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HIV vasculopathy: role of mononuclear cell-associated Krüppel-like factors 2 and 4.
Hale, AT, Longenecker, CT, Jiang, Y, Debanne, SM, Labatto, DE, Storer, N, Hamik, A, McComsey, GA
AIDS (London, England). 2015;(13):1643-50
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Abstract
OBJECTIVE To determine the relationships between Krüppel-like factors (KLF) 2 and 4, immune-activation, and subclinical vascular disease in HIV-infected patients on antiretroviral therapy (ART). DESIGN Double-blind, randomized, placebo-controlled trial. METHODS We studied 74 HIV-infected adults on ART enrolled in a randomized clinical trial of statin therapy. KLF2 and KLF4 gene expression was measured by quantitative PCR from peripheral blood mononuclear cells (PBMCs) at baseline and after 24 weeks of 10 mg daily rosuvastatin or placebo. At the same time points, T-cell and monocyte activation were assessed by flow cytometry and vascular health was assessed by cardiac computed tomography and carotid ultrasound. RESULTS KLF4 expression was negatively correlated with duration of ART (r = -0.351, P = 0.004) and positively correlated with measures of immune activation: proinflammatory monocytes [CD14CD16 (r = 0.343, P = 0.003)], patrolling monocytes [CD14CD16 (r = 0.276, P = 0.017)], and activated CD8 T-lymphocytes [CD8DRCD38 (r = 0.264, P = 0.023)]. KLF2 expression was negatively correlated with subclinical atherosclerosis: mean-mean common carotid artery intima-media thickness (r = -0.231, P = 0.048), mean-max carotid artery intima-media thickness (r = -0.271, P = 0.020), and coronary artery calcium score (r = -0.254, P = 0.029). There were no statistically significant changes in KLF2/4 expression in PBMCs after 24 weeks of rosuvastatin. CONCLUSION Expression of KLF4 in PBMCs positively correlates with cellular markers of immune activation, whereas KLF2 expression negatively correlates with markers of subclinical atherosclerosis in this HIV-infected population on ART. Additional studies are needed to determine if targeted interventions might alter KLF2/4 expression to reduce inflammation and vascular risk in humans.
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Statin therapy decreases N-terminal pro-B-type natriuretic peptide in HIV: randomized placebo-controlled trial.
Dirajlal-Fargo, S, Kinley, B, Jiang, Y, Longenecker, CT, Hileman, CO, Debanne, S, McComsey, GA
AIDS (London, England). 2015;(3):313-21
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Abstract
OBJECTIVE HIV-infected participants are at a higher risk for cardiovascular disease (CVD). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a significant predictor of CVD in the general population and is associated with mortality in HIV. DESIGN AND METHODS The 96-week Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial randomized 147 patients on stable antiretroviral therapy with low-density lipoprotein-cholesterol level lower than 130 mg/dl and without overt heart failure to 10 mg daily rosuvastatin or placebo. We measured NT-proBNP levels by enzyme-linked immunosorbent assay (ELISA). Baseline and changes in NT-proBNP were compared between groups. Spearman correlation was used to explore relationships between baseline NT-proBNP, inflammation, and CVD risk markers. Multivariable analyses were conducted to assess associations with NT-proBNP levels. RESULTS Median age was 46 years, 80% were men, 69% were African American, and 46% were on protease inhibitors. At baseline, median (Q1, Q3) NT-proBNP was higher in the rosuvastatin group than placebo [41 (20, 66.5) versus 25 pg/ml (11, 56), P = 0.012)]. Baseline NT-proBNP correlated with bulb and common carotid artery intima-media thickness, coronary calcium score, interleukin 6, and cystatin C. After 96 weeks, median NT-proBNP decreased significantly in the rosuvastatin group versus placebo (-1.50 versus +4.50 pg/ml, P = 0.041). Within the rosuvastatin group, changes in NT-proBNP were negatively correlated with changes in insulin resistance and total limb fat. CONCLUSION Rosuvastatin reduces plasma NT-proBNP in HIV-infected participants on antiretroviral therapy. NT-proBNP correlated with several measures of CVD risk, independent of inflammation markers.
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Using mobile technology to support lower-salt food choices for people with cardiovascular disease: protocol for the SaltSwitch randomized controlled trial.
Eyles, H, McLean, R, Neal, B, Doughty, RN, Jiang, Y, Ni Mhurchu, C
BMC public health. 2014;:950
Abstract
BACKGROUND Cardiovascular disease (CVD) is the leading cause of early death worldwide, responsible for an estimated 29% of all global deaths. Reducing salt intake lowers blood pressure and risk of secondary cardiac events. However, identifying low salt foods can be challenging. SaltSwitch is a simple smartphone application (app) that enables shoppers to scan the barcode of packaged foods and receive an immediate, interpretive, traffic light nutrition label on the screen, along with suggestions for healthier lower-salt alternatives. A growing body of evidence suggests mobile technologies can support healthy behaviour change. However, robust evidence for the impact of smartphone interventions is lacking. This manuscript outlines the rationale and methods for a randomized controlled trial designed to determine the effectiveness of SaltSwitch in supporting people with CVD to make lower-salt food choices. DESIGN/METHODS A 6-week, two-arm, parallel, randomized controlled trial is being undertaken in New Zealand (2 weeks baseline and 4 weeks intervention). Three hundred adults aged 40 years and older with CVD and their main household shoppers are recruited from research lists, cardiac rehabilitation clinics, and communities in Auckland. Participants are randomized to receive either the SaltSwitch smartphone app or no intervention (control). Randomisation is stratified by ethnicity and age. The primary outcome is the salt content of household food purchases. Secondary outcomes are the saturated fat and energy content of household food purchases, household food expenditure, use and acceptability of the SaltSwitch app by shoppers, and urinary sodium and blood pressure of participants with CVD. Ambulatory blood pressure and potential longer-term impact (12 weeks) of SaltSwitch will be assessed in sub-studies (n ~ 40 and n ~ 20, respectively). Household purchases of salt and other nutrients will be assessed using till receipt data electronically linked with branded food composition data. DISCUSSION The results of the SaltSwitch trial will determine the effectiveness, use and acceptability of a smartphone application to support lower salt food choices and secondary prevention of CVD. TRIAL REGISTRATION ACTRN12614000206628. Registered 30 March 2014.
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Effects of Avena nuda L. on metabolic control and cardiovascular disease risk among Chinese patients with diabetes and meeting metabolic syndrome criteria: secondary analysis of a randomized clinical trial.
Ma, X, Gu, J, Zhang, Z, Jing, L, Xu, M, Dai, X, Jiang, Y, Li, Y, Bao, L, Cai, X, et al
European journal of clinical nutrition. 2013;(12):1291-7
Abstract
BACKGROUND/OBJECTIVES Most patients with Type 2 diabetes mellitus(DM) also have metabolic syndrome (MetS), which is associated with an increased risk of coronary heart disease prevalence. Limited information is available on the effect and effective doses of oat intake with a structured dietary intervention in metabolic control and cardiovascular disease (CVD) risk prevention with the population who has Type 2 DM and meets the MetS criteria. SUBJECTS/METHODS A total of 260 Type 2 DM patients meeting MetS National Cholesterol Education Program Adult Treatment Panel III criteria were selected from 445 patients between 50 and 65 years of age, and they participated in a single-blinded, 30-day centralized management of a dietary program in China. Participants in the program were randomly assigned into one of the four groups: usual care group (control group, only basic health advice), diet group (systematic diet plans and intensive education), 50 g-organic naked oat with whole germ group (ONOG) and 100 g-organic naked oat with whole germ group (daily ONOG replacement boiled into porridge based on diet group). The primary outcomes were the relative changes in glycosylated hemoglobin (HbA1c) and insulin resistance after a 30-day intervention among the four groups. RESULTS HbA1c decreased significantly with the increase in interventions (Ptrend<0.05). Similar results were also obtained in plasma glucose, serum lipid and hypersensitive C-reactive protein (hs-CRP). For the 100 g-ONOG group but not 50 g-ONOG group, HbA1c and hs-CRP reduced significantly by 0.51% and 1.29 mg/l (P<0.05, vs diet group), respectively. The 100 g-ONOG group showed a reduction by 0.22 U*mol/l(2) in insulin resistance, compared with the 50 g-ONOG group (P=0.039). CONCLUSIONS Compared with diet alone or no diet, 50-100 g/day ONOG supplement to structured dietary intervention, at a dose of 100 g/day especially, contributes to the Type 2 DM patients meeting MetS criteria in their metabolic control and CVD risk prevention, with external factors being controlled.