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Hypothyroidism, an important cause of reversible hyperlipidemia.

Primary hypothyroidism was found to be the cause of hyperlipidemia in 22 patients. The mean age was 46 years, 59% were males, 27% had vascular disease, 14% had xanthomas and 86% had thyroid antibodies. Familial involvement was shown in 3 propositi. All patients were treated with L-thyroxine, 0.05--0.2 mg/day for a mean of 16 months. Combined hyperlipidemia was common (77%), and lipoprotein phenotyping revealed types IIB hyperlipopro-teinemia in 11, IIA in 5, III in 3 and IV in 3 patients. With treatment, normal plasma cholesterol (less than 265 mg/dl) and triglycerides (less than 200 mg/dl) were obtained in 91% and 86%, respectively. The mean maintenance L-thyroxine dose was 0.15 mg/day, but smaller doses often showed marked hypolipidemic effect. The mean +/- S. D. pretreatment fasting plasma cholesterol and triglycerides were 387 +/- 120 and 328 +/-247 mg/dl and on thyroid treatment the mean minimum levels were 205 +/- 46 and 133 +/- 65 mg/dl, respectively (both p values less than 0.005). Hypothyroidism has proved to be a common reversible form of hyperlipidemia. One cardiac patient died and three others had to have their L-thyroxine titrated to prevent angina. Family screening has been of use in case finding for auto-immune disease in 3 families.

Adolescent↗

Elevation of red cell sodium-lithium countertransport in hyperlipidemias.

Red cell Na-Li countertransport was measured in 78 normal subjects, 64 patients with essential hypertension, and 67 patients with hyperlipidemias. Both hypertensive and hyperlipidemic patients had elevated Na-Li countertransport compared to normal controls (p less than 0.001). Subjects with hyperlipidemia and hypertension had higher countertransport (p less than 0.02) than patients with only hyperlipidemia. Normotensive hyperlipidemic subjects had higher countertransport than normotensive and normolipidemic controls (p less than 0.02). This suggest that hypertension and high plasma lipids can influence independently the Na-Li countertransport. In another group of 52 normotensive subjects, Na-Li countertransport was positively correlated with serum total and free (unesterified) cholesterol, phospholipids and triglycerides. No correlations were found with HDL-cholesterol or HDL-phospholipids. A very high positive correlation was found between Na-Li countertransport and plasma acetylcholinesterase (p less than 0.005). These findings suggest that plasma lipids, probably through membrane lipids, can affect the maximal rate of the Na-Li exchange in red cells. The relationship between plasma or membrane lipids and cation transport should be further studied in erythrocytes and other cells.

Adult↗

Pancreatic xanthomatous neuropathy associated with hyperlipidemia: a cause of abdominal pain mimicking chronic pancreatitis.

"Hyperlipidemic crisis" is a term used to describe episodic abdominal pain in patients with hyperlipidemia. The morphologic correlates of this phenomenon have not been investigated and the etiology of the disorder is uncertain. We report a unique histologic finding in the pancreas of a 34-year-old woman with a 17-year history of episodic abdominal pain, sometimes accompanied by hyperamylasemia. At the age of 18 years, grossly elevated cholesterol and triglyceride levels were documented and type V hyperlipidemia was diagnosed. At the age of 34 years, subtotal pancreatectomy was performed for intractable abdominal pain. Histologic examination identified an increased number of enlarged pancreatic nerves that were infiltrated by foamy macrophages and encircled by fibrous tissue; endoneurial infiltration with macrophages occasionally split nerves into individual fascicles. Otherwise, the pancreas had only minimal fibrosis, nesidioblastosis, mucinous metaplasia of some pancreatic ducts, and scattered small collections of chronic inflammatory cells, subtle features suggesting very mild chronic pancreatitis. We propose that this novel xanthomatous neuropathy mimicked pancreatitis and was one of the underlying pathophysiologic mechanisms of abdominal pain in this patient. Further studies are necessary to document the prevalence of this new entity in patients with hyperlipidemia and to correlate its occurrence with "hyperlipidemic crisis" in those individuals.

Abdominal Pain↗

Hyperlipidemia: a novel etiologic factor in deep vein thrombosis.

The possible association of hyperlipidemia and deep vein thrombosis (DVT) was investigated in 59 consecutive patients. The incidence of hyperlipidemia, judged by the value of serum total cholesterol and triglyceride, was unexpectedly high (overall 59%, high total cholesterol alone 25%, high triglyceride alone 9%, combined 25%), as compared with 29% of the control (p < 0.001). The idiopathic DVT patients (without known etiologic factors) had a higher incidence of hypercholesterolemia (63%) than the normal subjects (20%, p = 0.0002). The idiopathic DVT patients showed higher total cholesterol level of 255 +/- 72 mg/dl than that of 194 +/- 36 in the control subjects (p < 0.0001). And 67% of the idiopathic DVT patients were hyperlipidemic. Thereby, hyperlipidemia may be an important etiologic factor in DVT, which has not been recognized previously. The low incidence of DVT in Asians may, thus, be attributable to their lower cholesterol level.

Adolescent↗

Angiographically silent atherosclerosis detected by intravascular ultrasound in patients with familial hypercholesterolemia and familial combined hyperlipidemia: correlation with high density lipoproteins.

OBJECTIVES: This study sought to evaluate the extent of atherosclerosis in coronary and iliac arteries in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia, using intravascular ultrasound imaging. BACKGROUND: Intravascular ultrasound imaging provides cross-sectional tomographic views of the vessel wall and allows quantitative assessment of atherosclerosis. METHODS: Forty-eight nonsmoking, asymptomatic patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia underwent intravascular ultrasound imaging of the left anterior descending coronary, left main coronary and common iliac arteries. Angiography showed only minimal or no narrowing in these vessels. Intravascular ultrasound images obtained during catheter pullback underwent morphometric analysis. Plaque burden was expressed as the mean and maximal intimal index (ratio of plaque area and area within the internal elastic lamina) and as the percent of vessel surface covered by plaque. RESULTS: Intravascular ultrasound detected plaque more frequently than angiography in the left anterior descending (80% vs. 29%, respectively), left main (44% vs. 16%) and iliac arteries (33% vs. 27%). Plaque burden was higher in the left anterior descending (mean intimal index [+/- SD] 0.25 +/- 0.16) than in the left main (0.11 +/- 0.16, p < 0.001) and iliac arteries (0.02 +/- 0.04, p < 0.001). Angiography detected lumen narrowing only in coronary arteries with a maximal intimal index > or = 0.42 (left anterior descending artery) and > or = 0.43 (left main artery). The area within the internal elastic lamina increased with plaque area in the left anterior descending (r = 0.82, p < 0.001) and left main arteries (r = 0.53, p < 0.001). By stepwise multiple regression analysis, the strongest predictor for plaque burden in the left anterior descending artery was the level of high density lipoprotein (HDL) cholesterol and total/HDL cholesterol ratio for the left main artery. CONCLUSIONS: In patients with heterozygous familial hypercholesterolemia and familial combined hyperlipidemia, extensive coronary plaque is present despite minimal or no angiographic changes. Compensatory vessel enlargement and diffuse involvement with eccentric plaque may account for the lack of angiographic changes. Levels of HDL cholesterol and total/HDL cholesterol ratio are far more powerful predictors of coronary plaque burden than are low density lipoprotein cholesterol levels in these patients with early, asymptomatic disease.

Adult↗

Assessment of reaching goal in patients with combined hyperlipidemia: low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or apolipoprotein B.

It is well established that patients with combined hyperlipidemia, defined as elevated triglyceride levels between 200 and 500 mg/dL and elevated low-density lipoprotein cholesterol >130 mg/dL, are at increased risk for coronary artery disease. The optimal assessment of reaching lipid goals in patients with combined hyperlipidemia is still far from settled and has been an area of revision and modification in recent guidelines. Although controversy remains as to the best single measurement to be used in treatment goals, current focus is on the use of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. This article reviews the use of these 3 biomarkers in assessing cardiovascular risk, and the strategies for managing combined hyperlipidemia.

Apolipoproteins B↗

Paradoxical exacerbation of combined hyperlipidemia in human apolipoprotein A-II transgenic mice treated with fenofibrate.

Apolipoprotein (apo) A-II has been biochemically and genetically linked to familial combined hyperlipidemia. Human ApoA-II transgenic mice and peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice share some similar phenotypic characteristics. The aim of this study was to determine whether a fibrate-induced PPARalpha activation corrects the combined hyperlipidemia present in human apoA-II transgenic mice. ApoA-II transgenic mice were treated with fenofibrate (250 mg/kg) for 13 days. After this period, they presented a remarkable 8-fold increase in plasma triglycerides. This was concomitant with a 4-fold increase in non-high-density lipoprotein (non-HDL) cholesterol, a quantitatively similar decrease in HDL cholesterol and a severe reduction in mouse plasma apoA-I and apoA-II. Fenofibrate stimulated liver fatty acid beta-oxidation, increased the transcriptional expression of carnitine palmitoyltransferase 1 and phospholipid transfer protein, and decreased expression of apoA-I and apoC-III. However, very-low-density lipoprotein (VLDL)-triglyceride production and lipoprotein lipase (LPL) activities and the expression of other PPARalpha target genes were similar in mice treated with vehicle and fenofibrate. Further, fenofibrate-treated mice presented decreased in vivo [3H]VLDL catabolism and decreased VLDL-triglyceride hydrolysis by exogenous LPL. Therefore, the paradoxical enhancement of hyperlipidemia in fenofibrate-treated apoA-II transgenic mice is mainly due to decreased VLDL catabolism and, also, to a partial impairment in PPARalpha-signaling.

Animals↗

Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia.

Relations between hyperlipidemia and chronic pancreatitis remain unclear. Microcirculatory disturbances and oxidative stress are involved in pathogeneses of a high numbers of diseases. The objective of this study was to induce hyperlipidemia in rats by long-term high-fat diet intake, then investigate the biochemical, microcirculatory, and histological alterations in blood and pancreatic tissues of these animals, and discuss their potential significances. Pancreatic blood flow was detected by intravital microscope; malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured in pancreatic tissues for assessment of oxidative stress and alpha-smooth muscle actin (alpha-SMA) expression was determined by immunohistochemical staining and RT-PCR. The results showed that the velocity of pancreatic microvascular blood flow of rats with hyperlipidemia decreased significantly as compared to control value (p = 0.008). Pancreatic MDA content increased whereas SOD activity decreased in these rats (p = 0.022; p = 0.039, respectively). Histologically, microvesicles in acinar and islet cells, dilated rough endoplasmic reticulum, swollen mitochondrion and modified vascular endothelial cells were observed under light microscope and transmission electron microscope. In addition, alpha-SMA expression was up-regulated significantly (p < 0.05). These results suggest that long-term high-fat diet can induce chronic pancreatic injuries which could be considered as "nonalcoholic fatty pancreatic disease", and pancreatic microcirculatory disturbances and oxidative stress may play an important part in the underlying pathogenesis.

Adaptation, Physiological↗

Hyperlipidemia is a risk factor for lymphatic metastasis in superficial esophageal carcinoma.

Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of the serum lipid level on tumor metastasis has not been well documented. Fasting serum levels of total cholesterol (TC) and triglycerides (TG) were examined in 54 patients with superficial esophageal cancer (SEC) invading lamia musucularis or submucosal layer who underwent esophagectomy with classical lymphadenectomy. The association between lymph node metastasis and the preoperative serum lipid levels as well as the pathological findings was retrospectively analyzed. The levels of TC and TG were significantly higher in 18 node-positive than in 36 node-negative patients (TC: 205.4+/-38.9 vs. 174.5+/-26.8 mg/dl, P<0.01; TG: 152.0+/-68.5 vs. 88.7+/-28.6 mg/dl, P<0.001). Patients with hypercholesterolemia (TC >/= 220 mg/dl) and hypertriglyceridemia (TG >/= 150 mg/dl) showed extremely high rates of nodal metastasis (80 and 91%, respectively), that were significantly higher than those of patients with normal lipid levels (P<0.01 and P<0.001). When hyperlipidemia was defined as the presence of either hypertriglyceridemia or hypercholesterolemia, hyperlipidemia was an independent risk factor for nodal metastasis in SEC. Elevated serum lipid levels might bring favorable circumstances for the development of lymph node metastasis in the early stage of EC. Hyperlipidemia might prompt us to perform more studies to investigate possible metastasis.

Carcinoma, Squamous Cell↗

Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial.

BACKGROUND: Diabetes risk is often complicated by a mixed hyperlipoproteinemia not sufficiently controlled by a single antihyperlipidemic drug; however, there are some concerns about the safety of combined statin and fibrate treatments. OBJECTIVE: The aim of this study was to compare the efficacy and safety profile of fluvastatin + fenofibrate combination therapy and those of fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus (DM), and coronary heart disease (CHD) (ie, high risk for cardiovascular disease [CVD]). METHODS: This 12-month, randomized, double-blind, controlled trial was conducted at the University of Pavia, Pavia, Italy. Patients aged 18 to 80 years with combined hyperlipidemia, type 2 DM, and CHD were randomly assigned to receive combination therapy with extended-release fluvastatin 80 mg + micronized fenofibrate 200 mg or monotherapy with extended-release fluvastatin 80 mg. All treatments were given in tablet form, once daily with the evening meal, for 12 months. Lipid variables (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) at 6 and 12 months were the primary efficacy variables, and glycemic status (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose, and postprandial plasma glucose levels) at 6 and 12 months was the secondary efficacy variable. Tolerability was assessed using physical examination, including vital-sign assessment, body-weight measurement, electrocardiography, adverse events, and laboratory tests. A pharmacoeconomic analysis of both treatment regimens was also carried out using the incremental cost-effectiveness ratio (ICER). RESULTS: A total of 48 patients (24 men, 24 women; mean [SD] age, 60 [5] years) were enrolled. After 6 months, all primary efficacy variables, except for TG level, showed significant improvements from baseline only in the combination-therapy group (changes: LDL-C, -25%; HDL-C, +12%; and TC, -19%; all, P < 0.05 vs baseline). After 12 months, lipid variables showed significant improvements over baseline in both groups (all, P < 0.05), except for TG in the monotherapy group. Significant changes in LDL-C, HDL-C, and TG were found in the combination-therapy group (-35%, +34%, -32%, respectively) versus the monotherapy group (-25%, +14%, -17%, respectively; all, P < 0.05 between groups). The change from baseline in HbA(1c) level was significant with combination therapy (-12% vs -7%; P < 0.05). Both treatments were well tolerated, with no significant differences in the incidences of adverse events between the 2 groups. The ICER showed that each 1% decrease in LDL-C level achieved with the fenofibrate + fluvastatin combination added a cost of 14.97 Euros/y (US 12.25 US dollars/y), and each 1% increase in HDL-C level added a cost of 7.48 Euros/y (6.12/y US dollars), over the cost of monotherapy. CONCLUSIONS: In this selected sample of patients with combined hyperlipidemia, type 2 DM, and CHD, the combination of extended-release fluvastatin + micronized fenofibrate was associated with a more improved lipid profile than fluvastatin monotherapy, and was a well-tolerated and cost-effective therapeutic choice to treat these patients at high risk for CVD.

Adolescent↗

Hyperlipidemia in children after heart transplantation.

BACKGROUND: Long-term outcome after cardiac transplantation is limited by graft coronary vasculopathy (GCV). Hyperlipidemia may contribute to the development and progression of GCV. The purpose of this study was to determine the distribution of lipid levels in children after heart transplantation and to determine the incidence and risk factors for hyperlipidemia. METHODS: We compared the distribution of lipid values 1 year after heart transplantation in children participating in Pediatric Heart Transplant Study to those of normal U.S. children and then performed a multivariable analysis to identify risk factors for hyperlipidemia. RESULTS: The median values of total and LDL-cholesterol in heart transplant patients were similar to those of normal U.S. pediatric population. However, total cholesterol level was >200 mg/dl in 14% and >170 mg/dl in 33% of transplant patients. LDL-cholesterol was >130 mg/dl in 12%, >110 mg/dl in 27% and >100 mg/dl (greater than "optimal" levels) in 39% of transplant patients. The distribution curve for serum triglycerides was shifted to the right and that for HDL-cholesterol levels was shifted to the left of the normal U.S. pediatric curve. As a result, triglyceride levels were >75th centile of U.S. normal distribution in 59% of the transplant patients. HDL-cholesterol level was <25th centile of U.S. normal distribution in 61% of the transplant patients. Independent risk factors for elevated levels of total and LDL-cholesterol were patient age and use of cyclosporine and prednisone. CONCLUSIONS: Lipid levels considered to be in the intervention range in adults at high risk of coronary artery disease are a common finding after cardiac transplantation in children.

Adolescent↗

Optimal management of hyperlipidemia in primary prevention of cardiovascular disease.

Cardiovascular disease (CVD) in the developed countries continues to grow at an epidemic proportion. There are a significant number of young adults with no clinical evidence of CVD, but who have two or more risk factors that predispose them to CV events and death. Many of these risk factors are modifiable, and by controlling these factors, the CVD burden can be decreased significantly. Recent statistics have shown that, if all major forms of CVD were eliminated, the life expectancy would rise by almost 7 years. Hence it is imperative that primary prevention efforts should be initiated at a young age to avert decades of unattended risk factors. Hyperlipidemia has been linked to CVD almost a century ago. Since then various clinical trials have not only supported this link, but have also shown the CV benefits in aggressively treating patients with hyperlipidemia. In this generation, we have various therapeutic agents that are capable of reducing the elevated lipid levels. With drugs like statins, we are able to reduce the risk of CVD by about 30% and avoid major adverse events. Newer drugs are being researched and introduced in the treatment of hyperlipidemia in humans. These can be used in combination therapy resulting in optimal levels of lipids. The new National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) guidelines have come as a wake-up call to clinicians about primary prevention of CVD through strict lipid management and multifaceted risk management approach in the prevention of CVD.

Cardiovascular Diseases↗

The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia.

Hyperlipidemia is an important risk factor for atherosclerosis. Hemorheological factors contribute to morbidity and mortality in patients with dyslipidemia. We evaluated the effects of 3 antihyperlipidemic drugs (pravastatin, atorvastatin, and fenofibrate), which have different mechanisms of action and different patterns of action on lipid profiles, on erythrocyte deformability and fibrinogen levels in patients with type IIa and type IIb hyperlipidemia. Twenty-one patients ( 4 men and 17 women) with type IIa and IIb hyperlipidemia were randomized to 3 drugs (pravastatin 20 mg/d, atorvastatin 10 mg/d, fenofibrate 250 mg/d) for 8 weeks. Plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) analysis were performed on a BM-Hitachi 747-200 autoanalyzer (Hitachi-Roche, Tokyo, Japan). Fibrinogen analysis was performed according to Clauss method. Erythrocyte deformability was assessed with cell transit analysis device. There was no significant difference in body mass index, lipid profile, fibrinogen level, and erythrocyte deformability index values among the groups before treatment ( P > .05). In all groups, there were statistically significant reductions in total LDL-C levels ( P < .05). The triglyceride levels were significantly reduced in the atorvastatin and fenofibrate groups ( P < .05), but not in the pravastatin group ( P > .05). There was no significant change in HDL-C levels during the treatment with statins ( P > .05), but there was a significant increase in the fenofibrate group ( P < .05). Mean erythrocyte deformability index was improved in all the groups ( P < .05). There was no significant change in fibrinogen levels during the treatment of pravastatin and atorvastatin ( P > .05), but in fenofibrate group, fibrinogen levels were significantly decreased ( P < .05). The 3 groups of antihyperlipidemic drugs have beneficial effects on the erythrocyte deformability index. Only fenofibrate has significant beneficial effects on the fibrinogen levels.

Adult↗

Effects of soybean D-LeciVita product on serum lipids and fatty acid composition in type 2 diabetic patients with hyperlipidemia.

BACKGROUND AND AIM: Hyperlipidemia is one of the major risk factors of cardiovascular complication in diabetes. High intake of soy product has been suggested to prevent cardiovascular disease. The purpose of this study was to evaluate if dietary supplement of soybean D-LeciVita product, rich in polyunsaturated phospholipids (with 12% lecithin, 35% soy protein) affects serum lipids and serum and erythrocyte phospholipid fatty acid composition in type 2 diabetic patients. METHODS AND RESULTS: Forty-seven patients (men and post-menopausal women) with isolated hypertriglyceridemia (IHTG) and combined hyperlipidemia (CHL), aged 43-70 years, were given 15g of D-LeciVita powder as a water suspension in a single evening dose during the follow-up period of 12 weeks. Patients kept their diabetic diet relatively constant. Treatment was associated with a significant (p < or = 0.001) decrease in serum total cholesterol and triglyceride levels by 12% and 22%, respectively. LDL-cholesterol decreased by 16% and HDL-cholesterol increased by 11% (p < or = 0.001). Our study shows a 27% decrease in LDL-cholesterol (p < or = 0.001) and a 12% increase in HDL-cholesterol (p < or = 0.01) in CHL type 2 diabetic patients. Triglyceride levels decreased in type 2 diabetic patients with IHTG and CHL by 29% and 13%, respectively (p < or = 0.01 and p < or = 0.05). Our results show decrease in SFA and increase in n-6 and n-3 PUFA in serum and erythrocyte phospholipids. SFA decreased and n-3 PUFA increased in serum and erythrocyte phospholipids in IHTG and CHL groups. CONCLUSION: The present study indicated that added to a regular diet, soybean D-LeciVita product (combination of soy protein and lecithin) is associated not only with lipid-lowering effects but also with more favorable serum phospholipids fatty acid profile in type 2 diabetic patients with hyperlipidemia.

Adult↗

Dietitian intervention improves lipid values and saves medication costs in men with combined hyperlipidemia and a history of niacin noncompliance.

We asked if medical nutrition therapy (MNT) administered by registered dietitians could lead to beneficial clinical and financial outcomes in men with combined hyperlipidemia (hypercholesterolemia and hypertriglyceridemia). A retrospective chart review was conducted on 73 men with combined hyperlipidemia who were being considered for statin therapy because of a previous history of noncompliance with niacin therapy. Subjects participated in an 8-week dietitian intervention program as a qualifying requirement, before statin therapy. Patient records were reviewed to determine the beginning and ending serum lipid concentrations and the number and length of dietitian sessions. Complete information was available on 43 subjects, aged 60.7 +/- 10.1 years (mean +/- standard deviation). Total dietitian intervention time was 169 +/- 19 minutes in 2.7 +/- 0.6 sessions (range = 2 to 4 sessions) during 6.5 +/- 2.2 weeks of MNT (range = 4 to 8 weeks). MNT lowered levels of total cholesterol 11% (P < .001), low-density lipoprotein cholesterol 9% (P < .001), and triglycerides 22% (P < .0001) and body mass index 2% (P < .0001); MNT raised high-density lipoprotein cholesterol levels 4%. After dietitian intervention, only 15 of 30 eligible patients required antihyperlipidemic medications, which led to an annual cost savings of $27,449.10 or $638.35 per patient. A cost saving of $3.03 in statin therapy was realized for each dollar spent on MNT. We conclude that an average of 3 individualized dietitian visits of 1 hour each over an 8-week period has a beneficial effect in treating patients with combined hyperlipidemia and recommend consideration of MNT as a cost-effective intervention.

Adult↗

Development and evaluation of a computer-based system for dietary management of hyperlipidemia.

OBJECTIVE: To describe the development of a computer-based system for dietary management of hyperlipidemia and to evaluate its efficacy for lowering plasma cholesterol level. DESIGN: Using a stepwise approach, we developed and tested a three-part self-management system in five consecutive clinical studies. Each study assessed plasma cholesterol levels before and after dietary intervention using the system. These studies enabled progressive refinement of (a) a food frequency questionnaire used to assess food intake in the preceding month; (b) computer-generated progress reports, based on questionnaire responses, offering dietary change subgoals and strategies for change; and (c) a dietary workbook providing detailed information on how to achieve goals. SUBJECTS/SETTING: Persons with hyperlipidemia (n=814) were enrolled from worksite and clinical settings in the San Francisco Bay area of California. The attrition rate after randomization was 5%. INTERVENTION: Elements of the dietary intervention evolved in response to the results of five clinical studies. In each study, patients underwent a form of baseline assessment of dietary intake followed by counseling/instruction by various means. Follow-up dietary assessments were provided at specific intervals to facilitate subjects' progress toward their dietary goals. A dietary workbook provided the detailed instruction required to implement the recommendations contained in the periodic progress reports. STATISTICAL ANALYSES PERFORMED: Changes in plasma cholesterol level were measured by paired and unpaired t tests. The relationship between the reported reduction in dietary fat and cholesterol level assessed by food frequency questionnaires and the directly measured change in plasma cholesterol level was measured by multiple linear regression. RESULTS: The three major elements of the final computerized system (food frequency questionnaires, computer-generated progress reports, and dietary workbook) were developed and refined in the course of the five clinical studies. Reductions in total plasma cholesterol level of 5.0% to 6.5% achieved by participants in all five studies were consistent with self-reported reductions in intake of dietary saturated fat and cholesterol. Therefore, the computerized self-management system appears to be an effective tool for reducing plasma cholesterol levels. APPLICATIONS/CONCLUSIONS: A computer-based system for dietary self-management of hyperlipidemia, implemented by mail, was effective in short-term studies. This self-management system can potentially provide health-promoting services to large numbers of people at low cost.

Adult↗

A dietitian-delivered group nutrition program leads to reductions in dietary fat, serum cholesterol, and body weight: the Worcester Area Trial for Counseling in Hyperlipidemia (WATCH).

OBJECTIVE: To assess the effectiveness of a dietitian-based nutrition counseling and education program for patients with hyperlipidemia. DESIGN: A 4-session program implemented as a complement to a randomized physician-delivered intervention. SUBJECTS/SETTING: From 12 practice sites of the Fallon Clinic, 1,162 subjects with hyperlipidemia were recruited, 645 of whom had data sufficient for our primary analyses. INTERVENTION: Two individual and 2 group sessions conducted over 6 weeks. MAIN OUTCOME MEASURES: Total and saturated fat levels; serum low-density lipoprotein cholesterol levels; and body weight, measured at baseline and after 1 year. STATISTICAL ANALYSES: Multiple linear regression was used to evaluate changes in outcome measures. RESULTS: After 1 year, there were significant reductions in outcome measures for subjects attending 3 or 4 nutrition sessions vs subjects attending fewer than 3 sessions or those never referred to a nutrition session. Reductions (mean +/- standard error) in saturated fat (measured as percent of energy) were 2.7 +/- 0.5%, 2.1 +/- 0.5%, and 0.3 +/- 0.1%, respectively. These reductions correspond to roughly a 22% relative change from baseline in those attending 3 or 4 sessions. Corollary reductions were observed for total fat (measured as percent of energy): 8.2 +/- 1.4%, 5.0 +/- 1.4%, and 0.7 +/- 0.4%; low-density lipoprotein cholesterol: 0.48 +/- 0.11 mmol/L, 0.13 +/- 0.11 mmol/L, and 0.02 +/- 0.03 mmol/L; and body weight: 4.5 +/- 0.9 kg, 2.1 +/- 0.8 kg, and 1.1 +/- 0.2 kg. The specified changes were additive to those of the physician-delivered intervention. APPLICATIONS/CONCLUSIONS: This investigation provides empirical data demonstrating the effectiveness of a dietitian-delivered intervention in the care of patients with hyperlipidemia.

Adult↗

Effects of simvastatin (40 and 80 mg/day) in patients with mixed hyperlipidemia.

Mixed hyperlipidemia is characterized by both elevated total cholesterol and triglycerides. It is estimated to account for 10% to 20% of patients with dyslipidemia. This study assessed the lipid-altering efficacy and tolerability of simvastatin 40 and 80 mg/day as monotherapy. One hundred thirty patients (62 women [48%], 24 [16%] with type 2 diabetes mellitus, mean age 53 years) with mixed hyperlipidemia (baseline low-density lipoprotein [LDL] cholesterol 156 mg/dl [mean], and triglycerides 391 mg/dl [median) were randomized in a multicenter, double-masked, placebo-controlled, 3-period, 22-week, balanced crossover study, and received placebo, and simvastatin 40 and 80 mg/day each for 6 weeks. Compared with placebo, simvastatin produced significant (p <0.01) and dose-dependent changes in all lipid and lipoprotein parameters (LDL cholesterol 2.1%, -28.9%, and -35.5%; triglycerides -3.5%, -27.8%, and -33.0%; high-density lipoprotein cholesterol 3.3%, 13.1%, and 15. 7%; apolipoprotein B 3.8%, -23.1%, and -30.6%; and apolipoprotein A-I 4.0%, 8.2%, and 10.5% with placebo, and simvastatin 40 and 80 mg/day, respectively). The changes were consistent in patients with diabetes mellitus. One patient taking simvastatin 80 mg/day had an asymptomatic and reversible increase in hepatic transaminases 3 times above the upper limit of normal. Simvastatin 40 and 80 mg/day is effective in patients with mixed hyperlipidemia across the entire lipid and lipoprotein profile. The reductions in LDL cholesterol and triglycerides are large, significant, and dose dependent. The increase in high-density lipoprotein cholesterol was greater than that observed in patients with hypercholesterolemia, and appears dose dependent.

Adult↗