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Aims: We evaluated the impact of early rhythm control (ERC) on diabetes-related complications and mortality in subjects with type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF)., Methods: This observational cohort study based on the Korean National Health Insurance Service claims database from 2009 to 2016, divided newly diagnosed AF patients with T2DM into ERC or usual care groups based on receiving rhythm control treatment within 1 year of AF diagnosis. The primary outcome was ischemic stroke, and the secondary outcomes were macro/microvascular complications, and all-cause death., Results: Among 47,509 subjects (mean age 66.7 ± 10.5 years; 61.8 % men; mean CHA 2 DS 2 -VASc score 4.6 ± 1.8; mean follow-up 4.3 ± 2.3 years; mean DM duration 5.6 ± 4.7 years), 23.1 % received ERC, and 76.9 % did not (usual care group). ERC was associated with lower risks of ischemic stroke, macrovascular and microvascular complications, and all-cause death compared to usual care (adjusted hazard ratios [95 % confidence interval]: 0.77 [0.70-0.85], 0.79 [0.73-0.86], 0.86 [0.82-0.90], and 0.92 [0.87-0.98], p < 0.001, <0.001, <0.001, and 0.012, respectively)., Conclusions: Early rhythm control was associated with reduced risks of diabetes-related complications and mortality in subjects with T2DM and AF. Rhythm control within 1 year of AF diagnosis with proper anticoagulation should be considered to prevent adverse outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the association of high-normal blood pressure (BP) and impaired fasting glucose (IFG) with the risk of atrial fibrillation (AF) in two cohorts., Methods: The Korean National Health Insurance Service-Health Screening (K-NHIS-HealS, 2002-2003, follow-up until 2013) Study and the UK Biobank (2007-2010, follow-up until 2021) were evaluated. We used Cox proportional hazards regression models to evaluate the associations of high-normal BP and IFG with incident AF., Results: In the K-NHIS-HealS and the UK Biobank, 2346 and 5314 incident AF events were recorded during the mean follow-up of 7.4 and 11.8 years. The adjusted HRs (95% CIs) for AF in the Korean and UK cohorts were 1.11 (1.02 to 1.21) and 1.07 (1.01 to 1.13) in individuals with high-normal BP; and 1.14 (1.04 to 1.25) and 1.10 (1.01 to 1.20) in individuals with IFG, respectively. The AF risk showed a dose-response relationship with BP and fasting blood glucose level. The risk of incident AF was increased by the combination of high-normal BP and IFG., Conclusions: In healthy individuals, high-normal BP and IFG were important risk factors for AF. When high-normal BP and IFG were combined, the risk of new-onset AF was significantly increased. These findings may suggest that lifestyle interventions for high-normal BP and IFG should be considered to reduce the risk of AF., Competing Interests: Competing interests: BJ has served as a speaker for Bayer, BMS/Pfizer, Medtronic and Daiichi-Sankyo, and received research funds from Medtronic and Abbott. GL has served as a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. SCY reports being a chief technology officer of the PHI Digital Healthcare, and received a consulting fee from IQVIA. BJ, GL and SCY have received no fees directly or personally., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypertension (HTN) is the most prevalent co-morbidity among atrial fibrillation (AF) patients; the relationship between the two is bidirectional, with an incremental effect on adverse outcomes., Purpose: To study clinical features, treatment patterns and 1year outcomes amongst AF patients with HTN in the EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry, a prospective multi-national survey conducted by the European Society of Cardiology in 9 European countries., Methods: Of 3119 enrolled AF patients, 2194 were diagnosed with HTN (AF-HTN) and 909 were normotensive (AF-NT) (16 patients had unknown HTN status). We compared baseline clinical features, management strategy and 1-year outcomes in terms of all-cause death, cardiovascular (CV) death, and any thrombosis-related event (TE: stroke, transient ischemic attack, acute coronary syndrome, coronary intervention, cardiac arrest, peripheral/pulmonary embolism) in AF-HTN vs AF-NT patients., Results: The AF-HTN patients had more prevalent CV risk factors and comorbidities (median CHA2DS2-VASc score (IQR) 4 (3, 5) in AF-HTN, versus 2 (1, 3) in AF-NT; p<0.01). Crude rate of all-cause death and any TE event was higher in AF-HTN (194 (11.2%) versus 60 (8.2%), p=0.02). Kaplan-Meier analysis curves for death by hypertensive status showed no significant differences between the subgroups (log rank test, p=0.22). On logistic regression analysis, HTN did not emerge as an independent risk factor for outcomes (OR 1.08, 95% CI 0.76-1.54)., Conclusion: AF-HTN patients have a higher prevalence of comorbidities and this conferred a higher risk for a composite endpoint of all-cause death and thromboembolic events. In this cohort HTN did not independently predict all-cause mortality at 1-year., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Renal dysfunction is frequently associated with left ventricular (LV) hypertrophy and diastolic dysfunction in hypertensive patients. Limited data exist on renal dysfunction and diastolic impairment among British ethnic minorities with hypertension. We studied associations between renal impairment and diastolic dysfunction in hypertensive subjects of African-Caribbean and South Asian origin. Five hundred and ten hypertensive subjects with ejection fraction ⩾55% and with no history of ischaemic heart disease/valve pathology were included from the original population of the Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES). Diastolic function and cardiac remodelling were measured by echocardiography. LV hypertrophy was common and present in 62% of patients with normal estimated glomerular filtration rate (eGFR, >90 ml min -1 per 1.73 m 2 ), 73% in those with eGFR 60-89 ml min -1 per 1.73 m 2 and 87% with eGFR <60 ml min -1 per 1.73 m 2 . On both univariate and multivariable linear regression, reduced eGFR was associated with higher LV mass index (LVMI, P=0.01 and P=0.039, respectively). On multivariable analyses, increased LVMI (but not eGFR) was an independent predictor of echocardiographic parameters of diastolic dysfunction. Higher LVMI was an independent predictor of all-cause or cardiovascular death on multivariable analyses (both P=0.002), but not eGFR. LV hypertrophy is common in minority ethnic groups with hypertension, especially in the presence of renal dysfunction. Increased LVMI rather than renal impairment per se is a major determinant of diastolic dysfunction and increased risk of cardiovascular or all-cause death among hypertensive patients without end-stage renal failure.

Limited evidence is available on the safety and efficacy of anticoagulants in non-valvular atrial fibrillation (AF) patients with concomitant hypertension. We investigated the safety and efficacy of 476 consecutive anticoagulated Chinese outpatients with non-valvular AF and hypertension. Occurrence of ischaemic stroke and major bleeding, and international normalized ratio (INR) values during these events were recorded. There was no significant difference in anticoagulation control between patients with or without hypertension. INR-specific incidence rates of the events were calculated, which showed no excessive risk for ischaemic stroke (2.5 vs 1.6% per year, P=0.22) or major bleeding (3.9 vs 3.2% per year, P=0.29) in non-valvular AF patients with or without hypertension. In multivariate analysis, congestive heart failure, smoking and high CHADS2 score were independent predictors for ischaemic stroke, whereas use of antiplatelet agents was an independent predictor for bleeding. It can be noted that hypertension was not associated with ischaemic stroke or major bleeding. Hypertensive patients who achieved target blood pressure control (<130/80 mm Hg) had a lower ischaemic stroke (0.9 vs 3.1% per year, P=0.01), but similar bleeding risk compared with those not achieving target blood pressure. Our findings demonstrate the effects of hypertension on the outcomes of warfarin therapy; further investigation is needed to clarify whether more aggressive antihypertensive therapy could result in better outcomes in hypertensive patients with non-valvular AF.

Background: Abnormal levels of prothrombotic markers have been described in hypertension, but no such marker has yet been shown to reliably predict cardiovascular outcomes in hypertension. We hypothesized that raised circulating levels of soluble P-selectin (sP-sel, an index of platelet activation) and/or von Willebrand factor (vWF, an index of endothelial damage/dysfunction) would predict vascular events in patients treated for cardiovascular risk., Methods: We measured vWF and sP-sel levels by an ELISA in 234 hypertensive participants with no prior cardiovascular events who were participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Plasma vWF and sP-sel levels were related to the subsequent cardiovascular events over a mean (SD) follow-up period of 59.6 (19) months., Results: Plasma sP-sel was a significant predictor of myocardial infarction (P = 0.03), with the greatest risk amongst those with the highest sP-sel levels. sP-sel did not predict cerebrovascular events (P = 0.53) or composite cardiovascular events (P = 0.06). No significant relationships were found between vWF levels and outcomes. There was no relationship to the presence or absence of diabetes mellitus (DM) at baseline or subsequent development of DM during the follow-up period., Conclusions: Among 'high-risk' patients with hypertension, raised levels of sP-sel (platelet activation) were predictive of myocardial infarction. Levels of vWF (endothelial damage/dysfunction) were not associated with coronary events and neither marker predicted cerebrovascular or composite cardiovascular endpoints. Platelets (or P-selectin) might represent a target for novel therapies or an adjunctive aid to risk stratification in the setting of hypertension.

Introduction and Methods: We tested the hypothesis that there was a significant relationship between haemorheological markers [white blood cell count (WCC), plasma viscosity (PV), haematocrit (HCT) and fibrinogen], as well as plasma von Willebrand factor (vWf, an index of endothelial damage/dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation), to five global measures of cardiovascular risk [i.e. Framingham coronary heart disease (CHD), stroke and cardiovascular death score, the Pocock cardiovascular risk score and the sum of individual risk factors]., Results: Men with a high (> or = median, n = 156) Framingham 10-year CHD risk score had higher levels of WBC (P = 0.027), fibrinogen (P = 0.012) and vWF (P = 0.002) than 153 men with results < median. Men with a high 10-year stroke risk score had significantly higher levels of fibrinogen (P = 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) = 0.089, P < 0.0001). vWF, PV and fibrinogen were predictors of Pocock cardiovascular death risk (P < 0.0001) but vWF was the only independent predictor of Framingham cardiovascular death risk (P = 0.001)., Conclusions: Abnormal haemorheological factors (particularly high plasma fibrinogen levels) and endothelial damage/dysfunction (high vWF), but not platelet activation (sP-sel), are related to established cardiovascular and death risk scores. This relationship was most evident amongst male 'high-risk' hypertensive subjects.

Hypertension is a common condition and a well-known risk factor for cardiovascular morbidity and mortality. Hypertension is also associated with damage or dysfunction with other organs in the body, causing strokes, proteinuria, renal failure and retinopathy. Damage/ dysfunction in these areas are commonly termed as hypertensive target organ damage (TOD). The development of TOD is a multifactorial process affecting various elements of vascular biology such as the renin-angiotensin-aldosterone system, prothrombotic states, inflammatory processes and endothelial function. These factors are inter-related in their contribution to the development of TOD. As hypertension is an important public health challenge worldwide a better understanding of the underlying pathophysiological processes leaving to its complications would be beneficial towards improving management strategies. The purpose of this review is to describe the various mechanisms involved in the pathogenesis of TOD and highlight recent advances in this field.

Background: The increased risk of target organ damage (TOD) in hypertension may be related to a prothrombotic or hypercoagulable state, with abnormalities in platelet activation. Altered angiogenesis, possibly related to increased plasma vascular endothelial growth factor (VEGF) is also a feature of hypertension. We hypothesized a link between altered angiogenesis and TOD in hypertension. Accordingly, the angiogenic growth factors VEGF, angiopoietin 1 and 2 (Ang 1 & 2) and soluble angiopoietin receptor Tie-2 in plasma and in platelets were assessed in terms of the presence or absence of hypertensive TOD., Methods: We studied 199 patients (75% men; mean age 68 years) with hypertension. Of these, 125 had evidence of hypertensive TOD (stroke, previous myocardial infarction, angina, left ventricular hypertrophy and mild renal failure). Patients were compared with 74 healthy normotensive controls (69% men; mean age 68 years). Plasma VEGF, Ang 1 & 2 and Tie-2, and total platelet levels of VEGF and Ang-1 (obtained by lysing a known number of platelets with 0.5% Tween) were measured by an enzyme-linked immunosorbent assay., Results: Hypertensive patients had higher levels of plasma VEGF, Ang-1, Ang-2, Tie-2 and platelet VEGF (all P

Background: The metabolic syndrome (MetS), predicting coronary heart disease (CHD), is a compound of risk factors including diabetes, obesity and hypertension. The relationship between the development of MetS, diabetes and CHD in patients with established hypertension is unclear. We hypothesized that patients with hypertension developing MetS are at increased risk of type II diabetes and CHD compared with patients who do not develop MetS., Materials and Methods: We prospectively studied 284 patients (100 with existing/established MetS) with hypertension but without diabetes and CHD over 4 years. MetS and diabetes were diagnosed by the modified NCEP and ADA criteria, and CHD risk by the Framingham risk equation; all patients had annual fasting blood sampling., Results: Over 4 years of follow up, 75 of the 184 patients (41%) initially free of MetS at baseline subsequently fulfilled the criteria for MetS. These patients (i.e. 'developing MetS') had higher baseline BMI, triglycerides and lower HDL cholesterol, with a higher calculated CHD risk (all P

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.

Background: Data on the effect of hormone replacement therapy (HRT) on blood pressure (BP) in hypertensive menopausal women are limited., Objective: To investigate the association between HRT and longitudinal change in BP in hypertensive menopausal women., Patients and Methods: We recruited a total of 161 hypertensive menopausal women (mean age = 52.2 +/- 6.6 years) attending the hypertension clinic in our hospital that requires HRT to attenuate the effect of menopause symptoms. These women were followed for up tp 36 months, being evaluated every 6 months with measurements of their BP, weight and the number of drugs needed to control their BP. We also measured serum cholesterol levels before and after the initiation of HRT., Results: The systolic BP remained unaffected throughout the whole follow-up period, whereas the diastolic BP was slightly reduced at 6, 24 and 36 months. This decrease was accompanied by an increased need for antihypertensive medication throughout the entire follow-up period, while the body weight also increased at 18, 24, and 36 months. No particular differences were noted with respect to ethnicity, history of pre-eclampsia or surgical menopause, before and after the initiation of HRT. Serum cholesterol levels remained unchanged during the evaluation period. Oestrogen-progestogen combination therapy use was associated with a lower diastolic BP and a smaller number of antihypertensive drugs compared to other forms of HRT., Conclusion: HRT use does not have an adverse gross effect on BP in hypertensive menopausal women who need it, although there may be an increased need for antihypertensive therapy during the 36-moth follow-up period of our study.

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is associated with increased fibrosis of the extracellular matrix (ECM). Myocardial stiffness is a feature of diastolic dysfunction. We assessed circulating TIMP-1 as a marker of diastolic dysfunction in patients with type 2 diabetes mellitus (DM) and hypertension, who were compared with healthy controls., Methods: We recruited 54 patients (43 males; mean age 68 +/- 5 years) with treated type 2 DM (i.e. controlled glycaemia, hypertension, hyperlipidaemia), 35 (30 males; 69 +/- 8 years) treated nondiabetic hypertensives, and 31 healthy controls (18 males; 66 +/- 5 years). Circulating TIMP-1 was measured by ELISA. Using transthoracic echocardiography, the early (E) diastolic mitral inflow velocity was measured with pulse wave Doppler, and the early mitral annular velocity (e'), a recognized index of diastolic relaxation, was measured with tissue Doppler. The E/A ratio was also calculated and isovolumic relaxation time measured., Results: Mean e' levels differed significantly between controls, diabetics and hypertensives (P < 0.0001). Circulating TIMP-1 was significantly different between patients and controls (P = 0.006), but there was no statistically significant difference between the DM and hypertension group. In both groups, only e' was negatively correlated with TIMP-1 levels, with a stronger correlation among the hypertensive patients (Spearman r = -0.544, P = 0.001) when compared with the diabetic group (r = -0.341, P = 0.011)., Conclusion: Diastolic relaxation is impaired in diabetes and hypertensive patients. The relationship between TIMP-1 and e' may reflect increased myocardial fibrosis and consequent diastolic dysfunction, which may be more prominent in hypertension.

Background: Platelets carry angiogenic growth factors vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1). Although platelet-derived growth factors are important in the pathogenesis and metastasis of malignancy, their role in the pathogenesis of complications and the response to treatment in hypertension is less known., Objective: To test the hypotheses that there are differences in VEGF and Ang-1 in the plasma and within platelets from patients with hypertension, and that levels change with successful treatment., Methods: We recruited 42 previously untreated patients with hypertension (25 male; mean age 53 years) and 30 age- and sex-matched controls. Plasma VEGF, Ang-1 and soluble P-selectin (sPsel, an index of platelet activation), and total platelet [platelet VEGF (pVEGF) and platelet Ang-1 (pAng-1)] were measured by ELISA. The patients were then treated for 6 months with amlodipine-based antihypertensive therapy, achieving a mean blood pressure below 140/80 mmHg., Results: Patients with hypertension had significantly higher levels of plasma sPsel (P =0.01), VEGF (P < 0.001) and Ang-1 (P = 0.01), as well as pVEGF (P < 0.001) and pAng-1 (P =0.02). The levels of plasma and platelet angiogenic growth factors were significantly reduced after antihypertensive treatment (VEGF, P = 0.01; pVEGF, P < 0.001; Ang-1, P < 0.001; pAng-1, P = 0.04). There were no correlations with blood pressure or the levels of sPsel., Conclusion: Levels of plasma and intra-platelet VEGF and Ang-1 are increased in hypertension and are decreased with treatment. Platelet levels of VEGF and Ang-1 may be related to platelet activation but may also involve other mechanisms (for example, the general vascular and haemodynamic changes) that are seen in hypertension.

The objective of this study was to investigate differences in electrocardiographic (ECG) parameters and the prevalence of left ventricular hypertrophy (LVH) by various ECG criteria between different ethnic groups in west Birmingham, United Kingdom. In all, 380 consecutive patients, mean age 63 (7.8) years, 75 (20%) female patients assessed for inclusion in hypertension trials in a city centre teaching hospital were studied: 303 (80%) were Caucasian, 43 (11.4%) Afro-Caribbean and 32 (8.5%) South Asian. LVH was assessed using seven different criteria, with adjustment for age and body mass index (BMI). The performance of the various criteria were compared between the three ethnic groups. There were significant differences in the R-wave voltage in lead aVL, the Sokolow-Lyon voltage and in criteria based on limb lead voltages alone between the three ethnic groups. Highest ECG voltages were seen in Afro-Caribbeans, and this translated into a significantly higher prevalence of LVH when assessed by the R-wave in aVL and the Sokolow-Lyon criteria. There were no significant differences between Caucasians and South Asians. These differences were abolished after adjustment for age and BMI. There was no difference in the Cornell voltage or its derivatives in men between the three ethnic groups. In conclusion, apparent differences in electrocardiographic voltage and the prevalence of LVH between ethnic groups are dependent upon the criteria chosen and may simply be secondary to differences in BMI. Unlike Afro-Caribbean patients, South Asians do not demonstrate significant differences in ECG voltage compared with Caucasians.

Background: Although elevated systemic blood pressure results in high intravascular pressure, the main complications, coronary heart disease (CHD), ischaemic strokes and peripheral vascular disease (PVD), are related to thrombosis rather than haemorrhage. Some complications related to elevated blood pressure, heart failure or atrial fibrillation, are themselves associated with stroke and thromboembolism. It therefore seemed plausible that use of antithrombotic therapy may be particularly useful in preventing thrombosis-related complications of elevated blood pressure., Objectives: To conduct a systematic review of the role of antiplatelet therapy and anticoagulation in patients with blood pressure, including those with elevations in both systolic and diastolic blood pressure, isolated elevations of either systolic or diastolic blood pressure, 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., Search Strategy: Reference lists of papers resulting from this search, electronic database searching (MEDLINE, EMBASE, DARE), and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors of these studies were contacted to obtain further data., Selection Criteria: Randomised controlled trials (RCTs) in patients with elevated blood pressure were included if they were of at least 3 months in duration and compared antithrombotic therapy with control or other active treatment., Data Collection and Analysis: Data were independently collected and verified by two reviewers. Data from different trials were pooled where appropriate., Main Results: The ATC meta-analysis of antiplatelet therapy for secondary prevention in patients with elevated blood pressure reported an absolute reduction in vascular events of 4.1% as compared to placebo. Data on the patients with elevated blood pressure from the 29 individual trials included in this meta-analysis was requested but could not be obtained. Three additional trials met the inclusion criteria and are reported on here. Acetylsalicylic acid (ASA) did not reduce stroke or 'all cardiovascular events' compared to placebo in primary prevention patients with elevated blood pressure and no prior cardiovascular disease. Based on one large trial (HOT 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. There was no significant difference between ASA and clopidogrel for the composite endpoint of stroke, myocardial infarction or vascular death in one trial (CAPRIE 1996). In two small trials warfarin alone or in combination with ASA did not reduce stroke or coronary events., Reviewers' Conclusions: For primary prevention in patients with elevated blood pressure, anti-platelet 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 blood pressure (ATC meta-analysis: APTC 1994) 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 blood pressure cannot be recommended because of lack of demonstrated benefit. Glycoprotein IIb/IIIa inhibitors as well as ticlopidine and clopidogrel have not been sufficiently evaluated in patients with elevated blood pressure. Further trials of antithrombotic therapy with complete documentation of all benefits and harms are required in patients with elevated blood pressure.

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 < 0.001), but not plasma fibrinogen. There were no correlations between the fall in BP and the improvement in any of the research indices., Conclusions: Intensified cardiovascular risk management results in significant improvements in indices of endothelial, platelet and rheological function in a population of hypertensives at high risk of cardiovascular events. These improvements appear to be independent of the degree of change in BP. Given the fundamental role of interactions between the endothelium and circulating blood components in the pathogenesis of hypertensive complications this may be of importance in preventing adverse cardiovascular outcomes.

Background: Abnormalities in endothelial function, angiogenesis and thrombogenesis are found in essential hypertension. Angiotensin II has been postulated as an agent involved in these processes. We hypothesized that the treatment of essential hypertension with the angiotensin II receptor antagonist, losartan, would affect endothelial damage/dysfunction, angiogenesis and coagulation, when compared to treatment with a diuretic., Methods: Forty hypertensive patients (28 male, mean age 56 +/- 11.8 years) were randomized to treatment with losartan 50-100 mg o.d. or hydrochlorothiazide 12.5-25 mg o.d. over a 12-week period. Patients were assessed at week 0, 4 and 12. Endothelial damage/dysfunction was assessed using plasma levels of von Willebrand factor (vWf) and changes in flow-mediated dilation of the brachial artery (FMD). Vascular endothelial growth factor (VEGF) and its soluble receptor Flt-1 (sFlt-1) were measured as indices of angiogenesis, and plasma tissue factor (TF) as an index of coagulation. Baseline results in hypertensives were compared to 20 healthy controls (13 male, mean age 61.1 +/- 10.1 years)., Results: Mean patient BP was 161/95 +/- 21/18 mmHg compared to 134/81 +/- 11/7 mmHg in controls (p<0.002). Plasma levels of TF (p=0.023) were significantly higher in patients compared to controls, and FMD was significantly lower (p<0.001). There were no significant differences in baseline blood pressures, plasma indices or FMD between patients randomized to losartan and hydrochlorothiazide. There were no significant changes in levels of plasma indices or FMD over 12 weeks of treatment in either patient group. Significant correlations between levels of VEGF with sFlt-1 (Spearman p<0.001) and TF (p=0.009) and sFlt-1 and TF (p=0.035) were seen in the untreated state, amongst the patient group only., Conclusion: We have confirmed previous observations of increased levels of TF and decreased FMD in hypertensive patients compared to healthy controls. Contrary to previous observations in higher-risk hypertensive patient groups, the treatment of essential hypertension with either losartan or hydrochlorothiazide did not affect indices of endothelial damage/dysfunction, angiogenesis or coagulation.

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.

Background: Peripheral arterial disease (PAD) causes considerable morbidity and mortality. Hypertension is a risk factor for PAD. Therefore, treatment for hypertension must be compatible with the symptoms of PAD. Controversy regarding the effects of beta blockade for hypertension in patients with PAD has led many physicians to stop prescribing beta-blockers. Little is known about the effects of other classes of anti-hypertensive drugs in the presence of PAD., Objectives: To determine the effects of anti-hypertensive drugs on the: cardiovascular events and death in patients with hypertension and PAD; symptoms of claudication and critical leg ischaemia; progression of PAD, and revascularisation, or amputations., Search Strategy: Trials were sought via the Specialised Register of the Cochrane Peripheral Vascular Diseases Group (last searched July 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 2, 2003), and the NHS Database of Abstracts of Reviews of Effectiveness (DARE) (last searched August 2002). There were no language restrictions. Abstracts of cardiology meetings were studied. Reference lists of papers were also examined., Selection Criteria: Randomised controlled trials of at least one anti-hypertensive treatment against placebo, or two anti-hypertensive medications against each other, with interventions lasting at least one month. Trials had to include patients with symptomatic PAD. Trials of poor quality and execution were excluded, as were cross-over trials., Data Collection and Analysis: Data were extracted by one reviewer and checked by the other. Eligible studies were excluded when presentation prevented adequate extraction of data, and enquiries to authors did not yield the raw data., Main Results: Two studies were included in the review. In one trial using perindopril in small numbers of patients with PAD, there was a marginal increase in claudication distance (weighted mean difference (WMD) 8.0, 95% confidence interval (CI) -30.66 to 46.66), but no change in ankle brachial pressure index (ABPI), (WMD 0, 95% CI -0.14 to 0.14), and a reduction in walking distance (WMD -46, 95 % CI -169.24 to 77.24). In patients undergoing angioplasty, a second trial suggested that the calcium antagonist verapamil reduced restenosis, although this was not reflected in the maintenance of a high ABPI., Reviewer's Conclusions: The evidence for various anti-hypertensive drug classes in PAD is poor, so that it is unknown whether significant benefit or risk accrues from their use. In view of this, no definite recommendations on use or avoidance can be made from the available data.