21.1)###∧ <0.001
Previous MACE [n (%)] 16 (5.7) 28 (12.7) <0.01 10 (4.5) 1 (2.3) 43 (18.5)###∧∧ <0.001
Smoking status [%] 48 (17.1) 41 (18.6) 0.66 43 (19.2) 10 (22.7) 36 (15.5) 0.40
eGFR [mL/min/1.73 m2]* 49.0 (36.1–67.7) 49.7 (37.9–68.8) 0.46 51.7 (38.4–68.3) 48.3 (38.5–63.0) 48.5 (34.8–66.9) 0.28**
Proteinuria ≥1 g/24 h [n (%)] 15 (5.4) 18 (8.2) 0.21 16 (7.1) 4 (9.1) 15 (6.5) 0.82
Glucose [mmol/L]* 5.0 (4.6–5.5) 5.2 (4.8–5.8) <0.01 4.9 (4.6–5.5) 5.0 (4.4–5.4) 5.3 (4.8–5.9)# <0.01**
Calcium [mmol/L]* 2.39 (2.30–2.50) 2.36 (2.27–2.45) <0.05 2.4 (2.3–2.5) 2.4 (2.3–2.4) 2.4 (2.3–2.5) 0.25**
Phosphate [mmol/L]* 1.02 (0.87–1.18) 10.3 (0.87–1.15) 0.99 1.0 (0.9–1.2) 1.0 (0.8–1.2) 1.0 (0.9–1.1) 0.70**
iPTH [pg/mL]* 99 (68–171) 100 (60–148) 0.39 104 (70–174) 105 (70–149) 111 (66–177) 0.74**
IMT [mm]* 0.6 (0.5–0.6) 0.7 (0.7–0.8) <0.001 0.6 (0.5–0.7) 0.7 (0.6–0.7) 0.7 (0.6–0.8) <0.001**
Cholesterol [mmol/L] 5.3 (5.2–5.4) 5.4 (5.2–5.5) 0.33 5.3 (5.1–5.5) 5.4 (5.0–5.7) 5.3 (5.2–5.5) 0.94
Triglycerides [mmol/L]* 1.5 (1.0–2.0) 1.5 (1.0–2.2) 0.59 1.4 (1.0–2.0) 1.5 (1.1–2.0) 1.6 (1.1–2.2) 0.49**
Hyperlipidemia [n (%)] 145 (51.8) 117 (53.2) 0.76 116 (51.8) 22 (51.2) 127 (54.7) 0.75
Hyperuricemia [n (%)] 151 (52.9) 135 (61.4) 0.10 116 (51.8) 19 (43.2) 151 (65.1)##∧∧ <0.01
Hemoglobin [g%] 13.3 (13.0–13.5) 13.7 (13.5–14.0) <0.01 13.4 (13.1–13.6) 13.6 (12.5–14.6) 13.6 (13.3–13.8) 0.53
Data presented as means and 95 % Confidence Intervals or frequencies, except *medians and Q1–Q3 values. Statistics: ANOVA or χ2 test, except **Kruskal-Wallis test. # p < 0.05 vs. no plaques; ## p < 0.01 vs. no plaques; ### p < 0.001 vs. no plaques; ^ p < 0.05 vs. non-calcified plaques; ^^ p < 0.01 vs. non-calcified plaques; ^^^ p < 0.001 vs. non-calcified plaques. BMI, body mass index; MAP, mean arterial pressure; MACE, major adverse cardio- and cerebrovascular event; eGFR, estimated glomerular filtration rate; iPTH, intact parathormon; IMT, intima-media thickness.
Univariate logistic regression analyses revealed that age, male sex, the presence of coronary artery disease or calcified plaques and hemoglobin level were associated with the presence of IMT ≥0.66 mm (Table 3).
Results of univariate logistic regression analyses for the IMT value and for the presence of calcified carotid plaques.
IMT Calcified plaques
β χ2 p β χ2 p
Age [years] 0.05 10.6 <0.01 0.12 162.4 <0.001
Male sex 1.63 9.4 <0.01 0.57 9.8 <0.01
BMI [kg/m2] 0.04 0.63 0.43 0.06 8.6 <0.01
Hypertension 0.16 0.05 0.83 1.02 10.4 <0.01
Pulse pressure [mmHg] 0.01 0.5 0.48 0.03 16.2 <0.001
Number of antihypertensive drugs 0.03 0.03 0.85 0.42 30.9 <0.001
Coronary artery disease 1.46 4.67 <0.05 1.42 12.3 <0.001
Previous MACE –0.29 0.09 0.78 1.72 17.7 <0.001
Calcium [mmol/L] 0.63 0.27 0.61 0.11 0.06 0.81
Glucose [mmol/L] 0.03 0.09 0.76 0.12 5.7 <0.05
Hyperuricemia –0.30 0.38 0.54 0.62 10.4 <0.01
Hemoglobin [g%] 0.16 3.05 0.06 0.04 0.98 0.33
Duration of renal insufficiency period [years] –0.04 0.81 0.39 0.10 36.9 <0.001
IMT [mm] - - - 4.91 54.9 <0.001
Calcified plaques 1.71 12.3 <0.01 - - -
BMI, body mass index; MACE, major adverse cardio- and cerebrovascular event; IMT, carotid intima-media thickness.
Multivariate logistic regression analysis in the entire study group showed that age (rpartial = 0.409; p < 0.001), male sex (rpartial = 0.199; p < 0.001), and coronary artery disease (rpartial = 0.139; p < 0.01) independently increased IMT (R2 = 0.25).
3.3 Carotid Plaques
Among the 500 study patients, 276 (55.2%) had at least one plaque (non-calcified or calcified) in both carotids. Patients with the presence of plaques were significantly older [55.8 (54.5–57.0) vs. 42.7 (41.3–44.1) years; p < 0.001] in comparison with KTRs with no carotid atherosclerotic lesions. They more frequently were men (62.7 vs. 49.6%; p < 0.01) and were characterized by a greater BMI [26.5 (25.9–27.0) vs. 25.6 (24.9–26.3) kg/m2, respectively; p < 0.01], IMT [Me: 0.70 (0.60–0.80) vs. Me: 0.60 (0.50–0.68) mm, respectively; p < 0.001], pulse pressure [Me: 50 (45–60) vs. Me: 50 (40–59) mmHg, respectively; p < 0.001] and duration of renal insufficiency [Me: 13 (10–18) vs. Me: 9 (7–12); p < 0.001].
Calcified lesions were detected in 32.5% study subjects with an IMT ≤0.6 mm, including 17.9% of patients characterized by the presence of few calcified lesions and those with a heavily calcified carotid bulb. This finding was also present in 22.9% and 6.7% of subjects with an IMT ≤0.5 mm. Fig. 1 shows the distribution of calcified plaques in patients with different maximum IMT values.
The distribution of carotid calcified plaques in patients with different IMT max values.
All patients were divided into 3 groups, based on the presence and type of plaques detected in both carotid arteries. There were 224 (44.8%) patients without any plaque, 44 (8.8%) patients with only non-calcified plaque/plaques and 232 (46.4%) patients, in whom at least one calcified lesion was identified. The clinical characteristics of patients in these study groups are shown in Table 2. There were substantial differences between the study groups. However, except of age, where a significant increasing trend was noted across all 3 study groups (p < 0.001), other significant differences were noted between the calcified plaques group and one or both other groups (Table 2). Of note, the statistical strength of comparison between the non-calcified and calcified plaques groups was weakened by the low number of patients in the former group. There were no differences in the proportion of patients, in whom a parathyroidectomy was performed prior to the study (7 vs. 7 vs. 8%, respectively; p = 0.96).
In general, the occurrence of calcified plaques was associated with the primary cause of CKD (χ2: 12.2; p < 0.05). Patients with pyelonephritis had significantly less (χ2: 4.97; p < 0.05), whereas patients with hypertensive nephropathy significantly more (χ2: 8.3; p < 0.01) carotid calcified lesions as compared with other patients. Patients with pyelonephritis were significantly younger than all other groups (46.5 vs. 50.3 years; p < 0.05), but there was no age difference in case of patients with hypertensive nephropathy (52.5 vs. 50.0 years; p = 0.22).
Univariate logistic regression analyses revealed that age, male sex, BMI, IMT, pulse pressure, serum glucose level, the presence of hypertension, coronary artery disease, previous MACE, hyperuricemia, the number of antihypertensive drugs and the duration of renal insufficiency period prior to transplantation were associated with the presence of calcified carotid lesions (Table 3). There was also a significant relationship between the maximal carotid plaque score and the duration of the period of renal insufficiency (χ2: 52.7; p < 0.001).
Multivariate logistic regression analysis in the entire study group revealed that age (rpartial = 0.544; p < 0.001), male sex (rpartial = 0.127; p < 0.05), and the duration of the period of renal insufficiency (rpartial = 0.235; p < 0.001) independently increased the risk for the presence of calcified lesions in carotid arteries (R2 = 0.38). Notably, if we did not include the duration of the period of renal insufficiency among the potential independent variables, only age (rpartial = 0.538; p < 0.001) and previous MACE (rpartial = 0.130; p < 0.01) were confirmed in multivariate analysis (R2 = 0.32). The ROC analysis revealed that age >48.5 years and the duration of the period of renal insufficiency >11 years increased the risk for the occurrence of calcified lesions with 81.0% and 66.2% sensitivity and 68.3% and 68.2% specificity, respectively (Fig. 2A,B).
The ROC analysis for recipient age (A) and duration of the period of renal insufficiency (B) which increased the risk for the occurrence of calcified lesions in the cohort of kidney transplant patients.
In 319 study patients, the results of circulating markers of inflammation, vascular function and calcium-phosphate metabolism were also available. In this subgroup, there were significantly higher serum CRP levels in patients with calcified plaques [Me: 3.5 (1.5–7.3) vs. Me: 2.0 (1.2–5.2) mg/L; p < 0.01], whereas there were no differences in plasma OPG, ET-1, ADMA, ox-LDL, IL-6 and TNF-α levels (data not shown).
Plasma sclerostin and α-Klotho concentrations were measured in a subset of 146 study patients. Sclerostin levels were significantly higher [Me: 0.9 (0.7–1.1) vs. Me: 0.7 (0.6–0.1) ng/mL; p < 0.01] in patients with carotid calcified lesions, whereas the difference in α-Klotho levels [Me: 470 (392–577) vs. Me: 503 (440–616) pg/mL, respectively; p = 0.053] did not reach statistical significance.
Univariate logistic regression analyses revealed that serum CRP level (β = 0.05, χ2 = 5.9; p < 0.05), plasma OPG (β = 0.17, χ2 = 13.8; p < 0.001) and sclerostin (β = 1.82, χ2 = 12.8; p < 0.01) levels were associated with the presence of calcified carotid lesions. However, none of analyzed biomarkers independently influenced the occurrence of calcified plaques in the multivariate analysis.
3.4 Carotid Plaque Location
The atherosclerotic lesions distribution according to the plaque score and side involved is shown at Fig. 3.
The distribution of atherosclerotic lesions in carotid arteries according to the plaque score and side involved. 0 denoted no plaques on the given side, 1—non-calcified lesions, 2—at least one calcified lesion, 3—few calcified lesions, 4—carotid bulb heavily covered by calcified lesions.
Despite the comparable number of patients without any carotid lesion (274 vs. 279 at the right and left side, respectively), only 224 (44.8%) KTRs were free of plaques at both sides. In the group of 274 KTRs without plaques on the right side, 50 patients (18.2%) had atherosclerotic lesions on the left side, including 13 (4.7%) with uncalcified plaques and 37 (13.5%) with calcified plaques. Notably, 16 (5.8%) patients had an abundantly calcified left carotid bulb. In this group of 274 subjects, median left IMT was significantly greater in the subgroups with any ipsilateral plaques [Me: 0.6 (0.6–0.7); p < 0.01], calcified plaques [Me: 0.6 (0.6–0.7); p < 0.05] and abundantly calcified left carotid bulb [Me: 0.7 (0.6–0.8); p < 0.01] in comparison with subgroup without plaques [Me: 0.6 (0.5–0.6)].
Out of 279 patients without plaques on the left side, 55 patients (19.7%) had at least one atherosclerotic lesion on the right side, including 18 (6.5%) with uncalcified plaques and 37 (13.3%) with calcified plaques. Twelve patients (4.3%) had a heavily calcified right carotid bulb. Median right IMT was significantly greater in the subgroups with any ipsilateral plaques [Me: 0.6 (0.6–0.7); p < 0.001] and calcified plaques [Me: 0.6 (0.6–0.7); p < 0.001] in comparison with subgroup without plaques [Me: 0.6 (0.5–0.6)]. In contrast, there was no difference in IMT between subgroup with abundantly calcified right carotid bulb [Me: 0.6 (0.6–0.6)] as compared with the subgroup without plaques (p = 0.11).
This study analyzed the characteristics and relationship of two different ultrasound-based measures of carotid atherosclerosis, IMT and carotid plaques, in stable KTRs. In contrast to several previous studies, the IMT measurements were performed manually (to avoid IMT overestimation), which enable us to investigate the two different atherosclerotic carotid entities separately and to define their independent risk factors without overlapping bias. Age and male sex were confirmed as common independent risk factors for the occurrence of both IMT and calcified carotid plaques. Additionally, the presence of coronary artery disease was associated with increased IMT, whereas the duration of the period of pre-transplant renal insufficiency increased the risk for carotid calcified plaques in multivariate analyses. Notably, none out of the numerous analyzed biomarkers was shown to be independently associated with IMT or plaque occurrence in the study cohort. This finding preclude the use of biomarkers as surrogates of carotid atherosclerosis in daily clinical practice. Finally, we also described in detail the asymmetric distribution of carotid lesions and the relationships between IMT and the presence of calcified carotid lesions in KTRs.
IMT is recognized as an useful tool for CV risk stratification and therapy monitoring [18]. In the Carotid Atherosclerosis Progression Study during a mean follow-up of 4.2 years, IMT was highly predictive for the incidence of stroke, myocardial infarction and death [19]. Moreover, for this combined end-point, hazard ratios were considerably higher in the younger (<50 years) than in the older age group. IMT was also shown to increase over a 6-year follow-up period especially in patients suffering from CV events [20]. In contrast, in the Rotterdam Study, adding IMT to a model for predicting the increased CV risk did not enhance its power, however the IMT ROC area (0.71) was comparable with other well-established risk factors, including previous MACE, diabetes, smoking, systolic blood pressure and cholesterol (ROC 0.65–0.72) [21]. In the present study, age, male gender and the presence of coronary artery disease were independently associated with greater IMT values, similarly to previous findings in the general [22] and hemodialysis [23] populations, despite one contrary report based on a small KTRs cohort [24].
Decreased renal function was shown to independently increase IMT (4), even in patients with no known kidney disease and normal and/or moderately decreased eGFR values [25, 26]. Of note, in the Suita Study cohort, multivariable-adjusted carotid IMT was significantly greater in CKD patients only in a hypertensive subgroup [27]. Nevertheless, despite the previously described modest IMT regression observed after kidney transplantation [28], the range of IMT in the present study was similar to the values reported in hemodialysis patients [29], as well as in other KTRs cohorts with comparable recipient age [30, 31]. Notably, in all study subjects, IMT was measured manually by a single investigator, within the optimal location at the far wall below the bulb, omitting any visible local thickening [32]. Otherwise, both the manual and computer-based, automated methods for IMT assessment often yield higher scores, as they may not omit local intimal thickening or plaques [22, 33, 34, 35]. This study protocol was chosen to avoid the above mentioned biases and allowed us to perform a more accurate analysis of interrelationship between IMT and carotid plaque burden. In the analyzed cohort, only a small subgroup showed substantial IMT left-right asymmetry, which is in line with earlier reports [36, 37]. Interestingly, those KTRs were older and were more frequently men compared to the rest of the analyzed cohort.
The assessment of carotid plaques is a distinct measure of atherosclerosis, with advancing age as the most predominant risk factor. With aging, a decrease in fibrous plaques and an increase in atheromatous plaques is observed [38]. This discrepancy may be explained by the differences in arterial remodeling in response to plaque accumulation among the different types of arteries [39]. Carotid bulb geometry was shown to be associated with plaque volume [40, 41]. Moreover, in arteries with plaques, wall shear stress was significantly lower than in the plaque-free vessel and was linked to endothelial dysfunction [42]. This may result in partly asymmetric distribution of carotid calcified lesions that was seen in some study patients, which was also reported in another large non-CKD study [43].
Thus, the assessment of carotid plaques, particularly calcified lesions, using ultrasound may provide additional stroke risk information beyond the measurement of luminal stenosis [44]. In a population-based study, calcified carotid plaques independently increased the risk of combined vascular outcomes, including ischemic stroke, even after adjustment for IMT [45]. The presence of CKD additionally increases the total and calcified plaque burden, both in dialysis and transplant patients [46]. Moreover, the negative association between eGFR and the prevalence of carotid plaques was observed even in patients without CKD [25]. This effect is mainly mediated by phosphate retention, which constitutes an early trigger for the development of secondary hyperparathyroidism and accelerated macrovascular disease [47]. Such a mechanism is further confirmed by a consistent relationship between serum phosphate (even in the normal range) and CVD [48, 49], as well as with multiregional vascular calcification [50], and by the independent relationship between the duration of renal insufficiency (with concomitant impairment of urinary phosphate elimination) and calcified plaques found in the present study. This reciprocal relationship of vascular calcifications within different locations in CKD patients was also confirmed in other studies [22, 29, 51, 52].
In kidney transplant patients, the occurrence of carotid lesions was previously showed to be associated with age and the occurrence of arterial hypertension [53]. Importantly, despite satisfactory transplant organ function, substantial progression of carotid plaques was reported, which was associated with age, smoking, dialysis vintage and hyperphosphatemia [54]. In the present study we found that, except for age and male sex, only the duration of pre-transplant renal insufficiency independently increased the burden of calcified carotid plaques, and as we excluded the latter variable, only age and previous MACE remained significant. This is in line with another report, where the severity of the carotid plaque score was significantly higher in the MACE group than in the MACE-free group in asymptomatic CKD patients [55]. Similarly, age and coronary artery calcification score were independently associated with carotid plaques in dialysis patients [29]. Interestingly, in some reports a significantly greater plaque prevalence in dialysis patients in comparison with healthy controls was identified despite similar IMT [45, 56]. It is also worth noticing that in our cohort, there was a substantial percentage of patients with IMT ≤0.6 mm, in whom we found a high burden of calcified carotid plaques. More importantly, the accuracy for detecting carotid plaques was higher than for detecting abnormal IMT in examinations performed in a routine outpatient setting in a non-CKD cohort [57]. In the large Angina Prognosis Study in Stockholm, carotid IMT was a weak predictor for events, whereas carotid plaques were related to CV death or non-fatal myocardial infarction [58]. In a recent metanalysis, plaque assessment was found to be a better CV risk predictor than IMT in a non-CKD population and one large observational study provided evidence for its similar potential in CKD patients [59]. These studies suggest the greater utility of carotid plaque assessment compared to carotid IMT measurement, as a prognostic indicator for CV risk in CKD and KTRs.
Disappointingly, when we analyzed the potential associations of numerous biochemical or hormonal markers with IMT or the occurrence of carotid plaques, none of investigated inflammatory, vascular or calcium-phosphate parameters was confirmed as an independent variable in multivariate analyses. Previously, atherosclerotic plaque occurrence and progression were found to be associated with higher IL-6 levels [60] and α-Klotho polymorphism [61] in CKD patients. Plaque burden was also related to ET-1, OPG and nitric oxide metabolite levels in small cohorts of dialysis patients [62, 63, 64] and with CRP level in KTRs [65]. However, a majority of biomarkers included in the present analysis have not been previously examined in kidney transplantation patients.
The main limitation of our analysis is its cross-sectional character and inclusion of 3 KTRs cohorts. However, there was a high uniformity in the methodology of these 3 cohorts, with all ultrasound examinations performed by a single investigator, using the same measurement protocol. In our study cohort, several clinical characteristics and several biochemical parameters were not available for each of study patients. Only the smoking status at the time of the study was available, whereas we have no data concerning the lifetime smoking habits. This may have explained why smoking was not found to be an independent parameter which influenced IMT or the occurrence of calcified plaques in the univariate or multivariate analyses. Finally, as calcium-phosphate metabolism before and during dialysis therapy is the crucial factor for accelerated calcification of the vessel wall, it would have been important to analyze data concerning the maximum pre-transplant phosphate and iPTH levels, as well as the use and effect of phosphate-lowering regimens, which were not available in our study group.
In this study, we described in detail the distribution of two different atherosclerotic measures—IMT and carotid plaques—in a large cohort of stable kidney transplant recipients. In addition, the profiles of different clinical risk factors associated with both those vascular entities were identified. We large side-to-side differences in IMT values and carotid plaque distribution in a substantial percentage of KTRs, which presents a high epidemiologic burden for carotid and general atherosclerosis. None of the analyzed vascular and calcium-phosphate metabolism biomarkers was associated with any of the carotid atherosclerosis measurements. Due to the high risk for CV complications and death among recipients of successful kidney transplants, the independent assessment of both IMT and calcified carotid lesions should be advocated, as it may increase the ability to identify those KTRs with the highest CV risk.
AK designed the research study. AK, BS, MS and RS performed the research. RF and JC provided help and advice on statistical analysis, manuscript and figures preparation. AK analyzed the data and wrote the manuscript. AW critically reviewed the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
The study research was conducted as a part of our previous clinical studies, all were accepted by the Bioethics Committee of the Medical University of Silesia (KNW/0022/KB1/81/10, KNW/0022/KB1/93/13, KNW/0022/KB1/35/I/15). All participants gave their written informed consent. The study was conducted in accordance with the Declaration of Helsinki.
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Naqui TZ, Lee M-S. Carotid intima-media thickness and plaque in cardiovascular risk assessment. JACC: Cardiovasc Imaging. 2014; 7: 1025–1038.
Cited within: 1
| Google Scholar | PubMed | Crossref
Hollander M, Hak AE, Koudstaal PJ, Bots ML, Grobbee DE, Hofman A, et al. Comparison between Measures of Atherosclerosis and Risk of Stroke. Stroke. 2003; 34: 2367–2372.
Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease. Circulation Research. 2016; 118: 535–546.
Kajitani N, Uchida HA, Suminoe I, Kakio Y, Kitagawa M, Sato H, et al. Chronic kidney disease is associated with carotid atherosclerosis and symptomatic ischaemic stroke. Journal of International Medical Research. 2018; 46: 3873–3883.
Wyld M, Webster AC. Chronic Kidney Disease is a Risk Factor for Stroke. Journal of Stroke and Cerebrovascular Diseases. 2021; 30: 105730.
London GM, Pannier B, Marchais SJ. Vascular Calcifications, Arterial Aging and Arterial Remodeling in ESRD. Blood Purification. 2013; 35: 16–21.
Yerram P, Karuparthi PR, Hesemann L, Horst J, Whaley-Connell A. Chronic kidney disease and cardiovascular risk. Journal of the American Society of Hypertension. 2007; 1: 178–184.
Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transplant International. 2015; 28: 10–21.
Spence JD. Measurement of Intima-Media Thickness vs. Carotid Plaque: Uses in Patient Care, Genetic Research and Evaluation of New Therapies. International Journal of Stroke. 2006; 1: 216–221.
Spence JD. Technology Insight: ultrasound measurement of carotid plaque—patient management, genetic research, and therapy evaluation. Nature Clinical Practice Neurology. 2006; 2: 611–619.
Block GA. Control of serum phosphorus: implications for coronary artery calcification and calcific uremic arteriolopathy (calciphylaxis). Current Opinion in Nephrology and Hypertension. 2001; 10: 741–747.
Pelisek J, Assadian A, Sarkar O, Eckstein HH, Frank H. Carotid Plaque Composition in Chronic Kidney Disease: a Retrospective Analysis of Patients Undergoing Carotid Endarterectomy. European Journal of Vascular and Endovascular Surgery. 2010; 39: 11–16.
Benedetto FA, Tripepi G, Mallamaci F, Zoccali C. Rate of Atherosclerotic Plaque Formation Predicts Cardiovascular Events in ESRD. Journal of the American Society of Nephrology. 2008; 19: 757–763.
Kolonko A, Szotowska M, Kuczera P, Chudek J, Wiecek A. Extrarenal Factors Influencing Resistance Index in Stable Kidney Transplant Recipients. Transplantation. 2013; 96: 406–412.
Kolonko A, Bartmańska M, Słabiak-Błaż N, Kuczera P, Kujawa-Szewieczek A, Ficek R, et al. Arterial stiffness but not endothelial dysfunction is associated with multidrug antihypertensive therapy and nondipper blood pressure pattern in kidney transplant recipients. Medicine 2018; 97: e11870.
Kolonko A, Jurys M, Sirek S, Dwulit T, Pojda-Wilczek D, Więcek A. The effect of maintenance treatment with twice-daily or prolonged once-daily tacrolimus formulation on visual evoked potentials in stable kidney transplant recipients. Journal of Clinical Medicine. 2020; 9: 1827.
American Diabetes Association Classification and diagnosis of diabetes: Standards of medical care in diabetes – 2019. Diabetes Care. 2019; 42: S13–S28.
Simon A, Gariepy J, Chironi G, Megnien J, Levenson J. Intima–media thickness: a new tool for diagnosis and treatment of cardiovascular risk. Journal of Hypertension. 2002; 20: 159–169.
Lorenz MW, von Kegler S, Steinmetz H, Markus HS, Sitzer M. Carotid imtima-media thickening indicates a hugher vascular risk across a wide age range: prospective data from the Carotid Atherosclerosis Progression Study (CAPS). Stroke. 2006; 37: 87–92.
Uthoff H, Staub D, Meyerhans A, Hochuli M, Bundi B, Schmid H, et al. Intima-Media Thickness and Carotid Resistive Index: Progression over 6 Years and Predictive Value for Cardiovascular Events. Ultraschall in Der Medizin - European Journal of Ultrasound. 2008; 29: 604–610.
del Sol AI, Moons KGM, Hollander M, Hofman A, Koudstaal PJ, Grobbee DE, et al. Is Carotid Intima-Media Thickness Useful in Cardiovascular Disease Risk Assessment? The Rotterdam Study. Stroke. 2001; 32: 1532–1538.
Cohen GI, Aboufakher R, Bess R, Frank J, Othman M, Doan D, et al. Relationship between Carotid Disease on Ultrasound and Coronary Disease on CT Angiography. JACC: Cardiovascular Imaging. 2013; 6: 1160–1167.
Kurnatowska I, Grzelak P, Stefańczyk L, Nowicki M. Tight relations between coronary calcification and atherosclerotic lesions in the carotid artery in chronic dialysis patients. Nephrology. 2010; 15: 184–189.
Suwelack B. Studies on structural changes of the carotid arteries and the heart in asymptomatic renal transplant recipients. Nephrology Dialysis Transplantation. 1999; 14: 160–165.
Buscemi S, Geraci G, Massenti FM, Buscemi C, Costa F, D'Orio C, et al. Renal function and carotid atherosclerosis in adults with no known kidney disease. Nutrition, Metabolism and Cardiovascular Diseases. 2017; 27: 267–273.
Tanaka M, Abe Y, Furukado S, Miwa K, Sakaguchi M, Sakoda S, et al. Chronic Kidney Disease and Carotid Atherosclerosis. Journal of Stroke and Cerebrovascular Diseases. 2012; 21: 47–51.
Ohara T, Kokubo Y, Toyoda K, Watanabe M, Koga M, Nakamura S, et al. Impact of chronić kidney disease on carotid atherosclerosis according to blood pressure category. The Suita Study. Stroke. 2013; 44: 3537–3539.
De Lima JJG, Vieira MLC, Viviani LF, Medeiros CJ, Ianhez LE, Kopel L, et al. Long‐term impact of renal transplantation on carotid artery properties and on ventricular hypertrophy in end‐stage renal failure patients. Nephrology Dialysis Transplantation. 2002; 17: 645–651.
Kraśniak A, Drożdż M, Pasowicz M, Chmiel G, Michałek M, Szumilak D, et al. Factors involved in vascular calcification and atherosclerosis in maintenance haemodialysis patients. Nephrology Dialysis Transplantation. 2007; 22: 515–523.
Genís BB, Granada ML, Alonso N, Lauzurica R, Jiménez JA, Barluenga E, et al. Ghrelin, Glucose Homeostasis, and Carotid Intima Media Thickness in Kidney Transplantation. Transplantation. 2007; 84: 1248–1254.
Cofan F, Arias M, Nuñez I, Cofan M, Corbella E, Rosich E, et al. Impact of Carotid Atherosclerosis as Assessed by B-Mode Ultrasonography on the Evolution of Kidney Transplantation. Transplantation Proceedings. 2007; 39: 2236–2238.
Ludwig M, von Petzinger-Kruthoff A, von Buguoy M, Stumpe KO. Intima media thickness of the carotid arteries: early pointer to arteriosclerosis and therapeutic endpoint. Ultraschall in der Medizin. 2003; 24: 162–174.
Benetos G, Toutouzas K, Drakopoulou M, Tolis E, Masoura C, Nikolaou C, et al. Bilateral symmetry of local inflammatory activation in human carotid atherosclerotic plaques. Hellenic Journal of Cardiology. 2015; 56: 118–124.
Molinari F, Meiburger KM, Saba L, Acharya UR, Ledda G, Zeng G, et al. Ultrasound IMT easurement on a multiethnic and multi-institutional database: our review and experience using four fully automated and one semi-automated methods. Computer Methods and Programs in Biomedicine. 2012; 108: 946–960.
Torres FS, Fuchs SC, Maestri MK, Fuchs FD, Oliveira MM, Moreira LB, et al. Association between carotid intima-media thickness and retinal arteriolar and venular diameter in patients with hypertension: a cross-sectional study. Atherosclerosis. 2013; 229: 134–138.
Howard G, Burke GL, Evans GW, Crouse JR, Riley W, Arnett D, et al. Relations of intimal-medial thickness among sites within the carotid artery as evaluated by B-mode ultrasound. Stroke. 1994; 25: 1581–1587.
Bossuyt J, Van Bortel LM, De Backer TLM, Van De Velde S, Azermai M, Segers P, et al. Asymmetry in prevalence of femoral but not carotid atherosclerosis. Journal of Hypertension. 2014; 32: 1429–1434.
van Oostrom O, Velema E, Schoneveld AH, de Vries JPPM, de Bruin P, Seldenrijk CA, et al. Age-related changes in plaque composition. A study in patients suffering from carotid artery stenosis. Cardiovascular Pathology. 2005; 14: 126–134.
Pasterkamp G, Schoneveld AH, Hillen B, Banga JD, Haudenschild CC, Borst C. Is plaque formation in the common carotid artery representative for plaque formation and luminal stenosis in other atherosclerotic peripheral arteries? A post mortem study. Atherosclerosis. 1998; 137: 205–210.
Gregg S, Li TY, Hétu M, Pang SC, Ewart P, Johri AM. Relationship between carotid artery atherosclerosis and bulb geometry. The International Journal of Cardiovascular Imaging. 2018; 34: 1081–1090.
Spanos K, Petrocheilou G, Livieratos L, Labropoulos N, Mikhailidis DP, Giannoukas AD. Carotid Bifurcation Geometry as Assessed by Ultrasound is Associated with Early Carotid Atherosclerosis. Annals of Vascular Surgery. 2018; 51: 207–216.
Malík J, Kudlička J, Tuka V, Chytilová E, Adamec J, Ročínová K, et al. Common Carotid Wall Shear Stress and Carotid Atherosclerosis in End-Stage Renal Disease Patients. Physiological Research. 2012; 61: 355–361.
Gnasso A, Irace C, Carallo C, De Franceschi MS, Motti C, Mattioli PL, et al. In Vivo Association between Low Wall Shear Stress and Plaque in Subjects with Asymmetrical Carotid Atherosclerosis. Stroke. 1997; 28: 993–998.
Brinjikji W, Rabinstein AA, Lanzino G, Murad MH, Williamson EE, DeMarco JK, et al. Ultrasound Characteristics of Symptomatic Carotid Plaques: a Systematic Review and Meta-Analysis. Cerebrovascular Diseases. 2015; 40: 165–174.
Prabhakaran S, Singh R, Zhou X, Ramas R, Sacco RL, Rundek T. Presence of calcified carotid plaque predicts vascular events: the Northern Manhattan Study. Atherosclerosis. 2007; 195: e197–e201.
Leskinen Y, Lehtimäki T, Loimaala A, Lautamatti V, Kallio T, Huhtala H, et al. Carotid atherosclerosis in chronic renal failure—the central role of increased plaque burden. Atherosclerosis. 2003; 171: 295–302.
Toussaint ND, Pedagogos E, Tan S, Badve SV, Hawley CM, Perkovic V, et al. Phosphate in early chronic kidney disease: Associations with clinical outcomes and a target to reduce cardiovascular risk. Nephrology. 2012; 17: 433–444.
Narang R, Ridout D, Nonis C, Kooner JS. Serum calcium, phosphorus and albumin levels in relation to the angiographic severity of coronary artery disease. International Journal of Cardiology. 1997; 60: 73–79.
Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G. Relationship between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation. 2005; 112: 2627–2633.
Adeney KL, Siscovick DS, Ix JH, Seliger SL, Shlipak MG, Jenny NS, et al. Association of Serum Phosphate with Vascular and Valvular Calcification in Moderate CKD. Journal of the American Society of Nephrology. 2009; 20: 381–387.
San Norberto EM, Revilla A, Fernández-Urbón A, Gómez-Giralda B, Taylor JH, Vaquero C. Vascular calcification progression in patients with end-stage chronic kidney disease. International Angiology. 2021; 40: 528–536.
Pencak P, Czerwieńska B, Ficek R, Wyskida K, Kujawa-Szewieczek A, Olszanecka-Glinianowicz M, et al. Calcification of coronary arteries and abdominal aorta in relation to traditional and novel risk factors of atherosclerosis in hemodialysis patients. BMC Nephrology. 2013; 14: 10.
Barbagallo CM, Pinto A, Gallo S, Parrinello G, Caputo F, Sparacino V, et al. Carotid Atherosclerosis in Renal Transplant Recipients: Relationships with Cardiovascular Risk Factors and Plasma Lipoproteins. Transplantation. 1999; 67: 366–371.
Nankivell BJ, Lau SG, Chapman JR, O'Connell PJ, Fletcher JP, Allen RD. Progression of macrovascular disease after transplantation. Transplantation. 2000; 69: 574–581.
Sawai A, Yasuda Y, Suzuki S, Ishii H, Goto M, Kato S, et al. Impact of non-invasive cardiovascular screening programs as a predictor of cardiovascular events among asymptomatic chronic kidney disease patients. Clinical and Experimental Nephrology. 2016; 20: 416–424.
Savage T. Calcified plaque is common in the carotid and femoral arteries of dialysis patients without clinical vascular disease. Nephrology Dialysis Transplantation. 1998; 13: 2004–2012.
Ray A, Tamsma JT, Hovens MMC, op 't Roodt J, Huisman MV. Accuracy of carotid plaque detection and intima–media thickness measurement with ultrasonography in routine clinical practice. European Journal of Internal Medicine. 2010; 21: 35–39.
Held C. Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris. European Heart Journal. 2001; 22: 62–72.
Kousios A, Kouis P, Hadjivasilis A, Panayiotou A. Cardiovascular Risk Assessment Using Ultrasonographic Surrogate Markers of Atherosclerosis and Arterial Stiffness in Patients with Chronic Renal Impairment: a Narrative Review of the Evidence and a Critical View of their Utility in Clinical Practice. Canadian Journal of Kidney Health and Disease. 2020; 7: 205435812095493.
Addabbo F, Mallamaci F, Leonardis D, Tripepi R, Tripepi G, Goligorsky MS, et al. Searching for biomarker patterns characterizing carotid atherosclerosis burden in patients with reduced renal function. Nephrology Dialysis Transplantation. 2007; 22: 3521–3526.
Valdivielso JM, Bozic M, Galimudi RK, Bermudez-López M, Navarro-González JF, Fernández E, et al. Association of the rs495392 Klotho polymorphism with atheromatosis progression in patients with chronic kidney disease. Nephrology Dialysis Transplantation. 2019; 34: 2079–2088.
Demuth K, Blacher J, Guerin AP, Benoit M-O, Moatti N, Safar ME, et al. Endothelin and cardiovascular remodeling in end-stage renal disease. Nephrology Dialysis Transplantation. 1998; 13: 375–383.
Krzanowski M, Krzanowska K, Dumnicka P, Gajda M, Woziwodzka K, Fedak D, et al. Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients with Severe Artery Calcification. Therapeutic Apheresis and Dialysis. 2018; 22: 519–529.
Batko K, Krzanowski M, Pietrzycka A, Gajda M, Dumnicka P, Fedak D, et al. Interplay of nitric oxide metabilities and markers of endothelial injury, inflammation, and vascular disease in the spectrum of advanced chronic kidney disease. Kardiologia Polska. 2020; 78: 51–58.
Sanchez-Escuredo A, Pastor MC, Bayes B, Morales-Indiano C, Troya M, Dolade M, et al. Inflammation, metalloproteinases, and growth factors is the development of carotid atherosclerosis in renal transplant patients. Transplantation Proceedings. 2010; 42: 2905–2907.
Aureliusz Kolonko, Rafał Ficek, Beata Styrc, Michał Sobolewski, Roksana Stankowska, Jerzy Chudek, Andrzej Więcek. Divergent Occurrence of Carotid Intima-Media Thickness and Carotid Arteries Plaques in Stable Kidney Transplant Recipients. Rev. Cardiovasc. Med. 2022, 23(12), 386. https://doi.org/10.31083/j.rcm2312386
Rev. Cardiovasc. Med. Print ISSN 1530-6550 Electronic ISSN 2153-8174

redpajama_set_name: RedPajamaCommonCrawl


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Updated on : Wednesday, June 19, 2019, 4:25 PM IST
Tamil Nadu: Chennai water crisis hits construction sector
The shortfall in supply delays construction timelines and the handing over of the properties said Varun Manian
Representational Pic
Chennai: The water crisis in Chennai and in several other places in Tamil Nadu has affected the construction sector severely, said realty players. "We are not able to get good water fulfilling quality parameters from the ground hence we are forced to buy tanker water which is very costly and increases the cost of construction," Varun Manian, Managing Director, Radiance Realty Developers India Ltd, told IANS.
The shortfall in supply delays construction timelines and the handing over of the properties, he said. Queried about how Radiance Realty is managing, Manian said: "We started using self-curing concrete and plaster to reduce the consumption of water. We started constructing storm water collection system and rain water harvesting wells during the course of construction and this will increase the quality and yield of the ground water within two seasons."
He does not see any fall in property sales due to the water crisis. "The water crisis has affected the construction sector. The normal pace of activity during this period is not happening in Tamil Nadu," R.Thayumanavan, former state head of the Federation of All Civil Engineers Association of Tamil Nadu and Puduchery, told IANS over phone from Cuddalore.
Queried about retaining the workers from outside Tamil Nadu, Thayumanavan, also a Managing Partner of Alfa Building Construction, said: "We have not sent them back till now. We are adopting a wait and watch policy." The realty players said they were adopting a wait and watch policy to decide whether to send back the construction workers to their native states like Bihar and West Bengal.
The reservoirs Cholavaram (full capacity 1,081 mcft) and Redhills (3,300 mcft) which cater to Chennai's water needs are dry while the storage at Poondi reservoir is 24 mcft as against the full capacity of 3,231 mcft, according to the Chennai Metropolitan Water Supply and Sewerage Board (Chennai Metro). The Chembarambakkam lake (full capacity 3,645 mcft) has a water level of a mere 1 mcft.
(To download our E-paper please click here. The publishers permit sharing of the paper's PDF on WhatsApp and other social media platforms.)
construction sector
Chennai water crisis
shortfall in supply


Formative assessments are an important way to meet our students' learning needs. When we can see what our students know (or don't know) we can better adjust our teaching to meet them right at their level. Beyond giving feedback, the best formative assessments help students recognize and value the process of learning, not just the outcomes. These reflective, metacognitive moments can foster kids' genuine excitement, engagement, and lifelong learning.
There are lots of digital -- and non-digital -- formative assessment methods that teachers can employ. At times, something as simple as a show of hands, or a physical "thumbs up; thumbs sideways; thumbs down" poll can be just the right thing. But other times, it's valuable for us to get a closer look at exactly what our students are learning and comprehending.
Kahoot is a game-based classroom response system. Teachers can create quizzes using content from the web. Questions appear on a class screen; without needing an account, students answer in real-time on a mobile device. Kahoot is different in that it creates an engaging competition. Students can also create their own quizzes and assessments. Read full review.
Socrative is a student response system with a variety of activities: quizzes, assessments, games, and even exit notes. Teachers control the flow of exercises; students respond in real time. It generates reports to help teachers track learning over time. Read full review.
Turnitin is mostly a tool for promoting originality in students' writing (or catching plagiarism). However, it's also a tool to support the writing process -- from teacher feedback and grading to peer evaluation and review. There's also a handy discussion forum feature, with built-in moderation. Read full review.
Poll Everywhere isn't just for schools, but works well as a classroom response system. Students can respond via text message, Twitter, or a Web browser; teachers can project the results on the Web, or in a PowerPoint or Keynote presentation. Read full review.
Backchannel Chat is just for educational use. Students don't have to enter any personal information into the system, and teachers can save, search, and archive discussions. Teachers also get a lot of control with customizable moderation options, a room-locking feature, and filtering for unwelcome content. Read full review.
is a student response system offering teachers more than a standard quiz/poll tool. The social Q&A feature allows students to vote the most relevant questions to the top, and a "Confusion Barometer" tool lets teachers track understanding throughout a lesson. Read full review.
Blendspace allows teachers to collect resources from the web and create a customizable, blended-instruction experience for students. Formative assessment tools are built in, allowing multiple question types, and the ability to track students' progress over time. Read full review.
If you're using online formative assessments in your classroom, check out our tips for how to make formative assessment more student-centered.


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Chapter 272 – Firm Attitude
When we went to the meeting place, several horsemen with white flags came running in late for our arrival. Incidentally, a white flag was also fluttering on our air board. It seems that the concept of a white flag is almost the same as what I know, even though there is no concept of declaring war or starting a war after slapping an ultimatum on the enemy. It seems strange, but I can't complain.
"There were six of them. Maybe those two guys in the fine armor are the enemy commanders."
"Probably. The old knight with the scars on his armor is probably the commander of the Tigris Royal Army."
The one with the clean armor is the commander of the Duchy of Dihart's army, right? This one looks quite young. He definitely looks younger than Sir Leonard. Is he about the same age as Danan? I guess he is one generation older than me.
I took out chairs for me, Worg, and the other two commanders from my inventory and set them up since I didn't want to talk to them while standing up. They were surprised to see me take out a chair from an empty space.
"Do you think two chairs will be enough for you?"
"U-umu…"
I decided to sit in the chair first since it looked good. Well, it is a simple chair with a cloth on top of its X-shaped frame. My image of the chair is that of an old man sitting on the quay in a harbor, pitch-fishing. Well, I think I saw a warlord sitting on such a chair when a battlefield was depicted in a period drama.
"Well, what should I start with in such a situation? Should we start by introducing ourselves?"
"Well, I think it's a good idea to start by introducing our positions first. I'm Worg. I am the commander of the northern magic rifle battalion of the Royal Army of Merinard, and I am also the commander of the northern base."
"I'm Kosuke. Well, I'm not a soldier in the Royal Army of Merinard, am I?"
"Well, yeah… why don't you just call yourself the prince consort?"
"I see. Well, let me introduce myself again. My name is Kosuke. I am the consort of Sylphielle Danal Merinard, Queen of the Kingdom of Merinard, and I am what is called a prince consort. You can think of me as a military strategist or a general staff member in this situation. I've heard that it's a higher position than that of Worg."
"That's because you are the prince consort, after all. And what about you?"
The commanders on the other side, who had been watching our exchange with blank expressions on their faces, opened their mouths with a small cough as if to regain their composure, their expressions tightening.
"I am Marquis Macrito Jean Nicklaus. I am the commander of the Royal Army of Tigris."
"I am Antonius Dels Giranzam. A count. I lead the army of the Duchy of Dihart."
The older one is Macrito, and the younger one is Antonius.
"Let's get straight to the point. All we ask is an immediate withdrawal of the wounded and the bodies and the abandonment of the border forts between the two countries. Is one week too short a time? Let's wait two weeks. You have two weeks to withdraw your forces and abandon the forts. If you fail to comply, we will use force to destroy both forts without a trace in two weeks' time."
The two enemy generals' eyes widened at my demand. Yes, they would be surprised, wouldn't they? If I were in their shoes, I would be surprised, too. There was no way they would agree to such a request out of the blue. In the first place, they would not have the authority to accept such conditions and abandon the fort.
"How could we possibly accept such a condition?"
"There is no way we could accept such a condition. There is no way we can swallow it."
Macrito's face turns red, and he shouts angrily while Antonius smiles bitterly. This bitter smile is that, isn't it? Oh, you think I'm some kind of idiot, don't you? Well, actually, it's something like that.
"No, I don't mind if you don't swallow it. I don't care if it's full or empty; I'm just going to destroy it."
At my words, both of them peeled their eyes open again, revealing their surprise. Macrito-dono's face is still red, but is he all right? I don't want him to die suddenly from surprise and anger.
"I said it was a request, but in effect, it was not an order. I'm just informing you of my decision. We're going to destroy it in two weeks, so if you don't want to take casualties, you'll have to move out. In other words, this is our punitive response to the Duchy of Dihart and the Kingdom of Tigris, who suddenly attacked us without having specified the reason for starting the war."
"Punitive response…? You are talking from a very high place, aren't you? How can you destroy a fort if you can't even get out of your own camp?"
Antonius-dono stared at me with a threatening atmosphere. Oh, I'm afraid.
"I don't feel the need to explain how. In any case, in two weeks, we will destroy the fort near the border with the kingdom of Merinard. If you don't want your soldiers to be killed, evacuate them. In the meantime, there will be no further attacks from us until two weeks from now. We will also allow you to retrieve the wounded and the bodies from the battlefield. However, if we recognize another act of aggression against the Kingdom of Merinard, we will immediately counterattack and destroy all the armies involved in the aggression and destroy the forts of both sides without waiting two weeks. I recommend that you watch each other closely so that you do not act strangely."
"You are quite brazen, aren't you? We still have a total of 10,000 men. In contrast, you have only four hundred. No matter how many strange weapons you arm yourself with, you will not be able to overcome the numbers disadvantage."
"Shall we give it a try? I don't think your morale will hold up. Of course, in that case, I will destroy the fort immediately after I kill all of you."
I said this with a smile to Macrito-dono, who was threatening me.
"You no longer have a choice. Either you do as we ask and keep the death toll to a minimum, or else we will engage you in another battle and literally annihilate you. You don't know what you're getting into, do you?"
The two enemy generals are both silenced by my words.
In fact, the Duchy of Dihart's army is well within the bombing range of the harpies. If I send an instruction via the golem communicator, we can rain anti-personnel air bombs on the Duchy of Dihart's army at this very moment.
"I'd really like to get along with our neighbors, though. Well, if you hit us, we'll hit you back, and if we do, we'll have no choice but to beat you so thoroughly that you'll never think of hitting us again. Whether or not we can shake hands afterward is up to you―or rather, I'm sure that the corrupt priests of the Holy Kingdom are probably pulling the strings behind the scenes in this war as well."
The two did not change their expressions when they heard my words. Well, even though they are the suzerain state, it would be hard to say that they moved their armies at the behest of another country.
"That's all I have to say. If you have something to say, I'll listen, but is there anything?"
Antonius' POV
"That's all I have to say. If you have something to say, I'm all ears."
What the hell is this guy? The only thing I could think of him was that. I was surprised that he had pulled folding stools out of thin air, but to think that this man without dignity or power was the commander of the enemy, the prince consort of the Merinard Kingdom? Why would a prince consort go out of his way to appear on the battlefield? Is that the custom in the Kingdom of Merinard?
In any case, he is so different in every sense of the word that I don't know how to evaluate him.
First of all, his demands are nothing short of absurd. It is still understandable that he demands immediate withdrawal after retrieving the wounded and the dead. But what usually follows is a demand for the cession of territory or payment of reparations, right? Why is this followed by the abandonment of border forts?
Border forts are important bases for national defense. We are in charge of our own army, which is actually mixed with our territorial army, and we have a certain amount of authority, but we are not given the authority to do whatever we want with a strategic national base. But he is not empowered to do anything with the strategic centers of the country at his disposal. Only two weeks is just barely enough time to exchange correspondence with the capital.
"I cannot agree to that. I don't have that kind of authority in the first place."
"The same is true for me. It is difficult to communicate with the central government in two weeks."
It may or may not be possible, but I don't think the people in the capital would accept the abandonment of the forts on the border. In any case, I would be effectively surrendering without even exchanging spears, and I would be treated as incompetent and transferred to the lower positions, or worse, I could be accused of a crime and have my knighthood degraded.
I would not want to die in battle by running into them.
"As I said before, if you don't agree to it, it doesn't matter. We'll just move on with our business."
"…Are you really willing to negotiate? Such unilateral conditions――"
"I have no intention of negotiating!"
The man who called himself Kosuke interrupted Macrito-dono, whose face turned bright red, and a blue streak appeared on his temples to say so.
"Why should we listen to those who attacked us unilaterally and be beaten to a pulp? What if it were the other way around? Would you listen to us? You wouldn't, would you? If you had made diplomatic efforts in advance, given your own justifiable reasons, and given them an ultimatum before invading, we would still listen to you, but why should we listen to those who secretly stock up foodstuffs and suddenly invade without any negotiation at all? I would like you to look back at your own actions before you talk about civility to others."
I can't say anything. It is true that our side had attacked and lost and had its tail between its legs because it foresaw the danger, so there was no need for them to listen to anything we had to say. But still, what can't be done can't be done.
"But――"
"Stop making excuses. As I said before, this is neither a request nor a demand, just a notice. This is our intention: don't ever try to take advantage of us again. We will not compromise, and we will do it. If you resist, the fort will be your coffin. That's all I'm saying."
I guess this is what they mean when they say there is no way out. Well, it is true that our side that attacked and lost can't say anything, can it?
After this, I tried to extend the two-week deadline in every way I could, but Kosuke would not budge at all. Damn him.
Previous Post Goshujin-sama to Yuku Isekai Survival! – Chapter 271
Vero says:
hehe fort goes boom boom
Kanmuru says:
Kosuke can be really cool when he wants huh?
katsuraiyuuto says:
It's about time Kosuke let off the piled up steam after the strings of unreasonable treatments the Merinard populace are subjected to.
Even for a nice guy like Kosuke, why must he care for the scums of holy kingdom at this point?
Exfernal says:
"Why should we listen to those who attacked us unilaterally and be beaten to a pulp?"
be beaten –> were beaten


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Elvis 2009: The 40th Anniversary
Of Elvis' Return to Vegas in '69
Elvis anniversaries—there have been a bunch of them noted and celebrated to various degrees in recent years. In 2004 we had the 50th anniversary of Elvis' first commercial recording, "That's All Right." The next year marked 70 years since his birth. The year 2006 featured multiple anniversaries, including Elvis' first #1 record, his first movie, and his appearances on the Sullivan show. Then in 2007 we remembered the 50th anniversaries of Elvis' gold lamé suit and the films Jailhouse Rock and Loving You. (That year, however, Elvis Presley Enterprises chose to focus on the 30th anniversary of Elvis' death.) In 2008 we recalled both Elvis's 1958 entry into the army and his 1968 TV special.
In 2009 and the big anniversary push seemed to be Elvis' return to live performing in Las Vegas 40 years ago. I use the term "push" because all of these anniversaries are perfect themes for EPE to use in promoting their Presley merchandise. And the perfect product to fit all the anniversaries is the Teddy Bear. Of course, the cuddly toy has a perpetual connection to Elvis thanks to his charting topping record in 1957. Just by changing the bear's outfit, EPE has been able to align it with each new Elvis anniversary. They've sold the same bear in gold lamé, jailhouse stripes, army fatigues, and black leather. And in 2009 year all they had to do was slap a little jumpsuit on the bear, and they created the perfect collectible to remember Elvis' 1969 Las Vegas debut.
• "Elvis Insiders" address effect of the Vegas years
Now, those of you who are regular readers of this blog know I don't often deal with Elvis collectibles. It's certainly not that I look down upon those who enjoy accumulating Elvis items. It's just that this is elvis-history-blog.com, and I see collectibles as playing a minor role in the "history" of Elvis Presley. Neither is it my intent to demean EPE, which is ultimately a business that must sell Elvis collectibles to thrive.
In fact, in addition to selling doodads, EPE offers some services that are very useful to fans like me who are interested in Elvis history. One of those is the "Elvis Insiders" club that EPE administers. I became a member in 2002, the year the group started. From time to time, I'd scroll through the Insiders' on-line forum searching for interesting discussion threads. Occasionally, the site administrator posed a question and invited members to respond. In 2009 a thoughtful question drew some thoughtful replies.
The question—"What effect do you think Elvis' years performing in Las Vegas had on his career?" Of course, many responses portrayed Elvis as being like a Saint presiding over the faithful masses who made their pilgrimage to the desert. However, many others offered more balanced views of Elvis' work during those years. They were able to see how the Vegas stage influenced Elvis' career in both positive and negative ways. Here are a few examples.
"Some of his best live performances were on the Las Vegas stage. I do believe that Elvis should have concentrated more on 3-5 day engagements in large venues such as Las Vegas, Los Angeles, New York, Atlanta, Dallas and Houston rather than a grueling one or two day appearances in smaller venues …" — GiGi, Tennessee
" … Being in Vegas was probably good in the beginning but I think he performed there for too long. Two shows a night for seven years plus touring as well I think had a detrimental effect on his health. No stars today would do such a thing …" — Gary, United Kingdom
" … to his fans he was within reach again. Being Elvis, that sure was good for his career. However, as the years moved along the show with its repetition and high frequency of performances must have felt to Elvis somewhat like his once promising movie career—stuck. Elvis' professional career could have benefited more had he been able to pursue some other creative challenges that were offered to him. The blessings of the Las Vegas contract expired long before its duration was up." — Claudia, Canada
• Elvis made himself available to fans but overdid it
Claudia made a couple of important observations. First, by returning to live performances, Elvis made himself available to his fans once again. During the Hollywood years, most of his fans, including me, had no hope of ever seeing Elvis in any venue other than a movie theater. Without doubt his popularity began to dwindle away during the middle sixties. His return to the stage revitalized his career. It reawakened many of his old fans and won him multitudes of new ones.
I never saw Elvis perform in Las Vegas. (Once in 1970, however, I was visiting my father in Las Vegas while Elvis was appearing there. I couldn't get in, of course, but one night I went to the International, stood outside the closed showroom doors, and faintly heard Elvis singing inside.) Later, when he went on the road, I was able to see him perform, and it is something I'll never forget, something that would never have been possible without him first appearing in Las Vegas.
But, as Claudia pointed out, instead of focusing solely on live performances, Elvis's career would have been better served had he focused on a variety of "creative challenges." In the 1950s Elvis performed on stage often, but he also appeared on TV occasionally and made several movies. When he came out of the army in 1960, however, he made the mistake of concentrating solely on making films. There were no multiple TV appearances or annual concert tours. That course eventually drained his creativity and enthusiasm.
Unfortunately, when he returned to live performing, Elvis made the same mistake. For the rest of his life, he focused on concert work only, forsaking all other "creative challenges" open to him. That decision—and make no mistake, it was Elvis' decision alone—was inevitably fatal to his creative spirit.
Elvis was not a big fan of Frank Sinatra, but it would have done him some good to emulate Sinatra's career path. Frank played Vegas, but not nearly as often as Elvis. In addition to his recording work, Sinatra also went on tour occasionally (both in the U.S. and abroad), usually made one movie per year, and appeared on TV from time to time. Sinatra lived to the age of 82. Perhaps if Elvis had chosen to be moderate in his Vegas work and had learned to better diversify his career, he might have lived to celebrate his 75th birthday in January 2010. — Alan Hanson | © August 2009
Go to Elvis on Stage
"As the years moved along the show with its repetition and high frequency of performances must have felt to Elvis somewhat like his once promising movie career—stuck."


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Capsules - Herboplanet
ALLERSOL
Product included in the Register of supplements of the Italian Health Ministry, Code 1984. Product included in the Register of supplements of the Belgian Health Ministry, Code NUT/PL/AS 1653/29. ALLERSOL is an integrator of methyl sulfonil methane, Lactobacillus acidophylus, Manganese and herbal ingredients that provides a calming influence on the respiratory tract.
DIFLOR PLUS - Restoration of the intestinal flora and natural defenses of the organism and well-being of the urinary tract.
Product included in the Register of supplements of the Italian Health Ministry, code 46229. Product included in the register of supplements of the Spanish Ministry of Health, code 0599/13727/2015. Product included in the Register of supplements of the French Health Ministry, code 2018-3-794. Product included in the Register of supplements of the Belgian Health Ministry, code PL/AS 1653/9. DIFLOR PLUS is a food supplement based on lactobacillus and herbal extracts. CONE FLOWER contributes to the body's natural defenses and at welfare of the urinary tract. BLACKCURRANT contributes to the regularity of transit intestinal.
FLORASOL - Miscellaneous of Lactobacilli, Bifidobacteri and Vitamin B6
Product included in the Italian Health Ministry food supplements Register, code 7443. FLORASOL is a supplement based on lactobacillus and Vitamin B6, useful to re-establish the normal wellness of bacterial flora in the intestine.
LACTORIL - Lactic ferments - Probiotic - Regenerating bacterial flora
Product included in the Italian Health Ministry food supplements Register, code 9775. LACTORIL is a supplement based on lactobacillus, useful to re-establish the normal bacterial flora in the intestine.
PROSTASOL FORTE - Functionality of the prostate and urinary tract
Product VEGAN FRIENDLY - Product included in the Register of supplements of the Italian Health Ministry, Code 76071. Product included in the Register of supplements of the Spanish Health Ministry, code 0599/9387/2017. Product included in the Register of supplements of the French Health Ministry, code 2016-6-460. Product included in the Register of supplements of the Belgian Health Ministry, Code PL 1653/18. PROSIL is a supplement based on plant extracts. NETTLE contributes to the functionality of the prostate. SAW PALMETTO contributes to promote the normal functions of the urinary system.
SULFONIL - Collagen, cartilages, bones, skin, blood vessels
Product VEGAN FRIENDLY - Product included in the Register of supplements of the Italian Health Ministry, code 4573. Product included in the Register of supplements of the Spanish Health Ministry, code 0599/9372/2017. Product included in the Register of supplements of the French Health Ministry, code 2018-1-754. Product included in the Register of supplements of the Belgian Health Ministry, code NUT/AS 1653/35. SULFONIL is a food supplement based on Methyl Sulfonyl Methane and Vitamin C. Vitamin C contributes to the protection of cells from oxidative stress. Vitamin C contributes to normal collagen formation for the normal function of blood vessels, for the normal function of bones and for the normal function of cartilage. Vitamin C contributes to normal collagen formation for the normal function of gums, of teeth and of skin. Vitamin C contributes to normal energy-yielding metabolism, to normal functioning of the nervous system and to normal psychological function. Vitamin C contributes to the normal function of the immune system.