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Short Communication: The Effect of Rosuvastatin on Vascular Disease Differs by Smoking Status in Treated HIV Infection.
Hileman, CO, McComsey, GA
AIDS research and human retroviruses. 2018;(3):282-285
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Abstract
Smoking is an important contributor to cardiovascular disease risk and is highly prevalent in the HIV population. In the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV trial (SATURN-HIV), a 96-week, randomized placebo-controlled study testing the effect of rosuvastatin on subclinical vascular disease and immune activation in HIV-infected adults, rosuvastatin improved immune activation and arrested common carotid artery intima media thickness (CCA IMT) progression. In this exploratory analysis, ANOVA was used to test for effect modification by smoking. One-hundred forty-seven adults were included (72 in rosuvastatin group; 75 in placebo group). Groups were similar at baseline. Overall, mean ± SD age was 45.4 ± 9.9 years, 115 (78%) were men and 100 (68%) were African American. Ninety-three (63%) were current smokers (mean ± SD 0.6 ± 0.44 packs/day) and another 24 (16%) were smokers in the past. There were statistically significant randomization group by smoking status interactions for 0-24 (p = .01) and 0-48 (p < .01) week changes in proportion of activated CD4+ T cells and for 0-48 (p < .01) and 0-96 (trend only; p = .06) week changes in CCA IMT. No effect modification by smoking was detected for changes in markers of inflammation or monocyte activation. The beneficial effect of rosuvastatin on CCA IMT was not apparent in smokers although T cell activation improved to a greater degree in this subgroup.
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Autoantibodies and immune complexes to oxidation-specific epitopes and progression of aortic stenosis: Results from the ASTRONOMER trial.
Capoulade, R, Chan, KL, Mathieu, P, Bossé, Y, Dumesnil, JG, Tam, JW, Teo, KK, Yang, X, Witztum, JL, Arsenault, BJ, et al
Atherosclerosis. 2017;:1-7
Abstract
BACKGROUND AND AIMS Elevated levels of lipoprotein(a) [Lp(a)] and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict the progression of pre-existing mild-to-moderate calcific aortic valve stenosis (CAVS). Whether indirect markers of oxidation-specific epitopes (OSE) are also predictive is not known. The association between IgG and IgM autoantibodies and malondialdehyde-modified low density lipoprotein (MDA-LDL) and IgG and IgM apolipoprotein B immune complexes (apoB-IC), and the hemodynamic progression rate of CAVS was determined in the ASTRONOMER (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin, NCT00800800) trial. METHODS Plasma levels of IgG and IgM MDA-LDL and apoB-IC were measured in 220 patients with mild-to-moderate CAVS from the ASTRONOMER trial. The endpoint of this study was the progression rate of CAVS, measured by the annualized increase in peak aortic jet velocity (Vpeak) over a median follow-up of 3.5 [2.9-4.5] years. RESULTS There was no difference in the progression rate of CAVS across tertiles of IgG and IgM MDA-LDL and apoB-IC levels (all p > 0.05). After multivariable analysis, no marker reached significance level to predict faster CAVS progression or need for aortic valve replacement (all p > 0.05). There was no interaction between the OSE antibody titers and plasma levels of Lp(a) or OxPL-apoB, as well as age, with regards to the progression rate of CAVS. CONCLUSIONS Autoantibody titers to MDA-LDL and apoB-IC, which are an indirect measurement of OSE, unlike direct measurements of OxPL-apoB or their major lipoprotein carrier Lp(a), do not predict the progression of CAVS or need for AVR.
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Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy.
Hileman, CO, Tangpricha, V, Sattar, A, McComsey, GA
Journal of acquired immune deficiency syndromes (1999). 2017;(5):539-547
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Abstract
OBJECTIVE Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease. DESIGN SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy. This analysis focuses on the prespecified secondary endpoint 25-hydroxyvitamin D [25(OH)D] concentrations. METHODS Mixed effects linear modeling and analysis of variance were used to assess the rosuvastatin effect on plasma 25(OH)D concentrations over time and to determine whether baseline vitamin D modifies the rosuvastatin effect on changes in outcomes over the trial. RESULTS Hundred forty-seven adults were randomized (72 to rosuvastatin and 75 to placebo); 78% were men, 68% African American, with a mean age of 45 years. Baseline 25(OH)D concentrations were similar (overall mean 18 ng/mL) with 65% of participants below 20 ng/mL. Changes in 25(OH)D at 96 weeks were small and not significant within- or between-rosuvastatin and placebo groups. There were significant group by vitamin D status interactions for changes in low-density lipoprotein-cholesterol, proportion of patrolling monocytes expressing tissue factor (CD14dimCD16+TF+), lipoprotein-associated phospholipase A2, and common carotid artery intima media thickness at most time points. For each of these outcomes, the beneficial effects of rosuvastatin were either not apparent or attenuated in participants with 25(OH)D <20 ng/mL. CONCLUSIONS Although 25(OH)D did not change with rosuvastatin, baseline vitamin D deficiency decreased the effectiveness of rosuvastatin. Vitamin D supplementation may be warranted for deficient patients initiating statin therapy.
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Significant Decrease in Plasma Levels of D-Dimer, Interleukin-8, and Interleukin-12 After a 12-Month Treatment with Rosuvastatin in HIV-Infected Patients Under Antiretroviral Therapy.
Calza, L, Colangeli, V, Magistrelli, E, Contadini, I, Bon, I, Re, MC, Conti, M, Mancini, R, Viale, P
AIDS research and human retroviruses. 2017;(2):126-132
Abstract
OBJECTIVES Statins have shown anti-inflammatory and immune-modulatory properties in both general and HIV-infected population, but their effect on plasma D-dimer levels is controversial and it has not been investigated to date in HIV-positive patients. The aim of our study was to assess the effect of rosuvastatin on D-dimer and other serum inflammation markers among these subjects. METHODS Prospective, cohort study of HIV-1-infected adult patients receiving a stable combination antiretroviral therapy (cART), who started a lipid-lowering therapy with rosuvastatin (10 mg daily) and were followed up for at least 12 months. The primary endpoint was the change at month 12 in the median plasma concentration of D-dimer. The secondary endpoints included the variation in median plasma levels of these inflammatory biomarkers: interleukin-8 (IL-8), interleukin-10 (IL-10), and interleukin-12 (IL-12). RESULTS Sixty-two patients were enrolled in the study, and the endpoints were available for 54 subjects. After 12 months, a significant decrease in median plasma concentration of D-dimer was observed (-21.4%; interquartile range [IQR], -35.5; -4.2; p = .029). With regard to the inflammatory biomarkers, a significant decrease in median levels of IL-8 (-24.6%; IQR, -30.8; -1.8; p = .012) and IL-12 (-18.7%; IQR, -25.8; +2.5; p = .033) was also observed. Rosuvastatin led to a significant reduction in serum lipid values and showed a good tolerability profile. CONCLUSIONS Our findings show that a 12-month treatment with rosuvastatin associated with an effective cART can significantly decrease the plasma levels of D-dimer, IL-8, and IL-12, and suggest a potential role for this statin to reduce activated coagulation and systemic inflammation among HIV-infected persons.