The effects of plant stanol ester consumption on arterial stiffness and endothelial function in adults: a randomised controlled clinical trial

BMC Cardiovascular Disorders

Maarit Hallikainen⁵  Airi Talvi³  Aslak Savolainen⁶  Markku J Nissinen¹  Piia Simonen⁴  Jussi Konttinen⁷  Harri Lindholm⁷  Janne Halonen⁷  Helena Gylling² 

[1] Department of Medicine, Division of Gastroenterology, University of Helsinki, Helsinki, Finland;Biomedicum Helsinki C 4 22, P.O. BOX 700, FIN-00029, HUS, Helsinki, Finland;SOK Corporation, Helsinki, Finland;Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland;Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland;Finnish Broadcasting Company and Department of Public Health, University of Helsinki, Helsinki, Finland;Finnish Institute of Occupational Health, Helsinki, Finland

关键词: Coronary artery disease;    LDL cholesterol;    Plant stanol ester;    Augmentation index;    Reactive hyperemia index;    Cardio-ankle vascular index;    Endothelial function;    Arterial stiffness;   

Others  :  857593
DOI  :  10.1186/1471-2261-13-50

 received in 2013-02-01, accepted in 2013-07-02,  发布年份 2013

【 摘 要 】

Background

The hypocholesterolemic effect of plant stanol ester consumption has been studied extensively, but its effect on cardiovascular health has been less frequently investigated. We studied the effects of plant stanol esters (staest) on arterial stiffness and endothelial function in adults without lipid medication.

Methods

Ninety-two asymptomatic subjects, 35 men and 57 women, mean age of 50.8±1.0 years (SEM) were recruited from different commercial companies. It was randomized, controlled, double-blind, parallel trial and lasted 6 months. The staest group (n=46) consumed rapeseed oil-based spread enriched with staest (3.0 g of plant stanols/d), and controls (n=46) the same spread without staest. Arterial stiffness was assessed via the cardio-ankle vascular index (CAVI) in large and as an augmentation index (AI) in peripheral arteries, and endothelial function as reactive hyperemia index (RHI). Lipids and vascular endpoints were tested using analysis of variance for repeated measurements.

Results

At baseline, 28% of subjects had a normal LDL cholesterol level (≤3.0 mmol/l) and normal arterial stiffness (<8). After the intervention, in the staest group, serum total, LDL, and non-HDL cholesterol concentrations declined by 6.6, 10.2, and 10.6% compared with controls (p<0.001 for all). CAVI was unchanged in the whole study group, but in control men, CAVI tended to increase by 3.1% (p=0.06) but was unchanged in the staest men, thus the difference in the changes between groups was statistically significant (p=0.023). AI was unchanged in staest (1.96±2.47, NS) but increased by 3.30±1.83 in controls (p=0.034) i.e. the groups differed from each other (p=0.046). The reduction in LDL and non-HDL cholesterol levels achieved by staest was related to the improvement in RHI (r=−0.452, p=0.006 and −0.436, p=0.008).

Conclusions

Lowering LDL and non-HDL cholesterol by 10% with staest for 6 months reduced arterial stiffness in small arteries. In subgroup analyses, staest also had a beneficial effect on arterial stiffness in large arteries in men and on endothelial function. Further research will be needed to confirm these results in different populations.

Trial registration

Clinical Trials Register # NCT01315964

【 授权许可】

   
2013 Gylling et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Demonty I, Ras RT, van der Knaap HCM, Duchateau GSMJE, Meijer L, Zock PL, Geleijnse JM, Trautwein EA: Continuous dose–response relationship of the LDL-cholesterol–lowering effect of phytosterol intake. J Nutr 2009, 139:271-284.
• [2]Musa-Veloso K, Poon TH, Elliot JA, Chung C: A comparison of the LDL-cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range: results of a meta-analysis of randomized, placebo-controlled trials. Prostaglandins Leukot Essent Fatty Acids 2011, 85:9-28.
• [3]LaRosa JC: Low-density lipoprotein cholesterol reduction: The end is more important than the means. Am J Cardiol 2007, 100:240-242.
• [4]Raitakari OT, Salo P, Ahotupa M: Carotid artery compliance in users of plant stanol ester margarine. Eur J Clin Nutr 2008, 62:218-224.
• [5]Raitakari OT, Salo P, Gylling H, Miettinen TA: Plant stanol ester consumption and arterial elasticity and endothelial function. Br J Nutr 2008, 100:603-608.
• [6]Jakulj L, Vissers MN, Rodenburg J, Wiegman A, Trip MD, Kastelein JJ: Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels. J Pediatr 2006, 148:495-500.
• [7]Hallikainen M, Lyyra-Laitinen T, Laitinen T, Ågren JJ, Pihlajamäki J, Rauramaa R, Miettinen TA, Gylling H: Endothelial function in hypercholesterolemic subjects: effects of plant stanol and sterol esters. Atherosclerosis 2006, 188:425-432.
• [8]Gylling H, Hallikainen M, Raitakari OT, Laakso M, Vartiainen E, Salo P, Korpelainen V, Sundvall J, Miettinen TA: Long-term consumption of plant stanol and sterol esters, vascular function and genetic regulation. Br J Nutr 2009, 101:1688-1695.
• [9]Hallikainen M, Lyyra-Laitinen T, Laitinen T, Moilanen L, Miettinen TA, Gylling H: Effects of plant stanol esters on serum cholesterol concentrations, relative markers of cholesterol metabolism and endothelial function in type 1 diabetes. Atherosclerosis 2008, 199:432-439.
• [10]Vlachopoulos C, Aznaouridis K, Stefanadis C: Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 2010, 55:1318-1327.
• [11]Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, Pumper GM, Lerman LO, Lerman A: Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J 2010, 31:1142-1148.
• [12]Lindholm H, Punakallio A, Lusa S, Sainio M, Ponocny E, Winker R: Association of cardio-ankle vascular index with physical fitness and cognitive symptoms in aging Finnish firefighters. Int Arch Occup Environ Health 2011, 85:397-403.
• [13]Shirai K, Hiruta N, Song M, Kurosu T, Suzuki J, Tomaru T, Miyashita Y, Saiki A, Takahashi M, Suzuki K, Takata M: Cardio-ankle vascular index (CAVI) as a novel indicator of arterial stiffness: theory, evidence and perspectives. J Atheroscler Thromb 2011, 18:924-938.
• [14]Horinaka S, Yabe A, Yagi H, Ishimura K, Hara H, Iemura T, Ishimitsu T: Cardio-ankle vascular index could reflect plaque burden in the coronary artery. Angiology 2011, 62:401-408.
• [15]Huck CJ, Bronas UG, Williamson EB, Draheim CC, Duprez DA, Dengel DR: Noninvasive measurements of arterial stiffness: repeatability and interrelationships with endothelial function and arterial morphology measures. Vasc Health Risk Manag 2007, 3:343-349.
• [16]Miettinen TA: Cholesterol metabolism during ketoconazole treatment in man. J Lipid Res 1988, 29:43-51.
• [17]Kim B, Takada K, Oka S, Misaki T: Influence of blood pressure on cardio-ankle vascular index (CAVI) examined based on percentage change during general anesthesia. Hypertens Res 2011, 34:779-783.
• [18]Shirai K, Utino J, Otsuka K, Takata M: A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb 2006, 13:101-110.
• [19]Kubozono T, Miyata M, Ueyama K, Nagaki A, Otsuji Y, Kusano K, Kubozono O, Tei C: Clinical significance and reproducibility of new arterial distensibility index. Circ J 2007, 71:89-94.
• [20]Takaki A, Ogawa H, Wakeyama T, Iwami T, Kimura M, Hadano Y, Matsuda S, Miyazaki Y, Hiratsuka A, Matsuzak M: Cardio-ankle vascular index is superior to brachial-ankle pulse wave velocity as an index of arterial stiffness. Hypertens Res 2008, 31:1347-1355.
• [21]Suzuki H, Ishizuka N, Makoto M, Masuya N, Nobouyuki A, Arai C: Establishment of reference values of CAVI and disease characteristics. In From bench to bedside: CAVI as a novel indicator of vascular function. Edited by Orimo H, Saito Y. Tokio: Nikkei Medical Custom Publishing, Inc; 2009:30-41.
• [22]Usui T, Tochiya M, Sasaki Y, Muranaka K, Yamakage H, Himeno A, Shimatsu A, Inaguma A, Ueno T, Uchiyama S, Satoh-Asahara N: Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin Endocrinol (Oxf) 2013, 78:365-372.
• [23]Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP, Karas RH, Udelson JE: Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J 2003, 146:168-174.
• [24]Bonetti PO, Barsness GW, Keelan PC, Schnell TI, Pumper GM, Kuvin JT, Schnall RP, Holmes DR, Higano ST, Lerman A: Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. J Am Coll Cardiol 2003, 41:1761-1768.
• [25]Peled N, Shitrit D, Fox B, Shlomi D, Amital A, Bendayan M, Kramer M: Peripheral arterial stiffness and endothelial dysfunction in idiopathic and scleroderma associated pulmonary arterial hypertension. J Rheumatol 2009, 36:970-975.
• [26]Vartiainen E, Laatikainen T, Peltonen M, Juolevi A, Männistö S, Sundvall J, Jousilahti P, Salomaa V, Valsta L, Puska P: Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol 2010, 39:504-518.
• [27]Hallikainen M, Kurl S, Laakso M, Miettinen TA, Gylling H: Plant stanol esters lower LDL cholesterol level in statin-treated subjects with type 1 diabetes by interfering the absorption and synthesis of cholesterol. Atherosclerosis 2011, 217:473-478.
• [28]Satoh N, Shimatsu A, Kotani K, Himeno A, Majima T, Yamada K, Suganami T, Ogawa Y: Highly purified eicosapentaenoic acid reduces cardio-ankle vascular index in association with decreased serum amyloid A-LDL in metabolic syndrome. Hypert Res 2009, 32:1004-1008.
• [29]Miyashita Y, Endo K, Saiki A, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohira M, Oyama T, Shirai K: Effects of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, on cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb 2009, 16:539-545.
• [30]Miyashita Y, Endo K, Saiki A, Ban N, Nagumo A, Yamaguchi T, Kawana H, Nagayama D, Ohira M, Oyama T, Shirai K: Effect of ezetimive monotherapy on lipid metabolism and arterial stiffness assessed by cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb 2010, 17:1070-1076.
• [31]Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FU, Protogerou AD, Schillaci G, Segers P, Vermeersch S, Weber T: Artery Society, European Society of Hypertension Working Group on Vascular Structure and Function: European Network for noninvasive investigation of large arteries. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens 2012, 30:445-448.
• [32]Shearer GC, Pottala JV, Hansen SN, Brandenburg V, Harris WS: Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial. J Lipid Res 2012, 53:2429-2435.
• [33]Efrati S, Averbukh M, Dishy V, Faygenzo M, Friedensohn L, Golik A: The effect of simvastatin, ezetimibe and their combination on the lipid profile, arterial stiffness and inflammatory markers. Eur J Clin Pharmacol 2007, 63:113-121.
• [34]Kanaki AI, Sarafidis PA, Georgianos PI, Kanavos K, Tziolas IM, Zebekakis PE, Lasaridis AN: Effects of low-dose atorvastatin on arterial stiffness and central aortic pressure augmentation in patients with hypertension and hypercholesterolemia. Am J Hypert 2013, 26:608-616.
• [35]Tousoulis D, Oikonomou E, Siasos G, Chrysohoou C, Zaromitidou M, Kioufis S, Maniatis K, Dilaveris P, Miliou A, Michalea S, Papavassiliou AG, Stefanadis C: Dose-dependent effects of short term atorvastatin treatment on arterial wall properties and on indices of left ventricular remodeling in ischemic heart failure. Atherosclerosis 2013, 227:367-372.
• [36]Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Tielsch JM, Klein BE, Hubbard LD: Retinal arteriolar narrowing and risk of coronary heart disease in men and women: the Atherosclerosis Risk in Communities Study. JAMA 2002, 287:1153-1159.