Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension

Ferrier, K. E.; Muhlmann, M.; Baguet, Jean Philippe; Cameron, James D.; Jennings, Garry; Dart, Anthony M.; Kingwell, Bronwyn A.

doi:10.1016/s0735-1097(02)01717-5

Cited by 284 publications

(220 citation statements)

References 47 publications

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“…However, the 4.3 mmHg systolic and 1.6 mmHg reduction in diastolic blood pressure was unexpected. There is limited short-term trial evidence that atorvastatin treatment may reduce blood pressure in hypertensive and dyslipidaemic patients [30][31][32][33], possibly by improving endothelium-dependent vascular function [34]. A single uncontrolled trial [35] in patients with type 2 diabetes showed a 10 mmHg reduction in diastolic blood pressure, but this may partly be explained by habituation and regression to the mean.…”

Section: Discussionmentioning

confidence: 99%

“…No consistent relationship between atorvastatin treatment and changes in glycated haemoglobin or other glycaemic measure has been reported in short-term trials that have examined the efficacy and safety of statin therapy in diabetic patients [30,[36][37][38][39]. These small studies, however, did not have the statistical power to identify HbA 1c changes as small as the 0.3% increase observed in AFORRD.…”

Section: Discussionmentioning

confidence: 99%

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Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

et al. 2008

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Aims/hypothesis The aim of the study was to examine the impact of statin or omega-3-acid ethyl esters 90 (omega-3 EE90; omega-3-acid ethyl esters 90 refers to a mixture of ethyl esters of n-3 fatty acids) on estimated cardiovascular disease (CVD) risk in community-based people with type 2 diabetes but without known CVD and not taking lipid-lowering therapy. Methods A central computer randomised 800 patients in 59 UK general practices to atorvastatin (n=401, 20 mg/day) or placebo (n=399) and omega-3 EE90 (n=397, 2 g/day) or placebo (n=403) in a concealed factorial manner. Participants with LDL-cholesterol <2.6 mmol/l, triacylglycerol <1.5 mmol/l and estimated 10-year CVD risk <20% were compared at 4 months.Results Mean (SD) age was 63.5 (11.7) years, HbA 1c 6.9 (1.1) % and known diabetes duration (median [interquartile range]) was 4 (2-8) years. Fifty-seven per cent were men, 90% white and 74% had an estimated 10-year CVD risk ≥20%. Of 732 patients with 4-month data, more allocated atorvastatin (n=371) compared with placebo (n=361) achieved LDLcholesterol <2.6 mmol/l (91% vs 24%, p<0.001) and had estimated 10-year CVD risks <20% (38% vs 26%, p<0.001). No differences were seen between those allocated omega-3 EE90 (n=371) compared with placebo (n=361) for participants achieving triacylglycerol <1.5 mmol/l (65% vs 60%, p=0.18) or estimated 10-year CVD risks <20% (34% vs 30%, p=0.18). There were no side effects of note. Conclusions/interpretation Many community-based diabetic patients without known CVD remain at high CVD risk despite statin treatment and require additional risk-reduction strategies. The impact of omega-3 EE90 on CVD risk will remain uncertain until clinical endpoint trial results are available.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

et al. 2008

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“…Studies have shown that statins augment Akt activity in vessels, 40 improve blood flow by increasing NO synthase activation, 41 and may reduce vascular stiffening. 42 Statins also inhibit small GTPbinding proteins Rac1 and RhoA and thereby may impede development of cardiac hypertrophy. [43][44][45] Other strategies may involve enhancing NO synthase signaling by increasing substrate availability (arginase inhibition) or its cofactor tetrahydrobiopeterin (BH4).…”

Section: Destiffening Strategiesmentioning

confidence: 99%

Ventricular Arterial Stiffening

2005

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Abstract-Vascular stiffening of the large arteries is a common feature of aging and is exacerbated by many common disorders such as hypertension, diabetes, and renal disease. This change influences the phasic mechanical stresses imposed on the blood vessels that in turn is important to regulating smooth muscle tone, endothelial function, and vascular health. In addition, the heart typically adapts to confront higher and later systolic loads by both hypertrophy and ventricular systolic stiffening. This creates altered coupling between heart and vessel that importantly affects cardiovascular reserve function. In this overview, I discuss the notion of a coupling disease in which stiffness of both heart and arteries interact to limit performance and generate clinical symptoms. This involves changes in the mechanical interaction of both systems, changes in signaling within the arteries themselves, and alterations in coronary flow regulation. Lastly, I briefly review recent development in de-stiffening strategies that may pave the way to treat this syndrome and its clinical manifestations.

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“…Cholesterol lowering has been shown to improve arterial compliance in patients with familial hypercholesterolemia (Tomochika et al, 1996;Smilde et al, 2000) and hypertension (Ferrier et al, 2002). Stanol ester margarine lowers serum total and LDL cholesterol concentrations (Law 2000).…”

Section: Discussionmentioning

confidence: 99%

Carotid artery compliance in users of plant stanol ester margarine

2007

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Objective: To investigate the effects of stanol ester margarine use in healthy subjects on arterial compliance, endothelial function and intima-media thickness. Design: Case-control study comparing regular stanol ester margarine users to non-users. Setting: Occupational health service clinic. Subjects: We recruited 50 cases and 50 controls (mean age 5178, range 26-65 years). All subjects were non-smokers and the study groups were matched for age and sex. As cases, we invited subjects who had been using regularly (daily) plant stanol ester margarine for a period of 2 years or longer. Non-invasive ultrasound was used to measure carotid artery compliance, carotid intima-media thickness and brachial artery flow-mediated endothelial dependent vasodilatation. Results: The carotid artery compliance was non-significantly higher in cases compared with controls, 1.8471.02 vs 1.5870.76 %/10 mm Hg (P ¼ 0.13). The difference in compliance became statistically significant (P ¼ 0.04) when the unbalance between the groups in family history of coronary artery disease and years of education were taken into account. There was also a significant dose-response relationship between stanol margarine use and carotid compliance, longer use being associated with higher compliance. Serum lipoproteins, blood pressure, flow-mediated dilation and intima-media thickness values did not differ between cases and controls. Conclusion: These data raise the possibility that regular stanol ester margarine use may be associated with beneficial changes in arterial compliance. Intervention studies are needed to test this hypothesis and to reveal possible mechanisms.

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Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension

Abstract: Intensive cholesterol reduction may be beneficial in the treatment of patients with ISH and normal lipid levels, through a reduction in large artery stiffness.

Cited by 284 publications

References 47 publications

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

Atorvastatin in Factorial with Omega-3 EE90 Risk Reduction in Diabetes (AFORRD): a randomised controlled trial

Ventricular Arterial Stiffening

Carotid artery compliance in users of plant stanol ester margarine

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