Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.
The objective of this study was to re-evaluate the effect of arm position on blood pressure (BP) measurement with auscultatory and oscillometric methods including ambulatory blood pressure monitoring (ABPM). The setting was the hospital outpatient department and the subjects chosen were normotensive and hypertensive. The effect of lowering the arm from heart level on indirect systolic BP (SBP) and diastolic BP (DBP) measurement as well as the importance of supporting the horizontal arm were measured. In the sitting position, lowering the supported horizontal arm to the dependent position increased BP measured by a mercury device from 103 7 10/60 7 7 to 111 7 14/ 67 7 10 mmHg in normotensive subjects, a mean increase of 8/7 mmHg (Po0.01). In hypertensive subjects, a similar manoeuvre increased BP from 143 7 21/78 7 17 to 166 7 29/88 7 20 mmHg, an increase of 23/10 mmHg (Po0.01). Combined results from normotensive and hypertensive subjects demonstrate a direct and proportional association between BP (SBP and DBP) and the increase produced by arm dependency. Similar changes and associations were noted with oscillometric devices in the clinic situation. However, supporting the horizontal arm did not alter BP. Of particular interest, analysis of 13 hypertensive subjects who underwent ABPM on two occasions, once with the arm in the 'usual' position and once with the arm held horizontally for BP measurement during waking hours, demonstrated changes comparable to the other devices. The mean 12-hour BP was 154 7 19/82 7 10 mmHg during the former period and significantly decreased to 141 7 18/74 7 9 mmHg during the latter period (Po0.01). Regression analysis of the change in SBP and DBP with arm position change again demonstrated a close correlation (r 2 ¼ 0.8113 and 0.7273; Po0.001) with the artefact being larger with higher systolic and diastolic pressures. In conclusion, arm movements lead to significant artefacts in BP measurement, which are greater, the higher the systolic or diastolic pressure. These systematic errors occur when using both auscultatory and oscillometric (clinic and ABPM) devices and might lead to an erroneous diagnosis of hypertension and unnecessary medication, particularly in individuals with high normal BP levels. Since clinical interpretations of heart level vary, the horizontal arm position should be the unambiguous standard for all sitting and standing BP auscultatory and oscillometric measurements.
Arterial stiffness measured by pulse wave velocity (PWV) is an accepted strong, independent predictor of cardiovascular events and mortality. However, lack of a reliable reference range has limited its use in clinical practice. In this evidence-based review, we applied published data to develop a PWV risk stratification model and demonstrated its impact on the management of common clinical scenarios. After reviewing 97 studies where PWV was measured, 5 end-stage renal disease patients, 5 hypertensives, 2 diabetics, and 2 elderly studies were selected. Pooling the data by the "fixed-effect model" demonstrated that the mortality and cardiovascular event risk ratio for one level increment in PWV was 2.41 (1.81-3.20) or 1.69 (1.35-2.11), respectively.There was a significant difference in PWV between survived and deceased groups, both in the low and high risk populations. Furthermore, risk comparison demonstrated that 1 standard deviation increment in PWV is equivalent to 10 years of aging, or 1.5 to 2 times the risk of a 10 mmHg increase in systolic blood pressure. Evidence shows that PWV can be beneficially used in clinical practice for cardiovascular risk stratification. Furthermore, the above risk estimates could be incorporated into currently used cardiac risk scores to improve their predictive power and facilitate the clinical application of PWV.
This study supports the use of wrist-cuff monitors for self/home use and underlines the need for a more precise definition for arm position when using all BP devices -- mercury and oscillometric.
Evaluation of the ability of clinical staff to measure blood pressure as well as the functional state of hospital sphygmomanometers has consistently demonstrated marked deficiencies. In this study, the working order of all sphygmomanometers (manual and automated) in a teaching hospital was evaluated. Nursing staff were tested on their knowledge and use of such devices and were also asked to estimate the blood pressure from videotape. The accuracy of a commonly used automated device, Dinamap 8100, was also measured. Of 543 manual sphygmomanometers, 14% were in perfect working order although portable devices were more likely to be functional (47% of 36 units). In contrast, all 135 automated portable devices were in perfect working order although service requirements were seldom met. The mean time since last service was 18 months. There appeared to be an inverse correlation between the availability of automated and manual devices and the maintenance of wall-mounted bedside sphygmomanometers. Staff knowledge about manual devices was adequate as was their ability to accurately measure blood pressure using standardised videotape. Forty-two per cent of 31 nurses who completed the test were correct in 9 of 12 blood pressures. A comparison of this result with a comparable group of nurses tested in 1990 did not detect a significant change in competence. Direct evaluation of the commonly used Dinamap 8100 in 47 hospital patients demonstrated a poor correlation with a mercury sphygmomanometer with a D grade (fail) for systolic and a C grade for diastolic pressure. In summary, maintenance of manual sphygmomanometers was very poor, probably due to their lack of use by clinical staff. This was particularly true for units attached to bedside walls. Nursing staff demonstrated significant deficiencies in manual sphygmomanometer use although their skills were similar to those measured several years earlier. Because of the demonstrated inaccuracy of the Dinamap 8100 automated device, the strong trend towards the use of automated devices instead of manual sphygmomanometers within hospitals cannot be supported.
Erythropoietin (EPO) is a haematopoietic cytokine, mainly generated in the renal cortex, and its secretion and action is impaired in chronic kidney disease (CKD). Early renal damage in diabetes mellitus (DM) is usually not detected because diabetes-induced nephron hypertrophy maintains glomerular filtration rate (GFR) and an elevated plasma creatinine concentration is a relatively late manifestation of diabetic nephropathy. However, anaemia occurs more frequently in subjects with DM when compared with those with non-DM renal disease. While reduced production and a blunted response to EPO occurs in DM with early renal damage, other factors including chronic inflammation, autonomic neuropathy and iron deficiency are also important. Although recombinant human erythropoietin (rhEPO) has been an effective therapeutic agent in CKD anaemia, it appears to be more effective in patients with DM, even in earlier stages. Nevertheless, patients with DM are also more likely to be iron deficient, a barrier to effective rhEPO therapy. The effect of treatment on the reliability of haemoglobin A(1c) as an index of glycaemic control must be remembered. It is proposed that anaemia and its causes must be important components of care in subjects with early diabetic renal damage.
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