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Biomedical subjects

F M Sacks

Publications and source records attributed to F M Sacks.

At least 19 recordsLinked to original sources
PubMed1992

Coagulation activation following estrogen administration to postmenopausal women.

We investigated coagulation system activation following estrogen treatment in 29 healthy postmenopausal women. Study participants received conjugated estrogens at 0.625 and 1.25 mg per day, and placebo for 3-month periods in a randomized crossover protocol. Blood samples were obtained on two consecutive days at the end of each treatment period for immunoassays of F1+2 and fibrinopeptide A (FPA), markers of factor Xa action on prothrombin and thrombin action on fibrinogen in vivo, respectively. Treatment with estrogens at a dose of 0.625 or 1.25 mg resulted in significant increases in mean F1+2 levels of 40 and 98%, respectively, and in mean FPA levels of 37 and 71%, respectively. The measurements of F1+2 were significantly higher in women receiving 1.25 mg of estrogen than 0.625 mg. We also observed significant declines in the levels of antithrombin III and total protein S antigen. Immunologic levels of protein C increased modestly at only the 1.25 mg estrogen dose level. These data indicate that low doses of oral estrogens (< or = 1.25 mg per day) frequently increase the amount of thrombin generated in vivo. Our observations may help to explain the increased thrombotic risk that has been observed with higher doses of this medication (> or = 2.5 mg).

Adult↗
PubMed1992

Quantitative angiographic and statistical methods to assess serial changes in coronary luminal diameter and implications for atherosclerosis regression trials.

The purpose of this study was (1) to determine a threshold for categorizing individual coronary lesions as either significantly progressing or regressing, (2) to determine whether multiple lesions within individual patients progress at independent rates, and (3) to calculate sample sizes for atherosclerosis regression trials. Seventeen patients with 46 significant lesions (2.7 lesions/patient) underwent repeat coronary arteriography 3.0 years apart. With use of the standard error of the mean change in diameter from initial to repeat catheterization across 5 pairs of consecutive end-diastolic frames, individual lesions were categorized as either significantly (p less than 0.01) progressing or regressing if there was a 0.27 mm change in minimum diameter or a 7.8 percent point change in percent stenosis. The mean diameter change of a sample of lesions can also be analyzed as a continuous variable using either the lesions or the patient as the primary unit of analysis. A lesion-specific analysis can be accomplished using a multiple regression model that accounts for the intraclass correlation (rho) in the degree of change among multiple lesions within individual patients. The intraclass correlations in percent stenosis (rho = 0.01) and minimum diameter (rho = -0.24) were low, indicating that disease progression in different lesions within individual patients is nearly independent. With use of this model, 50 patients per treatment group would permit the detection of a 5.5% difference between treatment group means in the change in minimum diameter and a 2.7% percentage point (not percent) difference in the change in percent stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Comparison of measures of fatty acid intake by subcutaneous fat aspirate, food frequency questionnaire, and diet records in a free-living population of US men.

In 1986-1987, the authors assessed the fatty acid intake of 118 Boston-area men, aged 40-75 years, by a semiquantitative food frequency questionnaire administered twice, by two 7-day diet records, and by capillary gas chromatography of subcutaneous fat samples obtained by needle aspirate from the lateral buttock. Spearman correlation coefficients between diet record estimates of fatty acid intake (as a percentage of total fat) and fat aspirate measures (as a percentage of total peak area) were as follows: saturated fat, r = 0.16 (p = 0.09); monounsaturated fat, r = 0.22 (p = 0.01); and polyunsaturated fat, r = 0.49 (p = 0.0001). Spearman correlation coefficients between estimates derived from the food frequency questionnaire were as follows: saturated fat, r = 0.18 ( p = 0.05); monounsaturated fat, r = 0.14 (p = 0.14); polyunsaturated fat, r = 0.50 (p = 0.0001); and eicosapentaenoic acid, r = 0.47 (p = 0.0001). These data confirm that the polyunsaturated and eicosapentaenoic fatty acid content of subcutaneous fat is a measure of dietary intake of these fats. Although diet records are commonly thought to be the "gold standard" method of dietary assessment, the similar correlations observed between the fatty acid composition of adipose tissue and estimates of intake from the food frequency questionnaire and from diet records suggest that these two dietary assessment methods have similar validity in the measurement of polyunsaturated fatty acid intake.

Adipose Tissue↗
PubMed1991

Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE)

Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower than expected rate of recurrent events, the trial will be continued until a predetermined fixed number of coronary heart disease events occurs in the entire cohort so that the original sensitivity of the trial will be maintained.

Adult↗
PubMed1991

Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins.

BACKGROUND: Postmenopausal estrogen-replacement therapy may reduce the risk of cardiovascular disease, and this beneficial effect may be mediated in part by favorable changes in plasma lipid levels. However, the effects on plasma lipoprotein levels of postmenopausal estrogens in the low doses currently used have not been precisely quantified, and the mechanism of these effects is unknown. METHODS: We conducted two randomized, double-blind crossover studies in healthy postmenopausal women who had normal lipid values at base line. In study 1, 31 women received placebo and conjugated estrogens at two doses (0.625 mg and 1.25 mg per day), each treatment for three months. In study 2, nine women received placebo, oral micronized estradiol (2 mg per day), and transdermal estradiol (0.1 mg twice a week), each treatment for six weeks. The metabolism of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was measured by endogenously labeling their protein component, apolipoprotein B. RESULTS: In study 1, the conjugated estrogens at doses of 0.625 mg per day and 1.25 mg per day decreased the mean LDL cholesterol level by 15 percent (95 percent confidence interval, 11 to 19 percent; P less than 0.0001) and 19 percent (95 percent confidence interval, 15 to 23 percent; P less than 0.0001), respectively; increased the HDL cholesterol level by 16 percent (95 percent confidence interval, 12 to 20 percent; P less than 0.0001) and 18 percent (95 percent confidence interval, 14 to 22 percent; P less than 0.0001), respectively; and increased VLDL triglyceride levels by 24 percent (95 percent confidence interval, 8 to 40 percent; P less than 0.003) and 42 percent (95 percent confidence interval, 26 to 58 percent; P less than 0.0001), respectively. In study 2, oral estradiol increased the mean concentration of large VLDL apolipoprotein B by 30 +/- 10 percent (P = 0.05) by increasing its production rate by 82 +/- 18 percent (P less than 0.01). Most of this additional large VLDL was cleared directly from the circulation and was not converted to small VLDL or LDL. Oral estradiol reduced LDL cholesterol concentrations by 14 +/- 3 percent (P less than 0.005), because LDL catabolism increased by 36 +/- 7 percent (P less than 0.005). The oral estradiol increased the HDL cholesterol level by 15 +/- 2 percent (P less than 0.0001). Transdermal estradiol had no effect. CONCLUSIONS: The postmenopausal use of oral estrogens in low doses favorably alters LDL and HDL levels that may protect women against atherosclerosis, while minimizing potentially adverse effects on triglyceride levels. The decrease in LDL levels results from accelerated LDL catabolism; the increase in triglyceride levels results from increased production of large, triglyceride-rich VLDL.

Administration, Cutaneous↗
PubMed1991

A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.

BACKGROUND: The independent contributions of subfractions of high-density lipoprotein (HDL) cholesterol (HDL2 and HDL3) and apolipoproteins in predicting the risk of myocardial infarction are unclear. Prospective data are sparse, but HDL2 is widely believed to be a more important predictor than HDL3. METHODS: Blood samples were collected at base line from 14,916 men (ages, 40 to 84 years) who were participants in the Physicians' Health Study. After five years of follow-up, plasma samples from 246 men with new myocardial infarction (case subjects) were analyzed together with specimens from 246 men matched to them for age and smoking status who had not had a myocardial infarction. RESULTS: The levels of total cholesterol and apolipoprotein B-100 were significantly associated with an increased risk of myocardial infarction (data on levels of low-density lipoprotein cholesterol were unavailable). Both HDL cholesterol and HDL2 levels were associated with a substantially decreased risk of myocardial infarction, but the HDL3 level was the strongest predictor; the relative risk was 0.3 (95 percent confidence interval, 0.2 to 0.6) for those in the fifth of the group with the highest HDL3 levels, as compared with the fifth with the lowest levels. The benefit of a higher HDL cholesterol level was most pronounced among those with lower total cholesterol levels. Levels of apolipoprotein A-I and apolipoprotein A-II were also associated with decreased risk. However, the levels of HDL subfractions and apolipoproteins did not add significantly to the value of a multivariate model that included the ratio of total to HDL cholesterol in predicting myocardial infarction, whereas that ratio remained a significant independent predictor of risk. After adjustment for other risk factors, a change of one unit in the ratio of total to HDL cholesterol was associated with a 53 percent change in risk (95 percent confidence interval, 26 percent to 85 percent). CONCLUSIONS: This study underscores the importance of HDL cholesterol in predicting the risk of myocardial infarction and demonstrates protective effects of both the HDL3 and HDL2 subfractions of HDL cholesterol. We found little or no predictive value for the levels of apolipoproteins A-I, A-II, and B or HDL subfractions after conventional risk factors and the ratio of total to HDL cholesterol were considered.

Adult↗
PubMed1991

Comparison of the absorption and effect on platelet function of a single dose of n-3 fatty acids given as fish or fish oil.

To compare their relative absorption and effect on platelet function, concentrated fish oil and tuna were given to 10 subjects in a randomized crossover study. Although plasma enrichment of eicosapentaenoic acid (EPA) from either preparation was similar, relative absorption of EPA from tuna was significantly greater than that from fish oil (46.6 +/- 3.0 mg.L-1.g EPA-1 from tuna compared with 16 +/- 1.0 mg.L-1.g EPA-1 from fish oil, P less than 0.001). Relative absorption of docosahexaenoic acid (DHA) was equivalent (54.0 +/- 9.0 mg.L-1.g DHA-1 from tuna, 56 +/- 9.0 mg.L-1.g DHA-1 from fish oil, NS). Platelet aggregation in response to the endoperoxide analog U46619 was significantly diminished after either preparation but aggregation in response to other agonists, bleeding time, and membrane n-3 (omega-3) fatty acid content were not changed. Thus, n-3 fatty acids are well absorbed after one dose of either tuna or fish oil but EPA absorption appears to be more efficient from tuna. Additionally, a single dose of n-3 fatty acids decreases platelet aggregation by a mechanism not requiring incorporation into platelet membranes.

Absorption↗
PubMed1991

Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women.

The distributions of fatty acids in subcutaneous-adipose-tissue aspirates and their relation to intake as assessed by a semiquantitative food-frequency questionnaire were investigated in 115 postmenopausal US women free from cancer. Percentages of fatty acids in adipose tissue were significantly correlated with the percentage of total fat intake for polyunsaturated fatty acids (Spearman correlation = 0.37), n-3 fatty acids of marine origin (Spearman correlation = 0.48), and trans fatty acids (Spearman correlation = 0.51) but not for saturated and monounsaturated fatty acids. Correlations were somewhat stronger in 78 women with stable weight over the 6 mo before fat aspiration. These data suggest that intakes of polyunsaturated fatty acids, including n-3 fatty acids, and trans fatty acids are reflected in the adipose tissue but that intakes of saturated and monounsaturated fatty acids are not. The data also provide further support for the validity of the food-frequency questionnaire in the assessment of fat intake.

Adipose Tissue↗
PubMed1990

Effects of two types of fish oil supplements on serum lipids and plasma phospholipid fatty acids in coronary artery disease.

Fish oil has consistently been shown to lower triglyceride levels, but its effects on low-density lipoprotein (LDL) cholesterol remain controversial. The current study compares the long-term effects of 2 different fish oil preparations (ethyl ester and triglyceride) versus olive oil in patients with coronary artery disease. Eighty-nine subjects were randomly assigned to receive capsules containing 6 g/day (triglyceride group) or 7 g/day (ethyl ester group) of n-3 fatty acids, or capsules containing 12 g/day of olive oil for 6 months. Mean triglyceride levels decreased by 28% in the ester and 32% in the triglyceride fish oil groups (p less than 0.05 for both). LDL cholesterol levels increased by 3% (difference not significant) in the ester and 12% (p less than 0.05) in the triglyceride fish oil groups; in hypertriglyceridemic subjects the increase was 23% (p less than 0.01) and 14% (difference not significant), respectively. Plasma phospholipid fatty acid analysis showed a fivefold increase in eicosapentaenoic acid levels in both fish oil groups (p less than 0.001), and a long-term decrease in arachidonic acid levels (p less than 0.001). Achieved eicosapentaenoic acid level correlated with the degree of increase in LDL cholesterol (r = 0.38, p less than 0.05). These data suggest that fish oil administration is associated with an increase in LDL cholesterol levels in a diverse group of patients with coronary artery disease; this change appears to be correlated with n-3 fatty acid absorption. The impact of this increase in LDL is unknown, but should be considered as potentially adverse.

Coronary Disease↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗