Implication of fibrate therapy for homocysteine

Jonkers, Ijam; Man, Fhaf de; Onkenhout, W.; Laarse, A. Van Der; Smelt, A.H.M.

doi:10.1016/s0140-6736(05)75415-5

Cited by 37 publications

(24 citation statements)

References 4 publications

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“…One of these factors may be elevated levels of fasting homocysteine, which are associated with enhanced in vivo lipid peroxidation as measured by iPF 2␣ -III. 35 We observed, in accordance with a study of Dierkes et al, 36 an increase in serum homocysteine on bezafibrate therapy, 18 which might contribute to the enhanced oxidation of lipoproteins.…”

Section: November 2000supporting

confidence: 89%

“…16 In addition, 2,3-dinor-5,6-dihydro-8-isoprostaglandin F 2␣ (2,3-dinor-5,6-dihydro-iPF 2␣ -III), the major urinary metabolite of iPF 2␣ -III, was measured by use of the same method. Deuterium-labeled iPF 2␣ -III (1 ng/mL, Cayman Chemical) and 18 O-labeled ent-2,3-dinor-5,6-dihydro-iPF 2␣ -III (1 ng/mL) were used as internal standards. 17 Interassay variation was 6.8% for iPF 2␣ -III and 6.0% for 2,3-dinor-5,6-dihydro-iPF 2␣ -III; intra-assay variance was 6.5% for iPF 2␣ -III and 4.0% for 2,3-dinor-5,6-dihydroiPF 2␣ -III.…”

Section: Measurements Of F 2 -Isoprostanesmentioning

confidence: 99%

“…To compare the quantities of F 2 -isoprostanes excreted in urine between control subjects and HTG patients, F 2 -isoprostanes were corrected for creatinine excretion in urine. Because bezafibrate is known to increase urinary creatinine excretion, 18 absolute levels of both F 2 -isoprostanes in 24-hour urine were compared between HTG patients on placebo and on bezafibrate therapy. In 3 of 18 HTG patients, 24-hour urine collection was incomplete; therefore, 15 paired data were available for absolute F 2 -isoprostane analysis.…”

Section: Measurements Of F 2 -Isoprostanesmentioning

confidence: 99%

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Normal Oxidative Stress and Enhanced Lipoprotein Resistance to In Vitro Oxidation in Hypertriglyceridemia

Man

Jonkers

Schwedhelm

et al. 2000

ATVB

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Abstract-Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F 2 -isoprostanes (8-isoprostaglandin F 2␣ and 2,3-dinor-5,6-dihydro-8-isoprostaglandin F 2␣ ) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG and 20 matched control subjects. In addition, the effects of 6 weeks of bezafibrate therapy were assessed in a double-blind, placebo-controlled, crossover trial. Urinary levels of F 2 -isoprostanes were similar in the HTG and normolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F 2␣ (762Ϯ313 versus 552Ϯ245 ng/24 h for bezafibrate and placebo therapy, respectively; Pϭ0.03), whereas 2,3-dinor-5,6-dihydro-8-isoprostaglandin F 2␣ levels tended to be increased (1714Ϯ761 versus 1475Ϯ606 ng/24 h for bezafibrate and placebo therapy, respectively; Pϭ0.11). VLDLs and LDLs were more resistant to copper-induced oxidation in patients with HTG than in control subjects. Bezafibrate reversed the oxidation resistance to the normal range. In conclusion, these results indicate the following: (1)

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Section: November 2000supporting

confidence: 89%

Section: Measurements Of F 2 -Isoprostanesmentioning

confidence: 99%

Section: Measurements Of F 2 -Isoprostanesmentioning

confidence: 99%

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Normal Oxidative Stress and Enhanced Lipoprotein Resistance to In Vitro Oxidation in Hypertriglyceridemia

Man

Jonkers

Schwedhelm

et al. 2000

ATVB

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“…4,5 Increased Hcy levels have been also observed in hypertensive patients on hydrochlorothiazide treatment. 25 The effect of other antihypertensive drugs such as angiotensin-converting enzyme (ACE) inhibitors, b-blockers and calcium channel blockers on plasma Hcy levels has not been studied extensively. Atar et al 26 have reported that b-blocker treatment significantly decreases plasma Hcy levels in patients with hypertension, especially in women; 26 however, another study did not find any change in plasma Hcy with b-blocker therapy.…”

Section: Introductionmentioning

confidence: 99%

Effect of ACE inhibitors and β-blockers on homocysteine levels in essential hypertension

et al. 2008

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Recent studies have shown that antihypertensive drugs like diuretics increase plasma homocysteine (Hcy) levels. However, the effect of other antihypertensive drugs on plasma Hcy levels has not been tested extensively. The aim of present study was to investigate the effect of antihypertensive therapy (AHT) on Hcy levels in essential hypertensive subjects. A case-control study of 273 patients with essential hypertension (EH) and 103 normotensive controls was undertaken. Plasma Hcy levels were measured before and after 6 weeks of AHT. The genotyping of MTHFR C677T polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. Angiotensin-converting enzyme (ACE) inhibitors and b-blockers significantly decreased and hydrochlorothiazides significantly increased the plasma Hcy levels in hypertensive patients (Po0.05). No significant association between MTHFR C677T genotypes and changes in Hcy levels in response to antihypertensive was observed in EH patients. The decrease in Hcy induced by b-blockers and ACE inhibitors observed in our study may be due to the improvement of endothelial function along with improved renal function. Thus, our results suggest that ACE inhibitors and b-blockers may provide additional beneficial therapeutic effects to the EH patients by decreasing Hcy levels.

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“…Fenofibrate has been reported to increase homocysteine by 36% to 55%, 4,40 -46 gemfibrozil by 0% to 18%, 42,47 and bezafibrate by 18% to 19%. 41,48 The mechanism by which fibrates increase homocysteine is not known. Nor is it known whether this effect is of clinical importance.…”

Section: Safety and Tolerability Of Fibratesmentioning

confidence: 99%

Is There a Role for Fibrates in the Management of Dyslipidemia in the Metabolic Syndrome?

Barter

Rye

2008

ATVB

136

106

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The outcomes of fibrate trials have varied: positive with gemfibrozil in the primary prevention Helsinki Heart Study and the secondary prevention VA-HIT trial; positive with reservations in the primary prevention WHO trial (clofibrate); and mixed with bezafibrate in the secondary prevention BIP study and with fenofibrate in the combined primary and secondary prevention FIELD study. Overall, the mixed results, combined with potential for adverse effects when given in combination with statins, have limited the use of these fibrates as cardioprotective agents. However, post hoc analyses of several of the fibrate studies have shown that people with features of the metabolic syndrome, particularly overweight people with high plasma triglyceride levels and low levels of HDL cholesterol, derive a disproportionately large reduction in cardiovascular events when treated with these agents. Thus, there is a strong case for the use of a fibrate to reduce the cardiovascular risk in overweight people with high triglyceride and low HDL-C. However, it should be noted that such people also have their cardiovascular risk reduced by statin therapy. It remains to be determined whether the combination of a fibrate plus statin reduces the risk beyond that achieved with a statin alone.

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Implication of fibrate therapy for homocysteine

Cited by 37 publications

References 4 publications

Normal Oxidative Stress and Enhanced Lipoprotein Resistance to In Vitro Oxidation in Hypertriglyceridemia

Normal Oxidative Stress and Enhanced Lipoprotein Resistance to In Vitro Oxidation in Hypertriglyceridemia

Effect of ACE inhibitors and β-blockers on homocysteine levels in essential hypertension

Is There a Role for Fibrates in the Management of Dyslipidemia in the Metabolic Syndrome?

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