Lipid lowering: another method of reducing blood pressure? - Nature

Journal of Human Hypertension (2002) 16, 753–760 & 2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh

REVIEW ARTICLE

Lipid lowering: another method of reducing blood pressure? AS Wierzbicki Lipid Unit, Department of Chemical Pathology, St Thomas’ Hospital, London, UK

Modern management of cardiovascular risk depends on assessment of cardiovascular risk factors. Hypertension and hyperlipidaemia are synergistic risk factors for cardiovascular events. Both show a degree of crosscorrelation through sharing mechanisms of pathogenesis including insulin resistance and endothelial dysfunction. This article reviews the common pathways leading to dyslipidaemia and hypertension and the effects diet and lipid-lowering drug therapies have had on correcting blood pressure in patients with essential hypertension. Both statins and fibrates have shown a capability to lower blood pressure by up to 8/5 and 15/ 10 mmHg respectively, in some small-scale clinical trials and have effects on arterial wall structure and hence

pulse wave velocity. This blood pressure action may account for some of the clinical effects of lipid-lowering drugs on cardiovascular risk. Thus, lipid lowering may provide an additional method of correcting hypertension in some high-risk patients. However, data from largescale intervention trials are either absent or ambiguous. Definitive large-scale trials to investigate the antihypertensive effects of lipid-lowering drugs are required, although end point studies examining the interaction of lipid-lowering and antihypertensive drugs to determine optimum combinations are already under way. Journal of Human Hypertension (2002) 16, 753–760. doi:10.1038/sj.jhh.1001483

Keywords: cholesterol; cardiovascular risk; statin; fibrate; review; hypertension

Introduction Hyperlipidaemia and hypertension are common conditions that both contribute synergistically to cardiovascular risk. The management of cardiovascular risk now forms the principal function of both lipid and hypertension clinics, and this article will address what benefits over and beyond risk reduction can be achieved by management of the causes of hyperlipidaemia and, in particular, whether lipidlowering drugs have direct effects on blood pressure.

Epidemiology Surveys of hypertensive patients routinely identify other cardiovascular risk factors in this population. If lipids have effects in blood pressure, it would be expected that patients with hyperlipidaemia would show a greater incidence of hypertension. The common occurrence of both syndromes is often noted but, given the high prevalence of both hyperlipidaemia and hypertension, is often dismissed as coincidental.1 Up to 40% of hypertensive patients have hyperlipidaemia and 40% are Correspondence: AS Wierzbicki, Department of Chemical Pathology, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK. Received 13 March 2002; revised and accepted 2 September 2002

obese.2–4 In secondary hypertension, disorders associated with chronic renal failure cause a mixed hyperlipidaemia or, in the case of nephrotic syndrome, hypercholesterolaemia.3 Hypertension and hyperlipidaemia may be related at a deeper level as insulin resistance is a common feature in the pathogenesis of both conditions.5,6 In epidemiological studies, where hypertension has been linked to hyperlipidaemia, the principal factors seem to be insulin resistance and saturated fat intake (ie plasma cholesterol) (Table 1).7 Endothelial dysfunction has been described in association with hypertension in many studies; it also has strong associations with insulin resistance, dyslipidaemia, and other cardiovascular risk factors.8 Indeed, hypertension and hypercholesterolaemia act synergistically as cardiovascular risk factors, although the exact mechanisms are obscure but certainly include both insulin resistance and endothelial dysfunction.

Dietary management Lifestyle strategies are employed in the management of both hyperlipidaemia and hypertension, and both diets have remarkable similarities. Both aim to stop smoking, reduce saturated fat intake, reduce alcohol consumption, increase fruit and fibre intake, and improve exercise tolerance.6 The only difference is in the salt restriction, which is not routinely advised

Lipid lowering and blood pressure AS Wierzbicki 754 Table 1 Epidemiological studies that have identified links between hypertension and hypercholesterolaemia. After Goode et al7 Study Tecumseh Community Southern California Framingham Tromso LRC prevalence Williams

Numbers

Lipid factors

Possible pathology

3064 4839 5127 16 744 7747 6128

TC, TG TC, TG TC TC, LDL, VLDL-C TG, VLDL-C LDL

IRS, saturated fat IRS, saturated fat Saturated fat IRS, saturated fat IRS Saturated fat

Abbreviation: total cholesterol (TC); triglyceride (TG); low-density-lipoprotein cholesterol (LDL-C); very-low-density-lipoprotein cholesterol (VLDL-C); insulin resistance syndrome (IRS).

for patients with hyperlipidaemia. Diet remains controversial in the management of hyperlipidaemia as many intervention trials have shown only minimal effects on the surrogate endpoint of cholesterol reduction. Yet trials with polyunsaturated fatty acids achieve a 0.6 mmol/l reduction in cholesterol as opposed to 0.15–0.3 mmol/l achieved with lowcholesterol diet.9 The Mediterranean diet as used in 605 patients in the Lyons Diet Heart Study10 or polyunsaturated fatty acid supplements used in GISSI-P in 11 374 patients11 showed reductions in coronary events of 40–70 and 20%, respectively. The role of diet in hypertension is also controversial though again many studies show a reduction in blood pressure of 5 mmHg with diets rich in polyunsaturated fatty acids, which did not translate into significant benefits in coronary events or strokes probably due to the inadequate size of the studies.12 The most recent of these was the dietary approaches to the hypertension study (DASH) in 459 patients with a blood pressure 4160/80 mmHg, which showed reductions of 11.6/5.3 mmHg in hypertensive patients as opposed to 3.5/2 mmHg in nonhypertensive patients with a low-cholesterol and low-salt diet.13

Sodium–lithium countertransport and familial dyslipidaemic hypertension

Surrogate markers for hypertension have been defined. The most currently investigated are the effects of hyperlipidaemia on nitric oxide production and paracrine hormone production by the endothelium (vide infra). However, other markers also show a relationship between hyperlipidaemia and hypertension. Sodium–lithium countertransport is an ill-understood membrane transport marker associated with hypertension and insulin resistance.14,15 It has been shown to be a prospective marker for hypertension in the Gubbio study.16 The kinetics of SLC activity show similar correlations with ethnicity, hypertension, and cardiovascular risk.14 Sodium–lithium countertransport is highly genetically inherited and shows a 65–80% heritability in various cohort studies.14 The Rochester study of 900 patients showed that SLC activity modelled as a recessive monogenic trait predicted blood pressure Journal of Human Hypertension

over and above low HDL, and apolipoprotein C2 in men.17 In the Utah study, which included patients with familial combined hyperlipidaemia (FCH) and familial hypercholesterolaemia (FH), SLC activity also correlated strongly with blood pressure and lipids.18,19 Both these epidemiological studies linked SLC to triglycerides, insulin resistance, and lipoprotein lipase activity as have studies in patients with type V hyperlipidaemia.20 The Utah study population defined a subgroup of up to 10% of patients with essential hypertension who had a phenotype of dyslipidaemia allied with hypertension with a strong genetic component. This group was termed familial dyslipidaemic hypertension (FDH). Studies in patients with FCH have persistently shown the presence of hypertension in 30–40% of patients, suggesting a lower penetrance for hypertension compared to dyslipidaemia in this group.21 Recently, a study in a colony of 634 baboons colony localised the gene behind SLC activity to baboon chromosome 5, a homologue of human chromosome 4.22 Genetic mapping studies of hypertension in FCH kindreds also show quantitative trait linkage of SLC activity to human chromosome 4p in the region containing a fatty acid hydrolase (CD36) and a-adducin and secondary loci at chromosome 8p near the lipoprotein lipase gene and for diastolic blood pressure chromosome 19 close to the apolipoprotein B locus.21 Many, but not all, studies, have shown an association between a-adducin polymorphisms and hypertension in cross-sectional studies23 and a few have implicated the fatty acid hydrolase CD 36.24 These studies suggest that a subgroup of patients with essential hypertension are also dyslipidaemic. This may comprise up to 10% of patients with hypertension. The treatment of FCH is well established with the use of statins, fibrates, or often a combination of both. However, no studies have measured the blood pressure response to lipidlowering therapy using accurate methods in this patient group.

Endothelium and hyperlipidaemia The interaction of lipids and the endothelium has been extensively reviewed in many publications,

Lipid lowering and blood pressure AS Wierzbicki

and shows a strong relationship between endothelial function and cholesterol or oxidised cholesterol levels.25,26 Although the direct role of endothelial dysfunction in determining prognosis in cardiovascular disease remains to be fully confirmed, increasing circumstantial evidence has confirmed that endothelial dysfunction is a feature of patients with hypertension and also those with diabetes, insulin resistance and small, dense LDL, hypercholesterolaemia, homocysteinaemia, but interesting not gross hypertriglyceridaemia. The lack of endothelial dysfunction in type V hyperlipidaemia despite severe insulin resistance cannot be easily explained.27 Any treatment of hyperlipidaemia including diet, bile acid sequestrants, statins, and fibrates improves endothelial function.26 Many studies with statins have demonstrated improvements in endothelial function that can occur within 2 weeks.28,29 Similarly, fibrates improve endothelial function in patients with diabetes through actions on postprandial lipaemia and HDL.30 However, little effect was seen on blood pressure in any of these studies. The mechanism by which lipid lowering increases nitric oxide production probably involves recoupling of endothelial nitric oxide synthase to enhance the production of nitric oxide rather than the peroxynitrite production associated with the decoupled enzyme and reduction of angiotensin II receptor expression.31 How directly endothelial function relates to blood pressure is controversial32 because though cholesterol concentration correlates well with endothelial function the studies examining the relationship between endothelial function and blood pressure have been conflicting. Some studies using flow-mediated dilation have shown an association of endothelial function with hypertension while others using brachial plethysmography have either failed to show any relationship or show a mild association.33 Given the conflicting data on the endothelial actions of some antihypertensive drugs, it remains to be seen whether concomitant therapy with lipid-lowering drugs will be synergistic or antagonistic. The main criticism of these studies investigating the role of lipid-lowering drugs on endothelial function as a surrogate for blood pressure is that the blood pressure response over the study period is not usually quoted or accurately measured.

Hypertension-associated target-organ damage and lipid-lowering drugs Microalbuminuria, retinopathy, and left ventricular hypertrophy are measured as indices of target-organ damage.34 Microalbuminuria is an index of renal glomerular endothelial function, and numerous studies have documented the effects of antihypertensives, ACE-inhibitors, or angiotensin-2 antagonists on microalbuminuria in diabetic and nondiabetic (ie hypertensive) populations. A 4%

decrease in albuminuria was seen in patients with nephrotic syndrome with fibrate therapy compared with a 2% decrease with a statin.35 Statin therapy reduced microalbuminuria and endothelin levels in 60 patients with type II diabetes.36 However, in neither study was blood pressure significantly affected and it has been assumed that these were endothelial actions of lipid lowering. Other studies using apheresis have shown no difference in proteinuria. A trial is under way in 864 patients to examine the effect of statins in addition to ACEinhibitors on microalbuminuria.37 There are no data on the effect of lipid-lowering therapy on hypertensive retinopathy. In contrast, left ventricular hypertrophy (LVH) is associated with hypertension and also insulin resistance syndromes including high triglycerides allied with low HDL.38–40 Few studies of lipidlowering therapy have been performed, although one study using echocardiographic methods did show a 10% decrease in LVH with pravastatin therapy in 25 patients.41 The effect of statins on LVH seems to be mediated by isoprenoid intermediates and interference with the action of angiotensin2. Expression and sensitivity of the angiotensin-2 type 1 receptor, whose activation is involved in the pathogenesis of LVH, is proportional to plasma LDL; so an effect of statins is not surprising.31,42 There are no data on other lipid-lowering drugs, although the relationship between low HDL and LVH suggests that fibrates might have greater effects on LVH.

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Pulse wave analysis and lipid-lowering therapy Nitric oxide also plays a critical role in the paracrine autoregulation of blood flow and hence in the determination of the peripheral resistance component of blood pressure. The primary role of pulse pressure as the principal determinant behind hypertension-associated cardiovascular risk in the older patients has recently been demonstrated using data from the Framingham cohort.43 Pulse pressure augmentation occurs as a result of speedier pulse wave reflection in stiffer arteries and gives rise to the characteristic isolated systolic hypertension of the elderly.44–46 Numerous studies have shown an association of pulse wave velocity as measured by Doppler ultrasound techniques with hypertension and cardiovascular risk.47–49 Similarly, there is an association of reduced arterial compliance with cardiovascular risk and hypertension. Recent studies using portable pulse wave analysis machines derive pulse wave velocity or analogous measures (eg stiffness index) mathematically from the pulse waveform and, similarly, the extent of augmentation (augmentation/reflection index) of peripheral blood pressure.46 Recent cohort studies show that pulse wave velocity is a 2.3-fold independent risk factor above the Framingham study-derived parameters for Journal of Human Hypertension

Lipid lowering and blood pressure AS Wierzbicki 756

cardiovascular events in a prospective hypertension cohort study.47 Pulse wave velocity is altered by any agent altering blood pressure and also by lipidlowering drugs, suggesting that if arterial stiffness is an index of hypertension and atherosclerosis then lipid-lowering drugs should have profound effects on hypertension. One study of 22 patients with isolated systolic hypertension treated with 80 mg atorvastatin has examined this.50 It showed a 6/2 mmHg fall in electronically measured blood pressure, and increased vascular compliance from 0.37 to 0.43 ml/ mmHg with a 48% reduction in LDL. Larger scale studies are required to confirm these findings.

Lipid-lowering drugs and blood pressure The topic of blood pressure effects of lipid-lowering drugs has been reviewed previously and information is limited (Table 2).7 Data from the older cardiovascular prevention trials using bile acid sequestrants (Lipids Research Clinics (LRC) study)3 and fibrates (WHO clofibrate trial)55 are negative, although the incidence of new hypertension was decreased by 25% over the course of the LRC study. Data are not available from any of the other studies using bile acid sequestrants or fibrates, for example, Helsinki Heart Study. However, some recent reports are intriguing. The Air Force Regression with Gemfibrozil Study (AFREGS), a coronary regression study with the gemfibrozil, presented at the American Heart Association in 1998 showed a 12/6 mmHg reduction in blood pressure with expected effects on progression of stenosis. The magnitude of the blood pressure effect matched that seen in a study of the effects of fibrate therapy on insulin resistance (14.7/9.8 mmHg).56 Reductions in blood pressure through actions on insulin resistance and through lesser effects on

hyperlipidaemia are seen with PPAR-gamma agonists (thiazolidinediones) or metformin; so an effect of fibrates on blood pressure might be predicted but there are no large-scale studies. With statins data are currently scarce (Table 2), but small-scale studies showed a reduction in the hypertensive response to mental stress in hyperlipidaemic patients and a nonsignificant decrease in blood pressure of 3 mmHg with lovastatin in 26 patients.59 Other studies with fluvastatin in 49 patients and 23 patients, respectively, showed significant reductions in blood pressure (6/3 mmHg) after 6 weeks.60,61 One of these studies showed a clear correlation of blood pressure response with elevation in nitric oxide production. Similarly, pravastatin blunted the pressor effects of angiotensin II and noradrenaline on diastolic blood pressure in a trial in seven patients.62,63 Other reports show no or nonsignificant responses to statin therapy.64 A randomised double-blind crossover trial of pravastatin 20–40 mg in 30 patients with moderate hyperlipidaemia and hypertension showed a reduction of 8/5 mmHg in blood pressure, blunting in the cold pressor test response and reduction in plasma endothelin-1 levels.64 However, to date, there are no large studies using automated measurement of blood pressure, which improves standardisation, and no large studies that have examined the effects of lipid lowering using 24 h ambulatory monitoring. Long-term data beyond 3 months are also lacking. Thus the data to date, although limited by small numbers, tend to suggest that statins may also lower blood pressure at least over a short time scale.

Trial evidence Early meta-analyses of the results of trials of antihypertensive therapy in coronary and cerebro-

Table 2 Intervention studies on hypercholesterolaemia that have shown effects on blood pressure, extended after Goode et al7 Study

Leiden51 POSCH52 LRC53 PVD54 WHO55 AF-REGS Idzior-Walus56 Morgan57 Atarashi EXCEL58 Sung59 Jarai60 Abetel61 Glorioso64 Ferrier50

Numbers

39 838 3806 24 5000 150 37 49 16 8245 26 49 23 30 22

BP treated

n y y y y y n y y y y n n n n

Method

Hg Hg Hg Hg Hg Hg Hg Hg Hg Hg Hg Hg ABPM ABPM E

Follow-up (months)

24 120 84 24 84 12 1.5 3 6 11 1.5 3 3 8 3

Intervention

Diet Ileal bypass Cholestyramine Resin+clofibrate Clofibrate Gemfibrozil Fenofibrate Simvastatin Pravastatin Lovastatin Lovastatin Fluvastatin Fluvastatin Pravastatin Atorvastatin

LDL

BP

Baseline (mmol/l)

D (mmol/l)

Baseline (mmHg)

D (mmHg)

4.70 4.29 5.20 5.41 4.50 3.65 4.48 4.60 3.60 4.65 4.68 5.13 5.63 4.31 3.40

0.7 1.5 0.7 1.5 0.6 0.2 0.53 2.0 1.1 1.03–2.06 1.2 1.18 1.0 1.09 1.53

130/84 124/81 124/84 151/89 120/80 136/85 145/90 128/87 134/88 128/88 120/80 145/95 147/100 149/97 154/82

4.2/2.4 4.0/2.0 0.0/2.0 6.0/2.0 0a 12.0/8.0 14.7/9.8 5.2/3.5 3.9/0.0 1.3/0.7 3.0/0.0 5.0/2.0 4.0/2.0 8.0/5.0 6.0/2.0

a 25% reduction in new hypertension. Abbreviations: Program on Surgical Correction of Hyperlipidaemia (POSCH); peripheral vascular disease (PVD); World Health Organization (WHO); Air Force Regression with Gemfibrozil Study (AF-REGS); expanded clinical evaluation of lovastatin (EXCEL); sphygmomanometric blood pressure (Hg); electronic blood pressure (E); ambulatory blood pressure monitoring (ABPM).

Journal of Human Hypertension


vascular disease suggest that a 30% reduction in stroke and a 10% reduction in coronary heart disease can be achieved with a 5 mmHg reduction in systolic blood pressure.65 Although many endpoint trials have been performed using antihypertensive drugs, the uptake of lipid-lowering therapy in these trials has been small (o10%) and subgroup analyses with lipid-lowering agents have not been published. More recent meta-analyses suggested that reducing blood pressure by 15/6 mmHg will reduce stroke by 50% in young patients and by 34% in the elderly.66 Large-scale endpoint studies in the field of hyperlipidaemia show clear evidence of mortality benefit with cholesterol reduction. The trials in question have mostly used statins: the Scandinavian Simvastatin Survival Study (4S),67 Cholesterol and Recurrent Events (CARE),68 Lipid Intervention with Pravastatin in Ischemic Disease (LIPID)69 in secondary prevention and the primary prevention West Of Scotland Coronary Prevention Study (WOSCOPS),70 and the Air Force Texas Coronary Artery Prevention Study (AF-Tex CAPS)71 have undergone subgroup analysis with respect to hypertension. Lipid lowering had the same relative risk reduction in the hypertensive as nonhypertensive patients in these studies. In terms of cardiovascular risk, evidence of benefit has been shown to extend between 1.2 and 5%/year risk of coronary events. There is no heterogeneity between statin studies, but as patients with hypertension have greater absolute risk of cardiovascular events then statins have a greater effect on cardiovascular events in patients with hypertension. Whether this effect is solely due to lipid lowering or to any additional effects on blood pressure is uncertain. In stroke there is only a weak relationship between LDLcholesterol and risk of events, but the principal risk factors are age and hypertension or pulse pressure. Statins reduce cardiovascular events and also stroke through plaque stabilisation. It is interesting to note that a fall in shear stress due to a fall in blood pressure will benefit endothelial function and some of the action of statins may occur through this mechanism. One fibrate trial has recently been published. The Veterans Administration HDL Intervention Trial (VA-HIT) studied 2200 secondary prevention patients with low HDL (0.88 mmol/l) and low LDL (3.0 mmol/l/l) (Table 1).72 The intervention was 1200 mg of gemfibrozil, which had previously shown benefit in arteriographic regression studies but failed to demonstrate a reduction in mortality as opposed to coronary events in the Helsinki Heart Study. A secondary prevention study in 6000 patients with bezafibrateFthe Bezafibrate Infarct Prevention Study (BIPS)Falso failed to demonstrate any event or mortality benefit except in the hypertriglyceridaemic low-HDL subgroup.73 In VAHIT a 22% reduction in a composite event endpoint was achieved without any effect on LDL, and the benefit was similar in diabetics and ‘normoglycae-

mic’ patients. Most of the benefit related to a 30% reduction in strokes and carotid endarterectomies with little difference in coronary intervention rates. Blood pressure data are not yet available from this study with regard to outcomes, but the predominant reductions in stroke are intriguing if fibrates have major antihypertensive effects.56 Subgroup analyses of statin trials also indicate a 20–30% reduction in stroke in the secondary prevention trials. However, detailed data on the exact groups of antihypertensive drugs were not available, although a high usage of thiazide diuretics was likely. Additionally, beta-blockers were used in 40–55% of secondary prevention patients for post-infarct benefits independent of blood pressure. Initial analyses of the data from these studies showed little difference in relative risk reduction between the ‘hypertensive’ and ‘normotensive’ groups. The pooled analysis of the Pravastatin Atherosclerosis Intervention Project (PAIP) trials of high-risk patients showed an additional 12% risk reduction (69 vs 57%) in patients with hypertension in an analysis of 1891 patients.74 However, the prespecified pooled analysis of the pravastatin trials including 19 768 patients showed that pravastatin therapy had a greater effect on absolute risk in patients without hypertension than in hypertensive individuals (33 vs 14%; p ¼ 0.003). This effect was dependent on study selection, but independent of baseline risk factors and medications, although data on doses and combinations of antihypertensives were not analysed. It was noted that pravastatin therapy seemed to have no effect on blood pressure in any of the studies.75 This finding cannot easily be explained, but the role of final LDL values achieved on therapy was not considered and might account for the difference. Data are not available from the 4S study, but that is likely to be confounded by higher usage of betablockers (55 vs 40%) and lower usage of aspirin (50 vs 80%) than the pravastatin trials.67 Trials with other agents have been too small to allow any effects on blood pressure to be determined. The question remains to be answered of whether the benefit in reduction of strokes and TIAs seen in statin trials with pravastatin and simvastatin and the trend towards a reduction in heart failure events (p ¼ 0.08) seen in the Cholesterol And Recurrent Events (CARE) study could be related to effects on blood pressure as part of any effect on plaque stabilisation.76 Certainly, the effects of statins on stroke are easily expressed by the magnitude of a blood pressure change if it followed that seen in the small-scale trials. Similarly, in hydrodynamic terms, a reduction in blood pressure would lead to a reduction in shear stress and hence improvement in endothelial function and increased plaque surface stability. Could some of the vaunted ‘non-lipid lowering’ actions of statins simply be due to effects on blood pressure? As yet there are no studies to answer these questions.

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Studies are required that compare the efficacy of different classes of antihypertensive combined with lipid lowering to confirm whether lipid lowering is beneficial when added to blood pressure reduction. A study of 35 patients combining lisinopril with lovastatin showed a greater effect in patients of ACEinhibitor in patients on statin (18 vs 12%; po0.05) than in a group not receiving treatment.77 Large studies are required to define any particularly favourable or deleterious combinations as lipidlowering and antihypertensive therapies are often prescribed simultaneously. Two such studies are under way. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) of 70 000 patients compares thiazides, beta-blockers, calcium channel blockers, alpha antagonists, and ACE-inhibitors in patients with primary hypertension (4160/95 mmHg).78,79 Additional randomisation is performed with 40 mg pravastatin or placebo. Similarly the Anglo-Scandinavian Cardiac Outcomes (ASCOT) study examines four drug classes with atorvastatin in 4000 patients at moderate risk of atheromatous events.80

Conclusions Total atherosclerotic risk factor management is increasingly necessary to treat fully the burden of atherosclerotic disease and a variety of its manifestations. The latest guidelines from international associations including the Joint European Societies, Joint British Societies, and New Zealand guidelines and National Cholesterol Education Program stress the role of total risk management in patients with atheroma. Thus, blood pressure and cholesterol are viewed as individually uninformative unless indicative of severe primary disease, for example malignant hypertension, hypertension with targetorgan damage, or familial hypercholesterolaemia or other familial hyperlipidaemias. Lipid-lowering drugs have traditionally been viewed as only addressing a subset of cardiovascular risk factors and to have little effect on hypertension. This article has reviewed the evidence that lipid-lowering drugs may, by their direct methods of action, be antihypertensive and may at least modulate blood pressure. Data are now needed from large scale studies to ascertain which are the optimal combinations of blood-pressure-lowering drugs and lipidlowering drugs to treat individual patient groups.

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