Primary prevention of heart disease in women.

Women die from heart disease at the same rate as men. However, because women generally live longer than men, the effect of heart disease on women is often ignored.

Behenic acid is a cholesterol-raising saturated fatty acid in humans.

BACKGROUND: Dietary behenic acid (22:0) is poorly absorbed. Because of its low bioavailability compared with other fatty acids and because of its very long chain length, the effect of dietary behenic acid (behenate) on serum lipid concentrations in humans is assumed to be neutral. OBJECTIVE: The objective was to establish the cholesterol-raising potential of behenic acid by comparing the effects on lipid and lipoprotein concentrations of a specially formulated fat enriched with behenic acid with those of palm oil (rich in palmitic acid; 16:0) and high-oleic acid sunflower oil (rich in cis oleic acid; 18:1). DESIGN: In a randomized, crossover, metabolic-ward study, 7 mildly hypercholesterolemic men were fed 3 natural-food diets supplemented with behenate oil, palm oil, or high-oleic acid sunflower oil. Mean serum lipid and lipoprotein concentrations and plasma triacylglycerol fatty acid composition were determined from fasting blood drawn during the final 4 d of each 3-wk diet period. RESULTS: Behenate oil produced mean concentrations of total cholesterol (5.87+/-0.8 mmol/L) and LDL cholesterol (4.40+/-0.8 mmol/L) not significantly different from those produced by palm oil (5.84+/-0.7 and 4.42+/-0.7 mmol/L, respectively) but significantly higher than those produced by high-oleic acid sunflower oil (5.12+/-0.5 and 3.70+/-0.6 mmol/L, respectively). There were no significant differences in triacylglycerol or HDL-cholesterol concentrations. CONCLUSIONS: Despite its low bioavailability compared with oleic acid, behenic acid is a cholesterol-raising fatty acid in humans and is therefore not a suitable substitute for palmitic acid in manufactured triacylglycerols.

Connections between obesity and dyslipidaemia.

The importance of the obesity-lipid connection has suffered from the traditional reductionism view of science. Excess body weight has rarely been deemed an independent risk factor for coronary heart disease, directing physicians to target therapies towards the risk factors that excess body weight modifies (e.g. raising HDL, lowering blood pressure) instead of targeting the cause. The efforts of Adult Treatment Panel III to define and identify the metabolic syndrome as a secondary target may spur practitioners to revisit the need for weight management in patients with lipid disorders.

Cardiovascular risk factors in young adult survivors of childhood acute lymphoblastic leukemia.

PURPOSE: To assess cardiovascular risk factors (CVRF) in young adult survivors of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Twenty-six subjects (median age, 20.9 years; median interval since completion of therapy, 13.3 years) were evaluated. Ten participants had received cranial irradiation (CRT), whereas 16 had received only chemotherapy. Primary outcome measures included body mass index (BMI), blood pressure, fasting lipoprotein, glucose, and insulin levels. Secondary measures included insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 levels, physical activity index, a 7-day dietary recall, tobacco product use, and measurement of the intima-media thickness (IMT) of the common carotid artery. RESULTS: Sixty-two percent (16/26) of participants had at least one CVRF potentially related to their cancer treatment (obesity, dyslipidemia, increased blood pressure, or insulin resistance), with 30% (7/26) having more than two CVRF. Thirty-one percent (8/26) of subjects were obese (BMI > or = 30). Subjects who were treated with CRT (BMI, 30.4 +/- 6.7) had an increased BMI (P = 0.039) in comparison with those who received only chemotherapy (BMI, 25.4 +/- 5.1). Triglyceride and very low-density lipoprotein C levels were significantly higher in those treated with CRT (P = 0.027 and 0.022, respectively). The IGF-1 was inversely correlated with IMT (total group, -0.514, P = 0.009; females only, -0.729, P = 0.003). CONCLUSIONS: Young adult survivors of childhood ALL, especially those treated with CRT, are at risk for obesity and dyslipidemia, insulin resistance, hypertension, and cardiovascular disease. Further investigation of these risks is warranted.

Individual cholesterol variation in response to a margarine- or butter-based diet: A study in families.

CONTEXT: The effectiveness of dietary modification in reducing low-density lipoprotein cholesterol (LDL-C) levels can be reliably predicted for populations, but not for individuals. OBJECTIVE: To determine whether individual variation in cholesterol response to dietary modification is a familial trait. DESIGN: Two-period, outpatient crossover trial conducted from September 1997 to September 1999. SETTING AND PARTICIPANTS: Fifty-six families from the Dallas-Ft Worth, Tex, area with 2 biological parents and at least 2 children aged 5 years or older volunteered; 46 families (n = 92 adults and n = 134 children) completed the study. INTERVENTION: All families followed two 5-week dietary regimens that included individualized daily dietary prescriptions and emphasized a low-saturated fat diet supplemented with specially manufactured baked goods and spreadable fat. One regimen used butter only and the other used margarine only. MAIN OUTCOME MEASURE: Mean LDL-C levels during the last 2 weeks of each dietary period. RESULTS: Margarine intake compared with butter intake lowered LDL-C levels 11% in adults (95% confidence interval [CI], 13% to 9%) and 9% in children (95% CI, 12% to 6%) (P<.001 for both adults and children). The distribution of individual responses were peaked around the mean response. For adults and children together, family membership accounted for 19% of variability in response (P =.007). In children, family membership accounted for 40% of variability in response of percent change in LDL-C levels (P =.002). Body mass index and change in cholesterol ester (CE) 18:2/18:1 ratio accounted for 26% of variation, leaving 26% still attributable to family membership. In all participants, BMI predicted response-heavier individuals had higher LDL-C levels, less excursion in CE fatty acids, and less LDL-C response to dietary change. CONCLUSIONS: Our results suggest that individual variation in response to a cholesterol-lowering diet is a familial trait. Body weight is an important modifiable factor that influences response. JAMA. 2000;284:2740-2747.

Nutritional and health benefits of beer.

Physicians should be aware of the growing evidence supporting the nutritional and health benefits of moderate consumption of alcohol as part of a healthy lifestyle. The recently approved voluntary label on wine ("the proud people who made this wine encourage you to consult your family doctor about the health effects of wine consumption") implies that physicians should promote wine as the preferred source of dietary alcohol. However, studies evaluating the relative benefits of wine versus beer versus spirits suggest that moderate consumption of any alcoholic beverage is associated with lower rates of cardiovascular disease. From a nutritional standpoint, beer contains more protein and B vitamins than wine. The antioxidant content of beer is equivalent to that of wine, but the specific antioxidants are different because the barley and hops used in the production of beer contain flavonoids different from those in the grapes used in the production of wine. The benefits of moderate alcohol consumption have not been generally endorsed by physicians for fear that heavy consumers may consider any message as a permissive license to drink in excess. Discussions with patients regarding alcohol consumption should be made in the context of a general medical examination. There is no evidence to support endorsement of one type of alcoholic beverage over another. The physician should define moderate drinking (1 drink per day for women and 2 drinks per day for men) for the patient and should review consumption patterns associated with high risk.

Comparison of the effects of medium-chain triacylglycerols, palm oil, and high oleic acid sunflower oil on plasma triacylglycerol fatty acids and lipid and lipoprotein concentrations in humans.

Although medium-chain triacylglycerols (MCTs, composed of medium-chain fatty acids 8:0 and 10:0) have long been described as having neutral effects on serum cholesterol concentrations, experimental evidence supporting this claim is limited. In a randomized, crossover, metabolic-ward study, we compared the lipid effects of a natural food diet supplemented with either MCTs, palm oil, or high oleic acid sunflower oil in nine middle-aged men with mild hypercholesterolemia. Rather than having a neutral effect, MCT oil produced total cholesterol concentrations that were not significantly different from those produced by palm oil (MCT oil: 5.87 +/- 0.75 mmol/L; palm oil: 5.79 +/- 0.72 mmol/L) but significantly higher than that produced by high oleic acid sunflower oil (5.22 +/- 0.52 mmol/L). Low-density-lipoprotein (LDL)-cholesterol concentrations paralleled those of total cholesterol. MCT oil tended to result in higher triacylglycerol concentrations than either palm oil or high oleic acid sunflower oil, but this difference was not significant. There were no differences in high-density-lipoprotein cholesterol concentrations. The palmitic acid and total saturated fatty acid content of plasma triacylglycerols in the MCT-oil diet was not significantly different from that in the palm oil diet. On the basis of percentage of energy, this study suggests that medium-chain fatty acids have one-half the potency that palmitic acid has at raising total and LDL-cholesterol concentrations.

Hormone replacement therapy: benefit and safety issues.

Based on evidence that hormone replacement therapy is cardioprotective, enthusiasm for universal hormone replacement therapy in postmenopausal women has grown Estrogens lower LDL, raise HDL, dilate arteries and reduce LDL oxidation potential. However, the benefits of hormone replacement therapy must be weighed against potential risks of thrombotic events, endometrial cancer and breast cancer. Data from randomized, placebo-controlled trials are not yet available to verify whether benefits exceed risk. Tabulating the evidence discussed below, most postmenopausal women will benefit from hormone replacement therapy.

Review of human studies evaluating individual dietary responsiveness in patients with hypercholesterolemia.

Individual variation in the low-density-lipoprotein (LDL)-cholesterol response to a cholesterol-lowering diet has been well documented in inpatient and outpatient diet studies. This variation could be due to both clinical and biological factors. Clinical factors include adherence to dietary changes and changes in body weight. Biological factors include specific changes in dietary composition, initial serum cholesterol concentrations, presence of excess body weight, the fractional catabolic rate of LDL with a diet high in saturated fatty acid, the presence of specific isoforms of apoprotein E and apoprotein A-IV, changes in the gene encoding apoprotein B or the apoprotein A-I promoter region, and the ultracentrifugation pattern of LDL lipoproteins. Work exploring the metabolic basis for individual variation in responsiveness to a cholesterol-lowering diet is in its infancy. Careful studies controlling for the clinical influences of responsiveness are needed so that true biological determinants of response can be uncovered.

Effects of continuous combined hormone-replacement therapy on lipid levels in hypercholesterolemic postmenopausal women.

PURPOSE: To test the lipid-lowering effects of continuous combined hormone-replacement therapy in hypercholesterolemic postmenopausal women. PATIENTS AND METHODS: A total of 32 postmenopausal women identified through health fair and cholesterol screening records, whose ad libitum low-density lipoprotein (LDL) cholesterol level (mean of 2 measurements) was > 130 mg/dL, and whose fasting triglycerides were < 250 mg/dL, participated in a placebo-controlled, nonrandomized trial testing the lipid-lowering effect of continuous combined hormone-replacement therapy. Women with a history of uterine fibroids, thrombophlebitis, family or personal history of breast cancer, or recent hormone use were excluded. After a 1-month period to standardize baseline dietary intake (Hi-Sat), patients were taught a cholesterol-lowering, Step-One diet, which they followed for the remainder of the study. After 3 months, patients supplemented the Step-One diet with daily placebo tablets for 3 months, followed by supplementation with conjugated estrogens 0.625 mg/d plus medroxyprogesterone 2.5 mg/d for 3 months. The means of five fasting lipid and lipoprotein values at the end of each 3-month supplementation period were compared. RESULTS: Total cholesterol fell from 261 mg/dL to 250 mg/dL to 233 mg/dL, with LDL reduction from 181 mg/dL to 173 mg/dL to 150 mg/dL, on diet and diet plus continuous combined hormone-replacement therapy, respectively (all P < 0.05). Whereas 26 of the 32 women had LDL values above 160 mg/dL during the Hi-Sat diet, only 10 of the 32 women remained with LDL values in this range during Step-One diet plus hormone therapy. Besides improving LDL cholesterol levels, continuous combined hormone-replacement therapy was associated with an increase in high density lipoprotein (HDL) cholesterol levels from 51 mg/dL to 54 mg/dL (P < 0.05). The 2 women whose HDL cholesterol levels were < 35 mg/dL during the Step-One diet plus placebo achieved HDL cholesterol levels > 35 mg/dL during hormone therapy. Nevertheless, continuous combined hormone-replacement therapy was associated with a high frequency of side effects, including breast tenderness and uterine bleeding. Most bothersome side effects dissipated after an initial adjustment period. CONCLUSIONS: Continuous combined hormone-replacement therapy can produce significant and therapeutic reductions in LDL cholesterol levels in hypercholesterolemic postmenopausal women. After internists become familiar with the expected side effects and their time course, this regimen may provide an effective approach in the management of hypercholesterolemia in postmenopausal women who have not undergone hysterectomy.

Efficacy of low-dose cholesterol-lowering drug therapy in men with moderate hypercholesterolemia.

OBJECTIVE: To test the potency of low-dose cholesterol-lowering drug therapy in patients with moderate hypercholesterolemia and to evaluate the effectiveness for cholesterol lowering of a safe regimen to be used in primary prevention of coronary heart disease. DESIGN: The efficacy of three drug regimens (cholestyramine resin, 8 g/d; cholestyramine resin, 8 g/d, plus lovastatin, 5 mg/d; and lovastatin, 20 mg/d) was tested in 26 men aged 31 to 70 years with moderate hypercholesterolemia after a Step-One cholesterol-lowering diet. Each drug period was 3 months in duration, interspersed by a 1-month period of the Step-One diet only. Blood for lipid and lipoprotein measurements was obtained on 5 different days during the last 2 weeks of each drug and diet-only period. RESULTS: Cholestyramine resin therapy at 8 g/d achieved a significant reduction in low-density lipoprotein cholesterol levels from 4.47 mmol/L (173 mg/dL) to 3.90 mmol/L (151 mg/dL) (P < .005). The addition of 5 mg of lovastatin to cholestyramine therapy achieved even lower levels, averaging 3.39 mmol/L (131 mg/dL) (P < .005). Lovastatin therapy at 20 mg/d produced lowering of low-density lipoprotein cholesterol levels similar to that of the low-dose combination. CONCLUSIONS: Low-dose combination drug therapy for the management of hypercholesterolemia appears to be an effective means of lowering cholesterol levels that remain persistently elevated after dietary therapy, at the same time, it should carry a low risk of toxic effects.

Lack of efficacy of low-dose sitostanol therapy as an adjunct to a cholesterol-lowering diet in men with moderate hypercholesterolemia.

Plant sterols have been shown to reduce dietary cholesterol absorption and hence, total and low-density-lipoprotein (LDL)-cholesterol concentrations in humans. In this study the cholesterol-lowering effects of dietary supplementation with the hydrogenated plant sterol sitostanol (3 g/d) were tested in 33 men with moderate hypercholesterolemia who were consuming an outpatient diet in which dietary cholesterol was restricted to < 200 mg/d. Sitostanol therapy did not significantly lower LDL cholesterol compared with the diet alone. Similarly, sitostanol therapy in conjunction with a cholesterol-lowering regimen of diet and 8 g cholestyramine did not significantly lower LDL-cholesterol concentrations. Hence, although previous reports have suggested that low-dose sitostanol therapy is an effective means of reducing LDL-cholesterol concentrations, its effectiveness may be attenuated when the diet is low in cholesterol.