By: Professor Clemens von Schacky, Preventive Cardiology, University of Munich and Omegametrix, Martinsried
Cardiovascular disease (CVD) remains one of the biggest threats to human health and is a significant concern for medical and scientific communities globally. Currently, CVDs such as coronary heart disease (CHD) and stroke represent 31% of all global deaths, with an estimated 17.5 million people dying each year from the disease1. It is the leading cause of death among both men and women in the US2, and it is estimated that one in five adults in China has CVD, with the country having one of the highest CVD death rates in the world3.
Risk factors fall into two categories: those that cannot be prevented, such as age, and those that can be prevented. Of the latter, a surprising number can be attributed to lifestyle; these include smoking, high blood pressure, elevated blood lipids, sedentary lifestyles, obesity and, importantly, poor nutrition. Lowering one’s body mass index (BMI) to within the ‘normal’ range of 20 – 25kg/m2 can help to reduce blood pressure, blood lipids and the occurrence of a sedentary lifestyle. This can be achieved by maintaining caloric intake, if BMI already falls within this range, or via a negative balance of calories if BMI is greater than 25kg/m2, complemented by an increase in exercise to burn calories.
Although many risk factors are related to lifestyle, a change in lifestyle may not always be easy, possible or achieved rapidly. In such cases, drugs, such as statins, are needed to treat elevated blood lipids, and other drugs can be used to treat high blood pressure or even an addiction to smoking.
The composition of one’s diet is also an important factor in the occurrence of CVD. The Western diet, increasingly popular across the globe, is rich in sodium, sugar-sweetened beverages and deficient in marine based omega-3 fatty acids (EPA; DHA), vitamin D, nuts/seeds and wholegrains. As a result, individuals living on this diet are at greater risk of heart attack, stroke, type 2 diabetes and even death4, with dietary factors estimated to be associated with a substantial proportion of mortalities5. Alternatively, the Mediterranean diet, rich in nuts, oily fish, fruits and vegetables, with limited intake of red meat, sodium and sugar-sweetened beverages, has been found to reduce the occurrence of cardiovascular events6.
There is also a strong correlation between certain biomarkers, such as diabetes, and CVD; in fact, the American Heart Association has reported that adults with diabetes are up to four times more likely to die from heart disease than those without diabetes7.
Guidelines vary from region to region, but globally it is agreed that patients at elevated risk of CVD should follow a cardio-protective diet featuring fruits, vegetables, wholegrains, lean meats, poultry, fish, nuts, legumes and seeds, with a limited intake of added sugars8. The difficulty lies in the reliance on patients making changes to significantly improve their own lifestyles, as individuals are not necessarily following current advice. This is, in part, due to gaps in patient - and even physician - knowledge as to what constitutes a well-balanced, nutritious diet, and how to achieve it. Recently, biomarkers have been used to measure an individual’s supply of important ingredients. The most advanced biomarkers are for vitamin D and omega-3 fatty acids (EPA; DHA), and a large proportion of the populations tested have been found to be deficient in these two components9,10. Guidelines continue to evolve as more evidence comes to light11.
Just as poor nutrition can play a key role in increasing the risk of CVD, a well-balanced, nutrient-rich diet can help to prevent or dramatically reduce the risk of developing CVD. The World Health Organization (WHO) states that adequate changes in lifestyle can prevent three quarters of all CVD mortality, and there is growing evidence for the influences of different foods and nutrients, and their role in the prevention of CVD 12-15. There is also extensive research indicating that key nutrients, including omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as vitamin D, can support heart health16.
There is growing evidence to suggest that omega-3 EPA and DHA can help to reduce the risk of developing CVD. In fact, in 2012, the European Commission authorized an Article 13.1 health claim that 250mg per day of EPA and DHA contributes to normal heart function17. In 2013, additional Article 13.1 claims were authorised for “DHA and EPA contribute to the maintenance of normal blood pressure” (for a daily intake of 3g of EPA and DHA) and “DHA and EPA contribute to the maintenance of normal blood triglyceride levels” (for a daily intake of 2 g of EPA and DHA.18
In addition to this, a new meta-analysis of studies assessing the relationship of EPA and DHA on CHD found that the risk of CHD in individuals with elevated triglycerides or LDL cholesterol was significantly reduced with EPA and DHA supplementation19. However, a substantial number of large intervention trials with supplements of EPA and DHA in cardiovascular disease did not have positive results, or reported neutral results. Therefore, the European Society of Cardiology (ESC) does currently not endorse the use of EPA and DHA supplements in the guidelines for Cardiovascular Prevention.20 It is not likely that ineffectiveness of EPA and DHA can be linked to the restricted positive or neutral outcome of these trials. It is rather a question of bioavailability of EPA and DHA and issues related to the trial methodology, which were recently revealed by measuring levels of EPA and DHA using the standardized HS-Omega-3 Index®. 21. Currently, many say that a new generation of level-based large intervention trials are needed to gain a more accurate representation and understanding of the impact of EPA and DHA on cardiovascular health.
Nevertheless, based on positive results obtained from a number of trials and the totality of the evidence, the American Heart Association (AHA) recently issued a statement strongly supporting the use of EPA and DHA supplements in congestive heart failure and, less strongly, in patients who have had a recent heart attack.22.
Traditionally recognized for its importance in maintaining bone health, higher levels of vitamin D have also been found to be associated with longevity and a reduction in the occurrence of cardiovascular events.
Vitamin D levels are measured as 25(OH) vitamin D in serum, and risk for both mortality and cardiovascular events increases at levels lower than 30 ng/ml, equivalent to 75 nmol/l23. Vitamin D also plays a beneficial role in the regulation of high blood pressure24 and a reduction in the risk of hypertension and CHD25. Although a meta-analysis of intervention trials has found that increasing intake of vitamin D reduces total mortality, cardiac societies currently do not support the use of vitamin D as a supplement, although intake of up to 100µg per day is considered safe by EFSA26. Optimal levels of vitamin D can be achieved safely in adults by the daily intake of vitamin D3 of up to 100 mg or 4000 I.E. per day27.
Key nutrients, including vitamins C and E, and soluble fibers such as oat beta-glucan, have been also found to play a role in supporting heart health.
Vitamin E has been linked to a lowered risk of developing a cardiovascular condition due to oxidative stress and inflammation, as well as helping to protect cells from damage and maintaining arterial health28,29,30. Meanwhile, vitamin C can support heart health – higher levels of the vitamin have been linked to lower blood pressure31, as well as improved vasodilation in individuals with CHD 32.
Research on soluble fibers has also highlighted the cholesterol lowering potential of oat beta-glucan and a subsequent reduction in the risk of developing heart disease33. A claim on reduction of a disease risk factor has been authorised in the EU in 2011 for oat beta-glucan for a daily intake of 3 g: “Oat beta-glucan has been shown to lower/reduce blood cholesterol. High cholesterol is a risk factor in the development of coronary heart disease”34
The global shift to an increased consumption of nutrient-poor foods is likely an important factor behind the rising levels of CVD worldwide, but support from governments, regulatory bodies and healthcare practitioners can help the food industry to reverse this trend and ensure that a nutritious, well-balanced diet is accessible and affordable to all.
It is also crucial that efforts are made across the globe to increase public awareness and understanding of the importance of good nutrition to encourage the adoption of lifestyle and dietary habits that will support cardiovascular health. Reviewing current guidelines could help to achieve this, and providing a consistent approach in the recommendation of cardiovascular health strategies could lead to an increase in the intake of essential micronutrients to help improve cardiovascular health worldwide.
 World Health Organization: Cardiovascular diseases fact sheet, September 2016 http://www.who.int/mediacentre/factsheets/fs317/en/
 Heidereich, P, et al. Forecasting the future of cardiovascular disease in the United States, Circulation. 2011 https://www.ncbi.nlm.nih.gov/ pubmed/21262990
 Factsheet: Cardiovascular disease in China, World Heart Federation, 2016 http://www.world-heart federation.org/fileadmin/user_upload/documents/Fact_sheets/2016/Cardiovascular_diseases_in_China.pdf
 Micha et al, Association between dietary factors and mortality from heart disease, stroke and type 2 diabetes in the United States, J Am Med Soc, 2017, doi:10.1001/jama.2017.0947
 Estruch et al, PREDIMED Study Investigators. N Engl J Med, 2013 Apr 4;368(14):1279-90
 Van Horn et al, Recommended dietary pattern to achieve adherence to the American Heart Association/American College of Cardiology (AHA/ACC). Guidelines: a scientific statement from the AHA, Circulation 2016 https://www.ncbi.nlm.nih.gov/pubmed/27789558
 Gaksch et al, Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26,916 individuals from a European consortium. PLoS One, 2017 Feb 16;12(2):e0170791
 Stark et al, Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016 Jul ;63:132-52
 Perk et al, European Guidelines on cardiovascular disease prevention in clinical practice (version 2012), European Heart Journal 2012 http://eurheartj.oxfordjournals.org/content/33/13/1635.short
 D Colosia, Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review, Diabetes Metab Syndr Obes 2013 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798927/
 Williams CL et al, Dietary patterns and cardiovascular disease, ProcNutr Soc 2013 https://www.ncbi.nlm.nih.gov/pubmed/23953031
 Reedy J et al, Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease and cancer mortality among older adults, J Nutr 2014 https://www.ncbi.nlm.nih.gov/pubmed/24572039
 Stradling C et al, A review of dietary influences on cardiovascular heath: part 2: dietary patterns, Cardiovasc Hematol Disord Drug Targets 2014 https://www.ncbi.nlm.nih.gov/pubmed/24993125
 Mozaffarian et al, Plasma phospholipid long-chain -3 fatty acids and total and cause-specific mortality in older adults: a cohort study, Ann Intern Med 2013, and Arnoldussen et al, Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity, J Nutr Biochem 2016 https://www.ncbi.nlm.nih.gov/pubmed/27012634
 Official Journal of the European Union, 25.2.12, Commission regulation (EU) 432/2012 of 16th May 2012
 Commission Regulation (EU) 536/2013 of 11/06/2013
 Alexander, D, et al. A meta-analysis of randomized controlled trials and prospective cohort studies of eicosapentaenoic and docosahexaenoic long-chain omega-3 fatty acids and coronary heart disease risk, Mayo Clinic Proceedings2017 http://www. mayoclinicproceedings.org/article/S0025 6196%2816%2930681-4/abstract
 Piepoli et al, Authors/Task Force Members. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016 Aug 1;37(29):2315-81
 Rice et al, Conducting omega-3 clinical trials with cardiovascular outcomes: Proceedings of a workshop held at ISSFAL 2014. Prostaglandins Leukot Essent Fatty Acids. 2016;107:30-42
 Siscovick et al, Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation. 2017 Mar 13.
 Zhang et al, Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: dose-response meta-analysis of prospective studies. Am J Clin Nutr. 2017 Mar 1.
 Sigmund et al, Regulation of renin expression and blood pressure by vitamin D(3), J Clin Invest, 2002 https://www.jci.org/articles/view/16160
 Kunutsor et al, Vitamin D and risk of future hypertension: meta-analysis of 283,537 participants, Eur J Epidemiol, 2013 https://www.ncbi.nlm.nih.gov/pubmed/23456138
 Chowdhury et al, Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014 Apr 1;348:g1903
 EFSA, Scientific opinion on the tolerable upper intake limit of vitamin D. EFSA Journal 2012;10:2813
 Rimm et al, Antioxidants for vascular disease, Med Clin North Am, 2000
 Raederstorff et al, Vitamin E function and requirements in relation to PUFA, Br J of Nutrition, 2015
 Ashor et al, Antioxidant vitamin supplementation reduces arterial stiffness in adults: a systematic review and meta-analysis of randomized controlled trials, J Nutr, 2014 http://jn.nutrition.org/content/early/2014/08/06/jn.114.195826
 Block et al, Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young black and white women, Nutr J, 2008 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2621233/
 Carr et al, Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans, Am J of Clin Nutr, 1999 https://www.ncbi.nlm.nih.gov/pubmed/10357726
 Whitehead A, Beck EJ, Tosh S, Wolever TMS, Cholesterol lowering effects of oat b-glucan: a meta analysis of randomized controlled trials’; American Journal of Clinical Nutrition, doi 10.3945/ajcn.114.086108
 Commission Regulation (EU) 1160/2011 of 14/11/2011