Clonal characteristics of experimentally induced "atherosclerotic" lesions in the hybrid hare.

The female hybrid hare (Lepus timidus x Lepus europaeus) is heterozygous for electrophoretically separable, X-linked isoenzymes of glucose-6-phosphate dehydrogenase. The isoenzymes of this animal have been used as cellular markers in the study of the clonal origins of experimentally induced atherosclerotic lesions. Aortic lesions produced in the hybrid hare by feeding cholesterol and injuring the aortic wall with a catheter have been shown to have polyclonal characteristics and in this way are fundamentally different from atherosclerotic fibrous plaques in man.

Left ventricular hypertrophy as an independent predictor of acute cerebrovascular events in essential hypertension.

BACKGROUND: It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension. METHODS AND RESULTS: A total of 2363 initially untreated hypertensive patients (mean age 51+/-12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m(2)). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG conferred an increased risk for cerebrovascular events (relative risk [RR] 1.79; 95% CI 1.17 to 2.76). LVH by echocardiography also conferred a higher risk for cerebrovascular events (RR 1.64; 95% CI 1.07 to 2.68). For each increase in LV mass of 1 SD (29 g/m(2)), there was a significant independent increase in the risk for cerebrovascular events (RR 1.31; 95% CI 1.09 to 1.58). CONCLUSIONS: In apparently healthy patients with essential hypertension, LVH diagnosed by ECG or echocardiography confers an excess risk for stroke and transient ischemic attack independently of BP and other individual risk factors.

Normal triglyceride levels and coronary artery disease events: the Baltimore Coronary Observational Long-Term Study.

OBJECTIVES: This study sought to evaluate long-term predictors of coronary events in men and women with arteriographically defined coronary artery disease (CAD). BACKGROUND: There is conflicting evidence of the role of triglycerides (TGs) as a prognosticator of CAD, and no studies have examined the long-term outcome of "normal" levels in predicting new coronary events. METHODS: This was a retrospective cohort study that evaluated 740 consecutive patients presenting for diagnostic coronary arteriography between 1977 and 1978. Beginning in 1988, patients with arteriographic CAD (n=350) were recontacted and asked to complete detailed medical questionnaires. Case and control patients were stratified by development of new coronary events, including death from ischemic heart disease, nonfatal myocardial infarction and revascularization. RESULTS: There were 199 events during the 18-year follow-up period. The mean high density lipoprotein cholesterol (HDL-C) was significantly lower (35 vs. 39 mg/dl; p=0.002) and TGs higher (160 vs. 137 mg/dl; p=0.03) in case patients than in control patients; After adjusting for age, gender and beta-adrenergic blocking agent use, multiple logistic regression analysis revealed the following independent predictors of CAD events: diabetes mellitus (relative risk [RR] 2.1, 95% confidence interval [CI] 1.4% to 3.1%), HDL-C <35 mg/dl (RR 1.5, 95% CI 1.1% to 2.00) and TGs >100 mg/dl (RR 1.5, 95% CI 1.1% to 2.1%). A Kaplan-Meier analysis revealed significantly reduced survival from CAD events in patients with baseline TG levels > or = 100 mg/dl compared with TG levels <100 mg/dl (p=0.008). CONCLUSIONS: TG levels previously considered "normal" are predictive of new CAD events. The cutpoints established by the National Cholesterol Education Program for elevated TGs (>200 mg/dl) may need to be refined.

Task Force 4: The relationship between cardiovascular specialists and generalists.

1. An imbalance between generalists and cardiovascular subspecialists exists that will require decades to correct. We question the validity of the 50:50 generalist/specialist ratio in view of current practice patterns for cardiology. 2. There has been a large increase in the number of cardiovascular specialists in the past 30 years that will continue if training programs remain at their current size. 3. Cardiovascular specialists provide a substantial amount of inpatient care, care to older patients and care to those with cardiovascular symptoms, although generalists actually provide the majority of office-based cardiovascular care. 4. A significant portion of cardiovascular specialist care can be classified as comprehensive care to patients with and without cardiovascular disease. 5. Most generalists and cardiovascular specialists do not perceive a need for additional cardiovascular specialists. 6. Many providers perform cardiovascular procedures at levels below the recommended threshold for maintenance of clinical competence. 7. Managed care may result in a reduced demand for cardiovascular specialists. 8. If cardiovascular specialists provide general care, it may not be assumed that previous training prepares them for generalist practice. 9. The appropriate boundaries of cardiovascular care between generalists and cardiovascular specialists are indistinct. They are defined somewhat by the training programs from which the generalists graduate. 10. Many generalists have deficiencies in basic skills in clinical cardiology. 11. Desirable interactions between generalists and cardiovascular specialists involve referral of patients in both directions to the provider who can give care to a given patient, at a given time, with the best outcome and lowest cost.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors in siblings of people with premature coronary heart disease.

Prior studies of the contribution of coronary disease risk factors to familial aggregation of premature coronary disease may have underestimated risk factors by relying on self-reported risk factor prevalence levels or, when risk factors have been measured, by using cut points in excess of the 90th percentile. To determine the actual prevalence of hyperlipidemia, hypertension and diabetes, and the awareness of these coronary risk factors in unaffected family members, 150 apparently coronary disease-free siblings of 86 people who had documented coronary disease before 60 years of age were studied. All subjects participated in a 1 day screening preceded by a self-administered risk factor questionnaire and a personal interview. Participation of both the index patients and siblings exceeded 86%. With the use of nationally established recommendations for blood pressure and lipids, which are based on coronary disease risk curves, screening revealed that 48% of brothers and 41% of sisters were hypertensive, 45% of brothers and 22% of sisters had a lipid abnormality, 38% of siblings were current cigarette smokers and 4.7% were diabetic. Two or more risk factors were present in 42% of brothers and 26% of sisters. More than 75% of siblings had one or more risk factors that would require intervention. When compared with a race-, gender- and age-matched reference population from the Lipid Research Clinics Prevalence Study, distributions for blood pressure and for total and low density lipoprotein cholesterol were higher for the siblings in every gender and age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolysis with recombinant tissue plasminogen activator in atherosclerotic thrombotic occlusion.

Human tissue plasminogen activator holds promise for the dissolution of coronary thrombi by intravenous administration and without systemic anticoagulation. Prior animal experiments have been conducted only in vessels without disease. To test the thrombolytic efficacy of recombinant tissue plasminogen activator in the presence of diseased intima, an established model of atherosclerosis was utilized. The aorta of 16 New Zealand white rabbits (2 to 3 kg) was made atherosclerotic by balloon endothelial denudation and concurrent 1% cholesterol feeding for 8 weeks. An aged (24 hour) heterologous (human) clot, labeled with I-125 fibrinogen was injected into the distal aorta and produced thrombotic occlusion. After 1 hour of thrombosis (control period), recombinant tissue plasminogen activator (100,000 IU approximately equal to 1 mg protein, n = 6) or streptokinase (100,000 IU, n = 5) or saline solution (n = 5) was systemically infused over 30 minutes. Serial blood samples, obtained to determine fractional change in blood radioactivity over time, showed a fourfold increase of blood radioactivity after tissue plasminogen activator and streptokinase infusion compared with the control period (47,400 +/- 3,300 [mean +/- standard error] versus 11,800 +/- 300 counts/min, p less than 0.001). Time to 50% of maximal thrombolysis was 41 +/- 14 minutes (+/- standard deviation) for tissue plasminogen activator versus 63 +/- 16 minutes for streptokinase (p less than 0.01). In six of six rabbits receiving tissue plasminogen activator and four of five rabbits receiving streptokinase, reestablishment of distal aortic flow was detected via the indwelling catheter within 25 minutes of drug infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography.

Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis.

Plasma sphingomyelin level as a risk factor for coronary artery disease.

Only a fraction of the clinical complications of atherosclerosis are explained by known risk factors. Animal studies have shown that plasma sphingomyelin (SM) levels are closely related to the development of atherosclerosis. SM carried into the arterial wall on atherogenic lipoproteins may be locally hydrolyzed by sphingomyelinase, promoting lipoprotein aggregation and macrophage foam cell formation. A novel, high-throughput, enzymatic method to measure plasma SM levels has been developed. Plasma SM levels were related to the presence of coronary artery disease (CAD) in a biethnic angiographic case-control study (279 cases and 277 controls). Plasma SM levels were higher in CAD patients than in control subjects (60+/-29 versus 49+/-21 mg/dL, respectively; P:<0. 0001). Moreover, the ratio of SM to SM+phosphatidylcholine (PC) was also significantly higher in cases than in controls (0.33+/-0.13 versus 0.29+/-0.10, respectively; P:<0.0001). Similar relationships were observed in African Americans and whites. Plasma SM levels showed a significant correlation with remnant cholesterol levels (r=0.51, P:<0.0001). By use of multivariate logistic regression analysis, plasma SM levels and the SM/(SM+PC) ratio were found to have independent predictive value for CAD after adjusting for other risk factors, including remnants. The odds ratio (OR) for CAD was significantly higher for the third and fourth quartiles of plasma SM levels (OR 2.81 [95% CI 1.66 to 4.80] and OR 2.33 [95% CI 1.38 to 3. 92], respectively) as well as the SM/(SM+PC) ratio (OR 1.95 [95% CI 1.10 to 3.45] and OR 2.33 [95% CI 1.34 to 4.05], respectively). The findings indicate that human plasma SM levels are positively and independently related to CAD. Plasma SM levels could be a marker for atherogenic remnant lipoprotein accumulation and may predict lipoprotein susceptibility to arterial wall sphingomyelinase.

High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men.

Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (>/=50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively; P:=0.004), and only in this group was the presence of small apo(a) isoforms (<22 kringle 4 repeats) associated with CAD (P:=0.043). Elevated Lp(a) levels (>/=30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (P:<0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a).

The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals.

OBJECTIVE: To determine the percentage of patients in the multicenter Lipid Treatment Assessment Project receiving lipid-lowering therapy who are achieving low-density lipoprotein cholesterol (LDL-C) goals as defined by National Cholesterol Education Program (NCEP) guidelines. METHODS: Adult patients with dyslipidemia, who had been receiving the same lipid-lowering therapy for at least 3 months, were assessed at investigation sites. Lipid levels were determined once in each patient at the time of enrollment. The primary end point was the success rate, defined as the proportion of patients who achieved their LDL-C target level as specified by NCEP guidelines. RESULTS: A total of 4888 patients from 5 regions of the United States were studied. Of these, 23% had fewer than 2 risk factors for coronary heart disease (CHD) and no evidence of CHD (low-risk group), 47% had 2 or more risk factors and no evidence of CHD (high-risk group), and 30% had established CHD. Overall, only 38% of patients achieved NCEP-specified LDL-C target levels; success rates were 68% among low-risk patients, 37% among high-risk patents, and 18% among patients with CHD. Drug therapy was significantly (P< or =.001) more effective than nondrug therapy in all patient risk groups. However, many patients treated with lipid-lowering drugs did not achieve LDL-C target levels. CONCLUSIONS: Large proportions of dyslipidemic patients receiving lipid-lowering therapy are not achieving NCEP LDL-C target levels. These findings indicate that more aggressive treatment of dyslipidemia is needed to attain goals established by NCEP guidelines.

Gout and risk for subsequent coronary heart disease. The Meharry-Hopkins Study.

BACKGROUND: Patients with gout are encountered frequently in clinical practice. Previous studies have suggested that hyperuricemia and gout may represent risk factors for coronary heart disease (CHD), the most common cause of death in American men. METHODS: Prospectively collected data from 2 longitudinal cohort studies of former medical students--371 black men in the Meharry Cohort Study and 1181 white men in the Johns Hopkins Precursors Study--were analyzed. The development of gout and of CHD was determined by physician self-report, and validated by using published criteria. The risk for CHD associated with gout was evaluated using Cox proportional hazards analysis. RESULTS: During a median follow-up of 30 years, there were 38 gout cases and 44 CHD events among the Meharry men, and 68 gout cases and 138 CHD events among the Hopkins men. Prior gout was not associated with an increased risk for incident CHD (relative risk = 1.20; 95% confidence interval, 0.37-3.92) among the Meharry men or among the Hopkins men (relative risk = 0.66; 95% confidence interval, 0.24-1.79). Multivariate analysis adjusted for known CHD risk factors did not alter these findings. CONCLUSION: These results, in black and white male physicians, do not suggest a role in men for targeting gout identification in the primary prevention of CHD.

Effect of ACTH, alpha-MSH, and beta-Lipotropin on calcium and phosphorus metabolism in the rabbit.

Studies were undertaken to investigate the effects of synthetic 1-24 adrenocorticotropin (ACTH), bovine alpha melanocyte-stimulating hormone (alpha-MSH), and ovine beta lipotropin (beta-LPH) on plasma calcium and phosphate in rabbits. Equimolar concentrations of these hormones were infused intravenously in intact and thyroidectomized animals. In addition, ACTH was similarly administered to adrenalectomized rabbits. ACTH, alpha-MSH, and beta-LPH all lowered plasma calcium and raised plasma phosphate. These changes were not prevented by prior thyroidectomy. ACTH was equally effective in inducing hypocalcemia and hyperphosphatemia in the absence of the adrenal glands, while adrenalectomy alone raised plasma calcium. From these findings we have concluded that 1) ACTH, alpha-MSH, and betaLPH affect phosphate as well as calcium metabolism; 2) these hormones do not act by releasing calcitonin; and 3) ACTH exerts its hypocalcemic-hyperphosphatemic effect, at least in part, independently of its trophic action on the adrenal glands.

Cardiovascular reactivity to the cold pressor test as a predictor of hypertension.

Cardiovascular reactivity to stress is hypothesized to be a marker for subsequent neurogenic cardiovascular disease, but few prospective studies of this hypothesis are available. We studied 910 white male medical students who had their blood pressure and pulse rate measured before and during a cold pressor test in the years 1948-1964. Hypertensive status (requiring drug treatment) was ascertained by annual questionnaires in the 20- to 36-year follow-up period. An association was observed between maximum change in systolic blood pressure and later hypertension, with a cumulative incidence of hypertension by age 44 of 6.7%, 3.0%, and 2.4% for a change in systolic blood pressure in the upper, middle two, and lowest quartiles, respectively (Kaplan-Meier, p less than 0.02). After adjustment for study entry age, Quetelet Index, cigarette smoking, pretest systolic blood pressure, and paternal or maternal history of hypertension in a Cox model, the association persisted. The excess risk associated with systolic blood pressure reactivity was not apparent until the population aged some 20 years and was most apparent among those in whom hypertension developed before age 45 (relative risk = 2.5, 95% confidence intervals = 1.47, 4.71 for a 20 mm Hg change). Diastolic blood pressure and heart rate changes were not associated with later hypertension. These data suggest that persons prone to later hypertension manifest an altered physiology at a young age.

Moderate alcohol consumption and coronary artery disease. A review.

An inverse association between moderate alcohol consumption and coronary artery disease has been demonstrated in epidemiologic studies of diverse design. These include ecologic correlations, case-control, longitudinal and clinical studies. The consistency, strength and independence of the inverse relationship argues persuasively for a causal association. These data also suggest that both abstention and heavy alcohol use are associated with an increased risk for coronary artery disease. The effect of moderate alcohol consumption on lipoprotein and apolipoprotein levels is a biologically plausible and likely mechanism for this inverse association. Alcohol consumption elevates HDL cholesterol, although it is unclear whether the HDL subfractions HDL-2 and HDL-3 are beneficially altered. Recent evidence, however, suggests that the apolipoproteins may be more important indicators of coronary artery disease, and moderate alcohol consumption does beneficially alter these proteins. Alcohol may also affect coronary artery disease by other mechanisms, which may include fibrinolytic activity, coagulation, blood pressure, coronary vasoreactivity, and sociobehavioral factors.

Epidemiology of thrombotic-hemostatic factors and their associations with cardiovascular disease.

Abundant evidence proves that thrombosis is involved in the acute presentation of coronary, cerebrovascular, and peripheral vascular diseases. However, the role of thrombotic factors in the development of the atherosclerotic lesions themselves has been more difficult to prove. This difficulty has been due, at least in part, to several methodologic issues in the study of hemostatic factors and cardiovascular disease (CVD). These include the possibility that associations between CVD and hemostatic factors may not be causal but rather due to confounding by other factors, acting as part of an extended causal pathway or requiring interaction with other risk factors or atherosclerotic disease, or may result from disease rather than causing the disease. In addition, several challenges remain in the measurement of hemostatic factors. Nonetheless, a growing number of studies have examined the association of CVD with coagulation factors (fibrinogen, factor VII, factor VIII, and platelet aggregability) and fibrinolytic factors [tissue plasminogen activator, plasminogen activator inhibitor 1, lipoprotein(a), and plasminogen or global fibrinolytic activity]. Of these, only for fibrinogen is there significant, strong, and consistent evidence of a causal association. Given the preliminary nature of these associations, any association between dietary factors and hemostatic factors other than fibrinogen is difficult to invoke as evidence for a deleterious effect of diet on CVD risk via thrombogenic mechanisms.

Effects of a milk chocolate bar per day substituted for a high-carbohydrate snack in young men on an NCEP/AHA Step 1 Diet.

This study compares the plasma cholesterol response with the isoenergetic substitution of a milk chocolate bar (46 g) given daily for a high-carbohydrate snack in healthy young men on a Step 1 Diet. Normocholesterolemic men (n = 42) were fed a Step 1 Diet for 21 d (run-in diet) followed by a 27-d experimental period during which they consumed the same diet plus either a milk chocolate bar or a high-carbohydrate snack; after this they consumed the run-in diet for 21 d followed by the other snack for 27 d. When subjects consumed a milk chocolate bar instead of the high-carbohydrate snack, high-density-lipoprotein (HDL) cholesterol was 0.08 +/- 0.03 mmol/L higher (P < 0.01) and plasma triglycerides were 0.06 +/- 0.03 mmol/L lower (P < 0.05). Substitution of a milk chocolate bar for a high-carbohydrate snack did not adversely affect the low-density-lipoprotein-(LDL) cholesterol response to a Step 1 Diet despite an increase in total fat and saturated fatty acid content of the diet. This response may be due to stearic acid.

Comparative lipid and lipoprotein responses to solid-food diets and defined liquid-formula diets.

BACKGROUND: Liquid-formula diets (LFDs) are useful in metabolic studies of the cholesterolemic effects of dietary lipids because they can be formulated with accuracy, facilitating precise delivery of fatty acids of interest. However, because of differences in composition and nutrient delivery between LFDs and solid-food diets (SFDs), there is a need to determine differences in their effects. OBJECTIVE: Our objective was to compare lipid and lipoprotein responses to changes in total fat, saturated fatty acids (SFAs), and cholesterol in subjects consuming an SFD or LFD. DESIGN: Twenty-one healthy subjects consumed controlled diets representative of an average American diet [AAD; 37% of energy from fat (15% from SFAs), and <50 mg cholesterol/MJ] or a National Cholesterol Education Program (NCEP) Step II diet [26% fat (5% from SFAs) and <25 mg cholesterol/MJ]. Other nutrients were similar between diets. Diets were consumed for 23 d in a randomized, crossover design. RESULTS: For the AAD and NCEP Step II diet, there were no significant differences in lipids and apolipoproteins when the LFD or SFD versions were consumed. In contrast, consumption of the SFD was associated with significantly lower total cholesterol and triacylglycerols than was consumption of the corresponding AAD or Step II LFD (P < 0.05). Subjective ratings of satiety, hunger, and quality of life between diet forms did not differ significantly. CONCLUSIONS: Both LFDs and SFDs yield quantitatively similar cholesterolemic responses to changes in dietary fat, SFAs, and cholesterol. LFDs may offer advantages because they provide easily administered, complete, balanced nutrition without affecting satiety.

Translation of nutritional sciences into medical education: the Nutrition Academic Award Program.

For the past 40 y the scientific community has decried the inadequacy of the training of physicians and other health professionals in the subject of human nutrition. In 1997 the National Heart, Lung, and Blood Institute developed the Nutrition Academic Award (NAA) Program, an initiative to improve nutrition training across a network of US medical schools. The purpose of this funding, which began in 1998, is to support the development and enhancement of nutrition curricula for medical students, residents, and practicing physicians to learn principles and practice skills in nutrition. The NAA recipients developed the Nutrition Curricular Guide for Training Physicians, a plan to incorporate clinical guidelines into physician practice skills, create educational and assessment practice tools, and evaluate curricula, materials, and teaching tools. Dissemination of NAA activities and materials will be facilitated by a national website, presentations and publications, and consultants and advisors from the NAA nutrition education programs. The NAA Program constitutes a major new effort to enhance nutrition knowledge and skills among health care providers and to effectively apply the science of human nutrition to clinical medicine. This article describes the purpose and aims of the NAA Program, the organizational structure of the network of recipients, a profile of the recipients and individual programs at 21 medical schools, the various strategies to overcome barriers in training physicians in human nutrition, and collaborative and dissemination efforts.

High-monounsaturated fatty acid diets lower both plasma cholesterol and triacylglycerol concentrations.

BACKGROUND: Low-fat diets increase plasma triacylglycerol and decrease HDL-cholesterol concentrations, thereby potentially adversely affecting cardiovascular disease (CVD) risk. High-monounsaturated fatty acid (MUFA), cholesterol-lowering diets do not raise triacylglycerol or lower HDL cholesterol, but little is known about how peanut products, a rich source of MUFAs, affect CVD risk. OBJECTIVE: The present study compared the CVD risk profile of an Average American diet (AAD) with those of 4 cholesterol-lowering diets: an American Heart Association/National Cholesterol Education Program Step II diet and 3 high-MUFA diets [olive oil (OO), peanut oil (PO), and peanuts and peanut butter (PPB)]. DESIGN: A randomized, double-blind, 5-period crossover study design (n = 22) was used to examine the effects of the diets on serum lipids and lipoproteins: AAD [34% fat; 16% saturated fatty acids (SFAs), 11% MUFAs], Step II (25% fat; 7% SFAs, 12% MUFAs), OO (34% fat; 7% SFAs, 21% MUFAs), PO (34% fat; 7% SFAs, 17% MUFAs), and PPB (36% fat; 8% SFAs, 18% MUFAs). RESULTS: The high-MUFA diets lowered total cholesterol by 10% and LDL cholesterol by 14%. This response was comparable with that observed for the Step II diet. Triacylglycerol concentrations were 13% lower in subjects consuming the high-MUFA diets and were 11% higher with the Step II diet than with the AAD. The high-MUFA diets did not lower HDL cholesterol whereas the Step II diet lowered it by 4% compared with the AAD. The OO, PO, and PPB diets decreased CVD risk by an estimated 25%, 16%, and 21%, respectively, whereas the Step II diet lowered CVD risk by 12%. CONCLUSION: A high-MUFA, cholesterol-lowering diet may be preferable to a low-fat diet because of more favorable effects on the CVD risk profile.

Atherosclerosis in the hypercholesterolemic hare. Comparison of coronary artery lesions induced by dietary cholesterol in the hare and the rabbit.

Atherosclerotic lesions in coronary arteries were compared in 10 hybrid hares and 14 rabbits after induction of hypercholesterolemia, using a cholesterol-enriched diet. All proximal portions of hare coronary arteries contained intimal lesions, often with severe luminal stenosis. These lesions were characterized by the presence of foam cells, smooth muscle cells, and areas of atheronecrosis. Foam cells were also found focally in the media. As part of the intimal changes, iron deposition was present in 65% and calcification was present in 32.5% of proximal segments examined. The proportion of segments with intimal lesions and the intima/media cross-sectional area ratios (I/M ratios) were greatest in proximal segments with stepwise decreases in the mid and distal segments. As area of myocardial infarction was present in one hare. In contrast, 46.5% of proximal segments of rabbit coronary arteries had no intimal lesions and those lesions present had no calcium or iron deposition. No infarction was observed in rabbit hearts. The proportion of segments with lesions and the mean I/M ratios were significantly greater in the hare than the rabbit, with proximal and mid coronary segments showing the most marked differences. The hare appears to develop coronary artery lesions more like those seen in man, with high grade, proximal stenoses occurring uniformly in hypercholesterolemic animals. In contrast, the atherosclerosis developing in rabbit coronary arteries is less uniform and includes involvement of intramyocardial arterioles. The hare offers several advantages as a model of human atherosclerosis.