High Anthocyanin Intake Is Associated With a Reduced Risk of Myocardial Infarction in Young and Middle-Aged Women

Background— Our current knowledge of modifiable risk factors to prevent myocardial infarction (MI) in young and middle-aged women is limited, and the impact of diet is largely unknown. Dietary flavonoids exert potential beneficial effects on endothelial function in short-term trials; however, the relationship between habitual intake and risk of MI in women is unknown. Methods and Results— We followed up 93 600 women 25 to 42 years of age from the Nurses’ Health Study (NHS) II who were healthy at baseline (1989) to examine the relationship between anthocyanins and other flavonoids and the risk of MI. Intake of flavonoid subclasses was calculated from validated food-frequency questionnaires collected every 4 years using an updated and extended US Department of Agriculture database. During 18 years of follow-up, 405 cases of MI were reported. An inverse association between higher intake of anthocyanins and risk of MI was observed (hazard ratio, 0.68; 95% confidence interval, 0.49–0.96; P=0.03, highest versus lowest quintiles) after multivariate adjustment. The addition of intermediate conditions, including history of hypertension, did not significantly attenuate the relationship (hazard ratio, 0.70; 95% confidence interval, 0.50–0.97; P=0.03). Combined intake of 2 anthocyanin-rich foods, blueberries and strawberries, tended to be associated with a decreased risk of MI (hazard ratio, 0.66; 95% confidence interval, 0.40–1.08) in a comparison of those consuming >3 servings a week and those with lower intake. Intakes of other flavonoid subclasses were not significantly associated with MI risk. Conclusions— A high intake of anthocyanins may reduce MI risk in predominantly young women. Intervention trials are needed to further examine the health impact of increasing intakes of commonly consumed anthocyanin-rich foods.

[1]  H. Blackburn,et al.  Cardiovascular survey methods. , 1969, East African medical journal.

[2]  R. Doll,et al.  Risk factors for myocardial infarction in young women. , 1976, British journal of preventive & social medicine.

[3]  S. Shapiro,et al.  Alcoholic beverages and myocardial infarction in young women. , 1981, American journal of public health.

[4]  S. Shapiro,et al.  Myocardial infarction and cigarette smoking in women younger than 50 years of age. , 1985, JAMA.

[5]  M. Singer,et al.  Nutritional Epidemiology , 2020, Definitions.

[6]  R. Simon,et al.  Flexible regression models with cubic splines. , 1989, Statistics in medicine.

[7]  C. la Vecchia,et al.  Coffee consumption and myocardial infarction in women. , 1989, American journal of epidemiology.

[8]  G A Colditz,et al.  Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. , 1989, International journal of epidemiology.

[9]  D Feskanich,et al.  Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. , 1993, Journal of the American Dietetic Association.

[10]  J. Manson,et al.  The Nurses' Health Study: 20-year contribution to the understanding of health among women. , 1997, Journal of women's health.

[11]  Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. , 1997, Lancet.

[12]  M. Marmot,et al.  Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study , 1997, The Lancet.

[13]  Robert Gray,et al.  A Proportional Hazards Model for the Subdistribution of a Competing Risk , 1999 .

[14]  D Spiegelman,et al.  Dietary fat and coronary heart disease: a comparison of approaches for adjusting for total energy intake and modeling repeated dietary measurements. , 1999, American journal of epidemiology.

[15]  S. Shapiro,et al.  Low-Dose Oral Contraceptive Use and the Risk of Myocardial Infarction , 2001 .

[16]  Ilja C W Arts,et al.  Polyphenols and disease risk in epidemiologic studies. , 2005, The American journal of clinical nutrition.

[17]  W. Ling,et al.  An anthocyanin-rich extract from black rice enhances atherosclerotic plaque stabilization in apolipoprotein E-deficient mice. , 2006, The Journal of nutrition.

[18]  V. Schini-Kerth,et al.  Delphinidin and cyanidin inhibit PDGFAB‐induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK , 2006, British journal of pharmacology.

[19]  P. Dugo,et al.  Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. , 2006, Nitric oxide : biology and chemistry.

[20]  M. Heinonen,et al.  Anti-Inflammatory Effects of Flavonoids: Genistein, Kaempferol, Quercetin, and Daidzein Inhibit STAT-1 and NF-κB Activations, Whereas Flavone, Isorhamnetin, Naringenin, and Pelargonidin Inhibit only NF-κB Activation along with Their Inhibitory Effect on iNOS Expression and NO Production in Activated , 2007, Mediators of inflammation.

[21]  D. Jacobs,et al.  Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. , 2007, The American journal of clinical nutrition.

[22]  D. Spiegelman,et al.  Comparing smoothing techniques in Cox models for exposure–response relationships , 2007, Statistics in medicine.

[23]  J. Manson,et al.  Dietary intakes of flavonols and flavones and coronary heart disease in US women. , 2007, American journal of epidemiology.

[24]  H. Sies,et al.  How do dietary flavanols improve vascular function? A position paper. , 2008, Archives of biochemistry and biophysics.

[25]  C. Tonelli,et al.  Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reperfusion injury. , 2008, The Journal of nutrition.

[26]  K. Miyazaki,et al.  Anthocyanins from purple sweet potato Ipomoea batatas cultivar Ayamurasaki suppress the development of atherosclerotic lesions and both enhancements of oxidative stress and soluble vascular cell adhesion molecule-1 in apolipoprotein E-deficient mice. , 2008, Journal of agricultural and food chemistry.

[27]  Ian Harvey,et al.  Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. , 2008, The American journal of clinical nutrition.

[28]  U. Sechtem,et al.  Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR (Coronary Artery Spasm in Patients With Acute Coronary Syndrome) Study. , 2008, Journal of the American College of Cardiology.

[29]  Y. Hao,et al.  Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. , 2009, The American journal of clinical nutrition.

[30]  A. Minihane,et al.  Red wine anthocyanins are rapidly absorbed in humans and affect monocyte chemoattractant protein 1 levels and antioxidant capacity of plasma. , 2009, The Journal of nutritional biochemistry.

[31]  T. Jin,et al.  Protocatechuic acid, a metabolite of anthocyanins, inhibits monocyte adhesion and reduces atherosclerosis in apolipoprotein E-deficient mice. , 2010, Journal of agricultural and food chemistry.

[32]  S. de Pascual-Teresa,et al.  Flavanols and Anthocyanins in Cardiovascular Health: A Review of Current Evidence , 2010, International journal of molecular sciences.

[33]  Dong-Hyun Kim,et al.  Anti-inflammatory effects of black rice, cyanidin-3-O-beta-D-glycoside, and its metabolites, cyanidin and protocatechuic acid. , 2010, International immunopharmacology.

[34]  A. Zamilpa,et al.  Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa. , 2010, Journal of ethnopharmacology.

[35]  Edward L. Melnick,et al.  Modeling Survival Data , 2011, International Encyclopedia of Statistical Science.

[36]  W. Ling,et al.  Cyanidin-3-O-β-glucoside with the aid of its metabolite protocatechuic acid, reduces monocyte infiltration in apolipoprotein E-deficient mice. , 2011, Biochemical pharmacology.

[37]  D. Wood,et al.  Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease , 2011, Circulation.

[38]  E. Rimm,et al.  Habitual intake of flavonoid subclasses and incident hypertension in adults. , 2011, The American journal of clinical nutrition.

[39]  G. Rimbach,et al.  Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites , 2012, Genes & Nutrition.

[40]  D. Mozaffarian,et al.  Executive summary: heart disease and stroke statistics--2012 update: a report from the American Heart Association. , 2012, Circulation.

[41]  A. Brantsæter,et al.  Evaluation of flavonoids and enterolactone in overnight urine as intake biomarkers of fruits, vegetables and beverages in the Inter99 cohort study using the method of triads. , 2012, The British journal of nutrition.

[42]  E. Rimm,et al.  Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. , 2012, The American journal of clinical nutrition.

[43]  M. McCullough,et al.  Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. , 2012, American Journal of Clinical Nutrition.