BACKGROUND: Despite suppressive antiretroviral therapy (ART), increased levels of immune activation persist in HIV-infected subjects. Statins have anti-inflammatory effects and may reduce immune activation in HIV disease.
METHODS: Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN-HIV) is a randomized, double-blind placebo-controlled trial assessing the effect of rosuvastatin (10 mg daily) on markers of cardiovascular risk and immune activation in ART-treated patients. T-cell activation was measured by expression of CD38, HLA-DR, and PD1. Monocyte activation was measured with soluble markers (sCD14 and sCD163) and by enumeration of monocyte subpopulations and tissue factor expression. Markers of systemic and vascular inflammation and coagulation were also measured. SATURN-HIV is registered on clinicaltrials.gov (identifier: NCT01218802).
RESULTS: Rosuvastatin, compared with placebo, reduced sCD14 (-10.4% vs 0.5%, P = 0.006), lipoprotein-associated phospholipase A2 (-12.2% vs -1.7%, P = 0.0007), and IP-10 (-27.5 vs -8.2%, P = 0.03) levels after 48 weeks. The proportion of tissue factor-positive patrolling (CD14CD16) monocytes was also reduced by rosuvastatin (-41.6%) compared with placebo (-18.8%, P = 0.005). There was also a greater decrease in the proportions of activated (CD38HLA-DR) T cells between the arms (-38.1% vs -17.8%, P = 0.009 for CD4 cells, and -44.8% vs -27.4%, P = 0.003 for CD8 cells).
CONCLUSIONS: Forty-eight weeks of rosuvastatin treatment reduced significantly several markers of inflammation and lymphocyte and monocyte activation in ART-treated subjects.
ANTECEDENTES: Xuezhikang (XZK) es un extracto de arroz de levadura roja fermentada que tiene propiedades hipolipemiantes.
Objetivo: Evaluar los efectos de XZK sobre los lípidos en sujetos con dislipidemia pero no la enfermedad cardíaca coronaria.
MÉTODOS: Un total de 116 adultos con colesterol de lipoproteínas de línea de base no son de alta densidad (colesterol no HDL-C) los niveles de niveles de aproximadamente 175 mg, aproximadamente 208 mg / dl y de baja densidad de colesterol de lipoproteínas (LDL-C) / dl fueron aleatorizados con placebo o XZK 1200 o 2400 mg al día y tratados durante 12 semanas.
RESULTADOS: La mayoría de los pacientes eran de raza blanca (53,4%) o Asia (37,1%). XZK diaria de 1200 mg y 2.400 mg de 4 a 12 semanas dio lugar a estadísticamente significativa (p <0,001) y disminuciones clínicamente significativas en la no-HDL-C (~ 24% de reducción) y LDL-C (reducción de ~27%) en comparación con placebo. XZK tratamiento en cualquiera de las dosis habilitado aproximadamente el 50% de los sujetos para reducir sus niveles de LDL-C en un ≥ 30%. La duplicación de la dosis diaria XZK 1200-2400 mg en la semana 8 de tratamiento causó una reducción adicional del 4,6% en el colesterol LDL-C. importantes beneficios también fueron observados a través de las variables secundarias de eficacia, incluyendo el colesterol total (CT), apolipoproteína B (Apo B), triglicéridos, HDL-C, el índice TC / HDL-C, y la relación Apo B / Apo AI, en la semana de tratamiento 8 o 12. XZK fue segura y bien tolerada. Los perfiles de seguridad y tolerabilidad fueron similares en todos los grupos de tratamiento. La mayoría de los eventos adversos fueron gastrointestinales. Ningún sujeto experimentó miopatía o marcadamente elevados de transaminasas hepáticas o creatina quinasa.
CONCLUSIÓN: Xuezhikang redujo significativamente no-HDL-C y LDL-C, y fue bien tolerado. Además, se necesitan estudios a largo plazo en más diversas poblaciones de pacientes para corroborar estos hallazgos.
Recent studies have shown that rosuvastatin significantly decreases serum levels of inflammatory biomarkers and slows progression of carotid atherosclerosis in the general population. However, there are no data about its effect on progression of atherosclerosis in HIV-infected patients. Adult patients with HIV infection, on stable antiretroviral therapy, with asymptomatic carotid atherosclerosis and hypercholesterolemia, who started a rosuvastatin treatment at 10 mg daily during the period 2007-2009 were enrolled and followed-up for 24 months. Thirty-six patients (30 males) were enrolled, with a mean age of 49 years, a mean duration of current antiretroviral therapy of 38 months, and a mean 10-year risk of myocardial infarction of 18.5%. Rosuvastatin led to a significant decrease in mean values of intima-media thickness in all extracranial carotid arteries, with the greatest magnitude observed in carotid bifurcations (a mean decrease of 18.7% in the right artery and of 21.4% in the left artery) and in internal carotid arteries (a mean decrease of 23.7% in the right artery and of 25.6% in the left artery). Moreover, there was a significant reduction in mean levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides versus respective baseline values associated with a significantly decreased mean cardiovascular risk. The treatment with rosuvastatin was well tolerated, and serious adverse events were not reported. A 24-month treatment with rosuvastatin in HIV-infected patients on highly active antiretroviral therapy (HAART) with subclinical atherosclerosis and a moderate cardiovascular risk seems to promote significantly favorable changes in carotid atherosclerosis, associated with a favorable effect on serum lipid levels and a good tolerability profile.
Xuezhikang (XZK) es un producto de calidad farmacéutica botánica de arroz de levadura roja que se ha estudiado en pacientes estadounidenses y chinas. XZK contiene monacolina K (similar a la lovastatina) en 10 a 12 mg de la dosis de 1200 mg. Este ensayo aleatorio, controlado con placebo en 116 pacientes con LDL-C 160 a la 220 mg / dl en ningún otro LLT evaluó 1.200 mg / día y 2.400 mg / día de XZK frente a placebo durante 12 semanas. La reducción de LDL-C fue del 27% en ambos brazos y XZK fue de + 0,8% en el grupo placebo. No hubo reacciones adversas miopatía. Los autores concluyeron que XZK reduce el LDL-C en un grado similar se espera de 20 mg / día de lovastatina, fue bien tolerada, y que están planeando más ensayos con el fin de obtener la aprobación de la FDA.
BACKGROUND: Treatments that reduce inflammation and cardiovascular disease (CVD) risk among individuals with HIV infection receiving effective antiretroviral therapy (ART) are needed.
DESIGN AND METHODS: We conducted a 2 × 2 factorial feasibility study of lisinopril (L) (10 mg daily) vs L-placebo in combination with pravastatin (P) (20 mg daily) vs P-placebo among participants receiving ART with undetectable HIV RNA levels, a Framingham 10 year risk score (FRS) ≥ 3%, and no indication for ACE-I or statin therapy. Tolerability and adherence were evaluated. Longitudinal mixed models assessed changes in blood pressure (BP), blood lipids, and inflammatory biomarkers from baseline through months 1 and 4.
RESULTS: Thirty-seven participants were randomized and 34 [lisinopril/pravastatin (n=9), lisinopril/P-placebo (n=8), L-placebo/pravastatin (n=9), L-placebo/P-placebo (n=8)] attended at least one follow-up visit. Participants were 97% male, 41% white, 67% were current smokers, and 65% were taking a protease inhibitor. Median age was 48 years, CD4 count 483 cells/mm(3), FRS 7.79%, total cholesterol 184 mg/dL, and LDL-C 95 mg/dL. There was no treatment difference for pravastatin vs P-placebo in total cholesterol, LDL-C, or any of the inflammatory biomarkers. Participants randomized to lisinopril vs. L-placebo had significant declines in diastolic BP (-3.3 mmHg, p=0.05), hsCRP (-0.61 µg/mL, p=0.02) and TNF-α (-0.17 pg/mL, p=0.04). Participants taking lisinopril vs L-placebo were more likely to report missed doses (88 vs 35%; p=0.001) and have adherence <90% by pill count (42 vs. 0%; p=0.02). Few participants from either group reported side effects (n=3 vs. n=1).
CONCLUSIONS: The modest BP changes and decreased adherence with lisinopril and absence of lipid differences with pravastatin suggest future studies of these drug classes should consider a run-in period to assess adherence and use a different statin. Our results also indicate that ACE-I therapy may have anti-inflammatory benefits for ART-treated persons with HIV infection and this should be further evaluated.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00982189.
Revista»Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban
OBJECTIVE: To observe the clinical effects of lipid-reducing red rice minute powder (LRRMP) on the levels of blood lipids, carotid artery intima-media thickness (IMT), and the plaque integral of hyperlipidemia patients complicated with carotid atherosclerosis.
METHODS: This study was conducted from April 2005 to April 2006 according to inclusion criteria. Sixty hyperlipidemia patients complicated with carotid atherosclerosis were randomly assigned to the treatment group (20 cases), the Chinese medicine control group (CM control group, 20 cases), and the Western medicine control group (WM control group, 20 cases). They were recruited from the community of secondary machine tool factory of Jinan. Patients in the treatment group took LRRMP (175 mg/pill), one pill each time, twice daily. Patients in the CM control group took Xuezhikang Capsule (300 mg/pill), 2 pills each time, twice daily. Patients in the WM control group took Lovastatin Tablet (20 mg/tablet), 1 tablet each time, once daily. The course of treatment was 6 successive months for all. They avoided taking any lipid-regulating or anti-atherosclerotic drugs during the therapeutic course. The changes of Chinese medicine symptom scores, serum TC, TG, LDL-C, and HDL-C levels, IMT of the carotid artery, and the plaque integral before and after treatment were observed.
RESULTS: After 6 months of treatment the Chinese medicine symptom scores reduced in each group ( P<0.05 or P<0.01), and the treatment group was superior to WM control group (P<0.05). Serum TC, TG and LDL-C levels were significantly lowered (P<0.05 or P<0.01), showing no significant difference in inter-group comparison (P>0.05). There was no statistical significance of the serum HDL-C level in each group (P>0.05). The IMT and the plaque integral significantly reduced (P<0.05, P<0.01), showing no statistical difference among all groups. One patient in the WM control group dropped out because of transaminase elevation. No serious adverse reaction correlated with the drugs occurred during the therapeutic course in the rest two groups.
CONCLUSIONS: LRRMP showed definite effects on lipid-regulating and anti atherosclerosis. Its effects were equivalent to Xuezhikang Capsule and Lovastatin Tablet. Besides, it was safe and economic, and deserved further studies.
Varios ensayos previos de estudios de poblaciones occidentales han mostrado que las estatinas pueden ayudar a reducir la presión arterial (PA). Sin embargo, los datos clínico aleatorizado es limitado. Xuezhikang, una parte de extracto de arroz de levadura roja, contiene una familia de las estatinas producen de forma natural, y tiene un marcado efecto sobre los lípidos, pero se desconoce si Xuezhikang tiene ningún efecto sobre la presión arterial durante largo plazo de seguimiento en la población china. Se trata de un análisis de subgrupos post-hoc de un,,, ensayo aleatorio doble ciego controlado con placebo, de grupos paralelos clínica, coronaria secundaria Prevention Study Chino (CCSPS). Un total de 2704 pacientes hipertensos con infarto de miocardio previo (MI) fueron asignados o bien a placebo (n = 1341) o para Xuezhikang (n = 1363) al día durante una media de 4,5 años. El resultado primario fue sin ajustar los cambios en la presión arterial media (PAM) desde el inicio hasta 6 meses. También se evaluó la presión arterial sistólica (PAS), presión arterial diastólica (PAD) y la presión del pulso. El análisis de covarianza se utilizó para calcular los efectos ajustados del tratamiento sobre los cambios en estos resultados a los 6, 12, 24, y 48 meses después de la aleatorización, después de controlar los posibles factores de confusión. Este análisis incluyó 2704/4870 (55,5%) pacientes hipertensos para los que se midió la presión arterial al inicio del estudio y al menos una visita de seguimiento después de la aleatorización. La duración media del seguimiento fue de 4,5 años (54 meses), y 25 pacientes (0,92%) se perdieron durante el último seguimiento debido a los efectos adversos. Los resultados mostraron que los cambios no ajustados y ajustados en MAP, PAS, PAD, o la presión de pulso desde la línea de base no fueron significativamente diferentes para Xuezhikang o receptores de placebo a las 6, 12, 24, y 48 meses después de la aleatorización. En este análisis de subgrupos post-hoc, pero no hemos podido demostrar ningún efecto de reducción significativa de Xuezhikang sobre la presión arterial en pacientes hipertensos chinos con IM previo, lo que sugiere que sería necesario un mayor estudio prospectivo sobre los efectos de las estatinas sobre la PA, especialmente en pacientes de alto riesgo .
Despite suppressive antiretroviral therapy (ART), increased levels of immune activation persist in HIV-infected subjects. Statins have anti-inflammatory effects and may reduce immune activation in HIV disease.
METHODS:
Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN-HIV) is a randomized, double-blind placebo-controlled trial assessing the effect of rosuvastatin (10 mg daily) on markers of cardiovascular risk and immune activation in ART-treated patients. T-cell activation was measured by expression of CD38, HLA-DR, and PD1. Monocyte activation was measured with soluble markers (sCD14 and sCD163) and by enumeration of monocyte subpopulations and tissue factor expression. Markers of systemic and vascular inflammation and coagulation were also measured. SATURN-HIV is registered on clinicaltrials.gov (identifier: NCT01218802).
RESULTS:
Rosuvastatin, compared with placebo, reduced sCD14 (-10.4% vs 0.5%, P = 0.006), lipoprotein-associated phospholipase A2 (-12.2% vs -1.7%, P = 0.0007), and IP-10 (-27.5 vs -8.2%, P = 0.03) levels after 48 weeks. The proportion of tissue factor-positive patrolling (CD14CD16) monocytes was also reduced by rosuvastatin (-41.6%) compared with placebo (-18.8%, P = 0.005). There was also a greater decrease in the proportions of activated (CD38HLA-DR) T cells between the arms (-38.1% vs -17.8%, P = 0.009 for CD4 cells, and -44.8% vs -27.4%, P = 0.003 for CD8 cells).
CONCLUSIONS:
Forty-eight weeks of rosuvastatin treatment reduced significantly several markers of inflammation and lymphocyte and monocyte activation in ART-treated subjects.
