- •Mediterranean diet (MD) is associated with lower risk of death in CVD patients.
- •Statins reduce CVD death risk only in combination with Mediterranean diet.
- •Inflammation is likely to be on the pathway of the interaction of MD and statins.
- •Combination of MD and statins may be an optimal option for secondary prevention.
Statins are prescribed for patients with cardiovascular disease (CVD), along with the recommendation of adopting healthy diets. We evaluated the independent and the combined effect of statins and Mediterranean diet (MD) towards mortality risk in patients with previous CVD by using real-life data from a population-based prospective cohort.
Longitudinal analysis on 1180 subjects (mean age 67.7 ± 10) with prior CVD at enrollment in the Moli-sani Study and followed up for 7.9 y (median). Adherence to MD was appraised by a Mediterranean diet score. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated by multivariable Cox regression and competing risk models.
Multivariable risk estimates associated with a 2-point increase in MD score were 0.84 (95% CI 0.70–1.00), 0.77 (0.61–0.97) and 0.70 (0.52–0.93) for overall, cardiovascular and coronary artery disease (CAD)/cerebrovascular deaths, respectively. Statins were not associated with death risk. Subjects combining statins and average-high adherence to MD had much lower than expected risk of cardiovascular and CAD/cerebrovascular mortality (p for interaction = 0.045 and 0.0015, respectively) as compared to those neither using statins nor having average-high MD.
The combination of average-high MD and statins was associated in a likely synergistic way with reduced low-grade inflammation, but not with blood cholesterol.
MD lowered the risk of all-cause, cardiovascular and CAD/cerebrovascular mortality CVD patients, net of statins. In the same population, statins reduced CVD death risk only in combination with MD. Low-grade inflammation, rather than lipids, is likely to be on the pathway of the interaction between MD and statins towards mortality risk.
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- Global Atlas on Cardiovascular Disease Prevention and Control. World Health Organisation, Geneva2011
- Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke. Meta-analysis of randomized trials.Int. J. Clin. Pharmacol. Ther. 2003; 41: 567-577
- Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate.BMC Med. 2016; 14: 4
- Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US Preventive Services Task Force.JAMA. 2016; 316: 2008-2024
- Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.N. Engl. J. Med. 2008; 359: 2195-2207
- Statins for the primary prevention of cardiovascular disease.Cochrane Database Syst. Rev. 2013; 1CD004816
- Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: the ALLHAT-LLT randomized clinical trial.JAMA Intern. Med. 2017; 177: 955-965
- Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering.Am. J. Cardiol. 2000; 86: 257-262
- Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial.J. Am. Coll. Cardiol. 2005; 46: 1405-1410
- Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease.N. Engl. J. Med. 2005; 352: 1425-1435
- Long-term benefit of statin therapy initiated during hospitalization for an acute coronary syndrome: a systematic review of randomized trials.Am. J. Cardiovasc. Drugs. 2007; 7: 135-141
- The Sixth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice. 2016 European guidelines on cardiovascular disease prevention in clinical practice.Eur. J. Prev. Cardiol. 2016; 23: NP1-NP96
- Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis.Am. J. Clin. Nutr. 2010; 92: 1189-1196
- Primary prevention of cardiovascular disease with a Mediterranean diet.N. Engl. J. Med. 2013; 368: 1279-1290
- GISSI-Prevenzione Investigators. Mediterranean diet and all-causes mortality after myocardial infarction: results from the GISSI-Prevenzione trial.Eur. J. Clin. Nutr. 2003; 57: 604-611
- Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.Circulation. 1999; 99: 779-785
- Mediterranean diet and survival among patients with coronary heart disease in Greece.Arch. Intern. Med. 2005; 165: 929-935
- The Mediterranean-style dietary pattern and mortality among men and women with cardiovascular disease.Am. J. Clin. Nutr. 2014; 99: 172-180
- Dietary patterns and the risk of major adverse cardiovascular events in a global study of high-risk patients with stable coronary heart disease.Eur. Heart J. 2016; 1: 1993-2001
- Adherence to Mediterranean diet offers an additive protection over the use of statin therapy: results from the ATTICA study (2002–2012).Curr. Vasc. Pharmacol. 2015; 13: 778-787
- Dietary modulators of statin efficacy in cardiovascular disease and cognition.Mol. Asp. Med. 2014; 38: 1-53
- Randomized Controlled Trials and real life studies. Approaches and methodologies: a clinical point of view.Pulm. Pharmacol. Ther. 2014; 27: 129-138
- Distribution of short and lifetime risks for cardiovascular disease in Italians.Eur. J. Prev. Cardiol. 2012; 19: 723-730
- A score of low-grade inflammation and risk of mortality: prospective findings from the Moli-sani study.Haematologica. 2016; 101: 1434-1441
- Adherence to a Mediterranean diet and survival in a Greek population.N. Engl. J. Med. 2003; 348: 2599-2608
- Association between intensity of statin therapy and mortality in patients with atherosclerotic cardiovascular disease.JAMA Cardiol. 2017; 2: 47-54
- Kimura T; CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators. Effect of statin therapy on cardiovascular outcomes after coronary revascularization in patients ≥80 years of age: observations from the CREDO-Kyoto Registry Cohort-2.Atherosclerosis. 2014; 237: 821-828
- Cardiovascular and cancer mortality in very elderly post-myocardial infarction patients receiving statin treatment.J. Am. Coll. Cardiol. 2010; 55: 1362-1369
- Statins and the risks of stroke recurrence and death after ischemic stroke: the Fukuoka Stroke Registry.Atherosclerosis. 2013; 231: 211-215
- Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study.Heart. 2002; 88: 229-233
- Statin therapy is associated with lower mortality among patients with severe heart failure.Am. J. Cardiol. 2004; 93: 1124-1129
- Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies.Eur. Heart J. 2017; 38: 1608-1612
- Persistence and determinants of statin therapy among middle-aged patients for primary and secondary prevention.Br. J. Clin. Pharmacol. 2005; 59: 564-573
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389
- Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials.Eur. Heart J. 2018 Apr 7; 39: 1172-1180
- 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation. 2014; 129: S76-S99
- Association of flavonoid-rich foods and statins in the management of hypercholesterolemia: a dangerous or helpful combination?.Curr. Drug Metab. 2015; 16: 833-846
- Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial.JAMA. 2002; 287: 598-605
- The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia.N. Engl. J. Med. 1993; 328: 1213-1219
- Effect of dietary intervention and lipid-lowering treatment on brachial vasoreactivity in patients with ischemic heart disease and hypercholesterolemia.Am. Heart J. 2003; 145E19
- Association between statin use and serum cholesterol concentrations is modified by whole-grain consumption: NHANES 2003–2006.Am. J. Clin. Nutr. 2014; 100: 1149-1157
- Healthy eating and lower mortality risk in a large cohort of cardiac patients who received state-of-the-art drug treatment.Am. J. Clin. Nutr. 2015; 102: 1527-1533
- Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial.Ann. Intern. Med. 2006; 4: 1-11
- Beneficial cardiovascular pleiotropic effects of statins.Circulation. 2004; 109: III39-43
- MOLI-SANI Study Investigators. Mediterranean diet, dietary polyphenols and low grade inflammation: results from the MOLI-SANI study.Br. J. Clin. Pharmacol. 2017; 83: 107-113
- Dietary cholesterol and egg yolks: not for patients at risk of vascular disease.Can. J. Cardiol. 2010; 26: e336-e339
- Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance.Diabetes Care. 2009; 32: 2281-2287
- Red wine mitigates the postprandial increase of LDL susceptibility to oxidation.Free Radic. Biol. Med. 2001; 30: 1036-1044
- Antiinflammatory therapy with canakinumab for atherosclerotic disease.N. Engl. J. Med. 2017; 377: 1119-1131
- Effect of combining psyllium fiber with simvastatin in lowering cholesterol.Arch. Intern. Med. 2005; 165: 1161-1166
Published online: November 24, 2018
Accepted: November 23, 2018
Received in revised form: November 7, 2018
Received: June 13, 2018
© 2018 Elsevier B.V. All rights reserved.