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ABSTRACT: BACKGROUND: Adrenal vein sampling (AVS) is the preferred test for subtyping primary aldosteronism. However, the procedure is technically demanding and costly. In AVS it is common practice to take duplicate blood samples at each location. In this paper we explore whether a single sample procedure leads to a different conclusion concerning the location of adrenal aldosterone secretion than a duplicate sample procedure. METHODS: AVS procedures with duplicate measurements performed in our university medical centre between 2005 and 2010 were evaluated retrospectively. We compared the conclusions regarding selectivity and lateralization based on the first sample taken (A) to the conclusions based on the average of duplicate samples (AB). We also calculated the number needed to sample in duplicate to prevent one misclassification. RESULTS: Ninety-six AVS procedures of 82 patients were included. The concordance in AVS conclusions between sample A and AB was 98-100%, depending on the criteria used for selectivity and lateralization. With permissive and strict criteria the number needed to sample in duplicate were infinite and 48, respectively. CONCLUSIONS: The incremental benefit of duplicate sampling compared to single sampling is low. Therefore, in case of technical difficulties during AVS, conclusions can also be reliably drawn from a single blood sample.
Clinica chimica acta; international journal of clinical chemistry 04/2013; · 2.54 Impact Factor
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ABSTRACT: Maintaining blood pressure during orthostatic challenges is primarily achieved by baroreceptor-mediated activation of the sympathetic nervous system, which can be divided into preganglionic and postganglionic parts. Despite their preganglionic autonomic failure, spinal cord-injured individuals demonstrate a preserved peripheral vasoconstriction during orthostatic challenges. Whether this also applies to patients with postganglionic autonomic failure is unknown. Therefore, we assessed leg vasoconstriction during 60° head-up tilt in five patients with pure autonomic failure (PAF) and two patients with autonomic failure due to dopamine-β-hydroxylase (DBH) deficiency. Ten healthy subjects served as controls. Leg blood flow was measured using duplex ultrasound in the right superficial femoral artery. Leg vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow. DBH-deficient patients were tested off and on the norepinephrine pro-drug l-threo-dihydroxyphenylserine (l-DOPS). During 60° head-up tilt, leg vascular resistance increased significantly in PAF patients [0.40 ± 0.38 (+30%) mmHg·ml(-1)·min(-1)]. The increase in leg vascular resistance was not significantly different from controls [0.88 ± 1.04 (+72%) mmHg·ml(-1)·min(-1)]. In DBH-deficient patients, leg vascular resistance increased by 0.49 ± 0.01 (+153%) and 1.52 ± 1.47 (+234%) mmHg·ml(-1)·min(-1) off and on l-DOPS, respectively. Despite the increase in leg vascular resistance, orthostatic hypotension was present in PAF and DBH-deficient patients. Our results demonstrate that leg vasoconstriction during orthostatic challenges in patients with PAF or DBH deficiency is not abolished. This indicates that the sympathetic nervous system is not the sole or pivotal mechanism inducing leg vasoconstriction during orthostatic challenges. Additional vasoconstrictor mechanisms may compensate for the loss in sympathetic nervous system control.
Journal of Applied Physiology 02/2011; 110(2):416-22. · 3.75 Impact Factor
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ABSTRACT: The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found that γ-adducin interacts with the NCC transporter. γ-Adducin colocalized with NCC to the distal convoluted tubule. (22)Na(+) uptake experiments in the Xenopus laevis oocyte showed that γ-adducin stimulated NCC activity in a dose-dependent manner, an effect that occurred upstream from With No Lysine (WNK) 4 kinase. The binding site of γ-adducin mapped to the N terminus of NCC and encompassed three previously reported phosphorylation sites. Supporting this site of interaction, competition with the N-terminal domain of NCC abolished the stimulatory effect of γ-adducin on the transporter. γ-Adducin failed to increase NCC activity when these phosphorylation sites were constitutively inactive or active. In addition, γ-adducin bound only to the dephosphorylated N terminus of NCC. Taken together, our observations suggest that γ-adducin dynamically regulates NCC, likely by amending the phosphorylation state, and consequently the activity, of the transporter. These data suggest that γ-adducin may influence BP homeostasis by modulating renal NaCl transport.
Journal of the American Society of Nephrology 12/2010; 22(3):508-17. · 9.66 Impact Factor
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ABSTRACT: Spinal cord-injured (SCI) individuals demonstrate an increased baseline leg vascular resistance (LVR). In addition, despite the lack of sympathetic control, an increase in LVR is observed during orthostatic challenges. On the basis of the vasoconstrictive characteristics of angiotensin II, we examined the hypothesis that angiotensin II contributes to the LVR at baseline and during head-up tilt (HUT) in SCI individuals.
Supine baseline leg and forearm blood flow were measured using venous occlusion plethysmography and leg blood flow during 30° HUT using duplex ultrasound. Measurements were performed before and 4 h after an angiotensin II antagonist (irbesartan, 150 mg) administered in eight SCI individuals and eight age-matched and sex-matched able-bodied controls. Vascular resistance was calculated as the arterial-venous pressure gradient divided by blood flow.
Angiotensin II blockade significantly decreased baseline LVR in SCI individuals (P = 0.02) but not in controls, whereas no changes in forearm vascular resistance were found in both groups. Angiotensin II blockade did not alter the increase in LVR during HUT in SCI individuals nor in controls.
Our results indicate that angiotensin II contributes to the increased baseline LVR in SCI individuals. As angiotensin II does not contribute to forearm vascular resistance, the contribution to LVR may relate to the extreme inactivity of the legs in SCI individuals. Angiotensin II does not contribute to the increase in LVR during HUT in SCI individuals nor in controls.
Journal of hypertension 10/2010; 28(10):2094-101. · 4.02 Impact Factor
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Journal of hypertension 07/2010; 28(7):1591-2. · 4.02 Impact Factor
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ABSTRACT: Autonomic dysreflexia is a hypertensive episode in spinal cord-injured individuals induced by exaggerated sympathetic activity and thought to be alpha-adrenergic mediated. alpha-Adrenoceptor antagonists have been a rational first choice; nevertheless, calcium channel blockers are primarily used in autonomic dysreflexia management. However, alpha-adrenoceptor blockade may leave a residual vasoconstrictor response to sympathetic nonadrenergic transmission unaffected. The aim was to assess the alpha-adrenergic contribution and, in addition, the role of supraspinal control to leg vasoconstriction during exaggerated sympathetic activity provoked by autonomic dysreflexia in spinal cord-injured individuals and by a cold pressure test in control individuals. Upper leg blood flow was measured using venous occlusion plethysmography during supine rest and during exaggerated sympathetic activity in 6 spinal cord-injured individuals and 7 able-bodied control individuals, without and with phentolamine (alpha-adrenoceptor antagonist) and nicardipine (calcium channel blocker) infusion into the right femoral artery. Leg vascular resistance was calculated. In spinal cord-injured individuals, phentolamine significantly reduced the leg vascular resistance increase during autonomic dysreflexia (8+/-5 versus 24+/-13 arbitrary units; P=0.04) in contrast to nicardipine (15+/-10 versus 24+/-13 arbitrary units; P=0.12). In controls, phentolamine completely abolished the leg vascular resistance increase during a cold pressure test (1+/-2 versus 18+/-14 arbitrary units; P=0.02). The norepinephrine increase during phentolamine infusion was larger (P=0.04) in control than in spinal cord-injured individuals. These results indicate that the leg vascular resistance increase during autonomic dysreflexia in spinal cord-injured individuals is not entirely alpha-adrenergic mediated and is partly explained by nonadrenergic transmission, which may, in healthy subjects, be suppressed by supraspinal control.
Hypertension 03/2010; 55(3):636-43. · 6.21 Impact Factor
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ABSTRACT: Computed tomography (CT), magnetic resonance imaging (MRI), and adrenal vein sampling (AVS) are used to distinguish unilateral from bilateral increased aldosterone secretion as a cause of primary aldosteronism. This distinction is crucial because unilateral primary aldosteronism can be treated surgically, whereas bilateral primary aldosteronism should be treated medically.
To determine the proportion of patients with primary aldosteronism whose CT or MRI results with regard to unilateral or bilateral adrenal abnormality agreed or did not agree with those of AVS.
PubMed, MEDLINE, EMBASE, and Cochrane Library, 1977 to April 2009.
Studies describing adults with primary aldosteronism who underwent CT/MRI and AVS were included. Of 472 initially identified studies, 38 met the selection criteria; extractable data were available for 950 patients.
The CT/MRI result was considered accurate when AVS showed unilaterally increased aldosterone secretion on the same side as the abnormality seen on CT/MRI or when AVS showed symmetric aldosterone secretion and CT/MRI revealed bilateral or no unilateral abnormality.
In 37.8% of patients (359 of 950), CT/MRI results did not agree with AVS results. If only CT/MRI results had been used to determine lateralization of an adrenal abnormality, inappropriate adrenalectomy would have occurred in 14.6% of patients (where AVS showed a bilateral problem), inappropriate exclusion from adrenalectomy would have occurred in 19.1% (where AVS showed unilateral secretion), and adrenalectomy on the wrong side would have occurred in 3.9% (where AVS showed aldosterone secretion on the opposite side).
The lack of follow-up data in the included articles made it impossible to confirm that adrenalectomies were performed appropriately.
When AVS is used as the criterion standard test for diagnosing laterality of aldosterone secretion in patients with primary aldosteronism, CT/MRI misdiagnosed the cause of primary aldosteronism in 37.8% of patients. Relying only on CT/MRI may lead to inappropriate treatment of patients with primary aldosteronism.
Annals of internal medicine 10/2009; 151(5):329-37. · 16.73 Impact Factor
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Dirk G Dechering,
Marijke S van der Steen,
Ahmet Adiyaman,
Lutgarde Thijs, Jaap Deinum,
Yan Li,
Eamon Dolan,
Reinier Pm Akkermans,
Tom Richart,
Tine W Hansen,
Masahiro Kikuya,
Jiguang Wang,
Eoin O'brien,
Theo Thien,
Jan A Staessen
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ABSTRACT: We studied the repeatability of the ambulatory arterial stiffness index (AASI), which can be computed from 24-h blood pressure (BP) recordings as unity minus the regression slope of diastolic on systolic BP.
One hundred and fifty-two hypertensive outpatients recruited in Nijmegen (mean age = 46.2 years; 76.3% with systolic and diastolic hypertension) and 145 patients enrolled in the Systolic Hypertension in Europe (Syst-Eur) trial (71.0 years) underwent 24-h BP monitoring at a median interval of 8 and 31 days, respectively. We used the repeatability coefficient, which is twice the SD of the within-participant differences between repeat recordings, and expressed it as a percentage of four times the SD of the mean of the paired measurements.
Mean AASI (crude or derived by time-weighted or robust regression) and 24-h pulse pressure (PP) were similar on repeat recordings in both cohorts. In Nijmegen patients, repeatability coefficients of AASI and PP were approximately 50%. In Syst-Eur trial patients, repeatability coefficient was approximately 60% for AASI and approximately 40% for PP. For comparison, repeatability coefficients for 24-h systolic and diastolic BP were approximately 30%. Differences in AASI between paired recordings were correlated with differences in the goodness of fit (r2) of the AASI regression line as well as with differences in the night-to-day BP ratio. However, in sensitivity analyses stratified for type of hypertension, r2, or dipping status, repeatability coefficients for AASI did not widely depart from 50 to 60% range.
Estimates of mean AASI were not different between repeat recordings, and repeatability coefficients were within the 50-60% range.
Journal of Hypertension 11/2008; 26(10):1993-2000. · 4.02 Impact Factor
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ABSTRACT: The last decade has seen the introduction of renin inhibitors and new plasma renin and prorenin assays, which has led to a better understanding of the tissue renin-angiotensin system.
To clarify the consequences of these developments for the methodology and interpretation of measurements of renin and prorenin.
The principles and application of the newly developed immunosorbent assays (ISAs) are surveyed and the results are compared with those of enzyme-kinetic assays (EKAs).
Angiotensin (Ang) II in cardiac, renal and adrenal tissue is known to originate mainly from locally produced Ang I. Experimental evidence and theoretical considerations show that a simple relation between Ang II receptor occupancy, in tissue micromilieu, and the circulating levels of Ang II or renin may not exist. This supports the clinicians' view that the plasma level of renin tells more about the mechanisms regulating its release into the circulation than about the Ang II-dependency of hypertension. ISAs are a welcome addition to clinical studies of renin inhibitors. By comparing the results of ISAs with those of EKAs, the inhibitor-bound forms of renin and prorenin can be distinguished from the unbound forms. ISAs also provide important information on the molecular basis of prorenin activation. We propose a single kinetic model to incorporate the conformational changes of prorenin induced by cryo-activation and acid-activation, and by binding to renin inhibitors. It explains why renin ISAs can overestimate the rise of renin in response to these drugs, and shows how to deal with this artefact.
Journal of Hypertension 06/2008; 26(5):928-37. · 4.02 Impact Factor
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ABSTRACT: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism-related differences in ACE concentration do not result in differences in angiotensin levels.
To investigate whether this relates to differences in the contribution of the ACE C-domain and N-domain, we quantified, using the C-domain-selective inhibitors quinaprilat and RXPA380, and the N-domain-selective inhibitor RXP407, the contribution of both domains to the metabolism of angiotensin I, bradykinin, the C-domain-selective substrate Mca-BK(1-8), and the N-domain-selective substrate Mca-Ala in serum of IIs, DDs, and 'hyperACE' subjects (i.e., subjects with increased ACE due to enhanced shedding). During incubation with angiotensin I, the highest angiotensin II levels were observed in sera with the highest ACE activity. This confirms that ACE is rate-limiting with regard to angiotensin II generation. C-domain-selective concentrations of quinaprilat fully blocked angiotensin I-II conversion in DDs, whereas additional N-domain blockade was required to fully block conversion in IIs. Both domains contributed to bradykinin hydrolysis in all subjects, and the inhibition profile of RXP407 when using Mca-Ala was identical in IIs and DDs. In contrast, the RXPA380 concentrations required to block C-domain activity when using Mca-BK (1-8) were three-fold higher in IIs than DDs.
The contributions of the C-domain and N-domain differ between DDs and IIs, and RXPA380 is the first inhibitor capable of distinguishing D-allele ACE from I-allele ACE. The lack of angiotensin II accumulation in DDs in vivo is not because of the often quoted concept that ACE is a nonrate-limiting enzyme. It may relate to the fact that in IIs both the N-domain and C- domain generate angiotensin II, whereas in DDs only the C-domain converts angiotensin I.
Journal of Hypertension 05/2008; 26(4):706-13. · 4.02 Impact Factor
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ABSTRACT: To determine which physiological mechanism is responsible for the blood pressure increase during leg crossing at knee-level in the sitting position.
Finger blood pressure was measured with the Finometer in 102 participants (47 men) before and during leg crossing: 24 treated hypertensive patients, 50 diabetic individuals (25 with and 25 without antihypertensive medication) and 28 healthy volunteers. Mean age, 53 +/- 15 years (range 21-82 years). All participants crossed their legs at knee-level, with the upper part of the popliteal fossa on the suprapatellar bursa, in the sitting position. Differences in mean blood pressure, cardiac output, stroke volume, heart rate and total peripheral resistance were assessed with legs crossed versus legs uncrossed.
Mean blood pressure [+3.3 +/- 5.5 mmHg; 95% confidence interval (CI) = 2.7-3.8], stroke volume (+7.6 +/- 5.4 ml; 95% CI = 6.7-8.6) and cardiac output (+0.4 +/- 0.9 l/min; 95% CI = 0.3-0.5) were significantly higher with legs crossed than in the uncrossed position, while the heart rate (-1.8 +/- 3.9 beats/min; 95% CI = -2.2 to -1.4) was significantly lower. Total peripheral resistance did not differ significantly (-0.01 +/- 0.16 AU; 95% CI = -0.03 to 0.00). The largest differences occurred in the hypertensive diabetic individuals, the smallest in the healthy volunteers. The changes were similar in men and women. There were no significant correlations in the total group between the differences of the hemodynamic variables and sex, age, body mass index or leg circumference.
The study shows that higher blood pressure with legs in the crossed position is due to higher cardiac output and not to a higher total peripheral resistance.
Journal of Hypertension 04/2008; 26(3):433-7. · 4.02 Impact Factor
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ABSTRACT: Background: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism-related differences in ACE concentration do not result in differences in angiotensin levels.
Methods and results: To investigate whether this relates to differences in the contribution of the ACE C-domain and N-domain, we quantified, using the C-domain-selective inhibitors quinaprilat and RXPA380, and the N-domain-selective inhibitor RXP407, the contribution of both domains to the metabolism of angiotensin I, bradykinin, the C-domain-selective substrate Mca-BK(1-8), and the N-domain-selective substrate Mca-Ala in serum of IIs, DDs, and 'hyperACE' subjects (i.e., subjects with increased ACE due to enhanced shedding). During incubation with angiotensin I, the highest angiotensin II levels were observed in sera with the highest ACE activity. This confirms that ACE is rate-limiting with regard to angiotensin II generation. C-domain-selective concentrations of quinaprilat fully blocked angiotensin I-II conversion in DDs, whereas additional N-domain blockade was required to fully block conversion in IIs. Both domains contributed to bradykinin hydrolysis in all subjects, and the inhibition profile of RXP407 when using Mca-Ala was identical in IIs and DDs. In contrast, the RXPA380 concentrations required to block C-domain activity when using Mca-BK (1-8) were three-fold higher in IIs than DDs.
Conclusion: The contributions of the C-domain and N-domain differ between DDs and IIs, and RXPA380 is the first inhibitor capable of distinguishing D-allele ACE from I-allele ACE. The lack of angiotensin II accumulation in DDs in vivo is not because of the often quoted concept that ACE is a nonrate-limiting enzyme. It may relate to the fact that in IIs both the N-domain and C- domain generate angiotensin II, whereas in DDs only the C-domain converts angiotensin I.
Journal of Hypertension 03/2008; 26(4):706-713. · 4.02 Impact Factor
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ABSTRACT: To determine whether crossing of the legs at the knee or at the ankles during blood pressure measurement in sitting position has an effect on blood pressure.
One hundred and eleven patients, 60 women, mean age 52+/-17 years (19-80): 49 chronically treated hypertensives, 28 treated diabetics and 34 normotensives were measured by one trained investigator, with an oscillometric device (Omron 705CP) on the left arm. We looked for the difference of blood pressure with the ankle or the knee crossed versus the uncrossed position.
Leg crossing at the knee during blood pressure measurement increased systolic blood pressure significantly by 6.7 (95% confidence interval 5.0-8.4) mmHg in the hypertensives and 7.9 (4.0-11.8) mmHg in the treated diabetics. Diastolic blood pressure increased by 2.3 (0.8-3.8) mmHg in the hypertensives and 1.7 (0.1-3.4) mmHg for the treated diabetics. Normotensive participants showed a smaller, though significant, increase of systolic blood pressure 2.7 (1.2-4.2) mmHg, but not significant for diastolic blood pressure, -0.1 (-1.5-1.3) mmHg, respectively. In all groups there was no effect of crossing the ankles on blood pressure. No differences were found between men and women. No significant correlation between the increase of the blood pressure when the knees were crossed and BMI, age or baseline blood pressure was present.
Blood pressure increased when legs were crossed at the knee in the sitting position. No significant increase of blood pressure was found when crossing the legs at the ankles. Leg position during measurement of blood pressure should be standardized and mentioned in publications.
Blood Pressure Monitoring 07/2007; 12(3):189-93. · 1.52 Impact Factor
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Marie Josee E van Rijn,
Anna F C Schut,
Yurii S Aulchenko, Jaap Deinum,
Fakhredin A Sayed-Tabatabaei,
Mojgan Yazdanpanah,
Aaron Isaacs,
Tatiana I Axenovich,
Irina V Zorkoltseva,
M Carola Zillikens,
Huib A P Pols,
Jacqueline C M Witteman,
Ben A Oostra,
Cornelia M van Duijn
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ABSTRACT: To study the heritability of four blood pressure traits and the proportion of variance explained by four blood-pressure-related genes.
All participants are members of an extended pedigree from a Dutch genetically isolated population. Heritability and genetic correlations of systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure were assessed using a variance components approach (SOLAR). Polymorphisms of the alpha-adducin (ADD1), angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and G protein beta3 (GNB3) genes were typed.
Heritability estimates were significant for all four blood pressure traits, ranging between 0.24 and 0.37. Genetic correlations between systolic blood pressure, diastolic blood pressure and mean arterial pressure were high (0.93-0.98), and those between pulse pressure and diastolic blood pressure were low (0.05). The ADD1 polymorphism explained 0.3% of the variance of pulse pressure (P = 0.07), and the polymorphism of GNB3 explained 0.4% of the variance of systolic blood pressure (P = 0.02), 0.2% of mean arterial pressure (P = 0.05) and 0.3% of pulse pressure (P = 0.06).
Genetic factors contribute to a substantial proportion of blood pressure variance. In this study, the effect of polymorphisms of ADD1, AGT, AT1R and GNB3 explained a very small proportion of the heritability of blood pressure traits. As new genes associated with blood pressure are localized in the future, their effect on blood pressure variance should be calculated.
Journal of Hypertension 04/2007; 25(3):565-70. · 4.02 Impact Factor
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ABSTRACT: Determining the influence of the position of the arm on blood pressure measurement in the sitting position.
Blood pressure of 128 individuals (the majority being treated hypertensive patients) visiting the outpatient clinic was measured simultaneously on both arms with arms in two different positions. First, both arms were placed at the chair support level and blood pressure was measured three times on both arms after 10 min of rest. Subsequently, while still remaining in the same sitting position, five blood pressure measurements were made simultaneously at both arms with one arm placed on the desk and one arm placed and supported at heart level (mid-sternal). The arm placed at heart level served as the reference arm. The choice of which arm was placed at desk level and which arm was placed at heart level was randomized.
Both at desk level and at chair support level, mean (+/-SD) systolic and diastolic blood pressures were higher than blood pressure at heart level by 6.1/5.7+/-4.6/3.1 and 9.3/9.4+/-5.4/3.4 mmHg, respectively. The effect of the height differences between the arm positions on the blood pressure readings was smaller than predicted (0.49 mmHg/cm systolic and 0.47 mmHg/cm diastolic). No significant correlation was found between blood pressure difference in the different arm positions (desk and heart level) and age, sex, weight or baseline blood pressure.
Different arm positions below heart level have significant effects on blood pressure readings. The leading guidelines about arm position during blood pressure measurement are not in accordance with the arm position used in the Framingham study, the most frequently used study for risk estimations.
Blood Pressure Monitoring 01/2007; 11(6):309-13. · 1.52 Impact Factor
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Journal of Renin-Angiotensin-Aldosterone System 01/2006; 6(3):163-5. · 2.44 Impact Factor
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ABSTRACT: Cardiac angiotensin-I converting enzyme (ACE) activity is influenced by the ACE I/D polymorphism. Evidence suggests that the DD-genotype may be a risk factor for cardiac hypertrophy and heart failure, especially in hypertensive subjects. We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects.
We investigated 4264 normotensive and 2174 hypertensive participants of the Rotterdam Study, a population based prospective cohort study. All subjects were available for follow-up from 1990 until 2000. Incidence rates (IR) of heart failure in normotensive subjects were the same over all genotype strata (10 per 1000 person-years). In hypertensive subjects, the IR increased with the number of D-alleles present (II: IR=13, ID: IR=18 and DD: IR=20 per 1000 person-years). Hypertensive subjects carrying the II-genotype did not have an increased risk of heart failure compared to normotensive II subjects. However, hypertensive subjects carrying one or two copies of the D-allele did have a significantly increased risk of heart failure (ID: RR: 1.4 (1.1-1.9) and DD: RR: 1.5 (1.2-2.1)).
Our findings suggest that the ACE I/D polymorphism may play a modifying role in the development of heart failure in hypertensive subjects.
European Heart Journal 01/2005; 25(23):2143-8. · 10.48 Impact Factor
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ABSTRACT: Measurement of plasma renin is important for the treatment of patients with congenital adrenal hyperplasia (CAH) and in the evaluation of patients with suspected hyperaldosteronism. Immunologic assays for plasma renin offer easier implementation and standardization than enzyme-kinetic assays for plasma renin activity, but their sensitivity and specificity have been questioned. We studied a renin immunochemiluminescence assay on an automated platform.
Renin was measured by an enzymatic assay, by IRMA, and by the new Nichols Advantage Specialty System immunochemiluminometric assay (ICMA), in plasmas from unselected individuals from our outpatient departments and in samples from patients with selected diagnoses.
The detection limit in the ICMA was 0.1 mU/L. The recovery was >90%, and the imprecision (CV) was generally <9%. Mean (SD) concentrations measured by ICMA were 32 (21)% lower than those measured by IRMA. Renin concentrations as measured by ICMA were identical in serum and EDTA-, heparin-, and citrate-anticoagulated plasmas. Prolonged incubation of whole blood at room temperature before centrifugation did not affect renin concentrations. The central 95% interval for 80 healthy adults was 6-85.5 mU/L. Plasma renin as assessed by ICMA in patients with primary hyperaldosteronism was <0.2 mU/L.
The performance characteristics of the new renin ICMA allow its use for patients with CAH and for the diagnosis of mineralocorticoid hypertension. In view of the variability of renin concentrations, use for other forms of hypertension or physiologic research calls for the development of uniform sampling protocols.
Clinical Chemistry 12/2004; 50(11):2111-6. · 7.91 Impact Factor
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ABSTRACT: Left ventricular hypertrophy (LVH) increases the risk of cardiovascular disease. We evaluated the association between antihypertensive therapy and echocardiographically determined LVH.
The Rotterdam Study is a population-based prospective cohort study among 7983 participants aged 55 years or over. Echocardiography was performed in 2823 participants. The study population consisted of 740 participants with grade 1 hypertension or antihypertensive monotherapy, without heart failure. Of these, 646 had an adequate echocardiogram for analysis of relative wall thickness (RWT) and 642 for left ventricular mass index. Participants were followed from 1 January 1991 until the date of echocardiography, between September 1992 and June 1993. Outcome measures were defined as being in the highest gender-specific quintile of left ventricular mass index and as having a RWT higher than 0.43. A Cox regression model with duration of use of antihypertensives defined as time-dependent covariates was used for data-analysis. Antihypertensive treatment lowered the risk of increased left ventricular mass index (RR 0.6, 95%CI 0.4-0.9). ACE-inhibitors, diuretics and beta-blockers all showed a risk reduction. Use of antihypertensives was also associated, although non-significantly, with a decrease of high RWT (RR 0.8, 95%CI 0.6-1.0). ACE-inhibitors, beta-blockers and calcium antagonists showed similar risk reductions, while diuretics seemed to increase the risk, possibly by reducing left ventricular end diastolic diameter.
The use of antihypertensive drugs is associated with a decreased risk of echocardiographically determined LVH in a population-based setting.
Pharmacoepidemiology and Drug Safety 11/2004; 13(10):703-9. · 2.53 Impact Factor
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ABSTRACT: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma renin concentration (PRC).
We studied 76 healthy normotensive volunteers and 28 patients with confirmed PHA. PAC and PRC were measured immunochemically in EDTA plasma on the Nichols Advantage chemiluminescence analyzer, and PRA was determined by an activity assay.
In volunteers, PAC varied from 33.3 to 1930 pmol/L, PRA from 1.13 to 19.7 ng.mL(-1).h(-1) (0.215 ng.mL(-1).h(-1) = 1 pmol.L(-1).s(-1)), and PRC from 5.70 to 116 mU/L. PAC/PRA ratios ranged from 4.35 to 494 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios from 0.69 to 71.0 pmol/mU. In PHA patients, PAC ranged from 158 to 5012 pmol/L, PRA from 0.40 to 1.70 ng.mL(-1).h(-1), and PRC from 0.80 to 11.7 mU/L. PAC/PRA ratios were between 298 and 6756 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios between 105 and 2328 pmol/mU. Whereas PAC or PRC showed broad overlap between PHA patients and volunteers, the PAC/PRC ratio indicated distinct discrimination of these two groups at a cutoff of 71 pmol/mU.
The PAC/PRC ratio offers several practical advantages compared with the PAC/PRA screening method. The present study offers preliminary evidence that it may be a useful screening test for PHA. Further studies are required to validate these results, especially in hypertensive cohorts.
Clinical Chemistry 10/2004; 50(9):1650-5. · 7.91 Impact Factor
