Effects of Atorvastatin on Nuclear Magnetic Resonance-Defined Lipoprotein Subclasses and Inflammatory Markers in Patients with Hypercholesterolemia

Ikewaki, Katsunori; Terao, Yoshio; Ozasa, Hideki; Nakada, Yoshinobu; Tohyama, Junichiro; Inoue, Yae; Yoshimura, Michihiro

doi:10.5551/jat.e563

Cited by 24 publications

(19 citation statements)

References 15 publications

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“…18 In the ACTG A5087 randomized, multi-center, 48 week open-label non-inferiority study of two lipid-lowering agents in HIV-infected persons with combined hyperlipidemia, pravastatin and fenofibrate improved lipid profile but did not alter markers of glucose homeostasis, thrombogenesis, endothelial function, and inflammation. 19 In this prior study, effect of statins on mitochondrial oxidative stress in HIV infection was not evaluated.…”

Section: Prior Datamentioning

confidence: 99%

Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort

et al. 2015

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Background Association of lipoprotein particle size/number and HDL function with mitochondrial oxidative stress and function may underlie the excess cardiovascular (CVD) risk in HIV. Methods and Results Among HIV infected individuals on stable highly active antiretroviral therapy, we related standard and novel lipid measures [plasma total cholesterol, triglycerides, HDL-C, LDL-C, lipoprotein particle (-P) subclass size and number and HDL function (via cholesterol-efflux capacity)] with oxidative stress [peripheral blood mononuclear cell’s mitochondrial-specific 8-oxo-deoxyguanine (8-oxo-dG)] and function markers [oxidative phosphorylation (OXPHOS) NADH dehydrogenase (Complex I) and cytochrome c oxidase (Complex IV) enzyme activities]. Multivariable-adjusted logistic and linear regression analyses were employed adjusting for age, gender, CD4 nadir, viral load, smoking, diabetes, HOMA-IR, hypertension and lipid medications. Among 150 HIV-infected persons (mean age 52 years, 12% women, median CD4 count 524 cell/mm3), low HDL-C and high total cholesterol/HDL-C ratio were related to PBMC 8-oxo-deoxyguanine (p=0.01 and 0.02 respectively). Large HDL-P and HDL-P size were inversely related to PBMC 8-oxo-deoxyguanine (p=0.04). Small LDL-P (p=0.01) and total LDL-P (p=0.01) were related to decreased OXPHOS Complex I activity. LDL-P was related to decreased OXPHOS Complex IV activity (p=0.02). Cholesterol efflux capacity was associated with increased OXPHOS Complex IV activity. Conclusions HDL concentration and particle size and number are related to decreased PBMC mitochondrial oxidative stress whereas HDL function is positively related to mitochondrial oxidative function. The association we find between atherogenic lipoprotein profile and increased oxidative stress and function suggests these pathways may be important in the pathogenesis of cardiometabolic disease in HIV disease.

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Section: Prior Datamentioning

confidence: 99%

Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort

et al. 2015

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“…Regarding atorvastatin, a previous, uncontrolled, small trial (n = 26) of hypercholesterolemic patients using nuclear magnetic resonance (NMR) revealed that atorvastatin 10 mg a day significantly lowered LDL-C levels, significantly reduced LDL particle number, significantly reduced the cholesterol content of LDL subclasses (large and small), significantly increased overall LDL particle size, but had no significant effect upon Pattern B[26]. In a larger, placebo-controlled study of 217 dyslipidemic patients with type 2 diabetes mellitus, using polyacrylamide gradient gel electrophoresis, atorvastatin 10 mg and 80 mg significantly lowered LDL-C levels, significantly reduced apo B, and produced no significant effects upon LDL particle size.…”

Section: Discussionmentioning

confidence: 99%

Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

Bays

Conard²,

Leiter

et al. 2010

Lipids Health Dis

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BackgroundSome patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL.ResultsBoth treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL.ConclusionsWhen assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels.Trial Registration(Registered at clinicaltrials.gov: Clinical trial # NCT00276484)

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“…The TG/HDL-C ratio, a rough measure of the predominance of sdLDL particles over large-buoyant ones [71], is an independent determinant of AS in older adults, younger adults and adolescents, particularly in those with central obesity, regardless of the presence of hypertension [69,72,73]. The treatment of choice for elevated sdLDL is statins because, beside the preferential reduction in sdLDL particles, they reduce markers of inflammation such as lipoprotein-associated phospholipase A2 (Lp-PLA2) [74][75][76][77]. Ezetimibe decreases the large and medium LDL particles and, to a lesser extent, the sdLDL particles, while it has no influence on LDL size; however, its sdLDL-lowering capacity may be enhanced in individuals with elevated TG levels [78].…”

Section: As In Mets-associated Atherogenic Dyslipidaemiamentioning

confidence: 99%

Treating Arterial Stiffness Associated with Features of Metabolic Syndrome Not Included in its Diagnostic Criteria: Cutting Off the Heads of Lernaean Hydra, Keeper of the Underworld

Athyros¹,

Ferlita²,

Τζιόμαλος³

et al. 2013

TOHYPERJ

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Abstract:The clustering of cardio-metabolic risk factors, regardless if this is called metabolic syndrome (MetS) or not, substantially increases the risk of cardiovascular disease (CVD) and all-cause mortality. One of the possible mechanisms of the rise in CVD incidence is the increase in arterial stiffness (AS), which is a significant and independent CVD risk factor. Hypertension has long been connected to AS. Besides MetS components (obesity, dyslipidaemia, hypertension, dysglycaemia), MetS-associated disease states, not included in the MetS diagnostic criteria (renal dysfunction, hyperuricaemia, non alcoholic fatty liver disease, obstructive sleep apnea, polycystic ovary syndrome and hypercoaglutability) have been implicated in the increase of CVD risk through the increase of AS, among other mechanisms. Treatment options for AS induced by these non-diagnostic features of MetS are discussed. The impact of lifestyle changes is analyzed. Among pharmacological interventions, statin treatment seams to hold a pivotal role. Furthermore, we discuss specific measures for each disease state separately.

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Effects of Atorvastatin on Nuclear Magnetic Resonance-Defined Lipoprotein Subclasses and Inflammatory Markers in Patients with Hypercholesterolemia

Cited by 24 publications

References 15 publications

Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort

Lipoprotein concentration, particle number, size and cholesterol efflux capacity are associated with mitochondrial oxidative stress and function in an HIV positive cohort

Are post-treatment low-density lipoprotein subclass pattern analyses potentially misleading?

Treating Arterial Stiffness Associated with Features of Metabolic Syndrome Not Included in its Diagnostic Criteria: Cutting Off the Heads of Lernaean Hydra, Keeper of the Underworld

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