Showing papers by "Frank M. Sacks published in 1996"
TL;DR: It is demonstrated that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels and was also greater in patients with higher pretreatment levels of LDL cholesterol.
Abstract: Background In patients with high cholesterol levels, lowering the cholesterol level reduces the risk of coronary events, but the effect of lowering cholesterol levels in the majority of patients with coronary disease, who have average levels, is less clear. Methods In a double-blind trial lasting five years, we administered either 40 mg of pravastatin per day or placebo to 4159 patients (3583 men and 576 women) with myocardial infarction who had plasma total cholesterol levels below 240 mg per deciliter (mean, 209) and low-density lipoprotein (LDL) cholesterol levels of 115 to 174 mg per deciliter (mean, 139). The primary end point was a fatal coronary event or a nonfatal myocardial infarction. Results The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group, an absolute difference of 3 percentage points and a 24 percent reduction in risk (95 percent confidence interval, 9 to 36 percent; P = 0.003). Coronary bypass surgery was needed in 7.5 per...
7,272 citations
TL;DR: Findings indicate that nonfasting triglyceride levels appear to be a strong and independent predictor of future risk of MI, particularly when the total cholesterol level is also elevated.
Abstract: Objective. —To test whether a predominance of small, dense low-density lipoprotein (LDL) particles and elevated triglyceride levels are independent risk factors for myocardial infarction (MI). Design. —Nested case-control study with prospectively collected samples. Setting. —Prospective cohort study. Participants. —Blood samples were collected at baseline (85% nonfasting samples) from 14916 men aged 40 to 84 years in the Physicians' Health Study. Main Outcome Measurements. —Myocardial infarction diagnosed during 7 years of follow-up. Results. —Cases (n=266) had a significantly smaller LDL diameter (mean [SD], 25.6 [0.9] nm) than did controls (n=308) matched on age and smoking (mean [SD], 25.9 [8] nm; P P r =-0.71), and a high direct correlation with high-density lipoprotein cholesterol (HDL-C) level (r=0.60). We observed a significant multiplicative interaction between triglyceride and total cholesterol (TC) levels ( P =.01). After simultaneous adjustment for lipids and a variety of coronary risk factors, LDL particle diameter was no longer a statistically significant risk indicator, with a relative risk (RR) of 1.09 (95% confidence interval [CI], 0.85-1.40) per 0.8-nm decrease. However, triglyceride level remained significant with an RR of 1.40 (95% CI, 1.10-1.77) per 1.13 mmol/L (100-mg/dl) increase. The association between triglyceride level and MI risk appeared linear across the distribution; men in the highest quintile had a risk about 2.5 times that of those in the lowest quintile. The TC level, but not HDL-C level, also remained significant, with an RR of 1.80 (95% CI, 1.44-2.26) per 1.03-mmol/L (40-mg/dL) increase. Conclusions. —These findings indicate that nonfasting triglyceride levels appear to be a strong and independent predictor of future risk of MI, particularly when the total cholesterol level is also elevated. In contrast, LDL particle diameter is associated with risk of MI, but not after adjustment for triglyceride level. Increased triglyceride level, small LDL particle diameter, and decreased HDL-C levels appear to reflect underlying metabolic perturbations with adverse consequences for risk of MI; elevated triglyceride levels may help identify high-risk individuals.
1,135 citations
TL;DR: In this article, the relation of nutritional factors with hypertension and blood pressure levels among 41 541 predominantly white US female nurses, aged 38 to 63 years, were examined prospectively.
Abstract: We examined prospectively the relation of nutritional factors with hypertension and blood pressure levels among 41 541 predominantly white US female nurses, aged 38 to 63 years, who comple
413 citations
Journal Article•
TL;DR: Combination drug therapy has been shown to decrease cholesterol levels in hyperlipidemic patients as mentioned in this paper, however, its efficacy has not been well studied in patients previously considered to be at risk.
Abstract: Background: Combination drug therapy has been shown to decrease cholesterol levels in hyperlipidemic patients. However, its efficacy has not been well studied in patients previously considered to b...
89 citations
TL;DR: The objective was to evaluate the efficacy and tolerability of a rationally designed program of stepped-care therapy for normolipidemic patients with coronary heart disease and to meet target goals for the aggressive reduction of LDL cholesterol levels.
Abstract: BACKGROUND Combination drug therapy has been shown to decrease cholesterol levels in hyperlipidemic patients. However, its efficacy has not been well studied in patients previously considered to be normolipidemic, many of whom are now candidates for this therapy. OBJECTIVE To determine the efficacy and tolerability of multidrug therapy designed to improve low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels in patients with coronary heart disease and average lipid levels. DESIGN Randomized, placebo-controlled, 2.5-year trial comparing patients receiving usual care with patients receiving stepped-care drug therapy. INTERVENTION Stepped-care therapy (pravastatin, nicotinic acid, cholestyramine, and gemfibrozil) to decrease total cholesterol levels to less than 4.1 mmol/L (160 mg/dL) and the ratio of LDL cholesterol to HDL cholesterol to less than 2.0. SETTING 2 academic, urban, tertiary care hospitals. PATIENTS 91 patients (80 men and 11 women) with coronary heart disease, a mean age of 60 years, total cholesterol levels less than 6.4 mmol/L (250 mg/dL) at baseline, and ratios of total cholesterol to HDL cholesterol greater than 4.0 at baseline. MEASUREMENTS Fasting serum lipoprotein profile, fasting apolipoprotein levels, and frequency of adverse effects. Patients were assessed every 6 weeks during drug titration and every 3 months thereafter. RESULTS Mean lipid levels at baseline were as follows: total cholesterol, 5.5 mmol/L (214 mg/dL); LDL cholesterol, 3.6 mmol/L (140 mg/dL); HDL cholesterol, 1.1 mmol/L (42 mg/dL); and triglycerides, 1.8 mmol/L (159 mg/dL). With pravastatin, changes in levels from baseline were -22% for total cholesterol, -32% for LDL cholesterol +8% for HDL cholesterol, and -15% for triglycerides (P < 0.001 for all comparisons). With the addition of 1.5 g of nicotinic acid, additional changes were -6% for total cholesterol (P < 0.002). -11% for LDL cholesterol, +8% for HDL cholesterol, and -10% for triglycerides (P < 0.001 for all comparisons). With 2.25 to 3 g of nicotinic acid, these changes were -7% for total cholesterol (P = 0.007), -14% for LDL cholesterol (P < 0.001), +6% for HDL cholesterol (P = 0.02), and -13% for triglycerides (P = 0.03). With cholestyramine, total cholesterol and LDL cholesterol levels were unchanged compared with the previous step; the change in HDL cholesterol level was -8% (P = 0.03); and the change in triglyceride level was +46% (P < 0.001). With gemfibrozil, total cholesterol level was unchanged; the additional change in LDL cholesterol level was +12% (P = 0.09); the change in HDL cholesterol level was +12% (P = 0.03); and the change in triglyceride level was -37% (P < 0.001). Apolipoprotein B levels decreased by 25% overall (P < 0.001); lipoprotein(a) levels did not change significantly. Adverse effects were primarily attributable to nicotinic acid or cholestyramine. In 18 of the 35 patients (50%) whose baseline LDL cholesterol levels were greater than 3.35 mmol/L (130 mg/dL), pravastatin decreased LDL cholesterol levels to 2.6 mmol/L (100 mg/dL) or less by 6 weeks; 70% of patients needed combination therapy to reach this National Cholesterol Education Program goal during the 2.5 years of the study. Adding nicotinic acid to pravastatin produced LDL cholesterol levels of 2.6 mmol/L or less in 15 more of these 35 patients, so that 94% (n = 33) of the patients receiving these two drugs reached this goal. CONCLUSIONS To reach current goals for LDL cholesterol levels, most normolipidemic patients with coronary heart disease in this study needed combination therapy. Pravastatin with nicotinic acid and pravastatin with gemfibrozil are well-tolerated combinations that can maintain target LDL cholesterol levels, decrease triglyceride levels, and increase HDL cholesterol levels. Adding resin to these combinations produced no further benefit.
83 citations
TL;DR: It is concluded that moderate shrimp consumption in normolipidemic subjects will not adversely affect the overall lipoprotein profile and can be included in "heart healthy" nutritional guidelines.
45 citations
TL;DR: Individuals have a reproducible plasma LDL-cholesterol response when changing their dietary fat intake and the day-to-day variation in total triacylglycerol, VLDL triacy lglycersol, and LDL- cholesterol concentrations decreases when day- to-day dietary variation is eliminated.
20 citations
TL;DR: The presence of clinically evident diffuse atherosclerosis is common and is associated with several modifiable risk factors and early identification of these individuals could affect treatment and clinical outcomes.
Abstract: PURPOSE To determine the prevalence and correlates of symptomatic peripheral atherosclerosis in individuals with a history of myocardial infarction (MI) and cholesterol levels lower than 240 mg/dL. MATERIALS AND METHODS A cross-sectional analysis was conducted at baseline of 4159 participants in the Cholesterol and Recurrent Events (CARE) Study. Symptomatic diffuse atherosclerosis was defined as a history of MI plus lower extremity or cerebrovascular atherosclerosis or claudication by Rose questionnaire. RESULTS The prevalence of symptomatic diffuse atherosclerosis was 12.9%; 353 participants (8.5%) had lower extremity disease and 219 (5.3%) had cerebrovascular disease. After controlling for other variables, diffuse atherosclerosis was associated with age (Odds Ratio [OR] = 1.44 per ten-year increase), systolic blood pressure (OR = 1.13 per 10 mm Hg increase), a history of multiple myocardial infarctions (OR = 1.76), diabetes (OR = 1.76), hypertension (OR = 1.38), reduced exercise performance (OR = 1.55), current smoking status (OR = 2.87), and lower alcohol intake (OR = 0.97 per drink per week). There was no association with race, gender, or lipid levels. CONCLUSIONS The presence of clinically evident diffuse atherosclerosis is common and is associated with several modifiable risk factors. Early identification of these individuals could affect treatment and clinical outcomes.
20 citations
TL;DR: Way in which premature coronary deaths in Asians in Britain might be avoided is discussed, and high levels of trans-fatty acids, which adversely affect blood lipid concentrations, are discussed.
Abstract: EDITOR,—Sandeep Gupta and colleagues discuss ways in which premature coronary deaths in Asians in Britain might be avoided.1 When cooking, many people in India and Pakistan use a semisolid fat obtained by partially hydrogenating vegetable oils. This product, called vanaspathi or vegetable ghee, contains high levels of trans-fatty acids, which adversely affect blood lipid concentrations and are thus …
6 citations
TL;DR: In this article, the extent to which apo E is involved in the cell binding and uptake of VLDL from different normolipidemic persons is not well defined.
Abstract: Apolipoprotein E (apo E) can mediate the cell binding of normal human very low density lipoproteins (VLDL). However, the extent to which apo E is involved in the cell binding and uptake of VLDL from different normolipidemic persons is not well defined. The VLDL (d < 1.006 g/l) of eight subjects were fractionated into VLDL with apo E and without apo E using a monoclonal antibody that binds to the LDL receptor recognition region of apo E. VLDL particles that expressed the 1D7 binding region of apo E comprised an average of 34% (range 7-51%) of the VLDL particles. Anti-apo E blocked an average of 43% (range 8-63%) of the binding of unfractionated VLDL to U937 cells. Anti-apo E blocked a similar proportion of binding to U937 cells of three VLDL subfractions of different density ranges (Sf20-60, Sf60-100, Sf100-400). The proportion of the VLDL particles that contained apo E correlated with the extent of uptake of the total VLDL by U937 cells, but not with stimulation by total VLDL of cholesterol ester formation. The binding to cells of VLDL without apo E varied by six-fold among persons, and caused most of the binding of the total VLDL of some subjects. Therefore, normolipidemic VLDL contains particles across its density range that use apo E to bind to U937 macrophages. In some VLDL samples, apo E provides most of the cell binding activity, whereas in others the binding activity occurs by other means.
6 citations
TL;DR: A procedure is proposed that predicts the value of an average based on n measurements serially obtained on a patient during the screening phase when only m < n measurements are available, which is applied to population screening for lipid levels above a treatment threshold.
01 Jan 1996
TL;DR: In normocholesterolaemic patients, intensive step drug therapy does not alter the angiographic rate of structural disease progression, and there was no correlation between baseline lipids or the change in lipids with disease progression.
Abstract: Although several trials have shown that lipid lowering improves angiographic disease progression in patients with elevated LDL-cholesterol levels, the potential benefit of drug therapy in normocholesterolaemic patients has not been examined in a randomized prospective fashion Patients with symptomatic coronary artery disease with at least one lesion narrowed by >30% were randomized to either placebo (n = 39), or stepped drug therapy using pravastatin, niacin, cholestyramine and gemfibrozil as needed to reach a target total cholesterol of ≤41mmol/L and LDL-cholesterol/HDL-cholesterol ≤20 (n = 40) Baseline lipid values (mmol/L) and the average percent changes between the groups over the 25 years of treatment were: total cholesterol 548, -28%; LDL-cholesterol 355, -41%; HDL-cholesterol 107, +13%; and triglycerides 188, -26% (p 012 mm or > 16% stenosis, which are differences that have been observed in previous lipid-lowering trials There was no correlation between baseline lipids or the change in lipids with disease progression In normocholesterolaemic patients, intensive step drug therapy does not alter the angiographic rate of structural disease progression