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.

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.

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.

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.

A comprehensive assessment of cardiac structure and function in patients with treated malignant phase hypertension: the West Birmingham Malignant Hypertension project.

BACKGROUND: Previous studies have confirmed that cardiac structural and functional abnormalities exist in patients with malignant hypertension (MHT). The effect of long-term blood pressure control in MHT patients on cardiac structure and function is still unknown. METHODS: We performed detailed left ventricle (LV) assessment using two-dimensional (2DE) and three-dimensional (3DE) echocardiography, and tissue Doppler imaging (TDI) in patients with previous MHT (but now in stable phase) who were compared with patients with treated 'high risk' hypertension (HHT, but non-MHT) and healthy controls (HC). Vasodilator stress myocardial contrast echocardiography (in addition to wall motion analysis) was used to exclude significant coronary artery disease, as part of our comprehensive echocardiographic assessment. Septal and posterior wall thickness, LV mass index, LV volumes and ejection fraction, mitral valve inflow indices (E, A) mitral annular velocity (S, E') and left atrial volume index (LAVI), were calculated using 2DE, 3DE, and TDI. MHT patients had good blood pressure control for an average of 144months. RESULTS: A total of 95 subjects (MHT=15; HHT and HC=40 each) were studied. Both posterior and septal wall thickness were significantly higher in the MHT and hypertensive groups compared to normal controls with no difference between MHT and HHT. No significant difference in LV ejection fraction was found between the 3 groups. Increased LAVI (p<0.05 MHT vs. HC and HHT vs. HC), reduced 'S' velocity on TDI (p=0.05 MHT vs. HC and vs.HHT, p<0.001 HHT vs. HC) and higher E/E' (p=0.029 HHT vs. HC) and lower E/A ratio (p=0.001 MHT vs. HC, p<0.001 HHT vs. HC) values were detected in the two hypertensive groups. CONCLUSION: Despite long-term good blood pressure control, MHT patients have persistent structural and functional changes in LV function on echocardiography, comparable to that seen in HHT.

Lack of impact of pulse pressure on outcomes in patients with malignant phase hypertension: the West Birmingham Malignant Hypertension study.

OBJECTIVE: To investigate the impact of pulse pressure at presentation on the primary outcome (death or dialysis) in patients with malignant phase hypertension (MPH). METHODS: Three hundred and sixty-five patients [overall mean (SD) age 48 (13) years; 66% male; 63% white European; 23% African-Caribbean, 14% south Asian] from the West Birmingham MPH study were included. Baseline pulse pressure was divided into quartiles. Two hundred and forty-two primary outcomes (death or dialysis) occurred during a median (interquartile range) follow-up of 7 (1.5-14.8) years. RESULTS: Significantly higher pulse pressure was evident among older patients and white Europeans. Baseline BMI (P = 0.49), retinopathy (P = 0.56), proteinuria (P = 0.61), haematuria (P = 0.56) and left ventricular hypertrophy (P = 0.43) were not related to pulse pressure. Multivariate analyses found that baseline age [hazard ratio (95% confidence intervals] [1.05 (1.04-1.06); P < 0.0001], smoking [1.60 (1.16-2.21); P = 0.004], proteinuria [1.33 (1.10-1.61); P = 0.003] and creatinine level [1.002 (1.001-1.002); P < 0.0001] were independent predictors of the primary outcome of 'death or dialysis'. A multivariate analysis also revealed that independent predictors of future dialysis alone were as follows: baseline age [0.92 (0.89-0.95); P < 0.001) and haematuria [2.74 (1.17-6.42); P = 0.02), with a trend seen for baseline creatinine levels [1.001 (1.000-1.002); P = 0.052)]. Pulse pressure at baseline did not predict death or dialysis. CONCLUSION: Age, smoking status and severity of renal failure at presentation with MPH (represented by proteinuria and creatinine levels) are independent predictors of the risk of death or dialysis. Pulse pressure at presentation does not predict death or dialysis in patients with MPH. Careful monitoring of renal functioning and effective management of blood pressure is mandatory in patients with MPH to prevent/slow future complications.

Angiogenin and hemoxygenase in pregnancy: influence of hypertension.

The pathophysiology of hypertension and preeclampsia involves angiogenesis and endothelial damage/dysfunction, as shown by abnormal growth factors (vascular endothelial growth factor [VEGF], and its receptor sFlt-1) and von Willebrand factor (vWf) in the plasma. Angiogenin and hemoxygenase are abnormal in hypertension and angiogenesis but data on pregnancy are scant. We hypothesized altered angiogenin and hemoxygenase in 38 hypertensive pregnant women (HTPW) compared to 38 normotensive pregnant women (NTPW) and 50 nonpregnant controls (NonPCs). Plasma markers were measured by enzyme-linked immunosorbent assay (ELISA). Hypertensive pregnant women had lower VEGF than NonPCs (P < .01), vWf was raised in both pregnant groups (P < .01), but sFlt-1 was no different. Both angiogenin and hemoxygenase were lower in NTPW compared to NonPCs (both p<0.02). In both pregnancy groups, angiogenin correlated with vWf (r > .33, P < .05), but in NonPCs this was not significant (r = .13, P = .367). These changes may reflect differences in endothelial cell physiology and pathology in the hypertension in pregnancy.

Soluble Fas and Fas ligand in pregnancy: influence of hypertension.

The pathophysiology of pregnancy-induced hypertension and preeclampsia may involve abnormalities in placentation and the Fas/Fas ligand system. Hypothesizing abnormal plasma Fas and Fas ligand in pregnancy-induced hypertension, we recruited 20 hypertensive pregnant women at mean week 15 and 29 at week 30: 18 were studied at both time points. Control groups were 20 normotensive pregnant women at week 20, 29 women at week 27, and 50 nonpregnant women. sFas and sFas ligand (sFasL) were measured by enzyme-linked immunosorbent assay (ELISA). The hypertensive women had lower sFasL at both stages of their pregnancy (P < .05). There were no differences in sFas. In 18 hypertensive pregnant women, sFasL fell from week 15 to week 29 (P < .03). We conclude that sFas and sFasL is unchanged in normal pregnancy. Hypertension in pregnancy is characterized by low sFasL, and levels fall from weeks 15 to 29. This may reflect differences in placentation in the differing physiological and pathological states.

Persistent macrovascular and microvascular dysfunction in patients with malignant hypertension.

Endothelial dysfunction is characteristic of patients with essential hypertension, but only limited data are available on different aspects of endothelial function in patients with malignant-phase hypertension. We investigated myocardial perfusion using real-time quantitative myocardial contrast echocardiography with concurrent assessment of macrovascular and microvascular endothelial damage/dysfunction in patients with previous malignant hypertension (but now in stable phase), who were compared with patients with treated "high-risk" hypertension (hypertension) and healthy controls. We measured flow (hyperemia)-mediated dilation and response to glyceryl trinitrate of brachial artery (ultrasound), microvascular (forearm) response to acetylcholine and sodium nitroprusside (laser Doppler), pulse wave velocity, circulating endothelial and endothelial progenitor cells in 15 patients with malignant hypertension, 40 matched patients with hypertension, and 40 healthy controls. Patients with malignant hypertension had impaired endothelial-dependant response to acetylcholine (P<0.001, but not to sodium nitroprusside) compared with hypertension and impaired reaction to both stimuli compared with healthy subjects (P<0.001). Patients with malignant hypertension had increased circulating endothelial cells (P=0.001), endothelial progenitors (P=0.008), and stiffness (P=0.003). Both hypertensive groups had impaired response to hyperemia and glyceryl trinitrate when compared with healthy controls (P<0.05). Both hypertensive groups had similar myocardial perfusion, which was significantly lower than in healthy controls. There were no significant differences in hyperemia and endothelium-independent stimuli between the 2 hypertensive groups. In conclusion, despite fairly well-controlled blood pressure, malignant hypertension patients had more pronounced abnormalities of macrovascular and microvascular function (which seem to be both endothelium dependent and endothelium independent) compared with patients with hypertension and healthy controls.

Are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers safe in pregnancy: a report of ninety-one pregnancies.

BACKGROUND: Both angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor antagonists (ARBs) have been reported to be associated with an excess of congenital abnormalities in infants born to women who took these drugs in pregnancy. METHODS: To investigate this possible association further, we have examined the outcome in 91 pregnancies in which the mother took either an ACE-I (n = 71) or an ARB (n = 20) in early pregnancy. We also examined the United Kingdom adverse drug reaction reporting system to assess the total number of reported associations of ACE-I or ARB use in pregnancy and congenital anomalies reported. RESULTS: Eight (8.8%) of the pregnancies led to an infant with a developmental anomaly, but all save one of these (craniosynostosis with tower skull) anomalies were considered to be relatively minor. The adverse drug reaction reporting system revealed a total of 43 reported defects in women taking an ACE-I and 12 in women taking an ARB. CONCLUSION: We have not found any convincing excess of congenital anomalies in women taking angiotensin-blocking drugs in early pregnancy. However, this does not exclude the possibility that ACE-I or ARB use in pregnancy might lead to adverse obstetrical outcomes. Until this matter is settled, we support recommendations that these drugs should not be used in pregnancy or in women who are likely to become pregnant.

Hypertension in ethnic groups: epidemiological and clinical perspectives.

In the UK and other developed nations, hypertension and its vascular complications are more common in ethnically African and South-Asian communities compared with Europeans. While these conditions are less common in rural India and Africa, they present a rising problem in expanding cities in all developing countries. Hypertension is, therefore, mainly related to environmental and lifestyle factors rather than genetically determined racial differences. Studies in the USA and elsewhere show that the striking differences in the prevalence of hypertension between people of African and European origin are greatly reduced after adjustment for socio-economic status. One important and probably genuine racial difference between ethnic groups is the significantly suppressed activity of the renin-angiotensin-aldosterone system in African-origin hypertensive patients. As a consequence of this, they are rather more sensitive to a low-salt diet but significantly less sensitive to drugs that block the renin-angiotensin-aldosterone system (angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers) and beta-blockers. There is also evidence that renin suppression is common in Japanese and Chinese hypertensive patients as well, although no direct comparisons between these two groups with European-origin patients have been carried out. The management and control of hypertension is unsatisfactory in all ethnic groups and all nations. No one group needs particular targeting; all need better quality systematic care.

Improving survival of malignant hypertension patients over 40 years.

BACKGROUND: To examine changing demography and survival of patients with malignant phase hypertension (MHT) over 40 years. METHODS: Patients from our MHT registry whose survival status on 31 December 2006 was known were included, with analyses conducted based on decade of MHT diagnosis. RESULTS: Four-hundred and forty-six patients with MHT (overall mean (s.d.) age 48.2 (12.9), years; 65.5% male; 64.7% white-European; 20.4% African Caribbean, and 14.8% South-Asian) were included. No significant demographic differences at diagnosis were evident over the 40 years, with the exception of a significant increase (P = 0.001) in the proportion of MHT among ethnic minorities (South-Asian and Afro-Caribbeans). There were no significant differences in mean systolic blood pressure (SBP) at presentation but baseline diastolic BP (DBP) was significantly lower after 1976 (P < 0.0001). The total number of person-years of observation was 5,725.5 years, with a median (interquartile range (IQR)) length of follow-up of 103.8 (31.3-251.2) months. Overall 203 patients (55.6%) died, 125 (32.0%) within 5 years of diagnosis. There was a significant improvement in 5-year survival from 32.0% prior to 1977 to 91.0% for patients diagnosed between 1997 and 2006. SBP and DBP improved significantly during follow-up (P < 0.0001). Multivariate analyses revealed that age, decade of MHT diagnosis, baseline creatinine, and follow-up SBP were independent predictors of survival (all P < 0.0001). CONCLUSIONS: Demography and number of new cases of MHT have not changed dramatically over the past 40 years. Five-year post-MHT survival has improved significantly, possibly related to lower BP targets, tighter BP control, and availability of new classes of antihypertensive drugs.

Atrial fibrillation in primary aldosteronism.

INTRODUCTION: Primary aldosteronism (PA) is caused by autonomous hypersecretion of aldosterone from the adrenal cortex, classically from an adenoma, resulting in sodium and water retention, hypokalaemia and raised blood pressure. The sodium and water retention causes suppression of renin release. The possible cardiac sequelae of aldosterone excess are encountered primarily in patients with secondary hyperaldosteronism due to heart failure, where plasma renin, angiotensin and aldosterone levels are all raised. However, there is also evidence that primary aldosterone excess, in the presence of low renin levels, may also be cardiotoxic. PATIENTS: In this report, we describe five patients with PA, who developed atrial fibrillation (AF) in the absence of structural cardiac lesions and in one case despite good control of blood pressure and electrolytes. CONCLUSION: In patients with hypertension and AF, who have no evidence of coronary disease or any other underlying cause of AF with preserved systolic function, a diagnosis of PA should be considered.

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.

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.