Shane Carney

Estimation of an age-specific reference interval for pulse wave velocity: a meta-analysis.

Objective To estimate an age-specific reference interval for carotid–femoral pulse wave velocity (PWV), an index of aortic stiffness, and to determine the predictive values of the reference range for detecting those at moderate and high risk of cardiovascular disease (CVD). Design and methods We searched MEDLINE using PubMed from 1995 to 2005 for all studies in which Carotid–Femoral PWV was measured using a Complior (Colson, Paris, France) apparatus in Caucasian non-pregnant adults. Twenty-five studies were included, covering 30 groups of subjects; these groups were classified a priori into low (normal), moderate, and high CVD risk categories, with 2008, 5979, and 180 (total 8167) subjects, respectively. Individual-level data were simulated for each group, and an age-specific reference interval was calculated by using fractional polynomial functions. Results We plotted an age-adjusted normal curve for PWV with 2.5, 5, 50, 90, 95, and 97.5 centile limits. Applying this reference interval to the moderate- and high-risk groups using simulations yielded sensitivities of 34.3 [95% confidence interval (CI) 33.2–35.3] and 57.2 (95% CI 55.2–59.3), respectively, specificities of 95.3 (95% CI 94.8–95.8) and 95.3 (95% CI 94.4–96.2), respectively, and positive likelihood ratios of 7.3 and 12.2, respectively. Conclusion We constructed an age-adjusted reference curve for PWV. Using the 95th centile of this curve as a threshold (e.g. 10.94, 11.86, and 13.18 m/s for 20, 40, and 60 years old) shows construct validity, as it appears to identify medium and high CVD risk groups reasonably accurately. This reference range needs to be tested using other datasets.

Main results of the losartan versus amlodipine (LOA) study on drug tolerability and psychological general well-being

Objective To compare two losartan regimens (with and without hydrochlorothiazide) and amlodipine in treating mild-to-moderate hypertension regarding their blood-pressure-lowering effect, drug tolerability and quality of life. Design A 12-week, randomized, double-blind, parallel- group, multi-centre study. After 4 weeks of placebo, patients with a diastolic blood pressure (DBP) in the range 95–115 mmHg were allocated randomly to be administered 50 mg losartan (increased to 100 mg if the DBP was 90 mmHg or more after 6 weeks), 50 mg losartan (plus 12.5 mg hydrochlorothiazide under the above conditions), or 5 mg amlodipine (increased to 10 mg under the above condition). The tolerability of the treatment and the quality of life were evaluated by spontaneous reporting, active questioning and the Psychological General Well-Being (PGWB) index. Study population In total 898 hypertensives, mainly referred from primary health care (mean age 57.8 years) of whom 52% were men. Results Administration of 50 mg losartan (plus 12.5 hydrochlorothiazide if necessary) and of 5 mg amlodipine (or 10 mg if necessary) lowered the blood pressure as well as or better than did 50 mg losartan (or 100 mg if necessary). The incidence of ‘any discomfort’ and ‘swollen ankles’ increased with amlodipine but not with losartan treatment. The opposite was found for ‘dizziness upon standing’. The incidence of drug-related adverse events and the number of patients withdrawn from therapy were higher with amlodipine than they were with losartan treatment. The PGWB index at week 12 indicated that improvements from baseline had occurred in some domains for the losartan groups whereas it remained unchanged for the amlodipine group. Conclusion Both losartan and amlodipine were effective in lowering the blood pressure and were tolerated well. Administration of 50 mg losartan (plus 12.5 mg hydrochlorothiazide if necessary) and of 5 mg amlodipine (or 10 mg if necessary) lowered the blood pressure equally well or better than did 50 mg losartan (or 100 mg if necessary). Drug-related adverse effects and withdrawal from the study were more common for the amlodipine group. The clinical significance of the improvements in the PGWB index with losartan needs to be studied further.

Arm position and blood pressure: a risk factor for hypertension?

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±10/60±7 to 111±14/67±10 mmHg in normotensive subjects, a mean increase of 8/7 mmHg (P<0.01). In hypertensive subjects, a similar manoeuvre increased BP from 143±21/78±17 to 166±29/88±20 mmHg, an increase of 23/10 mmHg (P<0.01). 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±19/82±10 mmHg during the former period and significantly decreased to 141±18/74±9 mmHg during the latter period (P<0.01). Regression analysis of the change in SBP and DBP with arm position change again demonstrated a close correlation (r2=0.8113 and 0.7273; P<0.001) 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.

Better Management of Cardiovascular Diseases by Pulse Wave Velocity: Combining Clinical Practice with Clinical Research using Evidence-Based Medicine

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.

Antihypertensive drug treatment: a comparison of usual care with self blood pressure measurement.

Blood pressure self-measurement is increasing in most communities and yet its role in the management of hypertension is poorly understood. This study was devised to evaluate the behaviour of doctors in general practice when treating patients with poorly controlled essential hypertension who use self-measurement. Patients, most of whom were already taking antihypertensive medications were commenced on perindopril or indapamide at their doctor’s discretion and were randomly allocated to self-measurement (SM) using an OMRON HEM706 oscillometric device or a continuation of their usual care (UC) over an 8-week period. This was an observational study without any specific or set treatment goals for the doctor to follow. Sixty of 62 subjects completed the study and the two groups were equally matched for age, body mass index, gender, and blood pressure (BP). While additional perindopril or indapamide produced a significant fall in BP in both groups over the study period, the systolic pressure remained significantly higher in the SM group (sitting 148 ± 3 compared with 142 ± 3; 145 ± 3 compared with 138 ± 3 mm Hg respectively; P < 0.05). twenty-four hour and daytime ambulatory monitor systolic pressures were also significantly higher in the sm group. differences in diastolic bp were not statistically significant. furthermore, sm patients were less likely to have their medications increased and more likely to have them reduced or ceased. doctors and patients found self-measurement convenient and useful. this study suggests that doctors prescribing decisions are influenced by evidence from self-measurement of bp with consequential increases in office bp related to reduced drug use. while self-bp measurement can offer reassurance about adequacy of control when away from a physicians office, our best evidence of understanding target blood pressures comes from large randomised studies using office blood pressures as an end-point. there is an urgent need for further study to provide arbitration between self-measurement and office blood pressures although each measurement must contribute to the management of hypertension.

Inaccuracy of wrist-cuff oscillometric blood pressure devices: an arm position artefact?

BackgroundDespite the increasing popularity of wrist-cuff blood pressure (BP) devices, their accuracy has not been established and international guidelines do not support their use. Because arm position influences BP measurement, it is possible that conflicting reports on wrist-cuff device accuracy reflects diverse arm positions. MethodThis study compared BP measured by two oscillometric devices, the upper arm-cuff OMRON HEM 705 CP and the OMRON R6 oscillometric wrist-cuff device. In the former BP was measured with the arm in two supported positions, dependent on a table (manufacturers instructions) and horizontal (mid sternum), while the latter followed the manufacturers instructions. ResultsIn contrast to the dependent arm where BP was significantly higher (P<0.05), the horizontal arm position with the arm-cuff produced a mean systolic and diastolic BP comparable to the wrist-cuff device where the wrist was at heart level being respectively, 137±29/80±16 and 134±27/77±16 mmHg. A close relationship over a wide BP range was also confirmed by least squares, least product linear regression and Bland–Altman analysis. ConclusionThis 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.

Potential roles of erythropoietin in the management of anaemia and other complications diabetes

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 A1c 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.

Circulatory Syndrome: An Evolution of the Metabolic Syndrome Concept!

The metabolic syndrome has been a useful, though controversial construct in clinical practice as well as a valuable model in order to understand the interactions of diverse cardiovascular risk factors. However the increasing importance of the circulatory system in particular the endothelium, in both connecting and controlling organ function has underlined the limitations of the metabolic syndrome definition. The proposed “Circulatory Syndrome” is an attempt to refine the metabolic syndrome concept by the addition of recently documented markers of cardiovascular disease including renal impairment, microalbuminuria, arterial stiffness, ventricular dysfunction and anaemia to more classic factors including hypertension, dyslipidemia and abnormal glucose metabolism; all of which easily measured in clinical practice. These markers interact with each other as well as with other factors such as aging, obesity, physical inactivity, diet and smoking. The final common pathways of inflammation, oxidative stress and hypercoagulability thereby lead to endothelial damage and eventually cardiovascular disease. Nevertheless, the Circulatory (MARC) Syndrome, like its predecessor the metabolic syndrome, is only a small step toward an understanding of these complex and as yet poorly understood markers of disease.

ACUTE LITHIUM ADMINISTRATION IMPAIRS THE ACTION OF PARATHYROID HORMONE ON RAT RENAL CALCIUM, MAGNESIUM AND PHOSPHATE TRANSPORT*

1. Chronic lithium (Li+) treatment commonly produces a state of hyperparathyroidism in humans and rat although the mechanism is unknown.

Pro-haemorrhagic effects of calcium antagonists : a comparison of isradipine and atenolol on ex vivo platelet function in hypertensive subjects

It has been suggested that long term treatment with calcium antagonist drugs might inhibit platelet function and lead to an anti-atheromatous effect. However recent data have also suggested that such an effect might increase mortality due to an increased incidence of gastrointestinal bleeding. We identified 43 subjects from general practice with uncomplicated mild to moderate hypertension to compare the effects of the calcium antagonist isradipine with that of the β-blocker atenolol on platelet function, plasma β-thromboglobulin levels, fibrinolysis, and serum lipids in a randomised double-blind parallel group study. After careful evaluation to exclude concomitant aspirin use, only 24 subjects were eligible to enter the study. While isradipine and atenolol produced comparable and clinically significant falls in blood pressure (167 ± 2 /102 ± 1 to 153 ± 3/91 ± 2 mm Hg, and 165 ± 2/101 ± 1 to 156 ± 4/91 ± 2 mm Hg, respectively), neither drug produced a detectable effect on ex vivo platelet aggregation, platelet retention, or thromboxane generation with adrenaline, collagen, adenosine- di-phosphate, or platelet activating factor. However a decrease in plasma β-thromboglobulin levels was observed which reached statistical significance (P < 0.05) after 12 weeks treatment in the isradipine but not the atenolol group. a 39% reduction with isradipine compared with 34% following atenolol treatment. euglobulin clot lysis time was not altered by either drug. serum cholesterol concentrations were also unaltered by drug treatment. therapeutic doses of the calcium antagonist isradipine may produce a minor indirect effect on platelet function after several weeks of treatment. however, this is of doubtful clinical importance and may simply reflect an effect of lowered blood pressure on platelet function.