Beneficial Effects Of Grape Seed Proanthocyanidin Extract On Progression Of Carotid Atherosclerosis In Clinical Use

BackgroundAtherosclerosis is the main underlying cause of ischemic vascular diseases and is predicted to become the leading cause of global mortality by 2050. Atherosclerotic plaques indicate the occurrence of ischemia events, and how to deal with it is a difficult task for clinical physician. Animal experimental studies have indicated that grape seed proanthocyanidin extract (GSPE) exerts an antiatherogenic effect by inducing regression of atherosclerotic plaques. Whether GSPE can reverse the atherosclerotic progression and reduce the incidence rate of cardiovascular events in clinical use have not been reported by now.ObjectiveThe aim of this study is to observe the effect of GSPE on carotid atherosclerosis in clinical use and investigate the possible mechanism, providing a scientific basis for new treatments of atherosclerosis.Methods1 Study populationConsecutive 157 nonhypercholesterolemic patients diagnosed with asymptomatic carotid artery plaques or abnormal CIMT based on carotid ultrasonography were randomly assigned to control group (n=81) or GSPE group (n=76). In control group, all patients were enrolled in a lifestyle intervention. The patients in GSPE group received GSPE 400 mg/day (200mg bid) in addition to the same lifestyle intervention. The whole study lasted 24 months.2 History investigation and physical examination A full clinical history and physical examination of all patients were performed by a specialized physician. The following information was collected:age, sex, BMI (body mass index), blood pressure, current medications and history of hypertension or diabetes mellitus.3 Laboratory analysesPeripheral blood samples were collected in the early morning before breakfast at the beginning of the study and follow-up period. Serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) levels were assessed by standard techniques in the hospital laboratory. Assessments were performed at baseline, as well as at months 6,12 and 24 after the first infusion.4 Carotid B-Mode Ultrasound examinationHigh-resolution B-mode ultrasonography of the carotid artery was performed with an ultrasound scanner (iE33, Philips) equipped with a linear array 5-to7-MHz transducer. The effects of GSPE were monitored by blinded, serial assessments of mean maximum carotid intima-media thickness (MMCIMT) and the plaque score.5 Statistical AnalysisNumerical data are expressed as mean±SD (x±s). The significance of the differences in various parameters within each group between baseline and after treatment was tested using a paired Student t test. The significance of the differences between groups in these parameters was tested by an unpaired Student's t test. Categorical data were summarized as percentages and compared using chi-square analysis. All analyses were carried out by SPSS 13.0 software. All P values were two-tailed and statistical significance was set at P<0.05.Result1. All 157 patients completed the protocol. There was no significant difference in all baseline demographic parameters between the two groups.2. There was no significant difference between groups on serum lipid profile at baseline. In GSPE group, serum TC, TG and LDL-C level all decreased after treatment (P>0.05). In control group, there was no significant change on lipid profile during follow-up. Between-group comparison, significant difference of serum HDL-C level appeared after 12 months (P<0.05).3. GSPE resulted in significant reductions in serum hs-CRP concentration during follow-up. Serum hs-CRP concentration significantly increased in control group after 12 months (P<0.05). Significant difference of serum hs-CRP levels between the two groups appears after 6 months treatment (P<0.05).4. After treatment, GSPE resulted in significant reduction in MMCIMT progression (3.3% decrease after 6 months,6.2% decrease after 12 months and 9.4% decrease after 24 months) and plaque score (10.9% decrease after 6 months, 24.1% decrease after 12 months and 33.1% decrease after 24 months). While MMCIMT and plaque score was stable and even increased with the time going on in control group. The number of plaques and unstable plaques also decreased after treatment of GSPE.ConclusionGSPE can inhibit the development of carotid intima-media thickness, regress the carotid plaque and promote the stabilization of carotid plaque, and as the treatment of prolonged, the antiatherosclerosis effect of GSPE was more apparent. At last, after treatment of 24 months, GSPE can reduce the cardiovascular event significantly. In the light of our results, we can speculate that GSPE could be an effective therapeutic candidate for the primary prevention programs for the asymptomatic patient with atherosclerotic lesion. Future in vivo studies are required to investigate the mechanism. BackgroundAtherosclerosis is the main underlying cause of ischemic vascular diseases and is predicted to become the leading cause of global mortality by 2050. Atherosclerotic plaques indicate the occurrence of ischemia events, and how to deal with it is a difficult task for clinical physician.Animal experimental studies have indicated that grape seed proanthocyanidin extract (GSPE) exerts an antiatherogenic effect by inducing regression of atherosclerotic plaques. Whether GSPE can reverse the atherosclerotic progression and reduce the incidence rate of cardiovascular events in clinical use have not been reported by now.ObjectiveThe aim of this study is to observe the effect of the combination use of GSPE and atorvastatin on carotid atherosclerosis in clinical use and investigate the possible mechanism, providing a scientific basis for new treatments of atherosclerosis.Methods1. Study populationConsecutive 122 hypercholesterolemic patients diagnosed with asymptomatic carotid artery plaques based on carotid ultrasonography were randomly assigned to group A (n=63) or group B (n=59). All patients in group A received atorvastatin 20mg once a day. While the patients in group B received therapy of a combination of both atorvastatin 10 mg/day and GSPE 400mg/day. The whole study lasted 12 months.2. History investigation and physical examinationA full clinical history and physical examination of all patients were performed by a specialized physician. The following information was collected:age, sex, BMI (body mass index), blood pressure, current medications, smoking status and history of hypertension, coronary heart disease or diabetes mellitus.3. Laboratory analysesAll peripheral blood samples were collected in the early morning before breakfast. Serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and high-sensitive C-reactive protein (hs-CRP) levels were assessed by standard techniques in the hospital laboratory. Assessments were performed at baseline, as well as at months 3,6 and 12 after the first infusion.4. Carotid B-Mode Ultrasound examinationIn this study, standardized and validated scanning and measurement protocols were used. High-resolution B-mode ultrasonography of the carotid artery was performed with an ultrasound scanner (iE33, Philips) equipped with a linear array 5-to7-MHz transducer. The effects of GSPE were monitored by blinded, serial assessments of mean maximum carotid intima-media thickness (MMCIMT), the plaque score and stability of plaques.5. Statistical AnalysisNumerical data are expressed as mean±SD (x±s).The significance of the differences in various parameters within each group between baseline and after treatment was tested using a paired Student t test. The significance of the differences between groups in these parameters was tested by an unpaired Student's t test. Categorical data were summarized as percentages and compared using chi-square analysis. All analyses were carried out by SPSS 13.0 software. All p values were two-tailed and statistical significance was set at P<0.05.Result1. All 122 patients completed the protocol. There was no significant difference in all baseline demographic parameters between groups.2. There was no significant difference between groups on serum lipid profile at baseline. After treatment of 3 months, serum TC, TG and LDL-C level in both groups decreased significantly, serum HDL-C level increased significantly. The decrease of serum TC, TG and LDL-C level in group B was more significantly than in group A, but there was no statistically different at the same time point for between-group comparison. Serum HDL-C level in group A was significantly different from group B after 6 months (P<0.05).3. Serum hs-CRP concentration significantly decreased in both two groups after treatment. After treatment of 3 months, serum hs-CRP concentration in group A decreased 1.71mg/L (P<0.05), while serum hs-CRP concentration in group B decreased 3.55mg/L (P<0.05). Significant difference of serum hs-CRP levels between the two groups appears after 6 months treatment (P<0.05)4. After treatment, atorvastatin resulted in significant reduction in MMCIMT progression (5.1% decrease after12 months, P<0.05) and plaque score (19.2% decrease afterl2 months, P<0.05). While significant decrease of both MMCIMT and plaque score in group B appears after 6 months treatment.5. The number of total plaques and unstable plaques decreased in both group during follow-up. The decrease in group B was more significant than in group A.ConclusionAtorvastatin can inhibit the development of carotid intima-media thickness, regress the carotid plaque and promote the stabilization of carotid plaque, and as the treatment of prolonged, the the combination use of GSPE and atorvastatin have greater benefit.