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Biomedical subjects

F M Sacks

Publications and source records attributed to F M Sacks.

At least 109 records · Page 6Linked to original sources

Relation of moderate alcohol consumption and risk of systemic hypertension in women.

The relation between alcohol consumption and the risk of development of hypertension was studied among 58,218 US female registered nurses aged 39 to 59 years who were free of diagnosed systemic hypertension and other major diseases. In 1980, all of these women completed an independently validated dietary questionnaire, which included use of alcoholic beverages. During 4 years of follow-up, 3,275 women reported an initial diagnosis of hypertension; validity of the self-report measure was demonstrated in a subsample. When compared to nondrinkers, women drinking 20 to 34 g of alcohol per day (about 2 or 3 drinks) had a significantly elevated relative risk of 1.4; the 95% confidence interval (CI) was 1.2 to 1.7 after adjustment for age and Quetelet's index. For women consuming greater than 35 g/day, the relative risk was 1.9 (95% CI 1.6 to 2.2). Adjustment for smoking and dietary variables did not alter these results. Independent significant associations were observed for the consumption of beer, wine and liquor. These prospective data suggest that alcohol intake of up to about 20 g/day does not increase the risk of hypertension among women, but beyond this level, the risk increases progressively.

Adult↗

Comparison of the effects of oat bran and low-fiber wheat on serum lipoprotein levels and blood pressure.

Previous studies have shown that supplementation of the diet with oat bran may lower serum cholesterol levels. However, it is not known whether oat-bran diets lower serum cholesterol levels by replacing fatty foods in the diet or by a direct effect of the dietary fiber contained in oat bran. To determine which is the case, we compared the effect of isocaloric supplements of high-fiber oat bran (87 g per day) and a low-fiber refined-wheat product on the serum lipoprotein cholesterol levels of 20 healthy subjects, 23 to 49 years old. After a one-week base-line period during which they consumed their usual diets, the subjects were given each type of supplement for six-week periods in a double-blind, crossover trial. Mean serum cholesterol levels (+/- SD) were not significantly different during the high-fiber and low-fiber periods: total cholesterol, 4.44 +/- 0.73 and 4.46 +/- 0.64 mmol per liter (172 +/- 28 and 172 +/- 25 mg per deciliter); low-density lipoprotein, 2.69 +/- 0.63 and 2.77 +/- 0.59 mmol per liter (104 +/- 24 and 107 +/- 23 mg per deciliter); and high-density lipoprotein, 1.40 +/- 0.39 and 1.32 +/- 0.39 mmol per liter (54.2 +/- 15.0 and 50.9 +/- 15.2 mg per deciliter), respectively. However, both types of supplements lowered the mean base-line serum cholesterol level, 4.80 +/- 0.80 mmol per liter (186 +/- 31 mg per deciliter), by 7 to 8 percent (95 percent confidence interval for high fiber, 11 to 4 percent, and for low fiber, 11 to 3 percent). The subjects ate less saturated fat and cholesterol and more polyunsaturated fat during both periods of supplementation than at base line. Those changes in dietary fats were sufficient to explain all of the reduction in serum cholesterol levels caused by the high-fiber and low-fiber diets. The average blood pressure was 112/68 mm Hg at base line and did not change during either dietary period. We conclude that oat bran has little cholesterol-lowering effect and that high-fiber and low-fiber dietary grain supplements reduce serum cholesterol levels about equally, probably because they replace dietary fats.

Adult↗

Effect of a modified, well-tolerated niacin regimen on serum total cholesterol, high density lipoprotein cholesterol and the cholesterol to high density lipoprotein ratio.

One hundred one patients with coronary artery disease and pretreatment ratios of total cholesterol to high density lipoprotein (HDL) cholesterol greater than 4.0 were treated with niacin, commencing at low dosages (100 to 250 mg twice daily) and gradually increasing the dosage over 4 to 8 weeks to 1,000 mg twice daily. Dosage adjustments were made to minimize side effects. At a mean follow-up duration of 11 +/- 7 months, and a mean dosage of 1,415 +/- 698 mg/day, the group had a 13% reduction in total cholesterol, 31% increase in HDL and 32% decrease in the cholesterol to HDL ratio. A subgroup of 62 patients taking greater than 1,000 mg/day of niacin had an 18% reduction in total cholesterol, 32% increase in HDL and 36% improvement in the cholesterol to HDL ratio. A subgroup of 39 patients taking less than or equal to 1,000 mg/day of niacin had only a 5% reduction in total cholesterol, although a 29% increase in HDL and a 24% decrease in the cholesterol to HDL ratio were recorded. Side effects of niacin were reported in 38% of the patients, but led to discontinuation of therapy in only 4. Niacin can be administered in a fashion that is well tolerated, inexpensive and very effective in improving the cholesterol to HDL ratio.

Adult↗

Randomised trial of fish oil for prevention of restenosis after coronary angioplasty.

To examine the potential role of fish oil supplementation in the prevention of restenosis after coronary angioplasty (PTCA), a randomised double-blind trial was conducted in 204 patients. The treatment group received 6 g/day of n-3 fatty acids, beginning 5.4 (SD 3.2) days before PTCA, and continuing for 6 months; the control group received olive oil placebo. Compliance was assessed by pill count and plasma levels of eicosapentaenoic acid (EPA). Restenosis was identified by symptoms and exercise testing and confirmed by angiography. PTCA was successful in 186 patients (93%). The incidence of angiographic restenosis was 34% in the fish oil group and 23% in the control group (relative risk 1.7, 95% CI 0.9-3.4). The lack of benefit of fish oil was not influenced by length of pretreatment, compliance with study medication, or the concentrations of plasma EPA achieved.

Angioplasty, Balloon↗

Effects of alpha- and beta-adrenergic antagonists on plasma apolipoproteins and forearm blood flow in patients with mild hypertension.

To study the mechanisms by which adrenergic antagonists affect blood pressure and plasma lipid levels, the effects of alpha-blockade with prazosin were compared with those of beta-blockade with propranolol in 23 normolipidemic, mildly hypertensive patients. Plasma lipoprotein composition, apolipoproteins, and some of the processes involved in lipid synthesis and clearance from plasma were investigated also. Patients entered an eight-week placebo period during which they were free of all antihypertensive medications. They were then randomly assigned under double-blind conditions to treatment with either prazosin (mean dose, 5 mg per day) or propranolol (mean dose, 133 mg per day) for eight weeks. Doses of both drugs were titrated to achieve either a decrease in diastolic blood pressure of 10 mm Hg or more or a reduction of diastolic blood pressure to less than 85 mm Hg, whichever was lower. Total plasma cholesterol decreased by 9 percent during prazosin treatment and increased by 7 percent during propranolol treatment (p less than 0.005 between treatments). Low-density lipoprotein cholesterol decreased by 12 percent with prazosin and increased by 12 percent with propranolol (p less than 0.005). Apolipoprotein B decreased by 17 percent with prazosin and increased by 15 percent with propranolol (p less than 0.005). There were no significant changes in total high-density lipoprotein cholesterol, its subfractions high-density lipoprotein2 or high-density lipoprotein3, or in apolipoprotein A1 and apolipoprotein A2. Plasma very low-density lipoprotein and low-density lipoprotein triglycerides were not significantly affected by either treatment. Plasma post-heparin lipase activities, which clear triglyceride and high-density lipoprotein cholesterol from plasma, were not altered significantly. Since regional blood flow could affect the clearance of plasma lipoproteins, measurements were taken of forearm blood flow, forearm vascular resistance, and maximal forearm vasodilatory potential during reactive hyperemia. The adrenergic antagonists had no effect on these measurements, nor did they affect cellular cholesterol synthesis as measured by the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in blood mononuclear cells. The results of this study demonstrate differing actions between alpha- and beta-adrenergic antagonism. Alpha-blockade produced significantly lower levels of plasma low-density lipoprotein cholesterol and apolipoprotein B than beta-adrenergic antagonism without changes in high-density lipoproteins.

Adult↗

A prospective study of nutritional factors and hypertension among US women.

The relation of various nutritional factors with hypertension was examined prospectively among 58,218 predominantly white US female registered nurses, aged 34-59 years. In 1980, all women completed an independently validated dietary questionnaire. During 4 years of follow-up, 3,275 women reported a diagnosis of hypertension; the validity of the self-report was shown in a subsample. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary calcium and magnesium had independent and significant inverse associations with hypertension. For women with a calcium intake of at least 800 mg/day, the relative risk of hypertension was 0.78 (95% confidence interval, 0.69-0.88) when compared with an intake of less than 400 mg/day. The relative risk for magnesium intake of 300 mg/day or more compared with an intake of less than 200 mg/day was 0.77 (95% confidence interval, 0.67-0.88). For women with high intakes of both calcium and magnesium compared with those having low intakes of both, the relative risk of hypertension was 0.65 (95% confidence interval, 0.53-0.80). No independent associations with hypertension were observed for intakes of potassium, fiber, and saturated and polyunsaturated fatty acids. These prospective findings add to the growing evidence to support the need for randomized trials to determine whether there is a protective role of dietary calcium and magnesium in the regulation of blood pressure.

Adult↗

Effect of transport conditions on the stability of biochemical markers in blood.

We examined the stability of lipids, carotenoids, alpha-tocopherol, and endogenous hormones in plasma prepared from whole blood that had been mailed to a central location for processing. Initially, to simulate transport conditions, whole-blood samples were stored in the laboratory, either at room temperature or cooled, for up to 72 h before processing. In the latter samples, lipid concentrations changed up to 1.4% per day, carotenoids up to -5.5%, and hormones up to 9.5%. In a second study, analyte concentrations in plasma from cooled whole blood mailed via overnight courier were compared with those from plasma that had been immediately separated, frozen, and mailed via overnight courier. Concentrations of cholesterol, high-density lipoprotein subfraction 3, apolipoprotein B, and retinol were stable. Overall, for each marker except estradiol, the between-person variation was at least twice the within-person variation. In a third study, at least 340 micrograms of DNA was recovered from 30 mL of cool-shipped whole blood. Our results indicate that shipping whole-blood samples by overnight courier is feasible for assay of several biochemical markers of interest in epidemiological research.

Adult↗

Comparison of excretion of nicotinuric acid after ingestion of two controlled release nicotinic acid preparations in man.

We tested an inexpensive controlled-release nicotinic acid product (Bronson Pharmaceuticals, LaCanada, CA) and compared it with the standard, more expensive, controlled release product, Nicobid (Rorer Pharmaceuticals), by measuring the 24 hour urinary recovery of nicotinic and nicotinuric acids from ten subjects following 500 mg oral ingestion of each product. Nicotinuric acid is the major detoxification product of nicotinic acid and may serve as a simple quantitative index of hepatic biotransformation of nicotinic acid. Although both products demonstrated controlled release profiles, the rate of appearance of nicotinic and nicotinuric acid in the urine as well as the rate of in vitro drug dissolution of the Bronson product were more rapid compared with Nicobid. Moreover, the total amounts of nicotinic acid and nicotinuric acid recovered in the urine after 24 hours were greater for the Bronson product (P less than .05). Since sustained presentation of nicotinic acid to the liver may correlate with clinical antihyperlipidemic effects, our results suggest that the Bronson product may prove to be a clinically useful preparation.

Adult↗

Low blood pressure in vegetarians: effects of specific foods and nutrients.

Strict vegetarians, who eat little if any animal products and lactovegetarians, who regularly eat dairy products, have lower blood pressures than the general population after adjustment for the effects of age, sex, and body weight. Controlled dietary trials were undertaken to determine the dietary basis for the differences in BP between vegetarians and nonvegetarians. Exchanging meat and eggs for vegetable products; increasing total dietary protein or replacing soy protein with dairy protein; exchanging saturated, monounsaturated, and polyunsaturated fatty acids; and changing the content of total dietary fat and carbohydrate all had no substantial effect on BP. Therefore, animal products, carbohydrate, and different types of fats do not appear to explain the low BP in vegetarians. Rather, modest intake of animal products may be a marker for a large intake of other potentially beneficial nutrients from vegetable products.

Age Factors↗

The association of dietary fat with serum cholesterol in vegetarians: the effect of dietary assessment on the correlation coefficient.

The biologic relation between dietary fats and serum cholesterol established in controlled dietary studies usually has not been found in cross-sectional studies of the general population. In vegetarian groups, dietary variables and serum cholesterol have been correlated significantly. To examine the role of technique of dietary assessment versus the dietary pattern of vegetarians, the authors studied the relation of diet with total serum cholesterol in 46 predominantly vegetarian adults in the Boston, Massachusetts, area in 1973-1974. The basis of the dietary information was 10-day diet records. Total serum cholesterol was positively associated with dietary cholesterol (r = 0.53) and saturated fatty acids (r = 0.50) in partial correlation analysis adjusted for age, sex, and triceps skinfold. The use of one-day dietary records lowered these correlation coefficients to about 0.3. Analysis of the components of variation of nutrient intake demonstrated that the vegetarians had a lower within-person variance, a higher between-person variance, or both compared with nonvegetarian study groups. Biologic responsiveness to dietary fat in the vegetarians was similar to that predicted by the Keys equation derived from nonvegetarians. Therefore, multiple-day averaging of dietary records and relatively smaller ratio of within-person to between-person variation in intake favor the detection of cross-sectional associations of diet with serum cholesterol.

Adult↗

Effect of linoleic and oleic acids on blood pressure, blood viscosity, and erythrocyte cation transport.

It has been proposed that dietary linoleic acid lowers blood pressure (BP) by being converted to arachidonic acid and prostanoids of the two-ene series. We tested the effects of linoleic acid on plasma arachidonic acid, blood pressure, blood viscosity, and RBC cation transport. Oleic acid, the major dietary monounsaturated fat and which is not a prostanoid precursor, was used as a control. Seventeen adults consumed 23 g/d of linoleic acid or oleic acid provided by genetic variants of safflower seed, each for 4 weeks in a double-blind crossover design. Linoleic and oleic acids were enriched significantly in the plasma cholesteryl esters, phospholipids and triglycerides during the respective periods of supplementation but there was no increase in arachidonate. Mean BP was 116.1/76.8 during ingestion of oleic and 113.6/74.6 during ingestion of linoleic acid (p = 0.09 systolic, p = 0.12 diastolic). The power of the study was over 75% for detecting a significant (p less than 0.05) effect of 4 mm Hg in systolic BP or diastolic BP. Whole blood and plasma viscosity, and RBC Li/Na countertransport, Na/K cotransport, and Na pump systems (Vmax) were unchanged during the protocol. Therefore, variations in dietary linoleic or oleic acids are unlikely to have major effects on BP or on several membrane-dependent erythrocyte functions related to hypertension.

Adult↗

Effect of dietary fats and carbohydrate on blood pressure of mildly hypertensive patients.

The effect on blood pressure (BP) of replacing dietary saturated fat with either polyunsaturated fat (linoleic acid) or carbohydrate was studied in 21 untreated mildly hypertensive patients. In a randomized, double-blind, crossover protocol, all subjects received dietary supplements of cream, safflower oil, and carbohydrate in random sequence, each prepared in flavored yogurt or milk. Each supplement was administered for 6 weeks and followed by a 4-week washout period of no supplementation. Dietary linoleic acid increased from 4.6 to 13% of energy intake when the safflower oil replaced cream, while saturated fat decreased from 16 to 10%. Total fat intake was 37 to 38% during the cream and safflower oil periods but was 28% during the carbohydrate period. Compliance with the diets was demonstrated by significant changes in fasting plasma fatty acid measurements. Mean clinic BP was 135 +/- 9/93 +/- 6 mm Hg at baseline. There were no significant differences in BP measured in the clinic or at home among the three dietary periods. The protocol had more than 80% power to detect a mean effect of diet of 3 mm Hg systolic or 2 mm Hg diastolic BP. Therefore, replacing dietary saturated fat with carbohydrate or with linoleic acid does not affect BP in subjects with mild hypertension.

Adult↗

Regulation of lipoprotein metabolism by adrenergic mechanisms.

The available data on the adrenergic influences on lipoprotein metabolism are reviewed. It is clear that the influences are complex. It appears that adrenergic stimuli act at multiple sites in the lipoprotein metabolic pathways. This explains in part, the confusion in interpreting the literature. Based on the effects of alpha- and beta-adrenergic blocker administration in animals and humans, it is clear that the net effect of alpha 1-receptor stimulation is a decrease in HDL cholesterol and an increase in LDL cholesterol and VLDL triglyceride. On the other hand, beta-receptor stimulation will result in a net reduction of LDL and an increase in HDL. Further studies to elucidate the exact mechanism of action by the adrenergic stimuli on lipoprotein metabolism should provide insights into the relationship between the adrenergic nervous system and atherosclerosis and an enhanced understanding of the mechanisms by which antihypertensive-adrenergic mechanisms--alpha 1-Inhibition--Atherosclerosis--Serum lipids.

Adrenergic alpha-Antagonists↗

Adrenergic effects on plasma lipoprotein metabolism. Speculation on mechanisms of action.

Recently, the effects of alpha-adrenergic and beta-adrenergic antagonists on plasma lipoprotein concentrations have been reported. Evidence from diverse lines of research has been brought together that suggests three potential mechanisms by which these antihypertensive agents affect lipoprotein metabolism. First, the known alterations in plasma triglyceride levels caused by adrenergic antagonists may be mediated through the activity of lipoprotein lipase. This enzyme, located on the capillary endothelium of adipose tissue and skeletal muscle, catabolizes chylomicrons and very-low-density lipoproteins. Catecholamine-induced changes in precapillary sphincter tone could affect the delivery of triglyceride-rich lipoproteins to endothelial lipase, cause changes in capillary endothelial surface area for lipase-binding sites, and/or modulate the synthesis of lipoprotein lipase by adipocytes and myocytes. Since high-density lipoprotein levels increase by taking up components of chylomicrons released by lipoprotein lipase, these pathways might explain the adrenergic-induced changes in high-density lipoprotein that are reciprocal to those in plasma triglycerides. Second, hepatic production of very-low-density lipoproteins might be affected by adrenergic-induced changes in insulin release. Decreased insulin release may direct glucose metabolites from adipocytes to hepatocytes for lipogenesis. Catecholamines and other glucoregulatory hormones are known to alter hepatic cholesterol synthesis and secretion of very-low-density lipoproteins. These observations also suggest that dietary carbohydrate and fat might modulate adrenergic influences on lipoprotein metabolism by other than classic means. Third, as suggested by studies of cultured fibroblasts, alpha-adrenergic antagonists may increase receptor-mediated catabolism of low-density lipoprotein.

Animals↗

Effects of a low-fat diet on plasma lipoprotein levels.

Lowering the intake of fat to decrease serum cholesterol levels has unknown effects on the proportion of cholesterol in low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Twenty normolipidemic nonvegetarians were given dietary instruction and supervision in a low-fat, semivegetarian diet for three months. Mean consumption of total fat, saturated fat, and cholesterol decreased, whereas intake of carbohydrate increased significantly on a low-fat diet. Plasma LDL levels decreased by 18% and HDL levels by 7% from prestudy baseline levels. The LDL/HDL ratio declined by 11%. Plasma triglyceride levels and body weight were unchanged. In individual subjects, the decrements in consumption of saturated fat and the increments in ingestion of polyunsaturated fat were each significantly correlated with decreases in LDL. One year after the subjects had returned to a self-selected diet, levels of dietary saturated fat and cholesterol and the plasma LDL/HDL ratio remained significantly below prestudy levels. This study and others suggest that a low-fat, high-carbohydrate diet favorably affects the plasma LDL/HDL proportion by decreasing LDL on a percentage basis 2 1/2 to three times more than it decreases HDL.

Adolescent↗