Author, year Study design Interventions Statin dose Duration Population Number of participants Method of arterial stiffness assessment Main finding Wallace et al., 2010 [35 ] Randomized, double-blind, placebo-controlled 1. Simvastatin 40 mg/d 14 days Healthy volunteers aged 20–40 years 50 Aortic and brachial PWV, AIx, and AP Compared with placebo, pretreatment with simvastatin significantly suppressed the enhancement of aortic PWV following typhoid vaccination. John et al., 2015 [36 ] Randomized, double-blind, placebo-controlled 1. Simvastatin 20 mg/d 6 weeks COPD patients 64 Aortic PWV Compared to placebo, arterial stiffness significantly reduced in patients with a high baseline aortic PWV. Kurpesa et al., 2004 [37 ] Randomized, placebo-controlled 1. Simvastatin 20 mg/d 6 months Individuals with primary arterial hypertension and high-normal serum cholesterol level 52 PWV PWV lowered in simvastatin group compared to baseline Ballard et al., 2015 [38 ] Randomized, double-blind, cross-over 1. Simvastatin 20 mg/d 8 weeks Patients with a history of statin myalgia 100 Central PWV, peripheral PWV, AIx, and AP Central PWV improved in simvastatin treatment group. Shige et al., 2001 [39 ] Randomized, double-blind cross-over 1. Simvastatin 20 or 40 mg/d 4 weeks Hypercholesterolaemic patients 20 Central and peripheral PWV, arterial compliance Peripheral PWV significantly improved following simvastatin treatment. Mäki-Petäjä et al., 2007 [40 ] Randomized double-blind cross-over 1. Simvastatin 20 mg/d 6 weeks Patients with active rheumatoid arthritis 20 Aortic PWV, AIx, and AP There was substantial reduction in PWV following both treatments compared to baseline. Efrati et al., 2007 [41 ] Nonrandomized 1. Simvastatin 40 mg/d 3 months Hypercholesterolemic patients 40 AIx A marked reduction was observed in the simvastatin 40 mg group. Gepner et al., 2019 [42 ] Randomized, double-blind, placebo-controlled 1. Simvastatin 40 mg/d 12 months Middle-aged adults at increased risk for dementia 88 AIx A transient improvement was observed at 12 months. Balaguer et al., 2016 [43 ] Randomized, double-blind, placebo-controlled 1. Simvastatin 40 mg/d 12 weeks Stable COPD 18 PWV, AIx No significant changes were observed. Cash et al., 2013 [44 ] Randomized, single-blind, placebo-controlled 1. Simvastatin 20 mg/d 12 months Primary biliary cirrhosis patients with hypercholesterolaemia 13 Aortic PWV, AIx75, and Tr No significant changes were observed. Wang et al., 2012 [45 ] Single-arm Atorvastatin 20 mg/d 6 months Hypertensive patients 73 baPWV baPWV was reduced significantly compared with baseline. Shinohara et al., 2005 [46 ] Single-arm Atorvastatin 10 mg/d 6 months Type-2 diabetic patients with hypercholesterolemia 22 Femoral-ankle PWV, heart-carotid PWV, heart-brachial PWV, and heart-femoral PWV A reduction in femoral-ankle PWV was perceived. Castejon et al., 2017 [47 ] Single-arm Atorvastatin 20 mg/d 8 weeks Systemic lupus erythematosus females 37 Aortic PWV PWV significantly improved in patients with baseline pathological arterial stiffness. Van Doornum et al., 2004 [48 ] Single-arm Atorvastatin 20 mg/d 6 weeks Patients with rheumatoid arthritis 29 AIx AIx was decreased by the treatment. Ratchford et al., 2011 [49 ] Single-arm Atorvastatin 80 mg/d 14 days Stroke-free and statin-naive subjects over age 45 40 SI SI significantly reduced at day 30. Kontopoulos et al., 2002 [50 ] Single-arm Atorvastatin 20 mg/d 2 years Hypercholesterolemic patients 36 SI Aortic SI was significantly reduced by 14%. Leibovitz et al., 2001 [51 ] Single-arm Atorvastatin Starting dose: 10 mg/d 20 weeks Patients with severe hypercholesterolemia 17 Arterial compliance Small artery compliance was significantly increased with treatment. Leibovitz et al., 2003 [52 ] Single-arm Atorvastatin 10-20 mg/d 3 months Hypertensive hyperlipidemic patients 21 Arterial compliance (small and large arteries) Small artery compliance significantly elevated by atorvastatin treatment. Akgullu et al., 2008 [53 ] Single-arm Atorvastatin 40 mg/d 6 months Patients with coronary artery disease 33 Small and large arteries compliance Arterial compliance significantly improved after treatment. Yamaguchi et al., 2010 Single-arm Atorvastatin 20 mg/d 6 months Type-2 diabetic patients with high non-HDL-C levels receiving atorvastatin (10 mg/day) 39 CAVI CAVI declined substantially by 4.6%. Tulmaç et al., 2012 [54 ] Single-arm Atorvastatin 80 mg Acute Dyslipidemic patients without atherosclerosis 30 RI, SI Arterial stiffness did not improve with the treatment. Ozaki et al., 2006 [55 ] Single-arm Atorvastatin 10 mg/d 6 months Hypercholesterolemic patients 30 baPWV PWV was unaffected by the treatment. Grigoropoulou et al., 2019 [56 ] Nonrandomized 1. Atorvastatin (+Mediterranean diet) 10 mg/d 3 months Subjects with type-2 diabetes and dyslipidemia 79 Aortic PWV, carotid-radial PWV Aortic PWV significantly improved in simvastatin group compared to diet alone. Meng et al., 2009 [57 ] Nonrandomized 1. Atorvastatin (+low-fat diet) 10 mg/d 3 months CAD patients with hyperlipidemia 63 Aortic PWV, carotid-radial PWV, and carotid-distal PWV Compared with the control group and baseline, PWV substantially decreased after 6 months. Huang et al., 2014 [58 ] Randomized 1. Atorvastatin (in combination with levamlodipine besylate) 20 mg/d 8 weeks Hypertensive patients with dyslipidemia and body’s inflammatory response 120 PWV Atorvastatin significantly improved PWV compared to the levamlodipine besylate-treated group. Orr et al., 2009 [59 ] Randomized, double-blind, placebo-controlled 1. Atorvastatin 80 mg/d 12 weeks Overweight and obese middle-aged and older adults 26 Aortic and carotid-radial PWV, SI, and arterial compliance Aortic PWV, SI, and arterial compliance improved compared to placebo. Kanaki et al., 2013 [60 ] Randomized, double-blind, placebo-controlled 1. Atorvastatin 10 mg/d 6 months Hypertensive and hypercholesterolemic patients 50 Aortic PWV, normalized PWV, AIx75, and AP Arterial stiffness parameters significantly improved compare with placebo. Manisty et al., 2009 [61 ] Randomized, single-blind 1. Atorvastatin 10 mg/d 12–18 months Hypertensive patients 142 Carotid AIx, AP, and RI Carotid AIx, AP, and RI from the body significantly improved compared to placebo. Davenport et al., 2015 [62 ] Randomized, open-label Atorvastatin 10 mg/d 3 months Male patients with type-2 diabetes 51 Aortic PWV PWV decreased at 3 months and 12 months. Lee and Kim, 2008 [63 ] Randomized Atorvastatin 10 mg/d One week Patients with moderate cholesterolemia 51 Carotid-radial PWV PWV improved after 8 weeks of 40 mg atorvastatin treatment, and a significant difference was observed between the groups. Tousoulis et al., 2013 [64 ] Randomized, double-blind, cross-over Atorvastatin 10 mg/d 4 weeks Ischemic heart failure patients 22 AIx75 Compared with the low-dose group, 40 mg/d atorvastatin treatment significantly improved AIx75. Karter et al., 2003 [65 ] Randomized, double-blind Atorvastatin 20 mg/d 3 months Hypercholesterolemic patients 20 Distensibility coefficient There was noticeable increased in distensibility coefficient of both groups. Mukherjee et al., 2008 [66 ] Randomized, placebo-controlled 1. Atorvastatin 10 mg/d 6 months Normotensive normolipidemic persons with type-2 diabetes 57 baPWV baPWV improved significantly in the atorvastatin group compared with baseline. Kabaklić and Fras, 2017 [67 ] Randomized, double-blind, placebo-controlled 1. Atorvastatin 20 mg/d 3 months Patients with angina pectoris and normal coronary angiogram 58 AIx, AIx75 No marked change was perceived. Fassett et al., 2010 [68 ] Randomized, double-blind, placebo-controlled 1. Atorvastatin 10 mg/d 3 years Patients with CKD 37 Aortic PWV, AIx, arterial pressure No significant changes were observed. Joyeux-Faure et al., 2014 [69 ] Randomized, double-blind, placebo-controlled 1. Atorvastatin 40 mg/d 12 weeks Obstructive sleep apnea syndrome patients 51 Aortic PWV PWV did not alter compared to the placebo group. Hong et al., 2013 [70 ] Randomized, double-blind, cross-over, placebo-controlled 1. Atorvastatin 40 mg/d 6 weeks First-degree relatives of patients with premature coronary artery disease patients with endothelial dysfunction 35 AIx No marked difference was observed. Raison et al., 2001 [71 ] Randomized, double-blind, placebo-controlled 1. Atorvastatin 10 mg/d 12 weeks Patients with hypertension and hypercholesterolemia 23 Aortic PWV, carotid AIx No significant difference was perceived between the groups. Cohn et al., 2009 [72 ] Randomized, double-blind, placebo-controlled 1. Atorvastatin 10 mg/d 8 weeks Patients with concomitant hypertension and dyslipidemia 325 Small artery compliance, large artery compliance No significant changes were observed. Mikhin et al., 2016 [73 ] Single-arm Rosuvastatin 10-40 mg/d 1.5 years Arterial hypertensive patients with high and very high cardiovascular risk 114 CAVI, AIx CAVI and AIx were improved by rosuvastatin treatment, 12% and 17%, respectively. Canepa et al., 2018 [74 ] Single-arm Rosuvastatin 5-10 mg/d 3 months Newly diagnosed heterozygous familial hypercholesterolemia 20 Aortic PWV, AIx, AIx75, and arterial BP PWV significantly decreased. Ikdahl et al., 2015 [75 ] Single-arm Rosuvastatin 20-40 mg/d 18 months Patients with inflammatory joint diseases 85 Aortic PWV, AIx None of the arterial stiffness indices substantially altered. Ikdahl et al., 2016 [76 ] Single-arm Rosuvastatin 20-40 mg/d 18 months Patients with inflammatory joint diseases 89 Aortic PWV, AIx AIx and aPWV were noticeably decreased. Timár et al., 2013 [77 ] Single-arm Rosuvastatin 20 mg/d 6 months Patients with systemic sclerosis 28 Aortofemoral PWV, carotid-femoral PWV Arterial stiffness was not affected by the treatment. Deguchi et al., 2014 [78 ] Single-arm Rosuvastatin 5 mg/d 12 months Dyslipidemic patients with cerebral infarction 17 CAVI CAVI showed no substantial change after rosuvastatin therapy. Pirro et al., 2007 [79 ] Randomized open-label 1. Rosuvastatin (with low-fat diet) 10 mg/d 4 weeks Patients with primary hypercholesterolemia 71 Aortic PWV PWV decreased significantly with rosuvastatin compared to baseline. Igase et al., 2012 [80 ] Randomized, open-label 1. Rosuvastatin (+diet and exercise therapy) 2.5 mg/d 3 months Postmenopausal women with dyslipidemia 51 baPWV, SI Arterial stiffness markedly reduced compared to placebo after 3 and 12 months. Ott et al., 2012 [81 ] Randomized, double-blind, placebo-controlled, cross-over 1. Rosuvastatin 10 mg/d 42 days Hypercholesterolemic patients 29 AIx, AIx75 AIx75 was substantially lower compared to the placebo. Mitsiou et al., 2018 [82 ] Randomized Rosuvastatin 1. Low dose (5 mg/d) 6 months Patients with optimally controlled arterial hypertension 40 Aortic PWV, AIx75 Arterial stiffness significantly improved with both treatments, but the high dose was more effective on PWV improvement. Wang et al., 2014 [83 ] Clinical trial 1. Rosuvastatin 10 mg/d 12 weeks Hyperlipidemic patient without hypertension 120 Radial artery AIx, baPWV Rosuvastatin significantly decreased the levels of baPWV and radial AIx compared to baseline. Tam et al., 2011 [84 ] Randomized, double-blind placebo-controlled 1. Rosuvastatin 10 mg/d (starting with 5 mg/d) 12 months Patients with rheumatoid arthritis 42 AIx No noticeable change was observed. Kim et al., 2018 [85 ] Single-arm Pitavastatin 4 mg/d 3 months Hypercholesterolemic patients 48 Stiffness index-β 2, SI Stiffness index-β 2 improved substantially. Miyashita et al., 2009 [86 ] Single-arm Pitavastatin 2 mg/d 12 months Type-2 diabetics patients with hyperlipidemia 45 CAVI CAVI was reduced significantly. Muramatsu et al., 1997 [87 ] Single-arm Pravastatin 10 mg/d 6 months Hypercholesterolemic patients 59 PWV PWV showed significant improvement in patients with a higher reduction in TC (≥15%) compared with the group with <15% reduction in TC. Matsuo et al., 2005 [88 ] Quasiexperimental 1. Pravastatin 10 mg/d 6 months Hyperlipidemic patients 35 baPWV baPWV significantly reduced by the treatment. Duan et al., 2014 [89 ] Quasiexperimental 1. Pravastatin 5 or 10 mg/d 6 months Children with medium to giant coronary aneurysms due to Kawasaki disease 27 SI No significant change was observed. Forbat et al., 1998 [90 ] Single-arm Fluvastatin 40 or 80 mg/d 1 year Hypercholesterolemic patients 60 Aortic compliance There was a marked rise in aortic compliance. Ersoy et al., 2014 [91 ] Single-arm Fluvastatin 80 mg/d 6 months Dyslipidemic renal transplant recipients 14 Large and small vessel compliances Arterial compliance parameters did not change. Ichihara et al., 2002 [92 ] Randomized, double-blind placebo-controlled 1. Fluvastatin 20 mg/d 3 months Diabetic ESRD patients with normal serum lipid levels 22 PWV Fluvastatin significantly improved PWV compared with placebo after 6 months. Lunder et al., 2011 [93 ] Randomized, double-blind placebo-controlled 1. Fluvastatin 10 mg/d 14 days Apparently healthy, middle-aged males 50 PWV, SI PWV and SI significantly improved by the intervention. Yokoyama et al., 2005 [94 ] Randomized, open-label 1. Fluvastatin 40 mg/d 12 months Hyperlipidemic patients 40 SI, baPWV PWV significantly increased in the control group, while decreased in fluvastatin group. Hongo et al., 2008 [95 ] Randomized, single-blind 1. Fluvastatin 20–40 mg/d 3, 6, and 12 months and 2, 3, 4, and 5 years Patients with CAD and hyperlipidemia 93 baPWV After 12 months, baPWV decreased substantially in fluvastatin-treated group compared to bezafibrate-treated group and remained significant until the end of the study. Drapkina et al., 2012 [96 ] Randomized 1. Atorvastatin — 5 weeks Patients with arterial hypertension and dyslipidemia 82 AIx, AIx75, RI, and SI A marked reduction was observed in SI. Simsek et al., 2014 Clinical trial 1. Atorvastatin 20 mg/d 12 months Hyperlipidemic patients 108 PWA parameters Rosuvastatin showed a greater ameliorative effect on vascular stiffness than the atorvastatin. Liu et al., 2013 [97 ] Randomized controlled 1. Rosuvastatin 10 mg/d 8 weeks Patients with coronary artery disease 36 baPWV baPWV was significantly decreased in the rosuvastatin group compared to the simvastatin/ezetimibe group. Ilyukhin et al., 2005 [98 ] Clinical trial 1. Atorvastatin 10 mg/g 6 months Patients with ischemic heart disease 38 PWV Atorvastatin and simvastatin treatment was associated with -10.05% and -4.66% reduction in PWV. Hongo et al., 2011 [99 ] Randomized, open-labeled 1. Rosuvastatin 2.5–5 mg/d 3 months High-risk CVD patients with dyslipidemia 75 baPWV Both treatments significantly improved arterial elasticity after 12 months, and rosuvastatin was more effective. Ichihara et al., 2005 [100 ] Randomized, single-blind 1. Simvastatin 5 mg/d 3 months Hyperlipidemic hypertensive patients 85 baPWV After 12 months, fluvastatin treatment was associated with a significant reduction in baPWV.
