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PubMed2006

Hyperlipidemia and surfactants: the liver sieve is a link.

Poloxamer 407 is a ubiquitous synthetic surfactant that causes massive hyperlipidemia and atherosclerosis in the rodent. The initial step in hepatic metabolism of lipoproteins is their transfer through 100-200 nm pores (fenestrations) in the liver sinusoidal endothelial cell, prior to receptor-mediated uptake. The 'liver sieve hypothesis' emphasizes the role of these fenestrations in the regulation of lipoprotein disposition. Here we show that P407 causes dramatic defenestration of the liver sinusoidal endothelium in vivo. By 24h after intraperitoneal administration in mice, fenestrations were reduced by approximately 80% coincident with a 10-fold increase in plasma lipids. Moreover impulse-response experiments in the perfused rat liver showed that P407 prevented the passage of small chylomicrons across the liver sinusoidal endothelium. Defenestration was also induced acutely with P407 in isolated liver sinusoidal endothelial cells, indicating this is a direct effect of P407 on fenestrations. The results establish the role of the porosity of the liver sinusoidal endothelial cell as a pivotal yet relatively unrecognised mechanism for hyperlipidemia. Furthermore, the results establish an intriguing mechanism for surfactant-induced hyperlipidemia. Thus the liver sieve is a new and untapped target for the treatment and prevention of hyperlipidemia.

Animals↗
PubMed2005

Guggul for hyperlipidemia: a review by the Natural Standard Research Collaboration.

OBJECTIVE: To evaluate the scientific evidence on guggul for hyperlipidemia including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. METHODS: Electronic searches were conducted in nine databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on language or quality of publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy/lactation, interactions, alteration of laboratory assays, and mechanism of action. Standardized inclusion/exclusion criteria were utilized for selection. RESULTS: Before 2003, most scientific evidence suggested that guggulipid elicits significant reductions in serum total cholesterol, low-density lipoprotein (LDL), and triglycerides, as well as elevations in high-density lipoprotein (HDL) [Kotiyal JP, Bisht DB, Singh DS. Double blind cross-over trial of gum guggulu (Commiphora mukul) Fraction A in hypercholesterolemia. J Res Indian Med Yoga Hom 1979;14(2):11-6; Kotiyal JP, Singh DS, Bisht DB. Gum guggulu (Commiphora mukul) fraction 'A' in obesity-a double-blind clinical trial. J Res Ayur Siddha 1985;6(1, 3, 4):20-35; Gaur SP, Garg RK, Kar AM, et al. Gugulipid, a new hypolipidaemic agent, in patients of acute ischaemic stroke: effect on clinical outcome, platelet function and serum lipids. Asia Pacif J Pharm 1997;12:65-9; Urizar NL, Liverman AB, Dodds DT, et al. A natural product that lowers cholesterol as an antagonist ligand for the FXR. Science 3 May 2002 [Science Express Reports]; Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India 1989;37(5):323-8; Kuppurajan K, Rajagopalan SS, Rao TK, et al. Effect of guggulu (Commiphora mukul-Engl.) on serum lipids in obese, hypercholesterolemic and hyperlipemic cases. J Assoc Physicians India 1978;26(5):367-73; Gopal K, Saran RK, Nityanand S, et al. Clinical trial of ethyl acetate extract of gum gugulu (gugulipid) in primary hyperlipidemia. J Assoc Physicians India 1986;34(4):249-51; Agarwal RC, Singh SP, Saran RK, et al. Clinical trial of gugulipid-a new hypolipidemic agent of plant origin in primary hyperlipidemia. Indian J Med Res 1986;84:626-34; Verma SK, Bordia A. Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL-cholesterol. Indian J Med Res 1988;87:356-60; Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther 1994;8(4):659-64; Ghorai M, Mandal SC, Pal M, et al. A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum gugglu. Phytother Res 2000;14(3):200-02]. However, most published studies were small and methodologically flawed. In August 2003, a well-designed trial reported small significant increases in serum LDL levels associated with the use of guggul compared to placebo [Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003;290(6):765-72]. No significant changes in total cholesterol, high-density lipoprotein (HDL), or triglycerides were measured. These results are consistent with two prior published case reports [Das Gupta R. Gugulipid: pro-lipaemic effect. J Assoc Physicians India 1990;38(12):346]. CONCLUSION: The effects of guggulipid in patients with high cholesterol are not clear, with some studies finding cholesterol-lowering effects, and other research suggesting no benefits. At this time, there is not enough scientific evidence to support the use of guggul for any medical condition. Guggul may cause stomach discomfort or allergic rash as well as other serious side effects and interactions. It should be avoided in pregnant or breast-feeding women and in children. Safety of use beyond 4 months has not been well studied.

Clinical Trials as Topic↗
PubMed2006

Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia.

OBJECTIVES: This study sought to determine the long-term safety and efficacy of co-administered fenofibrate (FENO) and ezetimibe (EZE) in patients with mixed hyperlipidemia. BACKGROUND: Both EZE and FENO offer complementary benefits to the lipid profile of patients with mixed hyperlipidemia. METHODS: After completing the 12-week randomized, double-blind base study that compared EZE 10 mg, FENO 160 mg, FENO 160 mg plus EZE 10 mg, and placebo in patients with mixed hyperlipidemia, patients continued into a double-blind, 48-week extension phase. Those patients in the FENO plus EZE and FENO groups continued on their respective base study treatment, and patients in the EZE and placebo groups were switched to FENO plus EZE and FENO, respectively. RESULTS: Of the 587 patients who completed the base study, 576 continued into the extension study (n = 340 in FENO plus EZE and n = 236 in FENO). The FENO plus EZE produced significantly greater reductions in low-density lipoprotein-cholesterol compared with FENO (-22% vs. -9%, respectively; p < 0.001). There were also significantly greater improvements in triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol, non-HDL-C, and apolipoprotein B with FENO plus EZE compared with FENO. Changes in apolipoprotein A-I and high-sensitivity C-reactive protein were similar between groups. Overall, FENO plus EZE was well tolerated during the extension study. The proportion of patients with consecutive elevations of alanine aminotransferase/aspartate aminotransferase > or =3 times upper limit of normal were similar between the FENO plus EZE (1.2%) and FENO (1.7%) groups. No cases of creatine phosphokinase elevations > or =10 times upper limit of normal or myopathy were observed in either group. CONCLUSIONS: Long-term, 48-week co-administration of FENO plus EZE was well tolerated and more efficacious than FENO in patients with mixed hyperlipidemia.

Adult↗
PubMed2005

Hyperlipidemia in children.

Hyperlipidemia in children has emerged as an increasingly prevalent risk factor in children, concomitant with the worldwide epidemic of obesity. Hyperlipidemia can alter vascular endothelial function and impair some of its pro-fibrinolytic and anti-thrombotic regulatory properties, as well as initiate the atherosclerotic process. There are strong links between vascular changes and hyperlipidemia in children, both from pathologic and non-invasive assessment studies. More severe lipid abnormalities in children are related to primary familial dyslipidemias. Current recommendations for screening begin with assessment of family history for cardiovascular disease or events or parental hyperlipidemia. High-risk individuals merit more intensive investigation and intervention. While fat-restricted diets have been shown to be safe in children, lipid-lowering is modest. Those with more severe lipid abnormalities may meet criteria for drug therapy, and the statin agents commonly used in adults are increasingly being used in high-risk children, with similar efficacy and safety, although long-term concerns remain.

Adolescent↗
PubMed1998

A randomized trial of the effects of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. Collaborative Atorvastatin Study Group.

BACKGROUND: To assess the lipid-lowering effects and safety of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. METHODS: We performed a randomized, open-label, parallel-design, active-controlled, study in eight centers in the United States. We enrolled 108 patients with total cholesterol (TC) of > or =200 mg/dL, serum triglycerides (TG) > or =200 and < or =800 mg/dL, and apolipoprotein B (apo B) > or =110 mg/dL. Patients were randomly assigned to receive atorvastatin 10 mg once daily (n=55) or immediate-release niacin 1 g three times daily for 12 weeks (n=53). Patients were stratified based on low-density lipoprotein cholesterol (LDL-C): Patients with LDL-C > or =135 mg/dL were considered to have combined hyperlipidemia and patients with LDL-C <135 mg/dL were considered to have isolated hypertriglyceridemia. The primary outcome measure was percent change from baseline in LDL-C. Other lipid levels were evaluated as secondary parameters. RESULTS: Atorvastatin reduced LDL-C 30% and TC 26% from baseline, and increased high-density lipoprotein cholesterol (HDL-C) 4%. Total TG were reduced 17%. Niacin reduced LDL-C 2%, TC 7%, increased HDL-C 25%, and reduced total TG 29% from baseline. There was a significant difference in LDL-C reduction, the primary efficacy parameter, between the two treatment groups (P <0.05, favoring atorvastatin), as well as a significant difference in the improvement in HDL-C (P <0.05, favoring niacin). The effect of atorvastatin was relatively consistent between patients with combined hyperlipidemia and isolated hypertriglyceridemia, whereas there was more variability between these strata in the niacin treatment group. Atorvastatin was better tolerated than niacin. CONCLUSION: Atorvastatin may allow patients with combined hyperlipidemia to be treated with monotherapy and offers an efficacious and well-tolerated alternative to niacin for the treatment of patients with isolated hypertriglyceridemia.

Adult↗
PubMed1998

Dopamine agonist treatment ameliorates hyperglycemia, hyperlipidemia, and the elevated basal insulin release from islets of ob/ob mice.

One of the characteristics of obesity-associated diabetes is an elevated fasting plasma insulin concentration with a weak insulin secretory response to subsequent glucose stimulation. Evidence suggests that hyperglycemia and hyperlipidemia may contribute to the initiation and progression of this disordered islet glucose sensing. It has been proposed that reducing hyperglycemia and hyperlipidemia per se may improve islet glucose sensing. Here we studied glucose-dependent insulin release in islets isolated from ob/ob mice treated with dopamine agonists (bromocriptine and SKF38393, BC/SKF) which significantly reduced circulating glucose and lipid levels of ob/ob mice. Islets from BC/SKF-treated mice showed a marked decrease of the elevated basal insulin release to levels similar to lean mice. Such treatment also induced a higher secretory response to glucose stimulation compared with that in ob/ob mice with sustained hyperglycemia and hyperlipidemia. Similarly, when islets from untreated ob/ob mice were cultured for 7 days in 11 mM glucose in the absence of free fatty acid, the basal insulin release was significantly decreased and high glucose stimulated insulin release increased compared with that from islets cultured in medium containing 30 mM glucose and 2 mM oleate. The BC/SKF-induced reduction of elevated basal insulin release was associated with decreased hexokinase activity and basal cyclic AMP content in islet tissue. Our results demonstrate that dopamine agonist treatment improves basal insulin release in ob/ob mice and this effect may be mediated, in part, by a reduction of hyperglycemia and hyperlipidemia.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1999

[Opposable medical references of the ANDEM concerning hyperlipidemia and its treatment].

INTRODUCTION: Cardiovascular diseases are the main cause of morbidity and mortality in France, and frequently result from hyperlipidemia. Physicians are therefore often faced with the diagnosis and treatment of hyperlipidemia. However, this issue must be considered within the general context of the global vascular risk of a given subject. CURRENT KNOWLEDGE AND KEY POINTS: Even though French health laws recently introduced do not take place of literature search to help guide the diagnosis and implement treatment, they may be considered as relevant summaries and guidelines with regard to current scientific knowledge. These laws mainly concern hypercholesterolemia and mixed hyperlipidemia and remind the physician that the patient's diet, values above which treatment is necessary and treatment objectives should be assessed before introducing any hypolipidemic treatment. FUTURE PROSPECTS AND PROJECTS: These new French laws are also an initial approach to treatment of hyperlipidemia, even though some ambiguities and issues are still unanswered. They should be considered as guidelines subject to modifications related to new findings.

Adult↗
PubMed1994

Posttransplant hyperlipidemia: the treatment dilemma.

Hyperlipidemia occurs in the majority of renal transplant recipients and may play an important role in the development of posttransplant cardiovascular disease. Although many clinical factors are associated with posttransplant hyperlipidemia, corticosteroids and cyclosporine clearly play key pathogenetic roles. Aside from cautious reduction of immunosuppression and appropriate dietary restrictions, therapeutic strategies for the management of posttransplant hyperlipidemia are limited, in part, due to special pharmacologic considerations in transplant recipients receiving cyclosporine. Based on recent studies suggesting that low doses of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors are safe and effective, these agents have emerged as the drugs of first choice in the pharmacologic treatment of posttransplant hypercholesterolemia. Considering the increasing importance of cardiovascular disorders as major causes of posttransplant morbidity and mortality, additional studies are warranted to delineate the relationship between posttransplant hyperlipidemia and posttransplant cardiovascular disease, and to find safe and effective strategies for reducing lipid levels after renal transplantation.

Humans↗
PubMed2004

[Patients with hyperlipidemia: inappropriate nutritional intake].

OBJECTIVE: Gather knowledge on nutritional supplementation in patients with hyperlipidemia. METHODS: In an observational study on patients with hyperlipidemia, nutritional intake was assessed using a 7-day dietary questionnaire, provided on the first visit to a lipid clinic. RESULTS: 291 patients (201 men and 90 women) were studied. Calorie intake and proportion of energetic nutrients revealed low carbohydrate intake, low intake of dietary fibres, and excessive lipid and saturated fatty acid intakes. Patients with isolated hypercholesterolemia had nutritional intake very similar to the daily allowances recommended in France. Men with type III hyperlipidemia had the highest calorie intake and those with type IV dyslipidemia had the highest alcohol intake. Triglycerides increased with total energy intake and with fat intake (%). Body mass index was inversely correlated to carbohydrate intake. The duration of dyslipidemia was related to low vitamin C and B9 intake. The existence of risk factors (type 2 diabetes, hypertension, smoking or inactivity) was associated with less well-balanced diet and low protective micronutrient status. In the case of atherosclerosis, vitamin B9, C, E and beta-carotene intake was insufficient. Interactions existed between nutrient intake with correlations between fibres, vitamin B9, C and beta-carotene, suggesting that nutritional education should favour foodstuffs that provide them simultaneously. CONCLUSION: Nutritional intake in patients with hyperlipidemia is often far from that recommended and does not greatly differ from that in large non-selected populations. It can be considered as inappropriate because of the metabolic and cardiovascular risks in these patients. Adapted nutritional management is crucial.

Adolescent↗
PubMed2003

Increase of inflammatory state in overweight adults with combined hyperlipidemia.

BACKGROUND AND AIM: Elevated levels of acute phase reactants are found in patients with cardiovascular disease. It is suggested that adipose tissue is a determinant of a low level of inflammatory state in overweight persons. The aim of the study was to determine, whether combined hyperlipidemia, which is an important factor of atherosclerosis, has influence on the inflammatory response in overweight adults. METHODS AND RESULTS: Levels of soluble cell adhesion molecules sICAM-1, sE-selectin and sP-selectin, PAI-1 Ag (by Elisa test), orosomucoid (ORM) and transferrin (TRF) (by microturbidimetry) and fibrinogen (FBG) according to Clauss were examined in peripheral blood of overweight adults (n 33, body mass index 27.1 +/- 1.8 kg/m2) with combined hyperlipidemia and in equal numbers of age, sex and BMI matched non-hyperlipidemic group. Overweight adults with combined hyperlipidemia had significantly higher plasma levels of sICAM-1 (376.5 +/- 107.4 ng/mL vs 239.3 +/- 60.4 ng/mL; p < 0.001), sE-selectin (70.4 +/- 20.2 ng/mL vs 48.5 +/- 25.6 ng/mL; p = 0.005), sP-selectin (228.2 +/- 88.6 ng/mL vs 123.1 +/- 45.3 ng/mL; p < 0.001) and positive acute phase proteins ORM (0.82 +/- 0.16 g/L vs 0.64 +/- 0.20 g/L; p = 0.005), FBG (3.42 +/- 0.54 g/L vs 2.74 +/- 0.57 g/L; p = 0.037) and PAI-1 Ag (97.9 +/- 40.6 ng/mL vs 56.4 +/- 25.6 ng/mL; p < 0.05), and a decrease of negative acute phase protein TRF (2.14 +/- 0.40 g/L vs 2.77 +/- 0.45 g/L; p < 0.001) compared to the results in overweight non-hyperlipidemic controls. CONCLUSIONS: It is suggested that overweight adults have an increase of inflammatory response dependent on hyperlipidemia. It was apparent from the elevation of sE--selectin, sP--selectin and sICAM-1 and from an increase of systemic inflammatory response according to the increase of "positive" acute phase proteins (APRs) and the decrease of "negative" APR protein levels in these patients.

Acute-Phase Proteins↗
PubMed2001

Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study.

Mixed hyperlipidemia is a common risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of ciprofibrate versus gemfibrozil for the treatment of patients with mixed hyperlipidemia carefully selected for similar lipid profiles. A total of 68 patients who had mixed hyperlipidemia after following an isocaloric American Heart Association (AHA) phase I diet for 4 weeks were included. The plasma lipid levels at the inclusion were low-density lipoprotein-cholesterol (LDL-C) > or = 130 mg/dL, cholesterol > or = 240 mg/dL, and triglycerides > or = 200 mg/dL. Patients were randomly assigned to receive ciprofibrate 100 mg/d or gemfibrozil 1,200 mg/d. At the end of the 8-week treatment period, efficacy and safety parameters were compared with baseline values. The primary efficacy parameters of the study were percentage changes in triglycerides and LDL-C from baseline. After 8 weeks, plasma triglyceride concentrations were decreased by 43.5% and 54% compared with baseline during ciprofibrate and gemfibrozil therapy, respectively (P <.001). High-density lipoprotein-cholesterol (HDL-C) concentrations were increased 20.8% and 19.3% during ciprofibrate and gemfibrozil, respectively (P <.001). Apoprotein B, cholesterol, and very-low-density lipoprotein-cholesterol (VLDL-C) concentrations were also improved by the study drugs (18.6%, 13.2%, and 30.9%, respectively, during ciprofibrate and 44%, 13.8%, and 14.4%, respectively, during gemfibrozil). Meanwhile, the effect of the drug was minimal on LDL-C. A significant decrease in non-HDL-C resulted from both treatments (19% and 19.5%, respectively, P <.05). The only statistically significant difference observed between treatments was the effects on fibrinogen concentration, a coronary risk factor. Ciprofibrate significantly decreased its concentration by 18.8%, fibrinogen was slightly increased during gemfibrozil treatment. No patient had a significant modification on any of the safety tests. In summary, ciprofibrate and gemfibrozil are well-tolerated and efficacious treatments for mixed hyperlipidemia. Significant reductions in triglycerides, non-HDL-C, and apolipoprotein B were achieved with both drugs. A significant fibrinogen reduction was obtained with ciprofibrate.

Adolescent↗
PubMed2003

[Hyperlipidemia - side-effect of "Atypical" neuroleptics?].

After the introduction of the so-called 'atypical antipsychotics' some reports concerning hyperlipidemia observed in patients treated with these drugs have been published. The studies and case reports available up to now were reviewed. The available data show that hyperlipidemia particularly occurred in patients receiving clozapine, olanzapine and also quetiapine. Predominately elevated serum levels of triglycerides have been reported. The underlying pathomechanism still remains widely unclear. Since hyperlipidemia is an important symptom of the so called 'metabolic syndrome' which is often associated with severe complications like cardial and vascular diseases, more attention should be paid to hyperlipidemia as a potential side effect of antipsychotics.

Antipsychotic Agents↗
PubMed2002

Contemporary management of hyperlipidemia in women.

OBJECTIVE: The objective of this paper is to review prospective, large-scale studies of lipid-lowering therapy and hormone replacement therapy, and to provide clinical recommendations for the management of hyperlipidemia in women within the context of the revised National Cholesterol Education Program (NCEP) guidelines. METHODS: Recent English language literature derived from a MEDLINE search (January 1990-July 2001) and bibliographies of relevant papers were reviewed, and data were abstracted from identified papers. RESULTS: Hyperlipidemia is largely undertreated in women. Previously, hormone replacement therapy (HRT) was considered first-line treatment for the management of hypercholesterolemia to prevent coronary artery disease (CAD) in women. Recent studies, however, show no benefit of HRT for secondary prevention of coronary events, despite its beneficial effects on lipids. Large-scale, controlled clinical trials indicate that women, even those with only moderately elevated cholesterol, benefit from the lipid-lowering effects of statins for both high-risk primary and secondary prevention of CAD. Based on this evidence, the recently revised NCEP guidelines recommend statins as first-line therapy for women with hyperlipidemia, an approach that is supported by the American Heart Association and the American College of Cardiology. With its emphasis on aggressive intervention for persons with multiple risk factors, the new guidelines substantially increase the number of women eligible for pharmacological therapy. CONCLUSIONS: All women with hyperlipidemia should receive counseling regarding lifestyle approaches for lowering cholesterol. The decision to use HRT should be made in the context of other conditions hormones may affect. Alternative hormonal regimens for lipid management may include selective estrogen receptor modulators and phytoestrogens, but results of randomized clinical trials are necessary before firm recommendations can be made regarding their clinical value in preventing CAD.

Aged↗
PubMedDate not supplied

The Hyperlipidemia: Attitudes and Beliefs in Treatment (HABIT) survey for patients: results of a validation study.

Patient adherence with cholesterol-lowering medications is a crucial component in helping patients achieve lipid goals. Understanding patient attitudes and beliefs about hyperlipidemia and its pharmacological treatments may be useful in improving patient adherence with their treatment plan. The objectives of this study were to develop a theoretically based, statistically reliable, and valid survey instrument for measuring the attitudes and beliefs of patients towards hyperlipidemia and its treatments, and to determine whether the attitudes measured were associated with patient-reported medication adherence. We assessed the reliability of the instrument through an examination of the internal consistency and factor structure of 8 attitude constructs including attitudes about the effectiveness of medications and the quality of doctor-patient communication. Validity was assessed through correlations among the attitudes and the relationship between the attitudes and the number of medication adherence problems the patient experienced in the past month. Internal consistency scores for the 8 constructs ranged from .46 to .82. Factor loadings indicated that the individual items belonged to their respective constructs, as hypothesized. The validity of the instrument was demonstrated by significant relationships between 4 of the attitudinal constructs and self-reported medication adherence problems. This study provides preliminary evidence of the reliability and validity of the HABIT (Hyperlipidemia: Attitudes and Beliefs in Treatment) patient survey of attitudes about the treatment of hyperlipidemia.

Communication↗
PubMed1987

Persistent hyperlipidemia in renal transplant patients.

The exact nature and significance of posttransplant hyperlipidemia is controversial. In the present study, serum lipids were examined in 201 clinically stable renal transplant recipients before, 1 year after, and at the time of the last follow-up, 5.0 +/- 0.1 yr after transplantation. Hypertriglyceridemia, present in 36% of patients treated with dialysis before transplantation, occurred in 23% 1 year after successful transplantation. At last follow-up, 29% had elevated triglyceride levels. Hypercholesterolemia, present in only 8% of patients before transplantation, was found in 27% 1 year after receiving a renal allograft. At the time of last follow-up, 30% had elevated cholesterol levels. HDL cholesterol levels were normal 1 year after transplantation, and increased significantly during the posttransplant follow-up period. Multivariate stepwise linear regression analysis was used to determine factors independently associated with serum lipid levels. Age, body weight, pretransplant serum lipids, and variables linked to allograft function (urine protein excretion, serum creatinine, and the use of loop diuretics) were independently associated with posttransplant cholesterol and triglycerides. Diabetes, the use of alternate day steroids, beta-adrenergic-blocking antihypertensive medications, and thiazide diuretics were not linked to hyperlipidemia. In addition, changes in variables associated with renal function helped to explain why different factors were associated with lipid levels at 1 year than at the time of last follow-up. Thus, the results of this study suggest that hyperlipidemia is a frequent and persistent complication in clinically stable renal transplant recipients. Multiple factors, including several associated with declining allograft function, appear to be involved in the pathogenesis of posttransplant hyperlipidemia.

Adult↗
PubMed2001

Hyperlipidemia and cardiovascular disease after organ transplantation.

Hyperlipidemia, a frequent and persistent complication after solid organ transplantation, contributes to cardiovascular morbidity and mortality and may influence the development of allograft vasculopathy. The pathogenesis of posttransplantation hyperlipidemia is not fully understood, although several epidemiological factors are strongly implicated including age, weight, pretransplantation lipid levels, and immunosuppressive therapy. Management strategies to reduce hyperlipidemia and modify cardiovascular risk include dietary restrictions and the use of lipid-lowering agents. The selective use of immunosuppressants, such as tacrolimus, that have neutral or fewer adverse effects on lipid metabolism may also provide a useful option. A combination of lipid-lowering therapies and optimization of immunosuppressive regimens compatible with prolonged allograft survival is probably necessary to significantly reduce posttransplantation hyperlipidemia and its potentially harmful consequences.

Graft Rejection↗
PubMed1995

Increased carotid arterial wall thickness in common hyperlipidemia.

BACKGROUND: Intima-media thickness has been reported to be increased in several patients with disorders such as diabetes mellitus, systolic hypertension and familial hypercholesterolemia. No data are available for the less severe but more frequent forms of hyperlipidemia. The aim of the present study was to compare the intima-media thickness in men with mild to moderate hyperlipidemia with that in age- and sex-matched normolipidemic controls. METHODS: Fifty hyperlipidemic patients and 50 controls were enrolled in this study. Intima-media thickness was evaluated from high-resolution B-mode echo-Doppler images. Blood lipids and glucose were measured using standard methods. Cigarette consumption was recorded by questionnaire. RESULTS: Intima-media thickness was significantly higher in hyperlipidemic patients than in controls. Smokers, both hyperlipidemic and controls, had higher values of intima-media thickness, although not significantly so, than non-smokers. The distribution of intima-media thickness values ranged from 0.52 to 1.24 mm in hyperlipidemic patients and from 0.46 to 0.82 mm in controls. Eighteen patients with hyperlipidemia had an intima-media thickness larger than 0.82 mm and, of these, 14 had atherosclerotic plaques in the carotid arteries. Furthermore, 11 hyperlipidemic patients showed signs of cardiovascular disease and had significantly enlarged intima-media thickness compared with participants without cardiovascular disease. CONCLUSIONS: Intima-media thickness in the common carotid artery is enlarged in patients with mild to moderate forms of hyperlipidemia and the highest values of intima-media thickness are frequently associated with atherosclerotic plaques in the carotid arteries and signs of cardiovascular disease.

Carotid Artery Diseases↗
PubMed2004

AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and glomerulosclerosis in the Imai rat.

BACKGROUND: The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed. METHODS: The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months. RESULTS: As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade. CONCLUSION: The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.

Angiotensin II Type 1 Receptor Blockers↗