S A McG Thom

Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV.

Summary of recommendationsProvide advice on life-style modifications for all people with high blood pressure (BP) and those with borderline or high-normal BP. Advice on effective nonpharmacological interventions is provided (A).Initiate antihypertensive drug therapy in people with sustained systolic BP (SBP) ⩾160 mmHg or sustained diastolic BP (DBP) ⩾100 mmHg (A).Make treatment decisions in people with sustained SBP between 140 and 159 mmHg and/or sustained DBP between 90 and 99 mmHg according to the presence or absence of cardiovascular disease, other target organ damage, or an estimated cardiovascular disease (CVD) risk of ⩾20% over 10 years, according to the Joint British Societies CVD risk assessment programme/risk chart (A).CVD risk replaces CHD risk estimation to reflect the importance of stroke prevention as well as CHD prevention. The new CVD risk threshold of ⩾20% is equivalent to a CHD risk of approximately ⩾15% over 10 years.In people with diabetes mellitus, initiate antihypertensive drug therapy if SBP is sustained ⩾140 mmHg and/or DBP is sustained ⩾90 mmHg (B).In nondiabetic people with hypertension, the optimal BP treatment goals are: SBP <140 mmHg and DBP <85 mmHg. The minimum acceptable level of control (Audit Standard) recommended is <150/<90 mmHg. Despite the best practice, these levels will be difficult to achieve in some hypertensive people (B).In people with diabetes and high BP, optimal BP goals are: SBP <130 mmHg and DBP <80 mmHg. The minimum acceptable level of control (Audit Standard) recommended is <140/<80 mmHg. Despite the best practice, these levels will be difficult to achieve in some people with diabetes and hypertension (B).Meta-analyses of BP-lowering trials have confirmed that, in general, the main determinant of benefit from BP-lowering drugs is the achieved BP, rather than choice of therapy. In some circumstances, there are compelling indications and contraindications for specific classes of antihypertensive drugs, and these are specified (A).Most people with high BP will require at least two BP-lowering drugs to achieve the recommended BP goals. A treatment algorithm (AB/CD) is provided to advise on the sequencing of drugs and logical drug combinations (C). When there are no cost disadvantages, fixed drug combinations are recommended to reduce the number of medications, which may enhance adherence to treatment (C).Other drugs that reduce CVD risk must also be considered, notably, low-dose aspirin and statin therapy (A).Unless contraindicated, low-dose aspirin (75 mg/day) is recommended for all people needing secondary prevention of ischaemic CVD, and primary prevention in people with hypertension over the age of 50 years who have a 10-year CVD risk ⩾20% and in whom BP is controlled to the audit standard (A).Statin therapy is recommended for all people with high BP complicated by CVD, irrespective of baseline total cholesterol or low-density lipoprotein (LDL)-cholesterol levels. Similarly, statin therapy is also recommended for primary prevention in people with high BP who have a 10-year CVD risk ⩾20%, estimated from the Joint British Societies CVD risk-assessment programme/chart. Optimal cholesterol lowering should reduce the total cholesterol by 25% or LDL-cholesterol by 30% or achieve a total cholesterol of <4.0 mmol/l or LDL-cholesterol of <2.0 mmol/l, whichever is the greatest reduction (A).Glycaemic control should be optimised in people with diabetes, for example, HbA1c <7% (A).Advice is provided on the clinical management of hypertension in specific patient groups, that is, the elderly, ethnic minorities, people with diabetes mellitus, chronic renal disease, and in women (pregnancy, oral contraceptive use and hormone-replacement therapy).Suggestions for the improved implementation and audit of these guidelines in primary care are provided.

Pre-eclampsia, antiretroviral therapy, and immune reconstitution

Antiretrovirals are standard treatment for HIV-1-positive women during pregnancy in the UK, but little is known about maternal or fetal safety. In our cohort study of 214 pregnant women with HIV-1 infection, those who received no antiretroviral therapy had a rate of pre-eclampsia significantly lower (none of 61) than those on triple antiretroviral therapy (8 of 76; odds ratio 15.3, 95% CI 0.9-270, p=0.0087). However, the rate of pre-eclampsia in HIV-1-positive women on treatment did not differ from that in uninfected controls (12 of 214; p=0.2). The association of HIV-1-related immune deficiency with a low rate of pre-eclampsia, and the restoration of this rate in women treated with triple antiretroviral therapy to the expected rate indicates a pivotal role of the immune system in the pathogenesis of pre-eclampsia. The clinical presentation of pre-eclampsia and toxic effects of antiretroviral therapy could overlap and complicate diagnosis and management in these patients.

Effect of tumour necrosis factor‐α and interleukin 1β on endothelium‐dependent relaxation in rat mesenteric resistance arteries in vitro

Pre‐eclampsia is associated with elevated proinflammatory cytokine levels and endothelial dysfunction. This study examined the effect of two cytokines, tumour necrosis factor‐α (TNF) and interleukin‐1β (IL‐1) on endothelium‐dependent relaxation in response to acetylcholine (ACH), bradykinin (BK) and histamine (HIS) in rat mesenteric small arteries in vitro. Rat mesenteric arteries were mounted in an isometric myograph. Tone was induced with phenylephrine (PE) or a depolarizing solution containing 80 mM KCl (K80). Relaxation was measured in response to ACH, BK, HIS and sodium nitroprusside (SNP), an endothelium‐independent relaxant. Inhibition of NO synthase by a combination of Nω‐monomethyl‐L‐arginine (L‐NMMA) and Nω‐nitro‐L‐arginine methyl ester (L‐NAME) significantly inhibited relaxation in response to ACH and BK. Addition of an inhibitor of cyclooxygenase, indomethacin, had no additional effect when added to L‐NMMA and L‐NAME. Inhibition of endothelium‐derived hyperpolarizing factor (EDHF) by K80 partially reduced responses to ACH and BK. Inhibition of HIS‐induced relaxation was more marked with K80. L‐NMMA and L‐NAME largely abolished the remaining relaxation to ACH, BK and HIS in arteries contracted with K80. Preincubation with TNF for 30 min caused an inhibition of relaxation in response to ACH and BK in arteries contracted with PE. Responses to HIS and SNP were not affected by TNF under these conditions. TNF also inhibited ACH‐induced relaxation in arteries contracted with K80. IL‐1 had no effect on responses to ACH and the combination of TNF and IL‐1 was not more effective than TNF alone. The inhibitory effect of TNF on ACH‐induced relaxation was abolished by coincubation with superoxide dismutase (SOD) and was not seen if NO synthase was inhibited by L‐NMMA and L‐NAME. TNF inhibits the NO‐dependent component of endothelium‐dependent relaxation in response to ACH and BK, but does not inhibit the EDHF‐dependent component. This effect may be attributable to the ability of TNF to increase levels of superoxide anions (O2−) and the ability of O2− to inactivate NO. This mechanism could contribute to the endothelial dysfunction seen in situations where TNF is elevated, such as pre‐eclampsia.

Image-based carotid flow reconstruction: a comparison between MRI and ultrasound.

Atherosclerosis is a major cause of morbidity and mortality. Its apparent link with wall shear stress (WSS) has led to considerable interest in the in vivo estimation of WSS. Determining WSS by combining medical images with computational fluid dynamics (CFD) simulations can be performed both with magnetic resonance imaging (MRI) and three-dimensional ultrasound (3DUS). This study compares predicted 3D flow patterns based on black blood MRI and 3DUS. Velocity fields in the carotid arteries of nine subjects have been reconstructed, and the haemodynamic wall parameters WSS, oscillatory shear index (OSI), WSS gradients (WSSG) and angle gradients (WSSAG) were compared between the two imaging techniques. There was a good qualitative agreement between results derived from MRI and 3DUS (average correlation strength above 0.60). The root mean square error between haemodynamic wall parameters was comparable to the range of the expected variability of each imaging technique (WSS: 0.411 N m(-2); OSI: 0.048; temporal WSSG: 150 N s(-1) m(-2); spatial WSSG: 2.29 N m(-3); WSSAG: 87.6 rad m(-1)). In conclusion, MRI and 3DUS are capable of providing haemodynamic parameters when combined with CFD, and the predictions are in most cases qualitatively and quantitatively similar. The relatively high cost of MRI and continuing improvement in ultrasound favour US to MRI for future haemodynamic studies of superficial arteries.

Carotid geometry reconstruction: a comparison between MRI and ultrasound

Image-based Computational Fluid Dynamics (CFD) has become a popular tool for the prediction of in vivo flow profiles and hemodynamic wall parameters. Currently, Magnetic Resonance Imaging (MRI) is most widely used for in vivo geometry acquisition. For superficial arteries such as the carotids and the femoral artery, three-dimensional (3-D) extravascular ultrasound (3-DUS) could be a cost-effective alternative to MRI. In this study, nine healthy subjects were scanned both with MRI and 3-DUS. The reconstructed carotid artery geometries for each subject were compared by evaluating cross-sectional areas, centerlines, and carotid nonplanarity. Lumen areas agreed very well between the two different acquisition techniques, whereas centerlines and nonplanarity parameters showed measurable disagreement, possibly due to the different neck and head positions adopted for 3-DUS versus MRI. With the current level of agreement achieved, 3-DUS has the potential to become an inexpensive and fast alternative to MRI for image-based CFD modeling of superficial arteries.

Various issues relating to computational fluid dynamics simulations of carotid bifurcation flow based on models reconstructed from three-dimensional ultrasound images.

Abstract Computational fluid dynamics (CFD) flow simulation techniques have the potential to enhance understanding of how haemodynamic factors are involved in atherosclerosis. Recently, three-dimensional ultrasound has emerged as an alternative to other three-dimensional imaging techniques, such as magnetic resonance angiography (MRA). The method can be used to generate accurate vascular geometry suitable for CFD simulations and can be coupled with Doppler ultrasound to provide physiologically realistic flow boundary conditions. However, there are various ways to utilize the flow data acquired, possibly leading to different results regarding both flow and wall shear stress patterns. A disadvantage of three-dimensional ultrasound for imaging the carotid bifurcation has been established as being the scanning limitation of the jawbone position. This may make artificial extensions of the internal and/or external carotid arteries necessary, which in turn may influence the predicted flow patterns. Flow simulations were carried out for three outflow calculation schemes as well as four geometries with different extensions to the carotid daughter vessels. It was found that variation of flow patterns was more strongly influenced by the outflow conditions than by the extensions of the daughter vessels. Consequently, it is recommended that for future CFD simulations of carotid flow using three-dimensional ultrasound data, the outflow boundary conditions should rely on the most accurate measurement available, and flow data recorded in the common and internal carotid are considered more reliable than data from the external carotid. Even though the extended lengths of the daughter vessels have insignificant effects on the predicted haemodynamic parameters, it would be a safer option to extend the internal carotid by approximately three times the diameter of the common carotid artery.

Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis

Background  Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs.

Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men

Summary.  Background: Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects.Methods: Fifty‐four male subjects (age 49–79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid‐femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B‐mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet‐monocyte complexes (PMC), platelet expression of PAC‐1 binding site and CD62P, and expression of L‐selectin on leukocytes.Results: Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C‐reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity.Conclusions: Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

3D ultrasound-based CFD for carotid flow prediction: a reproducibility study

Image-based CID has been a prime technique for studying arteriosclerosis, plaque formation, aneurysm rupture and bypass design in the past decade. The imaging techniques used for vessel geometry acquisition are usually X-ray (CT-scan), intravascular ultrasound or most frequently MRI. It has been shown in previous studies that 3D extravascular ultrasound (3D US) can provide a cost-effective alternative for imaging superficial arteries like the carotid bifurcation or femoral arteries. In this study, the carotid bifurcation of 9 healthy subjects have been scanned twice within two to six weeks. CFD models for each subject and each scan were built using the corresponding anatomical data acquired in vivo. Overall reproducibility was satisfactory. Two main sources of error were identified. (1) Blurred border between vessel lumen and endothelium, causing the operator to overestimate the lumen area; and (2) altered neck angles. It is expected that with further improvement in ultrasound image quality and with standardisation of the imaging protocol, 3D US has a huge potential to become a viable alternative to MRI both for clinical and research uses.

Arterial waveform parameters in a large, population-based sample of adults: relationships with ethnicity and lifestyle factors.

Little is known about how aortic waveform parameters vary with ethnicity and lifestyle factors. We investigated these issues in a large, population-based sample. We carried out a cross-sectional analysis of 4798 men and women, aged 50–84 years from Auckland, New Zealand. Participants were 3961 European, 321 Pacific, 266 Maori and 250 South Asian people. We assessed modifiable lifestyle factors via questionnaires, and measured body mass index (BMI) and brachial blood pressure (BP). Suprasystolic oscillometry was used to derive aortic pressure, from which several haemodynamic parameters were calculated. Heavy alcohol consumption and BMI were positively related to most waveform parameters. Current smokers had higher levels of aortic augmentation index than non-smokers (difference=3.7%, P<0.0001). Aortic waveform parameters, controlling for demographics, antihypertensives, diabetes and cardiovascular disease (CVD), were higher in non-Europeans than in Europeans. Further adjustment for brachial BP or lifestyle factors (particularly BMI) reduced many differences but several remained. Despite even further adjustment for mean arterial pressure, pulse rate, height and total:high-density lipoprotein cholesterol, compared with Europeans, South Asians had higher levels of all measured aortic waveform parameters (for example, for backward pressure amplitude: β=1.5 mm Hg; P<0.0001), whereas Pacific people had 9% higher loge (excess pressure integral) (P<0.0001). In conclusion, aortic waveform parameters varied with ethnicity in line with the greater prevalence of CVD among non-white populations. Generally, this was true even after accounting for brachial BP, suggesting that waveform parameters may have increased usefulness in capturing ethnic variations in cardiovascular risk. Heavy alcohol consumption, smoking and especially BMI may partially contribute to elevated levels of these parameters.