Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database

Barter, Philip J.; Brandrup‐Wognsen, Gunnar; Palmér, Mats; Nicholls, Stephen J.

doi:10.1194/jlr.p002816

Cited by 214 publications

(204 citation statements)

References 37 publications

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“…Data indicate HCQ also increases LDL receptors and activity of HMG-Co reductase and slows degradation of the enzyme (26,27,40). The consistent finding of a lack of HDL benefit in our and other cohorts may imply that HCQ lacks the mechanism whereby statins raise HDL levels and exhibits similar discordance as statins in its ability to lower LDL but not increase HDL, or has a dose-dependent relationship (as statins have) in raising HDL levels (41)(42)(43). At the clinical level, HCQ is associated with a decreased prevalence of DM (an absent observation in our cohort), but our findings endorse those of a large epidemiologic study that indicates the lipid associations of HCQ to be unrelated to its antiinflammatory action, considering it occurs independent of disease activity (44).…”

Section: Discussionmentioning

confidence: 52%

Associations of Hydroxychloroquine Use With Lipid Profiles in Rheumatoid Arthritis: Pharmacologic Implications

Kerr

Aujero

Richards

et al. 2014

Arthritis Care & Research

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Results. In an elderly, predominantly male VARA cohort, 1,011 patients had lipid profiles; 787 patients (77.8%) were white. Statin use was recorded in 11.6% of patients, diabetes mellitus in 33.5%, and CVD in 31.2%. HCQ users (n ‫؍‬ 150) were older, had longer rheumatoid arthritis (RA) disease duration, and had lower disease activity. Optimum lipid profiles, including total cholesterol:high-density lipoprotein (HDL) and HDL:low-density lipoprotein ratios (P < 0.001), were more frequent in HCQ users, with the exception of HDL (P ‫؍‬ 0.165), and persisted in multivariate analyses. Similarly, more HCQ users had NCEP-ATP III target levels. Varied periods of HCQ exposure suggested lipid changes to occur early, but lost within a year of drug discontinuation. HCQ users had less prevalent CVD. Conclusion. In RA patients, HCQ use of at least 3 months' duration was associated with better lipid profiles irrespective of disease activity or statin use. Given the increased CVD risks in RA and the relative low cost and toxicity of HCQ, continued use, regardless of treatment regimen, should be considered.

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Section: Discussionmentioning

confidence: 52%

Associations of Hydroxychloroquine Use With Lipid Profiles in Rheumatoid Arthritis: Pharmacologic Implications

Kerr

Aujero

Richards

et al. 2014

Arthritis Care & Research

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“…In a similar manner among cardiac surgery patients, a low HDL cholesterol concentration could increase the risk of organ dysfunction, including postoperative AKI, and conversely, a high concentration of HDL cholesterol could decrease the risk of postoperative AKI. Furthermore, in patients undergoing cardiac surgery, who are frequently prescribed statins, any effect of HDL on postoperative AKI risk might be altered by statin exposure, because statin treatment both modestly increases HDL cholesterol concentration and increases the anti‐inflammatory and antioxidant capacities of HDL 23, 24, 25, 26…”

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confidence: 99%

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

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BackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High‐density lipoproteins (HDLs) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL's anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association.Methods and ResultsWe tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (P=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients (P=0.008) and was further enhanced with perioperative atorvastatin treatment (P=0.004) and increasing long‐term statin dose (P=0.003).ConclusionsA higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.

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“…At our center, pravastatin was included in our protocol for its immunomodulatory effects rather than for preventing lipid abnormalities; hence, pravastatin doses were not adjusted according to the individual patient lipid/ HDL levels, nor was there a protocol to switch to alternative more-potent statins, which may be more effective in ameliorating lipid abnormalities in the steroid-based group (38), thereby reducing the incidence of hypercholesterolemia in this cohort. A complex dose effect for some of the statins on HDL levels has been shown in previous studies, and hence dose adjustments (in either direction) may be a strategy to consider when aberrations in HDL levels are noted (39). Additionally, the use of strategies, both pharmacologic and nonpharmacologic that may help in increasing HDL-levels, may help in making steroidminimization even more attractive than it presently is (40).…”

Section: Discussionmentioning

confidence: 87%

Unusual Pattern of Dyslipidemia in Children Receiving Steroid Minimization Immunosuppression after Renal Transplantation

Lau

Tancredi

Perez

et al. 2010

Clinical Journal of the American Society of Nephrology

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Results: Twenty-nine patients were studied. Sixteen were receiving maintenance steroids, and 13 were on a steroid minimization regimen. Mixed effects analysis of covariance models demonstrated that at 1 month, children receiving maintenance steroids had higher cholesterol compared with the steroid minimization group. Statistically significant differences in total cholesterol were not seen at other time points. Similar findings were noted for the LDL cholesterol, LDL/HDL, and cholesterol/HDL ratios. At 1 month, the serum HDL cholesterol was substantially lower in the steroid minimization group. Differences in the HDL cholesterol levels remained significant throughout the first year.Conclusions: Steroid use is a significant independent risk factor for hypercholesterolemia during the first post-transplant month. The significance of lower HDL cholesterol among patients receiving steroid minimization needs further study and may be cause for concern.

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Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER Database

Cited by 214 publications

References 37 publications

Associations of Hydroxychloroquine Use With Lipid Profiles in Rheumatoid Arthritis: Pharmacologic Implications

Associations of Hydroxychloroquine Use With Lipid Profiles in Rheumatoid Arthritis: Pharmacologic Implications

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Unusual Pattern of Dyslipidemia in Children Receiving Steroid Minimization Immunosuppression after Renal Transplantation

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