Search

Spencer CGC, Felmeden DC, Blann AD, Lip GY (City Hospital, Birmingham, UK). Haemorheolo- gical, platelet and endothelial indices in relation to global measures of cardiovascular risk in hypertensive patients. J Intern Med 2007; 261: 82-90. Introduction and Methods. We tested the hypothesis that there was a significant relationship between haemorhe- ological markers (white blood cell count (WCC), plasma viscosity (PV), haematocrit (HCT) and fibrin- ogen), as well as plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction) and sol- uble P-selectin (sP-sel, an index of platelet activation), to five global measures of cardiovascular risk (i.e. Fra- mingham coronary heart disease (CHD), stroke and car- diovascular death score, the Pocock cardiovascular risk score and the sum of individual risk factors). Results. Men with a high (‡median, n ¼ 156) Framing- ham 10-year CHD risk score had higher levels of WBC (P ¼ 0.027), fibrinogen (P ¼ 0.012) and vWF (P ¼ 0.002) than 153 men with results < median. Men with a high 10-year stroke risk score had signifi- cantly higher levels of fibrinogen (P ¼ 0.01) and vWF (P < 0.0001). In stepwise linear regression analysis in men, vWF and fibrinogen were independent predictors of the number of risk factors (P < 0.0001), whilst WCC, vWF and fibrinogen emerged as independent predictors of Framingham CHD risk (P < 0.0001), and fibrinogen and vWF predicted Framingham stroke risk (R 2 ¼ 0.089, P < 0.0001). vWF, PV and fibrinogen were pre- dictors of Pocock cardiovascular death risk (P < 0.0001) but vWF was the only independent predictor of Framingham cardiovascular death risk (P ¼ 0.001). Conclusions. Abnormal haemorheological factors (particularly high plasma fibrinogen levels) and endo- thelial damage/dysfunction (high vWF), but not platelet activation (sP-sel), are related to established cardiovas- cular and death risk scores. This relationship was most evident amongst male 'high-risk' hypertensive subjects.

Endothelial dysfunction is a characteristic aspect of most of the conditions associated with atherosclerosis and is commonly found as an early feature in atherothrombotic vascular disease. An appreciation of the underlying mechanisms of endothelial function, as well as dysfunction, is essential as this has critical influence on the different methods in the assessment of endothelial function and effects of various treatments on its quantification. Furthermore, endothelial dysfunction is recognised as a type of 'target organ damage' in common cardiovascular conditions (e.g., hypertension) and the area is of increasing interest for new drug development, as therapies that modulate the endothelium will have added advantages; thus, for the development of new/experimental drugs, an awareness of ways to assess the endothelium is necessary. In this review, an overview of different methods including biochemical markers, and invasive and non-invasive tools, to determine endothelial function is presented as well as their clinical relevance. Furthermore, the effects of various treatments on endothelial dysfunction and their underlying mechanisms are elucidated.

Increasing evidence points toward a prothrombotic state in hypertension and atherosclerosis, conditions associated with thrombosis-related complications, such as myocardial infarction and stroke. We hypothesized that this increased risk of thrombogenesis may be related to endothelial damage/dysfunction and abnormal angiogenesis, and thus, an increased risk of future cardiovascular disease. Thrombogenesis, endothelial damage/dysfunction, and angiogenesis can be assessed by measurement of tissue factor (TF), von Willebrand Factor (vWF), flow-mediated dilatation (FMD), and vascular endothelial growth factor (VEGF), respectively. To test this hypothesis, we measured TF, vWF, FMD, and VEGF in 76 patients with systemic hypertension (71 men; mean age 64; mean blood pressure 167/72 mm Hg), considered additional risk factors such as diabetes, and related them to the patient's 10-year cardiovascular and cerebrovascular risk score using the Framingham equation. Patients were compared with 48 healthy normotensive controls. In these patients, the effects of 6 months of intensified blood pressure and (where appropriate) lipid-lowering treatment were investigated. In our patients, TF, VEGF, and vWF levels were higher, but FMD was lower (all p

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.

Felmeden DC, Spencer CGC, Blann AD, Beevers DG, Lip GYH (University Department of Medicine, City Hospital, Birmingham, UK). Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). J Intern Med 2003; 253: 81–91. Background. Hypertension is an important risk factor for cardiovascular disease. The latest guidelines recommend regular physical exercise as initial step or adjunct in the treatment of hypertension. We investigated the association between physical activity and the degree of hypertension, as well as the relation to indices of endothelial damage/dysfunction and angiogenesis. Methods. We studied 234 patients with hypertension (198 males; mean age 64 years; mean blood pressure 166/90 mmHg), who were compared with 60 age and sex-matched healthy normotensive controls. We assessed the patient's physical activity using the validated Baecke physical activity questionnaire and measured flow-mediated dilatation (FMD) of the brachial artery and von Willebrand factor (vWf) as indices of endothelial damage/dysfunction, whilst angiogenesis was assessed by measurement of plasma vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1) both by ELISA. Results. When hypertensive patients were compared with the controls, there was no statistically significant difference in total physical activity score using the Baecke questionnaire although plasma VEGF and vWf levels were higher, but sFlt-1 levels and FMD lower (all P

It is well recognised from many clinical trials that there is a blood pressure lowering effect when placebo is administered to patients with essential hypertension ("placebo effect"). The reduction in blood pressure, however, may also be partly due to loss of the alerting response ("white coat effect") as a result of familiarisation with the clinical environment. To investigate the hypothesis that there may be a more marked placebo effect and white coat effect in isolated systolic hypertension (ISH) compared with systo-diastolic hypertension (SDH), we studied 78 patients with hypertension: 34 had ISH and 44 patients had SDH. The 34 patients with ISH were older (68.7 vs 54.9 years), had a higher SBP (192.2 vs 169.6 mmHfg) and lower DBP (85.5 vs 102.0 mmHg) when compared to patients with SDH. Amongst the patients with ISH, there were no significant changes in mean blood pressures pre-placebo (paired t-test, p = NS). In the placebo period, there was a significant reduction in systolic blood pressures at all three points, and a significant reduction in diastolic blood pressures after 2 and 3 months placebo (paired t-test, p < 0.05). There was a mean reduction in mean systolic blood pressure at visit 1 by 5.2%, visit 2 by 5.1% and visit 3 by 4.6%, when compared to mean pre-placebo systolic blood pressures (p < 0.05). The mean reduction in diastolic blood pressure was 5.8% at visit 2 and 3.5% at visit 3, when compared to mean pre-placebo diastolic blood pressure (p < 0.05). At the 4-week visit after receiving placebo, the mean systolic blood pressure decreased by 9.4 mmHg (p = 0.003) and mean diastolic blood pressure by 2.7 mmHg (p = NS) in the patients with ISH. In patients with SDH, there were no statistically significant changes in recorded BP readings following the introduction of placebo. We suggest blood pressures in some patients with ISH may settle with careful follow up and initiation of treatment in these patients could potentially be delayed for at least 3 months, as therapy may not prove necessary.

For many years, Hormone Replacement Therapy (HRT) was considered to be contraindicated in postmenopausal women with hypertension and many such women were excluded from HRT because of concerns that HRT may have an adverse effect on blood pressure. This perception was mainly due to the effects of oral contraceptive drugs, especially the oestrogen component, in increasing blood pressure. Differences exist between the formulation and doses of oestrogen preparations used, either as oral contraceptives in premenopausal women (in whom high-dose synthetic oestrogens are used) or as HRT in postmenopausal women (in whom low "replacement" doses of natural oestrogens are used). This is not inconsequential, as postmenopausal women represent the largest category of women at risk for hypertension. The aim of this review is to give a balanced view on the effects of HRT on blood pressure in postmenopausal women.

BackgroundThe main complications of elevated systemic blood pressure (BP), coronary heart disease, ischaemic stroke, and peripheral vascular disease, are related to thrombosis rather than haemorrhage. Therefore, it is important to investigate if antithrombotic therapy may be useful in preventing thrombosis-related complications in patients with elevated BP.ObjectivesTo conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with elevated BP, including elevations in systolic or diastolic BP alone or together. To assess the effects of antiplatelet agents on total deaths or major thrombotic events or both in these patients versus placebo or other active treatment. To assess the effects of oral anticoagulants on total deaths or major thromboembolic events or both in these patients versus placebo or other active treatment.Search methodsThe Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to January 2021: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 12), Ovid MEDLINE (from 1946), and Ovid Embase (from 1974). The World Health Organization International Clinical Trials Registry Platform and the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) were searched for ongoing trials. SELECTION CRITERIA: RCTs in patients with elevated BP were included if they were ≥ 3 months in duration and compared antithrombotic therapy with control or other active treatment.Data collection and analysisTwo review authors independently extracted data for inclusion criteria, our prespecified outcomes, and sources of bias. They assessed the risks and benefits of antiplatelet agents and anticoagulants by calculating odds ratios (OR), accompanied by the 95% confidence intervals (CI). They assessed risks of bias and applied GRADE criteria. MAIN RESULTS: Six trials (61,015 patients) met the inclusion criteria and were included in this review. Four trials were primary prevention (41,695 patients; HOT, JPAD, JPPP, and TPT), and two secondary prevention (19,320 patients, CAPRIE and Huynh). Four trials (HOT, JPAD, JPPP, and TPT) were placebo-controlled and two studies (CAPRIE and Huynh) included active comparators. Four studies compared acetylsalicylic acid (ASA) versus placebo and found no evidence of a difference for all-cause mortality (OR 0.97, 95% CI 0.87 to 1.08; 3 studies, 35,794 participants; low-certainty evidence). We found no evidence of a difference for cardiovascular mortality (OR 0.98, 95% CI 0.82 to 1.17; 3 studies, 35,794 participants; low-certainty evidence). ASA reduced the risk of all non-fatal cardiovascular events (OR 0.63, 95% CI 0.45 to 0.87; 1 study (missing data in 3 studies), 2540 participants; low-certainty evidence) and the risk of all cardiovascular events (OR 0.86, 95% CI 0.77 to 0.96; 3 studies, 35,794 participants; low-certainty evidence). ASA increased the risk of major bleeding events (OR 1.77, 95% CI 1.34 to 2.32; 2 studies, 21,330 participants; high-certainty evidence). One study (CAPRIE; ASA versus clopidogrel) included patients diagnosed with hypertension (mean age 62.5 years, 72% males, 95% Caucasians, mean follow-up: 1.91 years). It showed no evidence of a difference for all-cause mortality (OR 1.02, 95% CI 0.91 to 1.15; 1 study, 19,143 participants; high-certainty evidence) and for cardiovascular mortality (OR 1.08, 95% CI 0.94 to 1.26; 1 study, 19,143 participants; high-certainty evidence). ASA probably reduced the risk of non-fatal cardiovascular events (OR 1.10, 95% CI 1.00 to 1.22; 1 study, 19,143 participants; high-certainty evidence) and the risk of all cardiovascular events (OR 1.08, 95% CI 1.00 to 1.17; 1 study, 19,143 participants; high-certainty evidence) when compared to clopidogrel. Clopidogrel increased the risk of major bleeding events when compared to ASA (OR 1.35, 95% CI 1.14 to 1.61; 1 study, 19,143 participants; high-certainty evidence). In one study (Huynh; ASA verus warfarin) patients with unstable angina or non-ST-segment elevation myocardial infarction, with prior coronary artery bypass grafting (CABG) were included (mean age 68 years, 79.8% males, mean follow-up: 1.1 year). There was no evidence of a difference for all-cause mortality (OR 0.98, 95% CI 0.06 to 16.12; 1 study, 91 participants; low-certainty evidence). Cardiovascular mortality, non-fatal cardiovascular events, and all cardiovascular events were not available. There was no evidence of a difference for major bleeding events (OR 0.13, 95% CI 0.01 to 2.60; 1 study, 91 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is no evidence that antiplatelet therapy modifies mortality in patients with elevated BP for primary prevention. ASA reduced the risk of cardiovascular events and increased the risk of major bleeding events. Antiplatelet therapy with ASA probably reduces the risk of non-fatal and all cardiovascular events when compared to clopidogrel. Clopidogrel increases the risk of major bleeding events compared to ASA in patients with elevated BP for secondary prevention. There is no evidence that warfarin modifies mortality in patients with elevated BP for secondary prevention. The benefits and harms of the newer drugs glycoprotein IIb/IIIa inhibitors, clopidogrel, prasugrel, ticagrelor, and non-vitamin K antagonist oral anticoagulants for patients with high BP have not been studied in clinical trials. Further RCTs of antithrombotic therapy including newer agents and complete documentation of all benefits and harms are required in patients with elevated BP.

Different antihypertensive therapies may exert benefits via not only a reduction in blood pressure but also in improving the risk of thrombosis.We tested the hypothesis that a more modern antihypertensive drug regimen (ie, amlodipine +/- perindopril) would have a more beneficial effect on hemorheological markers (white blood-cell count [WCC], plasma viscosity [PV], hematocrit [HCT], and fibrinogen)--and on plasma von Willebrand factor (vWf, an index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation), compared with an older antihypertensive drug regimen (ie, atenolol +/- bendroflumethiazide).After 6 months, PV, sP-sel, and HCT fell in both groups (P.01), while fibrinogen was unchanged. However, those 74 patients randomized to amlodipine +/- perindopril had significant reductions in WCC (P = .005), with no significant changes in vWF or platelet count. Conversely, in those 85 patients randomized to atenolol +/- bendroflumethiazide, there were significant reductions in vWF (P = .001) and platelet count (P = .011) but no significant reductions in WCC. There were no significant differences in the levels of any of the variables between the two arms of the trial, nor a significant difference in the magnitude of reduction between the two treatment arms.Within the constraints of this substudy design, there was no differential effect apparent of the two antihypertensive treatment arms on hemorheological parameters or endothelial and platelet function (as assessed by vWF and sP-sel), suggesting that other pathophysiological mechanisms may be involved.

Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment. To the Editor: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor and plays a key role in postnatal angiogenesis in human pathophysiology, including cardiovascular disease. The activation of the renin-angiotensin system has been similarly implicated in the cardiovascular pathophysiology. Indeed, an interaction between the renin-angiotensin system and VEGF has been established. It is against this background that we read with great interest the report by Zhao and colleagues1 on the central role of VEGF …

Although elevated systemic blood pressure (BP) results in high intravascular pressure, the main complications of hypertension are related to thrombosis rather than haemorrhage. It therefore seemed plausible that use of antithrombotic therapy may be useful in preventing thrombosis-related complications of elevated BP. The objectives were to conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with BP, to address the following hypotheses: (i) antiplatelet agents reduce total deaths and/or major thrombotic events when compared to placebo or other active treatment; and (ii) oral anticoagulants reduce total deaths and/or major thromboembolic events when compared to placebo or other active treatment. A systematic review of randomised studies in patients with elevated BP was performed. Studies were included if they were >3 months in duration and compared antithrombotic therapy with control or other active treatment. One meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated BP reported an absolute reduction in vascular events of 4.1% as compared to placebo. Acetylsalicylic acid (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in primary prevention patients with elevated BP and no prior cardiovascular disease. Based on one large trial, ASA taken for 5 years reduced myocardial infarction (ARR, 0.5%, NNT 200 for 5 years), increased major haemorrhage (ARI, 0.7%, NNT 154), and did not reduce all cause mortality or cardiovascular mortality. In two small trials, warfarin alone or in combination with ASA did not reduce stroke or coronary events. Glycoprotein IIb/IIIa inhibitors as well as ticlopidine and clopidogrel have not been sufficiently evaluated in patients with elevated BP. To conclude for primary prevention in patients with elevated BP, antiplatelet therapy with ASA cannot be recommended since the magnitude of benefit, a reduction in myocardial infarction, is negated by a harm of similar magnitude, an increase in major haemorrhage. For secondary prevention in patients with elevated BP, antiplatelet therapy is recommended because the magnitude of the absolute benefit is many times greater. Warfarin therapy alone or in combination with aspirin in patients with elevated BP cannot be recommended because of lack of demonstrated benefit. Further trials of antithrombotic therapy are required in patients with elevated BP.

To examine the relationship between plasma homocysteine (HCY) and rheological, endothelial and platelet markers in "high risk" hypertensive patients.Cross-sectional study.A total of 165 consecutive hypertensive patients (136 male; mean age 63 years (S.D. 8)) at high risk of cardiovascular disease who screened for inclusion in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) were studied along with 38 population normotensive healthy controls. We measured levels of plasma homocysteine [high pressure liquid chromatography (HPLC)], soluble P-selectin, a marker of platelet function, von Willebrand factor (vWF), an index of endothelial damage/dysfunction [both by ELISA] and fibrinogen (CLAUSS). The Framingham cardiovascular and cerebrovascular risk scores were calculated.Hypertensives had significantly higher blood pressure (BP) [165/90(16/10) vs. 138/82(12/8) mm Hg, p0.0001], sP-sel [54(44-67) vs. 45(35-57) ng/ml, p=0.002], vWF [133(34) vs. 110(28) IU/dl, p0.0001], and fibrinogen [2.98(2.52-3.47) vs. 2.43(2.20-2.83)g/l, p=0.0001]. Homocysteine were lower in our hypertensives compared with controls [8.7(6.9-11.2) vs. 10.5(8.5-13.1) micromol/l, p=0.005], but there were significant correlations between homocysteine levels and both calculated 10-year coronary heart disease risk (Spearman r=0.197, p=0.026) and stroke risk (r=0.210, p=0.018), using the Framingham equation. There was a positive correlation between plasma homocysteine and soluble P-selectin (r=0.180, p=0.025), which persisted in multiple linear regression analysis. There was no significant relationship between homocysteine and HCT, PV, or the endothelial marker, vWF.Hypertensives demonstrate abnormalities of endothelial, platelet and rheological function. Homocysteine is related to both 10-year coronary heart disease risk and stroke risk, and is significantly correlated with soluble P-selectin, a marker of platelet activation, in hypertensives but only weakly or not at all to other thrombotic markers. Increased platelet activation as reflected by soluble P-selectin may be one mechanism by which hyperhomocysteinaemia confers an increased thrombotic risk in hypertension.

Objective. To investigate the impact of intensified cardiovascular risk management on soluble markers of platelet, endothelial and rheological function in a population of middle-aged hypertensive patients at high risk of cardiovascular complications. Design. Prospective follow-up study. Subjects and methods. A total of 159 hypertensive patients [138 male, mean age 64 (±8) years] and 80 healthy controls were studied. Plasma levels of soluble P-selectin (sP-sel, a marker of platelet function), von Willebrand factor (vWF, an index of endothelial damage/dysfunction) and rheological indices [fibrinogen (Fib), plasma viscosity (PV), haematocrit (HCT), white blood count (WBC) and platelet count] were measured at baseline and again (in the patients) after 6 months’ treatment. Results. As expected, 6 months of intensified cardiovascular risk management resulted in a significant fall in mean blood pressure (BP) and total cholesterol. It also resulted in reduced haematocrit, vWF, sP-sel, WBC and PV levels (all P

The development of new blood vessels is essential to embryonic growth and throughout life for physiological repair processes such as wound healing, post-ischaemic tissue restoration, and the endometrial changes of the menstrual cycle. However, abnormal development of new blood vessels has been implicated in numerous pathophysiological processes. For example, inhibited growth of blood vessels is associated with bowel atresia and peptic ulcers.1–3 Furthermore, although generally focussing on tumour growth, increased vascular growth has been demonstrated in many other non-malignant diseases such rheumatoid arthritis, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis.3–5 It is therefore clear that the subject is currently attracting considerable research energies as tools are becoming available to assess possible therapeutic options. The formation of the vascular system is fashioned by three processes. During embryogenesis, there is differentiation of embryonic mesenchymal cells (the endothelial precursor cells or angioblasts) into endothelial cells resulting in de novo development of blood vessels (vasculogenesis).6 Secondly, angiogenesis refers to the formation of new blood vessels by sprouting from pre-existing small vessels in adult and embryonic tissue (sprouting angiogenesis) or by intravascular subdivision (intussusception). The existing vasculature can betransformed into a mature network by processes of pruning and remodelling. Thirdly, arteriogenesisis defined as rapid proliferation of pre-existingcollateral vessels.7 Angiogenesis also seems to bean organ-specific process reliant on the stage of microvascular network.8 Since angiogenesis seems to play a key role inthe pathophysiology of various disease processes,recent attempts have been made to utilize this knowledge in the development of new therapeutic approaches. For example, inhibition of angiogenesis has been used in the restriction of tumour growth and the seeding of metastases, as well asin rheumatoid arthritis, where an aim is to reduce the infiltration of inflammatory cells and soluble mediators.9–11 Angiogenesis related research in cardiovascular medicine has initially been …

Although hypertensive patients are at particular risk of vascular complications, the possible contribution of an atherogenic lipoprotein profile and endothelial dysfunction to this risk is unclear. We investigated this by measuring LDL subfractions and flow-mediated dilation (FMD) (reflecting endothelial dysfunction) in a cohort of high-risk hypertensive patients. We studied 84 hypertensive patients (74 men; mean age, 64 years; SD 8). Chylomicron-free LDL subfractions were analyzed by disc polyacrylamide gel electrophoresis, producing an LDL score, with higher scores being equivalent to a greater proportion of the more atherogenic LDL subfractions. High-resolution ultrasound was used to assess endothelium-dependent brachial artery FMD after reactive hyperemia after vessel occlusion. Baseline levels were compared with 61 age- and gender-matched healthy normotensive control subjects. Mean LDL score was higher and FMD impaired in hypertensive subjects compared with control subjects. These indexes were significantly improved after 6 months of cardiovascular risk factor management. LDL score correlated significantly with the 10-year Framingham coronary heart disease risk score, with a negative correlation with FMD (both P

Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. These pathophysiologic processes are assessable by measurement of plasma levels of von Willebrand factor (vWf), and by vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). We hypothesized that these markers would correlate with the Framingham cardiovascular risk score and would be responsive to treatment.We measured these markers by enzyme-linked immunosorbent assay in 286 patients with hypertension (239 men; mean age 63 years; mean systolic blood pressure [BP]/diastolic BP 162/89 mm Hg) and additional risk factors, and related them to the patient's cardiovascular disease (CVD) and cerebrovascular accident (CVA) risk, using the Framingham equation. Patients were compared with 60 healthy normotensive controls. In 248 patients, the effects of 6 months of intensified cardiovascular risk factor management, including BP and (where appropriate) lipid-lowering treatment, were investigated.Plasma VEGF and vWf levels were higher, but sFlt-1 levels lower (all P.001), in the hypertensive patients compared with the controls. The VEGF and vWf levels correlated significantly with age, systolic and diastolic BP, 10-year CVD risk, and CVA risk scores (all P.01), whereas sFlt-1 was negatively correlated with these risk scores (P.01). After intensified cardiovascular risk factor management, total cholesterol, BP, VEGF, and vWf levels were all reduced, yet sFlt-1 levels increased (all P.05).In hypertension, the processes of endothelial damage and angiogenesis are abnormal, and correlate with overall cardiovascular risk. Indices of endothelial damage and angiogenesis are beneficially changed by intensive cardiovascular risk factor management.

JRAAS 2001;2:43–4 Introduction The syndrome of hypertension due to a benign aldosterone-secreting adenoma of the zona glomerulosa of the adrenal cortex was first described by Jerome Conn in 1955. Since then, a great many case series have been published and the criteria for the biochemical and histopathological diagnosis have been extensively reported. The tumours are classically canary yellow and rarely more than 1 cm in diameter. We report the clinical course of a long-standing hypertensive patient with possibly the largest benign adenoma in the Western medical literature.

The aim of this article is to provide an overview of the available data linking antihypertensive drug therapy to cancer risk. In recent years, a number of mainly retrospective studies have reached different conclusions on the risk of cancer in patients with hypertension being treated with different antihypertensive drugs. At some point or another nearly all antihypertensive drugs have been suggested to increase the risk of cancer. Some studies have even found an association between hypertension itself and increased carcinogenesis. For calcium channel antagonists, beta-blockers and alpha-blockers, the available evidence seems to favour a neutral effect on cancer development and death rate. For ACE inhibitors, the overall data suggest a similar neutral effect on cancer or, possibly, a small protective effect. Perhaps the strongest evidence in favour of a link, although probably weak, between cancer and antihypertensive drugs is with the diuretics. Until further solid data are available from prospective clinical trials, we suggest that the management of hypertension should continue according to current treatment guidelines with little fear of any substantial cancer risk.

Recent guidelines for the treatment of hypertension place great emphasis on tighter blood pressure control, especially in the presence of hypertensive target organ damage and diabetes. In order to achieve these treatment targets, more patients will require a combination of antihypertensive medications. However, resistant hypertension may have many possible underlying causes, and clinicians should appreciate how to detect and tackle these potential problems. Effective and synergistic combinations are therefore of vital importance, especially in patients with resistant hypertension. The choice of rational first- and second-line drugs that act in synergy could lead to better blood pressure management as well as significant financial savings for health care resources. The use of the Birmingham Hypertension Square for the optimum choice of add-in drugs for the treatment of resistant hypertension may aid management.

Activation of the RAAS has been linked with an increased risk of myocardial infarction and stroke,(1,2,37,38) and recently these beneficial effects have, in part, been attributed to the effects of the RAAS on the fibrinolytic system. Indeed, ACE seems to occupy a central position in modulating the fibrinolytic balance, where an angiotensin II-mediated increase of PAI-1 plays a major role. By contrast, the effect on bradykinin stimulated t-PA release may be of lesser importance, although the data are conflicting. Importantly, the impact of the RAAS on the fibrinolytic balance may also contribute to the favourable effects of ACE inhibition and AT1-receptor antagonists on cardiovascular events, particularly when considering the activation of the RAAS in hypertension and heart failure. More work is clearly required in this area to elucidate potential therapeutic targets.

We read with interest the report by Malik et al. [1] that both atorvastatin and fenofibrate equally improved endothelium-dependent arterial vasoreactivity in patients with combined hyperlipidaemia. Interestingly, a recent study by Sebestjen et al. [2] reported similar observations using cerivastatin and fenofibrate, although the effects seemed to be greater in the patients receiving the statin. Indeed, most of us now recognise that the beneficial effects of statins on the early cardiovascular events reduction in major clinical trials may involve mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation which may be unrelated, or indirectly related, to their lipid-lowering abilities [3]. Endothelial dysfunction has been regarded as an early event in atherogenesis, preceding the formation of atherosclerotic plaques. An important functional consequence of endothelial damage / dysfunction is a reduced vasodilatory responses to a variety of pharmacological and physiological stimuli …