December 7992: 407-412

The Effect of Nutritional Prevention of Cardiovascular Diseases on Longevity D. Gonzalez Biosca, M.D., S. Mizushima, M.D., M. Sawamura, Ph.D., M.D., Y. Nara, Ph.D., and Y. Yamori, Ph.D., M.D.

Introduction

In both males and females, life span is negatively related to mortality rates from coronary heart disease (CHD) and stroke. Cardiovascular diseases (CVD) are still the first cause of death, disability, and economic loss in most developed countries. Epidemiological analysis of the relationship between nutrition and CVD shows that societies becoming more affluent are adopting dietary habits similar to those of the industrialized nations, leading to an increase in the prevalence of CHD and other atherosclerotic consequences. Improvement of nutritional habits and other life-style factors would make it possible to avoid this situation. Human nutrition is a complex process, depending on a number of factors, many of which are interrelated, as shown in Figure 1. Ecological and sociocultural factors determine how and what people in different populations eat. Some dietary habits and so-called social habits have been firmly rooted in the culture for centuries, for example, the tradition of drinking green tea in Japan, wine in Mediterranean countries, or “mate” tea in many countries of Latin America. Cigarette smoking is a relatively new habit by comparison. The health status of a population is in part a consequence of nutrition. Modern “disturbances of human culture,” operating from early childhood onward, are responsible for the epidemic of atherosclerotic diseases.’ These “disturbances” include a “rich” diet, associated with elevated blood pressure, serum cholesterol, and body weight, as well as a high prevalence of diabetes, cigarette smoking as a mass habit, and a sedentary life-style. The authors are at the WHO Collaborating Center for Research on Primary Prevention of Cardiovascular Diseases and Department of Pathology, Shimane Medical University, 693 Izumo, Japan; Dr. Biosca is also a member of the Internal Medicine Department, San Carlos University Hospital, 28049, Madrid, Spain. Nutrition Reviews, Vol. 50, No. 72

In developed countries, diseases related to lifestyle-including diet-account for most morbidity and mortality (Figure 2). Total and cardiovascular mortality rates vary considerably among and within countries for both sexes, reflecting in part the variety of life-styles. Japan, the Mediterranean European countries, and Switzerland are on the lowest level of CVD mortality for both sexes. In fact, Japan has the lowest total mortality rate for both men and women. In the upper part of the ranking for both sexes and for total cardiovascular mortality are Hungary, the former Soviet Union, Czechoslovakia, Poland, Bulgaria, and Rumania. Although death rates from CVD have declined in many countries during the last two decades, they remain the first cause of death, disability, and economic loss. Moreover, in some countries, the death rates are increasing, and it is expected that regions of the world that are becoming more affluent will also adopt negative dietary habits and become part of this group.* Life expectancy was low in ancient times and remained low in most countries until the 20th century, when it increased notably in industrialized nations. (In the United States, for example, life expectancy rose over 50% from 1900 to 1980. However, from the 1960s to the 1970s the change was very small: from 69.7 to 70.9.) Life span vanes in different countries, depending on their public health policy (including the quantity and quality of medical services and the control of epidemic, waterborne, and airborne diseases); the nutritional state of the population (degree of access to adequate and balanced diets); social habits (exercise, smoking, alcohol, diet); housing quality; safety from natural or violent disasters; and the level of environmental pollution. Longevity results from a gradual learning of good health practices by the public, the institutionalization of effective public health systems, rigid control over environmental hazards, and adequate medical fa~ilities.~ 407

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Figure 1. Interactions in human nutrition.

Until the 1960s, increases in life expectancy around the world were accomplished by controlling infectious and parasitic diseases. Then a new era began. Control of noncommunicable degenerative diseases of aging is essential for further extending life expectancy in industrialized countries.

Main Risk Factors for Cardiovascular Disease

Atherosclerosis is a multifactorial disease, and genetic and environmental factors are involved in its pathogenesis, with life-style playing a very important role. Hypertension, hypercholesterolemia, and smoking have been recognized as three major risk factors, and many others also seem to be present. More than 200 possible risk factors have been studied; some of these are controver~ial.~ The effect of some combined factors on the pathogenesis of CVD is not additive but exponential, as was demonstrated in the Framingham s t ~ d y . ~ Risk factors interact with genetic predisposition, leading to the development of atherosclerosis and to some of its major events. The fundamental importance of diet in the development of CHD is through its effects on the development of hypercholesterolemia and hypertension. Body weight changes induced by changes in diet and physical activity are strongly related to changes in total serum cholesterol and blood pressure, and obesity is also strongly related to diabetes, a further i-isk factor for CHD. Hypertension is the most important risk factor for ~ t r o k e . Its ~ . ~pathogenesis is considered to be the interaction of genetic and environmental factors such as excessive caloric intake resulting in obesity and high sodium and alcohol intakes. Epidemiological data have shown that elevations in systolic as well as diastolic blood pressures continue to contribute to the risk of such disease end points as stroke, heart attack, congestive heart failure, aortic aneurysms, and renal failure after age 65. Treat408

ment of hypertension also has been shown to be effective in the elderly up to age 80.7 Hypercholesterolemia is a risk factor for CHD and other atherosclerotic diseases. The Seven Countries Study' suggested that, on a population level, total serum cholesterol was strongly related to the incidence of CHD. A strong correlation was also observed between saturated fat intake and total serum cholesterol, suggesting that the interpopulation variation in levels of cholesterolemia could be largely explained by differences in saturated fat intake. In this study,' a strong positive relation was shown between saturated fat intake and the tenyear incidence of CHD. Mediterranean countries with a high intake of total fat derived predominantly from monounsaturated fatty acids (primarily from olive oil) have low rates of CHD. Eskimos, who also have a diet rich in total fat and in n - 3 polyunsaturated fatty acids (mainly derived from marine foods) also have low rates of CHD. In the United States, the reduction in average serum cholesterol level was estimated to account for 30% of the decline in mortality rates for CHD.9 Smoking is the other main risk factor in CVD (smoking is also implicated in certain cancers and in respiratory and other diseases).

The Main Cardiovascular Disease Risk Factors and Nutrition

Three main risk factors-hypertension, hypercholesterolemia, and smoking-are closely related to diet.

Hypertension and Nutrition Blood Pressure and Sodium." There is a strong positive correlation between blood pressure and sodium intake in interpopulation analyses. Hypertension is very rare in populations where sodium intake is low (below 50 mmol/day). A positive, but weaker, correlation is found within some populations but not in others. Salt restriction reduces the dosage requirements of most antihypertensive drugs. It is now recognized from animal experiments that some individuals are "salt-sensitive" and others are "salt-resistant. " Blood Pressure and Potassium. Epidemiologic studies suggest that a relative deficiency of dietary potassium increases the risk of h y p e r t e n ~ i o n . ' ~In .'~ addition, potassium might be protective against cardiovascular morbidity and mortality, independent of its effect on blood p r e ~ s u r e . ' ~ Nutrition Reviews, Vol. 50, No. 12

Rate per 100.000 Population' Hungary Soviet Union Czechoslovakia Poland Bulgaria Romania (84) Scotland No. Ireland Finland Yu slavia Iregd Germany, DR New Zealand (86) EnglandMlales Norway Austria Denmark" United States Germany, FR Sweden Israel 186) Australia. Be1 ium (86) Netzerlands Canada

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Romania (84) Soviet Union Bulgaria Hungary Czec hoslovakia Yu oslavia Potnd Scotland Germany, DR No. Ireland Israel 86) Ireland New Zealand (86) Finland EngIandlWales United States Portugal Austria Greece (86 Belgium (8& Germany, FA Australia Denmark" Italy (86) Norwa Spain r85) Sweden Canada Netherlands Japan Switzerland" France

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Figure 2. Death rates for all causes and cardiovascular diseases (CVD) men (top) and women (bottom) 35-74 years in selected countries, 1987. From World Health Organization (WHO). Rates are adjusted to European standard population.

Blood Pressure and Calcium. Observational data from numerous studies have shown a consistent, although modest, association between higher calcium intake and lower blood pressure.'6 Trials have been inconsistent, h o ~ e v e r . ' ~ Blood Pressure and Prorein. This relationship is not clear epidemiologically, although a blood presNutrition Reviews, Vol. 50,No. 12

sure-lowering effect of fish protein has been demonstrated experimentally.'8 Some epidemiological studies show an inverse correlation between vegetable protein intake and blood pressure," but it is difficult to separate the effects of potassium and dietary fiber. One cross-sectional study in Chinese populations showed an inverse correlation between the urinary taurine:creatinine ratio (a biological 409

marker of fish-protein intake) and systolic blood pressure. Blood Pressure and Alcohol. Alcohol per se has deleterious effects on the heart, apart from the liver, stomach, and nervous system,” and is positively, strongly, and independently correlated with systolic and diastolic blood pressure.20 Hypercholesterolemiaand Nutrition Diets have a major influence on the level of blood cholesterol and the risk of CHD. Diet and Health, a report of the US. National Research Council,21 concluded unequivocally that high levels of saturated fat and cholesterol in the American diet raised blood cholesterol levels and that lowering intake of saturated fat and cholesterol would reduce serum cholesterol levels and CHD rates. Intake of cholesterol is also independently related to the long-term risk of atherosclerotic disease and CHD mortality.22 Saturated fatty acids elevate total serum cholesterol, whereas polyunsaturated fatty acids reduce it;23some monounsaturated fatty acids (e.g., oleic acid) decrease low-density lipoprotein (LDL) cholesterol without decreasing high-density lipoprotein (HDL) c h o l e ~ t e r o l . ~ ~ The dietary factors that affect serum cholesterol tend to cluster together in many diets, making it difficult to assess quantitatively the effects of individual risk factors on the atherosclerosis process. Smoking and Nutrition In a recent study of the dietary habits of smoker^,^' some differences were found that could in part be derived from the taste alterations due to smoking. Further studies are necessary to clarify this finding. It has recently been that hypertension has a direct effect on heart failure and stroke, but it would seem that hypercholesterolemia should be a prerequisite for the development of CHD, while hypertension and smoking accelerate the process. Studies of various populations around the world show that those with lower blood cholesterol levels have lower rates of CHD.8 In some remote areas, where the cholesterol level is lower than 150 mg/dL, no cases of CHD were detected in the adult population.26

crease familiarity with other nations’ eating habits. Therefore, a coordinated Cardiovascular Diseases and Alimentary Comparison Study was proposed to the World Health Organization (WHO) in order to assess the nutritional characteristics of various populations in the world and to analyze their relationship with blood pressure levels and cardiovascular mortality.28 Thus far, the WHO-CARDIAC Study has been carried out in 48 participating centers of 20 countries that have very different dietary customs and different prevalences of and mortality rates for the major CVDs. Findings to date are summarized as follows: Body mass index and blood pressure. Crosscenter analyses showed that body mass index (BMI) was strongly related to both systolic (r = 0.45; p < 0.01) and diastolic (r = 0.48; p < 0.001) blood pressures, so adjustment by BMI was done to assess the relationship between blood pressure and some other variables (Figure 3). Sodium and blood pressure. Salt intake (estimated by 24-hour urinary sodium excretion) was positively related to systolic (r = 0.38; p < 0.001) and diastolic (r = 0.35; p < 0.05) pressures, independently of BMI (Figure 4). Taurine and CHD mortality. The CARDIAC Study confirmed that CHD mortality was positively related to the serum cholesterol level as previously reported by the Seven Countries Study.8 In our preliminary analysis, urinary taurine excretion, which reflects in part the amount of fish and seafood intake, was inversely related to CHD mortality (r = 0.512; p < 0.01). Taurine could be beneficial for health and is postulated to act by at least two mechanisms-decreasing both blood pressure and serum cholesterol levels, two major risk factors for atherosclerosis. lo Moreover, a high seafood intake is usually related to a lower intake of saturated fat and a higher intake of polyunsaturated fatty acids that may intervene

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Worldwide Dietary Patterns and Cardiovascular Disease Risk Factors

Interpopulation differences in dietary habits are rapidly decreasing with accelerating changes in traditional life-styles, due to the widespread use of commercial food products in rural as well as urban areas and to improving communications that in410

Body Mass Index (kg/m’)

Figure 3. Body mass index (BMI) and blood pressure (BP). 0 Systolic blood pressure: y = 1 . 4 1 ~+ 89.42, r = 0.450, ? = 0.203, p < 0.01. 0 Diastolic blood pressure: y = 1 . 1 6 ~+ 47.31, r = 0.479, ? = 0.229, p < 0.001. Nutrition Reviews, Vol. 50, No. 12

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eating more broadly balanced diets than in the past. However, fat intake has increased recently, and more total energy is being consumed. In 1984, the Dietetic Association set up a program to combat these adverse tendencies.

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Dietary Prevention of Cardiovascular Disease

50 100 150 200 250 Adjusted Sodium Excretion (mmoV24h)

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Figure 4. Urinary sodium (Na) excretion and blood pressure (BP). 0 Systolic blood pressure: y = 0 . 0 5 8 ~+ 112.27, r = 0.359, ? = 0.129, p < 0.05. Diastolic blood pressure: y = 0.044~+ 67.21, r = 0.347, ? = 0.121, p < 0.05.

with the progression to atherosclerotic and thrombotic vascular diseases. Cardiovascular Disease, Life Span, and Nutrition

Since CVD is a major cause of mortality in most countries, the average life expectancy of men and women, based on data from WHO,29is also negatively related to mortality rates for CHD and stroke in those countries participating in the WHOCARDIAC Study. Japan has become the country with the world's longest life span. The incidence of stroke, which used to be the major cause of mortality, decreased recently and the mortality from CHD remains at a low level. Socioeconomic development over the last 30 years, accompanied by an improvement in the diet of the Japanese population as a whole, could be the cause of these favorable changes." A decrease in daily rice intake by about 140 g together with an increase in meat and milk consumption as well as an unchanged average intake of fish, as shown in Figure 5 , indicates that the Japanese are

Figure 5. Changes in daily per capita intakes of foods in Japan. From WHO, 1990.' Nutrition Reviews, Vol. 50, No. 12

Atherosclerosis has its origins in childhood or early adult life.' Therefore, the ideal is to start prevention at a young age. Obviously, the ideal is not always possible, and secondary prevention also has much to offer, by both reducing the risk of reinfarction in an individual patient and making a major contribution to reducing the overall burden of CHD in the population.30 Two recent nonpharmacological intervention trials show that secondary prevention is also effective, even in the elderly and within short periods of Several epidemiological studies showed that treatment alters the natural history of atherosclerotic lesions: progression of lesions can be slowed and existing lesions can regress. Dietary interventions to control total cholesterol and LDL cholesterol are beneficial." A therapeutic as well as a preventive approach to atherosclerosis in its various manifestations must be multifactorial at any age. Attention must be paid to lifestyle factors, such as smoking, drinking alcohol, diet, physical activity, and stress, as well as to personal and familial background and the existence of other diseases or disorders. Conclusions

The role of diet in the pathogenesis of CVD is mediated through the effect of dietary factors on the development of hypertension and hypercholesterolemia, other major risk factors of CVD. Thus, nutritional measures are useful in primary and secondary prevention of CVD, together with control of other risk factors, such as smoking. Mortality rates from CVD are inversely related to average life expectancy. Therefore, population (if not always individual) longevity can be achieved by controlling CVD through improvement of nutritional and other major risk factors. WHO Technical Report. Prevention in childhood and youth of adult CVD: time for action. Report of a WHO Expert Committee. Technical Report Series 792. Geneva: World Health Organization, 1990 National Heart, Lung and Blood Institute, US Department of Health and Human Services. International activities report, fiscal year 1989. Washington, DC: US Government Printing Office, 1990 411

3. Bogue DJ. Life expectancy. Chicago, IL: Encyclopedia Americana, vol. 17, 1987:426-7 4, Balaguer-Vintro I, Sans S. Coronary heart disease mortality trends and related factors in Spain. Cardiology 1985;72:97-104 5. Kannel WB. Role of blood pressure in cardiovascular morbidity and mortality. Prog Cardiovasc Dis 1974;17:5-24 6. Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D. Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men. Lancet 1986;2:933-6 7. Viscoli CM, Ostfeld A. Epidemiology of hypertension in the elderly. In: Laragh JH, Brenner BM, eds. Hypertension: pathology, diagnosis, and management. New York: Raven Press, 1990:191-

dietary prevention of cardiovascular diseases in animal models and epidemiologic evidence for the applicability in man. In: Yamori Y, Lenfant C, eds. Prevention of cardiovascular diseases and approach to active long life. Orlando, FL: Academic Press, 1987 19. Joffres MR, Reed DM, Yano K. Relationship of magnesium intake and other dietary factors to blood pressure: the Honolulu heart study. Am J Clin Nutr 1987;45:469-75 20. Schuckit MA. Alcohol and alcoholism. In: Wilson JD, ed. Harrison’s principles of internal medicine, 12th ed., vol 2. New York: McGraw-Hill, 1991:

21 46-51 21. Criqui MH, Langer RD, Reed DM. Dietary alcohol, calcium, and potassium. Independent and combined effects on blood pressure. Circulation 1989;

202 8. Keys AB. Seven countries: a multivariate analysis of death and coronary heart disease. Cambridge, MA: Harvard University Press, 1980 9. Goldman L, Cook EF. The decline in ischemic heart disease mortality rates. An analysis of the comparative effects of medical interventions and changes in lifestyle. Ann Intern Med 1984;lOl: 825-36 10. Fielding JE. Smoking: health effects and control, I. N Engl J Med 1985;313:491-8 1 1 . Simpson OF. Blood pressure and sodium intake. In: Laragh JH, Brenner BM, eds. Hypertension: pathophysiology, diagnosis, and management. New York: Raven Press, 1990 12. Kawasaki T, Delea CS, Bartter FC, Smith H. The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 1978;64:193-8 13. Rose G, Stamler J. The INTERSALT study: background, methods and main results. INTERSALT cooperative research group. J Hum Hypertens 1989;3:283-8 14. US Department of Health, Education and Welfare. Blood pressure of persons 16-74 years. United States, 1972. National health survey, National Centers for Health Statistics series 1 1 , number 150. Washington DC: US Government Printing Office, 1975 15. Shaw KT, Barrett-Connor E. Dietary potassium and stroke-associated mortality: a 12-year prospective population study. N Engl J Med 1987;316: 235-40 16. Harlan WR, Narlan LC. Blood pressure and calcium and magnesium intake. In: Laragh JH, Brenner BM, eds. Hypertension: pathophysiology, diagnosis, and management. New York: Raven Press, 1990 17. McCarron DA, Holly JH, Morris CD. Human nutrition and blood pressure regulation: an integrated approach. Hypertension 1982;4(suppl. 111):S2-13 18. Yamori Y, Horie R, Nara Y, et al. Pathogenesis and

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cations for reducing chronic disease risk. Washington DC: National Academy Press, 1989 Grundy SM. Cholesterol and coronary heart disease. Future directions. Scand J Clin Lab Invest (SU ppl) 1990;1 99 :1 7-24 Montgomery R, Conway TW, Spector AA. Cholesterol. In: Montgomery R, ed. Biochemistry: a caseoriented approach, 5th ed. St. Louis: Mosby, 1990 Oya M, Mata P, Garrido JA, et al. Olive oil in human nutrition: a review. CVRF May 1991 :270-6 Subar AF, Harlan LC, Mattson ME. Food and nutrient intake differences between smokers and non-smokers in the US. Am J Public Health 1990;

80:1323-29 27. Roverts WC. Atherosclerotic risk factors-Are there ten or is there only one? Am J Cardiol 1989; 64:552-4 28. Arzenius AC. Hypertension, cholesterol and coronary heart disease. CVRF 1990;1:107-15 29. CARDIAC Study Group. Hypertension and biolog-

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