For Debate: The 2023 European Society of Hypertension guidelines - cause for concern.

Originally, the beta-blockers were equally ranked alongside the other antihypertensive drug classes. Things changed when two major long-term randomized controlled trials, ASCOT-BPLA and LIFE showed that the patients receiving the beta-blockers based regimes suffered 25-30% more strokes than those receiving a calcium channel blocker based regime or an angiotensin receptor blocker based regime. The inferiority of the beta-blockers at stroke prevention was not due to differences in blood pressure control during the follow-up period in both trials. The 2023 European Society of Hypertension (ESH) guidelines still argue in favour of beta-blockers that their clinical inferiority was simply to lesser blood pressure reduction rather than class effect. The analysis argues that the return of beta-blockers as a first-line option for the management of uncomplicated hypertension by the ESH is a cause for concern and should be reconsidered.

Self-care and adherence to medication: a survey in the hypertension outpatient clinic.

BACKGROUND: Self-care practices for patients with hypertension include adherence to medication, use of blood pressure self-monitoring and use of complementary and alternative therapies (CAM) The prevalence of CAM use and blood pressure self-monitoring have not been described in a UK secondary care population of patients with hypertension and their impact on adherence to medication has not been described. Adherence to medication is important for blood pressure control, but poor adherence is common. The study aimed to determine the prevalence of self-care behaviours in patients attending a secondary care hypertension clinic. METHODS: Cross-sectional questionnaire survey. 196 patients attending a secondary care hypertension clinic in a teaching hospital serving a multiethnic population, Birmingham, UK. MAIN OUTCOME MEASURES: Prevalence of use of CAM, home monitors, adherence to anti-hypertensive medication. RESULTS: CAM use in previous 12 months was reported by 66 (43.1%) respondents. CAM users did not differ statistically from non-CAM users by age, gender, marital status or education. Vitamins, prayer a dietary supplements were the most commonly used CAM. Nine (12.7%) women reported using herbal CAM compared to one man (1.2%), (p = 0.006). Ten (6.7%) respondents reported ever being asked by a doctor about CAM use. Perfect adherence to anti-hypertensive medication was reported by 26 (44.8%) CAM-users and 46 (60.5%) non-CAM users (p = 0.07). Being female and a CAM user was significantly associated with imperfect adherence to anti-hypertensive medication. Older and white British respondents were significantly more likely to report perfect adherence. Blood pressure monitors were used by 67 (43.8%) respondents, which was not associated with gender, CAM use or adherence to medication. CONCLUSION: Hypertensive patients use a variety of self-care methods, including CAM, home blood pressure monitors, and adherence to prescribed medication. This study found the prevalence of CAM use in hypertensive patients was higher than in the UK population. It is important to acknowledge the self-care behaviour of hypertensive patients, in order to assess potential harm, and encourage effective methods of self-care.

A randomized trial of ambulatory blood pressure monitoring versus clinical blood pressure measurement in the management of hypertension in pregnancy. A feasibility study.

To assess the feasibility of a prospective randomised trial of ambulatory blood pressure monitoring (ABPM) versus clinic blood pressure (CBP) readings for managing pregnancy hypertension. The primary outcome measure was admission to hospital. The secondary measures were number of antenatal attendances, use of anti-hypertensive drugs and duration of hospital stay. In general, there were no statistical differences between the two groups including the primary outcome, the rate of hospital admission p=0.76. 89% of participants would undergo ABPM in future pregnancies. A randomised trial of ABPM in pregnancy using this methodology is feasible and acceptable to pregnant women.

Low-dose spironolactone in the management of resistant hypertension: a surveillance study.

METHODS: We have conducted an open observational study of the use of spironolactone 25-50 mg in the management of patients with resistant hypertension. This drug was recommended in 133 patients who were already receiving an angiotensin-blocking drug in addition to other therapies. RESULTS: Of these, three defaulted from follow-up and 11 could not tolerate spironolactone. We therefore have outcome data on 119 patients. The addition of spironolactone (median dose 25 mg) was associated with a mean (SD) fall in systolic blood pressure of 21.7 mmHg (24.0; P < 0.001) and diastolic blood pressure of 8.5 mmHg (14.9; P < 0.001). In two patients spironolactone had to be discontinued on account of a rise of serum potassium to above 6.0 mmol/l, whereas overall the mean increase in serum potassium was 0.3 mmol/l. CONCLUSION: With careful monitoring of plasma electrolytes, spironolactone at a low dose is an effective add-in drug in patients with hypertension resistant to a regime that includes an angiotensin-blocking agent.

Circulating endothelial cells, arterial stiffness, and cardiovascular risk stratification in hypertension.

BACKGROUND: Given the growing burden of cardiovascular disease, there is increasing interest in strategies to help predict future cardiovascular risk. AIMS: To investigate the relationship between endothelial damage/dysfunction, arterial stiffness, and their association with predicted risk of future cardiovascular death among patients with hypertension. METHODS: We studied three patient groups 35 to 74 years old: healthy control subjects (n=63), subjects with high-risk hypertension (HHT) [n=65], and patients with treated, previously diagnosed, malignant-phase hypertension (MHT) [n=43]. We measured comparative indexes of arterial stiffness (stiffness index [SI] using digital volume photoplethysmography), endothelial damage/dysfunction (venous circulating endothelial cells [CECs], immunobead technique), and 5-year predictive risk of future cardiovascular death (Pocock scoring system). RESULTS: CEC counts, SI, and 5-year prediction of cardiovascular death were significantly higher in both hypertension groups (HHT and MHT), compared with healthy control subjects. CEC counts were significantly higher in the MHT group (p<0.05). There was a significant correlation between CECs and SI in the HHT group (r=0.61; p<0.0001) and the MHT group (r=0.59, p<0.0001) and between CEC, SI, and predicted 5-year risk of cardiovascular death in the two hypertension groups. On multiple linear regression analysis, arterial SI and CECs remained as significant predictors of the calculated 5-year risk of cardiovascular death (R2=0.37; p<0.0001). CONCLUSION: There is a consistent association between CECs, arterial stiffness, and the predictive risk of cardiovascular death among a group of patients with HHT or previously treated MHT. Registration number 05/Q2709/1.

Predictors of 5-year outcomes in malignant phase hypertension: the West Birmingham Malignant Hypertension Registry.

OBJECTIVE: Malignant hypertension represents a high-risk condition and there are scarce data on current clinical patterns of this condition. The aim of the study is to identify the clinical and demographic factors associated with poor outcome. METHODS: The data collected from 1958 to May 2016 included a total of 351 patients whose 5-year survival status was known: 221 white Caucasians (63%, age 51 ±â€Š13 years, 64% male), 83 African-Caribbeans (24%, 45 ±â€Š11 years, 61% male), and 47 South Asians (13%, 42 ±â€Š11 years, 74% male). RESULTS: During the 5-year follow-up 119 (34%) patients suffered a primary outcome, defined as the composite endpoint of death or dialysis. The 5-year mortality ranged from 76% in patients diagnosed before 1967 to 7% in patients diagnosed between 1997 and 2006. The independent predictors of outcome were advanced age (vs. a reference group of < 40-year-old; P = 0.01 for age at presentation 51-60 years, P < 0.001 for age > 60 years), prior use of antihypertensive medications (P = 0.002), higher serum creatinine (P = 0.006), and proteinuria (P < 0.01). Also, white Caucasian (odds ratio12.02, 95% confidence interval 1.64-88.15, P = 0.01) and African-Caribbean (odds ratio 15.55, 95% confidence interval 2.06-117.29, P = 0.008) origins were associated with higher mortality vs. South Asians. The years of the diagnosis after 1977 were significantly associated with lower composite endpoint of death or dialysis, all P < 0.01. CONCLUSION: There has been a major improvement in 5-year survival in patients with malignant hypertension over recent decades. Abnormal renal function at presentation still predicts worse outcome. South Asian ethnicity is also associated with better outcome, although mechanisms involved are yet to be established.

Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial.

BACKGROUND: The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril. METHODS: We did a multicentre, prospective, randomised controlled trial in 19 257 patients with hypertension who were aged 40-79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5-10 mg adding perindopril 4-8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50-100 mg adding bendroflumethiazide 1.25-2.5 mg and potassium as required (atenolol-based regimen; n=9618). Our primary endpoint was non-fatal myocardial infarction (including silent myocardial infarction) and fatal CHD. Analysis was by intention to treat. FINDINGS: The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106 153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79-1.02, p=0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.66-0.89, p=0.0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78-0.90, p<0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81-0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63-0.78, p<0.0001). INTERPRETATION: The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents.

Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA).

BACKGROUND: Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0.86 and 0.77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation. METHODS: We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates. FINDINGS: We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0.86 (0.77-0.96) to 0.88 (0.79-0.98) and from 0.77 (0.66-0.89) to 0.83 (0.72-0.96), respectively. Multivariate adjustment gave HRs of 0.94 (0.81-1.08) for coronary events (HDL cholesterol being the largest contributor) and 0.87 (0.73-1.05) for stroke events. INTERPRETATION: Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.

Platelet indexes in relation to target organ damage in high-risk hypertensive patients: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

OBJECTIVES: We sought to investigate the relationship between target organ damage (TOD) in hypertension and a prothrombotic/hypercoagulable state, using a new technique of "platelet lysis" to quantify the amount of P-selectin per platelet (pP-sel), and to correlate it with other platelet markers (e.g., mass, volume and granularity, soluble P-selectin [sP-sel], and beta-thromboglobulin [beta-TG]). BACKGROUND: The increased risk of TOD in hypertension may be related to a prothrombotic/hypercoagulable state, with abnormalities in platelets, such as increased expression of P-selectin. METHODS: We studied 199 patients (mean age 68 years, 75% men) with hypertension. Of these, 125 had TOD (e.g., stroke, previous myocardial infarction, angina, left ventricular hypertrophy). Values obtained were compared with those from 59 healthy normotensive control subjects (mean age 68 years, 58% men). RESULTS: Hypertensive patients had a higher mean platelet volume, mass, pP-sel, sP-sel, and beta-TG and lower platelet granularity (all p < 0.01), but a similar platelet count, as compared with controls. Within the hypertensive group, those with evidence of TOD had significantly larger platelets with greater mass but had lower granularity, sP-sel, and pP-sel levels than those without TOD, possibly reflecting increased aspirin use. On multivariate analysis, aspirin use was a determinant of pP-sel (p = 0.03) and sP-sel (p = 0.01), but the use of other drugs or other co-morbidity (e.g., diabetes, smoking) did not influence either P-selectin value. CONCLUSIONS: Patients with hypertension have evidence of changes in platelet physiology, as reflected by a higher level of pP-sel. Patients with TOD also had larger platelets, with greater mass, and the use of aspirin lowered pP-sel and sP-sel levels. These changes may have implications for the pathophysiology of cardiovascular and cerebrovascular disease in hypertension.

Ethnic differences in cardiovascular and all-cause mortality in Birmingham, England: the Birmingham Factory Screening Project.

OBJECTIVES: To compare cardiovascular and all-cause mortality, among white Europeans, African-Caribbeans and South-Asians, in relation to baseline demographic characteristics and blood pressure variables. DESIGN: Observational follow-up study. SETTING: Community settings in Birmingham, UK. PARTICIPANTS: Two thousand and eighty-nine white European and 340 African-Caribbean men and women, and 195 South-Asian men whose survival status on 31 December 2003 was known. INTERVENTIONS: Follow-up for assessment of all-cause and cardiovascular mortality over a mean (SD) 20.3 (4.2) years. MAIN OUTCOME MEASURES: All-cause and cardiovascular mortality. RESULTS: There were no significant ethnic differences in all-cause or cardiovascular mortality for men [adjusted hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.80-1.28 and HR = 1.33; 95% CI, 0.99-1.79, respectively] or women (adjusted HR = 0.61; 95% CI, 0.29-1.32 and HR = 1.19; 95% CI, 0.41-3.45, respectively) in either univariate or multivariate analyses. The only independent predictors of both all-cause and cardiovascular mortality were age, sex, smoking and mean systolic blood pressure or hypertension. CONCLUSIONS: It appears that ethnicity per se is not an independent risk factor for all-cause and cardiovascular mortality between white Europeans and African-Caribbeans in the present study. The data concerning ethnic differences in all-cause and cardiovascular mortality for South-Asians is limited, given that significantly fewer South-Asian men could be traced by the Office for National Statistics (ONS), hence we do not know their survival status, and the total lack of data on South-Asian women.

Circulating matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 and -2 levels in gestational hypertension.

BACKGROUND: Gestational hypertension (GH) is dangerous to both mother and child. Arterial invasiveness and growth are dependent on successful extracellular matrix (ECM) breakdown, which may be abnormal in GH. We hypothesized abnormalities in circulating matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinases-1 and -2 (TIMP-1 and TIMP-2, respectively) in patients with GH, when compared with normotensive women with normal pregnancies and healthy nonpregnant control subjects. METHODS: Plasma MMP-9, TIMP-1, and TIMP-2 were measured by ELISA in 23 women with GH, 30 normotensive pregnant women, and 28 nonpregnant women who were matched for age, gestational age, and parity. RESULTS: Levels of circulating MMP-9, TIMP-1 and TIMP-2, and the MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were significantly different among the three groups (P = .026, P = .006, P = .007, P = .001 and P = .008 respectively). Within the GH group, MMP-9 and the MMP-9/TIMP-1 ratio correlated negatively with age (r = -0.581, P = .004 and r = -0.563, P = .005, respectively) and levels of diastolic blood pressure (r = -0.432, P = .040 and r = -0.461, P = .027, respectively). With multiple regression analysis, only age independently correlated with circulating levels of MMP-9 (P = .010); neither age nor levels of diastolic blood pressure had any effect on the MMP-9/TIMP-1 ratio. CONCLUSIONS: We have demonstrated altered MMP/TIMP ratios in maternal blood during GH. These observations suggest pregnancy-related changes in ECM breakdown and turnover. Given the importance of changes in ECM composition to vascular and cardiac structure in hypertension, we suggest that these observations may be related to the pathophysiology of human GH.

Salt intake and Helicobacter pylori infection.

BACKGROUND: The chance finding of an association between Helicobacter pylori infection and hypertension and the known relationship between salt intake and blood pressure led us to speculate whether these two environmental factors might be related. A positive relationship between them might suggest that a high-salt diet could in some way facilitate gastric H. pylori infection. METHODS: We have therefore conducted an ecological study of the national H. pylori infection rates in the EUROGAST study and national salt excretion levels with the INTERSALT project. Ten nations were included in both projects. RESULTS: Statistically significant correlation between H. pylori infection rates and salt excretion were found in older men and women (r = 0.728 and r = 0.827, respectively) and in younger men (r = 0.728), but not younger women (r = 0.519). CONCLUSIONS: Our findings raise the possibility that salt intake may in some way facilitate H. pylori infection. A dedicated population survey is now justifiable to investigate the role of salt intake in H. pylori infection with the measurement of all possible confounding variables including particularly socio-economic status

Inter-arm differences in blood pressure: when are they clinically significant?

OBJECTIVE: To determine whether there is significant disparity in blood pressure between the two arms. DESIGN: Prospective, observational study. SETTING: One general hospital in Birmingham, England. PARTICIPANTS: Four hundred participants [age 56.3 +/- 19.7 years (mean +/- SD), 50% male] were recruited from staff and patients. Simultaneous bilateral blood pressure measurements were obtained using Omron HEM-705CP automated oscillatory devices; with two measurements taken in each arm. MAIN OUTCOME MEASURES: Mean inter-arm blood pressure differences and frequency of clinically important disparities. RESULTS: Mean +/- SD inter-arm differences in systolic and diastolic blood pressure were 1.81 +/- 8.6 mmHg and -0.23 +/- 8.3 mmHg, respectively. The analogous figures for mean +/- SD absolute differences were 6.32 +/- 6.12 mmHg and 5.06 +/- 6.57 mmHg, respectively. Significant differences were present between the mean right and left arm systolic blood pressure [t(399) = 4.20, P < 0.0001], and the mean absolute difference for both systolic [t(399) = 20.65; P < 0.0001] and diastolic [t(399) = 15.39; P < 0.0001] blood pressure. The variation in mean inter-arm blood pressure was unrelated to age, sex, ethnicity, arm circumference, handedness, being hypertensive, diabetic, or previous history of cardiovascular disease. Clinically significant inter-arm differences in systolic blood pressure of > 10 and > 20 mmHg were found in 20 and 3.5%, respectively; diastolic differences of > 10 and > 20 mmHg were present in 11 and 3.5%, respectively. Age was the only significant predictor of clinically significant variations in inter-arm blood pressures and mean absolute blood pressure differences. CONCLUSIONS: Significant differences in mean inter-arm systolic blood pressure, and mean absolute inter-arm systolic and diastolic blood pressure are present. This emphasizes the importance of measuring blood pressure in both arms initially to prevent this misdiagnosis of hypertension, due to normal differences in blood pressure between the arms.

Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT]).

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 <0.001) compared with the controls. All markers correlated with each other and with both cardiovascular and cerebrovascular risk scores (all p <0.001). After intensified blood pressure and hypercholesterolemia treatment, total cholesterol, blood pressure, TF, VEGF, and vWF levels all decreased, whereas FMD increased (all p <0.001). Thus, in subjects with hypertension and other risk factors, endothelial damage/dysfunction (and thus, atherogenesis), thrombogenesis, and angiogenesis are abnormal, correlate with overall cardiovascular risk, and importantly, can be related to each other in a "Birmingham Vascular Triangle." Furthermore, these processes are beneficially affected by intensive blood pressure and lipid treatment.

In-hospital symptoms of depression do not predict mortality 3 years after myocardial infarction.

BACKGROUND: The main aim of this study was to examine the relationship between symptoms of depression following myocardial infarction (MI) and 3-year survival status. METHODS: The Beck Depression Inventory was completed by 288 patients hospitalized for MI. Patients' cardiological status, including indices of disease severity, were recorded or derived from hospital notes. Three-year survival status was determined using patient information systems and cause of death ascertained from death certificates. RESULTS: During the 3 years of follow-up, 38 patients (13%) died, 33 (11%) from cardiac causes. Symptoms of depression did not predict either cardiac-specific or all-cause mortality. Similarly, in-hospital levels of anxiety were not associated with prognosis. In contrast, measures of disease severity and discharge medication status were strong prognostic indicators. Depression was not related to measures of disease severity at entry to the study. CONCLUSIONS: Symptoms of depression following MI do not predict longer-term survival, although measures of disease severity and discharge medication status do. Previous positive results for depression and cardiac mortality in MI patients could reflect the occasional confounding of depression with disease severity.

beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension.

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.

Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Primary hyperaldosteronism.

Primary hyperaldosteronism is an important cause of hypertension. Its true prevalence is still a matter of debate, since about 10% of hypertensives may have underlying hyperaldosteronism. Primary hyperaldosteronism is due to aldosterone-secreting tumours, bilateral adrenal hyperplasia or, rarely, adrenal carcinoma or genetic causes. There is considerable debate over the optimal screening methods for detecting hyperaldosteronism. The patients who benefit the most from screening are young hypertensives, those with resistant hypertension and patients with serum potassium of less than 3.5 mmol/L, especially in the presence of a high sodium. Various tests are available for screening patients with hypertension for hyperaldosteronism. Serum potassium is an unreliable marker for hyperaldosteronism, although a low value in a patient not taking diuretics should make one suspect the diagnosis. The use of serum potassium as a screening test would miss about a third of cases. Determination of the ratio of plasma aldosterone concentration to plasma renin activity is widely accepted as the test of choice for screening. Tests such as diurnal variations in aldosterone concentration and response to angiotensin II help to demonstrate the autonomy of the aldosterone secretion. Once the diagnosis of hyperaldosteronism is made, further tests such as magnetic resonance imaging or computed tomographic scanning and adrenal vein sampling should be undertaken to determine the aetiology of the hyperaldosteronism. Depending on the findings and the lateralization of the lesion, either surgery or medical therapy may be advised for the patient. Spironolactone would be the drug of choice for medical treatment. Laparoscopic adrenalectomy has become a widely employed method of surgically removing adrenal tumours. Hyperaldosteronism represents one of the few treatable causes of hypertension and a systematic approach is therefore needed to ensure that the few patients with an aldosterone-secreting adrenal adenoma are identified. It is important to identify these patients so that only those patients with proven adenomas are referred for adrenalectomy.

Does obesity influence target organ damage and outcomes in patients with malignant phase hypertension? The West Birmingham Malignant Hypertension Project.

Several studies have suggested that hypertension has a stronger detrimental impact on cardiovascular outcome in lean than in obese persons, but neutral or opposite results have also been reported. We investigated the impact of baseline body mass index (BMI) at presentation with the most severe form of hypertension, that is, malignant phase hypertension (MPH) on the primary outcome of 'death or dialysis' in these patients. A total of 184 patients (overall mean (s.d.) age 48 (13) years; 61% male; 62% White-European; 20% African-Caribbean, 18% South-Asian) from the West Birmingham MPH Register were included. The patients were grouped according to their BMI (underweight, normal weight, overweight and obese groups). Ninety-three primary outcomes occurred during a median (interquartile range) follow-up of 10.7 (5.8-18.6) years. No significant baseline differences in age or ethnicity were seen between the study groups. Overweight and obese patients included a larger proportion of females, but less smokers than those underweight or of normal weight. There was no inter-group difference in retinopathy (P=0.25), proteinuria (P=0.08), haematuria (P=0.56) and left ventricular hypertrophy (P=0.14). In univariate analyses, BMI was predictive of death or dialysis (0.95 (0.90-1.00), P=0.046) but multivariate analyses showed that only baseline age (odds ratio (95% confidence intervals) 1.06 (1.03-1.09), P<0.001), smoking (2.89 (1.40-5.92), P=0.004), creatinine level (1.01 (1.01-1.02), P=0.001) and estimated glomerular filtration rates (0.99 (0.93-1.00), P=0.047) were independently associated with death or dialysis. BMI was not an independent predictor of adverse outcomes in MPH patients. Age, smoking status, creatinine levels and estimated glomerular filtration rates at diagnosis of MPH were independent predictors for death or dialysis in this high-risk population of hypertensive patients.