September 2019 Issue

Stroke in Younger Adults — Strategies for Counseling Clients
By Jamie Santa Cruz
Today’s Dietitian
Vol. 21, No. 9, P. 26

Actor Luke Perry, known for his starring role as Dylan McKay on the hit TV series Beverly Hills, 90210, was just 52 when he died following an ischemic stroke in March 2019. John Singleton, director of the Oscar-nominated movie Boyz n the Hood, was even younger—only 51—when he died of a stroke one month later. Olympic track legend Michael Johnson escaped death when he suffered a stroke the previous year at the age of 50, but Johnson spent months in rehabilitation and has some residual numbness on the left side of his body.1 This string of recent high-profile stroke victims dramatically illustrates what a series of research studies have shown in recent years: “younger” adults—those in their 50s, 40s, and even 30s—aren’t immune to stroke.

In fact, the incidence of stroke in younger adults appears to be increasing. According to a 2017 report, the rate of young adults aged 35–44 who were hospitalized in the United States for ischemic stroke rose 35.6% between 2003 and 2012.2 The rate also increased substantially in the 18–34 age group (by 27.3%) and in the 45–54 age group (by 20.5%). The reasons for the increase are still somewhat unclear,3 but previous research suggests the rate of stroke among younger adults in the United States has been rising at least since the mid 1990s,2 and the trends are similar in other countries.4 This increase in stroke among younger adults has occurred even as stroke has been decreasing among older adults.3

Stroke Types and Causes
The most common form of stroke is ischemic stroke, which involves the blockage of a large blood vessel leading to the brain and accounts for about 87% of all strokes.5 In high-income countries, approximately one-fourth of ischemic strokes occur in individuals of working age, and about 10% occur in individuals younger than age 50.3 The other major type of stroke, hemorrhagic stroke, occurs when a blood vessel ruptures and begins bleeding into the brain. Although hemorrhagic strokes disproportionately affect younger individuals, they’re less common overall.6

The causes of stroke are different in younger than in older adults. In many cases, the cause of stroke in younger adults is unknown, and this is especially true of stroke in adults younger than 30.3 In instances where the cause is known, stroke in younger individuals sometimes results from genetic factors, such as heart valve abnormalities or congenital holes in the heart (such conditions can cause stroke in older adults, but they account for a higher percentage of stroke in younger adults).7 According to Mitchell Elkind, MD, MS, a professor of neurology and epidemiology at Columbia University Vagelos College of Physicians and Surgeons and president-elect of the American Heart Association, stroke in younger adults also can occur as the result of trauma, including relatively minor sports-related injuries such as those sustained in windsurfing, wrestling, or kickboxing.

Stroke also may be related to modifiable lifestyle factors. The blockages that cause ischemic stroke usually are the result of atherosclerosis, a hardening of the arteries that can occur from having high blood pressure, smoking, diabetes, abnormal cholesterol, physical inactivity, and obesity. Traditionally, atherosclerosis and modifiable lifestyle factors have been thought to be more relevant to stroke in older adults, but they’re becoming a greater concern in young adult stroke.3 Among men and women aged 18–64 who were hospitalized for acute ischemic stroke, the percentage of individuals with at least three of the five most common stroke risk factors (all modifiable) nearly doubled between 2003 and 2012.2

“We know that the prevalence of high blood pressure has gone up over time among [younger adult stroke] patients,” says Mary G. George, MD, MSPH, deputy associate director for science and senior medical officer at the Centers for Disease Control and Prevention’s Division for Heart Disease and Stroke Prevention. “We know that tobacco use has gone up over time. We know that obesity has increased over time, and we know that having high cholesterol has increased over time. We can’t say necessarily that those risk factors caused their stroke, but we know that more younger people are having those risk factors.”

The Role of Ethnicity and Sex
Some ethnic groups have a higher risk of young stroke than others. “African Americans are hit the hardest,” George says. Black Americans have a genetic predisposition to salt retention, which increases their risk of hypertension, one of the most important stroke risk factors, particularly for intracerebral hemorrhage. The ethnic disparity in stroke rates between black and white Americans is most significant in middle age: Among adults aged 45–54, the risk of stroke is four times higher for blacks than for whites.8

The relative risk of stroke for men vs women varies based on age. In childhood and in older age, stroke is more common among males, but in the younger adult years, risk between the two sexes is more equal, and some research suggests that younger women may be at a slightly greater risk than younger men.3 “As people get into their late teens and twenties, hormonal factors seem to increase risk of stroke in women. Pregnancy, for example, is a stroke risk factor in women, and possibly some hormonal therapies as well,” Elkind says.

Diet and Stroke Prevention
Lifestyle choices play a large role in stroke risk. Multiple studies have shown that engaging in five specific healthful lifestyle behaviors—not smoking, moderate alcohol intake, a normal BMI/waist circumference, moderate physical exercise, and a healthful diet—is collectively associated with a 60% to 80% reduction in stroke risk.9-11 Diet in particular plays a key role in stroke risk, and suboptimal diet has been estimated to be a factor in ~52% of stroke deaths in the United States.12 The following is a discussion on how fruits and vegetables, nuts, chocolate, dairy, eggs, meat, and certain beverages play a role in stroke risk.

Fruits and Vegetables
Prospective studies consistently show that higher fruit and vegetable consumption is associated with reduced stroke risk.13,14 In one meta-analysis, consumption of each additional 200 g/day of total fruits was associated with a 16% lower risk of stroke, and consumption of each additional 200 g/day of total vegetables was associated with a 13% lower risk.14 The benefits of fruits and vegetables for stroke risk can’t be attributed to any one individual component but are probably due to the array of nutrients and phytochemicals (including fiber, carotenoids, antioxidants, potassium, flavonoids) in these plant foods, which act both separately and synergistically through various mechanisms to reduce cardiovascular risk. Fiber, for instance, is known to reduce cholesterol, blood pressure, and inflammation while improving immune function. Specific vitamins and minerals found in fruits and vegetables, such as magnesium, potassium, and vitamin C, all have been linked to reduced blood pressure, among other benefits.12 And antioxidants in fruits and vegetables reduce oxidative damage and protect against destructive DNA mutations.15

A large body of evidence suggests that nut consumption reduces risk of coronary heart disease and mortality, but whether it lowers stroke risk has been less clear. Several reviews and meta-analyses failed to find any association between nut consumption and stroke risk.16,17 However, many other recent reviews and meta-analyses have concluded that nuts may indeed be protective against stroke.18-21 In a 2017 prospective study that included three large cohorts, total nut consumption wasn’t associated with stroke risk, but higher intake of peanuts and walnuts in particular was associated with reduced likelihood of stroke.22

Chocolate is rich in flavonoids, which are known for their antioxidant and anti-inflammatory effects. Randomized controlled trials suggest that chocolate consumption has beneficial (albeit moderate) effects on several factors relevant to stroke risk, including blood pressure, endothelial function, and insulin resistance.23 Separate meta-analyses have found that higher chocolate consumption is associated with a 19% to 21% lower risk of stroke.24,25

Globally, not much consensus exists on the role dairy products play in CVD. A 2016 review of dairy and stroke risk found a nonlinear association of stroke risk with milk intake, with the lowest risk being observed at 125 g/day. However, there was significant heterogeneity in the designs of the studies included in the review, and milk consumption was associated with reduced stroke risk in Asia but not in Europe or the United States.26 A 2017 systematic review and meta-analysis found no relation between consumption of dairy products and stroke, except in the case of cheese, where higher consumption was associated with a 7% decrease in risk.27 A review article on dietary approaches for stroke prevention concluded there’s minimal evidence for either harmful or beneficial impacts of dairy intake on stroke risk.12

There has been substantial controversy in the last few decades over the role eggs may play in CVD and stroke risk. Because of their high cholesterol content, in the past eggs were blamed for causing CVD. However, a 2016 meta-analysis of seven studies found that higher egg intake was associated with a 12% decreased risk of stroke compared with lower intake,28 and since then other large prospective studies in various countries likewise have found that eggs are associated with either a neutral or beneficial impact on stroke risk.29,30

However, the evidence isn’t uniform. A prospective study of Greek adults with diabetes found that eating one egg per day was associated with a five-fold increased risk of death from coronary events.31 In 2019, an analysis of almost 30,000 adults pooled from six prospective cohort studies across the United States found that each additional 300 mg of cholesterol intake per day increased the risk of CVD by 17%, and each additional half egg consumed daily increased the risk of CVD by 6% and the risk of all-cause mortality by 8%. Importantly, cholesterol intake was more strongly associated with stroke than with heart disease.32

Regarding the inconsistencies in research on eggs, J. David Spence, MD, MBA, a professor of neurology and clinical pharmacology at the University of Western Ontario, observes that most of the studies touting the healthfulness of eggs have been funded by the egg industry, drawing into question the reliability of the findings. Spence also argues that multiple egg studies have either failed to measure confounders or have overadjusted for those confounders. Speaking of one influential recent study that found a beneficial impact of eggs on stroke risk in Chinese adults,33 Spence explains, “The study participants who ate eggs were younger, they were almost twice as likely to be urban residents, they had a higher education, they had higher income, they were less likely to be smokers, and they were five times as likely to be affluent. So there were lots of confounding factors in that study that could explain the differences they observed.” According to Spence, consumption of eggs (specifically, egg yolks) remains a cause for concern for people at risk of stroke.34 Not only are the yolks high in cholesterol, but consumption of egg yolks also results in the production in the liver of trimethylamine N-oxide (TMAO), a major newly recognized independent risk factor for atherosclerosis.35,36

A growing body of evidence shows that consumption of red meat increases stroke risk, and that the risk is especially high with processed meats. A 2017 meta-analysis found that higher consumption of red and processed meats was associated with an 11% and 17% higher risk of stroke, respectively. Higher total meat consumption, meanwhile, was associated with an 18% higher risk of stroke.37 These findings are consistent with multiple previous meta-analyses, all of which found that red meat consumption was associated with increased stroke risk.38-40 Of particular concern is the fact that red meat is high in carnitine, a major source of atherosclerosis-promoting TMAO.41 Processed meats also contain added sodium, which increases blood pressure, as well as nitrite preservatives, which appear to promote atherosclerosis and vascular dysfunction while decreasing insulin secretion.38

Conversely, coffee and tea are both significant sources of phenolic compounds, including chlorogenic acids, which moderately lower blood pressure.12 The two beverages have been associated in separate meta-analyses with a 17% to 18% reduction in stroke risk (in the case of coffee, the association was nonlinear, and the greatest reduction in risk was seen with consumption of three to four cups per day).42,43 In small to moderate amounts, alcohol is associated with reduced risk of stroke, but in larger quantities, it’s linked with increased risk.44 Because of its association with violence, accidents, and certain diseases (including cardiomyopathy, arrhythmias, liver disease, and certain cancers), consuming alcohol isn’t recommended as a method of lowering stroke risk.12

Mediterranean and DASH Diets
The most-studied dietary pattern for reduction of stroke risk is the Mediterranean diet, a largely plant-based diet high in fruits, vegetables, unrefined cereals, nuts, and olive oil, with moderate amounts of fish and poultry and very low amounts of whole-fat dairy products, red/processed meats, and sweets.45

The evidence isn’t uniform,46 but an array of observational studies do suggest that adherence to the Mediterranean diet is associated with significant reduction in stroke risk.47-51 Observational studies can’t show cause and effect, but two major randomized controlled trials have shown such a cause-and-effect relationship. In the Lyon Diet Heart Study, patients recovering from a myocardial infarction were randomized either to a control group, where they were advised to follow a low-fat diet, or to a Mediterranean-type diet. The Mediterranean-type diet used in this study deviated from the traditional Mediterranean diet in that it made use of a special margarine rather than the olive oil characteristic of a traditional Mediterranean diet. Nevertheless, those on the Mediterranean-type diet in the Lyon study saw a greater than 70% reduction in their risk of additional cardiovascular events and stroke over the subsequent four years.52

In the second trial, the Spanish Primary Prevention of Cardiovascular Disease with a Mediterranean Diet, or PREDIMED, study, 7,447 participants without a history of CVD were assigned either to a low-fat diet or one of two Mediterranean diets—one fortified with mixed nuts and the other fortified with olive oil. Participants on both versions of the Mediterranean diet had a 30% lower risk of major cardiovascular events than those on the low-fat diet over five years. This study was later criticized for methodological problems, but a reanalysis correcting the methodological issues confirmed the initial results.53

In contrast with the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet emphasizes high consumption of fruits, vegetables, and low-fat dairy alongside moderate amounts of whole grains, fish, poultry, and nuts. A randomized controlled trial of 459 adults found that consumption of the DASH diet significantly reduced both systolic and diastolic blood pressure compared with a control diet that was lower in fruits and vegetables and higher in fat.54 Prospective studies also have shown that high adherence to the DASH diet has a protective effect against stroke.55,56

Counseling Strategies for Dietitians
Given this research, dietitians should consider discussing the following talking points for stroke prevention with young adult clients and patients:

Stress the value of diet. In a 2017 analysis, suboptimal diet was associated with a higher proportional risk of cardiometabolic mortality for younger adults than for older adults.57 “With the younger adults, sometimes they feel more invincible and they don’t think that they need to make changes until they get much older—to that age range of over 65. But they definitely should start a lot sooner,” says Jerlyn Jones, MS, MPA, RDN, LD, a spokesperson for the Academy of Nutrition and Dietetics.

Focus first on fruit and vegetable intake. In one comparative analysis of individual dietary components associated with increased risk of stroke mortality, the single largest factors were low fruit and vegetable consumption, followed by excess sodium intake.57 Meanwhile, intake of 800 g/day of fruits and vegetables has been associated with a 33% reduction in stroke risk.14 “We can’t stress filling your plate with fruits and vegetables enough,” Jones says. “All the other lifestyle changes are important too, but I would say focus on fruits and vegetables.”

Watch sodium levels. Jones generally avoids emphasizing individual nutrients and aims instead to keep the focus on whole foods and overall dietary patterns. But sodium is the exception. “Sodium reduction is considered a key health strategy in reducing the risk of stroke,” since it’s so strongly connected to blood pressure, Jones says.46,58 The American Heart Association recommends consuming no more than 2,300 mg of sodium per day (equivalent to one teaspoon of salt).

Recommend a Mediterranean diet pattern. Bear in mind, Spence says, that although the Mediterranean diet allows for consumption of some fish and poultry, it’s a mainly vegetarian diet, and patients should be encouraged to move toward a plant-based eating pattern. “You should limit intake of animal flesh,” especially red meat, he says. “What I ask my patients to do is go meatless three days per week.”

Discuss other healthful behaviors. According to George, diet is “one key strategy” for stroke prevention, but it’s still just one of several crucial healthful behaviors. Other aspects of lifestyle behaviors that strongly influence stroke risk include physical activity, alcohol consumption, drug use, and smoking.

— Jamie Santa Cruz is a health and medical writer in Parker, Colorado.

1. A stroke slowed Olympic legend Michael Johnson. Responding F.A.S.T. sped his recovery. American Heart Association website. Published May 1, 2019.

2. George MG, Tong X, Bowman BA. Prevalence of cardiovascular risk factors and strokes in younger adults. JAMA Neurol. 2017;74(6):695-703.

3. Putaala J. Ischemic stroke in the young: current perspectives on incidence, risk factors, and cardiovascular prognosis. Eur Stroke J. 2016;1(1):28-40.

4. Ekker MS, Verhoeven JI, Vaartjes I, van Nieuwenhuizen KM, Klijn KJM, de Leeuw FE. Stroke incidence in young adults according to age, subtype, sex, and time trends. Neurology. 2019;92(21).

5. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics — 2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67-e492.

6. Singhal AB, Biller J, Elkind MS, et al. Recognition and management of stroke in young adults and adolescents. Neurology. 2013;81(12):1089-1097.

7. Mandalenakis Z, Rosengren A, Lappas G, Eriksson P, Hansson PO, Dellborg M. Ischemic stroke in children and young adults with congenital heart disease. J Am Heart Assoc. 2016;5(2):e003071.

8. Spence JD, Rayner BL. Hypertension in blacks: individualized therapy based on renin/aldosterone phenotyping. Hypertension. 2018;72(2):263-269.

9. Chiuve SE, Rexrode KM, Spiegelman D, Logroscino G, Manson JE, Rimm EB. Primary prevention of stroke by healthy lifestyle. Circulation. 2008;118(9):947-954.

10. Larsson SC, Akesson A, Wolk A. Healthy diet and lifestyle and risk of stroke in a prospective cohort of women. Neurology. 2014;83(19):1699-1704.

11. Akesson A, Larsson SC, Discacciati A, Wolk A. Low-risk diet and lifestyle habits in the primary prevention of myocardial infarction in men: a population-based prospective cohort study. J Am Coll Cardiol. 2014;64(13):1299-1306.

12. Larsson SC. Dietary approaches for stroke prevention. Stroke. 2017;48(10):2905-2911.

13. Hu D, Huang J, Wang Y, Zhang D, Qu Y. Fruits and vegetables consumption and risk of stroke: a meta-analysis of prospective cohort studies. Stroke. 2014;45(6):1613-1619.

14. Aune D, Giovannucci E, Boffetta P, et al. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality — a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol. 2017;46(3):1029-1056.

15. Lampe JW. Health effects of vegetables and fruit: assessing mechanisms of action in human experimental studies. Am J Clin Nutr. 1999;70(Suppl 3):475S-490S.

16. Shi ZQ, Tang JJ, Wu H, Xie CY, He ZZ. Consumption of nuts and legumes and risk of stroke: a meta-analysis of prospective cohort studies. Nutr Metab Cardiovasc Dis. 2014;24(12):1262-1271.

17. Schwingshackl L, Hoffmann G, Missbach B, Stelmach-Mardas M, Boeing H. An umbrella review of nuts intake and risk of cardiovascular disease. Curr Pharm Des. 2017;23(7):1016-1027.

18. Shao C, Tang H, Zhao W, He J. Nut intake and stroke risk: a dose-response meta-analysis of prospective cohort studies. Sci Rep. 2016;6:30394.

19. Bitok E, Sabaté J. Nuts and cardiovascular disease. Prog Cardiovasc Dis. 2018;61(1):33-37.

20. Zhang Z, Xu G, Wei Y, Zhu W, Liu X. Nut consumption and risk of stroke. Eur J Epidemiol. 2015;30(3):189-196.

21. Aune D, Keum N, Giovannucci E, et al. Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies. BMC Med. 2016;14(1):207.

22. Guasch-Ferré M, Liu X, Malik VS, et al. Nut consumption and risk of cardiovascular disease. J Am Coll Cardiol. 2017;70(20):2519-2532.

23. Larsson SC. Coffee, tea, and cocoa and risk of stroke. Stroke. 2014;45(1):309-314.

24. Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke: a prospective cohort of men and meta-analysis. Neurology. 2012;79(12):1223-1229.

25. Kwok CS, Boekholdt SM, Lentjes MA, et al. Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women. Heart. 2015;101(16):1279-1287.

26. de Goede J, Soedamah-Muthu SS, Pan A, Gijsbers L, Geleijnse JM. Dairy consumption and risk of stroke: a systematic review and updated dose-response meta-analysis of prospective cohort studies. J Am Heart Assoc. 2016;5(5):e002787.

27. Gholami F, Khoramdad M, Shakiba E, Alimohamadi Y, Shafiei J, Firouzi A. Subgroup dairy products consumption on the risk of stroke and CHD: a systematic review and meta-analysis. Med J Islam Repub Iran. 2017;31:25.

28. Alexander DD, Miller PE, Vargas AJ, Weed DL, Cohen SS. Meta-analysis of egg consumption and risk of coronary heart disease and stroke. J Am Coll Nutr. 2016;35(8):704-716.

29. Qin C, Lv J, Guo Y, et al. Associations of egg consumption with cardiovascular disease in a cohort study of 0.5 million Chinese adults. Heart. 2018;104(21):1756-1763.

30. Abdollahi AM, Virtanen HEK, Voutilainen S, et al. Egg consumption, cholesterol intake, and risk of incident stroke in men: the Kuopio Ischaemic Heart Disease Risk Factor Study [published online May 16, 2019]. Am J Clin Nutr. doi: 10.1093/ajcn/nqz066.

31. Trichopoulou A, Psaltopoulou T, Orfanos P, Trichopoulos D. Diet and physical activity in relation to overall mortality amongst adult diabetics in a general population cohort. J Intern Med. 2006;259(6):583-591.

32. Zhong VW, Van Horn L, Cornelis MC, et al. Associations of dietary cholesterol or egg consumption with incident cardiovascular disease and mortality. JAMA. 2019;321(11):1081-1095.

33. Spence JD, Jenkins D. Cardiovascular benefit of egg consumption is most unlikely. Heart. 2018;104(21):1805-1806.

34. Spence JD. Nutrition and risk of stroke. Nutrients. 2019;11(3):E647.

35. Bogiatzi C, Gloor G, Allen-Vercoe E, et al. Metabolic products of the intestinal microbiome and extremes of atherosclerosis. Atherosclerosis. 2018;273:91-97.

36. Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575-1584.

37. Kim K, Hyeon J, Lee SA, et al. Role of total, red, processed, and white meat consumption in stroke incidence and mortality: a systematic review and meta-analysis of prospective cohort studies. J Am Heart Assoc. 2017;6(9):e005983.

38. Kaluza J, Wolk A, Larsson SC. Red meat consumption and risk of stroke: a meta-analysis of prospective studies. Stroke. 2012;43(10):2556-2560.

39. Yang C, Pan L, Sun C, Xi Y, Wang L, Li D. Red meat consumption and the risk of stroke: a dose-response meta-analysis of prospective cohort studies. J Stroke Cerebrovasc Dis. 2016;25(5):1177-1186.

40. Chen GC, Lv DB, Pang Z, Liu QF. Red and processed meat consumption and risk of stroke: a meta-analysis of prospective cohort studies. Eur J Clin Nutr. 2013;67(1):91-95.

41. Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576-585.

42. Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies. Am J Epidemiol. 2011;174(9):993-1001.

43. Zhang C, Qin YY, Wei X, Yu FF, Zhou YH, He J. Tea consumption and risk of cardiovascular outcomes and total mortality: a systematic review and meta-analysis of prospective observational studies. Eur J Epidemiol. 2015;30(2):103-113.

44. Larsson SC, Wallin A, Wolk A, Markus HS. Differing association of alcohol consumption with different stroke types: a systematic review and meta-analysis. BMC Med. 2016;14(1):178.

45. Martínez-González MA, Gea A, Ruiz-Canela M. The Mediterranean diet and cardiovascular health. Circ Res. 2019;124(5):779-798.

46. Khan SU, Khan MU, Riaz H, et al. Effects of nutritional supplements and dietary interventions on cardiovascular outcomes: an umbrella review and evidence map [published online July 9, 2019]. Ann Intern Med. doi: 10.7326/M19-0341.

47. Knoops KT, de Groot LC, Kromhout D, et al. Mediterranean diet, lifestyle factors and 10-year mortality in elderly European men and women: the HALE project. JAMA. 2004;292(12):1433-1439.

48. Rosato V, Temple NJ, La Vecchia C, Castellan G, Tavani A, Guercio V. Mediterranean diet and cardiovascular disease: a systematic review and meta-analysis of observational studies. Eur J Nutr. 2019;58(1):173-191.

49. Paterson KE, Myint PK, Jennings A, et al. Mediterranean diet reduces risk of incident stroke in a population with varying cardiovascular disease risk profiles. Stroke. 2018;49(10):2415-2420.

50. Misirli G, Benetou V, Lagiou P, Bamia C, Trichopoulos D, Trichopoulou A. Relation of the traditional Mediterranean diet to cerebrovascular disease in a Mediterranean population. Am J Epidemiol. 2012;176(12):1185-1192.

51. Chen GC, Neelakantan N, Martín-Calvo N, et al. Adherence to the Mediterranean diet and risk of stroke and stroke subtypes. Eur J Epidemiol. 2019;34(4):337-349.

52. Renaud S, de Lorgeril M, Delaye J, et al. Cretan Mediterranean diet for prevention of coronary heart disease. Am J Clin Nutr. 1995;61(6 Suppl):1360S-1367S.

53. Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378(25):e34.

54. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336(16):1117-1124.

55. Larsson SC, Wallin A, Wolk A. Dietary approaches to stop hypertension diet and incidence of stroke: results from 2 prospective cohorts. Stroke. 2016;47(4):986-990.

56. Kontogianni MD, Panagiotakos DB. Dietary patterns and stroke: a systematic review and re-meta-analysis. Maturitas. 2014;79(1):41-47.

57. Micha R, Peñalvo JL, Cudhea F, Imamura F, Rehm CD, Mozaffarian D. Association between dietary factors and mortality from heart disease, stroke, and type 2 diabetes in the United States. JAMA. 2017;317(9):912-924.

58. Aburto NJ, Ziolkovska A, Hooper L, Elliott P, Cappuccio FP, Meerpohl JJ. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ. 2013;346:f1326.