Chapter 13 : Dietary fat, hypertension and stroke
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Cholesterol and total fat
While salt intake and obesity have been related to hypertension, studies on the possible roles of dietary fat in the regulation of blood pressure and the pathogenesis of hypertension have shown many inconsistent results (Beilin, 1987; Sacks, 1989; Iacono and Dougherty, 1993).
Cholesterol and total fat
In stroke-prone, spontaneously hypertensive rats, cholesterol-rich, high-fat diets decreased blood pressure and decreased the incidence of stroke (Yamori, 1977). This may be due to the attenuation of vascular activity (Yamori, 1981). Epidemiological data are generally consistent with the animal experiments, they indicate that diets which are very low in fat increase the occurrence of some forms of stroke (Jacobs et al., 1992). Societies with a low intake of fat and animal protein, such as traditional Japan, tend to have high rates of haemorrhagic stroke. An elevated risk of stroke is found among segments of the Japanese population with low levels of serum cholesterol, particularly among those with high blood pressure (Komachi et al., 1976). In a large, screened population of men in the USA, those with the lowest serum cholesterol levels had an elevated risk of haemorrhagic stroke, even though the risks of ischemic stroke, coronary heart disease and total cardiovascular disease were positively and linearly related to serum cholesterol (Kagan, Popper and Rhoads, 1980; Iso et al., 1989). While not proving causality, the rates of stroke have declined greatly in Japan since the early 1950s, during which time the amount of fat consumed increased from about 10 percent to 25 percent of total dietary energy. This increase was due primarily to the greater consumption of animal fat.
A number of large epidemiological studies (Kay, Sabry and Csima, 1980; Salonen, Tuomilehto and Tanskanen, 1983; Khaw and garret-Conner, 1984; Gruchow, Sobocinsky and Barboriak, 1985; Elliott et al., 1987; Joffres, Reed and Yano, 1987) did not find any association between blood pressure and either dietary fat or cholesterol. Only one epidemiological study of Japanese immigrants living in Hawaii showed that blood pressure fell with an increase in total dietary fat and cholesterol (Reed et al., 1985). The WHO CARDIAC cross-sectional study, which was conducted on a world-wide basis, demonstrated a significant positive correlation between serum cholesterol levels and diastolic blood pressure (Yamori et al., 1993). Although there are methodological limitations in determining the effect of dietary fat on hypertension, the current evidence indicates that chronic elevation of plasma cholesterol is associated with higher diastolic blood pressure, probably as a result of atherosclerotic vascular changes.
Saturated fat and monounsaturated fatty acids. Two dietary surveys carried out in Finland showed a significant inverse association between the intakes of saturated fat and blood pressure (Salonen, Tuomilehto and Tanskanen, 1983; Salonen et al., 1988), however, many other studies found no such association (Gruchow, Sobocinski and Barboriak, 1985; Elliott et al., 1987; Joffres, Reed and Yano, 1987; Williams et al., 1987; Rubba et al., 1987). In several populations studied, the level of saturated fatty acids in the adipose tissue tended to be inversely related to blood pressure (Riemersma et al., 1986; Hudgins, Hirsch and Emken, 1991).
Controlled trials testing the effect of various dietary monounsaturated fatty acids showed no significant effects (Mensink, Janssen and Katan, 1988; McDonald et al., 1989).
Polyunsaturated fatty acids. Regulation of blood pressure is impaired in animals which are deficient in linoleic acid. When such animals were made hypertensive by 9 days of drinking saline, the addition of linoleic acid to the diet normalized blood pressure despite the continued administration of saline (Cox et al., 1982). When there is no deficiency, linoleic acid has little effect on blood pressure in animals (Smith-Barbaro et al., 1980; McGregor, Morazain and Renaud, 1981; Mogenson and Box, 1982; Tobian et al., 1982; Singer et al., 1990; Shimamura and Wilson, 1991).
The results of human cross-sectional studies provide little evidence of an effect of n-6 fatty acid intake on blood pressure. The National Health and Nutrition Examination Surveys (NHANES) of adults in the USA indicated that the nutritional factor most strongly and consistently related to blood pressure was body mass index (Harlan et al., 1984); serum calcium was related directly and serum phosphorus was related indirectly to systolic blood pressure. The study failed to show any relationship between diastolic blood pressure and dietary fats. In general, intakes of fatty acids and total fat, as determined by dietary histories, are not significantly correlated with blood pressure (Sacks, 1989). Moreover, there is little convincing evidence that the amount or type of dietary fat has an effect in persons with normal or mildly elevated blood pressure. Cross-sectional population studies are often confounded by the complexity of dietary and other life-style differences. The NI-HON-SAN study found that fat provided 15 percent of energy intake in Japan. Among ethnic Japanese in Hawaii and San Francisco, energy intakes from fats were 33 percent and 38 percent, respectively. The differences were mainly due to intakes of saturated fat (Kagan, Marmot and Kato, 1980). Blood cholesterol levels paralleled fat intake among all three groups. While blood pressures were similar in studies in Japan and Hawaii, they were higher in San Francisco. The prevalence of stroke, hypertension, hypertensive heart disease and left ventricular hypertrophy were higher in Japan than in the other two populations, possibly because of the higher intake of salt and alcohol and the lower intake of protein.
The ratio of polyunsaturated fat to saturated fat is generally higher in vegetarians than in non-vegetarians. The consumption of food of animal origin has been found to be highly correlated with both systolic and diastolic blood pressures (Sacks, Rosner and Kass, 1974). Vegetarian Seventh-Day Adventists in western Africa had lower blood pressures than non-vegetarians and showed a gradient of increasing blood pressure with increasing egg consumption (Armstrong, van Merwyk and Coates, 1977). With a lacto-ovo-vegetarian diet, normotensive persons showed a lowering of blood pressure (Rouse, Armstrong and Beilin, 1983). In line with this, a fall in systolic blood pressure in untreated, mildly hypertensive persons who changed to a vegetarian diet has been demonstrated (Margetts et al., 1986). Replacing saturated fat with carbohydrate or with oils high in linoleic acid, however, does not always produce a favourable change in blood pressure (Sacks et al., 1987). Many factors are influenced by vegetarian dietary habits, consequently the interpretation of studies from these populations is limited. It would be difficult to find an association of dietary fat with blood pressure, even if it exists, because of the low sensitivity of dietary methods such as the 24-hour recall and 3-4 day record of food frequency. However, biochemical analyses on the ratio of polyunsaturated to saturated fatty acids in adipose tissue also showed no association with blood pressure (Berry and Hirsch, 1986; Riemersma et al., 1986; Ciocca et al., 1987; Rubba et al., 1987).
Seven studies have shown a significant decline in systolic blood pressure, up to 13 mm Hg, and diastolic blood pressure, 7 mm Hg, in mildly hypertensive individuals eating n-6 enriched diets (Iacono and Dougherty, 1993). Seven other studies were identified in which no significant change in blood pressure occurred in individuals eating similarly enriched diets. Differences in subject selection or adherence to diet may account for these observations. Five community-based intervention studies in Finland, Italy and the USA showed decreases in blood pressure with an increased ratio of intake of n6 polyunsaturated fat to saturated fat. Two extensive, prospective cohort studies of health professionals in the USA, one covering females (Witteman et al., 1989) and the other involving males (Ascherio et al., 1992) did not show any association between dietary polyunsaturated fatty acids and the development of hypertension during a period of 4 years. In two, large, controlled intervention trials, conducted by the National Diet Heart Study Research Group (1968) and the Research Committee to the Medical Research Council (1968), no significant influence of dietary fat on blood pressure was observed in normotensives.
N-3 fatty acids. Many experimental studies have examined the effect of the n-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The discrepancies in observations on blood pressure may be due to the complexity of regulatory mechanisms. The syntheses of vasodilator prostaglandins, such as prostacyclin and PGE2, as well as constrictors such as thromboxane A2 and leukotriene B2, are suppressed by the production of three series of eicosanoids. Thromboxane A3 from n-3 fatty acids is not as active as the 2-series of eicosanoids. The effect of n-3 fatty acids on blood pressure is, therefore, due to the balance of vasodilator and vasoconstrictor eicosanoids in the vascular wall and in the kidney (Yin, Chu and Beilin, 1992; Shimokawa et al., 1987; Lorenz et al., 1983; Beilin, 1992).
In a controlled trial, 50 ml of fish oil (lSg of n-3 fatty acids) decreased systolic and diastolic blood pressure in mildly hypertensive subjects, but 10 ml of fish oil was ineffective (Knapp and Fitzgerald, 1989). Supplementation of a diet with EPA plus DHA, compared to linoleic acid or a -linolenic acid, also lowered blood pressure (Kestin et al., 1990).
When the consumption of fish (100 g of mackerel per day) was compared to meat, there was no effect on blood pressure and bleeding times were significantly prolonged (Houwelingen et al., 1987). A trial in which there was supplementation of either oil containing EPA + DHA or the same amount of corn oil indicated that a reduction in blood pressure depended on the increase in plasma phospholipid n-3 fatty acids (Bonaa et al., 1990).
In the elderly, a reduction in blood pressure occurred with fish oil only when it was combined with a low intake of sodium (Cobiac et al., 1992). It may be noted that there was a high incidence of hypertension and haemorrhagic stroke among the Japanese who ate fish with salt.
The WHO multi-centre, cross-sectional study, known as CARDIAC, involving 55 centres in 24 countries, showed that serum cholesterol levels were positively related to diastolic blood pressure in populations worldwide (Yamori et al., 1992).
For effective treatment of hypertension, intakes of n-3 fatty acids from foods would generally be too high for practical use. Such use should be based on their potential benefits for preventing atherosclerotic or thrombotic disease.
Modification of dietary fat to lower blood lipids indirectly affects blood pressure by slowing down or reversing the atherosclerotic process. Although higher levels of n-6 and long chain n-3 fatty acids lower elevated blood pressure, their effect is modest, especially when compared to the effects of weight reduction or sodium restriction.
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