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Biomedical subjects

D G Beevers

Publications and source records attributed to D G Beevers.

At least 37 records · Page 2Linked to original sources
PubMed2003

A comparison of flow-mediated dilatation and von Willebrand factor as markers of endothelial cell function in health and in hypertension: relationship to cardiovascular risk and effects of treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.

Loss of adequate endothelial cell function (associated with various cardiovascular syndromes such as hypertension) is most widely quantified by assessing flow-mediated dilatation (FMD) or measuring plasma markers such as von Willebrand factor (vWF). However, the relationship between these two methods is unclear, as is their relationship to 10-year cardiovascular risk (defined by the Framingham equation) and their response to intensive cardiovascular risk factor management. We tested the hypothesis that there is an inverse relationship between vWF and FMD by measuring both in 132 subjects, of whom 89 were hypertensive (mean blood pressure, 167/91 mmHg) and 43 were healthy normotensive (mean blood pressure, 133/80 mmHg). High-resolution ultrasound assessed endothelium-dependent brachial artery FMD following reactive hyperaemia after occlusion. Plasma vWF was defined by enzyme-linked immunosorbent assay. These measurements were repeated in the patients after 6 months of intensive cardiovascular risk factor management. vWF and FMD correlated significantly (r = -0.517, P < 0.001), and both correlated with 10-year cardiovascular risk using the Framingham equation (vWF, r = 0.48, P < 0.001; FMD, r = -0.624, P < 0.001). Following 6 months intensive cardiovascular risk factor management, plasma vWF was significantly reduced whereas FMD significantly increased (both P < 0.002). We conclude that two fundamentally different methods for assessing endothelial function correlate well with each other, as well as with 10-year cardiovascular risk. Six months of intensive risk factor management is beneficial to the endothelium, as defined by improved vWF and FMD. These methods might therefore be useful indices to identify patients at risk of future cardiovascular events, and may also assist in the understanding of early developments in the pathogenesis of vascular risk in hypertension.

Aged↗
PubMed2002

The epidemiology of salt and hypertension.

The relationship between salt intake and blood pressure was once highly controversial. Early comparisons of populations did support the salt hypothesis but were difficult to interpret because of unmeasured confounding variables. However, the INTERSALT project, published in 1988 overcame many of these problems and reported within - and between - population gradients of sodium excretion and blood pressure or the rise in blood pressure with advancing age. Of the five long-term follow-up studies of salt intake and cardiovascular disease, two suggested that a low salt intake might be harmful. These studies are however open to much criticism. The three other studies reported positive relationships between salt intake and stroke or heart attack. Whilst there is little doubt that salt restriction lowers blood pressure in hypertensive patients, there remains some uncertainty whether any effect is seen in normotensives. The effects, if present, are small (reducing systolic pressure by about 2 mmHg) and not clinically useful, although if applied on a population-wide basis they might reduce the prevalence of hypertension by about 17 %. In many countries food producers and food standards agencies are beginning to respond by cutting the salt content of processed foods.

Cardiovascular Diseases↗
PubMed2002

Ethnic differences in blood pressure and the prevalence of hypertension in England.

The objective of this study was to examine the prevalence of hypertension and mean blood pressures among Afro-Caribbeans and South-Asians in England compared with Caucasians. Data from the Birmingham Factory Screen, Birmingham INTERSALT volunteers, and four West Midlands churches were combined into a single database (n = 2853), since all three studies employed identical methods. The cohort comprised 2169 (76%) Caucasians (71% men); 453 (16%) Afro-Caribbean (60% men); and 231 (8%) South-Asian men. The results were that overall prevalence of hypertension (> or =160/95 mm Hg or taking antihypertensives) was greater in both Afro-Caribbean men (31%) and women (34%) (both P < 0.001), compared with Caucasians (19% and 13% respectively), while South-Asian men had a similar overall prevalence to Caucasians (16%). Compared with Caucasians, Afro-Caribbeans had significantly higher mean systolic blood pressure, with higher mean diastolic blood pressures evident among Afro-Caribbean women. After adjustment for age, body mass index, smoking, and weekly alcohol intake, the odds ratios (95% CI) for being hypertensive were 1.56 (1.14 to 2.13; P = 0.005) and 2.40 (1.51 to 3.81; P = 0.0002) for Afro-Caribbean men and women, respectively and 1.31 (0.88 to 1.97; P = 0.19) for South-Asian men, compared with Caucasians. In conclusion the prevalence of hypertension and mean blood pressures are higher among Afro-Caribbeans compared with Caucasians. South-Asian men had similar rates of hypertension and mean blood pressures to Caucasians.

Adult↗
PubMed2002

Oxidative stress in malignant and non-malignant phase hypertension.

Malignant hypertension (MHT) is a rare and severe form of hypertension characterised by arteriolar necrosis and severe vascular damage, leading to stroke, myocardial infarction and death. We hypothesised that in addition to endothelial damage, MHT may be associated with increased oxidative stress. Lipid hydroperoxides (LHP, an index of oxidative damage) and plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction) were measured in 16 patients with MHT and compared with 16 non-malignant essential hypertensives and 32 normotensive controls. vWf was greater in MHT (mean 117 iU/dL) than in non-malignant hypertensives (97 iU/dL) or normotensive controls (100 iU/dL) (ANOVA P = 0.017). However, although LHP were greater in MHT (mean 10.6 micromol/L) than in normotensives (4.5 micromol/L, P < 0.001), the levels in MHT were similar to those in non-malignant hypertension (12.3 micromol/L). In conclusion endothelial damage (raised vWf) was more evident in MHT compared with both normotensive controls and with non-malignant hypertension, whilst oxidative stress (raised LHP) was increased to a similar extent in both hypertension groups when compared with normotensive controls. These observations raise the possibility abnormal oxidative stress is probably not the mechanism responsible for the endothelial damage seen in malignant phase hypertension.

Analysis of Variance↗
PubMed2002

Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1.

At least four independent studies in different clinical settings showed that angiotensin-converting enzyme inhibitors (ACE-Is) such as enalapril effectively decrease plasma levels of circulating adhesion molecules (cAMs). To examine whether this effect may be mediated by the decreased action of angiotensin, we compared the effects of enalapril with the direct angiotensin-II antagonist, losartan, on plasma levels of cAMs, and monocyte chemotactic protein-1 (MCP-1). In a randomized trial, we recruited 32 untreated patients (19 male, aged 59+/-13 years) with hypertension, who received either enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day) at equipotent doses. Enalapril decreased plasma levels of all cAMs after 8 weeks of treatment: cE-selectin levels decreased by 13% (P=0.007), intercellular adhesion molecule-1 (cICAM-1) by 15% (P=0.002) and vascular cell adhesion molecule-1 (cVCAM-1) by 19% (P=0.003). Similarly, enalapril decreased plasma levels of MCP-1 by 13% (P<0.001). Losartan did not significantly change cAM or MCP-1 plasma concentrations after 8 weeks of treatment: cE-selectin levels decreased by 3%, cICAM-1 by 5%, cVCAM-1 by 8%, whereas MCP-1 increased by 2% (all P=NS; not significant). The enalapril effect on percentage changes of cVCAM-1 was significantly different from losartan (P=0.0429). Eight weeks of antihypertensive treatment with enalapril but not losartan, significantly decreased plasma levels of cAMs and MCP-1 in hypertensive patients. The beneficial effects of ACE-Is on cAMs may have implications for atherogenesis and the reduction of cardiovascular events, which cannot be fully explained by their antihypertensive effects alone.

Aged↗
PubMed2002

Anti-hypertensive drugs in pregnancy and fetal growth: evidence for "pharmacological programming" in the first trimester?

OBJECTIVES: To determine the timing and exact nature of the effect of the drug atenolol upon fetal growth. Also to discover if the reduction in fetal growth is due to superimposed pre-eclampsia or any other confounding variable. DESIGN: A retrospective cohort study of prospectively collected data in a hypertensive pregnancy database. SETTING: Two district general hospitals in the midlands of England. Both hospitals have specialised medical antenatal clinics for pregnant women with chronic hypertension. PARTICIPANTS: 491 pregnancies in 380 women with essential or secondary hypertension. OUTCOME MEASURES: The outcome measures used were the infant birth weight, birth weight standardized for gestational age, and the ponderal index at birth, a surrogate measure for in utero growth restriction. RESULTS: The babies of women taking atenolol at conception or during the first trimester had significantly lower birth weights (by 139-512 g, p<0.01) than women on calcium channel blockers or no medication. Likewise the ponderal index was also significantly reduced, p<0.01. In addition most of these babies were small for gestational age (SGA) with 70% on or below the 10th centile and 40% below the third centile. No such independent association was seen with anti-hypertensives taken in the second trimester. CONCLUSIONS: Atenolol taken at the time of conception and/or during the first trimester of pregnancy was associated with low birth weight. This finding was independent of the development of superimposed pre-eclampsia. Other anti-hypertensives were not found to be associated with low birth weight. Use of atenolol in the second trimester of pregnancy did not produce the same effect and was not materially different in its effects from the other anti-hypertensive drugs. In the second trimester, the development of superimposed pre-eclampsia is the over-riding effect in the reduction of infant birth weight. Atenolol used in the first trimester could be pharmacologically programming these infants to restricted growth patterns.

Antihypertensive Agents↗
PubMed2002

Abnormal low-density lipoprotein subfraction profile in patients with untreated hypertension.

BACKGROUND: Low-density lipoprotein (LDL) consists of a heterogeneous group of particles of varying size and electrophoretic mobility. A predominance of small, more mobile particles is a risk factor for cardiovascular disease. AIM: To investigate the hypothesis that untreated patients with essential hypertension in the absence of vascular disease may exhibit abnormalities of LDL subfractions. SETTING: Specialist hypertension clinic. DESIGN: Cross-sectional study. METHODS: Following disc polyacrylamide gel electrophoresis, the mean (LDL locus) and heterogeneity (LDL spread) of mobility was recorded in 41 patients (mean age 52.6 years, 24 men) presenting with untreated essential hypertension (in the absence of vascular disease or diabetes mellitus) and in 45 healthy controls (age 56.9 years, 22 men) recruited from primary-care lists. RESULTS: Although there were no significant differences in total, low- or high-density lipoprotein cholesterol concentrations, LDL locus was significantly greater in the hypertensive group: mean (95%CI) 36.7 (35.7-37.6) vs. 34.8 (34.1-35.5), p=0.002. LDL locus was significantly elevated even in hypertensives with triglyceride concentrations below the median (<1.25 mmol/l). LDL spread was also greater in the hypertensive group, but not significantly: 5.6 (5.2-6.0) vs. 5.5 (5.3-5.8), p=0.10. DISCUSSION: Hypertensive patients have a preponderance of smaller LDL subfractions. This dyslipidaemia is not readily detected by conventional lipid assays.

Cross-Sectional Studies↗
PubMed2002

Baseline abnormalities of endothelial function and thrombogenesis in relation to prognosis in essential hypertension.

The present study was designed to test the hypothesis that markers of a hypercoagulable state predict subsequent cardiovascular events in hypertensives. To do this, we performed a prospective follow-up analysis of 178 patients (86 male; mean age, 54 years (standard deviation, 15); mean blood pressure, 188/103 mmHg) recruited from a hypertension clinic in a city-centre teaching hospital serving a multi-ethnic population. The main outcome measures were clinical and echocardiographic details, and laboratory markers of thrombosis and haemostasis (fibrinogen, fibrin D-dimer, plasminogen activator inhibitor, soluble P-selectin, von Willebrand factor, and viscosity) that were measured at baseline. After a mean follow-up of 45 months (interquartile range, 37-54), 30 subjects experienced one of a number of endpoints that included death or adverse cardiovascular event. These patients were older (P<0.001) and had significantly higher plasma von Willebrand factor (P=0.015) and fibrin D-dimer levels (P=0.005) compared with those 148 who were free of endpoints at follow-up. There were no statistically significant differences in mean blood pressure, other measured parameters, and the left ventricular mass index between the groups. Using univariate 'time to event' analysis, only high (> or = median) baseline systolic blood pressures were associated with a shortened event-free survival (log rank test, P= 0.0078). We conclude that hypertensive patients who experienced a new cardiovascular event were much older and had more endothelial dysfunction and thrombogenesis than those who were free of complications. However, only high baseline systolic blood pressures were associated with a shortened event-free survival.

Adult↗
PubMed2002

Sequential alterations in haemorheology, endothelial dysfunction, platelet activation and thrombogenesis in relation to prognosis following acute stroke: The West Birmingham Stroke Project.

Abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial function [von Willebrand factor (vWf)], platelet activation (soluble P-selectin) and thrombogenesis [plasminogen activator inhibitor (PAI), and fibrin D-dimer] are common in cardiovascular disease. We investigated changes in these markers in 86 patients (58 males) presenting with acute stroke (all age < 75 years, with ictus < 12 h), and sequential changes at six time points (baseline on admission, 48 h, 1 week, 2 weeks, 3 months and 6 months following the onset of stroke). Baseline plasma viscosity, haematocrit, fibrinogen, vWf, PAI, soluble P-selectin and fibrin D-dimer levels were increased in the acute stroke patients compared with 35 age-matched and sex-matched controls. Following admission, there were significant increases in haematocrit at 2 weeks, vWf at 48 h and 1 week, fibrinogen at 1 week, PAI at 48 h and 1 and 2 weeks, soluble P-selectin at 48 h, and fibrin D-dimer at 48 h and 1 week following admission. Using univariate 'time to event' analysis, high (> median) mean age (log-rank test, P = 0.0262), diastolic blood pressure (P = 0.01), haematocrit (P = 0.0234), PAI-1 (P = 0.0066) and fibrin D-dimer levels (P = 0.0356) were associated with a shortened event-free survival. Using a multivariate Cox survival analysis, only PAI-1 levels remained an independent predictor of survival (P = 0.0349). We conclude that acute stroke patients have marked baseline abnormalities of haemorheology, endothelial disturbance, thrombogenesis, platelet activation and abnormal fibrinolysis, with further changes over the subsequent follow-up period. Abnormal thrombogenesis and fibrinolysis may significantly influence survival in patients with acute stroke. These changes may have potential implications for the pathogenesis of stroke and its complications, although the possibility remains that we are documenting an acute phase response that previous studies, which included stroke patients with a wide time range since ictus onset, have neglected to consider.

Aged↗
PubMed2001

Plasma levels of vascular endothelial growth factor and its soluble receptor (SFlt-1) in essential hypertension.

In this study of 27 untreated patients with uncomplicated essential hypertension, we report on elevated plasma levels of vascular endothelial growth factor and its soluble receptor Flt-1 compared with healthy controls; these increased levels are reduced by the treatment of hypertension. This raises the possibility that abnormal angiogenesis may contribute to the pathogenesis of complications related to hypertension and merits exploration in larger studies.

Antihypertensive Agents↗
PubMed2001

Predictors of attendance at cardiac rehabilitation after myocardial infarction.

OBJECTIVE: The purpose of this study was to determine predictors of attendance at cardiac rehabilitation after myocardial infarction (MI). METHODS: Various demographic, behavioural, and clinical variables were measured during hospitalisation in 288 MI patients. Of these, 263 were available to attend outpatient-based cardiac rehabilitation: 108 actually attended. RESULTS: Multiple logistic regression analyses indicated that nonattenders lived in more deprived areas and were less likely to have paid employment. Nonattenders also registered more symptoms of depression and anxiety and exercised less frequently prior to their MI, although only the last of these variables were predicted in a multivariate model. In terms of clinical status, whether patients had been thrombolysed or not was the strongest predictor of attendance. CONCLUSIONS: Attendance at cardiac rehabilitation is not an arbitrary matter. Strategies should be developed for encouraging greater attendance among those not in paid employment, those from deprived areas, and those who exercise infrequently.

Aged↗
PubMed2001

Effect of antihypertensive therapy using enalapril or losartan on haemostatic markers in essential hypertension: a pilot prospective randomised double-blind parallel group trial.

To test the hypothesis that the hypercoagulable state in hypertension is significantly altered by anti-hypertensive therapy, we conducted a pilot prospective randomised double-blind trial of 40 untreated hypertensive patients (30 males, mean age 59 years) who were treated with either enalapril (10-20 mg per day) or losartan (50-100 mg per day) for 8 weeks. Thrombogenicity was assessed by measurement of plasma fibrinogen, soluble P-selectin (an index of platelet activation), plasminogen activator inhibitor 1 (PAI-1, an index of fibrinolysis) and von Willebrand factor (an index of endothelial dysfunction). Baseline von Willebrand factor alone was significantly higher in untreated hypertensive patients compared to controls (P<0.001). Following 8 weeks treatment with enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day), there was a significant reduction in mean blood pressure from 169+/-11/94+/-8 mmHg (baseline) to 147+/-14/84+/-7 mmHg (post-treatment) (P<0.001). However, there were no statistically significant changes in the levels of haemostatic markers (von Willebrand factor, fibrinogen, s-Psel and PAI-1). Our pilot study confirms previous observations of endothelial dysfunction in hypertensives. However, plasma fibrinogen and indices of platelet activation, fibrinolysis or endothelial dysfunction were not significantly affected by antihypertensive treatment with enalapril or losartan, despite satisfactory blood pressure control.

Angiotensin Receptor Antagonists↗