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Biomedical subjects

F M Sacks

Publications and source records attributed to F M Sacks.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effect of pravastatin on cardiovascular events in women after myocardial infarction: the cholesterol and recurrent events (CARE) trial.

OBJECTIVES: We sought to determine the effect of pravastatin on recurrent cardiovascular events in women with average cholesterol levels after myocardial infarction (MI). BACKGROUND: Little information is available on the effectiveness of lipid lowering in secondary prevention of coronary heart disease (CHD) in women; in particular, those with CHD and average cholesterol levels. METHODS: In the Cholesterol and Recurrent Events (CARE) trial, 576 postmenopausal women, between 3 and 20 months after MI, with a total cholesterol level <240 mg/dl and a low density lipoprotein cholesterol level 115 to 174 mg/dl, were randomized to receive pravastatin 40 mg/day or matching placebo for a median follow-up period of 5 years. The main outcome measures were combined coronary events (coronary death, nonfatal MI, percutaneous transluminal coronary angioplasty [PTCA] or coronary artery bypass graft surgery [CABG]), the primary trial end point (coronary death or nonfatal MI) and stroke. RESULTS: Women treated with pravastatin had a risk reduction of 43% for the primary end point (p = 0.035), 46% for combined coronary events (p = 0.001), 48% for PTCA (p = 0.025), 40% for CABG (p = 0.14) and 56% for stroke (p = 0.07). The 3,583 men in the CARE trial also showed a reduction in risk, but the magnitude tended to be less. Pravastatin improved plasma lipids similarly in men and women. There were no differences in risk of coronary events in the placebo group between men and women. Minor differences between men and women were present in baseline characteristics and treatment for MI, in general, conferring a higher risk status and a lower incidence of CABG in the women. CONCLUSIONS: Pravastatin led to significant early reduction of a wide range of cardiovascular events in post-MI women with average cholesterol levels.

Adult↗
PubMed1998

The relation between dietary intake and adipose tissue composition of selected fatty acids in US women.

We compared fatty acid amounts in adipose tissue with fatty acid intake calculated from 2 separate weeks of diet recording and two food-frequency questionnaires for 140 participants in the Nurses' Health Study. Our results showed that the amounts of polyunsaturated and trans fatty acids in adipose tissue reflect dietary intake and confirm those of previous studies. The correlation between the polyunsaturated fatty acid content of adipose tissue and polyunsaturated fatty acid intake from the average of the two food-frequency questionnaires was 0.40; this correlation for trans fatty acids was also 0.40. Linolenic acid amounts in adipose tissue were also moderately correlated with intake from the average of the food-frequency questionnaires (r = 0.34). An estimate of trans fatty acid intake from vegetable sources correlated much more strongly with adipose trans fatty acids than did an estimate of trans fatty acids from animal sources. Adipose tissue aspirates can be used to indicate intake of exogenous fatty acids.

Adipose Tissue↗
PubMed1998

Effect on blood pressure of potassium, calcium, and magnesium in women with low habitual intake.

In populations, dietary intakes of potassium, calcium, and magnesium each have been inversely associated with blood pressure. However, most clinical trials in normotensive populations have not found that dietary supplements of these minerals lowered blood pressure. We tested the hypothesis that normotensive persons who have low habitual intake of these minerals would be particularly responsive to supplementation. Three hundred normotensive women in the Nurses Health Study II (mean age, 39 years), whose reported intakes of potassium, calcium, and magnesium were between the 10th and 15th percentiles, received for 16 weeks' duration daily supplements of either potassium 40 mmol, calcium 30 mmol (1200 mg), magnesium 14 mmol (336 mg), all three minerals together or placebos. At baseline, mean (+/-SD) 24-hour ambulatory blood pressures were 116+/-8 and 73+/-6 mm Hg systolic and diastolic, respectively, and mean dietary intakes of potassium, calcium, and magnesium were 62+/-20 mmol/d, 638+/-265 mg/d, and 239+/-79 mg/d, respectively. The mean differences (with 95% confidence intervals) of the changes in systolic and diastolic blood pressures between the treatment and placebo groups were significant for potassium, -2.0 (-3.7 to -0.3) and -1.7 (-3.0 to -0.4), but not for calcium, -0.6 (-2.2 to 1.0) and -0.7 (-2.0 to 0.6), or for magnesium, -0.9 (-2.6 to 0.8) and -0.7 (-2.2 to 0.8). The administration of calcium and magnesium with potassium did not enhance the effect of potassium alone, and the changes in blood pressure were not significant -1.3 (-3.0 to 0.4) and -0.9 (-2.2 to 0.4). In conclusion, potassium, but not calcium or magnesium supplements, has a modest blood pressure-lowering effect in normotensive persons with low dietary intake. This study strengthens evidence for the importance of potassium for blood pressure regulation in the general population.

Adult↗
PubMed1998

Metabolism of Apo(a) and ApoB100 of lipoprotein(a) in women: effect of postmenopausal estrogen replacement.

The metabolism in plasma of apo(a) and apoB100, the major protein components of lipoprotein(a) [Lp(a)], and the mechanism by which estrogen lowers Lp(a) concentration are both not well understood. Estrogen or placebo were administered to 12 postmenopausal women in a double-blind cross-over design; and after each treatment, apo(a) and apoB100 in Lp(a) were endogenously labeled by i.v. trideuterated leucine. After estrogen treatment, mean Lp(a) concentration decreased during estrogen, from 25 mg/dL, by 20% (P < 0.01); and the mean production rate of apo(a) decreased, from 0.31 nmol/kg.day, by 34% (P = 0.046). In contrast, the mean fractional catabolic rates of apo(a) were similar, 0.36 vs. 0.31/day (P = 0.23). In 6 women, the kinetics of apo(a) and apoB100, the two major proteins of Lp(a), were studied during estrogen and placebo periods. During both periods, the rate of appearance of tracer was similar in Lp(a)-apo(a) and Lp(a)-apoB100, as were the resulting metabolic rates and the changes during estrogen treatment. In conclusion, the findings are more compatible with intracellular synthesis of Lp(a) from nascent apo(a) and apoB100 than extracellular assembly from plasma low-density lipoproteins. Reduced flux into plasma of Lp(a), an atherogenic lipoprotein, could contribute to the lower cardiovascular disease rates in women receiving estrogen replacement therapy.

Aged↗
PubMed1997

A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.

BACKGROUND: It is known that obesity, sodium intake, and alcohol consumption factors influence blood pressure. In this clinical trial, Dietary Approaches to Stop Hypertension, we assessed the effects of dietary patterns on blood pressure. METHODS: We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg. For three weeks, the subjects were fed a control diet that was low in fruits, vegetables, and dairy products, with a fat content typical of the average diet in the United States. They were then randomly assigned to receive for eight weeks the control diet, a diet rich in fruits and vegetables, or a "combination" diet rich in fruits, vegetables, and low-fat dairy products and with reduced saturated and total fat. Sodium intake and body weight were maintained at constant levels. RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg, respectively. The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more, respectively, than the control diet (P<0.001 for each); the fruits-and-vegetables diet reduced systolic blood pressure by 2.8 mm Hg more (P<0.001) and diastolic blood pressure by 1.1 mm Hg more than the control diet (P=0.07). Among the 133 subjects with hypertension (systolic pressure, > or =140 mm Hg; diastolic pressure, > or =90 mm Hg; or both), the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more, respectively, than the control diet (P<0.001 for each); among the 326 subjects without hypertension, the corresponding reductions were 3.5 mm Hg (P<0.001) and 2.1 mm Hg (P=0.003). CONCLUSIONS: A diet rich in fruits, vegetables, and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure. This diet offers an additional nutritional approach to preventing and treating hypertension.

Adult↗
PubMed1997

Effect of estrogen on very low density lipoprotein and low density lipoprotein subclass metabolism in postmenopausal women.

Estrogen decreases low density lipoprotein (LDL) particle size, and smaller LDL particles are associated with coronary atherosclerosis. To understand the metabolic basis for this change, we studied the effect of oral 17 beta-estradiol (2 mg/day) on apolipoprotein B-100 (apoB) metabolism, in eight healthy postmenopausal women. The study was a randomized, double blinded, placebo-controlled, cross-over trial with intervention sequences of 6 weeks each. ApoB in very low density lipoprotein, intermediate density lipoprotein, and LDL subclasses was endogenously labeled with [D3]L-leucine, and metabolic rates were calculated by computer modeling. The overall effect of oral estrogen therapy on apoB metabolism was to accelerate the fractional catabolic rates of all particles studied and production rates of all except IDL. For light LDL (density = 1.019-1.036 g/mL), estrogen increased the mean fractional catabolic rate by 63% from 0.59 to 0.96 pools/day (P = 0.02), whereas the production rate increased by a lesser amount (42%) from 575 to 817 mg/day (P = 0.10). These metabolic changes reduced light LDL cholesterol and apoB concentrations by 26% (P = 0.005) and 19% (P = 0.03), respectively. In contrast, dense LDL (density = 1.036-1.063 g/mL) cholesterol and apoB concentrations were unchanged by the intervention, as both the apoB fractional catabolic rate and production rate were significantly increased by similar amounts, 39% (from 0.41 to 0.57 pools/day, P = 0.01) and 38% (from 434 to 601 mg/day; P = 0.003), respectively. Estrogen decreased the predominant LDL peak particle size from 273 to 268 A (P = 0.04). Thus, estrogen therapy increases the clearance of both light and dense LDL, counteracting increases in production rates. The reduced plasma residence times of light and dense LDL both may be antiatherogenic, even though, for dense LDL, the concentration did not change.

Adult↗
PubMed1996

The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.

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 percent of the patients in the pravastatin group and 10 percent of those in the placebo group, a 26 percent reduction (P=0.005), and coronary angioplasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group, a 23 percent reduction (P=0.01). The frequency of stroke was reduced by 31 percent (P=0.03). There were no significant differences in overall mortality or mortality from noncardiovascular causes. Pravastatin lowered the rate of coronary events more among women than among men. The reduction in coronary events was also greater in patients with higher pretreatment levels of LDL cholesterol. CONCLUSIONS: These results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels.

Adult↗
PubMed1996

Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels. A randomized, placebo-controlled trial. Harvard Atherosclerosis Reversibility Project (HARP) Study Group.

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.

Algorithms↗
PubMed1996

A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction.

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<.001). Cases also had higher median triglyceride levels (1.90 vs 1.49 mmol/L [168 vs 132 mg/dL]; P<.001). The LDL diameter had a high inverse correlation with triglyceride level (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.

Adult↗
PubMed1996

Effects of inherent responsiveness to diet and day-to-day diet variation on plasma lipoprotein concentrations.

We studied the biological variability and responsiveness to dietary fat of plasma lipoprotein cholesterol and triacylglycerol concentrations. Ten normal persons were studied on 3 consecutive days while they were eating their unrestricted usual diets and after 8, 9, and 10 d of eating a constant high-fat and low-fat diet administered in a crossover design. The changes in plasma low-density-lipoprotein (LDL)-cholesterol concentrations from baseline with the high-fat diet were inversely correlated with the changes from baseline with the low-fat diet (r = -0.74, P = 0.01), as well as with the changes from the low-fat to high-fat diet (r = -0.93, P < 0.001). The extent of increases in plasma LDL-cholesterol concentrations from the baseline to the high-fat diet were positively correlated with the increases from the low-fat to the high-fat diet (r = 0.93, P < 0.001). The responses of high-density-lipoprotein (HDL) cholesterol were not consistently correlated. The within-person between-day CV of LDL decreased from 10% with the unrestricted diet to 6% (P < 0.05) with the high-fat diet and to 7% with the low-fat diet (NS). The CV of total triacylglycerol (22%) and very-low-density-lipoprotein (VLDL) triacylglycerol (48%) on the unrestricted diet significantly decreased by 51-59% during both controlled diets (P = 0.03-0.06). The CV of HDL cholesterol was 5.3% during baseline, 4.2% during the high-fat diet, and 3.2% during the low-fat diet (P = 0.4, 0.19, respectively). In summary, individuals have a reproducible plasma LDL-cholesterol response when changing their dietary fat intake. The day-to-day variation in total triacylglycerol, VLDL triacylglycerol, and LDL-cholesterol concentrations decreases when day-to-day dietary variation is eliminated.

Adult↗
PubMed1996

Effects of shrimp consumption on plasma lipoproteins.

Shrimp is very low in total fat, yet it has a high cholesterol content. Although shrimp is a popular food in the American diet, many people avoid it because of its high cholesterol content. The objective of this study was to test the effect of the addition of cholesterol from shrimp to a low-fat baseline diet as well as to compare the effect of an equal amount of dietary cholesterol derived from shrimp or egg on the plasma lipoprotein pattern of normolipidemic subjects. In a randomized crossover trial, a diet containing 300 g shrimp/d, which supplied 590 mg dietary cholesterol/d, significantly increased low-density-lipoprotein (LDL) cholesterol by 7.1% (P = 0.014) and high-density-lipoprotein (HDL) cholesterol by 12.1% (P = 0.0001) when compared with a baseline diet matched for fat content but containing only 107 mg cholesterol/d. However, because the percentage increase in LDL cholesterol was less than for HDL cholesterol, the shrimp diet did not worsen the ratio of total cholesterol to HDL cholesterol or the ratio of LDL to HDL cholesterol. Moreover, shrimp consumption decreased triacylglycerol (triglyceride) concentrations by 13% (P = 0.004). The diet containing two large eggs per day with 581 mg dietary cholesterol/d also raised LDL- and HDL-cholesterol concentrations compared with baseline, but the percentage increase in LDL cholesterol (10.2%, P = 0.0001) was more than for HDL cholesterol (7.6%, P = 0.004) and there was a trend toward worse lipoprotein ratios. In a comparison of the two high-cholesterol diets, the shrimp diet produced significantly lower ratios of total to HDL cholesterol and lower ratios of LDL to HDL cholesterol than the egg diet as well as lower triacylglycerol concentrations. We conclude that moderate shrimp consumption in normolipidemic subjects will not adversely affect the overall lipoprotein profile and can be included in "heart healthy" nutritional guidelines.

Adult↗
PubMed1996

Prevalence and correlates of symptomatic peripheral atherosclerosis in individuals with coronary heart disease and cholesterol levels less than 240 mg/dL: baseline results from the Cholesterol and Recurrent Events (CARE) Study.

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.

Anticholesteremic Agents↗
PubMed1996

The influence of apolipoprotein E on the interactions between normal human very low density lipoproteins and U937 human macrophages: heterogeneity among persons.

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.

Adult↗
PubMed1995

The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypocholesterolemic therapy on coronary atherosclerosis in angiographic trials. Harvard Atherosclerosis Reversibility Project Research Group.

Angiographic trials of coronary atherosclerosis treatment have demonstrated that lowering low density lipoprotein (LDL) cholesterol concentrations improves coronary artery stenosis. Most patients in previous trials have had at least mildly elevated LDL. Recently, however, the Harvard Atherosclerosis Reversibility Project (HARP) did not find such benefit in patients with lower baseline LDL levels compared with previous trials. We reviewed and analyzed all cholesterol-lowering trials that used angiographic endpoints. Unifactorial trials of hypocholesterolemic dietary or drug therapy demonstrated that the higher the baseline LDL, the greater the improvement in quantitatively determined stenosis in the treatment group compared with the controls (r = .83). Considering the change in stenosis in the treatment group alone, regression was more common in trials in which baseline mean LDL was > 170 mg/dl (> 4.4 mmol/liter), whereas progression occurred when baseline mean LDL was < 170 mg/dl (< 4.4 mmol/liter). HARP had the lowest baseline LDL (137 mg/dl [3.54 mmol/liter]), and showed no tendency for improvement in lesions. In contrast to the influence of baseline LDL levels, neither a low LDL level achieved on treatment nor a large percentage reduction in LDL was related to improvement in lesions. Sample size differences between HARP and the other trials are unlikely to be a major explanatory factor, since trials of comparable sample size to HARP, but with higher initial LDL, demonstrated favorable results. We conclude that coronary lesions that develop in the context of average LDL levels show less angiographic improvement in response to substantial LDL reduction than lesions in hypercholesterolemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. CARE Investigators.

Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2 mmol/liter). The other inclusion criteria for this study were age 21-75 years, low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5 mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0 mmol/liter). A total of 4,159 eligible consenting patients without other study exclusions were then randomly assigned to receive either pravastatin 40 mg daily or matching placebo in addition to their individualized conventional therapy. The trial was designed to have a median follow-up of 5 years. Study endpoints will be evaluated with respect to predefined subgroups according to baseline lipid values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗