Grape Resveratrol in the Primary Prevention of Cardiovascular Disease
Abstract & Commentary
By Harold L. Karpman, MD, FACC, FACP
Clinical Professor of Medicine, UCLA School of Medicine
Dr. Karpman reports no financial relationships relevant to this field of study.
Synopsis: Supplemental grape resveratrol appears to improve both inflammatory and fibrinolytic markers in patients who are on statin therapy for primary prevention of cardiovascular disease.
Source: Tome-Carneiro J, et al. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am J Cardiol 2012;110:356-363.
THE SEARCH FOR TREATMENTS FOR THE PRIMARY PREVENTION OF CARdiovascular disease (CVD) has been a high-priority challenge for many years. Approximately 20 years ago, consumption of red grape wine was thought to be the explanation for the so-called French paradox, that is, for the low mortality from CVD noted in France compared to the mortality in other countries despite similar CVD risk factors.1 The polyphenol resveratrol found in red grape wine was subsequently identified as the probable chemical responsible for the beneficial properties of red wine.2 In animals and in-vitro models of human CVD, high resveratrol concentrations were found to be associated with cardiovascular benefits, possibly because they increase insulin sensitivity, and also were found to be associated with a decrease in ischemic heart disease, heart failure, and hypertension.3 However, even at this late date, the benefits of resveratrol have not been clearly demonstrated in human subjects at high risk for CVD.
Dr. Tome-Carneiro and his colleagues mounted a triple-blinded, randomized, parallel, dose-response, placebo-controlled 1-year trial in human subjects to demonstrate the benefits of resveratrol in the primary prevention of CVD in humans.4 Seventy-five patients who were receiving standard primary CVD prevention therapies were allocated into three groups for a 6-month trial period. One group consumed a placebo, a second group was given a resveratrol-rich grape supplement containing 8 mg of resveratrol, and the third group was given a conventional grape supplement lacking resveratrol. The dosage in each group was doubled during a second 6-month period. Improved inflammatory and fibrinolytic markers were found to be present in those CVD patients who were at high risk (i.e., those with diabetes and/or hypercholesterolemia) and those who received the resversatrol-rich grape supplement in addition to statin therapy. The authors concluded that grape resveratrol could complement the gold-standard therapy, which is currently used in the primary prevention of CVD.
Commentary
Blood cardio C-reactive protein (hs-CRP) measurements have gradually emerged as a leading biomarker of inflammation in the cardiovascular system and have been used for stratification of CVD risk.5-7 A key finding in the Tome-Carneiro study,4 with respect to the inflammatory status, was that the hs-CRP level decreased by 26% after 1 year of treatment with a grape nutraceutical containing 8 mg of resveratrol, which appeared to be well correlated with a decrease in the blood concentrations of the pro-inflammatory cytokine TNF-alpha and thrombogenic PAI-1. In this trial, patients were treated according to accepted guidelines for the primary prevention of CVD.8 Therefore, since all patients received statin therapy, a synergistic effect between statins and the grape nutraceutical could not be excluded. In fact, the combination of pravastatin and resveratrol previously had been demonstrated to be more effective than statins alone in preventing myocardial infarction in hypercholesterolemic rats.9 The authors concluded that, for the first time in human subjects, a dietary intervention with grape resveratrol was demonstrated to complement standard therapy used in the primary prevention of CVD. However, it is important to recognize that the sample size in this study was small, the follow-up period was relatively short (1 year), and this was a single-center trial; therefore, the statistical significance of the final results of the Tome-Carneiro trial4 were, at best, somewhat uncertain.
In summary, the authors have confirmed the results of previously reported clinical studies that a grape nutraceutical containing resveratrol is beneficial in the primary prevention of CVD probably by improving the inflammatory and fibrinolytic status of subjects who consumed adequate quantities of the compound. However, it is important to recognize that a larger and longer trial is absolutely necessary before coming to firm conclusions about the effects of these grape products in the prevention of CVD.
References
1. Renaud S, et al. Wine, alcohol, platelets and the French paradox for coronary heart disease. Lancet 1992;339: 1523-1526.
2. Bertelli A, et al. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exper Clin Res 1998;24:133-138.
3. Petrovski G, et al. Resveratrol in cardiovascular health and disease. Ann N Y Acad Sci 2011;1215:22-23.
4. Tome-Carneiro J, et al. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am J Cardiol 2012;110:356-363.
5. Braunwald E, et al. Creating controversy where none exists: The important role of C-reactive protein in CAREAFCAPS/TexCAps, PROVEIT, REVERSAL, A to Z, JUPITER, HEART REVENGE and ASCOT trials. Eur Heart J 2012;33:430-432.
6. Ridker PM, et al. Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001;344:1959-1965.
7. Weil BR, et al. Relation of C-reactive protein to endothelial fibrinolytic function in healthy adults. Am J Cardiol 2011;108:1675-1679.
8. Reiner Z, et al. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-1818.
9. Penumathsa SV, et al. Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat. J Mol Cell Cardiol 2007;42:508-516.
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