Ultrastructural changes in resistance arterioles of normotensive and hypertensive premenopausal women with uterine fibroids.

The association between uterine smooth muscle fibroids and systemic arterial hypertension is poorly understood. Therefore, we explored possible concomitant myocyte pathology of systemic resistance-sized arterioles (200 to 400 µm), isolated from omental samples donated by 19 women (mean age 42 y; SE 1) undergoing fibroid surgery. Vessels of 17 women (8 hypertensives) were available for transmission electron microscopy. We found ultrastructural vessel wall abnormalities in all patients, albeit with greater severity in hypertensives. In the endothelium, this ranged from moderate mitochondrial and endoplasmic reticulum stress in normotensives, to necrosis and sloughing in hypertensives. Myocyte-like cells were observed to migrate across the internal elastic lamina, with isolated subendothelial myocytes in normotensives, and focal subendothelial multicellular aggregates or myo-intimal "cushions" in hypertensives. Medial myocytes of all patients showed abnormalities similar to fibroids, with dilated sarco-endoplasmic reticulum, elongated mitochondria, and myofilament loss involving focal areas or entire cells. To our knowledge, the first study on the ultrastructure of systemic resistance arterioles of women with fibroids indicates that severe abnormalities are present that likely affect blood pressure regulation. Whether these perturbations are induced by fibroids, or represent systemic pathology that affects myocytes of both uterine and vascular tissue warrants further exploration.

Structure and function of resistance arteries from BB-creatine kinase and ubiquitous Mt-creatine kinase double knockout mice.

Increasing evidence indicates that the enzyme creatine kinase (CK) is intimately involved in microvascular contractility. The mitochondrial isoenzyme catalyses phosphocreatine synthesis from ATP, while cytoplasmic CK, predominantly the BB isoenzyme in vascular tissue, is tightly bound near myosin ATPase, where it favours ATP production from phosphocreatine to metabolically support vascular contractility. However, the effect of CK gene inactivation on microvascular function is hitherto unknown. We studied functional and structural parameters of mesenteric resistance arteries isolated from 5 adult male mice lacking cytoplasmic BB-CK and ubiquitous mitochondrial CK (CK-/-) vs 6 sex/age-matched controls. Using a Mulvany Halpern myograph, we assessed the acute maximum contractile force with 125 mM K+ and 10-5 M norepinephrine, and the effect of two inhibitors, dinitrofluorobenzene, which inhibits phosphotransfer enzymes (0.1 µM), and the specific adenylate kinase inhibitor P1, P5-di(adenosine 5') pentaphosphate (10-6 to 10-5 M). WT and CK-/- did not significantly differ in media thickness, vascular elasticity parameters, or acute maximum contractile force. CK-/- arteries displayed greater reduction in contractility after dinitrofluorobenzene 38%; vs 14% in WT; and after AK inhibition, 14% vs 5.5% in WT, and displayed abnormal mitochondria, with a partial loss of the inner membrane. Thus, CK-/- mice display a surprisingly mild phenotype in vascular dysfunction. However, the mitochondrial abnormalities and greater effect of inhibitors on contractility may reflect a compromised energy metabolism. In CK-/- mice, compensatory mechanisms salvage energy metabolism, as described for other CK knock-out models.

Creatine Kinase and Blood Pressure: A Systematic Review.

Background: Hypertension is a main risk factor for premature death. Although blood pressure is a complex trait, we have shown that the activity of the ATP-generating enzyme creatine kinase (CK) is a significant predictor of blood pressure and of failure of antihypertensive drug therapy in the general population. In this report, we systematically review the evidence on the association between this new risk factor CK and blood pressure outcomes. Method: We used a narrative synthesis approach and conducted a systematic search to include studies on non-pregnant adult humans that address the association between plasma CK and blood pressure outcomes. We searched electronic databases and performed a hand search without language restriction. We extracted data in duplo. The main outcome was the association between CK and blood pressure as continuous measures. Other outcomes included the association between CK and blood pressure categories (normotension and hypertension, subdivided in treated controlled, treated uncontrolled, and untreated hypertension). Results: We retrieved 139 reports and included 11 papers from 10 studies assessing CK in 34,578 participants, men and women, of African, Asian, and European ancestry, aged 18 to 87 years. In 9 reports, CK was associated with blood pressure levels, hypertension (vs. normotension), and/or treatment failure. The adjusted increase in systolic blood pressure (mmHg/log CK increase) was reported between 3.3 [1.4 to 5.2] and 8.0 [3.3 to 12.7] and the odds ratio of hypertension with high vs. low CK ranged between 1.2 and 3.9. In addition, CK was a strong predictor of treatment failure in the general population, with an adjusted odds ratio of 3.7 [1.2 to 10.9]. Discussion: This systematic review largely confirms earlier reports that CK is associated with blood pressure and failure of antihypertensive therapy. Further work is needed to address whether this new risk factor is useful in clinical medicine.

Body composition measures and cardiovascular risk in high-risk ethnic groups.

BACKGROUND & AIMS: Cardiovascular disease (CVD) is highly prevalent in Suriname, a middle-income country with predominantly people of African and Asian ancestry. We examined whether the more comprehensive body composition measures determined by bioelectrical impedance analysis (BIA) are superior to the more traditional BMI and waist measures in relation to cardiovascular risk. METHODS: Data from the cross-sectional Healthy Life in Suriname (HELISUR) study were used to calculate BMI, waist-hip ratio, waist-to-height ratio, and waist circumference. BIA was used to estimate fat percentage, fat-free mass index, and fat-to-fat-free mass ratio. High cardiovascular risk was defined as 1) a 10-year Framingham coronary heart disease risk score ≥10% in African-Surinamese and ≥12% in Asian-Surinamese, and 2) an increased arterial stiffness (pulse wave velocity >10 m/s). Using logistic regression analysis, we pre-selected the strongest correlate (i.e. lowest p-value below 0.05) of all body composition items for both outcomes of cardiovascular risk separately, and subsequently, used forward logistic regression modelling to determine whether other measures added value to the initial model with the strongest correlate (-2 log-likelihood (-2LL) of initial model minus -2LL of new model, χ-square statistic >3.841, 1 df). Analyses were adjusted for sex, age and ethnicity. RESULTS: We examined 691 participants (65% women; 48% African-Surinamese) with a mean age of 42 (SD 14) years. Waist circumference was the strongest correlate for high 10-year CVD risk in the total group, in men and African-Surinamese. In Asian-Surinamese, fat-free mass index was the strongest correlate of high 10-year CVD risk. Increased arterial stiffness was most strongly related with waist-to-height ratio in the total group and in African-Surinamese, and with BMI in men. None of the measures were significantly associated in women (for both outcomes) and Asian-Surinamese (for increased arterial stiffness). Forward selection showed that only BMI added value next to waist-to-height ratio in the total group in relation to increased arterial stiffness. CONCLUSIONS: Waist measures, in particular waist circumference and waist-to-height ratio, and BMI should be used in African and Asian-Surinamese to identify who is at increased cardiovascular risk. Overall, we found little advantage in using BIA measures rather than simple anthropometric measures.

Prevalence and reproducibility of differences between home and ambulatory blood pressure and their relation with hypertensive organ damage.

Home and ambulatory blood pressure (BP) better predict cardiovascular disease than office BP, but are not interchangeable. We hypothesised that home BP may be higher than office BP because of anticipatory reactions to self-measurement and studied prevalence and reproducibility of incremental differences between home and daytime ambulatory BP and their relation with hypertensive organ damage. A total of 176 participants (mean age 57.1±12.8 years, 43.2% female) measured their BP for 2 weeks and received a 24-h ambulatory BP in between. Hypertensive organ damage was assessed by urinary albumin-to-creatinine ratio and electrocardiographic criteria for left ventricular hypertrophy. Thresholds of 10/5 and 20/10 mm Hg were used to define relevant systolic/diastolic differences between home and ambulatory BP. A higher home compared to ambulatory BP was present in 92 (52.3%) and 35 (19.1%) participants, while lower home BP values were present in 36 (20.4%) and 8 (4.5%) subjects for differences ⩾10/5 and ⩾20/10 mm Hg. Participants with higher home than ambulatory BP differences were older, had higher body mass index, higher office BP, more antihypertensive medication and lower glomerular filtration rate (P<0.01). Differences between home and ambulatory BP were highly reproducible (r=0.80 and 0.67 for systolic and diastolic BP, P<0.001). Both home and ambulatory BPs were associated with organ damage, but their difference was not. Many patients have a significantly higher home than ambulatory BP. Differences between home and ambulatory BP are reproducible, but not associated with hypertensive organ damage. Our findings suggest that ambulatory BP remains the standard of reference when positive differences between home and ambulatory BP exist.

Creatine kinase inhibits ADP-induced platelet aggregation.

Bleeding risk with antiplatelet therapy is an increasing clinical challenge. However, the inter-individual variation in this risk is poorly understood. We assessed whether the level of plasma creatine kinase, the enzyme that utilizes ADP and phosphocreatine to rapidly regenerate ATP, may modulate bleeding risk through a dose-dependent inhibition of ADP-induced platelet activation. Exogenous creatine kinase (500 to 4000 IU/L, phosphocreatine 5 mM) added to human plasma induced a dose-dependent reduction to complete inhibition of ADP-induced platelet aggregation. Accordingly, endogenous plasma creatine kinase, studied in 9 healthy men (mean age 27.9 y, SE 3.3; creatine kinase 115 to 859 IU/L, median 358), was associated with reduced ADP-induced platelet aggregation (Spearman's rank correlation coefficient, -0.6; p < 0.05). After exercise, at an endogenous creatine kinase level of 4664, ADP-induced platelet aggregation was undetectable, normalizing after rest, with a concomitant reduction of creatine kinase to normal values. Thus, creatine kinase reduces ADP-induced platelet activation. This may promote bleeding, in particular when patients use platelet P2Y12 ADP receptor inhibitors.

High salt meals in staff canteens of salt policy makers: observational study.

OBJECTIVE: To assess the salt content of hot meals served at the institutions of salt policy makers in the Netherlands. DESIGN: Observational study. SETTING: 18 canteens at the Department of Health, the Health Council, the Food and Consumer Product Safety Authority, university hospitals, and affiliated non-university hospitals. INTERVENTION: A standard hot meal collected from the institutional staff canteens on three random days. MAIN OUTCOME MEASURE: Salt content of the meals measured with an ion selective electrode assay. RESULTS: The mean salt content of the meals (7.1 g, SE 0.2 g) exceeded the total daily recommended salt intake of 6 g and was high at all locations: 6.9 g (0.4 g) at the Department of Health and National Health Council; 6.0 g (0.9 g) at the Food and Consumer Product Safety Authority; 7.4 g (0.5 g) at university hospital staff canteens; and 7.0 g (0.3 g) at non-university hospital staff canteens. With data from a national food consumption survey, the estimated total mean daily salt intake in people who ate these meals was 15.4 g. This translates into a 23-36% increase in premature cardiovascular mortality compared with people who adhere to the recommended levels of salt intake. CONCLUSION: If salt policy makers eat at their institutional canteens they might consume too much salt, which could put their health at risk.

Ethnic differences in resistance artery contractility of normotensive pregnant women.

Black women are at a greater risk to develop hypertension during pregnancy, with a 4.5 times higher rate of fatal preeclampsia than white women. Therefore, it is important to identify factors that may affect this risk. Our group previously proposed that high activity of the central regulatory enzyme of energy metabolism, creatine kinase (CK), may increase ATP-buffering capacity and lead to enhanced vascular contractility and reduced nitric oxide bioavailability. Therefore, we assessed microvascular contractility characteristics in isolated resistance arteries from self-defined black and white normotensive pregnant women using a Mulvany-Halpern myograph. Additionally, morphology was assessed with electron microscopy. Resistance-sized arteries obtained from omentum donated during cesarean sections (11 black women and 20 white women, mean age: 34 yr) studied in series showed similar morphology but significantly greater maximum contractions to norepinephrine (10(-5) M) in blacks [14.0 mN (1.8 SE)] compared with whites [8.9 mN (1.4 SE), P = 0.02]. Furthermore, we found greater residual contractility after the specific CK inhibitor dinitrofluorobenzene (10(-6) M) in black women [55% (6 SE)] compared with white women [28% (4 SE), P = 0.001] and attenuated vasodilation after bradykinin (10(-7) M) in black women [103% (6 SE)] compared with white women [84% (5 SE), P = 0.023], whereas responses to sodium nitroprusside (10(-4) M) and amlodipine (10(-6) M) were similar. We conclude that compared with white women, normotensive pregnant black women display greater resistance artery contractility and evidence of higher vascular CK activity with attenuated nitric oxide synthesis. These findings in normotensives may imply that the black population is at risk for a further incline in pregnancy-related hypertensive disorders.

Value of retinal examination in hypertensive encephalopathy.

The presence of grade III or IV hypertensive retinopathy (HRP) is considered to distinguish hypertensive urgencies from emergencies. However, case-reports suggest that these retinal changes may be lacking in patients with hypertensive encephalopathy. To assess the frequency of grade III and IV retinopathy in this hypertensive emergency, we conducted a retrospective cohort study. We retrieved 162 patients with malignant hypertension and 34 patients (17%) fulfilled the predefined criteria for hypertensive encephalopathy. Data on retinal examination were incomplete for 6 patients (18%), thus leaving 28 patients who were analysed for the presence or absence of grade III and IV HRP. In 9 (32%) patients with hypertensive encephalopathy, grade III or IV HRP was absent, 11 (39%) patients presented with grade III and 8 (29%) patients with grade IV retinopathy. Patients without retinal abnormalities were on average 13 years younger (P=0.05), more often black (P=0.02) and displayed lower blood pressure (BP) values (P=0.04 for systolic and diastolic BP). A substantial proportion of patients with hypertensive encephalopathy lack grade III or IV HRP. This suggests that the decision to admit these patients should not only rely on the presence of grade III and IV retinopathy alone, but should also include a careful neurological examination.

Continuous non-invasive blood pressure monitoring, a validation study of Nexfin in a pregnant population.

OBJECTIVE: To assess the accuracy of a non-invasive beat-to-beat continuous blood pressure monitoring device (Nexfin) in pregnancy according to the International Protocol of the European Society of Hypertension. METHODS: The validation was performed according to the International Protocol of the European Society of Hypertension. The test device (Nexfin, BMEYE, Amsterdam, the Netherlands) calculates beat to beat blood pressure from finger pulse wave analysis. Measurements of systolic and diastolic BP in 33 volunteers were obtained using the mercury sphygmomanometer and the Nexfin alternatingly. RESULTS: The device passed phase 1 as 30 systolic and 32 diastolic readings fell within 5 mmHg (25 required). In addition, the device also passed phase 2.1 as 68 systolic and 67 diastolic readings fell within 5 mmHg (65 required). Finally, it failed to pass phase 2.2 as 24 subjects for systolic and 23 for diastolic had at least 2/3 of their comparisons falling within 5 mmHg (22 required) but 6 subjects for systolic and 8 for diastolic had all three comparisons more than 5 mmHg different from the mercury readings (three allowed). The mean differences were 2.3 mmHg (SD 6.8) for SBP and 0.8 mmHg (SD 6.3) for DBP. CONCLUSION: The Nexfin device passed phase 1 and phase 2.1 but failed to pass phase 2.2. However, adaptation of the data to the more permissive AAMI (mean difference <5 +/- 8 mmHg) and BHS (systolic grade B, diastolic grade A) protocols indicated adequate accuracy for application in research settings or for longitudinal within-patient tracking of blood pressure, given the possibility for continuous monitoring.

[Angiotensin II-receptor antagonists compared to other antihypertensives: still insufficient evidence for reducing the risk of cerebrovascular incidents]. / Angiotensine II-receptorantagonisten vergeleken met andere antihypertensiva: nog onvoldoende bewijs voor een lager risico op herseninfarcten.

--There is growing evidence that angiotensin II-receptor antagonists may have protective effects for preventing cerebrovascular incidents. --It is unlikely that these effects are due only to a decrease in blood pressure. --One hypothesis is that high concentrations ofangiotensin II result in improved cerebral perfusion ofangiotensin type 2-receptor mediated mechanisms such as local vasodilatation and angiogenesis. --Several clinical and preclinical studies support this hypothesis. --The results of these studies are discussed in this overview. There is still insufficient evidence that a protective effect on the brain occurs.

WITHDRAWN: Effect of antihypertensive drugs on mortality, morbidity and blood pressure in blacks.

BACKGROUND: Black people have a greater prevalence of elevated blood pressure leading to excess morbidity and mortality. OBJECTIVES: To systematically review the effects of different antihypertensive drugs on mortality, morbidity and blood pressure black adults with elevated blood pressure. SEARCH STRATEGY: Medline, Embase, LILACS, African Index Medicus, the Cochrane Library November 2003; Pubmed September 2003 to March 2004. Searches were conducted without language restriction. SELECTION CRITERIA: Randomised controlled trials of drugs versus placebo (blood pressure outcomes) or versus placebo or other drugs (morbidity and mortality outcomes). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data unblinded. Disagreements were resolved by discussion. Authors were contacted twice to obtain missing information. MAIN RESULTS: Full reports or abstracts from more than 2900 references of papers yielded 30 trials considering 53 interventions with 8 classes of antihypertensive drugs in 20,006 black patients from Africa, the Caribbean, and the United States of America, aged 18 to >80 years. In one large trial the main morbidity and mortality outcomes did not differ significantly between initial treatment drug classes when drugs were added to reach goal blood pressures. However, the comparison ACE Inhibitors vs diuretic favoured the diuretic for stroke 1.40 [1.17 to 1.68]; combined CHD 1.15 [1.02 to 1.30] and combined CVD 1.19 [1.09 to 1.30] and the comparison alpha blocker vs diuretic favoured the diuretic for combined CVD 1.40 [1.25 to 1.57]. In addition, all comparisons for heart failure favoured diuretic (1.47 [1.24 to 1.74] vs calcium blocker; 1.32 [1.11 to 1.58] vs ACE Inhibitor; and 2.18 [1.73 to 2.74] vs alpha blocker. The results also showed a greater occurrence of diabetes with diuretics. No significant differences were detected between placebo and beta adrenergic blockers in the reduction of systolic blood pressure (weighted mean difference [95% CI], -3.52 [-7.50 to 0.46] mm Hg). In addition, ACE inhibitors did not significantly differ from placebo in achievement of goal diastolic blood pressure (risk difference [95% CI], 5% [-10% to 21%]). Calcium blockers, diuretics, centrally acting agents, alpha adrenergic blockers and angiotensin II antagonists were all more effective than placebo in reducing blood pressure in the pooled analyses. Only calcium blockers remained effective in all prespecified subgroups, including baseline diastolic blood pressure >109 mm Hg. AUTHORS' CONCLUSIONS: When first-line drugs from different classes are compared in the treatment of black people, there is no evidence of differential effects on most mortality and morbidity outcomes. Those morbidity differences that were found favoured diuretics. Drugs differ in their ability to reduce blood pressure in black people. Calcium blockers were the only drug class that reduced blood pressure in all subgroups of black people including those with severe hypertension. Beta-blockers, angiotensin receptor blocker, alpha blockers and ACE Inhibitors were least good at reducing blood pressure in black adults.

[The most recent study into blood pressure lowering by amlodipine: the beginning of the end for the beta-blockers]. / De nieuwste studie naar bloeddrukverlaging door amlodipine: begin van de aftocht van beta-blokkers.

In the 'Anglo-Scandinavian cardiac outcomes trial-blood pressure lowering arm' (ASCOT-BPLA), a regimen ofamlodipine and perindopril was compared with a classic regimen of atenolol and bendroflumethiazide in over 19,000 hypertensive subjects. Most likely related to a lower systolic blood pressure, a better metabolic profile and inferiority of the comparator atenolol, the trial showed better outcomes for total and cardiovascular mortality, fatal and nonfatal stroke and cardiovascular events and procedures for the combination of newer agents. Additionally, the newer combination was associated with a 30% reduction in new-onset diabetes mellitus. It is expected that these newer drugs will quickly replace the beta-blockers as the medication for patients with high blood pressure.

Comparison of randomization techniques for clinical trials with data from the HOMERUS-trial.

BACKGROUND: Several methods of randomization are available to create comparable intervention groups in a study. In the HOMERUS-trial, we compared the minimization procedure with a stratified and a non-stratified method of randomization in order to test which one is most appropriate for use in clinical hypertension trials. A second objective of this article was to describe the baseline characteristics of the HOMERUS-trial. METHODS: The HOMERUS population consisted of 459 mild-to-moderate hypertensive subjects (54% males) with a mean age of 55 years. These patients were prospectively randomized with the minimization method to either the office pressure (OP) group, where antihypertensive treatment was based on office blood pressure (BP) values, or to the self-pressure (SP) group, where treatment was based on self-measured BP values. Minimization was compared with two other randomization methods, which were performed post-hoc: (i) non-stratified randomization with four permuted blocks, and (ii) stratified randomization with four permuted blocks and 16 strata. In addition, several factors that could influence outcome were investigated for their effect on BP by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: Minimization and stratified randomization did not lead to significant differences in 24-h ABPM values between the two treatment groups. Non-stratified randomization resulted in a significant difference in 24-h diastolic ABPM between the groups. Factors that caused significant differences in 24-h ABPM values were: region, centre of patient recruitment, age, gender, microalbuminuria, left ventricular hypertrophy and obesity. CONCLUSION: Minimization and stratified randomization are appropriate methods for use in clinical trials. Many outcome factors should be taken into account for their potential influence on BP levels. Recommendation. Due to the large number of potential outcome factors that can influence BP levels, minimization should be the preferred method for use in clinical hypertension trials, as it has the potential to randomize more outcome factors than stratified randomization.

[Atenolol or metoprolol as beta-blocker in the treatment of hypertension]. / Atenolol en metoprolol beide geschikt als beta-blokker voor de behandeling van hypertensie.

Recently the guideline committee of the Dutch College of General Practitioners advocated the use of metoprolol instead of atenolol in patients with an indication for beta-blockers. This recommendation was based on a recent meta-analysis in The Lancet in which no effect was observed in favour ofatenolol compared with placebo on all-cause mortality, cardiovascular mortality and myocardial infarction. Atenolol also had a higher total mortality and stroke risk compared with other antihypertensive agents. Apart from the presence of statistical heterogeneity and the inappropriate use of a fixed-effect model, the studies referred to in this meta-analysis were also clinically heterogeneous. Furthermore, in most studies, only older patients were included. In older patients with hypertension, it is known that beta-blockers are less effective than diuretics or calcium antagonists. Comparative trials between atenolol and metoprolol in the treatment of hypertension have not been performed with regard to cardiovascular endpoints. We conclude that there is no evidence that atenolol is better or worse than metoprolol in the treatment of the hypertensive patient. For the treatment of patients with heart failure, however, lipophilic beta-blockers such as metoprolol may be preferred, as these drugs have been more thoroughly evaluated for this indication.

[The practice guideline 'Hypertension' (third revision) from the Dutch College of General Practitioners; a response from the perspective of internal medicine]. / De standaard 'Hypertensie' (derde herziening) van het Nederlands Huisartsen Genootschap; reactie vanuit de interne geneeskunde.

The revised practice guideline on hypertension from the Dutch College of General Practitioners is a useful document for the management of hypertension. The decision to limit antihypertensive treatment to patients with at least a 20% risk of developing cardiovascular disease within 10 years may, however, be criticised. Prolonged untreated mild hypertension may lead to macro- and microvascular myocardial sclerosis and disturbed systolic and diastolic function of the left ventricle. A 10% risk is preferred. On the other hand, case-finding and treatment of patients with hypertension will increasingly be a major time-consuming activity in general practice. This calls for a change in organisation: well-trained vascular assistants should be employed to fulfill most of this task.

Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia.

PURPOSE: To evaluate whether differences in autonomic cardiovascular control between normal pregnant women and women who develop pre-eclampsia later in pregnancy can be detected even before or early in pregnancy. DESIGN: We studied 42 women, 21 multigravid with a history of pre-eclampsia and 21 primigravid, before pregnancy, at 6, 8, 12, 16, 20 and 32 weeks gestation and 15 weeks after delivery. METHODS: The outcome of pregnancy was classified after delivery as normal pregnancy (NP group) or pre-eclampsia (PE group). Continuous heart rate and blood pressure were recorded by Portapres (TNO, Amsterdam, The Netherlands) during orthostatic stress, during rest in a supine and sitting position, and during paced breathing for periods of 1 min at breathing frequencies of 6, 10 and 15 breaths/min. Baroreflex gain from heart rate and blood pressure variability and the phase angle between both signals at low (approximately 0.1 Hz) and high frequency (respiratory rate) were analyzed by spectral analysis. RESULTS: Eight women were diagnosed with pre-eclampsia. Subgroups did not differ in age, weight or height. The PE group showed a significantly higher mean arterial pressure before and during pregnancy [analysis of variance (ANOVA), P = 0.001], a significantly larger initial blood pressure drop to orthostatic stress before and in the first half of pregnancy (ANOVA, P = 0.002) and a significantly larger negative phase difference during supine rest at low frequency from 8 weeks onward (ANOVA P = 0.003). CONCLUSIONS: These findings are compatible with increased resting sympathetic activity and decreased circulating volume, already present before and early in pregnancy, in women who will later develop pre-eclampsia.

[Routine funduscopic examination in hypertensive patients not useful]. / Routinematig onderzoek van de retina bij patiënten met hypertensie niet zinvol.

Funduscopic examination according to the classification of Keith, Wagener and Barker has been used since 1939 to assess retinal damage in patients with hypertension. Improved treatment possibilities and the screening of patients with hypertension seem to have led to a decrease in the incidence and severity of the retinal abnormalities found. The following findings have been published during the past ten years. The assessment of retinopathy is subject to a large interobserver-variability, especially with respect to venous-crossings and arteriolar narrowing of retinal vessels. The positive and negative predictive value of retinopathy for high blood pressure is low. The association of retinopathy with other predictive indicators for organ damage is inconsistent and its association with cardiovascular complications is weak. These findings indicate that the usefulness of funduscopic examination as an instrument for assessing organ damage in patients with hypertension is limited. Therefore it should not be used as a routine diagnostic tool unless a hypertensive crisis is indicated.

[Hypertension in young adults: indication for possible aortic coarctation]. / Hypertensie bij jongvolwassenen: aanwijzing voor mogelijke coarctatio aortae.

Three adult patients, a woman aged 37 and two men aged 22 and 23 years respectively, were admitted due to an unexplained hypertension. After a significant delay, the diagnosis of aortic coarctation was established for these patients. In two of them the abnormality was operatively corrected and the blood pressure subsequently normalised; the third patient is on the waiting list for the operation. In all three patients an earlier diagnosis could have been established, had accurate blood-pressure measurements of both arms and at least one leg been performed. Late detection and treatment of aortic coarctation have a profound detrimental effect on survival. Therefore it is extremely important to accurately measure the blood pressure in the limbs of young patients with hypertension.