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Biomedical subjects

Peter W de Leeuw

Publications and source records attributed to Peter W de Leeuw.

At least 19 recordsLinked to original sources
PubMed2006

A low plasma volume in formerly preeclamptic women predisposes to the recurrence of hypertensive complications in the next pregnancy.

BACKGROUND: Formerly preeclamptic women with a subnormal plasma volume (PV) have an increased risk to develop a hypertensive disorder in a subsequent pregnancy as compared to women with normal PV. In the current study we tested the hypothesis that formerly preeclamptic women who develop recurrent disease in their next pregnancy differ from their counterparts with an uneventful next pregnancy by a lower pre-pregnant PV, a lower venous capacitance, smaller rises in these indices in early pregnancy, a lower renal adaptive response, and a lower response to mild exercise. PATIENTS AND METHODS: We enrolled 33 formerly preeclamptic women in this study. Only 14 conceived within the study period, with seven of them developing a recurrent hypertensive disorder in their next pregnancy (RECUR), while seven had an uneventful next pregnancy (NORM). Before pregnancy and at 12 weeks of gestational age, we compared the following variables between these subgroups: PV, venous capacitance, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and the responses in stroke volume (SV) and heart rate (HR) to mild exercise. To estimate venous capacitance, we infused 500 mL of a modified gelatine solution in 30 minutes while recording the change in cardiac output (pulse contour analysis). The ratio of percent change in blood volume to percent change in cardiac output in response to a standardized small volume load provides an estimate for venous capacitance. RESULTS: RECUR differed from NORM by a 20% lower pre-pregnant PV (P <.02) and venous capacitance (0.29 [0.11-0.55] vs 0.86 [0.64-2.03] P = .002). NORM and RECUR were comparable with respect to pregnancy-induced rise in PV, renal hemodynamics and function, and response to mild exercise at 12 weeks. Newborn weight correlated positively with pre-pregnancy PV (R(2) = 0.53 and P = .04). CONCLUSION: Formerly preeclamptic women with a recurrent hypertensive disorder in their next pregnancy differed from their counterparts with an uneventful next pregnancy by a lower pre-pregnant PV and a lower venous capacitance, the latter two indices correlating also inversely with the incidence of fetal growth restriction. The preserved acute response to volume-related stimuli in women with a low pre-pregnant PV supports the view that the predisposition of low pre-pregnant PV to adverse pregnancy outcome may result from a concomitant, PV-dependent change setpoint and/or gain in the stimulus/response interrelation of the volume regulatory system.

Adult↗
PubMed2006

Renal artery stenosis: today's questions.

Renal artery stenosis remains a challenge, not only in terms of diagnosis but also in regard to when and how to treat this disease. Diagnostic tools that seemed promising have been unmasked as unreliable, and new treatment options such as angioplasty have failed to demonstrate their superiority. In the light of these disappointments, the most fundamental question appears to be: when is a stenosis relevant and therefore clinically significant, and how to proceed from there?

Dilatation↗
PubMed2006

Polymorphisms in human connexin40 gene promoter are associated with increased risk of hypertension in men.

OBJECTIVE: Gap junctions, formed by connexins (Cx), are important in the regulation of vascular tone. Previously, we reported two closely linked polymorphisms (-44G --> A and +71A --> G) within regulatory regions of the gene for Cx40, a major connexin in the vascular wall and the kidney. In the present study, we examined the hypothesis that these polymorphic variants are associated with hypertension and that they interact with blood pressure in healthy individuals. METHODS: Cx40 genotypes were determined in 191 subjects with essential hypertension, 198 normotensive individuals, and a healthy control population (178 twin pairs, 108 monozygotic, 70 dizygotic). RESULTS: We found a significant contribution of the minor Cx40 allele or genotype (-44AA/+71GG) to the risk of hypertension in men (P = 0.013 or P = 0.035; odds ratio, 1.87 or 2.10, respectively), but not in women. Moreover, in the healthy control population a significant effect of Cx40 genotype and sex on systolic blood pressure was found (P < 0.05 and P < 0.0001, respectively). Women carrying the minor Cx40 genotype had significantly higher systolic blood pressure compared with non-carriers (P < 0.05). In men, systolic blood pressure in carriers of the minor Cx40 genotype was not significantly different from the other two genotypes, possibly because of the small number of men in this group. However, men carrying the -44GA/+71AG genotype had higher standing systolic blood pressure compared with the more common Cx40 genotype (-44GG; P = 0.033). CONCLUSION: These findings suggest that the Cx40 polymorphisms may form a genetic susceptibility factor for essential hypertension in men.

Aged↗
PubMed2006

The optimal scheme of self blood pressure measurement as determined from ambulatory blood pressure recordings.

OBJECTIVE: To determine how many self-measurements of blood pressure (BP) should be taken at home in order to obtain a reliable estimate of a patient's BP. DESIGN: Participants performed self blood pressure measurement (SBPM) for 7 days (triplicate morning and evening readings). In all of them, office blood pressure (three consecutive readings) and 24-h ambulatory blood pressure were obtained as well. Average SBPM values, obtained from several combinations of readings, were correlated with the results of ambulatory blood pressure measurement (ABPM). In addition, we assessed whether certain patient characteristics would influence such correlations. SETTING: Patients were recruited at hospital or general practice. PATIENTS: A total of 216 untreated hypertensive patients. RESULTS: The average SBPM value calculated from day 3 to day 7, omitting the first measurement of each morning and evening session, gave the best correlation with 24-h ABPM (r = 0.70). However, similar results were obtained from a SBPM value averaged from day 3 until 5 without the first measurement of each triplicate session. Overall, younger patients had significantly better correlations than older ones. Women had significantly better correlations with ABPM than men for systolic morning and daytime SBPM, whereas men had significantly better correlations for daytime and evening diastolic SBPM (P < 0.001). In addition, all correlations increased with lower systolic office blood pressure measurement (OBPM) values. CONCLUSIONS: A minimum number of 5 days of measurement is recommended to obtain a reliable estimate of a patient's usual BP. On each day, three consecutive morning and evening measurements should be performed. For calculating the average SBPM, the first 2 days and the first measurement of each triplicate measurements should be discarded. Moreover, patient characteristics may have an impact on the number of necessary self-measurements. However, because adhering to these recommendations will make SBPM a time-consuming procedure, this type of measurement should be performed only when a decision about starting or changing antihypertensive therapy is needed or in the case of special patient groups.

Adult↗
PubMed2006

A novel approach to the study of human microcirculation: Reactivity to locally applied angiotensin II in the conjunctival microvascular bed.

OBJECTIVE: To develop a state-of-the-art, computer-assisted intravital microscopy protocol to evaluate directly the effects of topically applied drugs on conjunctival arteriolar and venular diameters. METHODS: Fifty-one normotensive volunteers were studied. Video-recordings of the bulbar conjunctival microcirculation were made before and following eye drops containing angiotensin II (AngII) (0.001% w/w, or 0.01%) or phenylephrine (0.25%). The computer-assisted analyses of arteriolar and venular diameters were performed off-line. In different protocols the microvascular reactivity to the different eye drops were compared. RESULTS: AngII (0.01%) eye drops, but not AngII (0.001%), induced significant constriction in both arterioles (median, 19%) and venules (13%). Phenylephrine eye drops (pharmacological control) induced similar arteriolar (18%) and venular (12%) constrictions. Repeated AngII challenges with a 30-min interval revealed reproducible vasoconstriction responses (median arteriolar constriction, 11 and 17%, respectively; NS). The vasoconstriction responses following AngII challenges on two consecutive days revealed reproducible responses (median arteriolar constriction, 13 and 11%, respectively; NS). CONCLUSIONS: The present results demonstrate that the proposed model for noninvasive intravital video-microscopy of the conjunctival microcirculation is sensitive for measuring direct arteriolar and venular reactivity following topically applied drugs. We consider this model a valuable tool for sophisticated research on in-vivo microvascular reactivity in humans.

Administration, Topical↗
PubMed2006

Prevalence of the white-coat effect at multiple visits before and during treatment.

OBJECTIVE: To investigate the prevalence and persistence of the white-coat effect (WCE) and white-coat hypertension (WCH) on multiple blood pressure measurement occasions in hypertensive patients with and without treatment. DESIGN: Essential hypertensive patients in whom we took office blood pressure measurements (OBPM) at eight visits (three readings per visit) performed self blood pressure measurements (SBPM) for 1 week prior to each visit (42 readings per week) over a period of 1 year. All measurements were performed with the same automatic device (Omron 705CP). In addition, 24-h ambulatory blood pressure monitoring (ABPM) was performed at the start and at the end of the study. At the start, patients did not use any medication but on subsequent visits they were treated on the basis of their SBPM values. WCH was defined as an OBPM-value > or = 140 and/or 90 mmHg and a SBPM or daytime ABPM value < 135/85 mmHg. This definition was used irrespective of treatment. We also determined the prevalence of a substantial WCE (OBPM 20 mmHg systolic or 10 mmHg diastolic higher than SBPM or daytime ABPM). SETTING: Patients were recruited at hospital or general practice. PATIENTS: A total of 163 mild-to-moderate essential hypertensive patients with a mean age of 56 years (56% males). RESULTS: At eight blood pressure (BP) measurement occasions, 75% of all patients had a substantial WCE at least once, while 57% had WCH at least once. One-third of the patients consistently had a substantial WCE and 14% consistently had WCH on three or more occasions The magnitude of the WCE was significantly related to the height of blood pressure in treated but not in untreated patients. CONCLUSION: In some patients, WCH or a substantial WCE occurs consistently on multiple OBPM visits. Especially in untreated patients, the magnitude of the WCE varies widely among individuals. These results support the incorporation of SBPM and/or ABPM into optimal management of hypertension, not only to prevent misdiagnosis in untreated patients but also to determine the need for adjusting antihypertensive therapy in treated subjects.

Blood Pressure↗
PubMed2005

The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.

Despite increased pulsatile stress, thrombotic rather than hemorrhagic events represent a major complication of hypertension. The pathophysiology of thrombosis in hypertension involves the interaction among vascular endothelium and particularly the renin-angiotensin and kallikrein-kinin systems. Because hypertension is often associated with some degree of inflammation, the combination of chronic inflammation and chronic shear stress may convert the normal anticoagulant endothelium into a procoagulant surface, expressing tissue factor. Activation of the renin-angiotensin system leads to activation of nuclear factor kappaB-dependent proinflammatory genes, also accelerating the expression of tissue factor. Renin-angiotensin and kallikrein-kinin systems interact at several levels to modulate coagulation, fibrinolysis, and vasodilatation in such a way that these 2 systems could have a major influence on the occurrence of thrombotic complications. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists may favorably influence the balance between the renin-angiotensin and kallikrein-kinin axis, regulating blood pressure as well as reducing the risk of thrombosis, which may explain part of the clinical efficacy of these drugs.

Animals↗
PubMed2005

Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise.

INTRODUCTION: In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise. PATIENTS AND METHODS: We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC). RESULTS: The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups. CONCLUSION: The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise.

Adult↗
PubMed2005

Home blood pressure measurement: a systematic review.

The purpose of this research was to review the literature on home blood pressure measurement (HBPM) and to provide recommendations regarding HBPM assessment. Observational studies on HBPM, published after 1992, as identified by PubMed, EMBASE, and Cochrane literature searches were reviewed. Studies were selected if they met the following criteria: 1) self-measurements had been performed with validated devices; 2) measurement procedures were described in sufficient detail; and 3) papers clearly explained how final HBPM results were calculated upon which conclusions and/or treatment decisions were based. Office blood pressure measurement (OBPM) yields higher blood pressure values than HBPM. For systolic blood pressure, differences between OBPM and HBPM increase with age and the height of office pressure. Differences also tend to be greater in men than in women and greater in patients without than in those with antihypertensive treatment. Furthermore, HBPM can diagnose normotension with almost absolute certainty; it correlates better with target organ damage and cardiovascular mortality than OBPM, it enables prediction of sustained hypertension in patients with borderline hypertension, and it proves to be an appropriate tool for assessing drug efficacy. Despite some limitations and although more data are needed, HBPM is suitable for routine clinical practice.

Blood Pressure Monitoring, Ambulatory↗
PubMed2005

Associations of the angiotensin II type 1 receptor A1166C and the endothelial NO synthase G894T gene polymorphisms with silent subcortical white matter lesions in essential hypertension.

BACKGROUND AND PURPOSE: Silent white matter lesions (WMLs) may represent early target organ damage of the brain in patients with hypertension. Because these lesions may have a genetic background, we assessed the associations between polymorphisms of the renin-angiotensin system and the endothelial NO synthase (NOS3) genes and silent WMLs. METHODS: Ninety-three hypertensive individuals were studied. MRI of the brain was performed to obtain estimates of the total volume of subcortical and the extent of periventricular WMLs. Patients were genotyped for the angiotensinogen (M235T), the angiotensin-converting enzyme (insertion/deletion [I/D]), the angiotensin II type 1 receptor (AGTR1 A1166C), and the NOS3 (G894T) genes. A linear regression model was used to assess the relationship of these gene polymorphisms with both subtypes of WMLs. RESULTS: When adjusted for age, diabetes mellitus, and blood pressure, subcortical WML volume was lowest in the presence of 1 or 2 AGTR1 C alleles (unstandardized beta, -38.8 [95% CI, -66.1 to -11.4] and -112.6 [CI, -188.9 to -36.4], respectively), whereas it was highest in the presence of an NOS3 T allele (31.1[corrected] [CI, 3.6 to 58.4]). No interaction between these polymorphisms on WMLs could be demonstrated. No associations were present with the other polymorphisms, either with subcortical or periventricular lesions. CONCLUSIONS: We found the AGTR1 A1166C as well as the NOS3 G894T polymorphisms to be associated with silent WMLs in the subcortical area.

Adult↗
PubMed2005

Cost analysis of procedures related to the management of renal artery stenosis from various perspectives.

To determine the costs associated with the diagnostic work-up and percutaneous revascularization of renal artery stenosis from various perspectives. A prospective multicenter comparative study was conducted between 1998 and 2001. A total of 402 hypertensive patients with suspected renal artery stenosis were included. Costs were assessed of computed tomography angiography (CTA), magnetic resonance angiography (MRA), digital subtraction angiography (DSA), and percutaneous revascularization. From the societal perspective, DSA was the most costly (euro 1,721) and CTA the least costly diagnostic technique (euro 424). CTA was the least costly imaging procedure irrespective of the perspective used. The societal costs associated with percutaneous renal artery revascularization ranged from euro 2,680 to euro 6,172. Overall the radiology department incurred the largest proportion of the total societal costs. For the management of renal artery stenosis, performing the analysis from different perspectives leads to the same conclusion concerning the least costly diagnostic imaging and revascularization procedure.

Adolescent↗
PubMed2005

Birth weight and creatinine clearance in young adult twins: influence of genetic, prenatal, and maternal factors.

Previous studies have shown that low birth weight (LBW) is a risk factor for renal impairment in adult life. The effects of LBW and renal function were studied by using twins, which allows distinguishing among fetoplacental, maternal, and genetic influences. Perinatal data were obtained at birth, and absolute creatinine clearance (not corrected for body surface area) was measured at a mean age of 25.6 yr in 653 individuals. Twins were considered both as individuals and as members of twin pairs. Statistical analyses were performed with and without adjusting for gestational age, zygosity, gender, age, body mass index, glucose level, BP, and smoking status. Creatinine clearance was 4 ml/min lower in twins with LBW (<2500 g) than in twins with a high birth weight (P < 0.04, adjusted). Intrapair birth weight difference correlated positively with the intrapair difference in creatinine clearance equally in monozygotic and dizygotic twins (r = 0.35, P < 0.0001; r = 0.43, P < 0.0001, respectively). This suggests that fetoplacental factors are related to renal function and that genetic factors are less important. There was no significant difference in creatinine clearance between twins who both had LBW as compared with twins who both had a high birth weight. This may suggest that maternal factors, which influence the relation between LBW and renal function, are less important. LBW is related to a lower creatinine clearance at adult age. This relationship is probably due to fetoplacental factors. Surprising, genetic and maternal factors seem less important.

Adult↗
PubMed2005

A subnormal plasma volume in formerly preeclamptic women is associated with a low venous capacitance.

OBJECTIVE: Pregnancy induces a smaller rise in plasma volume in formerly preeclamptic women with a pre-existent subnormal plasma volume than in their counterparts with a normal plasma volume. These women also have a three times higher recurrence rate of pregnancy-induced hypertensive disorders. In this study we tested the hypothesis that a subnormal plasma volume in these women is related to a lower capacitance of their venous compartment. METHODS: In 31 nonpregnant formerly preeclamptic women with a subnormal plasma volume and eight parous controls, we infused intravenously 500 mL of a modified gelatin solution over 30 minutes. Before and after infusion we measured the circulating levels of alpha-atrial natriuretic peptide (alpha-ANP) and active plasma renin concentration (APRC). During volume loading, we recorded the change in heart rate, stroke volume, and cardiac output using pulse contour analysis. We measured the ratio of percent change in blood volume and percent change in cardiac output during volume loading as a marker for venous capacitance. RESULTS: During volume loading, patients differed from controls by a larger rise in alpha-ANP, pulse rate, and cardiac output, and by a lower estimated venous capacitance. The concomitant response of stroke volume and APRC did not differ appreciably between groups. CONCLUSION: Formerly preeclamptic women with a subnormal plasma volume differ from controls with a normal plasma volume by a reduced venous capacitance. These results support our hypothesis that, in these women, a subnormal plasma volume indicates the presence of a subnormal venous capacitance.

Adult↗
PubMed2005

Pre-pregnant prediction of recurrent preeclampsia in normotensive thrombophilic formerly preeclamptic women receiving prophylactic antithrombotic medication.

BACKGROUND: Both hemodynamic abnormalities and thrombophilia predispose to pregnancy-associated vascular complications such as fetal growth restriction, stillbirth, preeclampsia, and placental abruption. Antithrombotic treatment may reduce the risk for these events. In this study we tested the hypothesis that in normotensive thrombophilic formerly preeclamptic women certain alterations in hemodynamic function as measured under nonpregnant conditions predict the development of hypertensive disorders and/or fetal growth restriction in the subsequent pregnancy. METHODS: In 350 nondiabetic formerly preeclamptic women, we measured in the follicular phase of the menstrual cycle at least 5 months postpartum central hemodynamic, metabolic, and hemostatic variables. In the subsequent ongoing pregnancy we determined fetal outcome variables and the incidence of maternal vascular complications. In addition to a normotensive thrombophilic profile, inclusion for final analysis required a subsequent singleton pregnancy, established within 1 year following the pre-pregnant evaluation and ongoing beyond 16 weeks' gestation. As a consequence, 47 normotensive thrombophilic formerly preeclamptic women could be included for final analysis. All formerly preeclamptic participants received aspirin throughout pregnancy. Additionally, those with thrombophilia or hyperhomocysteinemia were treated with low molecular weight heparin and with pyridoxine and folic acid supplementation, respectively. RESULTS: Among 350 formerly preeclamptic women, 266 (76%) were normotensive and 84 (24%) hypertensive. About half (140/266) of normotensive formerly preeclamptic participants were thrombophilic. One hundred eighteen formerly preeclamptic participants succeeded in establishing an ongoing pregnancy within 1 year. From this subset of formerly preeclamptic women, 47 were normotensive thrombophilic; 23 remained normotensive (THROMB), whereas 24 developed at least gestational hypertension (COMPLITHROMB). Participants in the latter subgroup were more obese than those remaining normotensive. In addition, this former subset of women had a higher vascular resistance index, and a lower plasma volume and cardiac index. With respect to fetal outcome, COMPLITHROMB gave birth to an infant with a lower birth weight relative to THROMB. Preeclampsia with or without the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome recurred in 26% of the participants in the whole thrombophilic group, in which a low pre-pregnant plasma volume and a raised vascular resistance predisposed for recurrent hypertensive disorders. CONCLUSION: Pre-pregnant hemodynamic, metabolic, and clotting variables in formerly preeclamptic women can predict hypertension in the subsequent pregnancy.

Adult↗
PubMed2005

Cerebral hyperperfusion syndrome.

Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy is characterised by ipsilateral headache, hypertension, seizures, and focal neurological deficits. If not treated properly it can result in severe brain oedema, intracerebral or subarachnoid haemorrhage, and death. Knowledge of CHS among physicians is limited. Most studies report incidences of CHS of 0-3% after carotid endarterectomy. CHS is most common in patients with increases of more than 100% in perfusion compared with baseline after carotid endarterectomy and is rare in patients with increases in perfusion less than 100% compared with baseline. The most important risk factors in CHS are diminished cerebrovascular reserve, postoperative hypertension, and hyperperfusion lasting more than several hours after carotid endarterectomy. Impaired autoregulation as a result of endothelial dysfunction mediated by generation of free oxygen radicals is implicated in the pathogenesis of CHS. Treatment strategies are directed towards regulation of blood pressure and limitation of rises in cerebral perfusion. Complete recovery happens in mild cases, but disability and death can occur in more severe cases. More information about CHS and early institution of adequate treatment are of paramount importance in order to prevent these potentially severe complications.

Algorithms↗
PubMed2005

Microvascular adaptation to changes in dietary sodium is disturbed in patients with essential hypertension.

BACKGROUND: Several studies have shown microvascular changes in patients with hypertension, but the question is still open as to whether these alterations are functional or structural. In particular, it is unknown whether the microcirculation adapts to changes in sodium intake or remains relatively fixed. METHODS: We examined bulbar conjunctival microvascular densities after 1 week of low (55 mmol Na+/24 h) and high (220 mmol Na+/24 h) sodium diet, in untreated patients with essential hypertension and in normotensive control subjects. RESULTS: On a low sodium diet, venular density was lower in essential hypertension (EH) compared with controls [median and interquartile ranges: 4.77 (4.01-5.71) versus 6.43 (6.02-7.20) mm/mm2, P = 0.001], while arteriolar density was higher [3.80 (2.41-4.46) versus 2.06 (1.74-2.23) mm/mm2, P = 0.03]. In the whole group (patients and controls), venular density correlated inversely and arteriolar density correlated positively with mean arterial pressure (MAP). Switching to a high sodium intake resulted in opposite responses in the two groups with respect to venular density (P = 0.0001): a 33% (3-80) increase in EH, but a 28% (-3 to 34) decrease in controls. Changes in venular density with increased sodium intake correlated positively with MAP on a low sodium diet in the whole group. Arteriolar density did not change significantly in either group. Also, capillary density was similar on both diets. CONCLUSION: Functional microvascular density in EH patients differs from that in normotensive subjects in a way that is dependent upon sodium intake.

Adaptation, Physiological↗