Effect of Fluvastatin Slow-Release on Low Density Lipoprotein (LDL) Subfractions in Patients with Type 2 Diabetes Mellitus: Baseline LDL Profile Determines Specific Mode of Action

Winkler, Karl; Abletshauser, C.; Hoffmann, Michael M.; Friedrich, I.; Baumstark, Manfred W.; Wieland, Heinrich; März, Winfried

doi:10.1210/jc.2002-020370

Cited by 54 publications

(38 citation statements)

References 41 publications

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“…RESULTS -In this study, 63% of the patients with moderate hypertension had notable levels of dense LDL as defined previously (35). All patients had similar clinical characteristics and lipid and lipoprotein concentrations at baseline (Tables 1 and 2).…”

Section: Discussionsupporting

confidence: 63%

“…First, nondiabetic, normolipidemic patients with hypertension have a prevalence of dense LDL similar to newly diagnosed patients with type 2 diabetes (35). Second, pioglitazone substantially decreases dense LDL in this type of patient (Fig.…”

Section: Discussionmentioning

confidence: 82%

“…Density ranges of the subfractions were: LDL-1, Ͻ1.031 kg/l; LDL-2, 1.031-1.034 kg/l; LDL-3, 1.034 -1.037 kg/l; LDL-4, 1.037-1.040 kg/l; LDL-5, 1.040 -1.044 kg/l; and LDL-6, Ͼ1.044 kg/l. Atherogenic LDL-5 and LDL-6 are summarized as dense LDL (33,35). All centrifugation steps were carried out at 18°C using partially filled polycarbonate bottles (6 ml) in a 50-Ti rotor.…”

Section: Lipoprotein Separationmentioning

confidence: 99%

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Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension

Winkler

Konrad²,

Fullert³

et al. 2003

Diabetes Care

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103

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OBJECTIVE -The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension.RESEARCH DESIGN AND METHODS -We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n ϭ 26) and a placebo (n ϭ 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 Ϯ 0.8 mmol/l; HDL cholesterol, 1.1 Ϯ 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5-7.1) were studied at baseline and on treatment.RESULTS -At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 Ͼ250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P ϭ 0.024). The mean diameter of LDL particles increased from 19.83 Ϯ 0.30 to 20.13 Ϯ 0.33 nm (P Ͻ 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 Ϯ 0.0024 to 1.0371 Ϯ 0.0024 kg/l (P ϭ 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol.CONCLUSIONS -The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 82%

Section: Lipoprotein Separationmentioning

confidence: 99%

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Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension

Winkler

Konrad²,

Fullert³

et al. 2003

Diabetes Care

Self Cite

103

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“…In a multicenter, double-blind, randomized study on fluvastatin (which has a comparably weak effect in reducing LDL cholesterol levels), performed in 89 patients with type 2 diabetes mellitus, all LDL subfractions were reduced, but reductions in small, dense LDL were the greatest [55]. In contrast, two studies investigating the effects of pravastatin [56] and simvastatin [57] in small cohorts of patients with type 2 diabetes mellitus could not demonstrate a difference in the reduction of large and small LDL particles.…”

Section: Lipid Lowering Agents Targeting Ldl Particle Distributionmentioning

confidence: 99%

Small dense low-density lipoprotein particles: priority as a treatment target in Type 2 diabetes?

Gerber¹,

Spinas²,

Berneis³

2012

Diabetes Management

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During the past two decades, the importance of the quality of low-density lipoprotein (LDL) particles -in addition to its quantity -has become of increasing interest. The risk of cardiovascular events was recognized to be closely linked to a predominance of small, dense LDL particles. In addition, in patients with Type 2 diabetes mellitus, the disease itself and its severity (in particular the degree of insulin resistance) is associated with this subclass of LDL particles. Lipid lowering as well as antihyperglycemic drugs have been evaluated in many studies concerning their effect on LDL particle size. It has increasingly been recognized that a reduction of LDL quantity is not necessarily associated with a beneficial effect on LDL quality. Advances in the understanding of alterations in LDL quality may therefore influence the choice of the therapeutic regimen in patients with diabetes in the future. SummaryDuring the last two decades, the importance of the quality of low-density lipoprotein (LDL) particles -in addition to its quantity -has become of increasing interest. The risk of cardiovascular events was recognized to be closely linked to a predominance of small, dense LDL particles. In addition, in patients with type 2 diabetes mellitus, the disease itself and its severity (in particular the degree of insulin resistance) is associated with this subclass of LDL particles. Lipid lowering as well as antihyperglycemic drugs have been evaluated in many studies concerning their effect on LDL particle size. It has increasingly been recognized that a reduction of LDL quantity is not necessarily associated with a beneficial effect on LDL quality. Advances in the understanding of alterations in LDL quality may therefore influence the choice of the therapeutic regimen in patients with diabetes in the future.

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“…In pazienti diabetici, il farmaco ha determinato una riduzione di tutte le frazioni delle LDL e in particolare delle sd-LDL, portando inoltre ad un incremento delle dimensioni di queste ultime con una conseguente riduzione del potenziale aterogeno [45][46][47].…”

Section: O Zaniolo M Eandiunclassified

Bayesian statistic methods and theri application in probabilistic simulation models

Zaniolo¹,

Eandi²

2006

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Significant advances in the management of hypercholesterolemia have been made possible by the development of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. More recently, statins have demonstrated benefit in primary and secondary prevention of cardiovascular disease also in patients without hypercholesterolemia. Therefore statins help to reduce the impact of cardiovascular disease on morbility, mortality and social costs. Statins inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Prescribing statins as first line therapy in management of hypercholesterolemia as a part of a more comprehensive prevention program of cardiovascular disease is widely recommended by international guidelines (e.g. National Cholesterol Education Program -NCEP -Adult Treatment Panel -ATP-III reports). Currently in Italy there are five available statins: atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin; each of them presents some differences in physical and chemical characteristics (solubility), pharmacokinetics (absorption, proteic binding, metabolism and excretion) and pharmacodinamics (pleiotropic effects). Compared to other statins, fluvastatin extended-release (RP) 80 mg provides an equal efficacy in lowering total cholesterol and low-density lipoprotein cholesterol (LDL-C), with an important action on triglyceride (TG) levels and superior increases in HDL-C levels, reducing the incidence of major adverse cardiac events (MACE). Aim of this study is to outline an updated therapeutic and pharmacoeconomic profile of fluvastatin, particularly regarding extended-release (RP) 80 mg formulation. Keywords INTRODUZIONEL'introduzione delle statine ha rivoluzionato la terapia delle ipercolesterolemie e ha consentito un notevole progresso nella prevenzione primaria e secondaria del rischio cardiovascolare, riducendone l'impatto sulla morbilità, sulla mortalità e sui costi sociali [1][2][3].Si stima che il rischio cardiovascolare interessi oltre il 30% della popolazione adulta dei paesi industrializzati. Il rischio di eventi cardiovascolari maggiori (MACE) è correlato a diversi fattori modificabili (sedentarietà, tipo di alimentazione, fumo) e ad alcuni principali fattori biologici non modificabili (età, familiarità, ipertensione, diabete, dislipidemie) [4].In particolare, la moderna epidemiologia [4] ha evidenziato che:-la colesterolemia, e in particolare il colesterolo LDL (LDL-C), rappresenta un potente fattore di rischio di cardiopatia coronarica; -il grado di rischio cardiovascolare è direttamente proporzionale al livello plasmatico di LDL-C, entro un ampio range di variazione di questo parametro, con correlazione significativa a partire da livelli minimi di LDL-C ≤ 70mg/dl; -bassi livelli di HDL-C (≤ 40mg/dl) costituiscono un fattore di rischio indipendente; -elevati livelli di colesterolo totale e/o di LDL-C e ridotti livelli di HDL-C si associano ad un eccesso di r...

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Effect of Fluvastatin Slow-Release on Low Density Lipoprotein (LDL) Subfractions in Patients with Type 2 Diabetes Mellitus: Baseline LDL Profile Determines Specific Mode of Action

Cited by 54 publications

References 41 publications

Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension

Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension

Small dense low-density lipoprotein particles: priority as a treatment target in Type 2 diabetes?

Bayesian statistic methods and theri application in probabilistic simulation models

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