title: Pycnogenol® and Centella asiatica in the management of asymptomatic atherosclerosis progression.
abstract: OBJECTIVE
  The aim of the study was to evaluate the effect of the nutritional supplements Pycnogenol® and total triterpenic fraction of Centella asiatica (TTFCA) on atherosclerosis progression in low-risk asymptomatic subjects with carotid or femoral stenosing plaques.
  
  
  METHODS
  This was an observational pilot, substudy of the San Valentino epidemiological cardiovascular study. The study included 824 subjects aged 45-60 without any conventional risk factors who had a stenosing atherosclerotic plaque (>50-60%) in at least one carotid or common femoral bifurcation, allocated into 6 groups: Group 1 (Controls): management was based on education, exercise, diet and lifestyle changes. This same management plan was used in all other groups; group 2: Pycnogenol® 50 mg/day; group 3: Pycnogenol® 100 mg/day; group 4: Aspirin® 100 mg/day or ticlopidine 250 mg/day if intolerant to aspirin; group 5: Aspirin® 100 mg/day and Pycnogenol® 100 mg/day; group 6: Pycnogenol® 100 mg/day plus TTFCA 100 mg/day. The follow-up lasted 42 months. Plaque progression was assessed using the ultrasonic arterial score based on the arterial wall morphology and the number of plaques that progressed and on the number of subjects that had cardiovascular events. A secondary endpoint was to evaluate the changes in oxidative stress at baseline and at 42 months.
  
  
  RESULTS
  The ultrasonic score increased significantly in groups 1, 2, and 4 (>1%) but not in groups 3, 5 and 6 (<1%) suggesting a beneficial effect of Pycnogenol® 100 mg. Considering the percent of patients that progressed from class V (asymptomatic) to VI (symptomatic) there was a progression of plaques in 48.09% of controls. In the Pycnogenol® 100 (group 3, 10.4%) and in the Aspirin®+ Pycnogenol® (group 5, 10.68%) progression was half of what observed with antiplatelet agent (group 4, 20.93%); in the TTFCA+ Pycnogenol®group (group 6) progression was 7.4 times lower than in controls; 3.22 times lower than in the antiplatelet agents group (4). Events (hospital admission, specialized care) were observed in 16.03% of controls; there were 8.83% of subjects with events with Pycnogenol® 50 mg and 8% in group 3 (Pycnogenol® 100 mg). In group 4 (antiplatelets), 8.52% of subjects had events; in group 5, 6.87% of subjects had events and in group 6 (TTFCA+ Pycnogenol®) only 4.41% had events (this was the lowest event rate; P<0.05). All treatment groups had a significantly lower event rate (P<0.05) in comparison with controls. Considering treatments groups 2, 3, 5, 6 had a lower number (P<0.05) of subjects in need of cardiovascular management in comparison with controls. The need for risk factor management was higher in controls and lower in group 6 (P<0.05). In groups 2 to 6 the need for risk factor management was lower than in controls (P<0.05). Including all events (hospital admission, need for treatment or for risk management) 51.9% of controls were involved. In the other groups there was a reduction (from a -9.28% reduction in group 2 to a -26% in group 6) (P<0.002). The most important reduction (higher that in all groups; P<0.05) was in group 6. At 42 months, oxidative stress in all the Pycnogenol® groups was less than in the control group. In the combined group of Pycnogenol® and TTFCA the oxidative stress was less than with Pycnogenol® alone (P<0.001).
  
  
  CONCLUSIONS
  Pycnogenol® and the combination of Pycnogenol® +TTFCA appear to reduce the progression of subclinical arterial plaques and the progression to clinical stages. The reduction in plaque and clinical progression was associated with a reduction in oxidative stress. The results justify a large, randomized, controlled study to demonstrate the efficacy of the combined Pycnogenol® and TTFCA prophylactic therapy in preclinical atherosclerosis.
authors.affiliation: Department of Biomedical, Experimental and Surgical Sciences, Irvine3 Circulation Sciences, G. D'Annunzio University, Pescara, Italy - cardres@abol.it.
authors.forename: G
authors.initials: G
authors.lastname: Belcaro
authors.forename: E
authors.initials: E
authors.lastname: Ippolito
authors.forename: M
authors.initials: M
authors.lastname: Dugall
authors.forename: M
authors.initials: M
authors.lastname: Hosoi
authors.forename: U
authors.initials: U
authors.lastname: Cornelli
authors.forename: A
authors.initials: A
authors.lastname: Ledda
authors.forename: M
authors.initials: M
authors.lastname: Scoccianti
authors.forename: R D
authors.initials: RD
authors.lastname: Steigerwalt
authors.forename: M R
authors.initials: MR
authors.lastname: Cesarone
authors.forename: L
authors.initials: L
authors.lastname: Pellegrini
authors.forename: R
authors.initials: R
authors.lastname: Luzzi
authors.forename: M
authors.initials: M
authors.lastname: Corsi
mesh_terms: D058070:Asymptomatic Diseases; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D016893:Carotid Stenosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D028041:Centella; D003131:Combined Modality Therapy; D019587:Dietary Supplements / Q000009:adverse effects; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D010865:Pilot Projects; D010936:Plant Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D058226:Plaque, Atherosclerotic; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012042:Registries; D040242:Risk Reduction Behavior; D012422:Rupture, Spontaneous; D013997:Time Factors; D016896:Treatment Outcome; D014315:Triterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D014463:Ultrasonography
chemical_list: D002317:Cardiovascular Agents; C526146:Centella asiatica extract; D005419:Flavonoids; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D014315:Triterpenes; C024070:pycnogenols