Int J Angiol 2017; 26(02): 095-101
DOI: 10.1055/s-0036-1594292
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Variations in Echogenicity in Carotid and Femoral Atherosclerotic Plaques with Pycnogenol + Centella Asiatica Supplementation

Gianni Belcaro
1   Irvine Labs, Chieti-Pescara University, Spoltore, Pescara, Italy
,
Umberto Cornelli
1   Irvine Labs, Chieti-Pescara University, Spoltore, Pescara, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
26 December 2016 (online)

Abstract

This registry study evaluated echogenicity of carotid–femoral plaques in asymptomatic subjects with increased oxidative stress and risk factors (mild hypertension, hypercholesterolemia). Supplementation with the combination Pycnogenol–CA (centella asiatica) on the echogenicity of plaques was assessed at 6 months (79 subjects). A standard management (SM) plan was used in all subjects (control of risk factors, lifestyle changes); 36 subjects used the supplements +SM; 43 SM only. The groups were comparable. High-resolution ultrasound evaluated echogenicity and plaque structure. Pycnogenol (150 mg/day) and CA (Centellicum, 450 mg/day) were used.

At 6 months, cholesterol was reduced (p < 0.05) in both groups (difference between groups not significant). At 6 months, plasma free radicals were decreased with the supplements (17.64%; p < 0.05; vs <2% in controls). The plaque stability index increased from 11.22;2.3 to 22.4;1.1 (p < 0.05) with the supplements; no significant changes were seen in controls. Plaque echogenicity (% of “whiter” component in images) increased with supplementation from 16.7;1.7% to 34.2;2% (p < 0.05); no variations were observed in controls. The maximum plaque height decreased (p < 0.05) with the supplements. No significant variations were observed in controls. Plaque length was decreased (p < 0.05) in the supplement group with no changes in controls. The number of plaques (carotid, femoral bifurcations) decreased with supplementation; no significant changes were observed in controls. No adverse events, tolerability problems, or variations in routine blood tests were recorded. The combination Pycnogenol–CA appears to improve echogenicity and stability of complex plaques in 6 months.

 
  • References

  • 1 Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344 (8934) 1383-1389
  • 2 Shepherd J, Cobbe SM, Ford I , et al; West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333 (20) 1301-1307
  • 3 Sacks FM, Moyé LA, Davis BR , et al. Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the cholesterol and recurrent events trial. Circulation 1998; 97 (15) 1446-1452
  • 4 The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339 (19) 1349-1357
  • 5 Bellosta S, Ferri N, Arnaboldi L, Bernini F, Paoletti R, Corsini A. Pleiotropic effects of statins in atherosclerosis and diabetes. Diabetes Care 2000; 23 (Suppl. 02) B72-B78
  • 6 Axel DI, Riessen R, Runge H, Viebahn R, Karsch KR. Effects of cerivastatin on human arterial smooth muscle cell proliferation and migration in transfilter cocultures. J Cardiovasc Pharmacol 2000; 35 (4) 619-629
  • 7 Azuma J. Phase I study of antihyperlipidemic BAYw6228 (cerivastatin sodium): results on single administration studies in healthy male volunteers. Jpn Pharmacol Ther 1996; 24 (Suppl. 09) 29-36
  • 8 Farmer JA. Pleiotropic effects of statins. Curr Atheroscler Rep 2000; 2 (3) 208-217
  • 9 Kurata T, Kurata M, Okada T. Cerivastatin induces carotid artery plaque stabilization independently of cholesterol lowering in patients with hypercholesterolaemia. J Int Med Res 2001; 29 (4) 329-334
  • 10 Maji D, Shaikh S, Solanki D, Gaurav K. Safety of statins. Indian J Endocrinol Metab 2013; 17 (4) 636-646
  • 11 Tamraz B, Fukushima H, Wolfe AR , et al. OATP1B1-related drug–drug and drug–gene interactions as potential risk factors for cerivastatin-induced rhabdomyolysis. Pharmacogenet Genomics 2013; 23 (7) 355-364
  • 12 Furberg CD, Pitt B. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med 2001; 2 (5) 205-207
  • 13 Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther 2002; 40 (4) 158-168
  • 14 Golański J, Muchova J, Golański R, Durackova Z, Markuszewski L, Watała C. Does pycnogenol intensify the efficacy of acetylsalicylic acid in the inhibition of platelet function? In vitro experience. Postepy Hig Med Dosw (Online) 2006; 60: 316-321
  • 15 Grimm T, Schäfer A, Högger P. Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine bark extract (pycnogenol). Free Radic Biol Med 2004; 36 (6) 811-822
  • 16 Belcaro G, Dugall M, Hosoi M , et al. Pycnogenol® and centella asiatica for asymptomatic atherosclerosis progression. Int Angiol 2014; 33 (1) 20-26
  • 17 Enseleit F, Sudano I, Périat D , et al. Effects of pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J 2012; 33 (13) 1589-1597
  • 18 Belcaro G, Maquart FX, Scoccianti M , et al. TECA (Titrated Extract of Centella Asiatica): new microcirculatory, biomolecular, and vascular application in preventive and clinical medicine. A status paper. Panminerva Med 2011; 53 (3) (Suppl. 01) 105-118
  • 19 Cao W, Li XQ, Zhang XN , et al. Madecassoside suppresses LPS-induced TNF-alpha production in cardiomyocytes through inhibition of ERK, p38, and NF-kappaB activity. Int Immunopharmacol 2010; 10 (7) 723-729
  • 20 Won JH, Shin JS, Park HJ , et al. Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Med 2010; 76 (3) 251-257
  • 21 Belcaro G, Ippolito E, Dugall M , et al. Pycnogenol® and centella asiatica in the management of asymptomatic atherosclerosis progression. Int Angiol 2015; 34 (2) 150-157
  • 22 Belcaro G, Cornelli U, Dugall M, Luzzi R, Hosoi M, Ledda A , et al. Panel 2013 Supplements and green drugs studies; New rules 2013. London and Annecy Panel. Angiology Online 2012
  • 23 Belcaro G, Nicolaides AN. A new role for natural drugs in cardiovascular medicine. Angiology 2001; 52 (Suppl. 02) S1
  • 24 Cesarone MR, Belcaro G, Carratelli M , et al. A simple test to monitor oxidative stress. Int Angiol 1999; 18 (2) 127-130
  • 25 Veller MG, Fisher CM, Nicolaides AN , et al. Measurement of the ultrasonic intima-media complex thickness in normal subjects. J Vasc Surg 1993; 17 (4) 719-725
  • 26 Sabetai MM, Tegos TJ, Clifford C , et al. Carotid plaque echogenicity and types of silent CT-brain infarcts. Is there an association in patients with asymptomatic carotid stenosis?. Int Angiol 2001; 20 (1) 51-57
  • 27 Coen LD, Ramaswami G, Ma PC, Belcaro G, Nicolaides N. Ultrasonic image analysis of the arterial wall in atherosclerosis. Panminerva Med 1998; 40 (1) 1-7
  • 28 Belcaro G, Dugall M, Ippolito E , et al. Pycnogenol® and Centella Asiatica for preventing asymptomatic atherosclerosis progression into clinical events. Minerva Cardioangiol 2017; 65 (1) 24-31
  • 29 Incandela L, Belcaro G, Nicolaides AN , et al. Modification of the echogenicity of femoral plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, randomized, placebo-controlled trial. Angiology 2001; 52 (Suppl. 02) S69-S73
  • 30 Cesarone MR, Belcaro G, Nicolaides AN , et al. Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial. Angiology 2001; 52 (Suppl. 02) S19-S25
  • 31 Belcaro G, Nicolaides AN. Noninvasive Investigations in Vascular Disease. London: Imperial College Press; 2006
  • 32 Belcaro G, Nicolaides AN, Laurora G , et al. Ultrasound morphology classification of the arterial wall and cardiovascular events in a 6-year follow-up study. Arterioscler Thromb Vasc Biol 1996; 16 (7) 851-856
  • 33 Belcaro G, Nicolaides AN, Ramaswami G , et al. Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study(1)). Atherosclerosis 2001; 156 (2) 379-387
  • 34 Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999; 340 (2) 115-126
  • 35 Fuster V. Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 1994; 90 (4) 2126-2146
  • 36 Belcaro G, Cornelli U, Finco A. The Carotid intima-media thickness modification following atorvastatin is bound to the modification of the oxidative balance. J Cardiovasc Pharmacol Ther 2014; 19 (5) 446-450
  • 37 Yoshida M. Leucocyte-endothelial interaction during atherosclerosis. Junkanki Naika 2000; 48: 182-184
  • 38 Morishita R. Stabilization of plaque: the significance of vascular statins. Jpn Med J 2001; 4002: C5-C8
  • 39 Saha SP, Whayne Jr TF, Mukherjee D. Evidence-based management of carotid artery disease. Int J Angiol 2010; 19 (1) e21-e24
  • 40 Whayne Jr TF. Atherosclerosis: current status of prevention and treatment. Int J Angiol 2011; 20 (4) 213-222
  • 41 Hu S, Belcaro G, Cornelli U , et al. Effects of Pycnogenol® on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study. Int Angiol 2015; 34 (1) 43-52
  • 42 Putter M, Grotemeyer KH, Wurthwein G , et al. Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol. Thrombosis Research. 1999; 95 (4) 155-161
  • 43 Belcaro G. Pharma Standard Supplements: Clinical Applications. London: Imperial College Press; 2016